The Potential Utility of Urinary Biomarkers for Risk Prediction in Combat Casualties: A Prospective Observational Cohort Study

DTIC Science & Technology

2015-06-16

are associated with poor outcomes, including death and the need for renal replacement therapy. Methods : We conducted a prospective, observational study...penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE 16 JUN 2015...2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE The Potential Utility of Urinary Biomarkers for Risk Prediction in Combat

Twelve shifting paradigms in diabetic renal disease and hypertension.

PubMed

Mogensen, Carl Erik

2008-11-13

In the last 30 years we have seen considerable progress in the management of patients with diabetes, in particular with diabetic renal disease. A number of paradigms have been broken down, namely the following, as a consequence, clinical care has improved dramatically. . Significant renal involvement and albuminuria is rare in patients with essential hypertension. 2. High GFR is good for prognosis. 3. Only proteinuric diabetic patients have a poor prognosis. 4. Microalbuminuria only predicts renal disease. 5. Reducing blood pressure may cause low perfusion in the kidney and other organs with long-term negative effect, especially on the glomerular filtration rate. 6. Only in the presence of high blood pressure, should microalbuminuric patients receive anti-hypertensive treatment, including blockade of the RAS. 7. Only reducing blood pressure by blocking RAS in diabetes is relevant and justified. 8. Normoalbuminuria as indicated in the present definition is 'normal'. 9. ACE-I or ARB can only be used separately. 10. Diastolic blood pressure and later systolic pulse pressure are the best parameters for blood pressure recording. 11. Microalbuminuria is the strongest risk marker in patients with type 1 diabetes. 12. Screening for microalbuminuria is relevant, but follow-up was not proposed (also regarding microalbuminuria). In the present situation, it is well-known that patients with essential hypertension may sometimes have microalbuminuria, and it is known that it predicts a poor prognosis. Interestingly, in type 1 diabetes, hyperfiltration is a marker for poor prognosis related to metabolic control. Thus hyperfiltration is a marker for bad development, but microalbuminuria (below the proteinuric level) is also associated with a poor prognosis. It was originally believed that microalbuminuria only predicts renal disease. However, surprisingly it predicts as well cardiovascular disease and early mortality. The story about blood pressure and progression of renal disease is interesting, because it was earlier believed that a certain high blood pressure was mandatory for preservation of the renal function. This appeared to be a completely wrong concept. The data regarding microalbuminuria suggest that patients with microalbuminuria should receive anti-hypertensive treatment, even patients with so-called normal blood pressure. This was confirmed in several trials and also included in the guidelines. Reducing blood pressure is important, but it appeared to be especially beneficial to block the renin-angiontensin system, and it is clear that albuminuria is a continuous variable and is also a risk factor. Earlier it was suggested to use ACE-inhibitors or ARBs. Now it is clear that it is possible to use a combination, with good theoretical background. In the history of hypertension, it was earlier believed that diastolic blood pressure was most important, but later on it was generally accepted that systolic is a better predictor and the goal for treatment and pulse pressure may be even better. Not only is microalbuminuria an important risk marker, but it is as well clear that regression of microalbuminuria is a good marker for a better prognosis in patients. Microalbuminuria is believed to be the strongest risk factor, but new studies actually suggest that a simple parameter such as self-rated health is crucial along with other factors. Regarding new developments, it is clear that new studies have led to several advancements in management in patients, for instance the Steno II study shows positive effect on mortality by multifactorial intervention. Similarly, the ADVANCE study also showed positive effect on mortality by more intensified anti-hypertensive treatment with an ACE-inhibitor. We are eagerly awaiting the results from glucose arm in the ADVANCE study, especially in the light of the ACCORD study showing increased mortality with too strict glycemic control with a goal of 6% in HbA1c.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction.

PubMed

Iglesias, Jose; Frank, Elliot; Mehandru, Sushil; Davis, John M; Levine, Jerrold S

2013-07-13

Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction.

Predicting long-term renal damage in children with vesicoureteral reflux under conservative initial management: 205 cases in a tertiary referral center.

PubMed

Alvarez, Natalia; Alvira, Reyes Delgado; Ruiz, Yurema Gonzalez; Atuan, Rafael Fernandez; Hinojosa, Alexander Siles; Heras, Miguel Angel Rihuete; Roldan, Marisa Justa; Romero, Jesus Gracia

2018-01-01

Vesicoureteral reflux (VUR) is one of the most common ailments in children. Evidence-based guidelines recommend conservative treatment in children with VUR, followed by endoscopic surgery in those with breakthrough febrile urinary tract infections (UTIs). Despite this fact, the management of VUR is still controversial. Our objective is to evaluate the conservative strategy in children with primary VUR in terms of renal function and scarring, and identify factors associated with poor prognosis in those children. A retrospective study was carried out in a tertiary center in children with primary VUR under conservative strategy treatment from 1989 to 2015. Data extracted included age of presentation, family and prenatal backgrounds, radiographic evaluation including ultrasound (US), dimercaptosuccinic acid (DMSA) scans and voiding cystourethrogram (VCUG). The SPSS program was used for statistical analysis. Two-hundred and five patients were diagnosed and followed a conservative therapy scheme (49.8% males, 50.2% females) after febrile UTI (73.17%) or prenatal diagnosis (26.83%). VCUG showed 53.20% of low-moderate VUR grade, 46.80% high VUR grade. Renal damage was present at diagnosis in 40.89%. Mean follow-up reakthrough recurrent febrile UTIs and underwent surgery. Conservative therapy was followed in 189 patients. Renal scarring or decreased kidney function were shown in 15.12% respectively. Renal damage was identified as a risk factor for poor prognosis (p-value <0.005) only for renal function deterioration. Patients with high-grade VUR required surgery in a significantly greater proportion (p <0.005) due to recurrent febrile UTIs. Conservative strategy is a feasible treatment for primary VUR in children. The majority of cases could be managed conservatively with good outcomes after long-term follow-up. Decreased renal function is more frequent in patients with high-grade VUR. Renal damage at diagnosis increases the risk for surgical treatment.

Kidney disease physician workforce: where is the emerging pipeline?

PubMed Central

Pogue, Velvie A.; Norris, Keith C.; Dillard, Martin G.

2002-01-01

A predicted increase in the number of patients with end-stage renal disease in coming years, coupled with significant numbers of qualified nephrologists reaching retirement age, will place great demands on the renal physician workforce. Action is required on several fronts to combat the predicted shortfall in full-time nephrologists. Of particular importance is the need to recruit and train greater numbers of physicians from ethnic minority groups. Changes in the demographics of kidney disease make it increasingly a disease of ethnic minorities and the poor. These demographic changes, together with the existing racial disparities in the diagnosis and treatment of kidney disease, highlight the specific need for nephrologists who are cognizant of the issues and barriers that prevent optimal care of high-risk minority populations. The current lack of academic role models and the drive by medical schools and residency programs to encourage minority group physicians to become primary care providers, rather than specialists, are issues that must be urgently addressed. Equally, changes in the training of renal fellows are required to merge the critical need for cutting edge research activity in renal science and with the insights and sensitivity to equip clinicians with the necessary skills for the team-based approach to patient care that increasingly characterizes the management and care of the patient with chronic kidney disease. PMID:12152911

Congenital ureteropelvic junction obstruction: physiopathology, decoupling of tout court pelvic dilatation-obstruction semantic connection, biomarkers to predict renal damage evolution.

PubMed

Alberti, C

2012-02-01

The widespread use of fetal ultrasonography results in a frequent antenatally observation of hydronephrosis, ureteropelvic junction obstruction (UPJO) accounting for the greatest fraction of congenital obstructive nephropathy. UPJO may be considered, in most cases, as a functional obstructive condition, depending on defective fetal smooth muscle/nerve development at this level, with lack of peristaltic wave propagation--aperistaltic segment--and, therefore, poor urine ejection from the renal pelvis into the ureter. The UPJO-related physiopathologic events are, at first, the compliant dilatation of renal pelvis that, acting as hydraulic buffer, protects the renal parenchyma from the rising intrapelvic pressure-related potential damages, and, subsequently, beyond such phase of dynamic balance, the tubular cell stretch-stress induced by increased intratubular pressure and following parenchymal inflammatory lesions: inflammatory infiltrates, fibroblast proliferation, activation of myofibroblasts, tubulo-interstitial fibrosis. Reactive oxygen species (ROS), nitric oxide (NO), several chemo- and cytokines, growth factors, prostaglandins and eicosanoids, angiotensin-II are the main pathogenetic mediators of the obstructive nephropathy. Apoptosis of tubular cells is the major cause of the tubular atrophy, together with epithelial-mesenchymal transdifferentiation. Some criticisms on tout court semantic renal pelvis dilatation-obstruction connection have been raised considering that the renal pelvis expansion isn't, in any case, linked to an ostructive condition, as it may be verified by diuretic (furosemide) renogram together with scintiscan-based evaluation of differential renal function. In this regard, rather than repetitive invasive nuclear procedures that expose the children to ionizing radiations, an intriguing noninvasive strategy, based on the evaluation of urinary biomarkers and urinary proteome, can define the UPJO-related possible progress of parenchymal lesions, thus predicting which patients must require an obstruction correcting surgery and in which patients, instead, the hydronephrosis will spontaneously resolve.

Interobserver agreement for post mortem renal histopathology and diagnosis of acute tubular necrosis in critically ill patients.

PubMed

Glassford, Neil J; Skene, Alison; Guardiola, Maria B; Chan, Matthew J; Bagshaw, Sean M; Bellomo, Rinaldo; Solez, Kim

2017-12-01

The renal histopathology of critically ill patients dying with acute kidney injury (AKI) in intensive care units of high income countries remains uncertain. Retrospective observational assessment of interobserver agreement in the reporting of renal post mortem histopathology, and the ability of pathologists blinded to the clinical context to independently identify the presence of pre-mortem AKI from digital images of histological sections from 34 critically ill patients dying in teaching hospitals in Australia and Canada. We identified a heterogeneous cohort with a median age of 65 years (interquartile range [IQR], 56.5-77), APACHE II score of 27 (IQR, 19-33), and sepsis as the most common admission diagnosis (12/34; 35%). The most common proximate causes of death were cardiovascular (19/34; 56%) and respiratory (7/34; 21%) failure. AKI was common, with 23 patients (68%) developing RIFLE-F AKI, and 21 patients (62%) receiving renal replacement therapy. Structured reporting for tubular inflammation showed excellent agreement (kappa = 1), but no other subdomain demonstrated better than moderate agreement (kappa < 0.6). Only fair agreement (55.9% of cases; kappa = 0.23) was demonstrated on the diagnosis of moderate to severe acute tubular necrosis (ATN). Pathologist A predicted RIFLE-I or worse AKI with the diagnosis of ATN, with an overall accuracy of 61.8%; pathologist B predicted AKI with an accuracy of 35.3%. Post mortem assessment of the renal histopathology in critically ill patients is neither robust nor reproducible; independent pathologists agree poorly on the diagnosis of ATN, and their structural assessment appears dissociated from ante-mortem renal function.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction

PubMed Central

2013-01-01

Background Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Methods Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Results Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. Conclusion These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction. PMID:23849513

The Association Between PD-L1 Expression and the Clinical Outcomes to Vascular Endothelial Growth Factor-Targeted Therapy in Patients With Metastatic Clear Cell Renal Cell Carcinoma

PubMed Central

Shin, Su-Jin; Jeon, Yoon Kyung; Cho, Yong Mee; Lee, Jae-Lyun; Chung, Doo Hyun; Park, Ji Young

2015-01-01

Background. Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are used as the first-line treatment for patients with metastatic clear cell renal cell carcinoma (mCCRCC). Recently, programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) blockade emerged as promising therapy for renal cell carcinoma. However, the expression pattern and prognostic implication of programmed death-ligands (PD-Ls) in mCCRCC patients receiving VEGF-TKI remain unclear. Patients and Methods. PD-L1 and PD-L2 expression in tumor cells and the quantities of PD-1+ tumor-infiltrating lymphocytes were immunohistochemically evaluated in 91 mCCRCC patients treated with VEGF-TKI, and their associations with VEGF-TKI responsiveness and clinical outcome were analyzed. Results. PD-L1 immunopositivity was observed in 17.6% and significantly associated with a high International Society of Urological Pathology grade (p = .031) and sarcomatoid features (p = .014). PD-L2 immunopositivity was observed in 39.6% and was not associated with any of the assessed clinicopathological variables. PD-L1-positive cases showed poor VEGF-TKI responsiveness (p = .012) compared with PD-L1-negative cases. In univariate survival analysis, PD-L1 immunopositivity was significantly associated with shorter overall survival (OS) (p = .037) and progression-free survival (PFS) (p = .043). Multivariate survival analysis revealed that PD-L1 expression was independently associated with poor OS (p = .038) and PFS (p = .013) in addition to tumor necrosis (p = .006; p = .029, respectively) and Memorial Sloan Kettering Cancer Center score (p = .018; p = .032, respectively). PD-L2 expression was neither associated with VEGF-TKI responsiveness nor patients’ outcome. Conclusion. PD-L1 expression was significantly related to lack of VEGF-TKI responsiveness and independently associated with shorter survival in mCCRCC patients after VEGF-TKI treatment. PD-L1 may have a predictive and prognostic value for determining the value of VEGF-TKI treatment in patients with mCCRCC. Implications for Practice: Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are essential for the treatment of metastatic renal cell carcinoma patients, but the treatment suffers from a lack of predictive markers. This study demonstrates that PD-L1 expression is a predictor for unfavorable response to VEGF-TKI and a prognostic indicator for poor overall survival and progression-free survival in patients with metastatic clear cell renal cell carcinoma receiving VEGF-TKI. PMID:26424759

Neutrophil-to-lymphocyte ratio as a predictor of worsening renal function in diabetic patients (3-year follow-up study).

PubMed

Azab, Basem; Daoud, Jacques; Naeem, Fahad Ben; Nasr, Rabih; Ross, Jennifer; Ghimire, Pratima; Siddiqui, Ayesha; Azzi, Nadine; Rihana, Nancy; Abdallah, Marie; Azzi, Nassif; Patel, Parishram; Kleiner, Morton; El-Sayegh, Suzanne

2012-01-01

Previous studies have demonstrated the role of inflammation in diabetic nephropathy (DN). Neutrophil to lymphocyte ratio (NLR) rather than other white cell parameters was found to be a useful inflammatory marker to predict adverse outcomes in medical and surgical conditions. Nevertheless, the value of NLR in predicting DN has not been elucidated. An observational study included 338 diabetic patients, who were followed at our clinic between 2007 and 2009. We arranged our patients into tertiles according to their 2007 NLR. The primary outcome was continuous decrease of GFR >12 mL/min between 2007 and 2009 with the last GFR <60 mL/min. The lowest NLR tertile had fewer patients (2.7%) with primary outcome (i.e., worsening renal function) compared with middle and highest NLR tertiles, which had more patients with primary outcomes (8.7% and 11.5%, respectively) with a significant p-value 0.0164. When other potential confounders were individually analyzed with NLR tertile, the NLR tertiles remained a significant predictor of poor GFR outcome in the presence of other variables (hemoglobin A1C, systolic blood pressure, diastolic blood pressure, age, and congestive heart failure with p-values 0.018, 0.019, 0.017, 0.033, and 0.022, respectively). NLR predicted the worsening of the renal function in diabetic patients. Further studies are needed to confirm this result.

Procalcitonin for the early prediction of renal parenchymal involvement in children with UTI: preliminary results.

PubMed

Kotoula, Aggeliki; Gardikis, Stefanos; Tsalkidis, Aggelos; Mantadakis, Elpis; Zissimopoulos, Athanassios; Kambouri, Katerina; Deftereos, Savvas; Tripsianis, Gregorios; Manolas, Konstantinos; Chatzimichael, Athanassios; Vaos, George

2009-01-01

In order to establish the most reliable marker for distinguishing urinary tract infections (UTI) with and without renal parenchymal involvement (RPI), we recorded the clinical features and admission leukocyte count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum procalcitonin (PCT) in 57 children (including 43 girls) aged 2-108 months admitted with a first episode of UTI. RPI was evaluated by Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy within 7 days of admission. To establish cut-off points for ESR, CRP, and PCT, we used receiver operating characteristics curves and compared the area under the curve for ESR, CRP, and PCT. Twenty-seven children were diagnosed as having RPI based on positive renal scintigraphy. A body temperature of >38 degrees C, a history of diarrhea, and poor oral intake were more common in patients with RPI. ESR, CRP, and PCT, but not leukocyte count, were significantly higher in patients with RPI (P < 0.001). PCT was more sensitive and specific for the diagnosis of upper versus lower UTI than ESR and CRP. Using a cut-off value of 0.85 ng/ml, PCT had the best performance, with sensitivity, specificity, and positive and negative predictive values of 89%, 97%, 96%, and 91% respectively. Serum PCT is a better marker than ESR, CRP, and leukocyte count for the early prediction of RPI in children with a first episode of UTI.

Improved split renal function after percutaneous nephrostomy in young adults with severe hydronephrosis due to ureteropelvic junction obstruction.

PubMed

Zhang, Shiwei; Zhang, Qing; Ji, Changwei; Zhao, Xiaozhi; Liu, Guangxiang; Zhang, Shun; Li, Xiaogong; Lian, Huibo; Zhang, Gutian; Guo, Hongqian

2015-01-01

We evaluated percutaneous nephrostomy for adult kidneys with severe hydronephrosis due to ureteropelvic junction obstruction and less than 10% split renal function. In this retrospective analysis we included patients who underwent percutaneous nephrostomy for unilateral ureteropelvic junction obstruction of the kidneys with hydronephrosis and less than 10% split renal function at our hospital between May 2009 and January 2012. Adults (age 18 years or greater) were divided into those 35 years or younger (young adults) and older than 35 years (older adults). The percutaneous nephrostomy remained in situ a mean ± SD of 6.62 ± 2.55 weeks and patients underwent repeat renography before pyeloplasty. When there was no significant improvement in split renal function (10% or greater) and drainage (greater than 400 ml per day), nephrectomy was performed. Otherwise pyeloplasty was performed. Patients were followed by renography, ultrasound and contrast computerized tomography at 3 and 6 months, at 1 year and annually thereafter. Of 53 patients 30 (56.6%) showed improvement after percutaneous nephrostomy drainage and urine output greater than 400 ml per day with percutaneous nephrostomy. Pyeloplasty was then performed. Of 29 young adults 24 (82.8%) showed improved split renal function vs 6 of 24 older adults (25%). Nephrectomy of the other 23 kidneys was performed. At a mean followup of 19.27 ± 7.82 months (range 12 to 36), no patient showed hypertension or urinary tract infection. Split renal function detected by renography may not accurately predict recovered, poorly functioning kidneys, especially in young adults. First observing the recoverability of hydronephrotic kidneys by percutaneous nephrostomy drainage and then preserving select kidneys may be an effective method to manage poorly functioning kidneys due to ureteropelvic junction obstruction. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Predictors of renal and patient outcomes in anti-GBM disease: clinicopathologic analysis of a two-centre cohort.

PubMed

Alchi, Bassam; Griffiths, Meryl; Sivalingam, Murugan; Jayne, David; Farrington, Ken

2015-05-01

Patients with anti-glomerular basement membrane (GBM) disease are at increased risk of morbidity and mortality from renal failure, pulmonary haemorrhage or complications of treatment. One-third also have circulating anti-neutrophil cytoplasmic antibodies (ANCA). The aim of this study was to determine the clinicopathologic predictors of patient and renal outcomes in anti-GBM disease with or without ANCA. Retrospective review of 43 patients diagnosed with anti-GBM disease over 20 years in two centres, including nine with dual anti-GBM and ANCA positivity. Renal biopsies from 27 patients were scored for the presence of active and chronic lesions. Dual-positive patients were almost 20 years older than those with anti-GBM positivity alone (P = 0.003). The overall 1-year patient and renal survivals were 88 and 16%, respectively. Oligoanuria at diagnosis was the strongest predictor of mortality; none of the 16 patients without oligoanuria died. In a Cox regression model excluding oligoanuria, age was the only other independent predictor of survival. Pulmonary haemorrhage and dialysis dependence did not influence mortality. Thirty-five of the forty-three (81%) patients required dialysis at presentation, including all nine dual-positive patients. Of them, only two (5.7%) regained renal function at 1 year. By logistic regression, oligoanuria at diagnosis and percentage of crescents were independent predictors of dialysis independence at 3 months. However, in biopsied patients, the presence of crescents (>75%) added little to the presence of oligoanuria in predicting dialysis independence. Histological activity and chronicity indices did not predict renal outcome. Two of the nine (22%) dual-positive patients relapsed compared with none of the anti-GBM alone patients. Seven patients received kidney transplants without disease recurrence. Oligoanuria is the strongest predictor of patient and renal survival while percentage of glomerular crescents is the only pathologic parameter associated with poor renal outcome in anti-GBM disease. Kidney biopsy may not be necessary in oligoanuric patients without pulmonary haemorrhage. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Arterial spin labelling MRI for detecting pseudocapsule defects and predicting renal capsule invasion in renal cell carcinoma.

PubMed

Zhang, H; Wu, Y; Xue, W; Zuo, P; Oesingmann, N; Gan, Q; Huang, Z; Wu, M; Hu, F; Kuang, M; Song, B

2017-11-01

To evaluate prospectively the performance of combining morphological and arterial spin labelling (ASL) magnetic resonance imaging (MRI) for detecting pseudocapsule defects in renal cell carcinoma (RCC), and to predict renal capsule invasion confirmed histopathologically. Twenty consecutive patients with suspicious renal tumours underwent MRI. Renal ASL imaging was performed and renal blood flow was measured quantitatively. The diagnostic performance of T2-weighted images alone, and a combination of T2-weighted and ASL images for predicting renal capsule invasion were assessed. Twenty renal lesions were evaluated in 20 patients. All lesions were clear cell RCCs (ccRCCs) confirmed at post-surgical histopathology. Fifteen ccRCCs showed pseudocapsule defects on T2-weighted images, of which 12 cases showed existing blood flow in defect areas on perfusion images. To predict renal capsule invasion, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 71.4%, 86.7%, 100%, respectively, for T2-weighted images alone, and 92.3%, 100%, 100%, 87.5%, respectively, for the combination of T2-weighted and ASL images. ASL images can reflect the perfusion of pseudocapsule defects and as such, the combination of T2-weighted and ASL images produces promising diagnostic accuracy for predicting renal capsule invasion. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus.

PubMed

Roscioni, S S; de Zeeuw, D; Hellemons, M E; Mischak, H; Zürbig, P; Bakker, S J L; Gansevoort, R T; Reinhard, H; Persson, F; Lajer, M; Rossing, P; Lambers Heerspink, H J

2013-02-01

Microalbuminuria is considered the first clinical sign of kidney dysfunction and is associated with a poor renal and cardiovascular prognosis in type 2 diabetes. Detection of patients who are prone to develop micro- or macroalbuminuria may represent an effective strategy to start or optimise therapeutic intervention. Here we assessed the value of a urinary proteomic-based risk score (classifier) in predicting the development and progression of microalbuminuria. We conducted a prospective case-control study. Cases (n = 44) and controls (n = 44) were selected from the PREVEND (Prevention of Renal and Vascular End-stage Disease) study and from the Steno Diabetes Center (Gentofte, Denmark). Cases were defined by transition from normo- to microalbuminuria or from micro- to macroalbuminuria over a follow-up of 3 years. Controls with no transitions in albuminuria were pair-matched for age, sex and albuminuria status. A model for the progression of albuminuria was built using a proteomic classifier based on 273 urinary peptides. The proteomic classifier was independently associated with transition to micro- or macroalbuminuria (OR 1.35 [95% CI 1.02, 1.79], p = 0.035). The classifier predicted the development and progression of albuminuria on top of albuminuria and estimated GFR (eGFR, area under the receiver operating characteristic [ROC] curve increase of 0.03, p = 0.002; integrated discrimination index [IDI]: 0.105, p = 0.002). Fragments of collagen and α-2-HS-glycoprotein showed significantly different expression between cases and controls. Although limited by the relatively small sample size, these results suggest that analysis of a urinary biomarker set enables early renal risk assessment in patients with diabetes. Further work is required to confirm the role of urinary proteomics in the prevention of renal failure in diabetes.

Predicting postnatal renal function of prenatally detected posterior urethral valves using fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient determination.

PubMed

Faure, Alice; Panait, Nicoleta; Panuel, Michel; Alessandrini, Pierre; D'Ercole, Claude; Chaumoitre, Kathia; Merrot, Thierry

2017-07-01

The objective of this study was to evaluate the accuracy of fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) determination to predict postnatal renal function (nadir creatinine at 1 year and eGFR) of men with posterior urethral valves (PUV). Between 2003 and 2014, 11 MRI were performed on fetuses (between 28 and 32 weeks) in whom second trimester sonography suggested severe bilateral urinary tract anomalies, suspected of PUV. The ADC of the 11 fetuses ranged from 1.3 to 2.86 mm 2  s -1 (median = 1.79 mm 2  s -1 , normal range for fetal kidney: 1.1-1.8). Two pregnancies with ADC > 2.6 mm 2  s -1 were interrupted; the autopsy confirmed PUV and Potter syndrome. For the remaining nine babies, the follow-up was 5.4 years (0.8-10). Four children with abnormal ADC (1.8-2.3) had chronic kidney disease. The remaining five cases with normal nadir creatinine and eGFR had normal ADC. One case with unilateral elevated ADC had a poor ipsilateral renal function on dimercaptosuccinic acid scan. Here, it seems that diffusion-weighted magnetic resonance imaging with ADC determination could be useful in accurately evaluating fetal kidneys in PUV and predicting renal function. It may be an additional, non-invasive method when biologic and sonographic findings are inconclusive, especially in the case of oligohydramnios. Further studies are needed to confirm our data. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Renal arterial resistive index is associated with severe histological changes and poor renal outcome during chronic kidney disease

PubMed Central

2012-01-01

Background Chronic kidney disease (CKD) is a growing public health problem and end stage renal disease (ESRD) represents a large human and economic burden. It is important to identify patients at high risk of ESRD. In order to determine whether renal Doppler resistive index (RI) may discriminate those patients, we analyzed whether RI was associated with identified prognosis factors of CKD, in particular histological findings, and with renal outcome. Methods RI was measured in the 48 hours before renal biopsy in 58 CKD patients. Clinical and biological data were collected prospectively at inclusion. Arteriosclerosis, interstitial fibrosis and glomerulosclerosis were quantitatively assessed on renal biopsy in a blinded fashion. MDRD eGFR at 18 months was collected for 35 (60%) patients. Renal function decline was defined as a decrease in eGFR from baseline of at least 5 mL/min/ 1.73 m2/year or need for chronic renal replacement therapy. Pearson’s correlation, Mann–Whitney and Chi-square tests were used for analysis of quantitative and qualitative variables respectively. Kaplan Meier analysis was realized to determine renal survival according to RI value using the log-rank test. Multiple logistic regression was performed including variables with p < 0.20 in univariate analysis. Results Most patients had glomerulonephritis (82%). Median age was 46 years [21–87], eGFR 59 mL/min/ 1.73m2 [5–130], percentage of interstitial fibrosis 10% [0–90], glomerulosclerosis 13% [0–96] and RI 0.63 [0.31-1.00]. RI increased with age (r = 0.435, p = 0.0063), pulse pressure (r = 0.303, p = 0.022), renal atrophy (r = −0.275, p = 0.038) and renal dysfunction (r = −0.402, p = 0.0018). Patients with arterial intima/media ratio ≥ 1 (p = 0.032), interstitial fibrosis > 20% (p = 0.014) and renal function decline (p = 0.0023) had higher RI. Patients with baseline RI ≥ 0.65 had a poorer renal outcome than those with baseline RI < 0.65 (p = 0.0005). In multiple logistic regression, RI≥0.65 was associated with accelerated renal function decline independently of baseline eGFR and proteinuria/creatininuria ratio (OR=13.04 [1.984-85.727], p = 0.0075). Sensitivity, specificity, predictive positive and predictive negative values of RI ≥ 0.65 for renal function decline at 18 months were respectively 77%, 86%, 71% and 82%. Conclusions Our results suggest that RI ≥ 0.65 is associated with severe interstitial fibrosis and arteriosclerosis and renal function decline. Thus, RI may contribute to identify patients at high risk of ESRD who may benefit from nephroprotective treatments. PMID:23098365

Identification of subgroups by risk of graft failure after paediatric renal transplantation: application of survival tree models on the ESPN/ERA-EDTA Registry.

PubMed

Lofaro, Danilo; Jager, Kitty J; Abu-Hanna, Ameen; Groothoff, Jaap W; Arikoski, Pekka; Hoecker, Britta; Roussey-Kesler, Gwenaelle; Spasojević, Brankica; Verrina, Enrico; Schaefer, Franz; van Stralen, Karlijn J

2016-02-01

Identification of patient groups by risk of renal graft loss might be helpful for accurate patient counselling and clinical decision-making. Survival tree models are an alternative statistical approach to identify subgroups, offering cut-off points for covariates and an easy-to-interpret representation. Within the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data we identified paediatric patient groups with specific profiles for 5-year renal graft survival. Two analyses were performed, including (i) parameters known at time of transplantation and (ii) additional clinical measurements obtained early after transplantation. The identified subgroups were added as covariates in two survival models. The prognostic performance of the models was tested and compared with conventional Cox regression analyses. The first analysis included 5275 paediatric renal transplants. The best 5-year graft survival (90.4%) was found among patients who received a renal graft as a pre-emptive transplantation or after short-term dialysis (<45 days), whereas graft survival was poorest (51.7%) in adolescents transplanted after long-term dialysis (>2.2 years). The Cox model including both pre-transplant factors and tree subgroups had a significantly better predictive performance than conventional Cox regression (P < 0.001). In the analysis including clinical factors, graft survival ranged from 97.3% [younger patients with estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m(2) and dialysis <20 months] to 34.7% (adolescents with eGFR <60 mL/min/1.73 m(2) and dialysis >20 months). Also in this case combining tree findings and clinical factors improved the predictive performance as compared with conventional Cox model models (P < 0.0001). In conclusion, we demonstrated the tree model to be an accurate and attractive tool to predict graft failure for patients with specific characteristics. This may aid the evaluation of individual graft prognosis and thereby the design of measures to improve graft survival in the poor prognosis groups. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Predictors of Mortality in the Critically Ill Cirrhotic Patient: Is the Model for End-Stage Liver Disease Enough?

PubMed

Annamalai, Alagappan; Harada, Megan Y; Chen, Melissa; Tran, Tram; Ko, Ara; Ley, Eric J; Nuno, Miriam; Klein, Andrew; Nissen, Nicholas; Noureddin, Mazen

2017-03-01

Critically ill cirrhotics require liver transplantation urgently, but are at high risk for perioperative mortality. The Model for End-stage Liver Disease (MELD) score, recently updated to incorporate serum sodium, estimates survival probability in patients with cirrhosis, but needs additional evaluation in the critically ill. The purpose of this study was to evaluate the predictive power of ICU admission MELD scores and identify clinical risk factors associated with increased mortality. This was a retrospective review of cirrhotic patients admitted to the ICU between January 2011 and December 2014. Patients who were discharged or underwent transplantation (survivors) were compared with those who died (nonsurvivors). Demographic characteristics, admission MELD scores, and clinical risk factors were recorded. Multivariate regression was used to identify independent predictors of mortality, and measures of model performance were assessed to determine predictive accuracy. Of 276 patients who met inclusion criteria, 153 were considered survivors and 123 were nonsurvivors. Survivor and nonsurvivor cohorts had similar demographic characteristics. Nonsurvivors had increased MELD, gastrointestinal bleeding, infection, mechanical ventilation, encephalopathy, vasopressors, dialysis, renal replacement therapy, requirement of blood products, and ICU length of stay. The MELD demonstrated low predictive power (c-statistic 0.73). Multivariate analysis identified MELD score (adjusted odds ratio [AOR] = 1.05), mechanical ventilation (AOR = 4.55), vasopressors (AOR = 3.87), and continuous renal replacement therapy (AOR = 2.43) as independent predictors of mortality, with stronger predictive accuracy (c-statistic 0.87). The MELD demonstrated relatively poor predictive accuracy in critically ill patients with cirrhosis and might not be the best indicator for prognosis in the ICU population. Prognostic accuracy is significantly improved when variables indicating organ support (mechanical ventilation, vasopressors, and continuous renal replacement therapy) are included in the model. Copyright © 2016. Published by Elsevier Inc.

Urinary Angiostatin - A Novel Putative Marker of Renal Pathology Chronicity in Lupus Nephritis*

PubMed Central

Wu, Tianfu; Du, Yong; Han, Jie; Singh, Sandeep; Xie, Chun; Guo, Yuyuan; Zhou, Xin J.; Ahn, Chul; Saxena, Ramesh; Mohan, Chandra

2013-01-01

There is a critical need to identify biomarkers for Systemic Lupus Erythematosus (SLE) which has a high prevalence of renal failure. When urine from patients with lupus nephritis was recently screened for the levels of ∼280 molecules using an exploratory array-based proteomic platform, elevated angiostatin levels were noted. Angiostatin is a bioactive fragment of plasminogen, and has been known to have modulatory function in angiogenesis and inflammation. The significant elevation in urinary angiostatin was next validated in an independent cohort of SLE patients (n = 100) using ELISA. Among patients with SLE, urine angiostatin was significantly increased in active SLE compared with inactive SLE, correlating well with the SLEDAI disease activity index and SLICC renal activity score (r = 0.66, p < 0.0001). ROC curve analysis further confirmed that urinary angiostatin had the capacity to discriminate patients with active SLE from those with inactive disease. Patients with Class IV lupus nephritis exhibited the highest levels of urinary angiostatin. Immunohistochemistry staining localized angiostatin expression to the renal tubular cells in these patients. Finally, when paired urine-kidney samples procured concurrently from patients with LN were next examined, urine angiostatin levels correlated strongly with the renal pathology chronicity index, but not with the activity index. Given that Class IV lupus nephritis and renal pathology chronicity changes forebode poor renal and patient survival, urinary angiostatin emerges as a novel noninvasive marker of renal disease in SLE. Longitudinal studies are in progress to further assess the disease-predictive potential of urinary angiostatin. PMID:23345539

Inactivation of bone morphogenetic protein 2 may predict clinical outcome and poor overall survival for renal cell carcinoma through epigenetic pathways

PubMed Central

Mitsui, Yozo; Hirata, Hiroshi; Arichi, Naoko; Hiraki, Miho; Yasumoto, Hiroaki; Chang, Inik; Fukuhara, Shinichiro; Yamamura, Soichiro; Shahryari, Varahram; Deng, Guoren; Saini, Sharanjot; Majid, Shahana; Dahiya, Rajvir; Tanaka, Yuichiro; Shiina, Hiroaki

2015-01-01

We investigated whether impaired regulation of bone morphogenetic protein-2 (BMP-2) via epigenetic pathways is associated with renal cell carcinoma (RCC) pathogenesis. Expression and CpG methylation of the BMP-2 gene were analyzed using RCC cell lines, and 96 matched RCC and normal renal tissues. We also performed functional analysis using BMP-2 restored RCC cells. A significant association of BMP-2 mRNA expression was also found with advanced tumor stage and lymph node involvement, while lower BMP-2 mRNA expression was significantly associated with poor overall survival after radical nephrectomy. In RCC cells, BMP-2 restoration significantly inhibited cell proliferation, migration, invasion, and colony formation. In addition, BMP-2 overexpression induced p21WAF1/CIP1 and p27KIP1 expression, and cellular apoptosis in RCC cells. BMP-2 mRNA expression was significantly enhanced in RCC cells by 5-aza-2′-deoxycitidine treatment. The prevalence of BMP-2 promoter methylation was significantly greater and BMP-2 mRNA expression was significantly lower in RCC samples as compared to normal kidney samples. Furthermore, a significant correlation was found between BMP-2 promoter methylation and mRNA transcription in tumors. Aberrant BMP-2 methylation and the resultant loss of BMP-2 expression may be a useful molecular marker for designing improved diagnostic and therapeutic strategies for RCC. PMID:25797254

Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement.

PubMed

Córdova-Sánchez, Bertha M; Mejía-Vilet, Juan M; Morales-Buenrostro, Luis E; Loyola-Rodríguez, Georgina; Uribe-Uribe, Norma O; Correa-Rotter, Ricardo

2016-07-01

Several classification schemes have been developed for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with actual debate focusing on their clinical and prognostic performance. Sixty-two patients with renal biopsy-proven AAV from a single center in Mexico City diagnosed between 2004 and 2013 were analyzed and classified under clinical (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], renal limited vasculitis [RLV]), serological (proteinase 3 anti-neutrophil cytoplasmic antibodies [PR3-ANCA], myeloperoxidase anti-neutrophil cytoplasmic antibodies [MPO-ANCA], ANCA negative), and histopathological (focal, crescenteric, mixed-type, sclerosing) categories. Clinical presentation parameters were compared at baseline between classification groups, and the predictive value of different classification categories for disease and renal remission, relapse, renal, and patient survival was analyzed. Serological classification predicted relapse rate (PR3-ANCA hazard ratio for relapse 2.93, 1.20-7.17, p = 0.019). There were no differences in disease or renal remission, renal, or patient survival between clinical and serological categories. Histopathological classification predicted response to therapy, with a poorer renal remission rate for sclerosing group and those with less than 25 % normal glomeruli; in addition, it adequately delimited 24-month glomerular filtration rate (eGFR) evolution, but it did not predict renal nor patient survival. On multivariate models, renal replacement therapy (RRT) requirement (HR 8.07, CI 1.75-37.4, p = 0.008) and proteinuria (HR 1.49, CI 1.03-2.14, p = 0.034) at presentation predicted renal survival, while age (HR 1.10, CI 1.01-1.21, p = 0.041) and infective events during the induction phase (HR 4.72, 1.01-22.1, p = 0.049) negatively influenced patient survival. At present, ANCA-based serological classification may predict AAV relapses, but neither clinical nor serological categories predict renal or patient survival. Age, renal function and proteinuria at presentation, histopathology, and infectious complications constitute the main outcome predictors and should be considered for individualized management.

Contrast medium administration and image acquisition parameters in renal CT angiography: what radiologists need to know.

PubMed

Saade, Charbel; Deeb, Ibrahim Alsheikh; Mohamad, Maha; Al-Mohiy, Hussain; El-Merhi, Fadi

2016-01-01

Over the last decade, exponential advances in computed tomography (CT) technology have resulted in improved spatial and temporal resolution. Faster image acquisition enabled renal CT angiography to become a viable and effective noninvasive alternative in diagnosing renal vascular pathologies. However, with these advances, new challenges in contrast media administration have emerged. Poor synchronization between scanner and contrast media administration have reduced the consistency in image quality with poor spatial and contrast resolution. Comprehensive understanding of contrast media dynamics is essential in the design and implementation of contrast administration and image acquisition protocols. This review includes an overview of the parameters affecting renal artery opacification and current protocol strategies to achieve optimal image quality during renal CT angiography with iodinated contrast media, with current safety issues highlighted.

Renal failure and concurrent RAAS blockade in older CKD patients with renal artery stenosis: an extended Mayo Clinic prospective 63-month experience.

PubMed

Onuigbo, Macaulay A C; Onuigbo, Nnonyelum T C

2008-01-01

Concerns have been raised regarding a possible link between the increasing utilization of RAAS blocking strategies in the United States and the increasing ESRD epidemic. Most reports of accelerated renal failure in CKD patients with renal artery stenosis on RAAS blockade are retrospective. We hypothesized that this syndrome is therefore poorly understood, may be under-recognized, and demanded prospective analysis. As part of a larger cohort of 100 CKD patients on RAAS blockade presenting with worsening renal failure (>25% increased serum creatinine from baseline) while concurrently on an ACE inhibitor and/or an angiotensin receptor blocker, 26 patients (26%) enrolled between September 2002 and February 2005 had hemodynamically significant renal artery stenosis. RAAS blockade was discontinued, standard nephrology care applied, and eGFR by MDRD monitored. They consisted of 26 Caucasian patients, M:F = 10:16, age 75.3 +/- 6.4 (63-87) years. Mean follow-up was 26.4 +/- 16.4 (1-49) months. Duration of RAAS blockade prior to enrollment was 20.2 +/- 16.4 (0.5-48) months. Contrary to previous reports, precipitating factors were often absent (15/26), unilateral RAS lesions in patients with dual kidneys was common (19/26), and progression to ESRD was frequent (5/26). Four-fifths of the ESRD patients were dead after 5.5 +/- 4.1 (1-11) months. A fifth patient with improved eGFR died after 14 months from metastatic gastric cancer. Excluding five patients who progressed to ESRD and two patients lost early to follow-up, in 19 patients, eGFR increased from 27.8 +/- 9.5 (11-47) to 36.7 +/- 16 (14-68) mL/min/1.73 m(2) BSA (p = 0.014) after 34.8 +/- 10.1 (14-49) months of follow-up. This improvement in eGFR was evident after weeks to months of stopping RAAS blockade in these patients with and without renal PTA and stenting. Nevertheless, renal PTA/stenting further improved eGFR in selected patients. We conclude that renal failure/ESRD associated with concurrent RAAS blockade in older CKD patients with renal stenosis remains poorly understood and mostly unrecognized. Unilateral lesions in patients with dual kidneys, absent precipitating factors, and progression to ESRD with high mortality, despite discontinuation of RAAS blockade, are more common than previously thought. Lower baseline eGFR (<35) predicted ESRD. Our findings call for a larger prospective study, especially given growing concerns of iatrogenic renal failure from RAAS blockade in the aging U.S. population. An aging U.S. population further raises the probability of the presence of increasing and unrecognized renal artery stenosis in our CKD patient population.

Development of a wound healing index for patients with chronic wounds.

PubMed

Horn, Susan D; Fife, Caroline E; Smout, Randall J; Barrett, Ryan S; Thomson, Brett

2013-01-01

Randomized controlled trials in wound care generalize poorly because they exclude patients with significant comorbid conditions. Research using real-world wound care patients is hindered by lack of validated methods to stratify patients according to severity of underlying illnesses. We developed a comprehensive stratification system for patients with wounds that predicts healing likelihood. Complete medical record data on 50,967 wounds from the United States Wound Registry were assigned a clear outcome (healed, amputated, etc.). Factors known to be associated with healing were evaluated using logistic regression models. Significant variables (p < 0.05) were determined and subsequently tested on a holdout sample of data. A different model predicted healing for each wound type. Some variables predicted significantly in nearly all models: wound size, wound age, number of wounds, evidence of bioburden, tissue type exposed (Wagner grade or stage), being nonambulatory, and requiring hospitalization during the course of care. Variables significant in some models included renal failure, renal transplant, malnutrition, autoimmune disease, and cardiovascular disease. All models validated well when applied to the holdout sample. The "Wound Healing Index" can validly predict likelihood of wound healing among real-world patients and can facilitate comparative effectiveness research to identify patients needing advanced therapeutics. © 2013 by the Wound Healing Society.

Contrast medium administration and image acquisition parameters in renal CT angiography: what radiologists need to know

PubMed Central

Saade, Charbel; Deeb, Ibrahim Alsheikh; Mohamad, Maha; Al-Mohiy, Hussain; El-Merhi, Fadi

2016-01-01

Over the last decade, exponential advances in computed tomography (CT) technology have resulted in improved spatial and temporal resolution. Faster image acquisition enabled renal CT angiography to become a viable and effective noninvasive alternative in diagnosing renal vascular pathologies. However, with these advances, new challenges in contrast media administration have emerged. Poor synchronization between scanner and contrast media administration have reduced the consistency in image quality with poor spatial and contrast resolution. Comprehensive understanding of contrast media dynamics is essential in the design and implementation of contrast administration and image acquisition protocols. This review includes an overview of the parameters affecting renal artery opacification and current protocol strategies to achieve optimal image quality during renal CT angiography with iodinated contrast media, with current safety issues highlighted. PMID:26728701

Downregulation of long non-coding RNA ENSG00000241684 is associated with poor prognosis in advanced clear cell renal cell carcinoma.

PubMed

Su, Hengchuan; Wang, Hongkai; Shi, Guohai; Zhang, Hailiang; Sun, Fukang; Ye, Dingwei

2018-06-01

In order to identify potential novel biomarkers of advanced clear cell renal cell carcinoma (ccRCC), we re-evaluated published long non-coding RNA (lncRNA) expression profiling data. The lncRNA expression profiles in ccRCC microarray dataset GSE47352 were analyzed and an independent cohort of 61 clinical samples including 21 advanced and 40 localized ccRCC patients was used to confirm the most statistically significant lncRNAs by real time PCR. Next, the relationships between the selected lncRNAs and ccRCC patients' clinicopathological features were investigated. The effects of LncRNAs on the invasion and proliferation of renal carcinoma cells were also investigated. The PCR results in a cohort of 21 advanced ccRCC and 40 localized ccRCC tissues were used for confirmation of the selected lncRNAs which were statistically most significant. The PCR results showed that the expression of three LncRNA (ENSG00000241684, ENSG00000231721 and NEAT1) were significantly downregulated in advanced ccRCC. Kaplan-Meier analysis revealed that reduced expression of LncRNA ENSG00000241684 and NEAT1 were significantly associated with poor overall survival. The univariate and multivariate Cox regression indicated LncRNA ENSG00000241684 had significant hazard ratios for predicting clinical outcome. LncRNA ENSG00000241684 expression was negatively correlated with pTNM stage. Overexpression of ENSG00000241684 significantly impaired cell proliferation and reduced the invasion ability in 786-O and ACHN cells. lncRNAs are involved in renal carcinogenesis and decreased lncRNA ENSG00000241684 expression may be an independent adverse prognostic factor in advanced ccRCC patients. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Clinical types and drug therapy of renal impairment in cirrhosis

PubMed Central

Rodés, J.; Bosch, J.; Arroyo, V.

1975-01-01

Four separate types of renal failure in cirrhosis are described: functional renal failure; diuretic induced uraemia; acute tubular necrosis; chronic intrinsic renal disease. Functional renal failure may arise spontaneously or be precipitated by such factors as haemorrhage, surgery, or infection. It carries a poor prognosis but preliminary results of treating this condition with plasma volume expansion in combination with high doses of furosemide are encouraging. PMID:1234328

Can renal and bladder ultrasound replace CT urogram in patients investigated for microscopic hematuria?

PubMed

Tan, Wei Shen; Sarpong, Rachael; Khetrapal, Pramit; Rodney, Simon; Mostafid, Hugh; Cresswell, Joanne; Hicks, James; Rane, Abhay; Henderson, Alastair; Watson, Dawn; Cherian, Jacob; Williams, Norman; Brew-Graves, Chris; Feber, Andrew; Kelly, John D

2018-04-24

Computed tomography urogram (CTU) is recommended when investigating patients with hematuria. We determine the incidence of urinary tract cancer and compare the diagnostic accuracy of CTU and renal and bladder ultrasound (RBUS) at identifying urinary tract cancer. The DETECT I study (clinicaltrials.gov NCT02676180) is a prospective observational study recruiting patients ≥18 years following a presentation of macroscopic or microscopic haematuria at 40 hospitals. All patients had cystoscopy and upper tract imaging (CTU, RBUS or both). 3,556 patients with a median age of 68 years were recruited, of which 2166 had RBUS and 1692 had CTU in addition to cystoscopy. The incidence of bladder, renal and upper tract urothelial cancer (UTUC) were 11.0%, 1.4% and 0.8% respectively in macroscopic hematuria patients. Patients with microscopic hematuria had a 2.7%, 0.4% and 0% incidence of bladder, renal and UTUC respectively. The sensitivity and negative predictive value (NPV) of RBUS for the detection of renal cancer was 85.7% and 99.9% respectively but 14.3% and 99.7% for the detection of UTUC. RBUS was poor at identifying renal calculi. Sensitivity of RBUS was lower than CTU for the detection of bladder cancer (both <85%). Cystoscopy has a specificity and PPV of 98.3% and 83.9% respectively. CTU can be safely replaced with RBUS in patients with microscopic hematuria. The incidence of UTUC is 0.8% in patients with macroscopic hematuria and CTU is recommended. Patients with suspected renal calculi will require non-contrast renal tract CT. Imaging cannot replace cystoscopy to diagnose bladder cancer. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Biomarkers for acute kidney injury in decompensated cirrhosis: A Prospective Study.

PubMed

Jaques, David A; Spahr, Laurent; Berra, Gregory; Poffet, Vincent; Lescuyer, Pierre; Gerstel, Eric; Garin, Nicolas; Martin, Pierre-Yves; Ponte, Belen

2018-01-25

Acute kidney injury (AKI) is a frequent complication in cirrhotic patients. As serum creatinine is a poor marker of renal function in this population, we aimed to study the utility of several biomarkers in this context. A prospective study was conducted in hospitalized patients with decompensated cirrhosis. Serum creatinine (SCr), Cystatin C (CystC), NGAL and urinary NGAL, KIM-1, protein, albumin and sodium were measured on three separate occasions. Renal resistive index (RRI) was obtained. We analyzed the value of these biomarkers to determine the presence of AKI, its etiology [prerenal, acute tubular necrosis (ATN), or hepatorenal (HRS)], its severity and a composite clinical outcome at 30 days (death, dialysis and intensive care admission). We included 105 patients, of which 55 had AKI. SCr, CystC, NGAL (plasma and urinary), urinary sodium and RRI at inclusion were independently associated with the presence of AKI. SCr, CystC and plasma NGAL were able to predict the subsequent development of AKI. Pre-renal state showed lower levels of SCr, NGAL (plasma and urinary) and RRI. ATN patients had high levels of NGAL (plasma and urinary) as well as urinary protein and sodium. HRS patients presented an intermediate pattern. All biomarkers paralleled the severity of AKI. SCr, CystC and plasma NGAL predicted the development of the composite clinical outcome with the same performance as the MELD score. In patients with decompensated cirrhosis, early measurement of renal biomarkers provides valuable information on AKI etiology. It could also improve AKI diagnosis and prognosis. This article is protected by copyright. All rights reserved.

Heart failure and kidney dysfunction: epidemiology, mechanisms and management.

PubMed

Schefold, Joerg C; Filippatos, Gerasimos; Hasenfuss, Gerd; Anker, Stefan D; von Haehling, Stephan

2016-10-01

Heart failure (HF) is a major health-care problem and the prognosis of affected patients is poor. HF often coexists with a number of comorbidities of which declining renal function is of particular importance. A loss of glomerular filtration rate, as in acute kidney injury (AKI) or chronic kidney disease (CKD), independently predicts mortality and accelerates the overall progression of cardiovascular disease and HF. Importantly, cardiac and renal diseases interact in a complex bidirectional and interdependent manner in both acute and chronic settings. From a pathophysiological perspective, cardiac and renal diseases share a number of common pathways, including inflammatory and direct, cellular immune-mediated mechanisms; stress-mediated and (neuro)hormonal responses; metabolic and nutritional changes including bone and mineral disorder, altered haemodynamic and acid-base or fluid status; and the development of anaemia. In an effort to better understand the important crosstalk between the two organs, classifications such as the cardio-renal syndromes were developed. This classification might lead to a more precise understanding of the complex interdependent pathophysiology of cardiac and renal diseases. In light of exceptionally high mortality associated with coexisting HF and kidney disease, this Review describes important crosstalk between the heart and kidney, with a focus on HF and kidney disease in the acute and chronic settings. Underlying molecular and cellular pathomechanisms in HF, AKI and CKD are discussed in addition to current and future therapeutic approaches.

Feline chronic renal failure: clinical findings in 80 cases diagnosed between 1992 and 1995.

PubMed

Elliott, J; Barber, P J

1998-02-01

Clinical and laboratory findings at the time of first diagnosis in 80 cats with chronic renal failure (CRF) were examined in a prospective study to determine the survival time of these animals and identify possible factors contributing to the progression of feline CRF. On the basis of clinical presentation, animals were assigned to one of three groups; compensated (n = 15), uraemic (n = 39) and end-stage (n = 26) CRF. Loss of renal concentrating ability was a common finding, even before clinical signs of renal disease were evident. The plasma creatinine concentration at initial presentation was a poor predictor of survival time and the presence of significant anaemia was indicative of a poor prognosis. The study demonstrated the highly variable degree of renal impairment present at the time of diagnosis and the potentially long survival time of many compensated and uraemic cases.

Mortality in a cohort of remote-living Aboriginal Australians and associated factors.

PubMed

Hyde, Zoë; Smith, Kate; Flicker, Leon; Atkinson, David; Almeida, Osvaldo P; Lautenschlager, Nicola T; Dwyer, Anna; LoGiudice, Dina

2018-01-01

We aimed to describe mortality in a cohort of remote-living Aboriginal Australians using electronic record linkage. Between 2004 and 2006, 363 Aboriginal people living in remote Western Australia (WA) completed a questionnaire assessing medical history and behavioural risk factors. We obtained mortality records for the cohort from the WA Data Linkage System and compared them to data for the general population. We used Cox proportional hazards regression to identify predictors of mortality over a 9-year follow-up period. The leading causes of mortality were diabetes, renal failure, and ischaemic heart disease. Diabetes and renal failure accounted for 28% of all deaths. This differed from both the Australian population as a whole, and the general Indigenous Australian population. The presence of chronic disease did not predict mortality, nor did behaviours such as smoking. Only age, male sex, poor mobility, and cognitive impairment were risk factors. To reduce premature mortality, public health practitioners should prioritise the prevention and treatment of diabetes and renal disease in Aboriginal people in remote WA. This will require a sustained and holistic approach.

Mortality in a cohort of remote-living Aboriginal Australians and associated factors

PubMed Central

Hyde, Zoë; Smith, Kate; Flicker, Leon; Atkinson, David; Almeida, Osvaldo P.; Lautenschlager, Nicola T.; Dwyer, Anna

2018-01-01

Objectives We aimed to describe mortality in a cohort of remote-living Aboriginal Australians using electronic record linkage. Methods Between 2004 and 2006, 363 Aboriginal people living in remote Western Australia (WA) completed a questionnaire assessing medical history and behavioural risk factors. We obtained mortality records for the cohort from the WA Data Linkage System and compared them to data for the general population. We used Cox proportional hazards regression to identify predictors of mortality over a 9-year follow-up period. Results The leading causes of mortality were diabetes, renal failure, and ischaemic heart disease. Diabetes and renal failure accounted for 28% of all deaths. This differed from both the Australian population as a whole, and the general Indigenous Australian population. The presence of chronic disease did not predict mortality, nor did behaviours such as smoking. Only age, male sex, poor mobility, and cognitive impairment were risk factors. Conclusions To reduce premature mortality, public health practitioners should prioritise the prevention and treatment of diabetes and renal disease in Aboriginal people in remote WA. This will require a sustained and holistic approach. PMID:29621272

Renal angioplasty and stenting: is it still indicated after ASTRAL and STAR studies?

PubMed

Henry, M; Benjelloun, A; Henry, I; Polydorou, A; Hugel, M

2010-10-01

A renal artery stenosis (RAS) is common among patients with atherosclerosis, up to a third of patients undergoing cardiac catheterization. Fibromuscular dysplasia is the next cause of RAS, commonly found in young women. Atherosclerosis RAS generally progresses overtime and is often associated with loss of renal mass and worsening renal function (RF). Percutaneous renal artery stent placement is the preferred method of revascularization for hemodynamically significant RAS according to ACC and AHA guidelines. Several randomized trials have shown the superiority of endovascular procedures to medical therapy alone. However, two studies ASTRAL and STAR studies were recently published and did not find any difference between renal stenting and medical therapy. But these studies have a lot of limitations and flaws as we will discuss (poor indications, poor results, numerous complications, failures, poor technique, inexperienced operators, ecc.). Despite these questionable studies, renal stenting keeps indications in patients with: uncontrolled hypertension; ischemic nephropathy; cardiac disturbance syndrome (e.g. "flash" pulmonary edema, uncontrolled heart failure or uncontrolled angina pectoris); solitary kidney. To improve the clinical response rates, a better selection of the patients and lesions is mandatory with: good non-invasive or invasive imaging; physiologic lesion assessment using transluminal pressure gradients; measurements of biomarkers (e.g., BNP); fractional flow reserve study. A problem remains after renal angioplasty stenting, the deterioration of the RF in 20-30% of the patients. Atheroembolism seems to play an important role and is probably the main cause of this R.F deterioration. The use of protection devices alone or in combination with IIb IIa inhibitors has been proposed and seems promising as shown in different recent reports. Renal angioplasty and stenting is still indicated but we need: a better patient and lesion selection; improvements in techniques and maybe the use of protection devices to reduce the risk of RF deterioration after renal stenting.

Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy

PubMed Central

Seitz-Polski, Barbara; Dolla, Guillaume; Payré, Christine; Girard, Christophe A.; Polidori, Joel; Zorzi, Kevin; Birgy-Barelli, Eléonore; Jullien, Perrine; Courivaud, Cécile; Krummel, Thierry; Benzaken, Sylvia; Bernard, Ghislaine; Burtey, Stéphane; Mariat, Christophe; Esnault, Vincent L.M.

2016-01-01

The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR (n=23), CysRC1 (n=14), and CysRC1C7 (n=32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR–restricted activity were younger (P=0.008), had less nephrotic range proteinuria (P=0.02), and exhibited a higher rate of spontaneous remission (P=0.03) and lower rates of renal failure progression (P=0.002) and ESRD (P=0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio >4 g/g or eGFR<45 ml/min per 1.73 m2 at end of follow-up). High anti-PLA2R1 activity and epitope spreading beyond the CysR epitope were independent risk factors of poor renal prognosis in multivariable Cox regression analysis. Epitope spreading during follow-up associated with disease worsening (n=3), whereas reverse spreading from a CysRC1C7 profile back to a CysR profile associated with favorable outcome (n=1). We conclude that analysis of the PLA2R1 epitope profile and spreading is a powerful tool for monitoring disease severity and stratifying patients by renal prognosis. PMID:26567246

Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy.

PubMed

Seitz-Polski, Barbara; Dolla, Guillaume; Payré, Christine; Girard, Christophe A; Polidori, Joel; Zorzi, Kevin; Birgy-Barelli, Eléonore; Jullien, Perrine; Courivaud, Cécile; Krummel, Thierry; Benzaken, Sylvia; Bernard, Ghislaine; Burtey, Stéphane; Mariat, Christophe; Esnault, Vincent L M; Lambeau, Gérard

2016-05-01

The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR (n=23), CysRC1 (n=14), and CysRC1C7 (n=32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR-restricted activity were younger (P=0.008), had less nephrotic range proteinuria (P=0.02), and exhibited a higher rate of spontaneous remission (P=0.03) and lower rates of renal failure progression (P=0.002) and ESRD (P=0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio >4 g/g or eGFR<45 ml/min per 1.73 m(2) at end of follow-up). High anti-PLA2R1 activity and epitope spreading beyond the CysR epitope were independent risk factors of poor renal prognosis in multivariable Cox regression analysis. Epitope spreading during follow-up associated with disease worsening (n=3), whereas reverse spreading from a CysRC1C7 profile back to a CysR profile associated with favorable outcome (n=1). We conclude that analysis of the PLA2R1 epitope profile and spreading is a powerful tool for monitoring disease severity and stratifying patients by renal prognosis. Copyright © 2016 by the American Society of Nephrology.

Pain management in patients with chronic kidney disease

PubMed Central

Pham, Phuong-Chi T.; Toscano, Edgar; Pham, Phuong-Mai T.; Pham, Phuong-Anh T.; Pham, Son V.; Pham, Phuong-Thu T.

2009-01-01

Pain has been reported to be a common problem in the general population and end-stage renal disease (ESRD) patients. Although similar data for pre-ESRD patients are lacking, we recently reported that the prevalence of pain is also very high (>70%) among pre-ESRD patients at a Los Angeles County tertiary referral centre. The high prevalence of pain in the CKD population is particularly concerning because pain has been shown to be associated with poor quality of life. Of greater concern, poor quality of life, at least in dialysis patients, has been shown to be associated with poor survival. We herein discuss the pathophysiology of common pain conditions, review a commonly accepted approach to the management of pain in the general population, and discuss analgesic-induced renal complications and therapeutic issues specific for patients with reduced renal function. PMID:25949305

Can MR Measurement of Renal Artery Flow and Renal Volume Predict the Outcome of Percutaneous Transluminal Renal Angioplasty?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Binkert, Christoph A.; Debatin, Jorg F.; Schneider, Ernst

2001-07-15

Purpose: Predicting therapeutic benefit from percutaneous transluminal renal angioplasty (PTRA) in patients with renal artery stenosis (RAS) remains difficult. This study investigates whether magnetic resonance (MR)-based renal artery flow measurements relative to renal parenchymal volume can predict clinical outcome following PTRA.Methods: The data on 23 patients (13 men, 10 women; age range 47-82 years, mean age 64 years) were analyzed. The indication for treatment was hypertension (n = 18) or renal insufficiency (n = 5). Thirty-four cases of RAS were identified: bilateral disease was manifest in 11 and unilateral disease in 12 patients. The MR imaging protocol included a breath-hold,more » cardiac-gated cine phase-contrast sequence for renal flow measurement and a fast multiplanar spoiled gradient-echo sequence for renal volume measurement. MR measurements were performed on the day prior to and the day following PTRA. Clinical success was defined as (a) a reduction in diastolic blood pressure > 15% or (b) a reduction in serum creatinine > 20%. Kidneys were categorized as normal volume or low volume. A renal flow index (RFI) was calculated by dividing the renal flow (ml/min) by the renal volume (cm{sup 3}).Results: Clinical success was observed in 11 patients. Twelve patients did not benefit from angioplasty. Normal kidney volume was seen in 10 of 11 responders and in 8 of 12 nonresponders, resulting in a sensitivity of 91%, specificity of 33%, a positive predictive value (PPV) of 56% and a negative predictive value (NPV) of 80%. A RFI below a threshold of 1.5 ml/min/cm{sup 3} predicted successful outcome with 100% sensitivity, 33% specificity, 58% PPV, and 100% NPV. The combination of normal renal volume and a RFI below 1.5 ml/min/cm{sup 3} identified PTRA responders with a sensitivity of 91%, a specificity of 67%, a PPV of 71%, and a NPV of 89%. PTRA resulted in a greater increase in renal flow in responders compared with nonresponders (p < 0.001).Conclusion: A combination of cine phase-contrast MR renal flow and parenchymal volume measurements enables identification of patients benefiting from PTRA with a high sensitivity and NPV, but only moderate specificity and PPV.« less

Rhabdomyolysis case based on hypothyroidism

PubMed Central

Katipoglu, Bilal; Acehan, Fatih; Meteris, Ayşenur; Yılmaz, Nisbet

2016-01-01

Summary Hypothyroidism is a wide clinical spectrum disorder and only a few cases in literature show this. Rhabdomyolysis and acute renal impairment can be seen concurrently in a hypothyroid state. We report a case of severe hypothyroidism with poor drug compliance leading to rhabdomyolysis and acute kidney injury. Learning points: Hypothyroidism is a rare cause of acute kidney injury. In this case report, we studied a rare occurrence of acute renal impairment due to hypothyroidism with poor drug compliance, which induced rhabdomyolysis. Our report emphasized that thyroid status should be evaluated in patients with unexplained acute renal impairment or presenting with the symptoms of muscle involvement. PMID:27855234

[Doppler ultrasonography of the renal artery: Guidelines and predictive factors for the presence of a tight stenosis. Retrospective analysis of 450 consecutive examinations].

PubMed

Dejerome, C; Grange, C; De Laforcade, L; Bonin, O; Laville, M; Lermusiaux, P; Long, A

2018-05-01

Duplex ultrasonography screening for renal artery stenosis has been the object of guidelines published by four societies designed to optimize the cost-effectiveness of the examination. To determine how well guideline indications for ultrasonography matched with requests and results in our university hospital; to determine whether compliance with guidelines was predictive of renal artery stenosis; to identify guidelines predictive of presence of stenosis; and to determine whether other predictive factors can be recognized. Requests and results of 450 Duplex ultrasonography examinations of the renal arteries performed from January 1st 2014 to December 31st 2015 were compared with published guidelines. At least one guideline indication was identified for 212 of the 450 examinations performed (47.1%). Among these examinations, renal artery stenosis≥70% was identified in 18 patients (8.0%). No case of stenosis was identified during examinations performed outside guideline indications. Factors predictive of stenosis were: compliance with guidelines (OR=21.86 [2.88; 165.8]). Predictive guidelines were: resistant hypertension in spite of appropriate treatment (OR=3.85, [1.44; 10.33], P=0.011), accelerated hypertension (OR=7.30, [1.40; 37.99], P=0.049), sudden unexplained pulmonary edema (OR=7.30, [1.40; 37.99], P=0.049), unexplained renal insufficiency (OR=3.58, [1.37; 9.37], P=0.011), unexplained renal hypotrophy (OR=16.69, [4.38; 63.69], P<0.001), renal asymmetry (OR=4.32, [1.45; 12.85], P<0.016). No other factor was predictive of renal stenosis. These examinations had therapeutic consequences in only 50% of patients. This study confirms the relevance of published guidelines. The diagnostic-effectiveness of Duplex ultrasonography examinations to search for renal artery stenosis depends upon compliance with these guidelines. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Quality of sleep and health-related quality of life in renal transplant recipients.

PubMed

Liu, Hong-Xia; Lin, Jun; Lin, Xiao-Hong; Wallace, Linda; Teng, Sha; Zhang, Shu-Ping; Hao, Yu-Fang

2015-01-01

The purpose of this study was to examine the sleep quality and health-related quality of life (HRQOL) in patients after renal transplantation and to explore the relationship between the quality of sleep and the HRQOL. Sleep disorders are still an important clinical problem after renal transplantation. Previous studies mainly focused on patients' sleep quality before kidney transplant. More studies are needed to document sleep quality after renal transplantation. A cross-sectional design was used in this study. A convenience sample of renal transplant recipients was recruited at an outpatient transplant clinic of a general hospital in Beijing, China. The Pittsburgh Sleep Quality Index (PSQI) was used to measure quality of sleep. The Medical Outcomes Study 36-item Short Form (MOS SF-36) was used to measure health-related quality of life. The average PSQI score of the 204 renal transplant recipients was 5.81±3.52, significantly lower than the norm. Fifty (24.5%) recipients were classified as having poor sleep quality (global PSQI > 7). The mean scores of renal transplant recipients for SF-36 Mental Component Summary (MCS) and Physical Component Summary (PCS) were 47.57±6.71 and 48.26±9.66 respectively. Compared with residents in Sichuan province, recipients' scores for SF-36 dimensions were statistically lower except the dimension of mental health. SF-36 scores of poor sleepers (PSQI > 7) were significantly lower than the good sleepers (PSQI ≤ 7) in both the MCS and PCS. Significant differences exist between the groups in physical function, bodily pain, vitality, and mental health dimensions. Sleep quality and HRQOL of patients after renal transplantation were lower than the norm. Poor sleep is associated with lower HRQOL. Health professionals need to pay attention to sleep quality and HRQOL in renal transplant recipients and take appropriate measures to improve patients' sleep quality and HRQOL.

Is 3-compartment bioimpedance spectroscopy useful to assess body composition in renal transplant patients?

PubMed

Pellé, Gaëlle; Branche, Isabelle; Kossari, Niloufar; Tricot, Leila; Delahousse, Michel; Dreyfus, Jean-François

2013-09-01

Metabolic disorders, in particular weight gain, increase cardiovascular mortality risk and can cause serious problems after renal transplantation. Weight and body mass index are imprecise indicators of nutritional status. Accurate determination of the body composition of renal transplant patients is essential; therefore, a simple tool that allows appropriate patient monitoring is crucial. A new device, the Body Composition Monitor (BCM, Fresenius Medical Care, Bad Homburg, Germany), expresses body weight in terms of adipose tissue, lean tissue mass, and excess fluid. We compared the performance of this 3-compartment model with dual-energy X-ray absorptiometry (DEXA) as a reference method in determining body composition in a renal transplant population. Thirty-three clinically stable renal transplant patients were studied. Bland-Altman plots and Passing-Bablok regression were used to compare methods. Mean lean mass was 51.8 ± 12.3 kg with DEXA and 39.0 ± 9.9 kg with BCM. Despite the Passing-Bablok regression failing to find significant differences, the predictive value of BCM for DEXA was poor. Mean fat mass was 19.4 ± 9.7 kg with DEXA and 30.0 ± 16.0 kg with BCM. The slope of the regression line of BCM over DEXA significantly differed from 1. We conclude that, in this population, these methods cannot be substituted for one another. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Predictive abilities of cardiovascular biomarkers to rapid decline of renal function in Chinese community-dwelling population: a 5-year prospective analysis.

PubMed

Fu, Shihui; Liu, Chunling; Luo, Leiming; Ye, Ping

2017-11-09

Predictive abilities of cardiovascular biomarkers to renal function decline are more significant in Chinese community-dwelling population without glomerular filtration rate (GFR) below 60 ml/min/1.73m 2 , and long-term prospective study is an optimal choice to explore this problem. Aim of this analysis was to observe this problem during the follow-up of 5 years. In a large medical check-up program in Beijing, there were 948 participants with renal function evaluated at baseline and follow-up of 5 years. Physical examinations were performed by well-trained physicians. Blood samples were analyzed by qualified technicians in central laboratory. Median rate of renal function decline was 1.46 (0.42-2.91) mL/min/1.73m 2 /year. Rapid decline of renal function had a prevalence of 23.5% (223 participants). Multivariate linear and Logistic regression analyses confirmed that age, sex, baseline GFR, homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP) had independently predictive abilities to renal function decline rate and rapid decline of renal function (p < 0.05 for all). High-sensitivity cardiac troponin T (hs-cTnT), carotid femoral pulse wave velocity and central augmentation index had no statistically independent association with renal function decline rate and rapid decline of renal function (p > 0.05 for all). Homocysteine and NT-proBNP rather than hs-cTnT had independently predictive abilities to rapid decline of renal function in Chinese community-dwelling population without GFR below 60 ml/min/1.73m 2 . Baseline GFR was an independent factor predicting the rapid decline of renal function. Arterial stiffness and compliance had no independent effect on rapid decline of renal function. This analysis has a significant implication for public health, and changing the homocysteine and NT-proBNP levels might slow the rapid decline of renal function.

Prevalence and predictors of renal artery stenosis in patients undergoing peripheral and coronary angiography.

PubMed

Shukla, Anand N; Madan, Tarun H; Jayaram, Ashwal A; Kute, Vivek B; Rawal, Jayesh R; Manjunath, A P; Udhreja, Satyam

2013-12-01

Renal artery stenosis is a potential cause of secondary hypertension, ischemic nephropathy and end-stage renal disease. Atherosclerosis is by far the most common etiology of renal artery stenosis in elderly. We investigated whether the presence of significant atherosclerotic renal artery stenosis (ARAS) with luminal diameter narrowing ≥50 % could be predicted in patients undergoing peripheral and coronary angiography. The records of 3,500 consecutive patients undergoing simultaneous renal angiography along with peripheral and coronary angiography were reviewed. The patients with known renal artery disease were excluded. Prevalence of ARAS was 5.7 %. Significant ARAS (luminal diameter narrowing ≥50 %) was present in 139 patients (3.9 %). Hypertension with altered serum creatinine and triple-vessel CAD were associated with significant renal artery stenosis in multivariate analysis. No significant relationship between the involved coronary arteries like left anterior descending, left circumflex, right coronary artery and ARAS was found. Only hypertension and altered serum creatinine were associated with bilateral ARAS. Extent of CAD or risk factors like diabetes, hyperlipidemia or smoking did not predict the unilateral or bilateral ARAS. Prevalence of ARAS among the patients in routine cardiac catheterization was 5.7 %. Hypertension is closely associated with significant ARAS. Significant CAD in the form of triple-vessel disease and altered renal function tests are closely associated with ARAS. They predict the presence of significant renal artery stenosis in patients undergoing routine peripheral and coronary angiography. Moreover, hypertension and altered renal functions predict bilateral ARAS.

The utility of uric acid assay in dogs as an indicator of functional hepatic mass.

PubMed

Hill, J M; Leisewitz, A L; Goddard, A

2011-06-01

Uric acid was used as a test for liver disease before the advent of enzymology. Three old studies criticised uric acid as a test of liver function. Uric acid, as an end-product of purine metabolism in the liver, deserved re-evaluation as a liver function test. Serum totalbile acids are widely accepted as the most reliable liver function test. This study compared the ability of serum uric acid concentration to assess liver function with that of serum pre-prandial bile acids in dogs. In addition, due to the renal excretion of uric acid the 2 assays were also compared in a renal disease group. Using a control group of healthy dogs, a group of dogs with congenital vascular liver disease, a group of dogs with non-vascular parenchymal liver diseases and a renal disease group, the ability of uric acid and pre-prandial bile acids was compared to detect reduced functional hepatic mass overall and in the vascular or parenchymal liver disease groups separately. Sensitivities, specificities and predictive value parameters were calculated for each test. The medians of uric acid concentration did not differ significantly between any of the groups, whereas pre-prandial bile acids medians were significantly higher in the liver disease groups compared with the normal and renal disease group of dogs. The sensitivity of uric acid in detecting liver disease overall was 65% while the specificity of uric acid in detecting liver disease overall was 59%. The sensitivity and specificity of uric acid in detecting congenital vascular liver disease was 68% and 59%, respectively. The sensitivity and specificity of uric acid in detecting parenchymal liver disease was 63% and 60%, respectively. The overall positive and negative predictive values for uric acid in detecting liver disease were poor and the data in this study indicated uric acid to be an unreliable test of liver function. In dogs suffering from renal compromise serum uric acid concentrations may increase into the abnormal range due to its renal route of excretion.

Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

PubMed Central

Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-01

Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

Hair and bone as predictors of tissular mercury concentration in the western Alaska red fox, Vulpes vulpes.

PubMed

Dainowski, B H; Duffy, L K; McIntyre, J; Jones, P

2015-06-15

We evaluated if total mercury (THg) concentrations of keratin-based and bone-based tissues can predict THg concentrations in skeletal muscle, renal medulla, renal cortex, and liver. The THg concentration in matched tissues of 65 red foxes, Vulpes vulpes, from western Alaska was determined. Hair THg concentration had a significant positive correlation with liver, renal medulla, renal cortex, and muscle. The THg concentration for males and females is moderately predictive of THg concentration in the renal cortex and liver for these foxes based on R(2) values (R(2)=0.61 and 0.63, respectively). Bone is weakly predictive of THg concentration in muscle (R(2)=0.40), but not a reliable tissue to predict THg concentration in liver (R(2)=0.24), renal cortex (R(2)=0.35), or renal medulla (R(2)=0.25). These results confirm the potential use of trapped animals, specifically foxes, as useful Arctic sentinel species to inform researchers about patterns in THg levels over time as industrialization of the Arctic continues. Copyright © 2015 Elsevier B.V. All rights reserved.

Diagnostic accuracy of calculated serum osmolarity to predict dehydration in older people: adding value to pathology laboratory reports

PubMed Central

Hooper, Lee; Abdelhamid, Asmaa; Ali, Adam; Bunn, Diane K; Jennings, Amy; John, W Garry; Kerry, Susan; Lindner, Gregor; Pfortmueller, Carmen A; Sjöstrand, Fredrik; Walsh, Neil P; Fairweather-Tait, Susan J; Potter, John F; Hunter, Paul R; Shepstone, Lee

2015-01-01

Objectives To assess which osmolarity equation best predicts directly measured serum/plasma osmolality and whether its use could add value to routine blood test results through screening for dehydration in older people. Design Diagnostic accuracy study. Participants Older people (≥65 years) in 5 cohorts: Dietary Strategies for Healthy Ageing in Europe (NU-AGE, living in the community), Dehydration Recognition In our Elders (DRIE, living in residential care), Fortes (admitted to acute medical care), Sjöstrand (emergency room) or Pfortmueller cohorts (hospitalised with liver cirrhosis). Reference standard for hydration status Directly measured serum/plasma osmolality: current dehydration (serum osmolality >300 mOsm/kg), impending/current dehydration (≥295 mOsm/kg). Index tests 39 osmolarity equations calculated using serum indices from the same blood draw as directly measured osmolality. Results Across 5 cohorts 595 older people were included, of whom 19% were dehydrated (directly measured osmolality >300 mOsm/kg). Of 39 osmolarity equations, 5 showed reasonable agreement with directly measured osmolality and 3 had good predictive accuracy in subgroups with diabetes and poor renal function. Two equations were characterised by narrower limits of agreement, low levels of differential bias and good diagnostic accuracy in receiver operating characteristic plots (areas under the curve >0.8). The best equation was osmolarity=1.86×(Na++ K+)+1.15×glucose+urea+14 (all measured in mmol/L). It appeared useful in people aged ≥65 years with and without diabetes, poor renal function, dehydration, in men and women, with a range of ages, health, cognitive and functional status. Conclusions Some commonly used osmolarity equations work poorly, and should not be used. Given costs and prevalence of dehydration in older people we suggest use of the best formula by pathology laboratories using a cutpoint of 295 mOsm/L (sensitivity 85%, specificity 59%), to report dehydration risk opportunistically when serum glucose, urea and electrolytes are measured for other reasons in older adults. Trial registration numbers: DRIE: Research Register for Social Care, 122273; NU-AGE: ClinicalTrials.gov NCT01754012. PMID:26490100

Management of metastatic renal cell carcinoma patients with poor-risk features: current status and future perspectives.

PubMed

Santoni, Matteo; De Tursi, Michele; Felici, Alessandra; Lo Re, Giovanni; Ricotta, Riccardo; Ruggeri, Enzo Maria; Sabbatini, Roberto; Santini, Daniele; Vaccaro, Vanja; Milella, Michele

2013-06-01

With seven agents approved for renal cell carcinoma within the past few years, there has undoubtedly been progress in treating this disease. However, patients with poor-risk features remain a challenging and difficult-to-treat population, with the mTOR inhibitor, temsirolimus, the only agent approved in the first-line setting. Phase III trial data are still lacking VEGF-pathway inhibitors in patients with poor prognostic features. Poor-risk patients need to be considered as a heterogeneous population. Further understanding of biomarkers can lead to a better selection of patients who may benefit the most from treatment and improvements in prognosis. The presence of poor Karnofsky scores and liver or CNS disease may affect the outcome of these patients much more than other identified factors. This consideration may provide the rationale to further stratify poor-risk patients further subgroups destined to receive either cure or palliation.

Analysis of the Sensitivity and Specificity of Noninvasive Imaging Tests for the Diagnosis of Renal Artery Stenosis

PubMed Central

Borelli, Flavio Antonio de Oliveira; Pinto, Ibraim M. F.; Amodeo, Celso; Smanio, Paola E. P.; Kambara, Antonio M.; Petisco, Ana Claudia G.; Moreira, Samuel M.; Paiva, Ricardo Calil; Lopes, Hugo Belotti; Sousa, Amanda G. M. R.

2013-01-01

Background Aging and atherosclerosis are related to renovascular hypertension in elderly individuals. Regardless of comorbidities, renal artery stenosis is itself an important cause of cardiovascular morbidity and mortality. Objective To define the sensitivity, specificity, positive predictive value, and negative predictive value of noninvasive imaging tests used in the diagnosis of renal artery stenosis. Methods In a group of 61 patients recruited, 122 arteries were analized, thus permitting the definition of sensitivity, specificity, and the relative contribution of each imaging study performed (Doppler, scintigraphy and computed tomographic angiography in comparison to renal arteriography). Results The mean age was 65.43 years (standard deviation: 8.7). Of the variables related to the study population that were compared to arteriography, two correlated with renal artery stenosis, renal dysfunction and triglycerides. The median glomerular filtration rate was 52.8 mL/min/m2. Doppler showed sensitivity of 82.90%, specificity of 70%, a positive predictive value of 85% and negative predictive value of 66.70%. For tomography, sensitivity was 66.70%, specificity 80%, positive predictive value 87.50% and negative predictive value 55.20%. With these findings, we could identify the imaging tests that best detected stenosis. Conclusion Tomography and Doppler showed good quality and efficacy in the diagnosis of renal artery stenosis, with Doppler having the advantage of not requiring the use of contrast medium for the assessment of a disease that is common in diabetics and is associated with renal dysfunction and severe left ventricular dysfunction. PMID:24061685

Comparative Evaluation of Periodontal Status of Chronic Renal Failure Patients and Systemically Healthy Individuals.

PubMed

Gupta, Radhika; Kumar, Uttam; Mallapragada, Siddharth; Agarwal, Pallavi

2018-03-01

Periodontitis, a chronic infectious disease, affects most of the population at one time or the other and its expression is a combination of hosts, microbial agents, and environmental factors. Extensive literature exists for the relationship between periodontal disease and diabetes mellitus, cardiovascular diseases, and adverse pregnancy outcomes. Only a few studies performed in a limited number of patients have reported peri-odontal health status in chronic renal failure patients. Hence, the aim of the present study is to assess and compare the periodontal status of patients with chronic renal failure undergoing dialysis, predialysis with systemically healthy individuals. A total of 90 patients were divided into three groups. Group I: 30 renal dialysis patients. Group II: 30 predialysis patients. Control group comprised 30 systemically healthy patients who formed group III. Periodontal examination was carried out using oral hygiene index-simplified (OHI-S), plaque index (PI), gingival index (GI), probing depth, and clinical attachment loss. The results of the study showed that the periodontal status of patients with chronic renal failure undergoing dialysis (dialysis group) and patients with chronic renal failure not undergoing renal dialysis (predialysis) when compared with systemically healthy subjects showed significantly higher mean scores of OHI-S, PI, and clinical attachment loss. Thus, patients with chronic renal failure showed poor oral hygiene and higher prevalence of periodontal disease. The dental community's awareness of implications of poor health within chronic renal failure patients should be elevated.

Accuracy of cystatin C for the detection of abnormal renal function in children undergoing chemotherapy for malignancy: a systematic review using individual patient data.

PubMed

Whiting, Penny; Birnie, Kate; Sterne, Jonathan A C; Jameson, Catherine; Skinner, Rod; Phillips, Bob

2018-05-01

We conducted a systematic review and individual patient data (IPD) meta-analysis to examine the utility of cystatin C for evaluation of glomerular function in children with cancer. Eligible studies evaluated the accuracy of cystatin C for detecting poor renal function in children undergoing chemotherapy. Study quality was assessed using QUADAS-2. Authors of four studies shared IPD. We calculated the correlation between log cystatin C and GFR stratified by study and measure of cystatin C. We dichotomized the reference standard at GFR 80 ml/min/1.73m 2 and stratified cystatin C at 1 mg/l, to calculate sensitivity and specificity in each study and according to age group (0-4, 5-12, and ≥ 13 years). In sensitivity analyses, we investigated different GFR and cystatin C cut points. We used logistic regression to estimate the association of impaired renal function with log cystatin C and quantified diagnostic accuracy using the area under the ROC curve (AUC). Six studies, which used different test and reference standard thresholds, suggested that cystatin C has the potential to monitor renal function in children undergoing chemotherapy for malignancy. IPD data (504 samples, 209 children) showed that cystatin C has poor sensitivity (63%) and moderate specificity (89%), although use of a GFR cut point of < 60 ml/min/1.73m 2 (data only available from two of the studies) estimated sensitivity to be 92% and specificity 81.3%. The AUC for the combined data set was 0.890 (95% CI 0.826, 0.951). Diagnostic accuracy appeared to decrease with age. Cystatin C has better diagnostic accuracy than creatinine as a test for glomerular dysfunction in young people undergoing treatment for cancer. Diagnostic accuracy is not sufficient for it to replace current reference standards for predicting clinically relevant impairments that may alter dosing of important nephrotoxic agents.

Sleep disorders in kidney disease.

PubMed

De Santo, R M; Perna, A; Di Iorio, B R; Cirillo, M

2010-03-01

Sleep disorders are common in patients with end stage renal disease receiving hemodialysis or peritoneal dialysis. However also a well functioning renal graft does not cure the poor sleep pattern which now emerges as a problem even in early chronic kidney disease (CKD). When patients are made aware for the first time of a disease such as CKD, which may brink to dialysis or at the best to a renal transplant patients begin to experience a disordered sleep. Sleeping disorders include insomnia (I), sleep apnoea (SAS), restless legs syndrome (RLS), periodic limb movement disorder (PLMD), excessive daily sleeping (EDS), sleepwalking, nightmares, and narcolepsy. Disordered sleep did not meet the clinical and scientific interest it deserves, in addition and we do not have a well defined solution for sleeping complaints. However, awareness that a poor sleep is associated with poor quality of life and carries an increase in mortality risk has recently stimulated interest in the field. There are many putative causes for a disordered sleep in chronic kidney disease and in end-stage renal disease. For a unifying hypothesis demographic factors, lifestyles, disease related factors, psychological factors, treatment related factors, and social factor must be taken into consideration.

Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

PubMed

Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

2016-01-14

Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

Comparison of endopyelotomy and laparoscopic pyeloplasty for poorly functioning kidneys with ureteropelvic junction obstruction

PubMed Central

Singh, Pratipal; Kapoor, Rakesh; Suri, Amit; Singh, Kamal Jeet; Mandhani, Anil; Dubey, Deepak; Srivastava, Aneesh; Kumar, Anant

2007-01-01

Endopyelotomy and laparoscopic pyeloplasty are established procedures for ureteropelvic junction obstruction (UPJO) and historically a high failure rate has been observed in poorly functioning units with UPJ obstruction. The aim of this study is to compare the results of laparoscopic pyeloplasty with endopyelotomy in poorly functioning renal units, i.e., GFR under 25 ml/min. Materials and Methods: Retrospective analysis of all the patients who underwent either laparoscopic pyeloplasty or endopyelotomy for ureteropelvic junction obstruction in poorly functioning units between January 1998 and June 2005 was done. Follow-up renal scans, done at three, six, 12 months and yearly thereafter, were studied. Success was defined as symptomatic relief and/ or improvement in function (10% over baseline) in renal scan. Results: There were 23 patients in the endopyelotomy group and 15 patients in the laparoscopic pyeloplasty group with mean age of 25.3 years (9-53) and 26 years (10-44), respectively. Mean pelvic volume was 41.2 8cc ± 9.5 and 39.1cc ± 9.85 in the endopyelotomy group and laparoscopic pyeloplasty group, respectively. Mean preoperative GFR was 17.4 ± 5.7 ml/min and 21 ± 4.5 ml/min in the endopyelotomy group and laparoscopic pyeloplasty group, respectively and mean postoperative GFR was 21 ± 3.5 ml/min and 22 ± 3.9 ml/min, respectively. Eighteen and 11 patients were symptomatic in ethe ndopyelotomy group and laparoscopic pyeloplasty group, respectively while symptomatic improvement was seen in 14 and 11 patients, respectively. Mean follow-up was 12 months in the laparoscopy group and 28 months in the endopyelotomy group. Success rate was better for laparoscopic surgery group (15/15 = 100%) than for endopyelotomy (18/23 = 78.26%). Conclusions: Though the improvement in renal function is less in patients with UPJO with poorly functioning kidneys undergoing endopyelotomy or laparoscopic pyeloplasty, laparoscopic pyeloplasty gives better results in the form of symptomatic relief; however, renal function remains stable whichever the approach chosen. PMID:19675751

Renal rickets-practical approach

PubMed Central

Sahay, Manisha; Sahay, Rakesh

2013-01-01

Rickets/osteomalacia is an important problem in a tropical country. Many cases are due to poor vitamin D intake or calcium deficient diets and can be corrected by administration of calcium and vitamin D. However, some cases are refractory to vitamin D therapy and are related to renal defects. These include rickets of renal tubular acidosis (RTA), hypophosphatemic rickets, and vitamin D dependent rickets (VDDR). The latter is due to impaired action of 1α-hydroxylase in renal tubule. These varieties need proper diagnosis and specific treatment. PMID:24251212

A Rare Case of Renal Impairment Caused by Primary Hypothyroidism.

PubMed

Choy, Joleen; Yaxley, Julian; Yaxley, William

2018-05-01

An association between hypothyroidism and renal impairment has rarely been reported in the literature. We describe a case of hypothyroidism that was associated with otherwise unexplained acute kidney impairment, which was reversed with treatment. A 21-year-old female patient presented to her family physician with myalgia, and preliminary investigations revealed an elevated level of creatine kinase and poor renal function. Primary hypothyroidism was diagnosed and no other apparent etiology for renal failure could be identified despite extensive investigations by the Nephrology Department. Notably, the patient's renal impairment showed prompt resolution following thyroid hormone replacement.

Novel prediction model of renal function after nephrectomy from automated renal volumetry with preoperative multidetector computed tomography (MDCT).

PubMed

Isotani, Shuji; Shimoyama, Hirofumi; Yokota, Isao; Noma, Yasuhiro; Kitamura, Kousuke; China, Toshiyuki; Saito, Keisuke; Hisasue, Shin-ichi; Ide, Hisamitsu; Muto, Satoru; Yamaguchi, Raizo; Ukimura, Osamu; Gill, Inderbir S; Horie, Shigeo

2015-10-01

The predictive model of postoperative renal function may impact on planning nephrectomy. To develop the novel predictive model using combination of clinical indices with computer volumetry to measure the preserved renal cortex volume (RCV) using multidetector computed tomography (MDCT), and to prospectively validate performance of the model. Total 60 patients undergoing radical nephrectomy from 2011 to 2013 participated, including a development cohort of 39 patients and an external validation cohort of 21 patients. RCV was calculated by voxel count using software (Vincent, FUJIFILM). Renal function before and after radical nephrectomy was assessed via the estimated glomerular filtration rate (eGFR). Factors affecting postoperative eGFR were examined by regression analysis to develop the novel model for predicting postoperative eGFR with a backward elimination method. The predictive model was externally validated and the performance of the model was compared with that of the previously reported models. The postoperative eGFR value was associated with age, preoperative eGFR, preserved renal parenchymal volume (RPV), preserved RCV, % of RPV alteration, and % of RCV alteration (p < 0.01). The significant correlated variables for %eGFR alteration were %RCV preservation (r = 0.58, p < 0.01) and %RPV preservation (r = 0.54, p < 0.01). We developed our regression model as follows: postoperative eGFR = 57.87 - 0.55(age) - 15.01(body surface area) + 0.30(preoperative eGFR) + 52.92(%RCV preservation). Strong correlation was seen between postoperative eGFR and the calculated estimation model (r = 0.83; p < 0.001). The external validation cohort (n = 21) showed our model outperformed previously reported models. Combining MDCT renal volumetry and clinical indices might yield an important tool for predicting postoperative renal function.

Evidence of uncoupling between renal dysfunction and injury in cardiorenal syndrome: insights from the BIONICS study.

PubMed

Legrand, Matthieu; De Berardinis, Benedetta; Gaggin, Hanna K; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Sambhare, Rasika; Di Somma, Salvatore; Mebazaa, Alexandre; Vaidya, Vishal S; Januzzi, James L

2014-01-01

The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153).

Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

PubMed Central

Legrand, Matthieu; De Berardinis, Benedetta; Gaggin, Hanna K.; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Sambhare, Rasika; Di Somma, Salvatore; Mebazaa, Alexandre; Vaidya, Vishal S.; Januzzi, James L.; (GREAT), from the Global Research on Acute Conditions Team

2014-01-01

Objective The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). Methods In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. Results 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. Conclusions In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153). PMID:25386851

Evaluation of anatomic and morphologic nomogram to predict malignant and high-grade disease in a cohort of patients with small renal masses.

PubMed

Bagrodia, Aditya; Harrow, Brian; Liu, Zhuo-Wei; Olweny, Ephrem O; Faddegon, Stephen; Yin, Gang; Tan, Yung Khan; Han, Woong Kyu; Lotan, Yair; Margulis, Vitaly; Cadeddu, Jeffrey A

2014-01-01

To evaluate a nomogram using the RENAL Nephrometry Score (RENAL-NS) that was developed to characterize masses as benign vs. malignant and high vs. low grade in our patients with small renal masses treated with partial nephrectomy (PN). The nomogram was previously developed and validated in patients with widely variable tumor sizes. Retrospective review of PN performed between 1/2003 and 7/2011. Imaging was reviewed by a urologic surgeon for RENAL-NS. Final pathology was used to classify tumors as benign or malignant and low (I/II) or high (III/IV) Fuhrman grade. Patient age, gender, and RENAL score were entered into the nomogram described by Kutikov et al. to determine probabilities of cancer and high-grade disease. Area under the curve was determined to assess agreement between observed and expected outcomes for prediction of benign vs. malignant disease and for prediction of high- vs. low-grade or benign disease. A total of 250 patients with 252 masses underwent PN during the study period; 179/250 (71.6%) had preoperative imaging available. RENAL-NS was assigned to 181 masses. Twenty-two percent of tumors were benign. Eighteen percent of tumors were high grade. Area under the curve was 0.648 for predicting benign vs. malignant disease and 0.955 for predicting low-grade or benign vs. high-grade disease. The RENAL-NS score nomogram by Kutikov does not discriminate well between benign and malignant disease for small renal masses. The nomogram may potentially be useful in identifying high-grade tumors. Further validation is required where the nomogram probability and final pathologic specimen are available. Copyright © 2014 Elsevier Inc. All rights reserved.

Both in- and out-hospital worsening of renal function predict outcome in patients with heart failure: results from the Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH).

PubMed

Damman, Kevin; Jaarsma, Tiny; Voors, Adriaan A; Navis, Gerjan; Hillege, Hans L; van Veldhuisen, Dirk J

2009-09-01

The effect of worsening renal function (WRF) after discharge on outcome in patients with heart failure is unknown. We assessed estimated glomerular filtration rate (eGFR) and serum creatinine at admission, discharge, and 6 and 12 months after discharge, in 1023 heart failure patients. Worsening renal function was defined as an increase in serum creatinine of >26.5 micromol/L and >25%. The primary endpoint was a composite of all-cause mortality and heart failure admissions. The mean age of patients was 71 +/- 11 years, and 62% was male. Mean eGFR at admission was 55 +/- 21 mL/min/1.73 m(2). In-hospital WRF occurred in 11% of patients, while 16 and 9% experienced WRF from 0 to 6, and 6 to 12 months after discharge, respectively. In multivariate landmark analysis, WRF at any point in time was associated with a higher incidence of the primary endpoint: hazard ratio (HR) 1.63 (1.10-2.40), P = 0.014 for in-hospital WRF, HR 2.06 (1.13-3.74), P = 0.018 for WRF between 0-6 months, and HR 5.03 (2.13-11.88), P < 0.001 for WRF between 6-12 months. Both in- and out-hospital worsening of renal function are independently related to poor prognosis in patients with heart failure, suggesting that renal function in heart failure patients should be monitored long after discharge.

Stratifying risk in chronic kidney disease: an observational study of UK guidelines for measuring total proteinuria and albuminuria.

PubMed

Methven, S; Traynor, J P; Hair, M D; St J O'Reilly, D; Deighan, C J; MacGregor, M S

2011-08-01

Proteinuria predicts poor renal and cardiovascular outcomes. Some guidelines recommend measuring proteinuria using albumin:creatinine ratio (ACR), while others recommend total protein:creatinine ratio (TPCR). To compare renal outcomes and mortality in the populations identified by these different recommendations. Retrospective longitudinal cohort study. Baseline ACR and TPCR measurements were obtained from 5586 patients with chronic kidney disease (CKD) attending a Scottish hospital nephrology clinic. The cohort was divided into three groups with concordant results by ACR and TPCR (no proteinuria; low proteinuria; significant proteinuria) and one group with discordant results (significant proteinuria with TPCR, but not ACR). Outcomes were assessed using Kaplan-Meier plots and Cox proportional hazards models. Median follow-up was 3.5 years [interquartile range (IQR) 2.1-6.0]; 844 (15%) died at 3.0 years (IQR 1.8-4.7) and 468 (8%) started renal replacement therapy (RRT) at 1.7 years (IQR 0.6-3.4). Proteinuria was associated with a substantially increased risk of RRT and death. Patients with significant proteinuria by TPCR, but not ACR (n = 231) had high renal risk, and the highest all-cause mortality (log-rank P < 0.001). With multivariate analysis the risk fell below those with significant proteinuria with concordant results by ACR and TPCR but remained considerably higher than those without significant proteinuria. Proteinuria screening with TPCR identifies an additional 16% of patients with significant proteinuria, not identified using ACR. This subgroup has high renal risk, and high risk of all-cause mortality and therefore warrant identification. Guideline recommendations on proteinuria screening in CKD should be reconsidered.

Probability of reduced renal function after contrast-enhanced CT: a model based on serum creatinine level, patient age, and estimated glomerular filtration rate.

PubMed

Herts, Brian R; Schneider, Erika; Obuchowski, Nancy; Poggio, Emilio; Jain, Anil; Baker, Mark E

2009-08-01

The objectives of our study were to develop a model to predict the probability of reduced renal function after outpatient contrast-enhanced CT (CECT)--based on patient age, sex, and race and on serum creatinine level before CT or directly based on estimated glomerular filtration rate (GFR) before CT--and to determine the relationship between patients with changes in creatinine level that characterize contrast-induced nephropathy and patients with reduced GFR after CECT. Of 5,187 outpatients who underwent CECT, 963 (18.6%) had serum creatinine levels obtained within 6 months before and 4 days after CECT. The estimated GFR was calculated before and after CT using the four-variable Modification of Diet in Renal Disease (MDRD) Study equation. Pre-CT serum creatinine level, age, race, sex, and pre-CT estimated GFR were tested using multiple-variable logistic regression models to determine the probability of having an estimated GFR of < 60 and < 45 mL/min/1.73 m(2) after CECT. Two thirds of the patients were used to create and one third to test the models. We also determined discordance between patients who met standard definitions of contrast-induced nephropathy and those with a reduced estimated GFR after CECT. Significant (p < 0.002) predictors for a post-CT estimated GFR of < 60 mL/min/1.73 m(2) were age, race, sex, pre-CT serum creatinine level, and pre-CT estimated GFR. Sex, serum creatinine level, and pre-CT estimated GFR were significant factors (p < 0.001) for predicting a post-CT estimated GFR of < 45 mL/min/1.73 m(2). The probability is [exp(y) / (1 + exp(y))], where y = 6.21 - (0.10 x pre-CT estimated GFR) for an estimated GFR of < 60 mL/min/1.73 m(2), and y = 3.66 - (0.087 x pre-CT estimated GFR) for an estimated GFR of < 45 mL/min/1.73 m(2). A discrepancy between those who met contrast-induced nephropathy criteria by creatinine changes and those with a post-CT estimated GFR of < 60 mL/min/1.73 m(2) was detected in 208 of the 963 patients (21.6%). The probability of a reduced estimated GFR after CECT can be predicted by the pre-CT estimated GFR using the four-variable MDRD equation. Furthermore, standard criteria for contrast-induced nephropathy are poor predictors of poor renal function after CECT. Criteria need to be established for what is an acceptable risk to manage patients undergoing CECT.

Pretransplantation soluble CD30 level as a predictor of acute rejection in kidney transplantation: a meta-analysis.

PubMed

Chen, Yile; Tai, Qiang; Hong, Shaodong; Kong, Yuan; Shang, Yushu; Liang, Wenhua; Guo, Zhiyong; He, Xiaoshun

2012-11-15

The question of whether high pretransplantation soluble CD30 (sCD30) level can be a predictor of kidney transplant acute rejection (AR) is under debate. Herein, we performed a meta-analysis on the predictive efficacy of sCD30 for AR in renal transplantation. PubMed (1966-2012), EMBASE (1988-2012), and Web of Science (1986-2012) databases were searched for studies concerning the predictive efficacy of sCD30 for AR after kidney transplantation. After a careful review of eligible studies, sensitivity, specificity, and other measures of the accuracy of sCD30 were pooled. A summary receiver operating characteristic curve was used to represent the overall test performance. Twelve studies enrolling 2507 patients met the inclusion criteria. The pooled estimates for pretransplantation sCD30 in prediction of allograft rejection risk were poor, with a sensitivity of 0.70 (95% confidence interval (CI), 0.66-0.74), a specificity of 0.48 (95% CI, 0.46-0.50), a positive likelihood ratio of 1.35 (95% CI, 1.20-1.53), a negative likelihood ratio of 0.68 (95% CI, 0.55-0.84), and a diagnostic odds ratio of 2.07 (95% CI, 1.54-2.80). The area under curve of the summary receiver operating characteristic curve was 0.60, indicating poor overall accuracy of the serum sCD30 level in the prediction of patients at risk for AR. The results of the meta-analysis show that the accuracy of pretransplantation sCD30 for predicting posttransplantation AR was poor. Prospective studies are needed to clarify the usefulness of this test for identifying risks of AR in transplant recipients.

A classification tree for the prediction of benign versus malignant disease in patients with small renal masses.

PubMed

Rendon, Ricardo A; Mason, Ross J; Kirkland, Susan; Lawen, Joseph G; Abdolell, Mohamed

2014-08-01

To develop a classification tree for the preoperative prediction of benign versus malignant disease in patients with small renal masses. This is a retrospective study including 395 consecutive patients who underwent surgical treatment for a renal mass < 5 cm in maximum diameter between July 1st 2001 and June 30th 2010. A classification tree to predict the risk of having a benign renal mass preoperatively was developed using recursive partitioning analysis for repeated measures outcomes. Age, sex, volume on preoperative imaging, tumor location (central/peripheral), degree of endophytic component (1%-100%), and tumor axis position were used as potential predictors to develop the model. Forty-five patients (11.4%) were found to have a benign mass postoperatively. A classification tree has been developed which can predict the risk of benign disease with an accuracy of 88.9% (95% CI: 85.3 to 91.8). The significant prognostic factors in the classification tree are tumor volume, degree of endophytic component and symptoms at diagnosis. As an example of its utilization, a renal mass with a volume of < 5.67 cm3 that is < 45% endophytic has a 52.6% chance of having benign pathology. Conversely, a renal mass with a volume ≥ 5.67 cm3 that is ≥ 35% endophytic has only a 5.3% possibility of being benign. A classification tree to predict the risk of benign disease in small renal masses has been developed to aid the clinician when deciding on treatment strategies for small renal masses.

A new pathological scoring system by the Japanese classification to predict renal outcome in diabetic nephropathy.

PubMed

Hoshino, Junichi; Furuichi, Kengo; Yamanouchi, Masayuki; Mise, Koki; Sekine, Akinari; Kawada, Masahiro; Sumida, Keiichi; Hiramatsu, Rikako; Hasegawa, Eiko; Hayami, Noriko; Suwabe, Tatsuya; Sawa, Naoki; Hara, Shigeko; Fujii, Takeshi; Ohashi, Kenichi; Kitagawa, Kiyoki; Toyama, Tadashi; Shimizu, Miho; Takaichi, Kenmei; Ubara, Yoshifumi; Wada, Takashi

2018-01-01

The impact of the newly proposed pathological classification by the Japan Renal Pathology Society (JRPS) on renal outcome is unclear. So we evaluated that impact and created a new pathological scoring to predict outcome using this classification. A multicenter cohort of 493 biopsy-proven Japanese patients with diabetic nephropathy (DN) were analyzed. The association between each pathological factor-Tervaert' and JRPS classifications-and renal outcome (dialysis initiation or 50% eGFR decline) was estimated by adjusted Cox regression. The overall pathological risk score (J-score) was calculated, whereupon its predictive ability for 10-year risk of renal outcome was evaluated. The J-scores of diffuse lesion classes 2 or 3, GBM doubling class 3, presence of mesangiolysis, polar vasculosis, and arteriolar hyalinosis were, respectively, 1, 2, 4, 1, and 2. The scores of IFTA classes 1, 2, and 3 were, respectively, 3, 4, and 4, and those of interstitial inflammation classes 1, 2, and 3 were 5, 5, and 4 (J-score range, 0-19). Renal survival curves, when dividing into four J-score grades (0-5, 6-10, 11-15, and 16-19), were significantly different from each other (p<0.01, log-rank test). After adjusting clinical factors, the J-score was a significant predictor of renal outcome. Ability to predict 10-year renal outcome was improved when the J-score was added to the basic model: c-statistics from 0.661 to 0.685; category-free net reclassification improvement, 0.154 (-0.040, 0.349, p = 0.12); and integrated discrimination improvement, 0.015 (0.003, 0.028, p = 0.02). Mesangiolysis, polar vasculosis, and doubling of GBM-features of the JRPS system-were significantly associated with renal outcome. Prediction of DN patients' renal outcome was better with the J-score than without it.

Home blood pressure-guided antihypertensive therapy in chronic kidney disease: more data are needed.

PubMed

Georgianos, Panagiotis I; Champidou, Eleni; Liakopoulos, Vassilios; Balaskas, Elias V; Zebekakis, Pantelis E

2018-04-01

In the era of newly introduced hypertension guidelines recommending lower blood pressure (BP) targets for drug-treated hypertensives, the necessity for optimized management of hypertension becomes even more urgent. The concept of home BP-guided antihypertensive therapy is for long suggested as a simple and feasible approach to improve BP control rates and optimize the management of hypertension. Home BP-guided antihypertensive therapy is particularly applicable to hypertensives with chronic kidney disease (CKD) for several reasons including the following: (1) difficult-to-control BP and high BP variability in the CKD setting; (2) poor accuracy of office BP in determining hypertension control status and detecting "white-coat" and "masked" hypertension; (3) poor value of routine office BP recordings in predicting the longitudinal progression of target-organ damage; and (4) superiority of home BP over office BP recordings in prognosticating the risk of incident end-stage renal disease or death. The concept of home BP-guided antihypertensive therapy is even more relevant for those on hemodialysis, given the high intradialytic and interdialytic BP variability and poor value of conventional peridialytic BP recordings in estimating the actual BP load recorded outside of dialysis with the use of home or ambulatory BP monitoring. Randomized trials comparing home BP-guided antihypertensive therapy versus usual care are warranted to prove the feasibility and effectiveness of this therapeutic approach and convince clinicians for using home BP monitoring as the standard of care when managing hypertension, particularly in people with CKD or end-stage renal disease. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

Atherosclerotic renal artery stenosis: epidemiology, cardiovascular outcomes, and clinical prediction rules.

PubMed

Zoccali, Carmine; Mallamaci, Francesca; Finocchiaro, Pietro

2002-11-01

Atherosclerotic renal artery stenosis is the most common primary disease of the renal arteries, and it is associated with two major clinical syndromes, ischemic renal disease and hypertension. The prevalence of this disease in the population is undefined because there is no simple and reliable test that can be applied on a large scale. Renal artery involvement in patients with coronary heart disease and/or heart failure is frequent, and it may influence cardiovascular outcomes and survival in these patients. Suspecting renal arterial stenosis in patients with recurrent episodes of pulmonary edema is justified by observations showing that about one third of elderly patients with heart failure display atherosclerotic renal disease. Whether interventions aimed at restoring arterial patency may reduce the high mortality in patients with heart failure is still unclear because, to date, no prospective study has been carried out in these patients. Increased awareness of the need for cost containment has renewed the interest in clinical cues for suspecting renovascular hypertension. In this regard, the DRASTIC study constitutes an important attempt at validating clinical prediction rules. In this study, a clinical rule was derived that predicted renal artery stenosis as efficiently as renal scintigraphy (sensitivity: clinical rule, 65% versus scintigraphy, 72%; specificity: 87% versus 92%). When tested in a systematic and quantitative manner, clinical findings can perform as accurately as more complex tests in the detection of renal artery stenosis.

Aortic intimal sarcoma masquerading as bilateral renal artery stenosis.

PubMed

Sethi, Supreet; Pothineni, Naga Krishna; Syal, Gaurav; Ali, Syed Mujtaba; Krause, Michelle W

2013-01-01

Aortic intimal sarcoma is a rare tumor with poor prognosis. The most common manifestations are thromboembolic phenomena and vascular obstruction. We present a case of aortic intimal sarcoma causing bilateral renal artery stenosis which manifested as resistant hypertension and acute kidney inury. Multiple attempts to stent the renal arteries were unsuccessful. Eventually the patient developed acute limb ischemia and oliguric kidney failure as complications of the primary tumor.

Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.

PubMed

Jensen, Elisa P; Poulsen, Steen S; Kissow, Hannelouise; Holstein-Rathlou, Niels-Henrik; Deacon, Carolyn F; Jensen, Boye L; Holst, Jens J; Sorensen, Charlotte M

2015-04-15

Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats. Copyright © 2015 the American Physiological Society.

Surgery on spinal epidural metastases (SEM) in renal cell carcinoma: a plea for a new paradigm.

PubMed

Bakker, Nicolaas A; Coppes, Maarten H; Vergeer, Rob A; Kuijlen, Jos M A; Groen, Rob J M

2014-09-01

Prediction models for outcome of decompressive surgical resection of spinal epidural metastases (SEM) have in common that they have been developed for all types of SEM, irrespective of the type of primary tumor. It is our experience in clinical practice, however, that these models often fail to accurately predict outcome in the individual patient. To investigate whether decision making could be optimized by applying tumor-specific prediction models. For the proof of concept, we analyzed patients with SEM from renal cell carcinoma that we have operated on. Retrospective chart analysis 2006 to 2012. Twenty-one consecutive patients with symptomatic SEM of renal cell carcinoma. Predictive factors for survival. Next to established predictive factors for survival, we analyzed the predictive value of the Motzer criteria in these patients. The Motzer criteria comprise a specific and validated risk model for survival in patients with renal cell carcinoma. After multivariable analysis, only Motzer intermediate (hazard ratio [HR] 17.4, 95% confidence interval [CI] 1.82-166, p=.01) and high risk (HR 39.3, 95% CI 3.10-499, p=.005) turned out to be significantly associated with survival in patients with renal cell carcinoma that we have operated on. In this study, we have demonstrated that decision making could have been optimized by implementing the Motzer criteria next to established prediction models. We, therefore, suggest that in future, in patients with SEM from renal cell carcinoma, the Motzer criteria are also taken into account. Copyright © 2014 Elsevier Inc. All rights reserved.

IgA Vasculitis: Genetics and Clinical and Therapeutic Management.

PubMed

González-Gay, Miguel A; López-Mejías, Raquel; Pina, Trinitario; Blanco, Ricardo; Castañeda, Santos

2018-04-02

The purpose of the study is to perform an update on the current knowledge on genetics, clinical manifestations, and therapy in immunoglobulin A vasculitis (IgAV) (Henoch-Schönlein purpura). A strong genetic predisposition in individuals with IgAV was confirmed. It was due to the association with the HLA class II region that in people of European background is mainly related to HLA-DRB1*01 allele. Recent reports support the claim that kidney disease is more common in adults than in children with IgAV. The clinical spectrum and outcome of adults with IgAV depends on the age of onset. Relapses are not uncommon in IgAV. The presence of renal impairment or proteinuria excretion exceeding 1 g/24 h at the time of disease diagnosis and the degree of renal damage on the kidney biopsy are the best predictors of end-stage renal failure in adults with IgAV. The levels of urinary IgA at the onset of the disease may predict a poor renal outcome. The use of prednisone does not seem to prevent persistent kidney disease in children with IgAV. No additional benefit of adding cyclophosphamide to glucocorticoids in adults with IgAV was found. Rituximab seems to be a promising therapy in the management of adults with IgAV. In this overview, we focus on the genetics, clinical manifestations, and therapy of IgA vasculitis, emphasizing the main differences in the clinical expression of the disease between children and adults.

Incidence and risk factors for the metabolic syndrome and posttransplant diabetes in renal transplant recipients taking tacrolimus.

PubMed

Pérez-Flores, I; Sánchez-Fructuoso, A; Calvo, N; Valga, E F; Barrientos, A

2010-10-01

We investigated the incidence and risk factors for the metabolic syndrome (MS) and posttransplant diabetes mellitus (PTDM) among renal transplant recipients on tacrolimus-based immunosuppressive regimens during the first year posttransplant. In addition, we studied the relationship between MS and PTDM with transplant renal function at 1 year. We included the 100 patients who received a renal transplant in our unit between January 2007 and June 2008, collecting demographic, clinical and biochemical characteristics at 1, 6, and 12 months posttransplantation. We excluded 15% of patients with pretransplantation diabetes. MS was defined according to the National Cholesterol Education Program criteria and PTDM according to World Health Organization criteria. Insulin resistance at one year posttransplant was measured using the homeostasis model assessment (HOMA) index. Insulin therapy was required in 46% of patients during the first hospitalization and hyperglycemia was present in 65% of the cases. The incidence of PTDM decreased throughout the first year posttransplant, namely, 44%, 24%, and 13% at 1, 6, and 12 months, respectively. The incidence of MS increased to 33%, 48% and 50% at 1, 6, and 12 months, respectively. Age, body mass index, plasma fasting glucose levels at 1 month posttransplant, and pretransplant fasting triglyceridemia predicted PTDM. Rejection and in-patient hyperglycemia predicted MS. PTDM and MS were closely correlated (P=.004). The HOMA index was higher among patients with MS than other subjects at 1 year posttransplant: 3.2 (1.2) versus 2.3 (0.9; P=.035). Neither PTDM nor MS was associated with impaired plasma creatinine levels at 1 year after kidney transplantation. There was an high incidence of PTDM and MS among kidney transplant recipients treated with tacrolimus as the main immunosuppressive agent. The HOMA index was a good test of insulin resistance in this population. Screening and treatment of risk factors may avoid the development of these entities, which are related to poor cardiovascular outcomes. Copyright © 2010 Elsevier Inc. All rights reserved.

Furosemide/Fludrocortisone Test and Clinical Parameters to Diagnose Incomplete Distal Renal Tubular Acidosis in Kidney Stone Formers.

PubMed

Dhayat, Nasser A; Gradwell, Michael W; Pathare, Ganesh; Anderegg, Manuel; Schneider, Lisa; Luethi, David; Mattmann, Cedric; Moe, Orson W; Vogt, Bruno; Fuster, Daniel G

2017-09-07

Incomplete distal renal tubular acidosis is a well known cause of calcareous nephrolithiasis but the prevalence is unknown, mostly due to lack of accepted diagnostic tests and criteria. The ammonium chloride test is considered as gold standard for the diagnosis of incomplete distal renal tubular acidosis, but the furosemide/fludrocortisone test was recently proposed as an alternative. Because of the lack of rigorous comparative studies, the validity of the furosemide/fludrocortisone test in stone formers remains unknown. In addition, the performance of conventional, nonprovocative parameters in predicting incomplete distal renal tubular acidosis has not been studied. We conducted a prospective study in an unselected cohort of 170 stone formers that underwent sequential ammonium chloride and furosemide/fludrocortisone testing. Using the ammonium chloride test as gold standard, the prevalence of incomplete distal renal tubular acidosis was 8%. Sensitivity and specificity of the furosemide/fludrocortisone test were 77% and 85%, respectively, yielding a positive predictive value of 30% and a negative predictive value of 98%. Testing of several nonprovocative clinical parameters in the prediction of incomplete distal renal tubular acidosis revealed fasting morning urinary pH and plasma potassium as the most discriminative parameters. The combination of a fasting morning urinary threshold pH <5.3 with a plasma potassium threshold >3.8 mEq/L yielded a negative predictive value of 98% with a sensitivity of 85% and a specificity of 77% for the diagnosis of incomplete distal renal tubular acidosis. The furosemide/fludrocortisone test can be used for incomplete distal renal tubular acidosis screening in stone formers, but an abnormal furosemide/fludrocortisone test result needs confirmation by ammonium chloride testing. Our data furthermore indicate that incomplete distal renal tubular acidosis can reliably be excluded in stone formers by use of nonprovocative clinical parameters. Copyright © 2017 by the American Society of Nephrology.

APPETITE PREDICTS INTAKE AND NUTRITIONAL STATUS IN PATIENTS RECEIVING PERITONEAL DIALYSIS.

PubMed

Young, Valerie; Balaam, Sarah; Orazio, Linda; Bates, Annerley; Badve, Sunil V; Johnson, David W; Campbell, Katrina L

2016-06-01

Sub-optimal nutrition status is common amongst patients receiving peritoneal dialysis (PD) and leads to poor clinical outcome. This population experiences multi-factorial challenges to achieving optimal nutritional status, particularly driven by inadequate intake. The aim of this investigation was to identify factors associated with inadequate protein intake and sub-optimal nutritional status in patients undergoing PD. This was a cross-sectional study of 67 adult patients receiving PD (mean age 59 ± 14 years; 57% male) within a single centre. Participants were consecutively recruited and interviewed by renal dietitians, collecting: Subjective Global Assessment (SGA); quality of life (using EQ-5D); dietary intake (via dietary interview); and appetite (using Appetite and Diet Assessment Tool). Participant demographics were obtained via survey or medical charts. Main outcome measures were inadequate dietary protein intake (<1.1 g/kg adjusted body weight/day) and malnutrition (as defined by SGA rating B or C). Overall, 15 (22%) patients were malnourished and 29 (43%) had inadequate protein intake. Poor appetite (anorexia) was reported in 62% (18/29) of participants with inadequate protein malnourished patients reported anorexia versus 12 (23%) of the well-nourished patients (p = 0.0001). Anorexia was a key risk factor for inadequate protein intake and malnutrition in patients undergoing PD. These findings highlight a need to closely monitor patients with appetite disturbances. © 2016 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Low Expression of Mucin-4 Predicts Poor Prognosis in Patients With Clear-Cell Renal Cell Carcinoma

PubMed Central

Fu, Hangcheng; Liu, Yidong; Xu, Le; Chang, Yuan; Zhou, Lin; Zhang, Weijuan; Yang, Yuanfeng; Xu, Jiejie

2016-01-01

Abstract Mucin-4 (MUC4), a member of membrane-bound mucins, has been reported to exert a large variety of distinctive roles in tumorigenesis of different cancers. MUC4 is aberrantly expressed in clear-cell renal cell carcinoma (ccRCC) but its prognostic value is still unveiled. This study aims to assess the clinical significance of MUC4 expression in patients with ccRCC. The expression of MUC4 was assessed by immunohistochemistry in 198 patients with ccRCC who underwent nephrectomy retrospectively in 2003 and 2004. Sixty-seven patients died before the last follow-up in the cohort. Kaplan–Meier method with log-rank test was applied to compare survival curves. Univariate and multivariate Cox regression models were applied to evaluate the prognostic value of MUC4 expression in overall survival (OS). The predictive nomogram was constructed based on the independent prognostic factors. The calibration was built to evaluate the predictive accuracy of nomogram. In patients with ccRCC, MUC4 expression, which was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 3.891; P < 0.001), was negatively associated with tumor size (P = 0.036), Fuhrman grade (P = 0.044), and OS (P < 0.001). The prognostic accuracy of TNM stage, UCLA Integrated Scoring System (UISS), and Mayo clinic stage, size, grade, and necrosis score (SSIGN) prognostic models was improved when MUC4 expression was added. The independent prognostic factors, pT stage, distant metastases, Fuhrman grade, sarcomatoid, and MUC4 expression were integrated to establish a predictive nomogram with high predictive accuracy. MUC4 expression is an independent prognostic factor for OS in patients with ccRCC. PMID:27124015

Diagnostic accuracy of calculated serum osmolarity to predict dehydration in older people: adding value to pathology laboratory reports.

PubMed

Hooper, Lee; Abdelhamid, Asmaa; Ali, Adam; Bunn, Diane K; Jennings, Amy; John, W Garry; Kerry, Susan; Lindner, Gregor; Pfortmueller, Carmen A; Sjöstrand, Fredrik; Walsh, Neil P; Fairweather-Tait, Susan J; Potter, John F; Hunter, Paul R; Shepstone, Lee

2015-10-21

To assess which osmolarity equation best predicts directly measured serum/plasma osmolality and whether its use could add value to routine blood test results through screening for dehydration in older people. Diagnostic accuracy study. Older people (≥65 years) in 5 cohorts: Dietary Strategies for Healthy Ageing in Europe (NU-AGE, living in the community), Dehydration Recognition In our Elders (DRIE, living in residential care), Fortes (admitted to acute medical care), Sjöstrand (emergency room) or Pfortmueller cohorts (hospitalised with liver cirrhosis). Directly measured serum/plasma osmolality: current dehydration (serum osmolality>300 mOsm/kg), impending/current dehydration (≥295 mOsm/kg). 39 osmolarity equations calculated using serum indices from the same blood draw as directly measured osmolality. Across 5 cohorts 595 older people were included, of whom 19% were dehydrated (directly measured osmolality>300 mOsm/kg). Of 39 osmolarity equations, 5 showed reasonable agreement with directly measured osmolality and 3 had good predictive accuracy in subgroups with diabetes and poor renal function. Two equations were characterised by narrower limits of agreement, low levels of differential bias and good diagnostic accuracy in receiver operating characteristic plots (areas under the curve>0.8). The best equation was osmolarity=1.86×(Na++K+)+1.15×glucose+urea+14 (all measured in mmol/L). It appeared useful in people aged ≥65 years with and without diabetes, poor renal function, dehydration, in men and women, with a range of ages, health, cognitive and functional status. Some commonly used osmolarity equations work poorly, and should not be used. Given costs and prevalence of dehydration in older people we suggest use of the best formula by pathology laboratories using a cutpoint of 295 mOsm/L (sensitivity 85%, specificity 59%), to report dehydration risk opportunistically when serum glucose, urea and electrolytes are measured for other reasons in older adults. DRIE: Research Register for Social Care, 122273; NU-AGE: ClinicalTrials.gov NCT01754012. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Validation of the Lupus Nephritis Clinical Indices in Childhood-Onset Systemic Lupus Erythematosus.

PubMed

Mina, Rina; Abulaban, Khalid; Klein-Gitelman, Marisa S; Eberhard, Barbara A; Ardoin, Stacy P; Singer, Nora; Onel, Karen; Tucker, Lori; O'neil, Kathleen; Wright, Tracey; Brooks, Elizabeth; Rouster-Stevens, Kelly; Jung, Lawrence; Imundo, Lisa; Rovin, Brad; Witte, David; Ying, Jun; Brunner, Hermine I

2016-02-01

To validate clinical indices of lupus nephritis activity and damage when used in children against the criterion standard of kidney biopsy findings. In 83 children requiring kidney biopsy, the Systemic Lupus Erythematosus Disease Activity Index renal domain (SLEDAI-R), British Isles Lupus Assessment Group index renal domain (BILAG-R), Systemic Lupus International Collaborating Clinics (SLICC) renal activity score (SLICC-RAS), and SLICC Damage Index renal domain (SDI-R) were measured. Fixed effects and logistic models were calculated to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low-to-moderate versus high lupus nephritis activity (National Institutes of Health [NIH] activity index [AI]) score: ≤10 versus >10; tubulointerstitial activity index (TIAI) score: ≤5 versus >5; or the absence versus presence of lupus nephritis chronicity (NIH chronicity index) score: 0 versus ≥1. There were 10, 50, and 23 patients with ISN/RPS class I/II, III/IV, and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with lupus nephritis activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between lupus nephritis activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture lupus nephritis chronicity was 23.5% and 91.7%, respectively. Despite being designed to measure lupus nephritis activity, SLICC-RAS and SLEDAI-R scores significantly differed with lupus nephritis chronicity status. Current clinical indices of lupus nephritis fail to discriminate ISN/RPS class in children. Despite its shortcomings, the SLEDAI-R appears best for measuring lupus nephritis activity in a clinical setting. The SDI-R is a poor correlate of lupus nephritis chronicity. © 2016, American College of Rheumatology.

Validation of the Lupus Nephritis Clinical Indices in Childhood-Onset Systemic Lupus Erythematosus

PubMed Central

Mina, Rina; Abulaban, Khalid; Klein-Gitelman, Marisa; Eberhard, Anne; Ardoin, Stacy; Singer, Nora; Onel, Karen; Tucker, Lori; O’Neil, Kathleen; Wright, Tracey; Brooks, Elizabeth; Rouster-Stevens, Kelly; Jung, Lawrence; Imundo, Lisa; Rovin, Brad; Witte, David; Ying, Jun; Brunner, Hermine I.

2015-01-01

Objective To validate clinical indices of lupus nephritis (LN) activity and damage when used in children against the criterion standard of kidney biopsy findings. Methods In 83 children requiring kidney biopsy the SLE Disease Activity Index Renal Domain (SLEDAI-R); British Isles Lupus Assessment Group index Renal Domain (BILAG-R), Systemic Lupus International Collaborating Clinics Renal Activity (SLICC-RAS) and Damage Index Renal Domain (SDI-R) were measured. Fixed effect and logistic models were done to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low/moderate vs. high LN-activity [NIH Activity Index (NIH-AI) score: ≤ 10 vs. > 10; Tubulointerstitial Activity Index (TIAI) score: ≤ 5 vs. > 5) or the absence vs. presence of LN chronicity [NIH Chronicity Index (NIH-CI) score: 0 vs. ≥ 1]. Results There were 10, 50 and 23 patients with class I/II, III/IV and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with LN-activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between LN-activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture LN chronicity was 23.5% and 91.7%, respectively. Despite designed to measure LN-activity, SLICC-RAS and SLEDAI-R scores significantly differed with LN chronicity status. Conclusion Current clinical indices of LN fail to discriminate ISN/RPS Class in children. Despite its shortcomings, the SLEDAI-R appears to best for measuring LN activity in a clinical setting. The SDI-R is a poor correlate of LN chronicity. PMID:26213987

Versican Promotes Tumor Progression, Metastasis and Predicts Poor Prognosis in Renal Carcinoma.

PubMed

Mitsui, Yozo; Shiina, Hiroaki; Kato, Taku; Maekawa, Shigekatsu; Hashimoto, Yutaka; Shiina, Marisa; Imai-Sumida, Mitsuho; Kulkarni, Priyanka; Dasgupta, Pritha; Wong, Ryan Kenji; Hiraki, Miho; Arichi, Naoko; Fukuhara, Shinichiro; Yamamura, Soichiro; Majid, Shahana; Saini, Sharanjot; Deng, Guoren; Dahiya, Rajvir; Nakajima, Koichi; Tanaka, Yuichiro

2017-07-01

The proteoglycan versican (VCAN) promotes tumor progression and enhances metastasis in several cancers; however, its role in clear cell renal cell carcinoma (ccRCC) remains unknown. Recent evidence suggests that VCAN is an important target of chromosomal 5q gain, one of the most prevalent genetic abnormalities in ccRCC. Thus, we investigated whether VCAN expression is associated with the pathogenesis of ccRCC. VCAN expression was analyzed using three RCC and normal kidney cell lines as well as a clinical cohort of 84 matched ccRCC and normal renal tissues. Functional analyses on growth and progression properties were performed using VCAN-depleted ccRCC cells. Microarray expression profiling was employed to investigate the target genes and biologic pathways involved in VCAN-mediated ccRCC carcinogenesis. ccRCC had elevated VCAN expression in comparison with normal kidney in both cell lines and clinical specimens. The elevated expression of VCAN was significantly correlated with metastasis ( P < 0.001) and worse 5-year overall survival after radical nephrectomy ( P = 0.014). In vitro , VCAN knockdown significantly decreased cell proliferation and increased apoptosis in Caki-2 and 786-O cells, and this was associated with alteration of several TNF signaling-related genes such as TNFα, BID , and BAK Furthermore, VCAN depletion markedly decreased cell migration and invasion which correlated with reduction of MMP7 and CXCR4. These results demonstrate that VCAN promotes ccRCC tumorigenesis and metastasis and thus is an attractive target for novel diagnostic, prognostic, and therapeutic strategies. Implications: This study highlights the oncogenic role of VCAN in renal cell carcinogenesis and suggests that this gene has therapeutic and/or biomarker potential for renal cell cancer. Mol Cancer Res; 15(7); 884-95. ©2017 AACR . ©2017 American Association for Cancer Research.

Utility of the RENAL index -Radius; Exophytic/endophytic; Nearness to sinus; Anterior/posterior; Location relative to polar lines- in the management of renal masses.

PubMed

Konstantinidis, C; Trilla, E; Lorente, D; Morote, J

2016-12-01

The growing incidence of renal masses and the wide range of available treatments require predictive tools that support the decision making process. The RENAL index -Radius; Exophytic/endophytic; Nearness to sinus; Anterior/posterior; Location relative to polar lines- helps standardise the anatomy of a renal mass by differentiating 3 groups of complexity. Since the introduction of the index, there have been a growing number of studies, some of which have been conflicting, that have evaluated the clinical utility of its implementation. To analyse the scientific evidence on the relationship between the RENAL index and the main strategies for managing renal masses. A search was conducted in the Medline database, which found 576 references on the RENAL index. In keeping with the PRISM Declaration, we selected 100 abstracts and ultimately reviewed 96 articles. The RENAL index has a high degree of interobserver correlation and has been validated as a predictive nomogram of histological results. In active surveillance, the index has been related to the tumour growth rate and probability of nephrectomy. In ablative therapy, the index has been associated with therapeutic efficacy, complications and tumour recurrence. In partial nephrectomy, the index has been related to the rate of complications, conversion to radical surgery, ischaemia time, function preservation and tumour recurrence, a finding also observed in radical nephrectomy. The RENAL index is an objective, reproducible and useful system as a predictive tool of highly relevant clinical parameters such as the rate of complications, ischaemia time, renal function and oncological results in the various currently accepted treatments for the management of renal masses. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

A retrospective analysis of laparoscopic partial nephrectomy with segmental renal artery clamping and factors that predict postoperative renal function.

PubMed

Li, Pu; Qin, Chao; Cao, Qiang; Li, Jie; Lv, Qiang; Meng, Xiaoxin; Ju, Xiaobing; Tang, Lijun; Shao, Pengfei

2016-10-01

To evaluate the feasibility and efficiency of laparoscopic partial nephrectomy (LPN) with segmental renal artery clamping, and to analyse the factors affecting postoperative renal function. We conducted a retrospective analysis of 466 consecutive patients undergoing LPN using main renal artery clamping (group A, n = 152) or segmental artery clamping (group B, n = 314) between September 2007 and July 2015 in our department. Blood loss, operating time, warm ischaemia time (WIT) and renal function were compared between groups. Univariable and multivariable linear regression analyses were applied to assess the correlations of selected variables with postoperative glomerular filtration rate (GFR) reduction. Volumetric data and estimated GFR of a subset of 60 patients in group B were compared with GFR to evaluate the correlation between these functional variables and preserved renal function after LPN. The novel technique slightly increased operating time, WIT and intra-operative blood loss (P < 0.001), while it provided better postoperative renal function (P < 0.001) compared with the conventional technique. The blocking method and tumour characteristics were independent factors affecting GFR reduction, while WIT was not an independent factor. Correlation analysis showed that estimated GFR presented better correlation with GFR compared with kidney volume (R(2) = 0.794 cf. R(2) = 0.199) in predicting renal function after LPN. LPN with segmental artery clamping minimizes warm ischaemia injury and provides better early postoperative renal function compared with clamping the main renal artery. Kidney volume has a significantly inferior role compared with eGFR in predicting preserved renal function. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Renal Artery Embolization - A First Line Treatment Option For End-Stage Hydronephrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitra, Kakali; Prabhudesai, Vikramaditya; James, R. Lester

Conventionally poorly functioning hydronephrotic kidneys have been removed if they are symptomatic. In our unit, patients are offered renal artery embolization as an alternative treatment option. Patients and Methods: Fifteen patients (11 male, 4 female) with a mean age of 32.9 yr (20-51 yrs) have undergone renal artery embolization for symptomatic hydronephrosis with poor function. Mean follow-up was 64.13 weeks (range 14-200). All patients had loin pain and hydronephrosis. Twelve patients had primary pelvi-ureteric junction obstruction (PUJO). Two patients had poorly functioning hydronephrotic kidneys secondary to chronic calculous obstruction. One patient had chronic pain in an obstructed but reasonably functioningmore » kidney following a previous pyeloplasty for PUJO which demanded intervention. Mean split function on renography was 11% (range 0-46%). Selective renal artery embolization was carried out under antibiotic cover using a 7 Fr balloon occlusion catheter and absolute alcohol, steel coils, and polyvinyl alcohol particles.Results: Nine patients developed post-embolization syndrome of self-limiting pain and pyrexia with no evidence of sepsis. One patient required readmission with this condition. One patient developed a hematoma at the puncture site. Mean hospital stay was 2.3 days. Fourteen patients are happy with the result and are completely pain free. One patient has minor discomfort but is delighted with the result. Nine patients have had follow-up ultrasound confirming resolution of the hydronephrosis. Conclusion: Renal artery embolization is an effective, safe, well-tolerated minimally invasive treatment option in end-stage hydronephrosis and we routinely offer it as an alternative to nephrectomy.« less

Serum cystatin C concentration measured routinely is a prognostic marker for renal disease in dogs.

PubMed

Iwasa, Naoki; Takashima, Satoshi; Iwasa, Tatsuo; Iwasa, Kazuko; Suzuki, Tomomi; Kobatake, Yui; Kitagawa, Hitoshi; Nishii, Naohito

2018-06-14

This study examined the predictive value of serum cystatin C (Cys-C) concentration, measured during routine periodic health examinations, in the renal prognosis of dogs. A cohort of 140 dogs weighing <15 kg whose serum Cys-C concentrations were measured during periodic health examinations from December 2013 to March 2016 were prospectively studied, with renal disease-related death the predicted end point. Of the 140 dogs, nine died from renal diseases during the follow-up period (539 ± 249 days). Serum Cys-C concentrations were higher in the dogs that subsequently died of renal disease than in the censored group (0.8 ± 0.25 vs. 0.3 ± 0.1 mg/dl, respectively; P < .01). Dogs with high serum Cys-C concentrations (>0.55 mg/dl) had a shorter (P < .01) renal disease-specific survival period than those with low serum Cys-C concentrations (≤0.55 mg/dl). In conclusion, high serum Cys-C concentrations in periodic health examinations in dogs <15 kg predicted poorer prognosis for renal function. Copyright © 2018. Published by Elsevier Ltd.

Renal Interstitial Arteriosclerotic Lesions in Lupus Nephritis Patients: A Cohort Study from China

PubMed Central

Qin, Dan-dan; Wu, Li-hua; Song, Yan; Yu, Feng; Wang, Su-xia; Liu, Gang; Zhao, Ming-hui

2015-01-01

Objective The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their associations with clinical and pathological characteristics, especially cardio-vascular features. Design A retrospective cohort study. Participants Seventy-nine patients with renal biopsy-proven lupus nephritis, diagnosed between January 2000 and June 2008 from Peking University First Hospital. Results In clinico-pathological data, patients with arteriosclerosis had higher ratio of hypertension and more severe renal injury indices compared with patients with no renal vascular lesions. More importantly, patients with renal arteriosclerosis had worse cardiac structure and function under transthoracic echocardiographic examination. Patients with renal arteriosclerosis tend to have higher ratios of combined endpoints compared with those of no renal vascular lesions, although the difference didn’t reach statistical meanings (P = 0.104). Conclusion Renal arteriosclerotic lesion was common and associated with vascular immune complex deposits in lupus nephritis. It might have a certain degree of association with poor outcomes and cardiovascular events, which needs further explorations. PMID:26544865

[Predictive factors of all-cause mortality in patients attending the medical emergency unit of Kinshasa University Hospital].

PubMed

Mbutiwi Ikwa Ndol, F; Dramaix-Wilmet, M; Meert, P; Lepira Bompeka, F; Nseka Mangani, N; Malengreau, M; Makaula, P

2014-02-01

The management of medical emergencies is poorly organized in the Democratic Republic of Congo. In addition, the mortality of patients attending the medical emergency unit of Kinshasa University Hospital is relatively high, with death of patients occurring rather early. To date, factors associated with this mortality have been poorly elucidated. This study aimed to identify predictive factors of all-cause mortality in patients admitted to the medical emergency unit of the Kinshasa University Hospital. Analytical prospective study of all patients admitted from 15th January to 15th February 2011 in the emergency unit of the internal medicine department of Kinshasa University Hospital (427 patients). Among these patients, 13 were dead at arrival and were excluded from this study. The 414 patients included were followed until discharge from the hospital. Demographic, clinical, biological, diagnostic, therapeutical and evolutive data were collected. Four multivariate logistic regression models were used to identify risk factors associated with mortality. Patients' median age was 40 years (interquartile range, 28-58 years), 54.5% were male, and 15.9% had a life-threatening pathological condition on admission. The overall mortality was 12.3%. According to multivariate analyses, transfer from other health care structures (OR: 3.5; 95% CI: 1.7-7.1), Glasgow Coma Scale score less than 14 on admission (OR: 11.1; 95% CI: 4.7-26.3), high creatinine level (OR: 4.2; 95% CI: 1.8-9.7), presence of cardiovascular (OR: 2.9; 95% CI: 1.5-5.7), renal (OR: 7.4; 95% CI: 3.2-17.3), hematologic and/or respiratory (OR: 6.1; 95% CI: 1.7-21.4) diseases, presence of sepsis and/or meningitis and encephalitis (OR: 5.2; 95% CI: 1.6-17.0) were significantly associated with a high risk of death. However, the Glasgow Coma Scale score less than 14 on admission and renal disease were the only predictive factors of mortality remaining after including demographic, clinical, diagnostic and therapeutical variables in the logistic regression model. Our study showed that transfer from another health care structure, low Glasgow Coma Scale score on admission, high creatinine level, cardiovascular, renal, hematologic and/or respiratory diseases, sepsis and/or meningitis and encephalitis were associated with an increased risk of death in Kinshasa University Hospital patients admitted in the medical emergency unit. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

A pseudo-three-dimensional model for quantification of oxygen diffusion from preglomerular arteries to renal tissue and renal venous blood.

PubMed

Lee, Chang-Joon; Ngo, Jennifer P; Kar, Saptarshi; Gardiner, Bruce S; Evans, Roger G; Smith, David W

2017-08-01

To assess the physiological significance of arterial-to-venous (AV) oxygen shunting, we generated a new pseudo-three-dimensional computational model of oxygen diffusion from intrarenal arteries to cortical tissue and veins. The model combines the 11 branching levels (known as "Strahler" orders) of the preglomerular renal vasculature in the rat, with an analysis of an extensive data set obtained using light microscopy to estimate oxygen mass transfer coefficients for each Strahler order. Furthermore, the AV shunting model is now set within a global oxygen transport model that includes transport from arteries, glomeruli, peritubular capillaries, and veins to tissue. While a number of lines of evidence suggest AV shunting is significant, most importantly, our AV oxygen shunting model predicts AV shunting is small under normal physiological conditions (~0.9% of total renal oxygen delivery; range 0.4-1.4%), but increases during renal ischemia, glomerular hyperfiltration (~2.1% of total renal oxygen delivery; range 0.84-3.36%), and some cardiovascular disease states (~3.0% of total renal oxygen delivery; range 1.2-4.8%). Under normal physiological conditions, blood Po 2 is predicted to fall by ~16 mmHg from the root of the renal artery to glomerular entry, with AV oxygen shunting contributing ~40% and oxygen diffusion from arteries to tissue contributing ~60% of this decline. Arterial Po 2 is predicted to fall most rapidly from Strahler order 4 , under normal physiological conditions. We conclude that AV oxygen shunting normally has only a small impact on renal oxygenation, but may exacerbate renal hypoxia during renal ischemia, hyperfiltration, and some cardiovascular disease states. Copyright © 2017 the American Physiological Society.

Evaluation of the quality and health literacy demand of online renal diet information.

PubMed

Lambert, K; Mullan, J; Mansfield, K; Koukomous, A; Mesiti, L

2017-10-01

Dietary modification is critical in the self-management of chronic kidney disease. The present study describes the accuracy, quality and health literacy demand of renal diet information for adults with kidney disease obtained from the Internet and YouTube (www.youtube.com). A comprehensive content analysis was undertaken in April and July 2015 of 254 eligible websites and 161 YouTube videos. The accuracy of the renal diet information was evaluated by comparing the key messages with relevant evidence-based guidelines for the dietary management of people with kidney disease. The DISCERN tool (www.discern.org.uk) was used to evaluate the quality of the material. Health literacy demand was evaluated using the Patient Education Material Assessment Tool (www.ahrq.gov/professionals/prevention-chronic-care/improve/self-mgmt/pemat/index.html) and seven validated readability calculators. The most frequent renal diet topic found online was generic dietary information for people with chronic kidney disease. The proportion of renal diet information obtained from websites that was accurate was 73%. However, this information was mostly of poor quality with extensive shortcomings, difficult to action and written with a high health literacy demand. By contrast, renal diet information available from YouTube was highly understandable and actionable, although only 18% of the videos were accurate, and a large proportion were of poor quality with extensive shortcomings. The most frequent authors of accurate, good quality, understandable, material were government bodies, dietitians, academic institutions and medical organisations. Renal diet information found online that is written by government bodies, dietitians, academic institutions and medical organisations is recommended. Further work is required to improve the quality and, most importantly, the actionability of renal diet information found online. © 2017 The British Dietetic Association Ltd.

Fludrocortisone therapy for persistent hyperkalaemia.

PubMed

Dobbin, S J H; Petrie, J R; Lean, M E J; McKay, G A

2017-07-01

Type 4 renal tubular acidosis causes hyperkalaemia, for which diabetes and medications commonly used in this patient group are aetiological factors. Here we describe the novel use of fludrocortisone in this difficult condition. A 55-year-old woman with complex co-morbidities, including Type 2 diabetes (HbA 1c 37 mmol/mol 5.5%), was admitted with renal failure. Bloods on admission: eGFR 25 ml/min, creatinine 184 ?mol/L, urea 35.9 mmol/L, sodium 128 mmol/L, potassium 5.6 mmol/L, bicarbonate 15 mmol/L, and albumin 30 g/L. Her admission was prolonged, complicated by hospital-acquired sepsis (lower respiratory tract, urinary tract, and infected leg ulcers), poor venous access and severe depression. She had recurrent hyperkalaemia and deteriorating renal function, from presumed Type 4 renal tubular acidosis and excessive fluid losses from leg ulcers. Her renal function recurrently deteriorated, despite conventional treatment methods. After 69 days, she was commenced on fludrocortisone 50 mcg/day. Her renal function and serum potassium stabilized and she was discharged with potassium 4.3 mmol/L, eGFR 42 ml/min, and bicarbonate 23 mmol/L. She has remained stable on this treatment, without requiring further hospital admission for over 6 months, with eGFR 40 ml/min, and potassium 5.5 mmol/L, and albumin 26 g/L. This woman was presumed to have Type 4 renal tubular acidosis and recurrent hyperkalaemia due to renal insufficiency, in the context of underlying diabetes and chronic kidney disease, which was poorly responsive to conventional management. There is limited evidence for using fludrocortisone in this setting. Our case suggests that fludrocortisone might offer a novel therapeutic strategy when conventional management is not working. © 2017 Diabetes UK.

Hilar fat infiltration: A new prognostic factor in metastatic clear cell renal cell carcinoma with first-line sunitinib treatment.

PubMed

Kammerer-Jacquet, Solène-Florence; Brunot, Angelique; Bensalah, Karim; Campillo-Gimenez, Boris; Lefort, Mathilde; Bayat, Sahar; Ravaud, Alain; Dupuis, Frantz; Yacoub, Mokrane; Verhoest, Gregory; Peyronnet, Benoit; Mathieu, Romain; Lespagnol, Alexandra; Mosser, Jean; Edeline, Julien; Laguerre, Brigitte; Bernhard, Jean-Christophe; Rioux-Leclercq, Nathalie

2017-10-01

The selection of patients with metastatic clear cell renal cell carcinoma (ccRCC) who may benefit from targeted tyrosine kinase inhibitors has been a challenge, even more so now with the advent of new therapies. Hilar fat infiltration (HFI) is a validated prognostic factor in nonmetastatic ccRCC (TNM 2009 staging system) but has never been studied in metastatic patients. We aimed to assess its phenotype and prognostic effect in patients with metastatic ccRCC treated with first-line sunitinib. In a multicentric study, we retrospectively included 90 patients and studied the corresponding ccRCC at the pathological, immunohistochemical, and molecular levels. Patient and tumor characteristics were compared using univariate and multivariate analysis. All the features were then studied by Cox models for prognostic effect. HFI was found in 42 patients (46.7%), who had worse prognosis (Heng criteria) (P = 0.003), liver metastases (P = 0.036), and progressive diseases at first radiological evaluation (P = 0.024). The corresponding ccRCC was associated with poor pathological prognostic factors that are well known in nonmetastatic ccRCC. For these patients, median progression-free survival was 4 months vs. 13 months (P = 0.02), and median overall survival was 14 months vs. 29 months (P = 0.006). In a multivariate Cox model integrating all the variables, only poor prognosis, according to the Heng criteria and HFI, remained independently associated with both progression-free survival and overall survival. HFI was demonstrated for the first time to be an independent poor prognostic factor. Its potential role in predicting resistance to antiangiogenic therapy warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Prediction of the effect of atrasentan on renal and heart failure outcomes based on short-term changes in multiple risk markers.

PubMed

Schievink, Bauke; de Zeeuw, Dick; Smink, Paul A; Andress, Dennis; Brennan, John J; Coll, Blai; Correa-Rotter, Ricardo; Hou, Fan Fan; Kohan, Donald; Kitzman, Dalane W; Makino, Hirofumi; Parving, Hans-Henrik; Perkovic, Vlado; Remuzzi, Giuseppe; Tobe, Sheldon; Toto, Robert; Hoekman, Jarno; Lambers Heerspink, Hiddo J

2016-05-01

A recent phase II clinical trial (Reducing Residual Albuminuria in Subjects with Diabetes and Nephropathy with AtRasentan trial and an identical trial in Japan (RADAR/JAPAN)) showed that the endothelin A receptor antagonist atrasentan lowers albuminuria, blood pressure, cholesterol, hemoglobin, and increases body weight in patients with type 2 diabetes and nephropathy. We previously developed an algorithm, the Parameter Response Efficacy (PRE) score, which translates short-term drug effects into predictions of long-term effects on clinical outcomes. We used the PRE score on data from the RADAR/JAPAN study to predict the effect of atrasentan on renal and heart failure outcomes. We performed a post-hoc analysis of the RADAR/JAPAN randomized clinical trials in which 211 patients with type-2 diabetes and nephropathy were randomly assigned to atrasentan 0.75 mg/day, 1.25 mg/day, or placebo. A PRE score was developed in a background set of completed clinical trials using multivariate Cox models. The score was applied to baseline and week-12 risk marker levels of RADAR/JAPAN participants, to predict atrasentan effects on clinical outcomes. Outcomes were defined as doubling serum creatinine or end-stage renal disease and hospitalization for heart failure. The PRE score predicted renal risk changes of -23% and -30% for atrasentan 0.75 and 1.25 mg/day, respectively. PRE scores also predicted a small non-significant increase in heart failure risk for atrasentan 0.75 and 1.25 mg/day (+2% vs. +7%). Selecting patients with >30% albuminuria reduction from baseline (responders) improved renal outcome to almost 50% risk reduction, whereas non-responders showed no renal benefit. Based on the RADAR/JAPAN study, with short-term changes in risk markers, atrasentan is expected to decrease renal risk without increased risk of heart failure. Within this population albuminuria responders appear to contribute to the predicted improvements, whereas non-responders showed no benefit. The ongoing hard outcome trial (SONAR) in type 2 diabetic patients with >30% albuminuria reduction to atrasentan will allow us to assess the validity of these predictions. © The European Society of Cardiology 2015.

Urinary C‑X‑C motif chemokine 13 is a noninvasive biomarker of antibody‑mediated renal allograft rejection.

PubMed

Chen, Dajin; Zhang, Jian; Peng, Wenhan; Weng, Chunhua; Chen, Jianghua

2018-06-22

Noninvasive monitoring methods of immune status are preferred by transplant recipients. The present study investigated whether urinary C‑X‑C motif chemokine 13 (CXCL13) had the potential to reflect ongoing immune processes within renal allografts. Using an ELISA assay, the level of urinary CXCL13 was quantified in a total of 146 renal allograft recipients and 40 healthy controls at scheduled intervals and at the time of the indicated or protocol biopsy. The results of the present study revealed that urinary CXCL13/creatinine (Cr) was lower in normal transplants compared with in those with acute tubular necrosis (ATN; P=0.001), chronic allograft nephropathy (CAN; P=0.01), and acute rejection (AR; P<0.0001), which was associated with a good diagnostic performance for AR [area under the curve (AUC)=0.818, P<0.0001). In addition, urinary CXCL13/Cr levels in patients with AR were also higher than that of patients with graft dysfunction but no rejection, including ATN and CAN (P=0.034). Notably, urinary CXCL13 distinguished between acute antibody‑mediated rejection (ABMR) and acute cellular rejection, with an AUC of 0.856. Furthermore, patients with steroid‑resistant AR exhibited significantly increased urinary CXCL13/Cr levels than patients with reversible AR (P=0.001). Additionally, elevated levels of urinary CXCL13/Cr within the first month of transplant were predictive of graft function at 3 and 6 months (P=0.044 and P=0.04, respectively). Collectively, the findings of the present study indicated that the noninvasive investigation of urinary CXCL13/Cr may be valuable for the detection of AR, particularly ABMR. In addition, high urinary CXCL13/Cr levels predicted a poor response to steroid treatment and compromised graft function.

Computerized tomography with 3-dimensional reconstruction for the evaluation of renal size and arterial anatomy in the living kidney donor.

PubMed

Janoff, Daniel M; Davol, Patrick; Hazzard, James; Lemmers, Michael J; Paduch, Darius A; Barry, John M

2004-01-01

Computerized tomography (CT) with 3-dimensional (3-D) reconstruction has gained acceptance as an imaging study to evaluate living renal donors. We report our experience with this technique in 199 consecutive patients to validate its predictions of arterial anatomy and kidney volumes. Between January 1997 and March 2002, 199 living donor nephrectomies were performed at our institution using an open technique. During the operation arterial anatomy was recorded as well as kidney weight in 98 patients and displacement volume in 27. Each donor had been evaluated preoperatively by CT angiography with 3-D reconstruction. Arterial anatomy described by a staff radiologist was compared with intraoperative findings. CT estimated volumes were reported. Linear correlation graphs were generated to assess the reliability of CT volume predictions. The accuracy of CT angiography for predicting arterial anatomy was 90.5%. However, as the number of renal arteries increased, predictive accuracy decreased. The ability of CT to predict multiple arteries remained high with a positive predictive value of 95.2%. Calculated CT volume and kidney weight significantly correlated (0.654). However, the coefficient of variation index (how much average CT volume differed from measured intraoperative volume) was 17.8%. CT angiography with 3-D reconstruction accurately predicts arterial vasculature in more than 90% of patients and it can be used to compare renal volumes. However, accuracy decreases with multiple renal arteries and volume comparisons may be inaccurate when the difference in kidney volumes is within 17.8%.

[Osteomyelitis and papillary renal adenoma in a red panda (Ailurus fulgens fulgens)].

PubMed

Kummerfeld, M; Knieriem, A; Wohlsein, P

2008-11-01

A 13 year-old female Red Panda (Ailurus fulgens fulgens) kept in a zoological garden was euthanatized due to poor general condition. Pathological examination revealed a chronic bacterial ulcerative to necrotizing dermatitis and osteomyelitis at the lower jaw with subsequent pyogranulomatous pneumonia and diffuse hydropic degeneration of the liver. Additionally, in the kidney a papillary renal adenoma was found. Immunohistochemistry revealed an expression of cytokeratins 8 and/or 19 indicating an origin from the renal tubular epithelium.

Renal complications of lipodystrophy: A closer look at the natural history of kidney disease.

PubMed

Akinci, Baris; Unlu, Sadiye Mehtat; Celik, Ali; Simsir, Ilgin Yildirim; Sen, Sait; Nur, Banu; Keskin, Fatma Ela; Ozgen Saydam, Basak; Kutbay Ozdemir, Nilufer; Sarer Yurekli, Banu; Ergur, Bekir Ugur; Sonmez, Melda; Atik, Tahir; Arslan, Atakan; Demir, Tevfik; Altay, Canan; Tunc, Ulku Aybuke; Arkan, Tugba; Gen, Ramazan; Eren, Erdal; Akinci, Gulcin; Yilmaz, Aslihan Arasli; Bilen, Habib; Ozen, Samim; Celtik, Aygul; Savas Erdeve, Senay; Cetinkaya, Semra; Onay, Huseyin; Sarioglu, Sulen; Oral, Elif Arioglu

2018-07-01

Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports. In this multicentre study, prospective follow-up data were collected from 103 subjects with non-HIV-associated lipodystrophy registered in the Turkish Lipodystrophy Study Group database to study renal complications in treatment naïve patients with lipodystrophy. Main outcome measures included ascertainment of chronic kidney disease (CKD) by studying the level of proteinuria and the estimated glomerular filtration rate (eGFR). Kidney volume was measured. Percutaneous renal biopsies were performed in 9 patients. Seventeen of 37 patients with generalized and 29 of 66 patients with partial lipodystrophy had CKD characterized by proteinuria, of those 12 progressed to renal failure subsequently. The onset of renal complications was significantly earlier in patients with generalized lipodystrophy. Patients with CKD were older and more insulin resistant and had worse metabolic control. Increased kidney volume was associated with poor metabolic control and suppressed leptin levels. Renal biopsies revealed thickening of glomerular basal membranes, mesangial matrix abnormalities, podocyte injury, focal segmental sclerosis, ischaemic changes and tubular abnormalities at various levels. Lipid vacuoles were visualized in electron microscopy images. CKD is conspicuously frequent in patients with lipodystrophy which has an early onset. Renal involvement appears multifactorial. While poorly controlled diabetes caused by severe insulin resistance may drive the disease in some cases, inherent underlying genetic defects may also lead to cell autonomous mechanisms contributory to the pathogenesis of kidney disease. © 2018 John Wiley & Sons Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valdez, V.A.; Jacobstein, J.G.

Bone scans were performed with Tc-99m stannous polyphosphate on four patients with thalassemia major. Three of the scans show generalized decrease in skeletal uptake of the radiopharmaceutical, associated with renal enlargement and markedly increased renal radioactivity. The skeletal findings are consistent with the known bone abnormalities in thalassemia major, which are secondary to the extensive marrow hyperplasia and include loss of trabeculae and cortical thinning with consequent loss of bone mass. The increased renal uptake is probably due in part to the increased renal excretion (secondary to the poor bone uptake) and in part to the tubular dilatation and renalmore » enlargement associated with thalassemia major. In addition, the presence of excessive amounts of iron in these patients may play a role in both the skeletal and renal findings.« less

Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in Relation to Renal Function Over Time: Insights From the ARISTOTLE Randomized Clinical Trial.

PubMed

Hijazi, Ziad; Hohnloser, Stefan H; Andersson, Ulrika; Alexander, John H; Hanna, Michael; Keltai, Matyas; Parkhomenko, Alexander; López-Sendón, José L; Lopes, Renato D; Siegbahn, Agneta; Granger, Christopher B; Wallentin, Lars

2016-07-01

Renal impairment confers an increased risk of stroke, bleeding, and death in patients with atrial fibrillation. Little is known about the efficacy and safety of apixaban in relation to renal function changes over time. To evaluate changes of renal function over time and their interactions with outcomes during a median of 1.8 years of follow-up in patients with atrial fibrillation randomized to apixaban vs warfarin treatment. The prospective, randomized, double-blind Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) clinical trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Serial creatinine measurements were available in 16 869 patients. Worsening of renal function was defined as an annual decrease in estimated glomerular filtration more than 20%. The relations between treatment, outcomes, and renal function were investigated using Cox regression models, with renal function as a time-dependent covariate. Stroke or systemic embolism (primary outcome), major bleeding (safety outcome), and mortality were examined in relation to renal function over time estimated with both the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration equations. Among 16 869 patients, the median age was 70 years and 65.2% of patients were men. Worsening in estimated glomerular filtration more than 20% was observed in 2294 patients (13.6%) and was associated with older age and more cardiovascular comorbidities. The risks of stroke or systemic embolism, major bleeding, and mortality were higher in patients with worsening renal function (HR, 1.53; 95% CI, 1.17-2.01 for stroke or systemic embolism; HR, 1.56; 95% CI, 1.27-1.93 for major bleeding; and HR, 2.31; 95% CI, 1.98-2.68 for mortality). The beneficial effects of apixaban vs warfarin on rates of stroke or systemic embolism and major bleeding were consistent in patients with normal or poor renal function over time and also in those with worsening renal function. In patients with atrial fibrillation, declining renal function was more common in elderly patients and those with cardiovascular comorbidities. Worsening renal function was associated with a higher risk of subsequent cardiovascular events and bleeding. The superior efficacy and safety of apixaban as compared with warfarin were similar in patients with normal, poor, and worsening renal function. clinicaltrials.gov Identifier: NCT00412984.

Diagnostic Performance of CT for Diagnosis of Fat-Poor Angiomyolipoma in Patients With Renal Masses: A Systematic Review and Meta-Analysis.

PubMed

Woo, Sungmin; Suh, Chong Hyun; Cho, Jeong Yeon; Kim, Sang Youn; Kim, Seung Hyup

2017-11-01

The purpose of this article is to systematically review and perform a meta-analysis of the diagnostic performance of CT for diagnosis of fat-poor angiomyolipoma (AML) in patients with renal masses. MEDLINE and EMBASE were systematically searched up to February 2, 2017. We included diagnostic accuracy studies that used CT for diagnosis of fat-poor AML in patients with renal masses, using pathologic examination as the reference standard. Two independent reviewers assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity of included studies were calculated and were pooled and plotted in a hierarchic summary ROC plot. Sensitivity analyses using several clinically relevant covariates were performed to explore heterogeneity. Fifteen studies (2258 patients) were included. Pooled sensitivity and specificity were 0.67 (95% CI, 0.48-0.81) and 0.97 (95% CI, 0.89-0.99), respectively. Substantial and considerable heterogeneity was present with regard to sensitivity and specificity (I 2 = 91.21% and 78.53%, respectively). At sensitivity analyses, the specificity estimates were comparable and consistently high across all subgroups (0.93-1.00), but sensitivity estimates showed significant variation (0.14-0.82). Studies using pixel distribution analysis (n = 3) showed substantially lower sensitivity estimates (0.14; 95% CI, 0.04-0.40) compared with the remaining 12 studies (0.81; 95% CI, 0.76-0.85). CT shows moderate sensitivity and excellent specificity for diagnosis of fat-poor AML in patients with renal masses. When methods other than pixel distribution analysis are used, better sensitivity can be achieved.

Influence of CT-based depth correction of renal scintigraphy in evaluation of living kidney donors on side selection and postoperative renal function: is it necessary to know the relative renal function?

PubMed

Weinberger, Sarah; Klarholz-Pevere, Carola; Liefeldt, Lutz; Baeder, Michael; Steckhan, Nico; Friedersdorff, Frank

2018-03-22

To analyse the influence of CT-based depth correction in the assessment of split renal function in potential living kidney donors. In 116 consecutive living kidney donors preoperative split renal function was assessed using the CT-based depth correction. Influence on donor side selection and postoperative renal function of the living kidney donors were analyzed. Linear regression analysis was performed to identify predictors of postoperative renal function. A left versus right kidney depth variation of more than 1 cm was found in 40/114 donors (35%). 11 patients (10%) had a difference of more than 5% in relative renal function after depth correction. Kidney depth variation and changes in relative renal function after depth correction would have had influence on side selection in 30 of 114 living kidney donors. CT depth correction did not improve the predictability of postoperative renal function of the living kidney donor. In general, it was not possible to predict the postoperative renal function from preoperative total and relative renal function. In multivariate linear regression analysis, age and BMI were identified as most important predictors for postoperative renal function of the living kidney donors. Our results clearly indicate that concerning the postoperative renal function of living kidney donors, the relative renal function of the donated kidney seems to be less important than other factors. A multimodal assessment with consideration of all available results including kidney size, location of the kidney and split renal function remains necessary.

Functional genomic analysis identifies indoxyl sulfate as a major, poorly dialyzable uremic toxin in end-stage renal disease.

PubMed

Jhawar, Sachin; Singh, Prabhjot; Torres, Daniel; Ramirez-Valle, Francisco; Kassem, Hania; Banerjee, Trina; Dolgalev, Igor; Heguy, Adriana; Zavadil, Jiri; Lowenstein, Jerome

2015-01-01

Chronic renal failure is characterized by progressive renal scarring and accelerated arteriosclerotic cardiovascular disease despite what is considered to be adequate hemodialysis or peritoneal dialysis. In rodents with reduced renal mass, renal scarring has been attributed to poorly filtered, small protein-bound molecules. The best studied of these is indoxyl sulfate (IS). We have attempted to establish whether there are uremic toxins that are not effectively removed by hemodialysis. We examined plasma from patients undergoing hemodialysis, employing global gene expression in normal human renal cortical cells incubated in pre- and post- dialysis plasma as a reporter system. Responses in cells incubated with pre- and post-dialysis uremic plasma (n = 10) were compared with responses elicited by plasma from control subjects (n = 5). The effects of adding IS to control plasma and of adding probenecid to uremic plasma were examined. Plasma concentrations of IS were measured by HPLC (high pressure liquid chromatography). Gene expression in our reporter system revealed dysregulation of 1912 genes in cells incubated with pre-dialysis uremic plasma. In cells incubated in post-dialysis plasma, the expression of 537 of those genes returned to baseline but the majority of them (1375) remained dysregulated. IS concentration was markedly elevated in pre- and post-dialysis plasma. Addition of IS to control plasma simulated more than 80% of the effects of uremic plasma on gene expression; the addition of probenecid, an organic anion transport (OAT) inhibitor, to uremic plasma reversed the changes in gene expression. These findings provide evidence that hemodialysis fails to effectively clear one or more solutes that effect gene expression, in our reporter system, from the plasma of patients with uremia. The finding that gene dysregulation was simulated by the addition of IS to control plasma and inhibited by addition of an OAT inhibitor to uremic plasma identifies IS as a major, poorly dialyzable, uremic toxin. The signaling pathways initiated by IS and possibly other solutes not effectively removed by dialysis may participate in the pathogenesis of renal scarring and uremic vasculopathy.

Acute renal infarction: Clinical characteristics and prognostic factors.

PubMed

Caravaca-Fontán, Fernando; Pampa Saico, Saúl; Elías Triviño, Sandra; Galeano Álvarez, Cristina; Gomis Couto, Antonio; Pecharromán de las Heras, Inés; Liaño, Fernando

2016-01-01

Acute renal infarction (ARI) is an uncommon disease, whose real incidence is probably higher than expected. It is associated with poor prognosis in a high percentage of cases. To describe the main clinical, biochemical and radiologic features and to determine which factors are associated with poor prognosis (death or permanent renal injury). The following is a retrospective, observational, single-hospital-based study. All patients diagnosed with ARI by contrast-enhanced computed tomography (CT) over an 18-year period were included. Patients were classified according to the cardiac or non-cardiac origin of their disease. Clinical, biochemical and radiologic features were analysed, and multiple logistic regression model was used to determine factors associated with poor prognosis. A total of 62 patients were included, 30 of which had a cardiac origin. Other 32 patients with non-cardiac ARI were younger, had less comorbidity, and were less frequently treated with oral anticoagulants. CT scans estimated mean injury extension at 35%, with no differences observed between groups. A total of 38% of patients had an unfavourable outcome, and the main determinants were: Initial renal function (OR=0.949; IC 95% 0.918-0.980; p=0.002), and previous treatment with oral anticoagulants (OR=0.135; IC 95% 0.032-0.565; p=0.006). ARI is a rare pathology with non-specific symptoms, and it is not associated with cardiological disease or arrhythmias in more than half of cases. A substantial proportion of patients have unfavourable outcomes, and the initial renal function is one of the main prognostic factors. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

[Assisted peritoneal dialysis: home-based renal replacement therapy for the elderly patient].

PubMed

Wiesholzer, Martin

2013-06-01

The number of elderly patients with end stage renal disease is constantly increasing. Conventional hämodiaylsis as the mainstay of renal replacement therapy is often poorly tolerated by frail eldery patients with multiple comorbidities. Although many of these patients would prefer a home based dialysis treatment, the number of elderly patients using peritoneal dialysis (PD) is still low. Impaired physical and cognitive function often generates insurmountable barriers for self care peritoneal dialysis. Assisted peritoneal dialysis can overcome many of these barriers and give elderly patients the ability of a renal replacement therapy in their own homes respecting their needs.

Two-year analysis for predicting renal function and contralateral hypertrophy after robot-assisted partial nephrectomy: A three-dimensional segmentation technology study.

PubMed

Kim, Dae Keun; Jang, Yujin; Lee, Jaeseon; Hong, Helen; Kim, Ki Hong; Shin, Tae Young; Jung, Dae Chul; Choi, Young Deuk; Rha, Koon Ho

2015-12-01

To analyze long-term changes in both kidneys, and to predict renal function and contralateral hypertrophy after robot-assisted partial nephrectomy. A total of 62 patients underwent robot-assisted partial nephrectomy, and renal parenchymal volume was calculated using three-dimensional semi-automatic segmentation technology. Patients were evaluated within 1 month preoperatively, and postoperatively at 6 months, 1 year and continued up to 2-year follow up. Linear regression models were used to identify the factors predicting variables that correlated with estimated glomerular filtration rate changes and contralateral hypertrophy 2 years after robot-assisted partial nephrectomy. The median global estimated glomerular filtration rate changes were -10.4%, -11.9%, and -2.4% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The ipsilateral kidney median parenchymal volume changes were -24%, -24.4%, and -21% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The contralateral renal volume changes were 2.3%, 9.6% and 12.9%, respectively. On multivariable linear analysis, preoperative estimated glomerular filtration rate was the best predictive factor for global estimated glomerular filtration rate change on 2 years post-robot-assisted partial nephrectomy (B -0.452; 95% confidence interval -0.84 to -0.14; P = 0.021), whereas the parenchymal volume loss rate (B -0.43; 95% confidence interval -0.89 to -0.15; P = 0.017) and tumor size (B 5.154; 95% confidence interval -0.11 to 9.98; P = 0.041) were the significant predictive factors for the degree of contralateral renal hypertrophy on 2 years post-robot-assisted partial nephrectomy. Preoperative estimated glomerular filtration rate significantly affects post-robot-assisted partial nephrectomy renal function. Renal mass size and renal parenchyma volume loss correlates with compensatory hypertrophy of the contralateral kidney. Contralateral hypertrophy of the renal parenchyma compensates for the functional loss of the ipsilateral kidney. © 2015 The Japanese Urological Association.

Predictors of dietary and fluid non-adherence in Jordanian patients with end-stage renal disease receiving haemodialysis: a cross-sectional study.

PubMed

Khalil, Amani A; Darawad, Muhammad; Al Gamal, Eklas; Hamdan-Mansour, Ayman M; Abed, Mona A

2013-01-01

The purpose of this study is to provide insight into the relationship between dietary and fluid non-adherence, depressive symptoms, quality of life, perceived barriers and benefits of exercise, and perceived social support among Jordanian patients with end-stage renal disease receiving haemodialysis using Pender's health promotion model. Non-adherence to dietary and fluid restrictions is a leading cause of treatment failure and poor outcomes in end-stage renal disease. Yet, factors that interfere with the patients' ability to follow their dietary restrictions are unknown. A descriptive, correlational, cross-sectional design was used. Jordanian patients (n = 190) with end-stage renal disease receiving haemodialysis from three main Jordanian cities were included. The dialysis diet and fluid nonadherence questionnaire, Beck Depression Inventory-II, Quality Of Life Index, Dialysis Patient-Perceived Exercise Benefits and Barriers Scale, and the Multidimensional Perceived Social Support were employed to measure the key variables. Patients were more likely men with mean age of 48·2 ± 14·9. Only 27% of the patients showed full commitment to diet guidelines and 23% to fluid guidelines during the last 14 days. Depression (M = 18·8 ± 11·4) had significant negative association with quality of life (importance and satisfaction) (r = -0·60, r = -0·32, p = 0·001, respectively). Multiple hierarchal regressions revealed a predictive model of only two variables: age (B = -0·22, p = 0·05) and residual renal function (B = -0·23, p = 0·012) for dietary non-adherence. Non-adherence to diet and fluid guidelines association with individual characteristics, health perception and psychosocial variables should be investigated in a longitudinal design. Relationship of non-adherence with culture-related factors should deeply be assessed among Jordanian patients with end-stage renal disease receiving haemodialysis. Identification of the factors that may worsen dietary and fluid non-adherence may lead to improved therapeutic interventions within the mainstream of medical practice for Jordanian patients with end-stage renal disease receiving haemodialysis. © 2012 Blackwell Publishing Ltd.

Predictors of Recoverability of Renal Function after Pyeloplasty in Adults with Ureteropelvic Junction Obstruction.

PubMed

Li, Xiao-Dong; Wu, Yu-Peng; Wei, Yong; Chen, Shao-Hao; Zheng, Qing-Shui; Cai, Hai; Xue, Xue-Yi; Xu, Ning

2018-01-01

This study aimed to identify factors predicting the recoverability of renal function after pyeloplasty in adult patients with ureteropelvic junction obstruction. We retrospectively reviewed 138 adults with unilateral renal obstruction-induced hydronephrosis and who underwent Anderson-Hynes dismembered pyeloplasty from January 2013 to January 2016. Hydronephrosis was classified preoperatively according to the Society for Fetal Urology (SFU) grading system. All patients underwent Doppler ultrasonography, excretory urography, computed tomography, and technetium-99m-diethylenetriamine pentaacetic acid radioisotope (99mTc DTPA) renography before and after surgery. Renal resistive index (RRI) and 99mTc DTPA renography were repeated at 1, 3, 6, and 12 months. Multivariate analysis identified age, renal pelvic type, SFU grade, preoperative RRI, decline of RRI, and renal parenchyma to hydronephrosis area ratio (PHAR) as independent predictors of renal function recoverability after pyeloplasty. However, preoperative RRI and RRI decline were not significantly associated with recoverability of renal function in patients aged >35 years. Lower preoperative RRI, greater decline in RRI, higher PHAR, lower SFU grade, and extrarenal pelvis were associated with greater improvements in postoperative renal function. Preoperative differential renal function cannot independently predict the recoverability of postoperative renal function in adult patients with unilateral renal obstruction-induced hydronephrosis. SFU grade, renal pelvic type, PHAR, preoperative RRI, and decline in RRI were significantly associated with the recoverability of renal function in adult patients aged <35 years, while only SFU grade, renal pelvic type, and PHAR were significantly associated with renal function recoverability in patients aged ≥35 years. Renal function recovery was better in patients younger than 35 years when compared with older patients. © 2018 S. Karger AG, Basel.

[The therapeutic drug monitoring network server of tacrolimus for Chinese renal transplant patients].

PubMed

Deng, Chen-Hui; Zhang, Guan-Min; Bi, Shan-Shan; Zhou, Tian-Yan; Lu, Wei

2011-07-01

This study is to develop a therapeutic drug monitoring (TDM) network server of tacrolimus for Chinese renal transplant patients, which can facilitate doctor to manage patients' information and provide three levels of predictions. Database management system MySQL was employed to build and manage the database of patients and doctors' information, and hypertext mark-up language (HTML) and Java server pages (JSP) technology were employed to construct network server for database management. Based on the population pharmacokinetic model of tacrolimus for Chinese renal transplant patients, above program languages were used to construct the population prediction and subpopulation prediction modules. Based on Bayesian principle and maximization of the posterior probability function, an objective function was established, and minimized by an optimization algorithm to estimate patient's individual pharmacokinetic parameters. It is proved that the network server has the basic functions for database management and three levels of prediction to aid doctor to optimize the regimen of tacrolimus for Chinese renal transplant patients.

Renal cell carcinoma associated with transcription factor E3 expression and Xp11.2 translocation: incidence, characteristics, and prognosis.

PubMed

Klatte, Tobias; Streubel, Berthold; Wrba, Friedrich; Remzi, Mesut; Krammer, Barbara; de Martino, Michela; Waldert, Matthias; Marberger, Michael; Susani, Martin; Haitel, Andrea

2012-05-01

We studied the characteristics and prognosis of renal cell carcinoma (RCC) associated with Xp11.2 translocation and transcription factor E3 (TFE3) expression and determined the need for genetic analysis in routine diagnostics. Of 848 consecutive cases, 75 showed microscopic features suggestive of Xp11.2 translocation RCC or occurred in patients 40 years or younger. Of these cases, 17 (23%) showed strong nuclear TFE3 immunostaining, which was associated with more advanced tumors and inverse prognosis in univariate (P = .032) but not multivariate (P = .404) analysis. With fluorescence in situ hybridization and polymerase chain reaction, only 2 cases showed alterations of the X chromosome and the ASPL-TFE3 gene fusion, respectively. In our laboratory, the predictive value of TFE3 expression for the Xp11.2 translocation was 12%. Strong nuclear TFE3 expression is associated with metastatic spread and a poor prognosis. In our laboratory, TFE3 is not diagnostic for Xp11.2 translocation RCC. Diagnosis of Xp11.2 translocation RCC may be made only genetically.

Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study.

PubMed

Corrado, C; Santarelli, M T; Pavlovsky, S; Pizzolato, M

1989-12-01

Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.

Urinary 8-hydroxy-2'-deoxyguanosine (8-oxodG) level can predict acute renal damage in young children with urinary tract infection.

PubMed

Chien, Jien-Wen; Wang, Lien-Yen; Cheng, Yu-Shan; Tsai, Yi-Giien; Liu, Chin-San

2014-06-01

There are no good biomarkers to predict renal parenchymal involvement in children with urinary tract infection (UTI). Children (N = 73) younger than 5 years with UTI were enrolled. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8-oxodG) and total antioxidant capacity (TAC) were checked as markers of oxidative stress and antioxidant capacity, respectively. Tc99m-dimercaptosuccinic acid (DMSA) renal scintigraphy was used to find evidence of renal involvement. Patients with positive DMSA findings had higher levels of urinary 8-oxodG (p = 0.003) and higher urinary TAC (p = 0.001) than patients with normal DMSA findings. High level of urinary 8-oxodG may be a risk factor of severe renal damage.

Comparison of renal ultrasonography and dimercaptosuccinic acid renal scintigraphy in febrile urinary tract infection.

PubMed

Ayazi, Parviz; Mahyar, Abolfazl; Noroozian, Elham; Esmailzadehha, Neda; Barikani, Ameneh

2015-12-01

Accurate and early diagnosis and appropriate treatment of patient with urinary tract infection (UTI) are essential for the prevention or restriction of permanent damage to the kidneys in children. The aim of this study was to compare renal ultrasonography (US) and dimercaptosuccinic acid (DMSA) renal scan in the diagnosis of patients with febrile urinary tract infection. This study involved the medical records of children with febrile urinary tract infection who were admitted to the children's hospital in Qazvin, Iran. Pyelonephritis was diagnosed on the basis of clinical symptoms, laboratory tests and abnormal DMSA renal scans. The criteria for abnormality of renal US were an increase or a decrease in diffuse or focal parenchymal echogenicity, loss of corticomedullary differentiation, kidney position irregularities, parenchymal reduction and increased kidney size. Of the 100 study patients, 23% had an abnormal US and 46% had an abnormal DMSA renal scan. Of the latter patients, 15 had concurrent abnormal US (P value ≤ 0.03, concordance rate: 18%). Renal US had a sensitivity of 32%, specificity of 85%, positive predictive value of 65% and negative predictive value of 60%. Of the 77 patients with normal US, 31 (40.2%) had an abnormal DMSA renal scan. Despite the benefits and accessibility of renal US, its value in the diagnosis of pyelonephritis is limited.

Renal volume assessed by magnetic resonance imaging volumetry correlates with renal function in living kidney donors pre- and postdonation: a retrospective cohort study.

PubMed

Lange, Daniel; Helck, Andreas; Rominger, Axel; Crispin, Alexander; Meiser, Bruno; Werner, Jens; Fischereder, Michael; Stangl, Manfred; Habicht, Antje

2018-07-01

Renal function of potential living kidney donors is routinely assessed with scintigraphy. Kidney anatomy is evaluated by imaging techniques such as magnetic resonance imaging (MRI). We evaluated if a MRI-based renal volumetry is a good predictor of kidney function pre- and postdonation. We retrospectively analyzed the renal volume (RV) in a MRI of 100 living kidney donors. RV was correlated with the tubular excretion rate (TER) of MAG3-scintigraphy, a measured creatinine clearance (CrCl), and the estimated glomerular filtration rate (eGFR) by Cockcroft-Gault (CG), CKD-EPI, and modification of diet in renal disease (MDRD) formula pre- and postdonation during a follow-up of 3 years. RV correlated significantly with the TER (total: r = 0.6735, P < 0.0001). Correlation between RV and renal function was the highest for eGFR by CG (r = 0.5595, P < 0.0001), in comparison with CrCl, MDRD-GFR, and CKD-EPI-GFR predonation. RV significantly correlated with CG-GFR postdonation and predicted CG-GFR until 3 years after donation. MRI renal volumetry might be an alternative technique for the evaluation of split renal function and prediction of renal function postdonation in living kidney donors. © 2018 Steunstichting ESOT.

Prognostic value of three-dimensional ultrasound for fetal hydronephrosis

PubMed Central

WANG, JUNMEI; YING, WEIWEN; TANG, DAXING; YANG, LIMING; LIU, DONGSHENG; LIU, YUANHUI; PAN, JIAOE; XIE, XING

2015-01-01

The present study evaluated the prognostic value of three-dimensional ultrasound for fetal hydronephrosis. Pregnant females with fetal hydronephrosis were enrolled and a novel three-dimensional ultrasound indicator, renal parenchymal volume/kidney volume, was introduced to predict the postnatal prognosis of fetal hydronephrosis in comparison with commonly used ultrasound indicators. All ultrasound indicators of fetal hydronephrosis could predict whether postnatal surgery was required for fetal hydronephrosis; however, the predictive performance of renal parenchymal volume/kidney volume measurements as an individual indicator was the highest. In conclusion, ultrasound is important in predicting whether postnatal surgery is required for fetal hydronephrosis, and the three-dimensional ultrasound indicator renal parenchymal volume/kidney volume has a high predictive performance. Furthermore, the majority of cases of fetal hydronephrosis spontaneously regress subsequent to birth, and the regression time is closely associated with ultrasound indicators. PMID:25667626

Tubular damage and worsening renal function in chronic heart failure.

PubMed

Damman, Kevin; Masson, Serge; Hillege, Hans L; Voors, Adriaan A; van Veldhuisen, Dirk J; Rossignol, Patrick; Proietti, Gianni; Barbuzzi, Savino; Nicolosi, Gian Luigi; Tavazzi, Luigi; Maggioni, Aldo P; Latini, Roberto

2013-10-01

This study sought to investigate the relationship between tubular damage and worsening renal function (WRF) in chronic heart failure (HF) BACKGROUND: WRF is associated with poor outcome in chronic HF. It is unclear whether urinary tubular markers may identify patients at risk for WRF. In 2,011 patients with chronic HF, we evaluated the ability of urinary tubular markers (N-acetyl-beta-d-glucosaminidase (NAG), kidney injury molecule (KIM)-1, and neutrophil gelatinase-associated lipocalin (NGAL) to predict WRF. Finally, we assessed the prognostic importance of WRF. A total of 290 patients (14.4%) experienced WRF during follow-up, and WRF was a strong and independent predictor of all-cause mortality and HF hospitalizations (hazard ratio [HR]: 2.87; 95% CI: 2.40 to 3.43; p < 0.001). Patients with WRF had lower baseline glomerular filtration rate and higher KIM-1, NAG, and NGAL levels. In a multivariable-adjusted model, KIM-1 was the strongest independent predictor of WRF (HR: 1.23; 95% CI: 1.09 to 1.39 per log increase; p = 0.001). WRF was associated with strongly impaired outcome in patients with chronic HF. Increased level of urinary KIM-1 was the strongest independent predictor of WRF and could therefore be used to identify patients at risk for WRF and poor clinical outcome. (GISSI-HF-Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic CHF; NCT00336336). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Analysis of renal blood flow and renal volume in normal fetuses and in fetuses with a solitary functioning kidney.

PubMed

Hindryckx, An; Raaijmakers, Anke; Levtchenko, Elena; Allegaert, Karel; De Catte, Luc

2017-12-01

To evaluate renal blood flow and renal volume for the prediction of postnatal renal function in fetuses with solitary functioning kidney (SFK). Seventy-four SFK fetuses (unilateral renal agenesis [12], multicystic dysplastic kidney [36], and severe renal dysplasia [26]) were compared with 58 healthy fetuses. Peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the renal artery (RA) were measured; 2D and 3D (VOCAL) volumes were calculated. Renal length and glomerular filtration rate (GFR) were obtained in SFK children (2 years). Compared with the control group, the PSV RA was significantly lower in nonfunctioning kidneys and significantly higher in SFK. Volume measurements indicated a significantly larger volume of SFK compared with healthy kidneys. All but 4 children had GFR above 70 mL/min/1.73 m 2 , and compensatory hypertrophy was present in 69% at 2 years. PSV RA and SFK volume correlated with postnatal renal hypertrophy. No correlation between prenatal and postnatal SFK volume and GFR at 2 years was demonstrated. Low PSV RA might have a predictive value for diagnosing a nonfunctioning kidney in fetuses with a SFK. We demonstrated a higher PSV RA and larger renal volume in the SFK compared with healthy kidneys. © 2017 John Wiley & Sons, Ltd.

Stents in Renal Artery Bifurcation Stenosis: A Case Report

PubMed Central

Leonardou, Polytimi; Pappas, Paris

2011-01-01

A 39-year-old patient presented with poorly controlled hypertension, and she was referred to renal angiogram and potential renal angioplasty. Renal angiogram showed a bifurcation lesion of the right renal artery. A guide wire was used to cross the upper branch, while the lower branch was protected by another same-type guide wire through the same introducer. Two thin monorail balloons were used to dilate the two branches; however, despite balloon dilatation, the stenosis of the vessels persisted. The “kissing balloon” technique was then attempted by simultaneously inflating both branches using the same balloons, but more than a 70% residual stenosis persisted in each branch. Two stents were finally placed in a “kissing” way through the main renal artery. The imaging and clinical results were good, without any procedure-related complications. Three years clinical followup was also good, without any reason for further interventional approach. PMID:21789043

The renal compartment: a hydraulic view.

PubMed

Cruces, Pablo; Salas, Camila; Lillo, Pablo; Salomon, Tatiana; Lillo, Felipe; Hurtado, Daniel E

2014-12-01

The hydraulic behavior of the renal compartment is poorly understood. In particular, the role of the renal capsule on the intrarenal pressure has not been thoroughly addressed to date. We hypothesized that pressure and volume in the renal compartment are not linearly related, similar to other body compartments. The pressure-volume curve of the renal compartment was obtained by injecting fluid into the renal pelvis and recording the rise in intrarenal pressure in six anesthetized and mechanically ventilated piglets, using a catheter Camino 4B® inserted into the renal parenchyma. In healthy kidneys, pressure has a highly nonlinear dependence on the injected volume, as revealed by an exponential fit to the data (R (2) = 0.92). On the contrary, a linear relation between pressure and volume is observed in decapsulated kidneys. We propose a biomechanical model for the renal capsule that is able to explain the nonlinear pressure-volume dependence for moderate volume increases. We have presented experimental evidence and a theoretical model that supports the existence of a renal compartment. The mechanical role of the renal capsule investigated in this work may have important implications in elucidating the role of decompressive capsulotomy in reducing the intrarenal pressure in acutely injured kidneys.

The prevalence and implications of BK virus replication in non-renal solid organ transplant recipients: A systematic review.

PubMed

Viswesh, Velliyur; Yost, Sarah E; Kaplan, Bruce

2015-07-01

The significance of BK viruria and viremia in non-renal solid organ transplants is poorly understood. A systematic review was performed reviewing the incidence and implications of BK virus replication in non-renal solid organ transplants. Ninety-seven studies were identified, of which 18 including lung, heart, liver and pancreas transplants were included. The overall incidence of BK viruria and viremia was 20% and 3% respectively and 17 cases of BK nephropathy were identified. Heart transplant recipients had a higher overall incidence of BK viremia than other non-renal organ types, and the majority of cases of BK virus-associated nephropathy were in heart transplant recipients. The incidence of BK viremia was significantly lower in non-renal solid organ transplants than that of renal transplant recipients and BK virus-associated nephropathy was rare. BK virus-associated nephropathy may be considered in heart transplant recipients who have unexplained and persistent renal dysfunction not attributable to other causes. Copyright © 2015 Elsevier Inc. All rights reserved.

Microcirculation of human pancreatic islets transplanted under the renal capsule of nude mice.

PubMed

Jansson, L; Tyrberg, B; Carlsson, P O; Nordin, A; Andersson, A; Källskog O

2001-08-27

The aim was to measure the capillary blood pressure in transplanted human islets. Human islets were isolated at the Central Unit of the beta-cell Transplant in Brussels, Belgium. After transport to our laboratory, the islets were implanted under the renal capsule of normoglycemic nude mice. Two weeks later the capillary and venous blood pressures in the islet graft and adjacent renal parenchyma were measured with a micropuncture technique. Capillary blood pressure was approximately 5-8 mmHg in both graft and renal capillaries: twice as high as in native islets. Venous blood pressures were similar (4-5 mmHg) in the veins draining the graft and in the renal interlobular veins. All veins leading from the graft emptied into the renal parenchyma, that is, into interlobular veins. The capillary hypertension seen in transplanted human islets is probably necessary to secure adequate drainage through the renal veins. Whether this contributes to the poor results of long-term islet graft survival is unknown.

Novel Cancer Therapeutics with Allosteric Modulation of the Mitochondrial C-Raf-DAPK Complex by Raf Inhibitor Combination Therapy.

PubMed

Tsai, Yi-Ta; Chuang, Mei-Jen; Tang, Shou-Hung; Wu, Sheng-Tang; Chen, Yu-Chi; Sun, Guang-Huan; Hsiao, Pei-Wen; Huang, Shih-Ming; Lee, Hwei-Jen; Yu, Cheng-Ping; Ho, Jar-Yi; Lin, Hui-Kuan; Chen, Ming-Rong; Lin, Chung-Chih; Chang, Sun-Yran; Lin, Victor C; Yu, Dah-Shyong; Cha, Tai-Lung

2015-09-01

Mitochondria are the powerhouses of cells. Mitochondrial C-Raf is a potential cancer therapeutic target, as it regulates mitochondrial function and is localized to the mitochondria by its N-terminal domain. However, Raf inhibitor monotherapy can induce S338 phosphorylation of C-Raf (pC-Raf(S338)) and impede therapy. This study identified the interaction of C-Raf with S308 phosphorylated DAPK (pDAPK(S308)), which together became colocalized in the mitochondria to facilitate mitochondrial remodeling. Combined use of the Raf inhibitors sorafenib and GW5074 had synergistic anticancer effects in vitro and in vivo, but targeted mitochondrial function, rather than the canonical Raf signaling pathway. C-Raf depletion in knockout MEF(C-Raf-/-) or siRNA knockdown ACHN renal cancer cells abrogated the cytotoxicity of combination therapy. Crystal structure simulation showed that GW5074 bound to C-Raf and induced a C-Raf conformational change that enhanced sorafenib-binding affinity. In the presence of pDAPK(S308), this drug-target interaction compromised the mitochondrial targeting effect of the N-terminal domain of C-Raf, which induced two-hit damages to cancer cells. First, combination therapy facilitated pC-Raf(S338) and pDAPK(S308) translocation from mitochondria to cytoplasm, leading to mitochondrial dysfunction and reactive oxygen species (ROS) generation. Second, ROS facilitated PP2A-mediated dephosphorylation of pDAPK(S308) to DAPK. PP2A then dissociated from the C-Raf-DAPK complex and induced profound cancer cell death. Increased pDAPK(S308) modification was also observed in renal cancer tissues, which correlated with poor disease-free survival and poor overall survival in renal cancer patients. Besides mediating the anticancer effect, pDAPK(S308) may serve as a predictive biomarker for Raf inhibitors combination therapy, suggesting an ideal preclinical model that is worthy of clinical translation. ©2015 American Association for Cancer Research.

High-Sensitivity Cardiac Troponin and the Risk Stratification of Patients With Renal Impairment Presenting With Suspected Acute Coronary Syndrome

PubMed Central

Miller-Hodges, Eve; Anand, Atul; Shah, Anoop S.V.; Chapman, Andrew R.; Gallacher, Peter; Lee, Kuan Ken; Farrah, Tariq; Halbesma, Nynke; Blackmur, James P.; Newby, David E.; Mills, Nicholas L.

2018-01-01

Background: High-sensitivity cardiac troponin testing may improve the risk stratification and diagnosis of myocardial infarction, but concentrations can be challenging to interpret in patients with renal impairment, and the effectiveness of testing in this group is uncertain. Methods: In a prospective multicenter study of consecutive patients with suspected acute coronary syndrome, we evaluated the performance of high-sensitivity cardiac troponin I in those with and without renal impairment (estimated glomerular filtration rate <60mL/min/1.73m2). The negative predictive value and sensitivity of troponin concentrations below the risk stratification threshold (5 ng/L) at presentation were reported for a primary outcome of index type 1 myocardial infarction, or type 1 myocardial infarction or cardiac death at 30 days. The positive predictive value and specificity at the 99th centile diagnostic threshold (16 ng/L in women, 34 ng/L in men) was determined for index type 1 myocardial infarction. Subsequent type 1 myocardial infarction and cardiac death were reported at 1 year. Results: Of 4726 patients identified, 904 (19%) had renal impairment. Troponin concentrations <5 ng/L at presentation identified 17% of patients with renal impairment as low risk for the primary outcome (negative predictive value, 98.4%; 95% confidence interval [CI], 96.0%–99.7%; sensitivity 98.9%; 95%CI, 97.5%–99.9%), in comparison with 56% without renal impairment (P<0.001) with similar performance (negative predictive value, 99.7%; 95% CI, 99.4%–99.9%; sensitivity 98.4%; 95% CI, 97.2%–99.4%). The positive predictive value and specificity at the 99th centile were lower in patients with renal impairment at 50.0% (95% CI, 45.2%–54.8%) and 70.9% (95% CI, 67.5%–74.2%), respectively, in comparison with 62.4% (95% CI, 58.8%–65.9%) and 92.1% (95% CI, 91.2%–93.0%) in those without. At 1 year, patients with troponin concentrations >99th centile and renal impairment were at greater risk of subsequent myocardial infarction or cardiac death than those with normal renal function (24% versus 10%; adjusted hazard ratio, 2.19; 95% CI, 1.54–3.11). Conclusions: In suspected acute coronary syndrome, high-sensitivity cardiac troponin identified fewer patients with renal impairment as low risk and more as high risk, but with lower specificity for type 1 myocardial infarction. Irrespective of diagnosis, patients with renal impairment and elevated cardiac troponin concentrations had a 2-fold greater risk of a major cardiac event than those with normal renal function, and should be considered for further investigation and treatment. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123. PMID:28978551

The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients.

PubMed

Kaihan, Ahmad Baseer; Yasuda, Yoshinari; Katsuno, Takayuki; Kato, Sawako; Imaizumi, Takahiro; Ozeki, Takaya; Hishida, Manabu; Nagata, Takanobu; Ando, Masahiko; Tsuboi, Naotake; Maruyama, Shoichi

2017-12-01

The Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN). A retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine. In multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC. The JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.

Did Michelangelo (1475-1564) have high-functioning autism?

PubMed

Arshad, Muhammad; Fitzgerald, Michael

2004-05-01

In this paper evidence is presented that Michelangelo met the criteria for Asperger's disorder, or high-functioning autism. The evidence relates to his single-minded work routine, unusual lifestyle, limited interests, poor social and communication skills, and issues of life control. Depression and various medical conditions, including gout, renal colic and renal stones, did not stop his obsessive working habits.

Pregnancy and renal outcomes in lupus nephritis: an update and guide to management.

PubMed

Bramham, K; Soh, M C; Nelson-Piercy, C

2012-10-01

Systemic lupus erythematosis (SLE) commonly affects women of child bearing-age, and advances in treatment have resulted in an increasing number of women with renal involvement becoming pregnant. Knowledge of the relationship of the condition with respect to fertility and pregnancy is important for all clinicians involved in the care of women with lupus nephritis because they have complicated pregnancies. Presentation of lupus nephritis can range from mild asymptomatic proteinuria to rapidly progressive renal failure and may occur before, during, or after pregnancy. The timing of diagnosis may influence pregnancy outcome. Pregnancy may also affect the course of lupus nephritis. All pregnancies in women with lupus nephritis should be planned, preferably after more than six-months of quiescent disease. Predictors of poor obstetric outcome include active disease at conception or early pregnancy, baseline poor renal function with Creatinine >100 μmol/L, proteinuria >0.5 g/24 hours, presence of concurrent antiphospholipid syndrome and hypertension. In this review the most recent studies of pregnancies in women with lupus nephritis are discussed and a practical approach to managing women prepregnancy, during pregnancy and post-partum is described.

Pulmonary Catherization Data Correlate Poorly with Renal Function in Heart Failure.

PubMed

Masha, Luke; Stone, James; Stone, Danielle; Zhang, Jun; Sheng, Luo

2018-04-10

The mechanisms of renal dysfunction in heart failure are poorly understood. We chose to explore the relationship of cardiac filling pressures and cardiac index (CI) in relation to renal dysfunction in advanced heart failure. To determine the relationship between renal function and cardiac filling pressures using the United Network of Organ Sharing (UNOS) pulmonary artery catherization registry. Patients over the age of 18 years who were listed for single-organ heart transplantation were included. Exclusion criteria included a history of mechanical circulatory support, previous transplantation, any use of renal replacement therapy, prior history of malignancy, and cardiac surgery, amongst others. Correlations between serum creatinine (SCr) and CI, pulmonary capillary wedge pressure (PCWP), pulmonary artery systolic pressure (PASP), and pulmonary artery diastolic pressure (PADP) were assessed by Pearson correlation coefficients and simple linear regression coefficients. Pearson correlation coefficients between SCr and PCWP, PASP, and PADP were near zero with values of 0.1, 0.07, and 0.08, respectively (p < 0.0001). A weak negative correlation coefficient between SCr and CI was found (correlation coefficient, -0.045, p = 0.027). In a subgroup of young patients unlikely to have noncardiac etiologies, no significant correlations between these values were identified. These findings suggest that, as assessed by pulmonary artery catherization, none of the factors - PCWP, PASP, PADP, or CI - play a prominent role in cardiorenal syndromes. © 2018 S. Karger AG, Basel.

Wound Healing in Patients With Impaired Kidney Function

PubMed Central

Maroz, Natallia; Simman, Richard

2014-01-01

Renal impairment has long been known to affect wound healing. However, information on differences in the spectrum of wound healing depending on the type of renal insufficiency is limited. Acute kidney injury (AKI) may be observed with different wound types. On one hand, it follows acute traumatic conditions such as crush injury, burns, and post-surgical wounds, and on the other hand, it arises as simultaneous targeting of skin and kidneys by autoimmune-mediated vasculitis. Chronic kidney disease (CKD) and end-stage renal disease (ESRD) often occur in older people, who have limited physical mobility and predisposition for developing pressure-related wounds. The common risk factors for poor wound healing, generally observed in patients with CKD and ESRD, include poorly controlled diabetes mellitus, neuropathy, peripheral vascular disease, chronic venous insufficiency, and aging. ESRD patients have a unique spectrum of wounds related to impaired calcium–phosphorus metabolism, including calciphylaxis, in addition to having the risk factors presented by CKD patients. Overall, there is a wide range of uremic toxins: they may affect local mechanisms of wound healing and also adversely affect the functioning of multiple systems. In the present literature review, we discuss the association between different types of renal impairments and their effects on wound healing and examine this association from different aspects related to the management of wounds in renal impairment patients. PMID:26199882

Prediction of renal crystalline size distributions in space using a PBE analytic model. 1. Effect of microgravity-induced biochemical alterations.

PubMed

Kassemi, Mohammad; Thompson, David

2016-09-01

An analytical Population Balance Equation model is developed and used to assess the risk of critical renal stone formation for astronauts during future space missions. The model uses the renal biochemical profile of the subject as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating calcium oxalate crystals during their transit through the kidney. The model is verified through comparison with published results of several crystallization experiments. Numerical results indicate that the model is successful in clearly distinguishing between 1-G normal and 1-G recurrent stone-former subjects based solely on their published 24-h urine biochemical profiles. Numerical case studies further show that the predicted renal calculi size distribution for a microgravity astronaut is closer to that of a recurrent stone former on Earth rather than to a normal subject in 1 G. This interestingly implies that the increase in renal stone risk level in microgravity is relatively more significant for a normal person than a stone former. However, numerical predictions still underscore that the stone-former subject carries by far the highest absolute risk of critical stone formation during space travel. Copyright © 2016 the American Physiological Society.

A clinical nomogram to predict the successful shock wave lithotripsy of renal and ureteral calculi.

PubMed

Wiesenthal, Joshua D; Ghiculete, Daniela; Ray, A Andrew; Honey, R John D'A; Pace, Kenneth T

2011-08-01

Although shock wave lithotripsy is dependent on patient and stone related factors, there are few reliable algorithms predictive of its success. In this study we develop a comprehensive nomogram to predict renal and ureteral stone shock wave lithotripsy outcomes. During a 5-year period data from patients treated at our lithotripsy unit were reviewed. Analysis was restricted to patients with a solitary renal or ureteral calculus 20 mm or less. Demographic, stone, patient, treatment and 3-month followup data were collected from a prospective database. All patients were treated using the Philips Lithotron® lithotripter. A total of 422 patients (69.7% male) were analyzed. Mean stone size was 52.3±39.3 mm2 for ureteral stones and 78.9±77.3 mm2 for renal stones, with 95 (43.6%) of the renal stones located in the lower pole. The single treatment success rates for ureteral and renal stones were 60.3% and 70.2%, respectively. On univariate analysis predictors of shock wave lithotripsy success, regardless of stone location, were age (p=0.01), body mass index (p=0.01), stone size (p<0.01), mean stone density (p<0.01) and skin to stone distance (p<0.01). By multivariate logistic regression for renal calculi, age, stone area and skin to stone distance were significant predictors with an AUC of 0.75. For ureteral calculi predictive factors included body mass index and stone size (AUC 0.70). Patient and stone parameters have been identified to create a nomogram that predicts shock wave lithotripsy outcomes using the Lithotron lithotripter, which can facilitate optimal treatment based decisions and provide patients with more accurate single treatment success rates for shock wave lithotripsy tailored to patient specific situations. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Renal Atrophy Secondary to Chemoradiotherapy of Abdominal Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Gary Y., E-mail: Gary.Yang@RoswellPark.or; May, Kilian Salerno; Iyer, Renuka V.

2010-10-01

Purpose: To identify factors predictive of renal atrophy after chemoradiotherapy of gastrointestinal malignancies. Methods and Materials: Patients who received chemotherapy and abdominal radiotherapy (RT) between 2002 and 2008 were identified for this study evaluating change in kidney size and function after RT. Imaging and biochemical data were obtained before and after RT in 6-month intervals. Kidney size was defined by craniocaudal measurement on CT images. The primarily irradiated kidney (PK) was defined as the kidney that received the greater mean kidney dose. Receiver operating characteristic (ROC) curves were generated to predict risk for renal atrophy. Results: Of 130 patients, medianmore » age was 64 years, and 51.5% were male. Most primary disease sites were pancreas and periampullary tumors (77.7%). Median follow-up was 9.4 months. Creatinine clearance declined 20.89%, and size of the PK decreased 4.67% 1 year after completion of chemoradiation. Compensatory hypertrophy of the non-PK was not seen. Percentage volumes of the PK receiving {>=}10 Gy (V{sub 10}), 15 Gy (V{sub 15}), and 20 Gy (V{sub 20}) were significantly associated with renal atrophy 1 year after RT (p = 0.0030, 0.0029, and 0.0028, respectively). Areas under the ROC curves for V{sub 10}, V{sub 15}, and V{sub 20} to predict >5% decrease in PK size were 0.760, 0.760, and 0.762, respectively. Conclusions: Significant detriments in PK size and renal function were seen after abdominal RT. The V{sub 10}, V{sub 15}, and V{sub 20} were predictive of risk for PK atrophy 1 year after RT. Analyses suggest the association of lower-dose renal irradiation with subsequent development of renal atrophy.« less

Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL Nephrometry score.

PubMed

Kutikov, Alexander; Smaldone, Marc C; Egleston, Brian L; Manley, Brandon J; Canter, Daniel J; Simhan, Jay; Boorjian, Stephen A; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

2011-08-01

Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology. We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features. We retrospectively queried Fox Chase Cancer Center's prospectively maintained database for consecutive renal masses where a Nephrometry score was available. All patients in the cohort underwent either partial or radical nephrectomy. The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors. Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p < 0.0001) and histology (p < 0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study. The current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Open repair of chronic distal aortic dissection in the endovascular era: Implications for disease management.

PubMed

Pujara, Akshat C; Roselli, Eric E; Hernandez, Adrian V; Vargas Abello, Lina M; Burke, Jacob M; Svensson, Lars G; Greenberg, Roy K

2012-10-01

Controversy surrounds the treatment of chronic aortic dissection. Open surgical and endovascular experiences include mixed populations treated with evolving strategies and limited follow-up. We establish a standard against which endovascular repair can be compared by assessing outcomes after open repair of chronic distal aortic dissections anatomically suitable to stent-grafting. From 2000 to 2008, 169 patients underwent open repair of the descending thoracic artery only (n = 88) or thoracoabdominal (n = 81) chronic aortic dissection (elective in 98, urgent/emergency in 71). Chart review and 3-dimensional assessment of computed tomography were performed. Poor outcome included all-cause mortality or vascular reintervention. Thirty-day mortality was 8% (n = 14). Serious complications included neurologic (n = 12 [spinal cord n = 4, 2.4%]), respiratory (n = 32), and renal failure (n = 1 descending thoracic artery only vs 17 thoracoabdominal, P < .001). Chronic obstructive pulmonary disease predicted early mortality (hazard ratio 8.0, P = .005). Survival at 1, 2, and 5 years was 76%, 69%, and 55%, respectively; 23 patients (14%) required reintervention. Event-free survival at 5 years was 51% and 47% after descending thoracic artery only or thoracoabdominal repair, respectively. Greater maximum aortic diameter (hazard ratio 1.9, P = .03) and greater diameter at the diaphragm (hazard ratio 3.7, P = .01) or renal segment (hazard ratio 4.3, P = .03) predicted poor outcome. Early outcomes are good and late outcomes are less than desirable after open repair of chronic distal aortic dissection, regardless of the extent of repair. High-risk and late-stage patients with larger and more extensive aneurysmal degeneration warrant further investigation, including the use of newer, less-invasive techniques. Select patients at risk for aneurysmal degeneration should undergo a more aggressive initial approach with aortic dissection repair. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Algorithm for optimal dialysis access timing.

PubMed

Heaf, J G

2007-02-01

Acute initiation of dialysis is associated with increased morbidity due to access and uremia complications. It is frequent despite early referral and regular out-patient control. We studied factors associated with end-stage renal disease (ESRD) progression in order to optimize the timing of dialysis access (DA). In a retrospective longitudinal study (Study 1), the biochemical and clinical course of 255 dialysis and 64 predialysis patients was registered to determine factors associated with dialysis-free survival (DFS). On the basis of these results an algorithm was developed to predict timely DA, defined as >6 weeks and <26 weeks before dialysis initiation, with too late placement weighted twice as harmful as too early. The algorithm was validated in a prospective study (Study 2) of 150 dialysis and 28 predialysis patients. Acute dialysis was associated with increased 90-day hospitalization (17.9 vs. 9.0 days) and mortality (14% vs. 6%). P-creatinine and p-urea were poor indicators of DFS. At any level of p-creatinine, DFS was shorter with lower creatinine clearance and vice versa. Patients with systemic renal disease had a significantly shorter DFS than primary renal disease, due to faster GFR loss and earlier dialysis initiation. Short DFS was seen with hypoalbuminemia and cachexia; these patients were recommended early DA. The following algorithm was used to time DA (units: 1iM and ml/min/1.73 m2): P-Creatinine - 50 x GFR + (100 if Systemic Renal Disease) >200. Use of the algorithm was associated with earlier dialysis placement and a fall in acute dialysis requirements from 50% to 23%. The incidence of too early DA was unchanged (7% vs. 9%), and was due to algorithm non-application. The algorithm failed to predict imminent dialysis in 10% of cases, primarily due to acute exacerbation of stable uremia. Dialysis initiation was advanced by approximately one month. A predialysis program based on early dialysis planning and GFR-based DA timing may reduce the requirement for acute dialysis initiation and patient morbidity and mortality, at the cost of slightly earlier dialysis initiation.

Mucormycosis (zygomycosis) of renal allograft

PubMed Central

Gupta, Krishan L.; Joshi, Kusum; Kohli, Harbir S.; Jha, Vivekanand; Sakhuja, Vinay

2012-01-01

Fungal infection is relatively common among renal transplant recipients from developing countries. Mucormycosis, also known as zygomycosis, is one of the most serious fungal infections in these patients. The most common of presentation is rhino-cerebral. Isolated involvement of a renal allograft is very rare. A thorough search of literature and our medical records yielded a total of 24 cases with mucormycosis of the transplanted kidney. There was an association with cytomegalovirus (CMV) infection and anti-rejection treatment in these patients and most of these transplants were performed in the developing countries from unrelated donors. The outcome was very poor with an early mortality in 13 (54.5%) patients. Renal allograft mucormycosis is a relatively rare and potentially fatal complication following renal transplantation. Early diagnosis, graft nephrectomy and appropriate antifungal therapy may result in an improved prognosis for these patients. PMID:26069793

Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances

PubMed Central

Iacoviello, Massimo; Leone, Marta; Antoncecchi, Valeria; Ciccone, Marco Matteo

2015-01-01

Chronic kidney disease and its worsening are recurring conditions in chronic heart failure (CHF) which are independently associated with poor patient outcome. The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index (a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction. PMID:25610846

Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.

PubMed

Zhao, Juanjuan; Lupino, Katherine; Wilkins, Benjamin J; Qiu, Chengxiang; Liu, Jian; Omura, Yasuhiro; Allred, Amanda L; McDonald, Caitlin; Susztak, Katalin; Barish, Grant D; Pei, Liming

2018-05-22

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

Endourological treatment of nonmalignant upper urinary tract complications after urinary diversion.

PubMed

El-Nahas, Ahmed R; Shokeir, Ahmed A

2010-12-01

Endourological modalities are considered the first line of treatment for benign ureterointestinal anastomotic strictures except in long strictures, completely obliterated lumen, prior radiation, and poor renal function. Endoureterotomy provided better success than balloon dilatation. In poor-operative risk patients, metal or double-J stents are viable options. Endourological treatments of upper tract stones after diversion are indicated for stones not suitable for shock wave lithotripsy (SWL) or to salvage SWL failure. Percutaneous nephrolithotomy was preferred for large or complex renal stones, whereas ureteroscopy was used for smaller stones. The evaluation of stone-free status and regular follow-up are mandatory because of the high recurrence rate. Copyright © 2010 Elsevier Inc. All rights reserved.

Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges

PubMed Central

Shirazian, Shayan; Aina, Olufemi; Park, Youngjun; Chowdhury, Nawsheen; Leger, Kathleen; Hou, Linle; Miyawaki, Nobuyuki; Mathur, Vandana S

2017-01-01

Chronic kidney disease-associated pruritus (CKD-aP) is a distressing, often overlooked condition in patients with CKD and end-stage renal disease. It affects ~40% of patients with end-stage renal disease and has been associated with poor quality of life, poor sleep, depression, and mortality. Prevalence estimates vary based on the instruments used to diagnose CKD-aP, and standardized diagnostic instruments are sorely needed. Treatment studies have often yielded conflicting results. This is likely related to studies that are limited by small sample size, flawed designs, and nonstandardized diagnostic instruments. Several large well-designed treatment trials have recently been completed and may soon influence CKD-aP management. PMID:28176969

Multimarker assessment for the prediction of renal function improvement after percutaneous revascularization for renal artery stenosis.

PubMed

Staub, Daniel; Partovi, Sasan; Zeller, Thomas; Breidthardt, Tobias; Kaech, Max; Boeddinghaus, Jasper; Puelacher, Christian; Nestelberger, Thomas; Aschwanden, Markus; Mueller, Christian

2016-06-01

Identifying patients likely to have improved renal function after percutaneous transluminal renal angioplasty and stenting (PTRA) for renal artery stenosis (RAS) is challenging. The purpose of this study was to use a comprehensive multimarker assessment to identify those patients who would benefit most from correction of RAS. In 127 patients with RAS and decreased renal function and/or hypertension referred for PTRA, quantification of hemodynamic cardiac stress using B-type natriuretic peptide (BNP), renal function using estimated glomerular filtration rate (eGFR), parenchymal renal damage using resistance index (RI), and systemic inflammation using C-reactive protein (CRP) were performed before intervention. Predefined renal function improvement (increase in eGFR ≥10%) at 6 months occurred in 37% of patients. Prognostic accuracy as quantified by the area under the receiver-operating characteristics curve for the ability of BNP, eGFR, RI and CRP to predict renal function improvement were 0.59 (95% CI, 0.48-0.70), 0.71 (95% CI, 0.61-0.81), 0.52 (95% CI, 0.41-0.65), and 0.56 (95% CI, 0.44-0.68), respectively. None of the possible combinations increased the accuracy provided by eGFR (lower eGFR indicated a higher likelihood for eGFR improvement after PTRA, P=ns for all). In the subgroup of 56 patients with pre-interventional eGFR <60 mL/min/1.73 m(2), similar findings were obtained. Quantification of renal function, but not any other pathophysiologic signal, provides at least moderate accuracy in the identification of patients with RAS in whom PTRA will improve renal function.

Prognostic Significance of Interleukin-34 (IL-34) in Patients With Chronic Heart Failure With or Without Renal Insufficiency.

PubMed

Tao, Rong; Fan, Qin; Zhang, Hang; Xie, Hongyang; Lu, Lin; Gu, Gang; Wang, Fang; Xi, Rui; Hu, Jian; Chen, Qiujing; Niu, Wenquan; Shen, Weifeng; Zhang, Ruiyan; Yan, Xiaoxiang

2017-04-01

Renal dysfunction, commonly associated with cardiac dysfunction, has predictive value for adverse long-term outcomes in heart failure (HF). We previously identified a novel renal biomarker, interleukin-34 (IL-34), elevated in HF patients and associated with kidney dysfunction and coronary artery disease during HF. However, the prognostic value of IL-34 in HF remains unclear, so that the present study aimed to determine it. This prospective, observational study included 510 consecutive HF patients with their serum IL-34 as well as other variables measured at baseline, and they were followed up for 2 years. The primary end point was a composite of cardiovascular death or a first HF hospitalization, with cardiovascular death, HF hospitalization, and all-cause mortality as secondary outcomes. There was a significant and gradual increase in risk as IL-34 increased, determined by log-rank tests with Kaplan-Meier curves. Serum IL-34 was also a significant prognostic predictor of the primary end point (1.301 [1.115-1.518]; P =0.001), cardiovascular death (1.347 [1.096-1.655]; P =0.005), HF hospitalization (1.234 [1.018-1.494]; P =0.032), and all-cause mortality (1.343 [1.115-1.618]; P =0.002) in HF as per SD increase in the log IL-34 level after adjusting for age, sex, traditional risk factors, and N-terminal pro-brain natriuretic peptide. Especially, IL-34 had a more-significant prognostic value in HF patients with kidney impairment than those without. IL-34 is a significant predictor of cardiovascular death, HF hospitalization, and all-cause mortality in chronic HF, especially when concomitant with renal dysfunction. Serum IL-34 measurement may provide new insights linking kidney impairment to poor HF outcomes beyond other renal markers. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: data from the MAINTAIN Nephritis Trial

PubMed Central

Tamirou, Farah; Lauwerys, Bernard R; Dall'Era, Maria; Mackay, Meggan; Rovin, Brad; Cervera, Ricard; Houssiau, Frédéric A

2015-01-01

Background Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT). Methods Long-term (at least 7 years) renal function data were available for 90 patients randomised in the MNT. Receiver operating characteristic curves were built to test the performance of proteinuria measured within the 1st year as short-term predictor of long-term renal outcome. We calculated the positive and negative predictive values (PPV, NPV). Results After 12 months of treatment, achievement of a proteinuria <0.7 g/day best predicted good renal outcome, with a sensitivity and a specificity of 71% and 75%, respectively. The PPV was high (94%) but the NPV low (29%). Addition of the requirement of urine red blood cells ≤5/hpf as response criteria at month 12 reduced sensitivity from 71% to 41%. Conclusions In this cohort of mainly Caucasian patients suffering from a first episode of LN in most cases, achievement of a proteinuria <0.7 g/day at month 12 best predicts good outcome at 7 years and inclusion of haematuria in the set of criteria at month 12 undermines the sensitivity of early proteinuria decrease for the prediction of good outcome. The robustness of these conclusions stems from the very similar results obtained in two distinct LN cohorts. Trial registration number: NCT00204022. PMID:26629352

Management of metastatic renal cell carcinoma in the era of targeted therapies.

PubMed

Webber, K; Cooper, A; Kleiven, H; Yip, D; Goldstein, D

2011-08-01

Metastatic renal cell cancer is associated with poor prognosis and survival and is resistant to conventional chemotherapy. Therapeutic targeting of molecular pathways for tumour angiogenesis and other specific activation mechanisms offers improved tumour response and prolonged survival. To conduct a retrospective audit of metastatic renal cell carcinoma patients treated with targeted therapies. Data were extracted from clinical records of patients undergoing targeted treatment between 2005 and 2009 at two hospital sites. Data collected included pathology, systemic therapy class, toxicity and survival. Univariate and multivariate survival analyses were performed. Sixty-one patients were treated with 102 lines of therapy with a median overall survival (OS) of 23 months, median time to failure of first-line treatment (TTF1) of 10 months and median time to failure of second-line treatment (TTF2) of 5.2 months. Time from first diagnosis to treatment >12 months was significantly associated with improved OS, longer TTF1, TTF2 and response to first-line anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGF TKI) therapy. Variables associated with tumour biology, natural history and the systemic inflammatory response were associated with improved OS and TTF1. Development of hypertension was predictive of anti-VEGF TKI outcome. Toxicities were as expected for each drug class.   Survival and toxicity outcomes from two Australian sites are comparable to published data. The adverse event profile differs to conventional chemotherapy. Clinicians caring for patients with metastatic renal cancer will need to become familiar with these toxicities and their management as these agents enter widespread use. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

Wavelets analysis for differentiating solid, non-macroscopic fat containing, enhancing renal masses: a pilot study

NASA Astrophysics Data System (ADS)

Varghese, Bino; Hwang, Darryl; Mohamed, Passant; Cen, Steven; Deng, Christopher; Chang, Michael; Duddalwar, Vinay

2017-11-01

Purpose: To evaluate potential use of wavelets analysis in discriminating benign and malignant renal masses (RM) Materials and Methods: Regions of interest of the whole lesion were manually segmented and co-registered from multiphase CT acquisitions of 144 patients (98 malignant RM: renal cell carcinoma (RCC) and 46 benign RM: oncocytoma, lipid-poor angiomyolipoma). Here, the Haar wavelet was used to analyze the grayscale images of the largest segmented tumor in the axial direction. Six metrics (energy, entropy, homogeneity, contrast, standard deviation (SD) and variance) derived from 3-levels of image decomposition in 3 directions (horizontal, vertical and diagonal) respectively, were used to quantify tumor texture. Independent t-test or Wilcoxon rank sum test depending on data normality were used as exploratory univariate analysis. Stepwise logistic regression and receiver operator characteristics (ROC) curve analysis were used to select predictors and assess prediction accuracy, respectively. Results: Consistently, 5 out of 6 wavelet-based texture measures (except homogeneity) were higher for malignant tumors compared to benign, when accounting for individual texture direction. Homogeneity was consistently lower in malignant than benign tumors irrespective of direction. SD and variance measured in the diagonal direction on the corticomedullary phase showed significant (p<0.05) difference between benign versus malignant tumors. The multivariate model with variance (3 directions) and SD (vertical direction) extracted from the excretory and pre-contrast phase, respectively showed an area under the ROC curve (AUC) of 0.78 (p < 0.05) in discriminating malignant from benign. Conclusion: Wavelet analysis is a valuable texture evaluation tool to add to a radiomics platforms geared at reliably characterizing and stratifying renal masses.

Chronic kidney disease and poor outcomes in ischemic stroke: is impaired cerebral autoregulation the missing link?

PubMed

Castro, Pedro; Azevedo, Elsa; Rocha, Isabel; Sorond, Farzaneh; Serrador, Jorge M

2018-03-02

Chronic kidney disease increases stroke incidence and severity but the mechanisms behind this cerebro-renal interaction are mostly unexplored. Since both vascular beds share similar features, microvascular dysfunction could be the possible missing link. Therefore, we examined the relationship between renal function and cerebral autoregulation in the early hours post ischemia and its impact on outcome. We enrolled 46 ischemic strokes (middle cerebral artery). Dynamic cerebral autoregulation was assessed by transfer function (coherence, phase and gain) of spontaneous blood pressure oscillations to blood flow velocity within 6 h from symptom-onset. Estimated glomerular filtration rate (eGFR) was calculated. Hemorrhagic transformation (HT) and white matter lesions (WML) were collected from computed tomography performed at presentation and 24 h. Outcome was evaluated with modified Rankin Scale at 3 months. High gain (less effective autoregulation) was correlated with lower eGFR irrespective of infarct side (p < 0.05). Both lower eGFR and higher gain correlated with WML grade (p < 0.05). Lower eGFR and increased gain, alone and in combination, progressively reduced the odds of a good functional outcome [ipsilateral OR = 4.39 (CI95% 3.15-25.6), p = 0.019; contralateral OR = 8.15 (CI95% 4.15-15.6), p = 0.002] and increased risk of HT [ipsilateral OR = 3.48 (CI95% 0.60-24.0), p = 0.132; contralateral OR = 6.43 (CI95% 1.40-32.1), p = 0.034]. Lower renal function correlates with less effective dynamic cerebral autoregulation in acute ischemic stroke, both predicting a bad outcome. The evaluation of serum biomarkers of renal dysfunction could have interest in the future for assessing cerebral microvascular risk and relationship with stroke complications.

Renal Medullary and Urinary Oxygen Tension during Cardiopulmonary Bypass in the Rat

PubMed Central

Sgouralis, Ioannis; Evans, Roger G.; Layton, Anita T.

2017-01-01

Renal hypoxia could result from a mismatch in renal oxygen supply and demand, particularly in the renal medulla. Medullary hypoxic damage is believed to give rise to acute kidney injury, which is a prevalent complication of cardiac surgery performed on cardiopulmonary bypass (CPB). To determine the mechanisms that could lead to medullary hypoxia during CPB in the rat kidney, we developed a mathematical model which incorporates (i) autoregulation of renal blood flow and glomerular filtration rate, (ii) detailed oxygen transport and utilization in the renal medulla, and (iii) oxygen transport along the ureter. Within the outer medulla, the lowest interstitial tissue PO2, which is an indicator of renal hypoxia, is predicted near the thick ascending limbs. Interstitial tissue PO2 exhibits a general decrease along the inner medullary axis, but urine PO2 increases significantly along the ureter. Thus, bladder urinary PO2 is predicted to be substantially higher than medullary PO2. The model is used to identify the phase of cardiac surgery performed on CPB that is associated with the highest risk for hypoxic kidney injury. Simulation results indicate that the outer medulla’s vulnerability to hypoxic injury depends, in part, on the extent to which medullary blood flow is autoregulated. With imperfect medullary blood flow autoregulation, the model predicts that the rewarming phase of CPB, in which medullary blood flow is low but medullary oxygen consumption remains high, is the phase in which the kidney is most likely to suffer hypoxic injury. PMID:27281792

Renal alpha-smooth muscle actin: a new prognostic factor for lupus nephritis.

PubMed

Makni, Kaouthar; Jarraya, Faïçal; Khabir, Abdelmajid; Hentati, Basma; Hmida, Mohamed Ben; Makni, Hafedh; Boudawara, Tahia; Jlidi, Rchid; Hachicha, Jamil; Ayadi, Hammadi

2009-08-01

Systemic lupus erythematosus (SLE) is the prototype of autoimmune disease where renal involvement is frequent and always severe. Histological prognostic factors proposed for lupus nephritis (LN) including the World Health Organization and International Society of Nephrology/Renal Pathology Society--Working Group on the Classification classifications, active (AI) and chronicity (CI) indices may not predict response to treatment. The aim of this study was to correlate alpha-smooth muscle actin (alpha-SMA) expression, an early marker of glomerular and interstitial response to injury, to AI and CI, renal scarring progression and response to treatment. Fifty-seven kidney biopsy specimens obtained from 32 patients suffering from LN were studied. Twenty patients with class IV LN at first biopsy were identified to study renal progression to chronic renal failure until the use of immunosuppressive treatment. Interstitial alpha-SMA (I-alpha-SMA) was correlated only with CI (P < 0.001) whereas mesangial alpha-SMA (M-alpha-SMA) was correlated with neither LN activity (P = 0.126) nor sclerosis (P = 0.297). Only I-alpha-SMA was correlated with renal failure (P = 0.01). We divided patients with class IV LN into progressors and non-progressors based on the slope of serum creatinine. At first biopsy, M-alpha-SMA and I-alpha-SMA, but not AI and CI, were correlated with renal failure progression (M-alpha-SMA, 9.7b1.1 vs 7.8b1.4, P = 0.004; and I-alpha-SMA, 9.3b1.1 vs 6.5b3.2, P = 0.011). The study data highlight that I-alpha-SMA immunostain in class IV LN patients was correlated with chronicity indices. Moreover, M-alpha-SMA and I-alpha-SMA expression in first biopsy predicted renal progression modality. alpha-SMA expression may therefore be a useful marker to predict renal prognosis in LN.

Internal validation of the renal pelvic score: a novel marker of renal pelvic anatomy that predicts urine leak after partial nephrectomy.

PubMed

Tomaszewski, Jeffrey J; Smaldone, Marc C; Cung, Bic; Li, Tianyu; Mehrazin, Reza; Kutikov, Alexander; Canter, Daniel J; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

2014-08-01

To internally validate the renal pelvic score (RPS) in an expanded cohort of patients undergoing partial nephrectomy (PN). Our prospective institutional renal cell carcinoma database was used to identify all patients undergoing PN for localized renal cell carcinoma from 2007 to 2013. Patients were classified by RPS as having an intraparenchymal or extraparenchymal renal pelvis. Multivariate logistic regression models were used to examine the relationship between RPS and urine leak. Eight hundred thirty-one patients (median age, 60 ± 11.6 years; 65.1% male) undergoing PN (57.3% robotic) for low (28.9%), intermediate (56.5%), and high complexity (14.5%) localized renal tumors (median size, 3.0 ± 2.3 cm; median nephrometry score, 7.0 ± 2.6) were included. Fifty-four patients (6.5%) developed a clinically significant or radiographically identified urine leak. Seventy-two of 831 renal pelvises (8.7%) were classified as intraparenchymal. Intrarenal pelvic anatomy was associated with a markedly increased risk of urine leak (43.1% vs 3.0%; P <.001), major urine leak requiring intervention (23.6% vs 1.7%; P <.001), and minor urine leak (19.4% vs 1.2%; P <.001) compared with that in patients with an extrarenal pelvis. After multivariate adjustment, RPS (intraparenchymal renal pelvis; odds ratio [OR], 24.8; confidence interval [CI], 11.5-53.4; P <.001) was the most predictive of urine leak as was tumor endophyticity ("E" score of 3 [OR, 4.5; CI, 1.3-15.5; P = .018]), and intraoperative collecting system entry (OR, 6.1; CI, 2.5-14.9; P <.001). Renal pelvic anatomy as measured by the RPS best predicts urine leak after open and robotic partial nephrectomy. Although external validation of the RPS is required, preoperative identification of patients at increased risk for urine leak should be considered in perioperative management and counseling algorithms. Copyright © 2014 Elsevier Inc. All rights reserved.

Predicting 30-Day Hospital Readmissions in Acute Myocardial Infarction: The AMI "READMITS" (Renal Function, Elevated Brain Natriuretic Peptide, Age, Diabetes Mellitus, Nonmale Sex, Intervention with Timely Percutaneous Coronary Intervention, and Low Systolic Blood Pressure) Score.

PubMed

Nguyen, Oanh Kieu; Makam, Anil N; Clark, Christopher; Zhang, Song; Das, Sandeep R; Halm, Ethan A

2018-04-17

Readmissions after hospitalization for acute myocardial infarction (AMI) are common. However, the few currently available AMI readmission risk prediction models have poor-to-modest predictive ability and are not readily actionable in real time. We sought to develop an actionable and accurate AMI readmission risk prediction model to identify high-risk patients as early as possible during hospitalization. We used electronic health record data from consecutive AMI hospitalizations from 6 hospitals in north Texas from 2009 to 2010 to derive and validate models predicting all-cause nonelective 30-day readmissions, using stepwise backward selection and 5-fold cross-validation. Of 826 patients hospitalized with AMI, 13% had a 30-day readmission. The first-day AMI model (the AMI "READMITS" score) included 7 predictors: renal function, elevated brain natriuretic peptide, age, diabetes mellitus, nonmale sex, intervention with timely percutaneous coronary intervention, and low systolic blood pressure, had an optimism-corrected C-statistic of 0.73 (95% confidence interval, 0.71-0.74) and was well calibrated. The full-stay AMI model, which included 3 additional predictors (use of intravenous diuretics, anemia on discharge, and discharge to postacute care), had an optimism-corrected C-statistic of 0.75 (95% confidence interval, 0.74-0.76) with minimally improved net reclassification and calibration. Both AMI models outperformed corresponding multicondition readmission models. The parsimonious AMI READMITS score enables early prospective identification of high-risk AMI patients for targeted readmissions reduction interventions within the first 24 hours of hospitalization. A full-stay AMI readmission model only modestly outperformed the AMI READMITS score in terms of discrimination, but surprisingly did not meaningfully improve reclassification. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Noncontrast-enhanced magnetic resonance renal angiography using a repetitive artery and venous labelling technique at 3 T: comparison with contrast-enhanced magnetic resonance angiography in subjects with normal renal function.

PubMed

Park, Sung Yoon; Kim, Chan Kyo; Kim, EunJu; Park, Byung Kwan

2015-02-01

To investigate the feasibility of noncontrast-enhanced MR angiography (NC-MRA) using the repetitive artery and venous labelling (RAVEL) technique to evaluate renal arteries compared to contrast-enhanced MR angiography (CE-MRA). Twenty-five subjects with normal renal function underwent NC-MRA using a RAVEL technique and CE-MRA at 3 T. Two independent readers analysed the MRA images. Image quality, number of renal arteries, presence or absence of an early branching vessel, and diameter of the main renal arteries were evaluated. The overall image quality of NC-MRA was fair or greater in 88% of right and 92% of left renal arteries, while it was 96% in both sides with CE-MRA. On NC-MRA, the number of renal arteries in all subjects was perfectly predicted by both readers. Sensitivity and specificity for predicting early branching vessels were 82% and 100% for reader 1 and 82% and 95% for reader 2. Inter-modality agreement for comparing the diameters of main renal arteries was good or excellent at all segments for both readers. Inter-reader agreement was moderate or good at all segments except at the right distal segment on NC-MRA. NC-MRA with the RAVEL technique at 3 T may have comparable diagnostic feasibility for evaluating renal arteries compared to CE-MRA. • Accurate pre-treatment evaluation of renal artery anatomy helps clinical decision-making. • NC-MRA using RAVEL offers acceptable imaging quality for renal artery evaluation. • The 3 T RAVEL technique provides excellent diagnostic performance for renal artery evaluation. • The 3 T RAVEL technique may be an alternative to contrast-enhanced MRA.

Cutting Balloon Angioplasty (CBA) for the Treatment of Renal Artery Fibromuscular Dysplasia (FMD) in Six Patients: 5-Year Long-Term Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cotroneo, Antonio Raffaele; Amoroso, Luigi; Giammarino, Alberto

PurposeTo evaluate long-term outcomes in terms of hypertension control, recurrent stenosis, and reinterventions from patients who underwent cutting balloon angioplasty (CBA) for symptomatic renal artery fibromuscular dysplasia (FMD).Materials and MethodsFrom 2011, six consecutive renal artery FMD women underwent CBA for poorly controlled hypertension, despite antihypertensive therapy. Follow-up consisted of blood pressure monitoring and duplex ultrasonography at 1, 6, and 12 months and thereafter annually for 5 years.ResultsAll treatments were technically successful. Recurrence of hypertension was found in two patients within 12 months, and reinterventions were performed using CBA.ConclusionResults show the efficacy of CBA for renal artery FMD.

Atypical cells in a voided urine cytology specimen in a renal transplant recipient.

PubMed

Lu, Miao; Ho, Julie; Azordegan, Nazila; Perry, Anamarija M; Gibson, Ian W; Baker, Patricia

2017-01-01

Voided urine is routinely collected from renal transplant patients to screen for polyomavirus. In rare cases, atypical lymphoid cells can be detected in voided urine and raise the suspicion of post-transplant lymphoproliferative disorder (PTLD). However, further immunohistochemistry of the cell block and flow cytometry is frequently limited by the low cellularity and poor preservation of voided urine. Therefore, PTLD of the renal allograft is usually diagnosed from tissue biopsy or nephrectomy specimens. Herein, we report a rare case of atypical cells in a voided urine cytology specimen from a kidney transplant recipient. Needle core biopsy of the renal allograft showed monomorphic PTLD. Diagn. Cytopathol. 2017;45:69-72. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Are clinical, laboratory, and imaging markers suitable predictors of vesicoureteral reflux in children with their first febrile urinary tract infection?

PubMed

Mahyar, Abolfazl; Ayazi, Parviz; Mavadati, Shiva; Oveisi, Sonia; Habibi, Morteza; Esmaeily, Shiva

2014-08-01

This study was conducted to determine the predictive value of clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux in children with their first febrile urinary tract infection. One hundred fifty-three children with their first febrile urinary tract infection were divided into two groups according to the results of voiding cystourethrography: 60 children with vesicoureteral reflux and 93 children without. The sensitivity, specificity, positive and negative predictive value, likelihood ratio (positive and negative), and accuracy of the clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux were determined. Of the 153 children with febrile urinary tract infection, 60 patients (39.2%) had vesicoureteral reflux. There were significant differences between the two groups regarding fever>38℃, suprapubic pain, C-reactive protein quantitative level, number of red blood cells in the urine, and results of renal ultrasound and dimercaptosuccinic acid renal scanning (p<0.05). There were significant positive correlations between fever>38.2℃ and dimercaptosuccinic acid renal scanning and vesicoureteral reflux. Also, there were significant positive correlations between the erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound and high-grade vesicoureteral reflux. This study revealed fever>38.2℃ and dimercaptosuccinic acid renal scanning as the best predictive markers for vesicoureteral reflux in children with their first febrile urinary tract infection. In addition, erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound are the best predictive markers for high-grade vesicoureteral reflux.

Are Clinical, Laboratory, and Imaging Markers Suitable Predictors of Vesicoureteral Reflux in Children With Their First Febrile Urinary Tract Infection?

PubMed Central

Ayazi, Parviz; Mavadati, Shiva; Oveisi, Sonia; Habibi, Morteza; Esmaeily, Shiva

2014-01-01

Purpose This study was conducted to determine the predictive value of clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux in children with their first febrile urinary tract infection. Materials and Methods One hundred fifty-three children with their first febrile urinary tract infection were divided into two groups according to the results of voiding cystourethrography: 60 children with vesicoureteral reflux and 93 children without. The sensitivity, specificity, positive and negative predictive value, likelihood ratio (positive and negative), and accuracy of the clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux were determined. Results Of the 153 children with febrile urinary tract infection, 60 patients (39.2%) had vesicoureteral reflux. There were significant differences between the two groups regarding fever>38℃, suprapubic pain, C-reactive protein quantitative level, number of red blood cells in the urine, and results of renal ultrasound and dimercaptosuccinic acid renal scanning (p<0.05). There were significant positive correlations between fever>38.2℃ and dimercaptosuccinic acid renal scanning and vesicoureteral reflux. Also, there were significant positive correlations between the erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound and high-grade vesicoureteral reflux. Conclusions This study revealed fever>38.2℃ and dimercaptosuccinic acid renal scanning as the best predictive markers for vesicoureteral reflux in children with their first febrile urinary tract infection. In addition, erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound are the best predictive markers for high-grade vesicoureteral reflux. PMID:25132949

Mathematical model of renal elimination of fluid and small ions during hyper- and hypovolemic conditions.

PubMed

Gyenge, Christina C; Bowen, Bruce D; Reed, Rolf K; Bert, Joel L

2003-02-01

This study is concerned with the formulation of a 'kidney module' linked to the plasma compartment of a larger mathematical model previously developed. Combined, these models can be used to predict, amongst other things, fluid and small ion excretion rates by the kidney; information that should prove useful in evaluating values and trends related to whole-body fluid balance for different clinical conditions to establish fluid administration protocols and for educational purposes. The renal module assumes first-order, negative-feedback responses of the kidney to changes in plasma volume and/or plasma sodium content from their normal physiological set points. Direct hormonal influences are not explicitly formulated in this empiric model. The model also considers that the renal excretion rates of small ions other than sodium are proportional to the excretion rate of sodium. As part of the model development two aspects are emphasized (1): the estimation of parameters related to the renal elimination of fluid and small ions, and (2) model validation via comparisons between the model predictions and selected experimental data. For validation, model predictions of the renal dynamics are compared with new experimental data for two cases: plasma overload resulting from external fluid infusion (e.g. infusions of iso-osmolar solutions and/or hypertonic/hyperoncotic saline solutions), and untreated hypo volemic conditions that result from the external loss of blood. The present study demonstrates that the empiric kidney module presented above can provide good short-term predictions with respect to all renal outputs considered here. Physiological implications of the model are also presented. Copyright Acta Anaesthesiologica Scandinavica 47 (2003)

The Renal Arterial Resistance Index Predicts Worsening Renal Function in Chronic Heart Failure Patients

PubMed Central

Iacoviello, Massimo; Monitillo, Francesco; Leone, Marta; Citarelli, Gaetano; Doronzo, Annalisa; Antoncecchi, Valeria; Puzzovivo, Agata; Rizzo, Caterina; Lattarulo, Maria Silvia; Massari, Francesco; Caldarola, Pasquale; Ciccone, Marco Matteo

2016-01-01

Background/Aim The renal arterial resistance index (RRI) is a Doppler measure, which reflects abnormalities in the renal blood flow. The aim of this study was to verify the value of RRI as a predictor of worsening renal function (WRF) in a group of chronic heart failure (CHF) outpatients. Methods We enrolled 266 patients in stable clinical conditions and on conventional therapy. Peak systolic velocity and end diastolic velocity of a segmental renal artery were obtained by pulsed Doppler flow, and RRI was calculated. Creatinine serum levels were evaluated at baseline and at 1 year, and the changes were used to assess WRF occurrence. Results During follow-up, 34 (13%) patients showed WRF. RRI was associated with WRF at univariate (OR: 1.13; 95% CI: 1.07–1.20) as well as at a forward stepwise multivariate logistic regression analysis (OR: 1.09; 95% CI: 1.03–1.16; p = 0.005) including the other univariate predictors. Conclusions Quantification of arterial renal perfusion provides a new parameter that independently predicts the WRF in CHF outpatients. Its possible role in current clinical practice to better define the risk of cardiorenal syndrome progression is strengthened. PMID:27994601

Sensitivity and Specificity of Procalcitonin in Predicting Bacterial Infections in Patients With Renal Impairment

PubMed Central

El-sayed, Dena; Grotts, Jonathan; Golgert, William A.; Sugar, Alan M.

2014-01-01

Background  It is unclear whether procalcitonin is an accurate predictor of bacterial infections in patients with renal impairment, although it is used as a biomarker for early diagnosis of sepsis. We determined the sensitivity, specificity, positive and negative predictive values, accuracy and best predictive value of procalcitonin for predicting bacterial infection in adult patients with severe renal impairment. Methods  Retrospective study at a single-center community teaching hospital involving 473 patients, ages 18–65, with Modification of Diet in Renal Disease eGFR ≤30 ml/min per 1.73 m2, admitted between January 2009 and June 2012, with 660 independent hospital visits. A positive or negative culture (blood or identifiable focus of infection) was paired to the highest procalcitonin result performed 48 hours before or after collecting the culture. Results  The sensitivity and specificity to predict bacterial infection, using a procalcitonin level threshold of 0.5 ng/mL, was 0.80 and 0.35 respectively. When isolating for presence of bacteremia, the sensitivity and specificity were 0.89 and 0.35 respectively. An equation adjusting for optimum thresholds of procalcitonin levels for predicting bacterial infection at different levels of eGFR had a sensitivity and specificity of 0.55 and 0.80 respectively. Conclusions  Procalcitonin is not a reliably sensitive or specific predictor of bacterial infection in patients with renal impairment when using a single threshold. Perhaps two thresholds should be employed, where below the lower threshold (i.e. 0.5 ng/mL) bacterial infection is unlikely with a sensitivity of 0.80, and above the higher threshold (i.e. 3.2 ng/mL) bacterial infection is very likely with a specificity of 0.75. PMID:25734138

Sensitivity and specificity of procalcitonin in predicting bacterial infections in patients with renal impairment.

PubMed

El-Sayed, Dena; Grotts, Jonathan; Golgert, William A; Sugar, Alan M

2014-09-01

It is unclear whether procalcitonin is an accurate predictor of bacterial infections in patients with renal impairment, although it is used as a biomarker for early diagnosis of sepsis. We determined the sensitivity, specificity, positive and negative predictive values, accuracy and best predictive value of procalcitonin for predicting bacterial infection in adult patients with severe renal impairment. Retrospective study at a single-center community teaching hospital involving 473 patients, ages 18-65, with Modification of Diet in Renal Disease eGFR ≤30 ml/min per 1.73 m(2), admitted between January 2009 and June 2012, with 660 independent hospital visits. A positive or negative culture (blood or identifiable focus of infection) was paired to the highest procalcitonin result performed 48 hours before or after collecting the culture. The sensitivity and specificity to predict bacterial infection, using a procalcitonin level threshold of 0.5 ng/mL, was 0.80 and 0.35 respectively. When isolating for presence of bacteremia, the sensitivity and specificity were 0.89 and 0.35 respectively. An equation adjusting for optimum thresholds of procalcitonin levels for predicting bacterial infection at different levels of eGFR had a sensitivity and specificity of 0.55 and 0.80 respectively. Procalcitonin is not a reliably sensitive or specific predictor of bacterial infection in patients with renal impairment when using a single threshold. Perhaps two thresholds should be employed, where below the lower threshold (i.e. 0.5 ng/mL) bacterial infection is unlikely with a sensitivity of 0.80, and above the higher threshold (i.e. 3.2 ng/mL) bacterial infection is very likely with a specificity of 0.75.

Hepatorenal syndrome.

PubMed

Papper, S

1980-01-01

Renal failure without apparent cause (the hepatorenal syndrome) may develop in the course of cirrhosis of the liver. While the development of renal failure bears a poor prognosis, spontaneous recovery can occur. The data suggest that for the most part patients die in rather than of renal failure. The latter seems to be only part of a broader more fundamental disturbance. The pathogenesis of HRS is unknown, but the evidence supports an impairment of effective renal perfusion. The two major hypotheses concerning the nature of the impaired perfusion are that it is a physiologic response to alterations in the extrarenal circulation, and that there is an unidentified humoral agent(s) produced by or inadequately inactivated by or bypassing the diseased liver and causing circulatory changes in the kidney as well as in other organs. It is possible that both mechanisms are operative. Treatment is unsatisfactory and emphasis is presently best placed upon searching for more treatable causes of renal functional impairment in individual patients.

Acute renal failure after ingestion of guaifenesin and dextromethorphan.

PubMed

Small, Evan; Sandefur, Benjamin J

2014-07-01

Guaifenesin is a common nonprescription medication that has been implicated in drug-induced nephrolithiasis. Dextromethorphan, a nonprescription antitussive found in some guaifenesin-containing preparations, is increasingly recognized as a substance of abuse by many youth and young adults. Renally excreted medications known to have poor solubility in urine have the potential to precipitate when ingested in large quantity, leading to acute obstruction of the ureters and renal failure. We describe the case of a 22-year-old male who developed severe bilateral flank pain, hematuria, and oliguria after an isolated recreational ingestion of guaifenesin and dextromethorphan. The patient was found to have bilateral ureteral obstruction and acute renal failure, suspected to be secondary to precipitation of medication metabolites in the urine. This case highlights the potential for acute renal failure secondary to guaifenesin and dextromethorphan abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

[Clinical case of acute renal failure revealing an autoimmune hypothyroidism].

PubMed

Montasser, Dina Ibrahim; Hassani, Mohamed; Zajjari, Yassir; Bahadi, Abdelali; Alayoud, Ahmed; Hamzi, Amine; Hassani, Kawtar; Moujoud, Omar; Asseraji, Mohamed; Kadiri, Moncif; Aatif, Taoufik; El Kabbaj, Driss; Benyahia, Mohamed; Allam, Mustapha; Akhmouch, Ismail; Oualim, Zouhir

2010-04-01

Although the clinic picture is often indicative of muscle manifestations in patients with hypothyroidism, signs and symptoms of this condition are variable from simple elevation of serum muscle enzymes with myalgia, muscle weakness, cramps to rhabdomyolysis with acute renal failure which remains a rare event. Thyroid hormones affect the function of almost every body organ, and thyroid dysfunction produces a wide range of metabolic disturbances. Hypothyroidism is associated with significant effects on the kidney which the pathophysiology seems to be multifactorial, but the exact mechanisms remain poorly understood. Hypothyroidism as a cause of renal impairment is usually overlooked, leading to unnecessary diagnostic procedures. The main objective of our observation is to report a case of acute renal failure revealing an autoimmune hypothyroidism in which thyroid hormone substitution led to a significant improvement in muscular, thyroid and renal disorders. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Peritumoral Artery Scoring System: a Novel Scoring System to Predict Renal Function Outcome after Laparoscopic Partial Nephrectomy.

PubMed

Zhang, Ruiyun; Wu, Guangyu; Huang, Jiwei; Shi, Oumin; Kong, Wen; Chen, Yonghui; Xu, Jianrong; Xue, Wei; Zhang, Jin; Huang, Yiran

2017-06-06

The present study aimed to assess the impact of peritumoral artery characteristics on renal function outcome prediction using a novel Peritumoral Artery Scoring System based on computed tomography arteriography. Peritumoral artery characteristics and renal function were evaluated in 220 patients who underwent laparoscopic partial nephrectomy and then validate in 51 patients with split and total glomerular filtration rate (GFR). In particular, peritumoral artery classification and diameter were measured to assign arteries into low, moderate, and high Peritumoral Artery Scoring System risk categories. Univariable and multivariable logistic regression analyses were then used to determine risk factors for major renal functional decline. The Peritumoral Artery Scoring System and four other nephrometry systems were compared using receiver operating characteristic curve analysis. The Peritumoral Artery Scoring System was significantly superior to the other systems for predicting postoperative renal function decline (p < 0.001). In receiver operating characteristic analysis, our category system was a superior independent predictor of estimated glomerular filtration rate (eGFR) decline (area-under-the-curve = 0.865, p < 0.001) and total GFR decline (area-under-the-curve = 0.796, p < 0.001), and split GFR decline (area-under-the-curve = 0.841, p < 0.001). Peritumoral artery characteristics were independent predictors of renal function outcome after laparoscopic partial nephrectomy.

Multimarker assessment for the prediction of renal function improvement after percutaneous revascularization for renal artery stenosis

PubMed Central

Partovi, Sasan; Zeller, Thomas; Breidthardt, Tobias; Kaech, Max; Boeddinghaus, Jasper; Puelacher, Christian; Nestelberger, Thomas; Aschwanden, Markus; Mueller, Christian

2016-01-01

Background Identifying patients likely to have improved renal function after percutaneous transluminal renal angioplasty and stenting (PTRA) for renal artery stenosis (RAS) is challenging. The purpose of this study was to use a comprehensive multimarker assessment to identify those patients who would benefit most from correction of RAS. Methods In 127 patients with RAS and decreased renal function and/or hypertension referred for PTRA, quantification of hemodynamic cardiac stress using B-type natriuretic peptide (BNP), renal function using estimated glomerular filtration rate (eGFR), parenchymal renal damage using resistance index (RI), and systemic inflammation using C-reactive protein (CRP) were performed before intervention. Results Predefined renal function improvement (increase in eGFR ≥10%) at 6 months occurred in 37% of patients. Prognostic accuracy as quantified by the area under the receiver-operating characteristics curve for the ability of BNP, eGFR, RI and CRP to predict renal function improvement were 0.59 (95% CI, 0.48–0.70), 0.71 (95% CI, 0.61–0.81), 0.52 (95% CI, 0.41–0.65), and 0.56 (95% CI, 0.44–0.68), respectively. None of the possible combinations increased the accuracy provided by eGFR (lower eGFR indicated a higher likelihood for eGFR improvement after PTRA, P=ns for all). In the subgroup of 56 patients with pre-interventional eGFR <60 mL/min/1.73 m2, similar findings were obtained. Conclusions Quantification of renal function, but not any other pathophysiologic signal, provides at least moderate accuracy in the identification of patients with RAS in whom PTRA will improve renal function. PMID:27280085

Renal cell carcinoma, unclassified with medullary phenotype: poorly differentiated adenocarcinomas overlapping with renal medullary carcinoma.

PubMed

Sirohi, Deepika; Smith, Steven C; Ohe, Chisato; Colombo, Piergiuseppe; Divatia, Mukul; Dragoescu, Ema; Rao, Priya; Hirsch, Michelle S; Chen, Ying-Bei; Mehra, Rohit; Amin, Mahul B

2017-09-01

Renal medullary carcinoma (RMC) is a highly aggressive renal cell carcinoma arising in the collecting system and requiring careful correlation with status of sickle cell trait. A panel of international experts has recently proposed provisional diagnostic terminology, renal cell carcinoma, unclassified, with medullary phenotype, based on encountering an extraordinarily rare tumor with RMC morphology and immunophenotype in an individual proven not to have a hemoglobinopathy. Herein, we extend this observation to a cohort of 5 such tumors, morphologically similar to RMC, lacking SMARCB1 expression by immunohistochemistry, but each without evidence of a hemoglobinopathy. The tumors arose in 4 men and 1 woman with a mean age of 44 years, occurring in 3 left and 2 right kidneys. Clinically, aggression was apparent with involvement of perinephric adipose tissue in all 5 cases, nodal metastasis in 4 of 5 cases, and death of disease in 4 of 5 cases within 3-27 months. Histologic sections showed poorly differentiated adenocarcinoma, often with solid and nested growth patterns, as well as infiltrative glandular, tubulopapillary, cribriform, or reticular growth. Rhabdoid and sarcomatoid cytomorphology was seen in a subset. All tumors showed PAX8 nuclear positivity and SMARCB1 loss, with OCT3/4 expression in 4 of 5 cases. In summary, this first series of renal cell carcinoma, unclassified, with medullary phenotype documents tumors with morphologic, immunophenotypic, and prognostic features of RMC occurring in individuals without sickle cell trait. Although greater biologic and molecular understanding is needed, the available evidence points to these cases representing a sporadic counterpart to sickle cell trait-associated RMC. Copyright © 2017 Elsevier Inc. All rights reserved.

Types and Outcome of Fetal Urinary Anomalies in Low Resource Setting Countries: A Retrospective Study.

PubMed

Shalaby, Hend; Hemida, Reda; Nabil, Hanan; Ibrahim, Mohammad

2016-10-01

Congenital anomalies of the kidney and urinary tract in the developing countries have a poor prognosis due to limited experience in antenatal and postnatal management. A 3-year retrospective study was carried out from January 2011 to December 2013. The following data were collected and analyzed: maternal age, gravidity, parity, gestational age at diagnosis, and ultrasonography findings. Final diagnosis after birth, the performed surgeries, follow-up data, as well as survival at one year were also analyzed. The mean age of the included patients was 28 years (range 20-35 years). The mean parity was 1.7 (range 0-4). The mean gestational age at diagnosis was 26 weeks (range 15-36 weeks). Consanguinity was reported in 10 cases (24.4 %). There were 25 males and 16 females. Bilateral renal agenesis was the commonest type (19.5 %). The anomalies of kidneys and urinary tract in our cases were associated with other anomalies in 8 cases (19.5 %). Oligohydramnios was detected in bilateral renal agenesis and posterior urethral valve. Surgical interference during the first 6 months was performed in 6 cases; pyeloplasty for unilateral or bilateral hydronephrosis was performed in 5 cases; and excision of solitary renal cyst performed in one case. By the end of the first year, two of the three cases with chronic renal disease, who were under peritoneal dialysis, died, and three cases who had undergone pyeloplasty were lost to follow-up. Among the 41 cases with antenatally diagnosed renal and urinary malformations; bilateral renal agenesis was the commonest anomaly (19.5 %). There were high rates of induction of abortion, IUFD, and neonatal deaths. The poor outcome may be due to lack of experience in performing invasive therapeutic fetal procedures.

Brentuximab vedotin, an antibody–drug conjugate, in patients with CD30‐positive haematologic malignancies and hepatic or renal impairment

PubMed Central

Chen, Robert; O'Connor, Owen A.; Gopal, Ajay K.; Ramchandren, Radhakrishnan; Goy, Andre; Matous, Jeffrey V.; Fasanmade, Adedigbo A.; Manley, Thomas J.; Han, Tae H.

2016-01-01

Abstract Aims Brentuximab vedotin, an antibody–drug conjugate (ADC), selectively delivers the microtubule‐disrupting agent monomethyl auristatin E (MMAE) into CD30‐expressing cells. The pharmacokinetics of brentuximab vedotin have been characterized in patients with CD30‐positive haematologic malignancies. The primary objective of this phase 1 open label evaluation was to assess the pharmacokinetics of brentuximab vedotin in patients with hepatic or renal impairment. Methods Systemic exposures were evaluated following intravenous administration of 1.2 mg kg–1 brentuximab vedotin in patients with CD30‐positive haematologic malignancies and hepatic (n = 7) or renal (n = 10) impairment and compared with those of unimpaired patients (n = 8) who received 1.2 mg kg–1 brentuximab vedotin in another arm of the study. Results For any hepatic impairment, the ratios of geometric means (90% confidence interval) for AUC(0,∞) were 0.67 (0.48, 0.93) for ADC and 2.29 (1.27, 4.12) for MMAE. Mild or moderate renal impairment caused no apparent change in ADC or MMAE exposures. Severe renal impairment (creatinine clearance <30 ml min–1; n = 3) decreased ADC exposures (0.71 [0.54, 0.94]) and increased MMAE exposures (1.90 [0.85, 4.21]). No consistent pattern of specific adverse events was evident, but analysis of the safety data was confounded by the patients' poor baseline conditions. Five patients died due to adverse events considered unrelated to brentuximab vedotin. All had substantial comorbidities and most had poor baseline performance status. Conclusions Hepatic impairment and severe renal impairment may cause decreases in brentuximab vedotin ADC exposures and increases in MMAE exposures. PMID:27115790

Clinical Significance of Anti-Ribosomal P Protein Antibodies in Patients with Lupus Nephritis.

PubMed

Sarfaraz, Sabahat; Anis, Sabiha; Ahmed, Ejaz; Muzaffar, Rana

2018-04-09

Systemic lupus erythematosus (SLE) is achronic inflammatory disorder affecting multiplesystems of the body. Clinical features show wide variations in patients with different ethnic background. Renal involvement is a predictor of poor prognosis. Immunological workup is an integral part of SLE diagnostic criteria. Anti-ribosomal P Protein (anti-P) antibodies are highly specific for SLE. They may be present inantinuclear antibodies (ANA) negative SLE patients. Their role in lupus nephritis (LN) is under debate, some researchers found them associated with poor prognosiswhereasothers found favorable effect of these antibodies on renal disease. In this study we investigated frequency of anti-P antibodies and the effect of these antibodies on renal functions in LN patients. A total of 133SLE patientswere enrolled in this study. All patients had ANA in their sera. Anti-P antibodies along with other autoantibodiesagainstextractable nuclearantigens (anti-Sm, anti-SS-A, anti-SS-B, anti-histones and anti-RNP) were detected by Immunoblot assay. Anti-dsDNA antibodies were detected by indirect immunofluorescence assay (IFA). We found anti-P antibodies in 10.5% LN patients. Interestingly their presence in association with anti-dsDNA was associated with improved renal functions in comparison to those who had anti-dsDNA antibodies in isolation (serum creatinine: 1.3 ± 0.8 mg/dl vs. 3.0 ± 3.0; P= 0.091). Anti-dsDNA antibodies are directly involved in renal pathology in SLE patients. As these antibodies are nephrotoxic, concomitant occurrence of anti-P antibodies seems to offer a shielding effect on renal functions, which was evident by normal serum creatinine levels. Therefore anti-P antibodies may be considered as a good prognostic marker in these patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Urinary vitamin D-binding protein, a novel biomarker for lupus nephritis, predicts the development of proteinuric flare.

PubMed

Go, D J; Lee, J Y; Kang, M J; Lee, E Y; Lee, E B; Yi, E C; Song, Y W

2018-01-01

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Conventional biomarkers for assessing renal disease activity are imperfect in predicting clinical outcomes associated with LN. The aim of this study is to identify urinary protein biomarkers that reliably reflect the disease activity or predict clinical outcomes. A quantitative proteomic analysis was performed to identify protein biomarker candidates that can differentiate between SLE patients with and without LN. Selected biomarker candidates were further verified by enzyme-linked immunosorbent assay using urine samples from a larger cohort of SLE patients ( n = 121) to investigate their predictive values for LN activity measure. Furthermore, the association between urinary levels of a selected panel of potential biomarkers and prognosis of LN was assessed with a four-year follow-up study of renal outcomes. Urinary vitamin D-binding protein (VDBP), transthyretin (TTR), retinol binding protein 4 (RBP4), and prostaglandin D synthase (PTGDS) were significantly elevated in SLE patients with LN, especially in patients with active LN ( n = 21). Among them, VDBP well correlated with severity of proteinuria (rho = 0.661, p < 0.001) and renal SLE Disease Activity Index (renal SLEDAI) (rho = 0.520, p < 0.001). In the four-year follow-up, VDBP was a significant risk factor (hazard ratio 9.627, 95% confidence interval 1.698 to 54.571, p = 0.011) for the development of proteinuric flare in SLE patients without proteinuria ( n = 100) after adjustments for multiple confounders. Urinary VDBP correlated with proteinuria and renal SLEDAI, and predicted the development of proteinuria.

Application of a Physiologically Based Pharmacokinetic Model to Assess Propofol Hepatic and Renal Glucuronidation in Isolation: Utility of In Vitro and In Vivo Data

PubMed Central

Gill, Katherine L.; Gertz, Michael; Houston, J. Brian

2013-01-01

A physiologically based pharmacokinetic (PBPK) modeling approach was used to assess the prediction accuracy of propofol hepatic and extrahepatic metabolic clearance and to address previously reported underprediction of in vivo clearance based on static in vitro–in vivo extrapolation methods. The predictive capacity of propofol intrinsic clearance data (CLint) obtained in human hepatocytes and liver and kidney microsomes was assessed using the PBPK model developed in MATLAB software. Microsomal data obtained by both substrate depletion and metabolite formation methods and in the presence of 2% bovine serum albumin were considered in the analysis. Incorporation of hepatic and renal in vitro metabolic clearance in the PBPK model resulted in underprediction of propofol clearance regardless of the source of in vitro data; the predicted value did not exceed 35% of the observed clearance. Subsequently, propofol clinical data from three dose levels in intact patients and anhepatic subjects were used for the optimization of hepatic and renal CLint in a simultaneous fitting routine. Optimization process highlighted that renal glucuronidation clearance was underpredicted to a greater extent than liver clearance, requiring empirical scaling factors of 17 and 9, respectively. The use of optimized clearance parameters predicted hepatic and renal extraction ratios within 20% of the observed values, reported in an additional independent clinical study. This study highlights the complexity involved in assessing the contribution of extrahepatic clearance mechanisms and illustrates the application of PBPK modeling, in conjunction with clinical data, to assess prediction of clearance from in vitro data for each tissue individually. PMID:23303442

Pure Membranous Lupus Nephritis: Description of a Cohort of 150 Patients and Review of the Literature.

PubMed

Silva-Fernández, Lucía; Otón, Teresa; Askanase, Anca; Carreira, Patricia; López-Longo, Francisco Javier; Olivé, Alejandro; Rúa-Figueroa, Íñigo; Narváez, Javier; Ruiz-Lucea, Esther; Andrés, Mariano; Calvo, Enrique; Toyos, Francisco; Alegre-Sancho, Juan José; Tomero, Eva; Montilla, Carlos; Zea, Antonio; Uriarte, Esther; Calvo-Alén, Jaime; Marras, Carlos; Martínez-Taboada, Víctor M; Belmonte-López, María Ángeles; Rosas, José; Raya, Enrique; Bonilla, Gema; Freire, Mercedes; Pego-Reigosa, José María; Millán, Isabel; Hughes-Morley, Adwoa; Andreu, José Luis

2017-05-18

The course and long-term outcome of pure membranous lupus nephritis (MLN) are little understood. The aims of this study are to evaluate the clinical features, course, outcome and prognostic indicators in pure MLN and to determine the impact of ethnicity and the type of health insurance on the course and prognosis of pure MLN. We conducted a retrospective review of medical records of 150 patients with pure MLN from Spain and the USA. Mean age was 34.2±12.5 and 80% were women. Sixty-eight percent of patients had nephrotic syndrome at diagnosis. The average serum creatinine was 0.98±0.78mg/dl. Six percent of patients died and 5.3% developed end-stage renal disease (ESRD). ESRD was predicted by male sex, hypertension, dyslipidemia, high basal 24h-proteinuria, high basal serum creatinine and a low basal creatinine clearance. Age, cardiac insufficiency, peripheral artheriopathy, hemodialysis and not having received mycophenolate mofetil or antimalarials for MLN predicted death. Pure MLN frequently presents with nephrotic syndrome, high proteinuria and normal serum creatinine. Its prognosis is favourable in maintaining renal function although proteinuria usually persists over time. Baseline cardiovascular disease and not having a health insurance are related with poor prognosis. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Seroprevalence of Streptococcal Inhibitor of Complement (SIC) suggests association of streptococcal infection with chronic kidney disease

PubMed Central

2013-01-01

Background Group A streptococcus (GAS) is an etiological agent for the immune mediated sequela post streptococcal glomerulonephritis (PSGN). In some populations PSGN is recognized as a risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). It was found that a significantly greater proportion of subjects with past history of PSGN than without the history exhibited seroreactions to streptococcal antigens called streptococcal inhibitor of complement (SIC) and to distantly related SIC (DRS). These antigens are expressed by major PSGN-associated GAS types. We therefore predicted that in populations such as India, which is endemic for streptococcal diseases and which has high prevalence of CKD and ESRD, greater proportions of CKD and ESRD patients exhibit seroreaction to SIC and DRS than healthy controls. Methods To test this we conducted a SIC and DRS seroprevalence study in subjects from Mumbai area. We recruited 100 CKD, 70 ESRD and 70 healthy individuals. Results Nineteen and 35.7% of CKD and ESRD subjects respectively were SIC antibody-positive, whereas only 7% of healthy cohort was seropositive to SIC. Furthermore, significantly greater proportion of the ESRD patients than the CKD patients is seropositive to SIC (p=0.02; odds ratio 2.37). No association was found between the renal diseases and DRS-antibody-positivity. Conclusions Past infection with SIC-positive GAS is a risk factor for CKD and ESRD in Mumbai population. Furthermore, SIC seropositivity is predictive of poor prognosis of CKD patients. PMID:23642030

A medical oncologist's approach to immunotherapy for advanced renal tumors: is nephrectomy indicated?

PubMed

Cooney, Matthew M; Remick, Scot C; Vogelzang, Nicholas J

2004-02-01

Metastatic renal cell carcinoma is highly resistant to systemic therapy. Although interleukin-2 and interferon remain the most active agents for this disease, long-term survival rates remain poor. Two phase 3 trials, European Organization Research and Treatment of Cancer 30947 and Southwest Oncology Group 8949, have demonstrated a survival benefit of nephrectomy followed by interferon versus interferon alone in patients having an excellent performance status (PS 0 and 1). Removal of the primary tumor followed by interferon is not recommended for patients with a moderate or poor PS (PS 2-4). Even with this aggressive approach, most patients eventually will die from their kidney cancer; therefore, every patient with metastatic disease should be considered for enrollment into clinical trials.

An effective technique to facilitate radiographic stone visualization with an internal stent during shock wave lithotripsy.

PubMed

Sundaram, C P; Saltzman, B

1998-10-01

We describe a simple method to assist stone localization during shock wave lithotripsy in the presence of a Double J stent. A 4F whistle tip ureteral catheter is passed alongside a previously inserted 6F Double J stent. The tip of the ureteral stent is positioned in the lower or mid third of the ureter. Contrast material is injected through the ureteral catheter during lithotripsy to assist stone localization. This technique has been successful in localization of poorly opacified renal stones during lithotripsy. Radiolucent and poorly calcified renal stones can be easily localized during shock wave lithotripsy, despite the presence of a Double J stent. No special catheters or stents are required for this technique.

Renal hemodynamics in space.

PubMed

Kramer, H J; Heer, M; Cirillo, M; De Santo, N G

2001-09-01

Renal excretory function and hemodynamics are determined by the effective circulating plasma volume as well as by the interplay of systemic and local vasoconstrictors and vasodilators. Microgravity results in a headward shift of body fluid. Because the control conditions of astronauts were poorly defined in many studies, controversial results have been obtained regarding diuresis and natriuresis as well as renal hemodynamic changes in response to increased central blood volume, especially during the initial phase of space flight. Renal excretory function and renal hemodynamics in microgravity are affected in a complex fashion, because during the initial phase of space flight, variable mechanisms become operative to modulate the effects of increased central blood volume. They include interactions between vasodilators (dopamine, atrial natriuretic peptide, and prostaglandins) and vasoconstrictors (sympathetic nervous system and the renin-angiotensin system). The available data suggest a moderate rise in glomerular filtration rate during the first 2 days after launch without a significant increase in effective renal plasma flow. In contrast, too few data regarding the effects of space flight on renal function during the first 12 hours after launch are available and are, in addition, partly contradictory. Thus, detailed and well-controlled studies are required to shed more light on the role of the various factors besides microgravity that determine systemic and renal hemodynamics and renal excretory function during the different stages of space flight.

[Pleural metastases of renal carcinoma].

PubMed

Giigoruk, O G; Lazarev, A F; Doroshenko, V S

2007-01-01

Metastases in renal carcinoma are diagnosed at initial diagnosis in 25% examinees. Traditional renal carcinoma has higher metastatic potential, is associated with worse survival of the patients compared to papillary cancer. We studied cytological characteristics of renal carcinoma metastases to the pleura in comparison with histological studies of the primary lesion using immunohistochemical findings. We examined cytologically pleural liquid in renal carcinoma metastases to the pleura in 6 patients (2.3% of carcinomatous pleuricies). High efficacy was shown by a cytocentrifuge CYTOSPIN-4. In 3 cases initial cancer was renal cell carcinoma, pleural exudation developed 2 years later, clear cell carcinoma appeared 6 years later and papillary cancer--10 years later. In the other 3 cases malignant cells were detected in new-onset cases. Renal carcinoma was diagnosed in one case. Cytological preparations were studied with identification of cytological signs typical for classic clear cell, granulocell and papillary renal cancer. Immunohistochemical examination of primary tumor lesion in the kidney discovered high proliferative activity of tumor cells by Ki-67 index to 5.28%. The tumors had solitary Bcl-2 positive cells. Expression of mutant p-53 took place in 0.93%. Her-2/neu hyperexpression was not found in the tumors of the above patients. Such immunohistochemical parameters point to poor prognosis. This is confirmed by renal carcinoma metastases to the pleura.

Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin

PubMed Central

Liu, Qingdu; Binns, Thomas C.; Davidoff, Olena; Kapitsinou, Pinelopi P.; Pfaff, Andrew S.; Olauson, Hannes; Fogo, Agnes B.; Fong, Guo-Hua; Gross, Kenneth W.

2016-01-01

Renal peritubular interstitial fibroblast-like cells are critical for adult erythropoiesis, as they are the main source of erythropoietin (EPO). Hypoxia-inducible factor 2 (HIF-2) controls EPO synthesis in the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors. Renal interstitial cells with EPO-producing capacity are poorly characterized, and the role of the PHD/HIF-2 axis in renal EPO-producing cell (REPC) plasticity is unclear. Here we targeted the PHD/HIF-2/EPO axis in FOXD1 stroma-derived renal interstitial cells and examined the role of individual PHDs in REPC pool size regulation and renal EPO output. Renal interstitial cells with EPO-producing capacity were entirely derived from FOXD1-expressing stroma, and Phd2 inactivation alone induced renal Epo in a limited number of renal interstitial cells. EPO induction was submaximal, as hypoxia or pharmacologic PHD inhibition further increased the REPC fraction among Phd2–/– renal interstitial cells. Moreover, Phd1 and Phd3 were differentially expressed in renal interstitium, and heterozygous deficiency for Phd1 and Phd3 increased REPC numbers in Phd2–/– mice. We propose that FOXD1 lineage renal interstitial cells consist of distinct subpopulations that differ in their responsiveness to Phd2 inactivation and thus regulation of HIF-2 activity and EPO production under hypoxia or conditions of pharmacologic or genetic PHD inactivation. PMID:27088801

Renal cortical volume: High correlation with pre- and post-operative renal function in living kidney donors.

PubMed

Gardan, Edouard; Jacquemont, Lola; Perret, Christophe; Heudes, Pierre-Marie; Gourraud, Pierre-Antoine; Hourmant, Maryvonne; Frampas, Eric; Limou, Sophie

2018-02-01

CT volumetry has previously been proposed as an alternative to scintigraphy for the evaluation of pre-donation split renal function and the prediction of post-donation renal function in living kidney donors. The aim of our study was to retrospectively assess the relevance of three CT volumetry techniques for estimating pre-donation kidney function and predicting the risk for chronic kidney disease (CKD) at 1-year post-nephrectomy in a French cohort of living donors using isotopic measures of kidney function. Kidney volume was quantified pre-donation for 105 donors using three methods total parenchymal three-dimensional renal volume (3DRV), total parenchymal renal volume contouring (RVCt), and renal cortical volume (RCoV). Subjects also had a 51Cr-EDTA scintigraphy to measure glomerular filtration rate (mGFR) pre-donation and 1-year after donation. For each volume, we tested for association with mGFR using univariate regression models, and computed receiver operating characteristics analyses to assess their predictive potential of post-donation CKD. Our population was composed of healthy subjects, who were predominantly female (69%) with a median age at donation of 51yo. Median mGFR was 102 mL/min/1.73 m 2 at pre-donation and 66 mL/min/1.73 m 2 1-year after nephrectomy. The pre-donation median volume of the preserved kidney was 156 cm 3 , 163 cm 3 and 99 cm 3 for the 3DRV, RVCt and RCoV methods respectively, with a high correlation observed between each technique (R > 0.84). For all methods, total kidney volume was significantly associated with pre-donation mGFR (P < 0.001). Preserved kidney volume was also strongly correlated with post-donation mGFR (P < 0.0001), with the strongest correlation observed for RCoV (R = 0.60 vs. R = 0.39 and R = 0.51 for 3DRV and RVCt, respectively). Finally, the RCoV method yielded the best predictive value of 1-year post-donation CKD (AUC = 0.80 vs. AUC = 0.76 and 0.70 for RVCt and 3DRV, respectively). In our cohort of healthy donors with measured kidney function, cortical volumetry (RCoV) appears as the best volumetric technique to use as a surrogate to scintigraphy for estimating pre-donation split renal function and predicting post-donation renal outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Advanced chronic kidney disease in non-valvular atrial fibrillation: extending the utility of R2CHADS2 to patients with advanced renal failure.

PubMed

Bautista, Josef; Bella, Archie; Chaudhari, Ashok; Pekler, Gerald; Sapra, Katherine J; Carbajal, Roger; Baumstein, Donald

2015-04-01

The R2CHADS2 is a new prediction rule for stroke risk in atrial fibrillation (AF) patients wherein R stands for renal risk. However, it was created from a cohort that excluded patients with advanced renal failure (defined as glomerular filtration rate of <30 mL/min). Our study extends the use of R2CHADS2 to patients with advanced renal failure and aims to compare its predictive power against the currently used CHADS and CHA2DS2VaSc. This retrospective cohort study analyzed the 1-year risk for stroke of the 524 patients with AF at Metropolitan Hospital Center. AUC and C statistics were calculated using three groups: (i) the entire cohort including patients with advanced renal failure, (ii) a cohort excluding patients with advanced renal failure and (iii) all patients with GFR < 30 mL/min only. R2CHADS2, as a predictor for stroke risk, consistently performs better than CHADS2 and CHA2DS2VsC in groups 1 and 2. The C-statistic was highest in R2CHADS compared with CHADS or CHADSVASC in group 1 (0.718 versus 0.605 versus 0.602) and in group 2 (0.724 versus 0.584 versus 0.579). However, there was no statistically significant difference in group 3 (0.631 versus 0.629 versus 0.623). Our study supports the utility of R2CHADS2 as a clinical prediction rule for stroke risk in patients with advanced renal failure.

R.E.N.A.L. Nephrometry Score: A Preoperative Risk Factor Predicting the Fuhrman Grade of Clear-Cell Renal Carcinoma

PubMed Central

Chen, Shao-Hao; Wu, Yu-Peng; Li, Xiao-Dong; Lin, Tian; Guo, Qing-Yong; Chen, Ye-Hui; Huang, Jin-Bei; Wei, Yong; Xue, Xue-Yi; Zheng, Qing-Shui; Xu, Ning

2017-01-01

Objective: The purpose of this study was to evaluate the efficacy and feasibility of the R.E.N.A.L. Nephrometry Score to postoperatively predict high-grade clear-cell renal carcinoma (ccRCC). Methods: The study included 288 patients diagnosed with ccRCC who had complete CT/CTA data and R.E.N.A.L. Nephrometry Scores and underwent renal surgery at our center between January 2012 and December 2015. The relationship between the pathological grade of renal masses and R.E.N.A.L. Nephrometry Score was evaluated. Results: Univariate analysis indicated that diagnostic modality, cystic necrosis, enlargement of the regional lymph node, distant metastasis, clinical T stage, TNM stage, surgical modality, tumor size, nearness of the tumor to the collecting system or sinus, total Nephrometry Score and individual anatomic descriptor components were significantly associated with postoperative tumor grade (P < 0.05). Multivariate analysis showed that tumor size, the maximal diameter (R score), exophytic/endophytic properties (E score) and the location relative to the polar lines (L score) were independent prognostic factors to preoperatively predicting ccRCC pathological grade. The areas under the ROC curve with respect to the multi-parameter regression model (0.935, 95%CI: 0.904-0.966), tumor size (0.901, 95%CI: 0.866-0.937), R score (0.868, 95%CI: 0.825-0.911), E score (0.511, 95%CI: 0.442-0.581) and L score (0.842, 95%CI: 0.791-0.892) were calculated and compared. Conclusion: Tumor size, as well as R, E, and L scores were independent prognostic factors for high-grade pathology. Lager tumor sizes and higher R, E and L scores were more likely to be associated with high-grade pathological outcomes. Thus, the R.E.N.A.L. Score is of practical significance in facilitating urologists to make therapeutic decisions. PMID:29151960

A Mathematical Method to Calculate Tumor Contact Surface Area: An Effective Parameter to Predict Renal Function after Partial Nephrectomy.

PubMed

Hsieh, Po-Fan; Wang, Yu-De; Huang, Chi-Ping; Wu, Hsi-Chin; Yang, Che-Rei; Chen, Guang-Heng; Chang, Chao-Hsiang

2016-07-01

We proposed a mathematical formula to calculate contact surface area between a tumor and renal parenchyma. We examined the applicability of using contact surface area to predict renal function after partial nephrectomy. We performed this retrospective study in patients who underwent partial nephrectomy between January 2012 and December 2014. Based on abdominopelvic computerized tomography or magnetic resonance imaging, we calculated the contact surface area using the formula (2*π*radius*depth) developed by integral calculus. We then evaluated the correlation between contact surface area and perioperative parameters, and compared contact surface area and R.E.N.A.L. (Radius/Exophytic/endophytic/Nearness to collecting system/Anterior/Location) score in predicting a reduction in renal function. Overall 35, 26 and 45 patients underwent partial nephrectomy with open, laparoscopic and robotic approaches, respectively. Mean ± SD contact surface area was 30.7±26.1 cm(2) and median (IQR) R.E.N.A.L. score was 7 (2.25). Spearman correlation analysis showed that contact surface area was significantly associated with estimated blood loss (p=0.04), operative time (p=0.04) and percent change in estimated glomerular filtration rate (p <0.001). On multivariate analysis contact surface area and R.E.N.A.L. score independently affected percent change in estimated glomerular filtration rate (p <0.001 and p=0.03, respectively). On ROC curve analysis contact surface area was a better independent predictor of a greater than 10% change in estimated glomerular filtration rate compared to R.E.N.A.L. score (AUC 0.86 vs 0.69). Using this simple mathematical method, contact surface area was associated with surgical outcomes. Compared to R.E.N.A.L. score, contact surface area was a better predictor of functional change after partial nephrectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of the Chronic Kidney Disease Epidemiology Collaboration, the Modification of Diet in Renal Disease study and the Cockcroft-Gault equation in patients with heart failure.

PubMed

Szummer, Karolina; Evans, Marie; Carrero, Juan Jesus; Alehagen, Urban; Dahlström, Ulf; Benson, Lina; Lund, Lars H

2017-01-01

It is unknown how the creatinine-based renal function estimations differ for dose adjustment cut-offs and risk prediction in patients with heart failure. The renal function was similar with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (median 59 mL/min/1.73 m 2 , IQR 42 to 77) and Modification of Diet in Renal Disease Study (MDRD) (59 mL/min/1.73 m 2 , IQR 43 to 75) and slightly lower with the Cockcroft-Gault (CG) equation (57 mL/min, IQR 39 to 82). Across the commonly used renal function stages, the CKD-EPI and the MDRD classified patients into the same stage in 87.2% (kappa coefficient 0.83, p<0.001); the CKD-EPI and the CG equation agreed in 52.3% (kappa coefficient 0.39, p<0.001). Hence, a differing number of patients will receive dose adjustment depending on which formula is used as cut-off. The CG equation predicted worse prognosis better (c-statistics 0.740, 95% CI 0.734 to 0.746) than CKD-EPI (0.697, 95% CI 0.690 to 0.703, p<0.001) and MDRD (0.680, 95% CI 0.734 to 0.746). Using net reclassification improvement (NRI), the CG identified 12.8% more patients at higher risk of death as compared with the CKD-EPI equation. Patients registered in the Swedish Heart Failure Registry (n= 40 736) with standardised creatinine values between 2000 and 2012 had their renal function estimated with the CKD-EPI, the MDRD and the CG. Agreement between the formulas was compared for categories. Prediction of death was assessed with c-statistics and with NRI. The choice of renal function estimation formula has clinical implications and differing results at various cut-off levels. For prognosis, the CG predicts mortality better than the CKD-EPI and MDRD.

Comparison of the Chronic Kidney Disease Epidemiology Collaboration, the Modification of Diet in Renal Disease study and the Cockcroft-Gault equation in patients with heart failure

PubMed Central

Szummer, Karolina; Evans, Marie; Carrero, Juan Jesus; Alehagen, Urban; Dahlström, Ulf; Benson, Lina; Lund, Lars H

2017-01-01

Background It is unknown how the creatinine-based renal function estimations differ for dose adjustment cut-offs and risk prediction in patients with heart failure. Method and results The renal function was similar with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (median 59 mL/min/1.73 m2, IQR 42 to 77) and Modification of Diet in Renal Disease Study (MDRD) (59 mL/min/1.73 m2, IQR 43 to 75) and slightly lower with the Cockcroft-Gault (CG) equation (57 mL/min, IQR 39 to 82). Across the commonly used renal function stages, the CKD-EPI and the MDRD classified patients into the same stage in 87.2% (kappa coefficient 0.83, p<0.001); the CKD-EPI and the CG equation agreed in 52.3% (kappa coefficient 0.39, p<0.001). Hence, a differing number of patients will receive dose adjustment depending on which formula is used as cut-off. The CG equation predicted worse prognosis better (c-statistics 0.740, 95% CI 0.734 to 0.746) than CKD-EPI (0.697, 95% CI 0.690 to 0.703, p<0.001) and MDRD (0.680, 95% CI 0.734 to 0.746). Using net reclassification improvement (NRI), the CG identified 12.8% more patients at higher risk of death as compared with the CKD-EPI equation. Patients registered in the Swedish Heart Failure Registry (n= 40 736) with standardised creatinine values between 2000 and 2012 had their renal function estimated with the CKD-EPI, the MDRD and the CG. Agreement between the formulas was compared for categories. Prediction of death was assessed with c-statistics and with NRI. Conclusion The choice of renal function estimation formula has clinical implications and differing results at various cut-off levels. For prognosis, the CG predicts mortality better than the CKD-EPI and MDRD. PMID:28761677

Population pharmacokinetics of teicoplanin in hospitalized elderly patients using cystatin C as an indicator of renal function.

PubMed

Kasai, Hidefumi; Tsuji, Yasuhiro; Hiraki, Yoichi; Tsuruyama, Moeko; To, Hideto; Yamamoto, Yoshihiro

2018-04-01

Serum cystatin C (CysC) has recently been proposed as an alternative marker to serum creatinine (SCR) for estimating renal clearance. In the present study, we performed a population pharmacokinetic analysis of teicoplanin (TEIC), which is mainly eliminated through the kidneys, using CysC as a predictor for renal clearance. Thirty-six patients with MRSA infections who were administrated to the National Hospital Organization Beppu Medical Center between January 2012 and December 2013 were enrolled and gave 123 sets of blood TEIC concentration data. Renal clearance was estimated by the Hoek equation using CysC, by creatinine clearance predicted by the Cockcroft-Gault equation using SCR, or directly by CysC. One compartment open model with inter-individual variabilities for renal clearance and the volume of distribution as well as an additional residual error model was used to estimate population pharmacokinetic parameters for TEIC. The model with the best predictability was that with CysC as a predictor for renal clearance; it showed better significance than the models using estimated the glomerular filtration rate by the Hoek equation or CLcr. The final model was as follows: CL (L/hr) = 0.510 × (CysC/1.4) -0.68  × Total body weight/60 0.81 , omega (CL) = 19.8% CV, VC (L) = 78.1, omega (V) = 42.7% CV. The present results show the usefulness of CysC to more accurately predict the pharmacokinetics of drugs mainly eliminated through the kidneys, such as TEIC. However, since the sample size in this study was relatively small, further investigations on renal clearance predictability using CysC are needed. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats.

PubMed

Quesada, Andrés; Vargas, Félix; Montoro-Molina, Sebastián; O'Valle, Francisco; Rodríguez-Martínez, María Dolores; Osuna, Antonio; Prieto, Isabel; Ramírez, Manuel; Wangensteen, Rosemary

2012-01-01

This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p<0.011; r(2)>0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.

Acute kidney injury: not just acute renal failure anymore?

PubMed

Dirkes, Susan

2011-02-01

Until recently, no uniform standard existed for diagnosing and classifying acute renal failure. To clarify diagnosis, the Acute Dialysis Quality Initiative group stated its consensus on the need for a clear definition and classification system of renal dysfunction with measurable criteria. Today the term acute kidney injury has replaced the term acute renal failure, with an understanding that such injury is a common clinical problem in critically ill patients and typically is predictive of an increase in morbidity and mortality. A classification system, known as RIFLE (risk of injury, injury, failure, loss of function, and end-stage renal failure), includes specific goals for preventing acute kidney injury: adequate hydration, maintenance of renal perfusion, limiting exposure to nephrotoxins, drug protective strategies, and the use of renal replacement therapies that reduce renal injury.

Protein and calorie prescription for children and young adults receiving continuous renal replacement therapy: a report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

PubMed

Zappitelli, Michael; Goldstein, Stuart L; Symons, Jordan M; Somers, Michael J G; Baum, Michelle A; Brophy, Patrick D; Blowey, Douglas; Fortenberry, James D; Chua, Annabelle N; Flores, Francisco X; Benfield, Mark R; Alexander, Steven R; Askenazi, David; Hackbarth, Richard; Bunchman, Timothy E

2008-12-01

Few published reports describe nutrition provision for critically ill children and young adults with acute kidney injury receiving continuous renal replacement therapy. The goals of this study were to describe feeding practices in pediatric continuous renal replacement therapy and to evaluate factors associated with over- and under-prescription of protein and calories. Retrospective database study. Multicenter study in pediatric critical care units. Patients with acute kidney injury (estimated glomerular filtration rate < 75 mL/min/1.73 m at continuous renal replacement therapy initiation) enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. None. Nutrition variables: initial and maximal protein (g/kg/day) and caloric (kcal/kg/day) prescription and predicted resting energy expenditure (kcal/kg/day). We determined factors predicting initial and maximal protein and caloric prescription by multivariate analysis. One hundred ninety-five patients (median [interquartile range] age = 8.1 [12.8] yrs, 56.9% men) were studied. Mean protein and caloric prescriptions at continuous renal replacement therapy initiation were 1.3 +/- 1.5 g/kg/day (median, 1.0; range, 0-10) and 37 +/- 27 kcal/kg/day (median, 32; range, 0-107). Mean maximal protein and caloric prescriptions during continuous renal replacement therapy were 2.0 +/- 1.5 g/kg/day (median, 1.7; range, 0-12) and 48 +/- 32 kcal/kg/day (median, 43; range, 0-117). Thirty-four percent of patients were initially prescribed < 1 g/kg/day protein; 23% never attained > 1 g/kg/day protein prescription. By continuous renal replacement therapy day 5, median protein prescribed was > 2 g/kg/day. Protein prescription practices differed substantially between medical centers with 5 of 10 centers achieving maximal protein prescription of > 2 g/kg/day in > or = 40% of patients. Caloric prescription exceeded predicted resting energy expenditure by 30%-100%. Factors independently associated with maximal protein and caloric prescription while on continuous renal replacement therapy were younger age, initial protein and caloric prescription and number of continuous renal replacement therapy treatment days (p < 0.05). Protein prescription in pediatric continuous renal replacement therapy may be inadequate. Inter-center variation exists with respect to nutrition prescription. Feeding practice standardization and research in pediatric acute kidney injury nutrition are essential to begin providing evidence-based feeding recommendations.

Problems Associated With Access to Renal Replacement Therapy: Experience of the Sindh Institute of Urology and Transplantation.

PubMed

Mazhar, Farida; Nizam, Naveeda; Fatima, Nazia; Siraj, Sana; Rizvi, Syed Adibul Hasan

2017-02-01

The prevalence of end-stage renal disease is increasing worldwide. It is also one of the main health problems in Pakistan. Currently, hemodialysis represents the main mode of treatment for patients with end-stage renal disease in this country. Despite 24-hour free dialysis at the Sindh Institute of Urology and Transplantation (Karachi, Pakistan), a significant number of patients do not turn up for regular dialysis or miss regular sessions of dialysis. We conducted this study to identify and highlight the factors leading to poor compliance with regular hemodialysis treatment despite free dialysis treatment offered at our center. In 2014, 4565 patients with end-stage renal disease were registered at the Sindh Institute of Urology and Transplantation. Among these, 610 patients (13.4%) missed more than 2 sessions of dialysis and were included in the present study. Patients provided written informed consent before study participation. Data were collected from a questionnaire survey and analyzed by SPSS software (SPSS: An IBM Company, version 20.0, Chicago, IL, USA). Despite 24-hour dialysis facilities, the patient drop-out rate (779; 18%) was high. In addition, a significant minority of patients (610; 13.4%) was erratic in adherence to maintenance hemodialysis schedules, with > 2 missed appointments. The mean age of these 610 patients was 33.4 ± 7.4 years, and 345 patients (57%) were males. The main factors leading to poor compliance included cost of travel (33.2%), lack of affordable lodging and boarding facilities near dialysis center (30.9%), long distances from dialysis center (20.1%), and lack of family support (15.6%). This study shows that there is significant drop-out and poor compliance rates for regular dialysis despite free dialysis facilities.

RENAL MICROVASCULAR DISEASE DETERMINES THE RESPONSES TO REVASCULARIZATION IN EXPERIMENTAL RENOVASCULAR DISEASE

PubMed Central

Chade, Alejandro R.; Kelsen, Silvia

2011-01-01

Background Percutaneous trasluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolve renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesize that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. Methods and Results RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 was infused intra-renally (RAS+VEGF, 0.05 µg/kg). Single-kidney function was assessed in all pigs in vivo using ultra-fast CT after 6 weeks. Half of the RAS/RAS+VEGF completed their observation, and the other half underwent PTRA, VEGF was repeated, and CT studies repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex-vivo using 3D micro-CT, and renal fibrosis quantified. Degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Conclusion Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage. PMID:20587789

Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

PubMed

Liu, Xue-Jing; Wu, Xiao-Yue; Wang, Huan; Wang, Su-Xia; Kong, Wei; Zhang, Ling; Liu, George; Huang, Wei

2018-05-08

Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue (AT) and could lead to renal failure in humans. However, the effect of Seipin on renal function is poorly understood. Here we report that Seipin knockout (SKO) mice exhibited impaired renal function, enlarged glomerular and mesangial surface areas, renal depositions of lipid, and advanced glycation end products. Elevated glycosuria and increased electrolyte excretion were also detected. Relative renal gene expression in fatty acid oxidation and reabsorption pathways were impaired in SKO mice. Elevated glycosuria might be associated with reduced renal glucose transporter 2 levels. To improve renal function, AT transplantation or leptin administration alone was performed. Both treatments effectively ameliorated renal injury by improving all of the parameters that were measured in the kidney. The treatments also rescued insulin resistance and low plasma leptin levels in SKO mice. Our findings demonstrate for the first time that Seipin deficiency induces renal injury, which is closely related to glucolipotoxicity and impaired renal reabsorption in SKO mice, and is primarily caused by the loss of AT and especially the lack of leptin. AT transplantation and leptin administration are two effective treatments for renal injury in Seipin-deficient mice.-Liu, X.-J., Wu, X.-Y., Wang, H., Wang, S.-X., Kong, W., Zhang, L., Liu, G., Huang, W. Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

The profile of adult onset Henoch-Schönlein purpura in an Asian population.

PubMed

Yong, Adeline Mei-Yen; Lee, Shan-Xian; Tay, Yong-Kwang

2015-11-01

Henoch-Schönlein purpura (HSP) is less common in adults and has been linked with a more severe clinical syndrome as well as a higher frequency of renal disease and internal malignancy. Renal involvement in adult HSP has been significantly associated with antecedent infections, pyrexia at time of first presentation, and purpura above the waist. We aim to evaluate the frequency of cutaneous and extra-cutaneous features and identify the predictive factors for renal involvement in Asian adults with HSP. We performed a retrospective study of 48 adult Asian patients diagnosed with HSP based on the European League Against Rheumatism (EULAR) criteria at a tertiary hospital in Singapore between January 2000 and December 2011. The most common cutaneous manifestations were palpable purpura (73%), papules (31%), and petechiae (27%). Forty-percent had cutaneous lesions extending above the waist. Fifteen patients (31%) had gastrointestinal symptoms, 21 (44%) had joint involvement, and 27 (56%) had renal disease. Seventy-percent of patients with pyrexia at presentation experienced renal disease, whereas only 30% without pyrexia had renal involvement (P = 0.018). Sixty-six percent of patients with purpura had renal involvement as compared to 31% in those without purpura (P = 0.049). The frequency of renal involvement in patients with purpura above the waist (52%) was similar to those with purpura below the waist (55%). Our study confirms that HSP in adults tends to be more severe with a high incidence of extracutaneous manifestations, especially renal disease. Pyrexia at presentation and the presence of purpura were significant predictive factors for renal involvement. © 2015 The International Society of Dermatology.

A clinico-pathological study of lupus nephritis based on the International Society of Nephrology-Renal Pathology Society 2003 classification system.

PubMed

Satish, Suchitha; Deka, Pallavi; Shetty, Manjunath Sanjeev

2017-01-01

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Renal involvement is a major determinant of the prognosis of SLE. The histological classification of LN is a key factor in determining the renal survival of patients with LN. Prompt recognition and treatment of renal disease are important, as early response to therapy is correlated with better outcome and renal biopsy plays an important role in achieving this. The objective of this study was to correlate the clinical and laboratory findings with histopathological classes of LN as per the 2003 International Society of Nephrology-Renal Pathology Society (ISN/RPS) classification system. Fifty-six patients with SLE, undergoing a renal biopsy for renal dysfunction were studied. The comparison of data from multiple groups was made by Pearson's Chi-square test and between two groups by independent samples t -test. The values of P < 0.05 were considered statistically significant. Of the 56 cases studied, 51 (91.1%) were females. The most common presenting symptoms were edema, arthralgia, and hypertension. Class IV (55.4%) was the most common class. Thirty-nine (69.6%) cases showed full house immunostaining. Hypertension, hematuria, proteinuria, and tubulo-interstitial disease showed a significant correlation ( P < 0.05) with ISN/RPS classification, 2003. Assessment and management of patients with suspected LN are greatly facilitated through information obtained by renal biopsy. Since renal morphology may predict long-term prognosis, and no clinical or laboratory feature uniformly predicts prognosis, it is important to study the constellation of features in LN for better patient management.

Feasibility and accuracy of computational robot-assisted partial nephrectomy planning by virtual partial nephrectomy analysis.

PubMed

Isotani, Shuji; Shimoyama, Hirofumi; Yokota, Isao; China, Toshiyuki; Hisasue, Shin-ichi; Ide, Hisamitsu; Muto, Satoru; Yamaguchi, Raizo; Ukimura, Osamu; Horie, Shigeo

2015-05-01

To evaluate the feasibility and accuracy of virtual partial nephrectomy analysis, including a color-coded three-dimensional virtual surgical planning and a quantitative functional analysis, in predicting the surgical outcomes of robot-assisted partial nephrectomy. Between 2012 and 2014, 20 patients underwent virtual partial nephrectomy analysis before undergoing robot-assisted partial nephrectomy. Virtual partial nephrectomy analysis was carried out with the following steps: (i) evaluation of the arterial branch for selective clamping by showing the vascular-supplied area; (ii) simulation of the optimal surgical margin in precise segmented three-dimensional model for prediction of collecting system opening; and (iii) detailed volumetric analyses and estimates of postoperative renal function based on volumetric change. At operation, the surgeon identified the targeted artery and determined the surgical margin according to the virtual partial nephrectomy analysis. The surgical outcomes between the virtual partial nephrectomy analysis and the actual robot-assisted partial nephrectomy were compared. All 20 patients had negative cancer surgical margins and no urological complications. The tumor-specific renal arterial supply areas were shown in color-coded three-dimensional model visualization in all cases. The prediction value of collecting system opening was 85.7% for sensitivity and 100% for specificity. The predicted renal resection volume was significantly correlated with actual resected specimen volume (r(2) = 0.745, P < 0.001). The predicted estimated glomerular filtration rate was significantly correlated with actual postoperative estimated glomerular filtration rate (r(2) = 0.736, P < 0.001). Virtual partial nephrectomy analysis is able to provide the identification of tumor-specific renal arterial supply, prediction of collecting system opening and prediction of postoperative renal function. This technique might allow urologists to compare various arterial clamping methods and resection margins with surgical outcomes in a non-invasive manner. © 2015 The Japanese Urological Association.

Rickets–vitamin D deficiency and dependency

PubMed Central

Sahay, Manisha; Sahay, Rakesh

2012-01-01

Rickets is an important problem even in countries with adequate sun exposure. The causes of rickets/osteomalacia are varied and include nutritional deficiency, especially poor dietary intake of vitamin D and calcium. Non-nutritional causes include hypophosphatemic rickets primarily due to renal phosphate losses and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. This chapter highlights rickets/osteomalacia related to vitamin D deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic rickets and rickets due to renal tubular acidosis are discussed in other sections of the journal. PMID:22470851

Angiomyolipoma with Minimal Fat: Can It Be Differentiated from Clear Cell Renal Cell Carcinoma by Using Standard MR Techniques?

PubMed Central

Hindman, Nicole; Ngo, Long; Genega, Elizabeth M.; Melamed, Jonathan; Wei, Jesse; Braza, Julia M.; Rofsky, Neil M.

2012-01-01

Purpose: To retrospectively assess whether magnetic resonance (MR) imaging with opposed-phase and in-phase gradient-echo (GRE) sequences and MR feature analysis can differentiate angiomyolipomas (AMLs) that contain minimal fat from clear cell renal cell carcinomas (RCCs), with particular emphasis on small (<3-cm) masses. Materials and Methods: Institutional review board approval and a waiver of informed consent were obtained for this HIPAA-compliant study. MR images from 108 pathologically proved renal masses (88 clear cell RCCs and 20 minimal fat AMLs from 64 men and 44 women) at two academic institutions were evaluated. The signal intensity (SI) of each renal mass and spleen on opposed-phase and in-phase GRE images was used to calculate an SI index and tumor-to-spleen SI ratio. Two radiologists who were blinded to the pathologic results independently assessed the subjective presence of intravoxel fat (ie, decreased SI on opposed-phase images compared with that on in-phase images), SI on T1-weighted and T2-weighted images, cystic degeneration, necrosis, hemorrhage, retroperitoneal collaterals, and renal vein thrombosis. Results were analyzed by using the Wilcoxon rank sum test, two-tailed Fisher exact test, and multivariate logistic regression analysis for all renal masses and for small masses. A P value of less than .05 was considered to indicate a statistically significant difference. Results: There were no differences between minimal fat AMLs and clear cell RCCs for the SI index (8.05% ± 14.46 vs 14.99% ± 19.9; P = .146) or tumor-to-spleen ratio (−8.96% ± 16.6 and −15.8% ± 22.4; P = .227) when all masses or small masses were analyzed. Diagnostic accuracy (area under receiver operating characteristic curve) for the SI index and tumor-to-spleen ratio was 0.59. Intratumoral necrosis and larger size were predictive of clear cell RCC (P < .001) for all lesions, whereas low SI (relative to renal parenchyma SI) on T2-weighted images, smaller size, and female sex correlated with minimal fat AML (P < .001) for all lesions. Conclusion: The diagnostic accuracy of opposed-phase and in-phase GRE MR imaging for the differentiation of minimal fat AML and clear cell RCC is poor. In this cohort, low SI on T2-weighted images relative to renal parenchyma and small size suggested minimal fat AML, whereas intratumoral necrosis and large size argued against this diagnosis. © RSNA, 2012 PMID:23012463

Structural Predictors of Loss of Renal Function in American Indians with Type 2 Diabetes.

PubMed

Fufaa, Gudeta D; Weil, E Jennifer; Lemley, Kevin V; Knowler, William C; Brosius, Frank C; Yee, Berne; Mauer, Michael; Nelson, Robert G

2016-02-05

Diabetes is the leading cause of kidney failure in the United States, but early structural determinants of renal function loss in type 2 diabetes are poorly defined. We examined the association between morphometrically determined renal structural variables and loss of renal function in 111 American Indians with type 2 diabetes who volunteered for a research kidney biopsy at the end of a 6-year clinical trial designed to test the renoprotective efficacy of losartan versus placebo. Participants were subsequently followed in an observational study, in which annual measurements of GFR (iothalamate) initiated during the clinical trial were continued. Renal function loss was defined as ≥40% loss of GFR from the research examination performed at the time of kidney biopsy. Associations with renal function loss were evaluated by Cox proportional hazards regression. Hazard ratios (HRs) were reported per 1-SD increment for each morphometric variable. Of 111 participants (82% women; baseline mean [±SD] age, 46 years old [±10]; diabetes duration, 16 years [±6]; hemoglobin A1c =9.4% [±2.2]; GFR=147 ml/min [±56]; median albumin-to-creatinine ratio, 41 mg/g [interquartile range, 13-158]), 51 (46%) developed renal function loss during a median follow-up of 6.6 years (interquartile range, 3.1-9.0). Fourteen had baseline GFR <90 ml/min, and three had baseline GFR <60 ml/min. Higher mesangial fractional volume (HR, 2.27; 95% confidence interval [95% CI], 1.58 to 3.26), percentage of global glomerular sclerosis (HR, 1.63; 95% CI, 1.21 to 2.21), nonpodocyte cell number per glomerulus (HR, 1.50; 95% CI, 1.10 to 2.05), glomerular basement membrane width (HR, 1.48; 95% CI, 1.05 to 2.08), mean glomerular volume (HR, 1.42; 95% CI, 1.02 to 1.96), and podocyte foot process width (HR, 1.28; 95% CI, 1.03 to 1.60); lower glomerular filtration surface density (HR, 0.62; 95% CI, 0.41 to 0.94); and fewer endothelial fenestrations (HR, 0.68; 95% CI, 0.48 to 0.95) were each associated with GFR decline after adjustment for baseline age, sex, duration of diabetes, hemoglobin A1c, GFR, and treatment assignment during the clinical trial. Quantitative measures of glomerular structure predict loss of renal function in type 2 diabetes. Copyright © 2016 by the American Society of Nephrology.

Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

PubMed

Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang

2006-07-01

Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P < 0.01) than in patients with normal renal function (42.0%) or in the diabetes control group (40.6%). The Leu72Met polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

Preoperative Renal Volume: A Surrogate Measure for Radical Nephrectomy-Induced Chronic Kidney Disease.

PubMed

Wu, Fiona Mei Wen; Tay, Melissa Hui Wen; Tai, Bee Choo; Chen, Zhaojin; Tan, Lincoln; Goh, Benjamin Yen Seow; Raman, Lata; Tiong, Ho Yee

2015-12-01

Surgically induced chronic kidney disease (CKD) has been found to have less impact on survival as well as function when compared to medical causes for CKD. The aim of this study is to evaluate whether preoperative remaining kidney volume correlates with renal function after nephrectomy, which represents an individual's renal reserve before surgically induced CKD. A retrospective review of 75 consecutive patients (29.3% females) who underwent radical nephrectomy (RN) (2000-2010) was performed. Normal side kidney parenchyma, excluding renal vessels and central sinus fat, was manually outlined in each transverse slice of CT image and multiplied by slice thickness to calculate volume. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. CKD is defined as eGFR < 60 mL/min/1.73 m(2). Mean preoperative normal kidney parenchymal volume (mean age 55 [SD 13] years) is 150.7 (SD 36.4) mL. Over median follow-up of 36 months postsurgery, progression to CKD occurred in 42.6% (n = 32) of patients. On multivariable analysis, preoperative eGFR and preoperative renal volume <144 mL are independent predictors for postoperative CKD. On Kaplan-Meier analysis, median time to reach CKD postnephrectomy is 12.7 (range 0.03-43.66) months for renal volume <144 mL but not achieved if renal volume is >144 mL. Normal kidney parenchymal volume and preoperative eGFR are independent predictive factors for postoperative CKD after RN and may represent renal reserve for both surgically and medically induced CKD, respectively. Preoperative remaining kidney volume may be an adjunct representation of renal reserve postsurgery and predict later renal function decline due to perioperative loss of nephrons.

[Renal failure in patients with liver transplant: incidence and predisposing factors].

PubMed

Gerona, S; Laudano, O; Macías, S; San Román, E; Galdame, O; Torres, O; Sorkin, E; Ciardullo, M; de Santibañes, E; Mastai, R

1997-01-01

Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The aim of the present study was to evaluate the incidence, prognostic value of pre, intra and postoperative factors and severity of renal dysfunction in patients who undergo liver transplantation. Therefore, the records of 38 consecutive adult patients were reviewed. Renal failure was defined arbitrarily as an increase in creatinine (> 1.5 mg/dl) and/or blood urea (> 80 mg/dl). Three patients were excluded of the final analysis (1 acute liver failure and 2 with a survival lower than 72 hs.) Twenty one of the 35 patients has renal failure after orthotopic liver transplantation. Six of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 15 patients within the hospitalization (40 +/- 10 days) (Mean +/- SD). In he overall series, liver function, evaluated by Child-Pugh classification, a higher blood-related requirements and cyclosporine levels were observed more in those who experienced renal failure than those who did not (p < 0.05). Early renal failure was related with preoperative (liver function) and intraoperative (blood requirements) factors and several causes (nephrotoxic drugs and graft failure) other than cyclosporine were present in patients who developed late renal impairment. No mortality. No mortality was associated with renal failure. We conclude that renal failure a) is a common finding after liver transplantation, b) the pathogenesis of this complication is multifactorial and, c) in not related with a poor outcome.

Urinary type IV collagen excretion predicts subsequent declining renal function in type 2 diabetic patients with proteinuria.

PubMed

Katavetin, Pisut; Katavetin, Paravee; Susantitaphong, Paweena; Townamchai, Natavudh; Tiranathanagul, Khajohn; Tungsanga, Kriang; Eiam-Ong, Somchai

2010-08-01

Baseline urinary type IV collagen excretion was negatively correlated with the subsequent GFR change (r(s)=-0.39, p=0.04) in our cohort of 30 type 2 diabetic patients with proteinuria. Therefore, it could be used to predict subsequent declining renal function in type 2 diabetic patients with proteinuria. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of renal impairment on the pharmacokinetics of exenatide

PubMed Central

Linnebjerg, Helle; Kothare, Prajakti A; Park, Soomin; Mace, Kenneth; Reddy, Shobha; Mitchell, Malcolm; Lins, Robert

2007-01-01

What is already known about this subject Nonclinical studies have shown that exenatide is primarily cleared by the renal system. It was not known to what degree the clinical pharmacokinetics and tolerability would be affected by increasing renal impairment (RI). What this study adds Patients with mild to moderate RI adequately tolerate current therapeutic doses of exenatide.However, exenatide is not recommended in patients with severe RI or end-stage renal disease. Aims To evaluate the pharmacokinetics (PK), safety and tolerability of a single exenatide dose in patients with renal impairment (RI). Methods Exenatide (5 or 10 µg) was injected subcutaneously in 31 subjects (one with Type 2 diabetes) stratified by renal function [Cockcroft–Gault creatinine clearance (CrCL), number of subjects]: normal (>80 ml min−1, n = 8), mild RI (51–80 ml min−1, n = 8), moderate RI (31–50 ml min−1, n = 7) or end-stage renal disease (ESRD) requiring haemodialysis (n = 8). PK data were combined with four previous single-dose studies in patients with Type 2 diabetes to explore the relationship of exenatide clearance (CLp/F) and CrCL. Results Mean half-life for healthy, mild RI, moderate RI and ESRD groups were 1.5, 2.1, 3.2 and 6.0 h, respectively. After combining data from multiple studies, least squares geometric means for CLp/F in subjects with normal renal function, mild RI, moderate RI and ESRD were 8.14, 5.19, 7.11 and 1.3 l h−1, respectively. Exenatide was generally well tolerated in the mild and moderate RI groups, but not in subjects with ESRD due to nausea and vomiting. Simulations of exenatide plasma concentrations also suggest patients with ESRD should have a propensity for poor tolerability at the lowest available therapeutic dosage (5 µg q.d.). Conclusions Since tolerability and PK changes were considered clinically acceptable in patients with mild to moderate RI, it would be appropriate to administer exenatide to these patients without dosage adjustment. However, poor tolerability and significant changes in PK make the currently available therapeutic doses (5 and 10 µg) unsuitable in severe RI or ESRD. PMID:17425627

Nomograms for predicting graft function and survival in living donor kidney transplantation based on the UNOS Registry.

PubMed

Tiong, H Y; Goldfarb, D A; Kattan, M W; Alster, J M; Thuita, L; Yu, C; Wee, A; Poggio, E D

2009-03-01

We developed nomograms that predict transplant renal function at 1 year (Modification of Diet in Renal Disease equation [estimated glomerular filtration rate]) and 5-year graft survival after living donor kidney transplantation. Data for living donor renal transplants were obtained from the United Network for Organ Sharing registry for 2000 to 2003. Nomograms were designed using linear or Cox regression models to predict 1-year estimated glomerular filtration rate and 5-year graft survival based on pretransplant information including demographic factors, immunosuppressive therapy, immunological factors and organ procurement technique. A third nomogram was constructed to predict 5-year graft survival using additional information available by 6 months after transplantation. These data included delayed graft function, any treated rejection episodes and the 6-month estimated glomerular filtration rate. The nomograms were internally validated using 10-fold cross-validation. The renal function nomogram had an r-square value of 0.13. It worked best when predicting estimated glomerular filtration rate values between 50 and 70 ml per minute per 1.73 m(2). The 5-year graft survival nomograms had a concordance index of 0.71 for the pretransplant nomogram and 0.78 for the 6-month posttransplant nomogram. Calibration was adequate for all nomograms. Nomograms based on data from the United Network for Organ Sharing registry have been validated to predict the 1-year estimated glomerular filtration rate and 5-year graft survival. These nomograms may facilitate individualized patient care in living donor kidney transplantation.

Multidetector computed tomography for preoperative evaluation of vascular anatomy in living renal donors.

PubMed

Türkvatan, Aysel; Akinci, Serkan; Yildiz, Sener; Olçer, Tülay; Cumhur, Turhan

2009-04-01

Currently, multidetector computed tomographic (MDCT) angiography has become a noninvasive alternative imaging modality to catheter renal angiography for the evaluation of renal vascular anatomy in living renal donors. In this study, we investigated the diagnostic accuracy of 16-slice MDCT in the preoperative assessment of living renal donors. Fifty-nine consecutive living renal donors (32 men, 27 women) underwent MDCT angiography followed by open donor nephrectomy. All MDCT studies were performed by using a 16-slice MDCT scanner with the same protocol consisting of arterial and nephrographic phases followed by conventional abdominal radiography. The MDCT images were assessed retrospectively for the number and branching pattern of the renal arteries and for the number and presence of major or minor variants of the renal veins. The results were compared with open surgical results. The sensitivity and specificity of MDCT for the detection of anatomic variants of renal arteries including the accessory arteries (n = 9), early arterial branching (n = 7) and major renal venous anomalies including the accessory renal veins (n = 3), late venous confluence (n = 4), circumaortic (n = 2) or retroaortic (n = 3) left renal veins were 100%. However, the sensitivity for identification of minor venous variants was 79%. All of three ureteral duplications were correctly identified at excretory phase conventional abdominal radiography. Sixteen-slice MDCT is highly accurate for the identification of anatomic variants of renal arteries and veins. Dual-phase MDCT angiography including arterial and nephrographic phases followed by conventional abdominal radiography enables complete assessment of renal donors without significant increase of radiation dose. However, the evaluation of minor venous variants may be problematic because of their small diameters and poor opacification.

Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures.

PubMed

Kassemi, Mohammad; Thompson, David

2016-09-01

An analytic Population Balance Equation model is used to assess the efficacy of citrate, pyrophosphate, and augmented fluid intake as dietary countermeasures aimed at reducing the risk of renal stone formation for astronauts. The model uses the measured biochemical profile of the astronauts as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating renal calculi subject to biochemical changes brought about by administration of these dietary countermeasures. Numerical predictions indicate that an increase in citrate levels beyond its average normal ground-based urinary values is beneficial but only to a limited extent. Unfortunately, results also indicate that any decline in the citrate levels during space travel below its normal urinary values on Earth can easily move the astronaut into the stone-forming risk category. Pyrophosphate is found to be an effective inhibitor since numerical predictions indicate that even at quite small urinary concentrations, it has the potential of shifting the maximum crystal aggregate size to a much smaller and plausibly safer range. Finally, our numerical results predict a decline in urinary volume below 1.5 liters/day can act as a dangerous promoter of renal stone development in microgravity while urinary volume levels of 2.5-3 liters/day can serve as effective space countermeasures. Copyright © 2016 the American Physiological Society.

Diabetic nephropathy: a strong predictor of sleep quality in hemodialysis patients.

PubMed

Edalat-Nejad, Mahnaz; Jafarian, Nahid; Yousefichaijan, Parsa

2014-07-01

Sleep complaints are common in hemodialysis (HD) patients. Sleep quality (SQ) is a predictor of quality of life and mortality risk in HD. The aim of this study was to examine factors that may have a role in SQ. In this cross-sectional analytic study, 138 end-stage renal disease patients receiving maintenance HD for >3 months were included. The Pittsburgh Sleep Quality Index (PSQI) was used to measure individual's SQ. Patients with a global PSQI score >5 were assumed as poor sleepers. Eighty-eight patients (64%) were classified as poor sleepers. Poor sleepers were older and more likely had diabetes. They had significantly higher serum ferritin and calcium levels and lower serum parathyroid hormone level (all P-values <0.05). The global PSQI score was positively correlated with age, serum calcium level and presence of diabetes as the underlying cause of renal failure. In the multi-variable binary regression model, presence of diabetes (Odds Ratio (OR) = 3.67, P = 0.008) and body pain (OR = 1.182, P = 0.014) were the significant independent predictors for poor SQ. Poor SQ was common among our HD patients, especially among diabetic cases and, therefore, there is a need to pay more attention to the care of this subgroup with regard to the diagnosis and management of sleep complaints.

ALDOSTERONE DYSREGULATION WITH AGING PREDICTS RENAL-VASCULAR FUNCTION AND CARDIO-VASCULAR RISK

PubMed Central

Brown, Jenifer M.; Underwood, Patricia C.; Ferri, Claudio; Hopkins, Paul N.; Williams, Gordon H.; Adler, Gail K.; Vaidya, Anand

2014-01-01

Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal- and cardio-vascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1,124 visits) in a Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression-to-stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics, and the renal-vascular responses to dietary sodium manipulation and angiotensin II (AngII) infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β= -4.60, p<0.0001) and higher SASSI (β= -58.63, p=0.001) predicted lower RPF and a blunted RPF response to sodium loading and AngII infusion. We observed a continuous, independent, multivariate-adjusted interaction between age and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (p<0.05). Higher SASSI and lower RPF independently predicted higher Framingham Risk Score (p<0.0001) and together displayed an additive effect. Aldosterone regulation and age may interact to mediate renal-vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal-vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease. PMID:24664291

Aldosterone dysregulation with aging predicts renal vascular function and cardiovascular risk.

PubMed

Brown, Jenifer M; Underwood, Patricia C; Ferri, Claudio; Hopkins, Paul N; Williams, Gordon H; Adler, Gail K; Vaidya, Anand

2014-06-01

Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal vascular and cardiovascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1124 visits) in the General Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression to stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics and the renal vascular responses to dietary sodium manipulation and angiotensin II infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β=-4.60; P<0.0001) and higher SASSI (β=-58.63; P=0.001) predicted lower RPF and a blunted RPF response to sodium loading and angiotensin II infusion. We observed a continuous, independent, multivariate-adjusted interaction between age and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (P<0.05). Higher SASSI and lower RPF independently predicted higher Framingham Risk Score (P<0.0001) and together displayed an additive effect. Aldosterone regulation and age may interact to mediate renal vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease.

Accounting for oxygen in the renal cortex: a computational study of factors that predispose the cortex to hypoxia.

PubMed

Lee, Chang-Joon; Gardiner, Bruce S; Ngo, Jennifer P; Kar, Saptarshi; Evans, Roger G; Smith, David W

2017-08-01

We develop a pseudo-three-dimensional model of oxygen transport for the renal cortex of the rat, incorporating both the axial and radial geometry of the preglomerular circulation and quantitative information regarding the surface areas and transport from the vasculature and renal corpuscles. The computational model was validated by simulating four sets of published experimental studies of renal oxygenation in rats. Under the control conditions, the predicted cortical tissue oxygen tension ([Formula: see text]) or microvascular oxygen tension (µPo 2 ) were within ±1 SE of the mean value observed experimentally. The predicted [Formula: see text] or µPo 2 in response to ischemia-reperfusion injury, acute hemodilution, blockade of nitric oxide synthase, or uncoupling mitochondrial respiration, were within ±2 SE observed experimentally. We performed a sensitivity analysis of the key model parameters to assess their individual or combined impact on the predicted [Formula: see text] and µPo 2 The model parameters analyzed were as follows: 1 ) the major determinants of renal oxygen delivery ([Formula: see text]) (arterial blood Po 2 , hemoglobin concentration, and renal blood flow); 2 ) the major determinants of renal oxygen consumption (V̇o 2 ) [glomerular filtration rate (GFR) and the efficiency of oxygen utilization for sodium reabsorption (β)]; and 3) peritubular capillary surface area (PCSA). Reductions in PCSA by 50% were found to profoundly increase the sensitivity of [Formula: see text] and µPo 2 to the major the determinants of [Formula: see text] and V̇o 2 The increasing likelihood of hypoxia with decreasing PCSA provides a potential explanation for the increased risk of acute kidney injury in some experimental animals and for patients with chronic kidney disease. Copyright © 2017 the American Physiological Society.

Evaluation of stone volume distribution in renal collecting system as a predictor of stone-free rate after percutaneous nephrolithotomy: a retrospective single-center study.

PubMed

Atalay, Hasan Anıl; Canat, Lutfi; Bayraktarlı, Recep; Alkan, Ilter; Can, Osman; Altunrende, Fatih

2017-06-23

We analyzed our stone-free rates of PNL with regard to stone burden and its ratio to the renal collecting system volume. Data of 164 patients who underwent PNL were analyzed retrospectively. Volume segmentation of renal collecting system and stones were done using 3D segmentation software with the images obtained from CT data. Analyzed stone volume (ASV) and renal collecting system volume (RCSV) were measured and the ASV-to-RCSV ratio was calculated after the creation of a 3D surface volume rendering of renal stones and the collecting system. Univariate and multivariate statistical analyses were performed to determine factors affecting stone-free rates; also we assessed the predictive accuracy of the ASV-to-RCSV ratio using the receiving operating curve (ROC) and AUC. The stone-free rate of PNL monotherapy was 53% (164 procedures).The ASV-to-RCSV ratio and calyx number with stones were the most influential predictors of stone-free status (OR 4.15, 95% CI 2.24-7.24, <0.001, OR 2.62, 95% CI 1.38-4.97, p < 0.001, respectively). Other factors associated with the stone-free rate were maximum stone size (p < 0.029), stone surface area (p < 0.010), and stone burden volume (p < 0.001). Predictive accuracy of the ASV-to-RCSV ratio was AUC 0.76. Stone burden volume distribution in the renal collecting system, which is calculated using the 3D volume segmentation method, is a significant determinant of the stone-free rate before PCNL surgery. It could be used as a single guide variable by the clinician before renal stone surgery to predict extra requirements for stone clearance.

Renal microvascular disease determines the responses to revascularization in experimental renovascular disease.

PubMed

Chade, Alejandro R; Kelsen, Silvia

2010-08-01

Percutaneous transluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolving renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesized that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 0.05 microg/kg was infused intrarenally (RAS+VEGF). Single-kidney function was assessed in all pigs in vivo using ultrafast CT after 6 weeks. Observation of half of the RAS and RAS+VEGF pigs was completed. The other half underwent PTRA and repeated VEGF, and CT studies were repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex vivo using 3D micro-CT, and renal fibrosis quantified. The degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

PubMed Central

Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C.; Khadayate, Sanjay; Mas, Valeria R.; Nitsch, Dorothea D.; Wang, Zhen; Norman, Jill T.; Wilcox, Christopher S.; Wheeler, David C.; Leiper, James

2015-01-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. PMID:25855779

The renal concentrating mechanism and the clinical consequences of its loss

PubMed Central

Agaba, Emmanuel I.; Rohrscheib, Mark; Tzamaloukas, Antonios H.

2012-01-01

The integrity of the renal concentrating mechanism is maintained by the anatomical and functional arrangements of the renal transport mechanisms for solute (sodium, potassium, urea, etc) and water and by the function of the regulatory hormone for renal concentration, vasopressin. The discovery of aquaporins (water channels) in the cell membranes of the renal tubular epithelial cells has elucidated the mechanisms of renal actions of vasopressin. Loss of the concentrating mechanism results in uncontrolled polyuria with low urine osmolality and, if the patient is unable to consume (appropriately) large volumes of water, hypernatremia with dire neurological consequences. Loss of concentrating mechanism can be the consequence of defective secretion of vasopressin from the posterior pituitary gland (congenital or acquired central diabetes insipidus) or poor response of the target organ to vasopressin (congenital or nephrogenic diabetes insipidus). The differentiation between the three major states producing polyuria with low urine osmolality (central diabetes insipidus, nephrogenic diabetes insipidus and primary polydipsia) is done by a standardized water deprivation test. Proper diagnosis is essential for the management, which differs between these three conditions. PMID:23293407

Primary Renal Rhabdomyosarcoma in an Adolescent With Tumor Thrombosis in the Inferior Vena Cava and Right Atrium: A Case Report and Review of the Literature.

PubMed

Lin, Wei-Ching; Chen, Jeon-Hor; Westphalen, Antonio; Chang, Han; Chiang, I-Ping; Chen, Cheng-Hong; Wu, Hsi-Chin; Lin, Chien-Heng

2016-05-01

Although the second peak of the age distribution of rhabdomyosarcoma (RMS) is at adolescence, renal RMS is extremely rare at this age group. This tumor is indistinguishable from other renal tumors based on clinical and imaging findings, and the diagnosis relies on histology and immunohistochemical staining. We report a unique case of adolescent renal RMS associated with tumor thrombus extending into the inferior vena cava (IVC) and right atrium.An 18-year-old female adolescent presented with shortness of breath and palpitations, associated with right flank discomfort, and hematuria. A pleomorphic-type renal RMS with Budd-Chiari syndrome and arrhythmia induced by IVC and RA thrombosis was diagnosed. Despite complete tumor resection, the patient developed multiple lung metastases a month after surgery. Chemotherapy was recommended, but the patient declined. She died within a year of the initial operation.Adolescent renal RMS is rare and associated with poor outcome. Early aggressive multimodal therapy seems to be appropriate, in particular, in the presence of tumor thrombosis.

Incidence and aetiology of renal phosphate loss in patients with hypophosphatemia in the intensive care unit.

PubMed

Bech, Anneke; Blans, Michiel; Telting, Darryl; de Boer, Hans

2013-10-01

Hypophosphatemia is a common finding in patients in the intensive care unit (ICU). Its cause is often poorly understood. The aim of this study was to understand the incidence of renal phosphate loss in ICU-related hypophosphatemia, and to examine the role of phosphaturic hormones in its etiology. Plasma phosphate levels were measured on day 1, 3, 5 and 7 in 290 consecutive patients admitted to the ICU. Renal phosphate handling and phosphaturic hormones were studied in a subset of patients with phosphate levels <0.6 mmol/L. Renal phosphate loss was defined as a TmP/gfr < 0.6 mmol/L. Hypophosphatemia developed in 24% of all patients. This mainly occurred within the first 3 days of stay and in patients with serum creatinine levels <150 μmol/L. Renal phosphate loss was present in 80% of patients who developed hypophosphatemia, and was not related to serum levels of parathyroid hormone (PTH), PTH-related protein (PTH-rp), fibroblast growth factor 23 (FGF-23), or calcitonin. Hypophosphatemia in the ICU is commonly associated with renal phosphate loss. It mainly occurs within the first 3 days of admission, in particular in patients with preserved renal function. Renal phosphate loss is not explained by elevated PTH, PTH-rp, FGF-23 or calcitonin levels.

Accuracy of ultrasound versus computed tomography urogram in detecting urinary tract calculi.

PubMed

Salinawati, B; Hing, E Y; Fam, X I; Zulfiqar, M A

2015-08-01

To determine the (i) sensitivity and specificity of ultrasound (USG) in the detection of urinary tract calculi, (ii) size of renal calculi detected on USG, and (iii) size of renal calculi not seen on USG but detected on computed tomography urogram (CTU). A total of 201 patients' USG and CTU were compared retrospectively for the presence of calculi. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of USG were calculated with CTU as the gold standard. From the 201 sets of data collected, 59 calculi were detected on both USG and CTU. The sensitivity and specificity of renal calculi detection on USG were 53% and 85% respectively. The mean size of the renal calculus detected on USG was 7.6 mm ± 4.1 mm and the mean size of the renal calculus not visualised on USG but detected on CTU was 4 mm ± 2.4 mm. The sensitivity and specificity of ureteric calculi detection on USG were 12% and 97% respectively. The sensitivity and specificity of urinary bladder calculi detection on USG were 20% and 100% respectively. This study showed that the accuracy of US in detecting renal, ureteric and urinary bladder calculi were 67%, 80% and 98% respectively.

Hemodynamic Measurements for the Selection of Patients With Renal Artery Stenosis: A Systematic Review.

PubMed

van Brussel, Peter M; van de Hoef, Tim P; de Winter, Robbert J; Vogt, Liffert; van den Born, Bert-Jan

2017-05-22

Interventions targeting renal artery stenoses have been shown to lower blood pressure and preserve renal function. In recent studies, the efficacy of catheter-based percutaneous transluminal renal angioplasty with stent placement has been called into question. In the identification of functional coronary lesions, hyperemic measurements have earned a place in daily practice for clinical decision making, allowing discrimination between solitary coronary lesions and diffuse microvascular disease. Next to differences in clinical characteristics, the selection of renal arteries suitable for intervention is currently on the basis of anatomic grading of the stenosis by angiography rather than functional assessment under hyperemia. It is conceivable that, like the coronary circulation, functional measurements may better predict therapeutic efficacy of percutaneous transluminal renal angioplasty with stent placement. In this systematic review, the authors evaluate the available clinical evidence on the optimal hyperemic agents to induce intrarenal hyperemia, their association with anatomic grading, and their predictive value for treatment effects. In addition, the potential value of combined pressure and flow measurements to discriminate macrovascular from microvascular disease is discussed. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Rotational digital subtraction angiography of the renal arteries: technique and evaluation in the study of native and transplant renal arteries.

PubMed

Seymour, H R; Matson, M B; Belli, A M; Morgan, R; Kyriou, J; Patel, U

2001-02-01

Rotational digital subtraction angiography (RDSA) allows multidirectional angiographic acquisitions with a single injection of contrast medium. The role of RDSA was evaluated in 60 patients referred over a 7-month period for diagnostic renal angiography and 12 patients referred for renal transplant studies. All angiograms were assessed for their diagnostic value, the presence of anomalies and the quantity of contrast medium used. The effective dose for native renal RDSA was determined. 41 (68.3%) native renal RDSA images and 8 (66.7%) transplant renal RDSA images were of diagnostic quality. Multiple renal arteries were identified in 9/41 (22%) native renal RDSA diagnostic images. The mean volume of contrast medium in the RDSA runs was 51.2 ml and 50 ml for native and transplant renal studies, respectively. The mean effective dose for 120 degrees native renal RDSA was 2.36 mSv, equivalent to 1 year's mean background radiation. Those RDSA images that were non-diagnostic allowed accurate prediction of the optimal angle for further static angiographic series, which is of great value in transplant renal vessels.

Gadolinium-enhanced magnetic resonance angiography in renal artery stenosis: comparison with digital subtraction angiography.

PubMed

Law, Y M; Tay, K H; Gan, Y U; Cheah, F K; Tan, B S

2008-04-01

To evaluate the accuracy of gadolinium-enhanced magnetic resonance angiography in assessing renal artery stenosis compared to catheter digital subtraction angiography. Retrospective study. Singapore General Hospital. Records of patients who underwent magnetic resonance angiography as well as digital subtraction angiography for assessment of renal artery stenosis from January 2003 to December 2005 were reviewed. There were 27 patients (14 male, 13 female) with a mean age of 62 (range, 44-77) years. There were 10 patients with renal transplants; their native renal arteries were not evaluated. Each of the two experienced interventional and body magnetic resonance radiologists, who were blinded to the results, reviewed the digital subtraction angiography and magnetic resonance angiography images respectively. Digital subtraction angiography was used as the standard of reference. A total of 39 renal arteries from these 27 patients were evaluated. One of the arteries was previously stented and could not be assessed with magnetic resonance angiography due to severe artefacts. Of the remaining 38 renal arteries, two were graded as normal, seven as having mild stenosis (<50%), eight as having moderate stenosis (> or =50% but <75%), and 21 as having severe stenosis (> or =75%). Magnetic resonance angiography and digital subtraction angiography were concordant in 89% of the arteries; magnetic resonance angiography overestimated the degree of stenosis in 8% and underestimated it in 3% of them. In the evaluation of clinically significant renal artery stenosis (> or =50%) with magnetic resonance angiography, the overall sensitivity, specificity, positive predictive value, and negative predictive value were 97%, 67%, 90%, and 86% respectively. The sensitivity and specificity of magnetic resonance angiography in transplant renal artery stenosis was 100%. CONCLUSION. Our experience suggested that gadolinium-enhanced magnetic resonance angiography is a sensitive non-invasive modality useful in the assessment of clinically significant renal artery stenosis.

Live Donor Renal Anatomic Asymmetry and Posttransplant Renal Function.

PubMed

Tanriover, Bekir; Fernandez, Sonalis; Campenot, Eric S; Newhouse, Jeffrey H; Oyfe, Irina; Mohan, Prince; Sandikci, Burhaneddin; Radhakrishnan, Jai; Wexler, Jennifer J; Carroll, Maureen A; Sharif, Sairah; Cohen, David J; Ratner, Lloyd E; Hardy, Mark A

2015-08-01

Relationship between live donor renal anatomic asymmetry and posttransplant recipient function has not been studied extensively. We analyzed 96 live kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from computerized tomography angiograms) and their matching recipients. Split function differences (SFD) were quantified with technetium-dimercaptosuccinic acid renography. Implantation biopsies at time 0 were semiquantitatively scored. A comprehensive model using donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at 1 year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60 mL/min/1.73 m(2) at 1 year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the chronic kidney disease-epidemiology collaboration formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). In the study cohort, the mean Vol/Wgt and eGFR at 1 year were 2.04 mL/kg and 60.4 mL/min/1.73 m(2), respectively. Volume and split ratios between 2 donor kidneys were strongly correlated (r = 0.79, P < 0.001). The biopsy scores among SFD categories (<5%, 5%-10%, >10%) were not different (P = 0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR > 60 mL/min/1.73 m (odds ratio, 8.94, 95% CI 2.47-32.25, P = 0.001) and had a strong discriminatory power in predicting the risk of eGFR less than 60 mL/min/1.73 m(2) at 1 year [receiver operating curve (ROC curve), 0.78, 95% CI, 0.68-0.89]. In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at 1 year after transplantation. Renography can be replaced with CT volume calculation in estimating split renal function.

Live Donor Renal Anatomic Asymmetry and Post-Transplant Renal Function

PubMed Central

Tanriover, Bekir; Fernandez, Sonalis; Campenot, Eric S.; Newhouse, Jeffrey H.; Oyfe, Irina; Mohan, Prince; Sandikci, Burhaneddin; Radhakrishnan, Jai; Wexler, Jennifer J.; Carroll, Maureen A.; Sharif, Sairah; Cohen, David J.; Ratner, Lloyd E.; Hardy, Mark A.

2014-01-01

Background Relationship between live donor renal anatomic asymmetry and post-transplant recipient function has not been studied extensively. Methods We analyzed 96 live-kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from CT angiograms) and their matching recipients. Split function differences (SFD) were quantified with 99mTc-DMSA renography. Implantation biopsies at time-zero were semi-quantitatively scored. A comprehensive model utilizing donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at one-year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60ml/min/1.73 m2 at one-year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the CKD-EPI formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). Results In the study cohort, the mean Vol/Wgt and eGFR at one-year were 2.04 ml/kg and 60.4 ml/min/1.73m2, respectively. Volume and split ratios between two donor kidneys were strongly correlated (r=0.79, p-value<0.001). The biopsy scores among SFD categories (<5%, 5–10%, >10%) were not different (p=0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR>60ml/min/1.73 m2 (OR=8.94, 95% CI 2.47–32.25, p=0.001) and had a strong discriminatory power in predicting the risk of eGFR<60ml/min/1.73m2 at one-year (ROC curve=0.78, 95% CI 0.68–0.89). Conclusion In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at one-year post-transplantation. Renography can be replaced with CT volume calculation in estimating split renal function. PMID:25719258

Localized renal cell carcinoma management: an update.

PubMed

Heldwein, Flavio L; McCullough, T Casey; Souto, Carlos A V; Galiano, Marc; Barret, Eric

2008-01-01

To review the current modalities of treatment for localized renal cell carcinoma. A literature search for keywords: renal cell carcinoma, radical nephrectomy, nephron sparing surgery, minimally invasive surgery, and cryoablation was performed for the years 2000 through 2008. The most relevant publications were examined. New epidemiologic data and current treatment of renal cancer were covered. Concerning the treatment of clinically localized disease, the literature supports the standardization of partial nephrectomy and laparoscopic approaches as therapeutic options with better functional results and oncologic success comparable to standard radical resection. Promising initial results are now available for minimally invasive therapies, such as cryotherapy and radiofrequency ablation. Active surveillance has been reported with acceptable results, including for those who are poor surgical candidates. This review covers current advances in radical and conservative treatments of localized kidney cancer. The current status of nephron-sparing surgery, ablative therapies, and active surveillance based on natural history has resulted in great progress in the management of localized renal cell carcinoma.

Lethal morphine intoxication in a patient with a sickle cell crisis and renal impairment: case report and a review of the literature.

PubMed

Lagas, Jurjen S; Wagenaar, Jiri F P; Huitema, Alwin D R; Hillebrand, Michel J X; Koks, Cornelis H W; Gerdes, Victor E A; Brandjes, Desiderius P M; Beijnen, Jos H

2011-09-01

Morphine-6-glucuronide, the active metabolite of morphine, and to a lesser extent morphine itself are known to accumulate in patients with renal failure. A number of cases on non-lethal morphine toxicity in patients with renal impairment report high plasma concentrations of morphine-6-glucuronide, suggesting that this metabolite achieves sufficiently high brain concentrations to cause long-lasting respiratory depression, despite its poor central nervous system penetration. We report a lethal morphine intoxication in a 61-year-old man with sickle cell disease and renal impairment, and we measured concentrations of morphine and morphine-6-glucuronide in blood, brain and cerebrospinal fluid. There were no measurable concentrations of morphine-6-glucuronide in cerebrospinal fluid or brain tissue, despite high blood concentrations. In contrast, the relatively high morphine concentration in the brain suggests that morphine itself was responsible for the cardiorespiratory arrest in this patient. Given the fatal outcome, we recommend to avoid repeated or continuous morphine administration in renal failure.

Renal function decline predicted by left atrial expansion index in non-diabetic cohort with preserved systolic heart function.

PubMed

Hsiao, Shih-Hung; Chiou, Kuan-Rau

2017-05-01

Since natriuretic peptide and troponin are associated with renal prognosis and left atrial (LA) parameters are indicators of subclinical cardiovascular abnormalities, this study investigated whether LA expansion index can predict renal decline. This study analysed 733 (69% male) non-diabetic patients with sinus rhythm, preserved systolic function, and estimated glomerular filtration rate (eGFR) higher than 60 mL/min/1.73 m2. In all patients, echocardiograms were performed and LA expansion index was calculated. Renal function was evaluated annually. The endpoint was a downhill trend in renal function with a final eGFR of <60 mL/min/1.73 m2. Rapid renal decline was defined as an annual decline in eGFR >3 mL/min/1.73 m2. The median follow-up time was 5.2 years, and 57 patients (7.8%) had renal function declines (19 had rapid renal declines, and 38 had incidental renal dysfunction). Events were associated with left ventricular mass index, LA expansion index, and heart failure during the follow-up period. The hazard ratio was 1.426 (95% confidence interval, 1.276-1.671; P < 0.0001) per 10% decrease in LA expansion index and was independently associated with an increased event rate. Compared with the highest quartile for the LA expansion index, the lowest quartile had a 9.7-fold risk of renal function decline in the unadjusted model and a 6.9-fold risk after adjusting for left ventricular mass index and heart failure during the follow-up period. Left atrial expansion index is a useful early indicator of renal function decline and may enable the possibility of early intervention to prevent renal function from worsening. NCT01171040. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Downregulation of miR‑135a predicts poor prognosis in acute myeloid leukemia and regulates leukemia progression via modulating HOXA10 expression.

PubMed

Xu, Hongwei; Wen, Quan

2018-05-23

MicroRNA‑135a (miR‑135a) has been shown to exert important roles in various human cancer types, such as glioblastoma, thyroid carcinoma and renal carcinoma. However, the function of miR‑135a in acute myeloid leukemia (AML) remains largely unknown. In the present study, it was demonstrated that miR‑135a expression was significantly downregulated in AML cells compared with normal control cells. Furthermore, the downregulation of miR‑135a in patients with AML predicted poor prognosis. Through functional experiments, overexpression of miR‑135a was demonstrated to significantly inhibit the proliferation and cell cycle of AML cells, while it promoted cellular apoptosis. miR‑135a directly targeted HOXA10 in AML cells. miR‑135a overexpression significantly suppressed the mRNA and protein levels of HOXA10 in AML cells. Moreover, there was an inverse association between miR‑135a expression and HOXA10 level in AML samples. Additionally, by ectopic expression of HOXA10, restoration of HOXA10 significantly abolished the effects of miR‑135a overexpression on AML cell proliferation, cell cycle and apoptosis. In conclusion, the present study demonstrated that miR‑135a serves as a tumor suppressor in AML by targeting HOXA10, and miR‑135a may be a promising prognostic biomarker for AML patients.

Using OCT to predict post-transplant renal function

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Chen, Yu; Wierwille, Jeremiah; Joh, Daniel; Alexandrov, Peter; Rogalsky, Derek; Moody, Patrick; Chen, Allen; Cooper, Matthew; Verbesey, Jennifer E.; Gong, Wei; Wang, Hsing-Wen

2013-03-01

The treatment of choice for patients with end-stage renal disease is kidney transplantation. However, acute tubular necrosis (ATN) induced by an ischemic insult (e.g., from prolonged ex vivo storage times, or non-heart beating cadavers) is a major factor limiting the availability of donor kidneys. In addition, ischemic induced ATN is a significant risk factor for eventual graft survival and can be difficult to discern from rejection. Currently, there are no rapid and reliable tests to determine ATN suffered by donor kidneys and whether or not donor kidneys might exhibit delayed graft function. OCT (optical coherence tomography) is a rapidly emerging imaging modality that can function as a type of "optical biopsy", providing cross-sectional images of tissue morphology in situ and in real-time. In a series of recent clinical trials, we evaluated the ability of OCT to image those features of the renal microstructure that are predictive of ATN. Specifically, we found that OCT could effectively image through the intact human renal capsule and determine the extent of acute tubular necrosis. We also found that Doppler based OCT (i.e., DOCT) revealed renal blood flow dynamics that is also reported to be a determiner of post-transplant renal function. This kind of information will allow transplant surgeons to make the most efficient use of available donor kidneys, eliminate the possible use of bad donor kidneys, provide a measure of expected post-transplant renal function, and allow better distinction between post-transplant immunological rejection and ischemic-induced acute renal failure.

[Managing focal incidental renal lesions].

PubMed

Nicolau, C; Paño, B; Sebastià, C

2016-01-01

Incidental renal lesions are relatively common in daily radiological practice. It is important to know the different diagnostic possibilities for incidentally detected lesions, depending on whether they are cystic or solid. The management of cystic lesions is guided by the Bosniak classification. In solid lesions, the goal is to differentiate between renal cancer and benign tumors such as fat-poor angiomyolipoma and oncocytoma. Radiologists need to know the recommendations for the management of these lesions and the usefulness of the different imaging techniques and interventional procedures in function of the characteristics of the incidental lesion and the patient's life expectancy. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Clinical outcomes and survival in AA amyloidosis patients.

PubMed

Ayar, Yavuz; Ersoy, Alparslan; Oksuz, Mustafa Ferhat; Ocakoglu, Gokhan; Vuruskan, Berna Aytac; Yildiz, Abdülmecit; Isiktas, Emel; Oruc, Aysegül; Celikci, Sedat; Arslan, Ismail; Sahin, Ahmet Bilgehan; Güllülü, Mustafa

Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65±3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p=0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p=0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p=0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3±16 months. Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis. Copyright © 2017. Published by Elsevier Editora Ltda.

The rebirth of interest in renal tubular function.

PubMed

Lowenstein, Jerome; Grantham, Jared J

2016-06-01

The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate. Copyright © 2016 the American Physiological Society.

Ward mortality after ICU discharge: a multicenter validation of the Sabadell score.

PubMed

Fernandez, Rafael; Serrano, Jose Manuel; Umaran, Isabel; Abizanda, Ricard; Carrillo, Andres; Lopez-Pueyo, Maria Jesus; Rascado, Pedro; Balerdi, Begoña; Suberviola, Borja; Hernandez, Gonzalo

2010-07-01

Tools for predicting post-ICU patients' outcomes are scarce. A single-center study showed that the Sabadell score classified patients into four groups with clear-cut differences in ward mortality. To validate the Sabadell score using a prospective multicenter approach. Thirty-one ICUs in Spain. All patients admitted in the 3-month study period. We recorded variables at ICU admission (age, sex, severity of illness, and do-not-resuscitate orders), during the ICU stay (ICU-specific treatments, ICU-acquired infection, and acute renal failure), and at ICU discharge (Sabadell score). Statistical analyses included one-way ANOVA and multiple regression analysis with ward mortality as the dependent variable. We admitted 4,132 patients (mean age 61.5 +/- 16.7 years) with mean predicted mortality of 23.8 +/- 22.7%; 545 patients (13%) died in the ICU and 3,587 (87%) were discharged to the ward. Overall ward mortality was 6.7%; ward mortality was 1.5% (36/2,422) in patients with score 0 (good prognosis), 9% (64/725) in patients with score 1 (long-term poor prognosis), 23% (79/341) in patients with score 2 (short-term poor prognosis), and 64% (63/99) in patients with score 3 (expected hospital death). Variables associated with ward mortality in the multivariate analysis were predicted risk of death (OR 1.016), ICU readmission (OR 5.9), Sabadell score 1 (OR 4.7), Sabadell score 2 (OR 15.7), and Sabadell score 3 (OR 107.2). We confirm the ability of the Sabadell score at ICU discharge to define four groups of patients with very different likelihoods of hospital survival.

Select critically ill patients at risk of augmented renal clearance: experience in a Malaysian intensive care unit.

PubMed

Adnan, S; Ratnam, S; Kumar, S; Paterson, D; Lipman, J; Roberts, J; Udy, A A

2014-11-01

Augmented renal clearance (ARC) refers to increased solute elimination by the kidneys. ARC has considerable implications for altered drug concentrations. The aims of this study were to describe the prevalence of ARC in a select cohort of patients admitted to a Malaysian intensive care unit (ICU) and to compare measured and calculated creatinine clearances in this group. Patients with an expected ICU stay of <24 hours plus an admission serum creatinine concentration <120 µmol/l, were enrolled from May to July 2013. Twenty-four hour urinary collections and serum creatinine concentrations were used to measure creatinine clearance. A total of 49 patients were included, with a median age of 34 years. Most study participants were male and admitted after trauma. Thirty-nine percent were found to have ARC. These patients were more commonly admitted in emergency (P=0.03), although no other covariants were identified as predicting ARC, likely due to the inclusion criteria and the study being under-powered. Significant imprecision was demonstrated when comparing calculated Cockcroft-Gault creatinine clearance (Crcl) and measured Crcl. Bias was larger in ARC patients, with Cockcroft-Gault Crcl being significantly lower than measured Crcl (P <0.01) and demonstrating poor correlation (rs=-0.04). In conclusion, critically ill patients with 'normal' serum creatinine concentrations have varied Crcl. Many are at risk of ARC, which may necessitate individualised drug dosing. Furthermore, significant bias and imprecision between calculated and measured Crcl exists, suggesting clinicians should carefully consider which method they employ in assessing renal function.

Inhospital and Post-discharge Changes in Renal Function After Transcatheter Aortic Valve Replacement.

PubMed

Blair, John E A; Brummel, Kent; Friedman, Julie L; Atri, Prashant; Sweis, Ranya N; Russell, Hyde; Ricciardi, Mark J; Malaisrie, S Chris; Davidson, Charles J; Flaherty, James D

2016-02-15

The aim of this study was to determine the influence of inhospital and post-discharge worsening renal function (WRF) on prognosis after transcatheter aortic valve replacement (TAVR). Severe chronic kidney disease and inhospital WRF are both associated with poor outcomes after TAVR. There are no data available on post-discharge WRF and outcomes. This was a single-center study evaluating all TAVR from June 1, 2008, to June 31, 2014. WRF was defined as an increase in serum creatinine of ≥0.3 mg/dl. Inhospital WRF was measured from day 0 until discharge or day 7 if the hospitalization was >7 days. Post-discharge WRF was measured at 30 days after discharge. Descriptive statistics, Kaplan-Meier time-to-event analysis, and multivariate logistic regression were used. In a series of 208 patients who underwent TAVR, 204 with complete renal function data were used in the inhospital analysis and 168 who returned for the 30-day follow-up were used in the post-discharge analysis. Inhospital WRF was seen in 28%, whereas post-discharge WRF in 12%. Inhospital and post-discharge WRF were associated with lower rates of survival; however, after multivariate analysis, only post-discharge WRF remained a predictor of 1-year mortality (hazard ratio 1.18, p = 0.030 for every 1 mg/dl increase in serum creatinine). In conclusion, the rate of inhospital WRF is higher than the rate of post-discharge WRF after TAVR, and post-discharge WRF is more predictive of mortality than inhospital WRF. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment of hepatorenal syndrome as defined by the international ascites club by albumin and furosemide infusion according to the central venous pressure: a prospective pilot study.

PubMed

Péron, Jean-Marie; Bureau, Christophe; Gonzalez, Laurent; Garcia-Ricard, Franck; de Soyres, Olivier; Dupuis, Emmanuel; Alric, Laurent; Pourrat, Jacques; Vinel, Jean-Pierre

2005-12-01

Hepatorenal syndrome (HRS) is a functional renal failure that occurs late during cirrhosis. The prognosis is extremely poor with a mean survival of 1.7 wks from the time of diagnosis. The aim of the present study was to examine the effects of albumin and furosemide administration tailored to central venous pressure (CVP) on renal function and clinical outcome. We treated 20 consecutive patients with HRS. Albumin was given to increase and/or maintain CVP above 3 cm H(2)O. If diuresis remained below 50 mL/h despite effective volume expansion, furosemide was administrated. Patients were considered responders and treatment was discontinued when creatinine clearance rose above 40 mL/min or serum creatinine fell under 132 mumol/L. The need for albumin varied from patient to patient (extremes 40-600 g) and in the same patient from day to day. All but one needed furosemide. Eleven patients (55%) responded to treatment. In this population, diuresis, serum creatinine, and creatinine clearance were all significantly improved. Creatinine clearance at baseline was predictive of treatment efficacy. Survival increased in these patients compared to nonresponders defined as patients with no improvement in renal function (259 days +/- 113 compared to 14 days +/- 3, p < 0.0005). Response to treatment and the type of HRS were the only variables with an independent prognostic value. This study shows that HRS as defined by the International Ascites Club can be treated by albumin administration alone or with furosemide given according to the patient's specific need using CVP.

Predicting Renal Failure Progression in Chronic Kidney Disease Using Integrated Intelligent Fuzzy Expert System.

PubMed

Norouzi, Jamshid; Yadollahpour, Ali; Mirbagheri, Seyed Ahmad; Mazdeh, Mitra Mahdavi; Hosseini, Seyed Ahmad

2016-01-01

Chronic kidney disease (CKD) is a covert disease. Accurate prediction of CKD progression over time is necessary for reducing its costs and mortality rates. The present study proposes an adaptive neurofuzzy inference system (ANFIS) for predicting the renal failure timeframe of CKD based on real clinical data. This study used 10-year clinical records of newly diagnosed CKD patients. The threshold value of 15 cc/kg/min/1.73 m(2) of glomerular filtration rate (GFR) was used as the marker of renal failure. A Takagi-Sugeno type ANFIS model was used to predict GFR values. Variables of age, sex, weight, underlying diseases, diastolic blood pressure, creatinine, calcium, phosphorus, uric acid, and GFR were initially selected for the predicting model. Weight, diastolic blood pressure, diabetes mellitus as underlying disease, and current GFR(t) showed significant correlation with GFRs and were selected as the inputs of model. The comparisons of the predicted values with the real data showed that the ANFIS model could accurately estimate GFR variations in all sequential periods (Normalized Mean Absolute Error lower than 5%). Despite the high uncertainties of human body and dynamic nature of CKD progression, our model can accurately predict the GFR variations at long future periods.

Predictive value of myocardial perfusion single-photon emission computed tomography and the impact of renal function on cardiac death.

PubMed

Hakeem, Abdul; Bhatti, Sabha; Dillie, Kathryn Sullivan; Cook, Jeffrey R; Samad, Zainab; Roth-Cline, Michelle D; Chang, Su Min

2008-12-09

Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes than those without CKD. The prognostic utility of myocardial perfusion single-photon emission CT (MPS) in patients with varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction in patients undergoing MPS have not been investigated. We followed up 1652 consecutive patients who underwent stress MPS (32% exercise, 95% gated) for cardiac death for a mean of 2.15+/-0.8 years. MPS defects were defined with a summed stress score (normal summed stress score <4, abnormal summed stress score>or=4). Ischemia was defined as a summed stress score >or=4 plus a summed difference score >or=2, and scar was defined as a summed difference score <2 plus a summed stress score >or=4. Renal function was calculated with the Modified Diet in Renal Disease equation. CKD (estimated glomerular filtration rate <60 mL . min(-1) . 1.73 m(-2)) was present in 36%. Cardiac death increased with worsening levels of perfusion defects across the entire spectrum of renal function. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher unadjusted cardiac death event rates than those with no CKD and normal MPS (2.7% versus 0.8%, P=0.001). Multivariate Cox proportional hazards models revealed that both perfusion defects (hazard ratio 1.90, 95% CI 1.47 to 2.46) and CKD (hazard ratio 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptom status. Both MPS and CKD had incremental power for cardiac death prediction over baseline risk factors and left ventricular dysfunction (global chi(2) 207.5 versus 169.3, P<0.0001). MPS provides effective risk stratification across the entire spectrum of renal function. Renal dysfunction is also an important independent predictor of cardiac death in patients undergoing MPS. Renal function and MPS have additive value in risk stratisfying patients with suspected coronary artery disease. Patients with CKD appear to have a relatively less benign prognosis than those without CKD, even in the presence of a normal scan.

IGF-1 and IGF-binding proteins and bone mass, geometry, and strength: relation to metabolic control in adolescent girls with type 1 diabetes.

PubMed

Moyer-Mileur, Laurie J; Slater, Hillarie; Jordan, Kristine C; Murray, Mary A

2008-12-01

Children and adolescents with poorly controlled type 1 diabetes mellitus (T1DM) are at risk for decreased bone mass. Growth hormone (GH) and its mediator, IGF-1, promote skeletal growth. Recent observations have suggested that children and adolescents with T1DM are at risk for decreased bone mineral acquisition. We examined the relationships between metabolic control, IGF-1 and its binding proteins (IGFBP-1, -3, -5), and bone mass in T1DM in adolescent girls 12-15 yr of age with T1DM (n = 11) and matched controls (n = 10). Subjects were admitted overnight and given a standardized diet. Periodic blood samples were obtained, and bone measurements were performed. Serum GH, IGFBP-1 and -5, glycosylated hemoglobin (HbA(1c)), glucose, and urine magnesium levels were higher and IGF-1 values were lower in T1DM compared with controls (p < 0.05). Whole body BMC/bone area (BA), femoral neck areal BMD (aBMD) and bone mineral apparent density (BMAD), and tibia cortical BMC were lower in T1DM (p < 0.05). Poor diabetes control predicted lower IGF-1 (r(2) = 0.21) and greater IGFBP-1 (r(2) = 0.39), IGFBP-5 (r(2) = 0.38), and bone-specific alkaline phosphatase (BALP; r(2) = 0.41, p < 0.05). Higher urine magnesium excretion predicted an overall shorter, lighter skeleton, and lower tibia cortical bone size, mineral, and density (r(2) = 0.44-0.75, p < 0.05). In the T1DM cohort, earlier age at diagnosis was predictive of lower IGF-1, higher urine magnesium excretion, and lighter, thinner cortical bone (r(2) >or=0.45, p < 0.01). We conclude that poor metabolic control alters the GH/IGF-1 axis, whereas greater urine magnesium excretion may reflect subtle changes in renal function and/or glucosuria leading to altered bone size and density in adolescent girls with T1DM.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage.

PubMed

Tomlinson, James A P; Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C; Khadayate, Sanjay; Mas, Valeria R; Nitsch, Dorothea D; Wang, Zhen; Norman, Jill T; Wilcox, Christopher S; Wheeler, David C; Leiper, James

2015-12-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule-specific Ddah1 knockout (Ddah1(PT-/-)) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1(PT-/-) mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. Copyright © 2015 by the American Society of Nephrology.

Association between pulmonary function and renal function: findings from China and Australia.

PubMed

Yu, Dahai; Chen, Tao; Cai, Yamei; Zhao, Zhanzheng; Simmons, David

2017-05-01

The relationship between obstructive lung function and impaired renal function is unclear. This study investigated the dose-response relationship between obstructive lung function and impaired renal function. Two independent cross-sectional studies with representative sampling were applied. 1454 adults from rural Victoria, Australia (1298 with normal renal function, 156 with impaired renal function) and 5824 adults from Nanjing, China (4313 with normal renal function, 1511 with impaired renal function). Pulmonary function measurements included forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Estimated glomerular filtration rate (eGFR), and impaired renal function marked by eGFR <60 mL/min/1.73m 2 were used as outcome. eGFR increased linearly with FEV1 in Chinese participants and with FVC in Australians. A non-linear relationship with peaked eGFR was found for FEV1 at 2.65 L among Australians and for FVC at 2.78 L among Chinese participants, respectively. A non-linear relationship with peaked eGFR was found for the predicted percentage value of forced expiratory volume in 1 s (PFEV1) at 81-82% and for the predicted percentage value of forced vital capacity (PFVC) at 83-84% among both Chinese and Australian participants, respectively. The non-linear dose-response relationships between lung capacity measurements (both for FEV1 and FVC) and risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 3.05 L both for FEV1 and FVC, respectively. The non-linear relationship between PFEV and PVC and the risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 76-77% for PFEV1 and 79-80% for PFVC, respectively. In both Australian and Chinese populations, the risk of impaired renal function increased both with FEV1 and FVC below 3.05 L, with PFEV1 below 76-77% or with PFVC below 79-80%, respectively. Obstructive lung function was associated with increased risk of reduced renal function. The screen for impaired renal function in patients with obstructive lung disease might be useful to ensure there was no impaired renal function before the commencement of potentially nephrotoxic medication where indicated (eg diuretics).

The cell biology of polycystic kidney disease

PubMed Central

Chapin, Hannah C.

2010-01-01

Polycystic kidney disease is a common genetic disorder in which fluid-filled cysts displace normal renal tubules. Here we focus on autosomal dominant polycystic kidney disease, which is attributable to mutations in the PKD1 and PKD2 genes and which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis. The mechanisms that connect the underlying genetic defects to disease pathogenesis are poorly understood, but their exploration is shedding new light on interesting cell biological processes and suggesting novel therapeutic targets. PMID:21079243

Cutaneous metastasis of bilateral renal cell carcinoma.

PubMed

Abbasi, Fariba; Alizadeh, Mansur; Noroozinia, Farahnaz; Moradi, Amin

2013-01-01

Renal cell carcinoma (RCC) is a malignant lethal tumour with high potential of metastasis. However, metastasis from RCC to the skin is much less common. It is virtually a sign of poor prognosis. We represent a 42 years old man with bilateral RCC of clear cell type followed by metastasis to the scalp one month later. In this case the relatively young age of the patient, bilaterality of RCC and occurance of skin metastasis in the absence of recurrent kidney tumour are interesting.

Uptake of gentamicin by separated, viable renal tubules from rabbits.

PubMed

Barza, M; Murray, T; Hamburger, R J

1980-04-01

The proximal renal tubules have a marked affinity for gentamicin; they also are the major site of nephrotoxicity caused by this drug. The uptake of radiolabeled gentamicin in separated, viable renal tubules prepared by enzymatic digestion of rabbit kidneys was studied. The preparations showed rapid initial uptake of gentamicin followed by continued slower uptake. Accumulation was not affected by pH, but was significantly inhibited by ouabain, dinitrophenol, anoxia, and hypothermia in the absence of evident cellular damage. At gentamicin concentrations of greater than 50 microgram/ml in the medium, there was competition for drug uptake. Gentamicin efflux in tubules that were taken from a medium containing antibiotic and placed into antibiotic-free fluid was slow and incomplete. From these data it appears that gentamicin uptake by separated renal tubules occurs by a process that requires metabolic energy; thereafter, the drug resides in a poorly exchangeable cellular pool.

Renal cell carcinoma in the allograft: what is the role of polyomavirus?

PubMed

Neirynck, Valerie; Claes, Kathleen; Naesens, Maarten; De Wever, Liesbeth; Pirenne, Jacques; Kuypers, Dirk; Vanrenterghem, Yves; Poppel, Hendrik Van; Kabanda, Andre; Lerut, Evelyne

2012-07-01

BK virus (BKV) is known to cause subclinical infection in childhood. The virus remains latent in the human body, mainly in the urinary tract epithelium. After initiation of an immunosuppressive treatment, reactivation can occur in renal transplant recipients. BKV can cause hemorrhagic cystitis, ureteral stenosis and BKV nephropathy in immunocompromised patients. Furthermore, a number of case reports suggest an association between BKV infection and the development of urinary tract cancer. So far, an oncogenic potential of BKV has been observed in vitro and in animal models; however, its oncogenic capacity in humans remains unclear. We report the case of a 59-year-old patient who developed a poorly differentiated renal cell carcinoma in her renal allograft, with pulmonary and abdominal metastasis. Surgical removal of the allograft and cessation of the immunosuppressive therapy resulted in complete resolution of the metastatic disease.

Squamous cell carcinoma of the renal pelvis associated with kidney stones: a case report.

PubMed

Paonessa, J; Beck, H; Cook, S

2011-12-01

A 70-year-old female with a long-standing history of kidney calculi presented with vague abdominal pain. Work-up included a CT and MRI of the kidneys. A mass was demonstrated in the superior pole of the left kidney. The mass was biopsied percutaneously under CT guidance. Pathology revealed a poorly differentiated carcinoma, but was inconclusive for a definitive cell type. The patient subsequently underwent a nephrectomy that revealed squamous cell carcinoma of the renal collecting system. She had an uneventful postoperative recovery. Chronic renal calculi pose a risk for the development of squamous metaplasia that may lead to squamous cell carcinoma. Although this malignancy is rare in the upper urinary tracts, patients with long-standing nephrolithiasis should be monitored. This diagnosis should be included in one's differential when evaluating a renal mass that is associated with chronic inflammatory conditions.

Diuretic 99mTc DTPA renography in assessment of renal function and drainage in infants with antenatally detected hydronephrosis.

PubMed

Radulović, Marija; Pucar, Dragan; Jauković, Ljiljana; Sisić, Marija; Krstić, Zoran; Ajdinović, Boris

2015-12-01

The controversy over the postnatal management of infants with antenataly detected hydronephrosis (ANH) still exists. We presented the results of diuretic 99mTc diethylenetriamine pentaacetic acid (DTPA) renography in 30 infants with the antenatal diagnosis of unilateral renal pelvic dilatation. The aim of this study was to assess the renal function determined by the pattern of drainage and split renal function (SRF) on diuretic renography and to correlate these findings with anteroposterior pelvic diameter (APD) estimated by ultrasonography. A total of 30 infants with 60 renal units (RU) (25 boys and 5 girls, median age 6.0 months, range 2-24) presented with unilateral hydronephrosis on ultrasound in the newborn period, underwent DTPA diuretic renal scintigraphy (F+15 protocol). The median APD evaluated on perinatal ultrasound was 15 mm (range 5-30). The postnatal associated clinical diagnosis were pelviureteric junction obstruction (PUJ), simple hydronephrosis, megaureter, vesicoureteral reflux (VUR) and posterior urethral valves in 11, 10, 6, 2 and 1 infant, respectively. Images and Tmax/2 after diuretic stimulation on the background subtracted renographic curves were used as the criteria for classifying the drainage as good, partial, and poor or no drainage. The SRF was calculated with the integral method. Good drainage was shown in 36/60, partial drainage in 13/60 and poor or no drainage in 11/60 RU. The SRF > 40% was observed in 55/60 RU, with no RU showing SRF lower than 23.5%. In infants with severe ANH the obstruction was not excluded in 94.1%. Diuretic renography in antenatally detected hydronephrosis should be a useful tool in postnatal follow up, especially in differentiating nonobstructive hydronephrosis from obstructive. It is also importanat to assess and monitor the SRF. Our results suggest that even in the presence of partial or no drainage, SRF may not be significantly impaired.

Prediction of vesicoureteral reflux after a first febrile urinary tract infection in children: validation of a clinical decision rule.

PubMed

Leroy, S; Marc, E; Adamsbaum, C; Gendrel, D; Bréart, G; Chalumeau, M

2006-03-01

To test the reproducibility of a highly sensitive clinical decision rule proposed to predict vesicoureteral reflux (VUR) after a first febrile urinary tract infection in children. This rule combines clinical (family history of uropathology, male gender, young age), biological (raised C reactive protein), and radiological (urinary tract dilation on renal ultrasound) predictors in a score, and provides 100% sensitivity. A retrospective hospital based cohort study included all children, 1 month to 4 years old, with a first febrile urinary tract infection. The sensitivities and specificities of the rule at the two previously proposed score thresholds (< or =0 and < or =5) to predict respectively, all-grade or grade > or =3 VUR, were calculated. A total of 149 children were included. VUR prevalence was 25%. The rule yielded 100% sensitivity and 3% specificity for all-grade VUR, and 93% sensitivity and 13% specificity for grade > or =3 VUR. Some methodological weaknesses explain this lack of reproducibility. The reproducibility of the previously proposed decision rule was poor and its potential contribution to clinical management of children with febrile urinary tract infection seems to be modest.

Prediction of vesicoureteral reflux after a first febrile urinary tract infection in children: validation of a clinical decision rule

PubMed Central

Leroy, S; Marc, E; Adamsbaum, C; Gendrel, D; Bréart, G; Chalumeau, M

2006-01-01

Aims To test the reproducibility of a highly sensitive clinical decision rule proposed to predict vesicoureteral reflux (VUR) after a first febrile urinary tract infection in children. This rule combines clinical (family history of uropathology, male gender, young age), biological (raised C reactive protein), and radiological (urinary tract dilation on renal ultrasound) predictors in a score, and provides 100% sensitivity. Methods A retrospective hospital based cohort study included all children, 1 month to 4 years old, with a first febrile urinary tract infection. The sensitivities and specificities of the rule at the two previously proposed score thresholds (⩽0 and ⩽5) to predict respectively, all‐grade or grade ⩾3 VUR, were calculated. Results A total of 149 children were included. VUR prevalence was 25%. The rule yielded 100% sensitivity and 3% specificity for all‐grade VUR, and 93% sensitivity and 13% specificity for grade ⩾3 VUR. Some methodological weaknesses explain this lack of reproducibility. Conclusions The reproducibility of the previously proposed decision rule was poor and its potential contribution to clinical management of children with febrile urinary tract infection seems to be modest. PMID:15890693

Prevention of renal failure: the Malaysian experience.

PubMed

Hooi, Lai Seong; Wong, Hin Seng; Morad, Zaki

2005-04-01

Renal replacement therapy in Malaysia has shown exponential growth since 1990. The dialysis acceptance rate for 2003 was 80 per million population, prevalence 391 per million population. There are now more than 10,000 patients on dialysis. This growth is proportional to the growth in gross domestic product (GDP). Improvement in nephrology and urology services with widespread availability of ultrasonography and renal pathology has improved care of renal patients. Proper management of renal stone disease, lupus nephritis, and acute renal failure has decreased these as causes of end-stage renal disease (ESRD) in younger age groups. Older patients are being accepted for dialysis, and 51% of new patients on dialysis were diabetic in 2003. The prevalence of diabetes is rising in the country (presently 7%); glycemic control of such patients is suboptimal. Thirty-three percent of adult Malaysians are hypertensive and blood pressure control is poor (6%). There is a national coordinating committee to oversee the control of diabetes and hypertension in the country. Primary care clinics have been provided with kits to detect microalbuminuria, and ACE inhibitors for the treatment of hypertension and diabetic nephropathy. Prevention of renal failure workshops targeted at primary care doctors have been launched, opportunistic screening at health clinics is being carried out, and public education targeting high-risk groups is ongoing. The challenge in Malaysia is to stem the rising tide of diabetic ESRD.

Persistent Increase in Blood Pressure After Renal Nerve Stimulation in Accessory Renal Arteries After Sympathetic Renal Denervation.

PubMed

de Jong, Mark R; Hoogerwaard, Annemiek F; Gal, Pim; Adiyaman, Ahmet; Smit, Jaap Jan J; Delnoy, Peter Paul H M; Ramdat Misier, Anand R; van Hasselt, Boudewijn A A M; Heeg, Jan-Evert; le Polain de Waroux, Jean-Benoit; Lau, Elizabeth O Y; Staessen, Jan A; Persu, Alexandre; Elvan, Arif

2016-06-01

Blood pressure response to renal denervation is highly variable, and the proportion of responders is disappointing. This may be partly because of accessory renal arteries too small for denervation, causing incomplete ablation. Renal nerve stimulation before and after renal denervation is a promising approach to assess completeness of renal denervation and may predict blood pressure response to renal denervation. The objective of the current study was to assess renal nerve stimulation-induced blood pressure increase before and after renal sympathetic denervation in main and accessory renal arteries of anaesthetized patients with drug-resistant hypertension. The study included 21 patients. Nine patients had at least 1 accessory renal artery in which renal denervation was not feasible. Renal nerve stimulation was performed in the main arteries of all patients and in accessory renal arteries of 6 of 9 patients with accessory arteries, both before and after renal sympathetic denervation. Renal nerve stimulation before renal denervation elicited a substantial increase in systolic blood pressure, both in main (25.6±2.9 mm Hg; P<0.001) and accessory (24.3±7.4 mm Hg; P=0.047) renal arteries. After renal denervation, renal nerve stimulation-induced systolic blood pressure increase was blunted in the main renal arteries (Δ systolic blood pressure, 8.6±3.7 mm Hg; P=0.020), but not in the nondenervated renal accessory renal arteries (Δ systolic blood pressure, 27.1±7.6 mm Hg; P=0.917). This residual source of renal sympathetic tone may result in persistent hypertension after ablation and partly account for the large response variability. © 2016 American Heart Association, Inc.

Effect of first myocardial ischemic event on renal function.

PubMed

Eijkelkamp, Wouter B A; de Graeff, Pieter A; van Veldhuisen, Dirk J; van Dokkum, Richard P E; Gansevoort, Ronald T; de Jong, Paul E; de Zeeuw, Dick; Hillege, Hans L

2007-07-01

Effects of cardiovascular dysfunction on renal function have been poorly characterized. Therefore, we investigated the relation between a first ischemic cardiac event and long-term renal function changes in the general population from the PREVEND study. We studied 6,360 subjects with a total follow-up duration of 27.017 subject-years. The estimated mean proportional increase in serum creatinine after a first ischemic cardiac event was 3.1% compared with 0.4% per year of follow-up in subjects without such an event (p = 0.005). This represented a significantly larger decrease in estimated glomerular filtration rate after the event in subjects with an event versus the decrease in subjects without a first ischemic cardiac event (2.2 vs 0.5 ml/min/1.73 m(2)/year of follow-up, p = 0.006). In multivariate analysis with adjustment for renal risk factors, this event showed an independent association with serum creatinine change. In conclusion, a first ischemic cardiac event appears to enhance the natural decrease in renal function. Because even mild renal dysfunction should be considered a major cardiovascular risk factor after myocardial infarction, increased renal function loss after an ischemic cardiac event could add to the risk for subsequent cardiovascular morbidity, thus closing a vicious circle.

Renal dysfunction in liver cirrhosis and its correlation with Child-Pugh score and MELD score

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Gurning, M.

2018-03-01

Renal dysfunction (RD) is a serious and common complication in a patient with liver cirrhosis. It provides a poor prognosis. The aim of our study was to evaluate the renal function in liver cirrhosis, also to determine the correlation with the graduation of liver disease assessed by Child-Pugh Score (CPS) and MELD score. This was a cross-sectional study included patients with liver cirrhosis admitted to Adam Malik Hospital Medan in June - August 2016. We divided them into two groups as not having renal dysfunction (serum creatinine < 1.5 mg/dL) and having renal dysfunction (serum creatinine ≤ 1.5 mg/dL). For the processing of data, SPSS 22.0 was used. Statistical methods used: Chi-square, Fisher exact, one way ANOVA, Kruskal Wallis test and Pearson coefficient of correlation. The level of significance was p<0.05. 55 patients with presented with renal dysfunction were 16 (29.1 %). There was statistically significant inverse correlation between GFR and CPS (r = -0.308), GFR and MELD score (r = -0.278). There was a statistically significant correlation between creatinine and MELD score (r = 0.359), creatinine and CPS (r = 0.382). The increase of the degree of liver damage is related to the increase of renal dysfunction.

[Pregnancy in patients with renal transplantation: maternal and fetal morbidity].

PubMed

Romero Arauz, Juan Fernando; Ayala Méndez, José Antonio; Jiménez Solís, Guillermo

2008-11-01

Preeclampsia is a multisystemic syndrome with unknown etiology and characterized by abnormal vascular placentation response. Patients with renal transplantation restore them fertility 10 months after the intervention. To evaluate incidence of preeclampsia and maternal-perinatal outcome in patients with renal transplantation. Comparative, observational and retrospective study performed in pregnant patients with renal transplantation, from December 1999 to April 2008 at Perinatology of Hypertensive Diseases Department of the Unidad Medica de Alta Especialidad de Ginecoobstetricia Luis Castelazo Ayala, IMSS. Davison' guide, descriptive statistic, and Fischer exact test were used. Thirty patients were analyzed, 27 cases satisfy Davison's recommended guidelines, and the rest did not achieve these criteria (p = 0.001). Preeclampsia occurred in 15 cases (50%), preterm delivery in 15 (50%), and fetal growth restriction in 6 (20%). Among the 11 patients with previous chronic hypertension, 8 developed superimposed preeclampsia (72%), and 9 had delivery before 37 weeks of gestation (82%). Malfunction of renal transplantation, before pregnancy, was associated with maternal and perinatal poor outcome (p = 0.006). There were no maternal deaths, but one perinatal (3%) Successful pregnancy is possible in patients with renal transplantation, however there is a high risk of preeclampsia, infection, and fetal growth restriction. Patients with renal transplantation must fulfill Davison's pre-pregnancy guidelines.

Understanding cost of care for patients on renal replacement therapy: looking beyond fixed tariffs.

PubMed

Li, Bernadette; Cairns, John A; Fotheringham, James; Tomson, Charles R; Forsythe, John L; Watson, Christopher; Metcalfe, Wendy; Fogarty, Damian G; Draper, Heather; Oniscu, Gabriel C; Dudley, Christopher; Johnson, Rachel J; Roderick, Paul; Leydon, Geraldine; Bradley, J Andrew; Ravanan, Rommel

2015-10-01

In a number of countries, reimbursement to hospitals providing renal dialysis services is set according to a fixed tariff. While the cost of maintenance dialysis and transplant surgery are amenable to a system of fixed tariffs, patients with established renal failure commonly present with comorbid conditions that can lead to variations in the need for hospitalization beyond the provision of renal replacement therapy. Patient-level cost data for incident renal replacement therapy patients in England were obtained as a result of linkage of the Hospital Episodes Statistics dataset to UK Renal Registry data. Regression models were developed to explore variations in hospital costs in relation to treatment modality, number of years on treatment and factors such as age and comorbidities. The final models were then used to predict annual costs for patients with different sets of characteristics. Excluding the cost of renal replacement therapy itself, inpatient costs generally decreased with number of years on treatment for haemodialysis and transplant patients, whereas costs for patients receiving peritoneal dialysis remained constant. Diabetes was associated with higher mean annual costs for all patients irrespective of treatment modality and hospital setting. Age did not have a consistent effect on costs. Combining predicted hospital costs with the fixed costs of renal replacement therapy showed that the total cost differential for a patient continuing on dialysis rather than receiving a transplant is considerable following the first year of renal replacement therapy, thus reinforcing the longer-term economic advantage of transplantation over dialysis for the health service. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Comparison of magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) in the evaluation of unclear solid renal lesions.

PubMed

Rübenthaler, J; Paprottka, K; Marcon, J; Hameister, E; Hoffmann, K; Joiko, N; Reiser, M; Clevert, D A

2016-01-01

To compare the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) in the evaluation of unclear renal lesions to the histopathological outcome. A total of 36 patients with a single unclear solid renal lesion with initial imaging studies between 2005 and 2015 were included. CEUS and MRI were used for determining malignancy or benignancy and initial findings were correlated with the histopathological outcome. Out of the 36 renal masses a total of 28 lesions were malignant (77.8%) and 8 were found to be benign (22.2%). Diagnostic accuracy was testes by using the histopathological diagnosis as the gold standard. CEUS showed a sensitivity of 96.4%, a specificity of 100.0%, a positive predictive value (PPV) of 100.0% and a negative predictive value (NPV) of 88,9%. MRI showed a sensitivity of 96.4%, a specificity of 75.0%, a PPV of 93.1% and a NPV of 85.7%. Out of the 28 malignant lesions a total of 18 clear cell renal carcinomas, 6 papillary renal cell carcinomas and 4 other malignant lesions, e.g. metastases, were diagnosed. Out of the 8 benign lesions a total 3 angiomyolipomas, 2 oncocytomas, 1 benign renal cyst and 2 other benign lesions, e.g. renal adenomas were diagnosed. Using CEUS, 1 lesion was falsely identified as benign. Using MRI, 2 lesions were falsely identified as benign and 1 lesion was falsely identified as malignant. CEUS is an useful method which can be additionally used to clinically differentiate between malignant and benign renal lesions. CEUS shows a comparable sensitivity, specificity, PPV and NPV to MRI. In daily clinical routine, patients with contraindications for other imaging modalities can particularly benefit using this method.

Shock wave lithotripsy (SWL) induces significant structural and functional changes in the kidney

NASA Astrophysics Data System (ADS)

Evan, Andrew P.; Willis, Lynn R.; Lingeman, James E.

2003-10-01

The foundation for understanding SWL-injury has been well-controlled renal structural and functional studies in pigs, a model that closely mimics the human kidney. A clinical dose (2000 shocks at 24 kV) of SWL administered by the Dornier HM3 induces a predictable, unique vascular injury at F2 that is associated with transient renal vasoconstriction, seen as a reduction in renal plasma flow, in both treated and untreated kidneys. Unilateral renal denervation studies links the fall in blood flow in untreated kidneys to autonomic nerve activity in the treated kidney. SWL-induced trauma is associated with an acute inflammatory process, termed Lithotripsy Nephritis and tubular damage at the site of damage that leads to a focal region of scar. Lesion size increases with shock number and kV level. In addition, risk factors like kidney size and pre-existing renal disease (e.g., pyelonephritis), can exaggerate the predicted level of renal impairment. Our new protection data show that lesion size can be greatly reduced by a pretreatment session with low kV and shock number. The mechanisms of soft tissue injury probably involves shear stress followed by acoustic cavitation. Because of the perceived enhanced level of bioeffects from 3rd generation lithotripters, these observations are more relevant than ever.

[Renal arterial spin labeling magnetic resonance imaging in normal adults: a study with a 3.0 T scanner].

PubMed

Zhang, Fan; Zhang, Xuelin; Yang, Li; Shen, Jie; Gao, Wei

2013-10-01

To analyze the renal relative blood flow value (rBFV) and image quality in normal adults using single-shot fast spin echo, flow sensitive invention recovery (SSFSE-FAIR) magnetic resonance (MR) sequence and echo planar imaging, and flow sensitive invention recovery (EPI-FAIR) MR sequence, and assess its value for clinical application in routine renal examination. Forty volunteers (25 male and 15 female adults, aged 30 to 62 years) with normal renal function were included in this prospective study. All the subjects underwent 3.0 Tesla MR scanning using 3 MR scan modes, namely breath-holding EPI-FAIR, breath-holding SSFSE-FAIR and free breathing SSFSE-FAIR. SSFSE-FAIR without breath-holding was capable of differentiating the renal cortex and medulla with the corresponding rBFVs of 111.48∓9.23 and 94.98∓3.38, respectively. Breath-holding SSFSE-FAIR and EPI-FAIR failed to distinguish the borders of the renal cortex and medulla. The EPI-FAIR rBFV of mixed cortex and medulla value was 178.50∓17.17 (95%CI: 167.59, 189.41). Breath-holding SSFSE-FAIR and EPI-FAIR can not distinguish the renal cortex and medulla due to a poor spatial resolution but can be used for rough evaluation of renal blood perfusion. Free breathing SSFSE-FAIR with an improved spatial resolution allows evaluation of the status of renal perfusion of the cortex and medulla.

Impact of a quality improvement project on deceased organ donor management

PubMed Central

Olmos, Andrea; Feiner, John; Hirose, Ryutaro; Swain, Sharon; Blasi, Annabel; Roberts, John P.; Niemann, Claus U.

2017-01-01

Context Donors showed poor glucose control in the period between declaration of brain death and organ recovery. The level of hyperglycemia in the donors was associated with a decline in terminal renal function. Objective To determine whether implementation of a quality improvement project improved glucose control and preserved renal function in deceased organ donors. Methods Data collected retrospectively included demographics, medical history, mechanism of death, laboratory values, and data from the United Network for Organ Sharing. Results After implementation of the quality improvement project, deceased donors had significantly lower mean glucose concentrations (mean [SD], 162 [44] vs 212 [42] mg/dL; P < .001) and prerecovery glucose concentration (143 [66] vs 241 [69] mg/dL; P < .001). When the donor cohorts from before and after the quality improvement project were analyzed together, mean glucose concentration remained a significant predictor of terminal creatinine level (P < .001). Multivariate analysis of delayed graft function in kidney recipients matched to donors indicated that higher terminal creatinine level was associated with delayed graft function in recipients (P < .001). Conclusion The quality improvement project improved donor glucose homeostasis, and the data confirm that poor glucose homeostasis is associated with worsening terminal renal function. PMID:26645930

Hypomagnesemia and Chemotherapy, Diagnostic Dilemma, and Treatment Challenge: Case Report and Literature Review.

PubMed

Haroon, Nivin; Raza, Syed M; Bhat, Zeenat Y

2016-01-01

Magnesium is the second most common intracellular cation after potassium and plays pivotal role in the majority of metabolic process. Several studies have shown the prevalence of hypomagnesemia ranging from 2.5% to 12% in general population and even up to 60% in intensive care unit patients. Hypomagnesemia might be more prevalent in patients with cancer owing to a combination of several factors such as gastrointestinal loss, renal loss, poor intake, and use of certain chemotherapeutic drugs. It is imperative that we identify the exact cause of hypomagnesemia to aid and guide treatment. We report a case of a 63-year-old white woman with hypomagnesemia who was undergoing treatment for metastatic colon cancer. The chemotherapy regimen was with FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) and bevacizumab. This was followed by maintenance therapy with Xeloda (capecitabine). Her hypomagnesium was attributed to her chemotherapy. During our workup, the renal fractional excretion of magnesium was found to be low excluding the cause as renal wasting. This patient's hypomagnesemia could very well be explained by gastrointestinal losses (diarrhea) from short bowel after colectomy, her chemotherapeutic agents and metformin, as well as poor oral intake from medications, or malignancy itself.

Elevated serum creatinine at baseline predicts poor outcome in patients receiving cardiac resynchronization therapy.

PubMed

Shalaby, Alaa; El-Saed, Aiman; Voigt, Andrew; Albany, Constantine; Saba, Samir

2008-05-01

Renal insufficiency is recognized as a predictor of mortality and poor outcome in heart failure patients. We sought to study the impact of baseline serum creatinine on subsequent outcome in cardiac resynchronization therapy (CRT) recipients. We retrospectively reviewed hospital records of all CRT recipients at Pittsburgh Veterans Affairs (VA) Healthcare System (2003-2005) and University of Pittsburgh Medical Center (2004). We recorded clinical characteristics at the time of implantation including demographics, New York Heart Association (NYHA) functional class, ejection fraction, QRS duration, cardiomyopathy etiology, medical history, medication use, and serum creatinine. Mortality alone and mortality combined with heart failure hospitalization were the study endpoints. Out of the 330 patients studied, a total of 66 (20.0%) patients died over a mean follow-up duration of 19.7 +/- 9.0 months (range 1-44). The cohort was studied by three creatinine tertiles (0.6-1.0, 1.1-1.3, 1.4-3.0 mg/dL). Both study endpoints were observed more frequently in patients in the highest creatinine tertile compared to others (28.7% vs 14.0%, P = 0.008 for death and 41.6% vs 21.5%, P = 0.001 for the combined endpoint). High creatinine remained an independent predictor of mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.06-3.39, P = 0.032) and the combined endpoint (HR 1.94, 95% CI 1.20-3.13, P = 0.007) in multivariate adjusted models. Studied as a continuous variable, increase in creatinine level by 0.1 mg/dL was associated with an 11% increase in mortality risk and a 7% increase in the combined endpoint. In an unselected cohort of CRT recipients, the baseline creatinine was found to predict worse survival and poor outcome over a modest follow-up duration.

Renal ultrasound provides low utility in evaluating cardiac surgery associated acute kidney injury.

PubMed

Young, Allen; Crawford, Todd; Pierre, Alejandro Suarez; Trent Magruder, J; Fraser, Charles; Conte, John; Whitman, Glenn; Sciortino, Christopher

2017-09-02

Renal ultrasonography is part of the algorithm in assessing acute kidney injury (AKI). The purpose of this study was to assess the clinical utility of renal US in postoperative cardiac patients who develop AKI. We conducted a retrospective study of 90 postoperative cardiac surgery patients at a single institution from 1/19/2010 to 3/19/2016 who underwent renal US for AKI. We reviewed provider documentation to determine whether renal US changed management. We defined change as: administration of crystalloid or colloid, addition of inotropic or vasopressor, or procedural interventions on the renal system. Mean age of study patients was 68 ± 13 years. 48/90 patients (53.3%) had pre-existing chronic kidney disease of varying severity. 48 patients (53.3%) had normal renal US with incidental findings and 31 patients (34.4%) had US evidence of medical kidney disease. 10 patients (11.1%) had limited US results due to poor visualization and 1 patient (1.1%) had mild right-sided hydronephrosis. No patients were found to have obstructive uropathy or renal artery stenosis. Clinical management was altered in only 4/90 patients (4.4%), which included 3 patients that received a fluid bolus and 1 patient that received a fluid bolus and inotropes. No vascular or urologic procedures resulted from US findings. Although renal ultrasound is often utilized in the work-up of AKI, our study shows that renal US provides little benefit in managing postoperative cardiac patients. This diagnostic modality should be scrutinized rather than viewed as a universal measure in the cardiac surgery population.

The therapeutic potential of HIF-2 antagonism in renal cell carcinoma

PubMed Central

2017-01-01

Hypoxia, the insufficient delivery of oxygen for the demand of a tissue, contributes to the development of an aggressive phenotype, resistance to radiation therapy and chemotherapy, and is predictive of a poor outcome in numerous tumor types. Adaptation to hypoxia is mediated by hypoxia-inducible factors (HIFs), including HIF-1α and HIF-2α, which regulate genes promoting angiogenesis, increased tumor growth or metastasis. In kidney cancer, HIF-2α is believed to be the most important driver for development and progression of clear cell renal cell carcinoma (ccRCC), highlighting the therapeutic potential of HIF-2 antagonists in this disease. Recent studies show that HIF-2α can be targeted by selective, and orally active new class of inhibitors. In conjunction with the restricted expression of HIF-2α in normal adult physiology, these studies suggest that such therapeutic approach might be favorable for patients with lower toxicity than current anti-angiogenic drugs like sunitinib. However, the differential sensitivity to these HIF-2α antagonists along with the potential mechanisms of resistance reported in these studies advocate for the identification of biomarkers to determine which patients are more likely to benefit from these therapies as well as paving the way for second generation inhibitors or complementary inhibitory approaches. PMID:28217462

Cutaneous and renal glomerular vasculopathy as a cause of acute kidney injury in dogs in the UK

PubMed Central

Hawkins, I.; Robin, C.; Newton, R. J.; Jepson, R.; Stanzani, G.; McMahon, L. A.; Pesavento, P.; Carr, T.; Cogan, T.; Couto, C. G.; Cianciolo, R.; Walker, D. J.

2015-01-01

To describe the signalment, clinicopathological findings and outcome in dogs presenting with acute kidney injury (AKI) and skin lesions between November 2012 and March 2014, in whom cutaneous and renal glomerular vasculopathy (CRGV) was suspected and renal thrombotic microangiopathy (TMA) was histopathologically confirmed. The medical records of dogs with skin lesions and AKI, with histopathologically confirmed renal TMA, were retrospectively reviewed. Thirty dogs from across the UK were identified with clinicopathological findings compatible with CRGV. These findings included the following: skin lesions, predominantly affecting the distal extremities; AKI; and variably, anaemia, thrombocytopaenia and hyperbilirubinaemia. Known causes of AKI were excluded. The major renal histopathogical finding was TMA. All thirty dogs died or were euthanised. Shiga toxin was not identified in the kidneys of affected dogs. Escherichia coli genes encoding shiga toxin were not identified in faeces from affected dogs. CRGV has previously been reported in greyhounds in the USA, a greyhound in the UK, without renal involvement, and a Great Dane in Germany. This is the first report of a series of non-greyhound dogs with CRGV and AKI in the UK. CRGV is a disease of unknown aetiology carrying a poor prognosis when azotaemia develops. PMID:25802439

Renal Safety Pharmacology in Drug Discovery and Development.

PubMed

Benjamin, Amanda; Nogueira da Costa, Andre; Delaunois, Annie; Rosseels, Marie-Luce; Valentin, Jean-Pierre

2015-01-01

The kidney is a complex excretory organ playing a crucial role in various physiological processes such as fluid and electrolyte balance, control of blood pressure, removal of waste products, and drug disposition. Drug-induced kidney injury (DIKI) remains a significant cause of candidate drug attrition during drug development. However, the incidence of renal toxicities in preclinical studies is low, and the mechanisms by which drugs induce kidney injury are still poorly understood. Although some in vitro investigational tools have been developed, the in vivo assessment of renal function remains the most widely used methodology to identify DIKI. Stand-alone safety pharmacology studies usually include assessment of glomerular and hemodynamic function, coupled with urine and plasma analyses. However, as renal function is not part of the ICH S7A core battery, such studies are not routinely conducted by pharmaceutical companies. The most common approach consists in integrating renal/urinary measurements in repeat-dose toxicity studies. In addition to the standard analyses and histopathological examination of kidneys, novel promising urinary biomarkers have emerged over the last decade, offering greater sensitivity and specificity than traditional renal parameters. Seven of these biomarkers have been qualified by regulatory agencies for use in rat toxicity studies.

Serum creatinine and bilirubin predict renal failure and mortality in patients with spontaneous bacterial peritonitis: a retrospective study.

PubMed

Terg, Rubén; Gadano, Adrian; Cartier, Mariano; Casciato, Paola; Lucero, Romina; Muñoz, Alberto; Romero, Gustavo; Levi, Diana; Terg, Gonzalo; Miguez, Carlos; Abecasis, Raquel

2009-03-01

Patients with spontaneous bacterial peritonitis (SBP) are at a high risk for renal failure and death despite successful treatment of infection. Intravenous (IV) albumin administration combined with antibiotic treatment has been shown to significantly decrease these risks. Clinical evidence is lacking on which patients are appropriate candidates for albumin treatment. To retrospectively analyse the usefulness of serum creatinine and bilirubin levels in predicting renal failure and mortality of patients hospitalized for SBP. Between March 1995 and September 1998, 127 cirrhotic patients with SBP who had not received plasma expansion were evaluated. Eighty-one patients (64%) were classified as having a high risk for renal failure and mortality (serum bilirubin >4 mg/dl or serum creatinine >1 mg/dl) and 46 (36%) as having a low risk. At admission, 36.3% of all patients presented renal failure. Mortality during their hospitalization was 23% among those with a high risk and 6.5% among those with a low risk (P=0.01). Renal failure occurred in 23% of the high-risk patients, compared with 2.6% of the low-risk patients (P=0.006). The presence of hyponatraemia was significantly associated with higher mortality and renal failure in the high-risk group. Our retrospective review of patients with SBP suggests that serum bilirubin levels >4 mg and serum creatinine levels >1 mg/dl at the time of diagnosis represent significant risk factors for the clinical outcomes of patients with SBP. Patients without these risk factors may have a very low likelihood of death or renal failure.

Changes in renal function after implantation of continuous-flow left ventricular assist devices.

PubMed

Hasin, Tal; Topilsky, Yan; Schirger, John A; Li, Zhuo; Zhao, Yanjun; Boilson, Barry A; Clavell, Alfredo L; Rodeheffer, Richard J; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Joyce, Lyle; Daly, Richard; Park, Soon J; Kushwaha, Sudhir S

2012-01-03

The aim of this study was to determine renal outcomes after left ventricular assist device (LVAD) implantation. Renal dysfunction before LVAD placement is frequent, and it is unclear whether it is due to primary renal disease or to poor perfusion. A retrospective single-center analysis was conducted in 83 consecutive patients implanted with HeartMate II continuous-flow LVADs (Thoratec Corp., Pleasanton, California). Calculated glomerular filtration rate (GFR) was assessed on admission and 1, 3, and 6 months after implantation. To define predictors for improvement in GFR, clinical variables were examined in patients with decreased renal function (GFR <60 ml/min/1.73 m(2)) before LVAD, surviving and dialysis-free at 1 month (n = 44). GFR significantly increased from admission (53.2 ± 21.4 ml/min/1.73 m(2)) to 1 month after LVAD implantation (87.4 ± 27.9 ml/min/1.73 m(2)) (p < 0.0001). Subsequently, at 3 and 6 months, GFR remained significantly (p < 0.0001) above pre-LVAD values. Of the 51 patients with GFRs <60 ml/min/1.73 m(2) before LVAD surviving at 1 month, 34 (67%) improved to GFRs >60 ml/min/1.73 m(2). Univariate pre-operative predictors for improvement in renal function at 1 month included younger age (p = 0.049), GFR improvement with optimal medical therapy (p < 0.001), intra-aortic balloon pump use (p = 0.004), kidney length above 10 cm (p = 0.023), no treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (p = 0.029), higher bilirubin (p = 0.002), higher Lietz-Miller score (p = 0.019), and atrial fibrillation (p = 0.007). Multivariate analysis indicated pre-operative improved GFR (slope = 0.5 U per unit improved; 95% confidence interval: 0.2 to 0.8; p = 0.003), atrial fibrillation (slope = 27; 95% confidence interval: 8 to 46; p = 0.006), and intra-aortic balloon pump use (slope = 14; 95% confidence interval: 2 to 26; p = 0.02) as independent predictors. In most patients with end-stage heart failure considered for LVAD implantation, renal dysfunction is reversible and likely related to poor renal perfusion. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Amelioration of renal ischaemia–reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells

PubMed Central

Rogers, NM; Stephenson, MD; Kitching, AR; Horowitz, JD; Coates, PTH

2012-01-01

BACKGROUND AND PURPOSE Renal ischaemia–reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. EXPERIMENTAL APPROACH We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. KEY RESULTS Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. CONCLUSIONS AND IMPLICATIONS Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. PMID:21745189

NFκB-mediated cyclin D1 expression by microRNA-21 influences renal cancer cell proliferation.

PubMed

Bera, Amit; Ghosh-Choudhury, Nandini; Dey, Nirmalya; Das, Falguni; Kasinath, Balakuntalam S; Abboud, Hanna E; Choudhury, Goutam Ghosh

2013-12-01

MicroRNAs regulate post-transcriptomic landscape in many tumors including renal cell carcinoma. We have recently shown significantly increased expression of miR-21 in renal tumors and that this miRNA contributes to the proliferation of renal cancer cells in culture. However, the mechanism by which miR-21 regulates renal cancer cell proliferation is poorly understood. Addiction to constitutive NFκB activity is hallmark of many cancers including renal cancer. Using miR-21 Sponge in renal cancer cells to block endogenous function of miR-21, we show inhibition of phosphorylation of p65 subunit of NFκB, IKKβ and IκB, which results in attenuation of NFκB transcriptional activity. Subtle reduction in the tumor suppressor PTEN has been linked to various malignancies. We showed previously that miR-21 targeted PTEN in renal cancer cells. Inhibition of PTEN by siRNAs restored miR-21 Sponge-induced suppression of phosphorylation of p65, IKKβ, IκB and NFκB transcriptional activity along with reversal of miR-21 Sponge-reduced phosphorylation of Akt. Expression of constitutively active Akt protected against miR-21 Sponge- and PTEN-mediated decrease in p65/IKKβ/IκB phosphorylation and NFκB transcriptional activity. Furthermore, IKKβ and p65 were required for miR-21-induced renal cancer cell proliferation. Interestingly, miR-21 controlled the expression of cyclin D1 through NFκB-dependent transcription. Finally, we demonstrate that miR-21-regulated renal cancer cell proliferation is mediated by cyclin D1 and CDK4. Together, our results establish a molecular order of a phosphatase-kinase couple involving PTEN/Akt/IKKβ and NFκB-dependent cyclin D1 expression for renal carcinoma cell proliferation by increased miR-21 levels. © 2013.

NFκB-mediated cyclin D1 expression by microRNA-21 influences renal cancer cell proliferation

PubMed Central

Bera, Amit; Ghosh-Choudhury, Nandini; Dey, Nirmalya; Das, Falguni; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh

2013-01-01

MicroRNAs regulate post-transcriptomic landscape in many tumors including renal cell carcinoma. We have recently shown significantly increased expression of miR-21 in renal tumors and that this miRNA contributes to the proliferation of renal cancer cells in culture. However, the mechanism by which miR-21 regulates renal cancer cells proliferation is poorly understood. Addiction to constitutive NFκB activity is hallmark of many cancers including renal cancer. Using miR-21 Sponge in renal cancer cells to block endogenous function of miR-21, we show inhibition of phosphorylation of p65 subunit of NFκB, IKKβ and IκB, which results in attenuation of NFκB transcriptional activity. Subtle reduction in the tumor suppressor PTEN has been linked to various malignancies. We showed previously that miR-21 targeted PTEN in renal cancer cells. Inhibition of PTEN by siRNAs restored miR-21 Sponge-induced suppression of phosphorylation of p65, IKKβ, IκB and NFκB transcriptional activity along with reversal of miR-21 Sponge-reduced phosphorylation of Akt. Expression of constitutively active Akt protected against miR-21 Sponge- and PTEN-mediated decrease in p65/IKKβ/IκB phosphorylation and NFκB transcriptional activity. Furthermore, IKKβ and p65 were required for miR-21-induced renal cancer cell proliferation. Interestingly, miR-21 controlled the expression of cyclin D1 through NFκB-dependent transcription. Finally, we demonstrate that miR-21-regulated renal cancer cell proliferation is mediated by cyclin D1 and CDK4. Together, our results establish a molecular order of a phosphatase-kinase couple involving PTEN/Akt/IKKβ and NFκB-dependent cyclin D1 expression for renal carcinoma cell proliferation by increased miR-21 levels. PMID:23981302

Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

PubMed

Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

2012-05-01

Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers.

PubMed

Schievink, Bauke; de Zeeuw, Dick; Parving, Hans-Henrik; Rossing, Peter; Lambers Heerspink, Hiddo Jan

2015-10-01

Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation in short term effects may have important implications for the prediction of individual long term renal outcomes. Our aim was to assess intra-individual variability in multiple parameters in response to ARBs in type 2 diabetes. Changes in systolic blood pressure (SBP), albuminuria, potassium, haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by the relative integrative discrimination index (RIDI). SBP response showed high variability (mean -5.7 mmHg, 5(th) to 95(th) percentile -36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses to losartan in multiple parameters within individuals. Using individual responses in all risk markers significantly improved renal risk prediction (RIDI 30.4%, P < 0.01) compared with using only SBP changes. Results were successfully replicated in two independent trials with irbesartan, IDNT and IRMA-2. In this post hoc analysis we showed that ARBs have multiple off-target effects which vary between and within individuals. Combining all ARB-induced responses beyond SBP provides a more accurate prediction of who will benefit from ARB therapy. Prospective trials are required to validate these findings. © 2015 The British Pharmacological Society.

Pretransplantation Cystatin C, but not Creatinine, Predicts 30-day Cardiovascular Events and Mortality in Liver Transplant Recipients With Normal Serum Creatinine Levels.

PubMed

Kwon, H-M; Moon, Y-J; Jung, K-W; Jun, I-G; Song, J-G; Hwang, G-S

2018-05-01

The connection between renal dysfunction and cardiovascular dysfunction has been consistently shown. In patients with liver cirrhosis, renal dysfunction shows a tight correlation with prognosis after liver transplantation (LT); therefore, precise renal assessment is mandatory. Cystatin C, a sensitive biomarker for assessing renal function, has shown superiority in detecting mild renal dysfunction compared to classical biomarker creatinine. In this study, we aimed to compare cystatin C and creatinine in predicting 30-day major cardiovascular events (MACE) and all-cause mortality in LT recipients with normal serum creatinine levels. Between May 2010 and October 2015, 1181 LT recipients (mean Model for End-stage Liver Disease score 12.1) with pretransplantation creatinine level ≤1.4 mg/dL were divided into tertiles according to each renal biomarker. The 30-day MACE was a composite of troponin I >0.2 ng/mL, arrhythmia, congestive heart failure, death, and cerebrovascular events. The highest tertile of cystatin C (≥0.95 mg/L) was associated with a higher risk for a 30-day MACE event (odds ratio: 1.62; 95% confidence interval: 1.07 to 2.48) and higher risk of death (hazard ratio: 1.96; 95% confidence interval: 1.04 to 3.67) than the lowest tertile (<0.74 mg/L) after multivariate adjustments. However, the highest tertile of creatinine level showed neither increasing MACE event rate nor worse survival rate compared with the lowest tertile (both insignificant after multivariate adjustment). Pretransplantation cystatin C is superior in risk prediction of MACE and all-cause mortality in LT recipients with normal creatinine, compared to creatinine. It would assist further risk stratification which may not be detected with creatinine. Copyright © 2018 Elsevier Inc. All rights reserved.

The Utility of the Remnant Kidney Volume/Body Surface Area Ratio and Tumor Diameter as Predictors of Postoperative Degree of Renal Functional Decline in Patients With Renal Cell Carcinoma Treated by Radical Nephrectomy.

PubMed

Sejima, Takehiro; Yamaguchi, Noriya; Iwamoto, Hideto; Masago, Toshihiko; Morizane, Shuichi; Ono, Koji; Koumi, Tsutomu; Honda, Masashi; Takenaka, Atsushi

2015-08-01

To characterize the preoperative factors affecting renal cell carcinoma patients as predictive of post-radical nephrectomy (RN) mild (M-decline) or severe (S-decline) renal functional decline and to elucidate the histopathologic features of the resected normal kidney cortex, as well as the occurrence of cardiovascular disease (CVD) in both M-decline and S-decline patients. M-decline and S-decline were categorized as a percentage of postoperative estimated glomerular filtration rate decline of <20 and of >40, respectively. The preoperative factors analyzed were patient demographics, comorbidities, and radiographic findings, including remnant kidney status and tumor size. The factors based on postoperative information analyzed were tumor and normal cortex pathology and CVD events. In 175 patient cohort, 21 and 32 cases were categorized as M-decline and S-decline, respectively. Absence of comorbidities, larger remnant kidney volume (RKV)/body surface area (BSA) ratio, and larger tumor diameter were significantly predictive of M-decline, whereas smaller tumor diameter was significantly predictive of S-decline. The global glomerulosclerosis extent in nephrectomized normal cortex of S-decline cases was significantly higher than in other types of cases. No CVD event was observed in M-decline cases. This is the first report to identify the RKV/BSA ratio as a promising predictor of post-RN degree of renal functional decline. Post-RN prevention of life-threatening outcomes according to preoperative and postoperative information, including the degree of post-RN renal functional decline and histopathology of the nephrectomized normal cortex, should be considerable in future urological tasks. Copyright © 2015 Elsevier Inc. All rights reserved.

The Presence of Vascular Mimicry Predicts High Risk of Clear Cell Renal Cell Carcinoma after Radical Nephrectomy.

PubMed

Zhou, Lin; Chang, Yuan; Xu, Le; Liu, Zheng; Fu, Qiang; Yang, Yuanfeng; Lin, Zongming; Xu, Jiejie

2016-08-01

Vascular mimicry is a type of tumor cell plasticity. The aim of this study was to determine the prognostic value of vascular mimicry in patients with clear cell renal cell carcinoma. We performed a retrospective cohort study in 387 patients with clear cell renal cell carcinoma who underwent radical nephrectomy at Zhongshan Hospital, Fudan University between 2008 and 2009. Pathological features, baseline patient characteristics and followup data were recorded. Vascular mimicry in clear cell renal cell carcinoma tissue was identified by CD31-periodic acid-Schiff double staining. Univariate and multivariate Cox regression models were used to analyze the impact of prognostic factors on recurrence-free survival. The concordance index and the Akaike information criterion were used to assess the predictive accuracy and sufficiency of different models. Positive vascular mimicry staining occurred in 25 of 387 clear cell renal cell carcinoma cases (6.5%) and it was associated with an increased risk of recurrence (log-rank p <0.001). Incorporating vascular mimicry into pT stage, Fuhrman grade and Leibovich score helped refine individual risk stratification. Moreover, vascular mimicry was identified as an independent prognostic factor (p = 0.001). It was entered into a nomogram together with pT stage, Fuhrman grade, tumor size and necrosis. In the primary cohort the Harrell concordance index for the established nomogram to predict recurrence-free survival was slightly higher than that of the Leibovich model (0.850 vs. 0.823), which failed to reach statistical significance (p = 0.158). Vascular mimicry could be a potential prognosticator for recurrence-free survival in patients with clear cell renal cell carcinoma after radical nephrectomy. Further external validation and functional analysis should be pursued to assess its potential prognostic and therapeutic values for clear cell renal cell carcinoma. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Rapid improvement of renal function in patients with acute pulmonary embolism indicates favorable short term prognosis.

PubMed

Kostrubiec, Maciej; Łabyk, Andrzej; Pedowska-Włoszek, Justyna; Pacho, Szymon; Dzikowska-Diduch, Olga; Dul, Przemysław; Ciurzyński, Michał; Bienias, Piotr; Pruszczyk, Piotr

2012-09-01

Various clinical and biochemical parameters predict the prognosis of patients with acute pulmonary embolism(APE). Treatment of APE can improve a patient's hemodynamic status, restoring adequate peripheral organ perfusion. Therefore, we hypothesized that improvement of renal function can predict short term prognosis of APE patients. We evaluated 232 consecutive patients (94 men,aged 67 ± 18 years) with APE proven by spiral computer tomography. Blood samples were collected for creatinine assays on admission and 72 hours later, the glomerular filtration rate(eGFR) was estimated using the MDRD formula. During the first 72 hours, 6 subjects died, while during the first 30 days 24(10%) subjects died (APE mortality 8%). On admission eGFR<60 ml/min was present in 113 patients(49%) and after 72 hours in 85 patients(38%). In 26 patients(11%) eGFR on admission was <60 ml/min and renal function did not improve during subsequent 72 hours. In this group the 30-day all-cause and APE-related mortality rates were 27% and 23%, respectively, while serious adverse events occurred in 38% of them. 206 patients with eGFR>60 ml/min showed a more favorable prognosis (8% 30-day all-cause mortality) than subjects with eGFR<60 ml/min and a stable eGFR during the first 72 hours (27% mortality rate, p<0.003). Persistent renal dysfunction predicted all-cause and PE-related 30-day mortality (hazard risk 2.53(CI 95%:0.96-6.68),p=0.06 and 3.04(CI 95%:1.28-7.26),p=0.01, respectively). Approximately 50% of patients with APE have at least a moderately impaired renal function on admission. Renal function improves within 72 hours in patients with a good prognosis, while "persistent" renal dysfunction indicates an increased mortality. Copyright © 2012 Elsevier Ltd. All rights reserved.

Odour perception in chronic renal disease.

PubMed

Griep, M I; Van der Niepen, P; Sennesael, J J; Mets, T F; Massart, D L; Verbeelen, D L

1997-10-01

The sense of smell plays an important role in the quality of life. Many studies have shown a declining odour perception in the elderly, as well as in subjects in poor health or nutritional state. Considering the high prevalence of poor nutritional state in renal disease and the importance of odour perception in nutrition and health, the relationship between renal function, nutritional state, and odour perception is explored in this study. A total of 101 patients with chronic renal failure participated in the study. Thirty-eight haemodialysis patients (mean age = 64.3 years) were evaluated both before and after dialysis. Sixteen patients on peritoneal dialysis treatment (mean age = 64.0 years), 28 transplanted patients (mean age = 53.5 years, mean creatinine clearance = 64.0 ml/min) and 19 patients with varying degrees of renal insufficiency were also included (mean age = 63.7 years, mean creatinine clearance = 29.5 ml/min). Patients with cognitive deficits or upper respiratory airway diseases were excluded. A validated objective procedure was used to measure odour perception, by determining the detection threshold for isoamyl acetate (banana odour) as the lowest detectable odour concentration. Healthy control persons had significantly lower odour thresholds compared to patients on peritoneal (P = 0.001) and haemodialysis (P = 0.002). No significant difference was observed in odour perception between patients on peritoneal and haemodialysis (P = 0.779) and for patients on haemodialysis before and after a dialysis session. Transplanted patients had significantly better odour perception compared to matched patients on dialysis (P < 0.001). Odour perception of transplanted patients and matched healthy control persons was similar (P = 0.81). In patients with varying degrees of renal insufficiency, including healthy controls and transplanted patients, a significant positive correlation was found between odour perception and creatinine clearance (P = 0.02). A significant negative correlation was found between odour perception and serum concentration of urea (P < 0.001), serum phosphorus (P = 0.022) and protein catabolic rate (P < 0.05). Other parameters measuring nutritional status (albumin, BMI) were not correlated with odour perception. Our results show that the ability to smell is severely impaired in patients with chronic renal failure and is related to the degree of renal impairment and the degree of accumulation of uraemic toxins. After renal transplantation, patients have a normal odour perception, indicating the capacity of the olfactory system to recover once the concentration of uraemic toxins remains below a critical threshold. Acute removal of uraemic toxins by dialysis does not correct olfactory disturbances, suggesting a long lasting effect of uraemia on olfactory function.

NEK8 Links the ATR-regulated Replication Stress Response and S-phase CDK Activity to Renal Ciliopathies

PubMed Central

Choi, Hyo Jei Claudia; Lin, Jia-Ren; Vannier, Jean-Baptiste; Slaats, Gisela G.; Kile, Andrew C.; Paulsen, Renee D.; Manning, Danielle K.; Beier, David R.; Giles, Rachel H.; Boulton, Simon J.; Cimprich, Karlene A.

2013-01-01

Summary Renal ciliopathies are a leading cause of kidney failure, but their exact etiology is poorly understood. NEK8/NPHP9 is a ciliary kinase associated with two renal ciliopathies in humans and mice, nephronophthisis (NPHP) and polycystic kidney disease. Here, we identify NEK8 as a key effector of the ATR-mediated replication stress response. Cells lacking NEK8 form spontaneous DNA double-strand breaks (DSBs) which further accumulate when replication forks stall, and they exhibit reduced fork rates, unscheduled origin firing, and increased replication fork collapse. NEK8 suppresses DSB formation by limiting cyclin A-associated CDK activity. Strikingly, a mutation in NEK8 that is associated with renal ciliopathies affects its genome maintenance functions. Moreover, kidneys of NEK8 mutant mice accumulate DNA damage, and loss of NEK8 or replication stress similarly disrupts renal cell architecture in a 3D-culture system. Thus, NEK8 is a critical component of the DNA damage response that links replication stress with cystic kidney disorders. PMID:23973373

Changes in leucocyte migration after renal transplantation

PubMed Central

Smith, M. G. M.; Eddleston, A. L. W. F.; Dominguez, J. A.; Evans, D. B.; Bewick, M.; Williams, Roger

1969-01-01

The leucocyte migration test, an in-vitro measure of cellular immunity, has been used to follow the changes in cell-mediated hypersensitivity to kidney and histocompatibility antigens in three patients after renal transplantation. Inhibition of leucocyte migration, indicating strong sensitization to the antigens used, occurred in each patient, starting five to seven days after transplantation. Satisfactory renal function had not been established in any of the patients at this time. In one case inhibition of leucocyte migration persisted almost continuously until the 24th day and was associated with poor renal function proved histologically to be due to rejection. Treatment with increased dosage of prednisone was associated with a rapid reversion to normal of the migration index and improvement in renal function. Later, inhibition of migration occurred again, and shortly afterwards the graft ceased to function. In the other two cases the migration index became normal without alteration in immunosuppressive therapy and a satisfactory diuresis followed. It is suggested that this simple test should prove useful in the specific diagnosis of rejection and in control of immunosuppressive therapy. ImagesFig. 3Fig. 4 PMID:4899455

Functional renal imaging: new trends in radiology and nuclear medicine.

PubMed

Durand, Emmanuel; Chaumet-Riffaud, Philippe; Grenier, Nicolas

2011-01-01

The objective of this work is to compare the characteristics of various techniques for functional renal imaging, with a focus on nuclear medicine and magnetic resonance imaging. Even with low spatial resolution and rather poor signal-to-noise ratio, classical nuclear medicine has the advantage of linearity and good sensitivity. It remains the gold standard technique for renal relative functional assessment. Technetium-99m ((99m)Tc)-labeled diethylenetriamine penta-acetate remains the reference glomerular tracer. Tubular tracers have been improved: (123)I- or (131)I-hippuran, (99m)Tc-MAG3 and, recently, (99m)Tc-nitrilotriacetic acid. However, advancement in molecular imaging has not produced a groundbreaking tracer. Renal magnetic resonance imaging with classical gadolinated tracers probably has potential in this domain but has a lack of linearity and, therefore, its value still needs evaluation. Moreover, the advent of nephrogenic systemic fibrosis has delayed its expansion. Other developments, such as diffusion or blood oxygen level-dependent imaging, may have a role in the future. The other modalities have a limited role in clinical practice for functional renal imaging. Copyright © 2011 Elsevier Inc. All rights reserved.

Mitochondrial-targeted antioxidants represent a promising approach for prevention of cisplatin-induced nephropathy

PubMed Central

Mukhopadhyay, Partha; Horváth, Béla; Zsengellér, Zsuzsanna; Zielonka, Jacek; Tanchian, Galin; Holovac, Eileen; Kechrid, Malek; Patel, Vivek; Stillman, Isaac E.; Parikh, Samir M.; Joseph, Joy; Kalyanaraman, Balaraman; Pacher, Pál

2011-01-01

Cisplatin is a widely used anti-neoplastic agent; however, its major limitation is the development of dose-dependent nephrotoxicity whose precise mechanisms are poorly understood. Here we show that mitochondrial dysfunction is not only a feature of cisplatin nephrotoxicity, but that targeted delivery of superoxide dismutase mimetics to mitochondria largely prevents the renal effects of cisplatin. Cisplatin induced renal oxidative stress, deterioration of mitochondrial structure and function, an intense inflammatory response, histopathological injury, and renal dysfunction. A single systemic dose of mitochondrially-targeted antioxidants, MitoQ or Mito-CP, dose-dependently prevented cisplatin-induced renal dysfunction. Mito-CP also prevented mitochondrial injury and dysfunction, renal inflammation, and tubular injury and apoptosis. Despite being broadly renoprotective against cisplatin, Mito-CP did not diminish cisplatin’s anti-neoplastic effect in a human bladder cancer cell line. Our results highlight the central role of mitochondrially generated oxidants in the pathogenesis of cisplatin nephrotoxicity. Since similar compounds appear to be safe in humans, mitochondrially-targeted antioxidants may represent a novel therapeutic approach against cisplatin nephrotoxicity. PMID:22120494

Cerebro-renal interactions: impact of uremic toxins on cognitive function.

PubMed

Watanabe, Kimio; Watanabe, Tsuyoshi; Nakayama, Masaaki

2014-09-01

Cognitive impairment (CI) associated with chronic kidney disease (CKD) has received attention as an important problem in recent years. Causes of CI with CKD are multifactorial, and include cerebrovascular disease, renal anemia, secondary hyperparathyroidism, dialysis disequilibrium, and uremic toxins (UTs). Among these causes, little is known about the role of UTs. We therefore selected 21 uremic compounds, and summarized reports of cerebro-renal interactions associated with UTs. Among the compounds, uric acid, indoxyl sulfate, p-cresyl sulfate, interleukin 1-β, interleukin 6, TNF-α, and PTH were most likely to affect the cerebro-renal interaction dysfunction; however, sufficient data have not been obtained for other UTs. Notably, most of the data were not obtained under uremic conditions; therefore, the impact and mechanism of each UT on cognition and central nervous system in uremic state remains unknown. At present, impacts and mechanisms of UT effects on cognition are poorly understood. Clarifying the mechanisms and establishing novel therapeutic strategies for cerebro-renal interaction dysfunction is expected to be subject of future research. Copyright © 2014 Elsevier Inc. All rights reserved.

Basigin/CD147 promotes renal fibrosis after unilateral ureteral obstruction.

PubMed

Kato, Noritoshi; Kosugi, Tomoki; Sato, Waichi; Ishimoto, Takuji; Kojima, Hiroshi; Sato, Yuka; Sakamoto, Kazuma; Maruyama, Shoichi; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji

2011-02-01

Regardless of their primary causes, progressive renal fibrosis and tubular atrophy are the main predictors of progression to end-stage renal disease. Basigin/CD147 is a multifunctional molecule-it induces matrix metalloproteinases and hyaluronan, for example-and has been implicated in organ fibrosis. However, the relationship between basigin and organ fibrosis has been poorly studied. We investigated basigin's role in renal fibrosis using a unilateral ureteral obstruction model. Basigin-deficient mice (Bsg(-/-)) demonstrated significantly less fibrosis after surgery than Bsg(+/+) mice. Fewer macrophages had infiltrated in Bsg(-/-) kidneys. Consistent with these in vivo data, primary cultured tubular epithelial cells from Bsg(-/-) mice produced less matrix metalloproteinase and exhibited less motility on stimulation with transforming growth factor β. Furthermore, Bsg(-/-) embryonic fibro blasts produced less hyaluronan and α-smooth muscle actin after transforming growth factor β stimulation. Together, these results demonstrate for the first time that basigin is a key regulator of renal fibrosis. Basigin could be a candidate target molecule for the prevention of organ fibrosis. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Renal Parenchyma to Hydronephrosis Area Ratio (PHAR) as a Predictor of Future Surgical Intervention for Infants With High-grade Prenatal Hydronephrosis.

PubMed

Rickard, Mandy; Lorenzo, Armando J; Braga, Luis H

2017-03-01

To explore the potential value of an objective assessment, renal parenchyma to hydronephrosis area ratio (PHAR), as an early predictor of surgery. Initial sagittal renal ultrasound (US) images of patients prospectively entered into a prenatal hydronephrosis database from January 2008 to January 2016 with baseline Society for Fetal Urology (SFU) grades III and IV prenatal hydronephrosis, without vesicoureteral reflux, were evaluated using the National Institutes of Health-sponsored image processing software. PHAR, anteroposterior diameter, SFU grade, and urinary tract dilation risk categories were contrasted with nuclear scan data (differential renal function and drainage time [t 1/2 ]) and analyzed for predictive value in determining the decision to proceed with surgery by drawing receiver operating characteristic curves. Out of 196 infants (162 male; 138 left sided hydronephrosis), 58 (30%) underwent surgery to address obstruction. Surgical patients compared with those managed conservatively had longer t 1/2 (60 vs 18 min; P < .01) and lower differential renal function (46 vs 50%; P = .01). Of the initial US parameters, PHAR (area under the curve = 0.816; P < .001) had a better predictive performance than anteroposterior diameter, SFU grade, or urinary tract dilation classification. PHAR values correlated with subsequent parameters obtained on nuclear scan. PHAR is a promising parameter that can be estimated on presentation US to help predict future need for surgery in newborns with high-grade hydronephrosis. Copyright © 2016 Elsevier Inc. All rights reserved.

The natural history of renal function after surgical management of renal cell carcinoma: Results from the Canadian Kidney Cancer Information System.

PubMed

Mason, Ross; Kapoor, Anil; Liu, Zhihui; Saarela, Olli; Tanguay, Simon; Jewett, Michael; Finelli, Antonio; Lacombe, Louis; Kawakami, Jun; Moore, Ronald; Morash, Christopher; Black, Peter; Rendon, Ricardo A

2016-11-01

Patients who undergo surgical management of renal cell carcinoma (RCC) are at risk for chronic kidney disease and its sequelae. This study describes the natural history of renal function after radical and partial nephrectomy and explores factors associated with postoperative decline in renal function. This is a multi-institutional cohort study of patients in the Canadian Kidney Cancer Information System who underwent partial or radical nephrectomy for RCC. Estimated glomerular filtration rate (eGFR) and stage of chronic kidney disease were determined preoperatively and at 3, 12, and 24 months postoperatively. Linear regression was used to determine the association between postoperative eGFR and type of surgery (radical vs. partial), duration of ischemia, ischemia type (warm vs. cold), and tumor size. With a median follow-up of 26 months, 1,379 patients were identified from the Canadian Kidney Cancer Information System database including 665 and 714 who underwent partial and radical nephrectomy, respectively. Patients undergoing radical nephrectomy had a lower eGFR (mean = 19ml/min/1.73m 2 lower) at 3, 12, and 24 months postoperatively (P<0.001). Decline in renal function occurred early and remained stable throughout follow-up. A lower preoperative eGFR and increasing age were also associated with a lower postoperative eGFR (P<0.01). Ischemia type and duration were not predictive of postoperative decline in eGFR (P>0.05). Severe renal failure (eGFR<30ml/min/1.73m 2 ) developed postoperatively in 12.5% and 4.1% of radical and partial nephrectomy patients, respectively (P<0.001). After the initial postoperative decline, renal function remains stable in patients undergoing surgery for RCC. Patients undergoing radical nephrectomy have a greater long-term reduction in renal function compared with those undergoing partial nephrectomy. Ischemia duration and type are not predictive of postoperative renal function when adhering to generally short ischemia durations. Copyright © 2016 Elsevier Inc. All rights reserved.

Neutrophil Gelatinase-Associated Lipocalin: Utility In Urologic Conditions

PubMed Central

Forster, Catherine S.; Devarajan, Prasad

2016-01-01

Neutrophil gelatinase-associated lipocalin (NGAL) is best known as a non-invasive early marker of acute kidney injury (AKI). However, recent reports in the literature have described additional utility of both plasma NGAL (pNGAL) and urine NGAL (uNGAL) in various pathologic conditions within the pediatric urinary tract, including urinary tract infection (UTI), vesicoureteral reflux (VUR), renal scarring, and obstructive uropathy. These two forms of NGAL have different applications related to their mechanisms of upregulation: pNGAL can serve as a marker of systemic inflammatory conditions, whereas uNGAL is specific for insults to the renal epithelium. Therefore, pNGAL has good predictive accuracy in systemic inflammation associated with pyelonephritis and renal damage, while uNGAL is effective in identifying infection with the genitourinary environment as well as subclinical renal damage as a result of scarring or obstruction. Continued work should focus on the effect of trending NGAL values in patients with pyelonephritis, VUR, and hydronephrosis, to determine if longitudinal NGAL patterns have value in predicting adverse outcomes. PMID:27785626

Surrogate markers of subtle renal injury in patients with visceral leishmaniasis.

PubMed

Elnojomi, N A A; Musa, A M; Younis, B M; Elfaki, M E E; El-Hassan, A M; Khalil, E A G

2010-09-01

Sudanese visceral leishmaniasis (VL) is a disease of children that is characterized by fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, and renal injury. Microalbuminuria (MA) and urinary retinol binding protein (urRBP) are useful markers for glomerular and tubular dysfunctions, respectively. We report the prevalence of subtle renal injury in 88 parasitologically confirmed VL patients in a cross-sectional and hospital-based study. Blood and urine were collected before treatment for hematological, biochemical profiles in addition to MA and urRBP measurement using competitive solid phase, sandwich enzyme-linked immune sorbent assay (ELISA), and immunoturbidometry. All the patients had normal serum urea and creatinine levels and no detectable urRBP. However, 40% of the patients had MA detected by ELISA, and 42% were reactive with turbidometry. The sensitivity, specificity, positive and negative predictive values for MA turbidometric technique were calculated as 100%; 96%; 95% and 100%, respectively. In conclusion; subtle renal injury in VL is mainly glomerular. Turbidometry for MA measurement is a simple, inexpensive, sensitive, and specific technique with high predictive values.

The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease.

PubMed

Cornec-Le Gall, Emilie; Audrézet, Marie-Pierre; Rousseau, Annick; Hourmant, Maryvonne; Renaudineau, Eric; Charasse, Christophe; Morin, Marie-Pascale; Moal, Marie-Christine; Dantal, Jacques; Wehbe, Bassem; Perrichot, Régine; Frouget, Thierry; Vigneau, Cécile; Potier, Jérôme; Jousset, Philippe; Guillodo, Marie-Paule; Siohan, Pascale; Terki, Nazim; Sawadogo, Théophile; Legrand, Didier; Menoyo-Calonge, Victorio; Benarbia, Seddik; Besnier, Dominique; Longuet, Hélène; Férec, Claude; Le Meur, Yannick

2016-03-01

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0-3 points), intermediate risk (4-6 points), and high risk (7-9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD. Copyright © 2016 by the American Society of Nephrology.

Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure

PubMed Central

Damman, Kevin; A.E. Valente, Mattia; J. van Veldhuisen, Dirk; G.F. Cleland, John; M. O’Connor, Christopher; Metra, Marco; Ponikowski, Piotr; Cotter, Gad; Davison, Beth; M. Givertz, Michael; M. Bloomfield, Daniel; L. Hillege, Hans; A. Voors, Adriaan

2017-01-01

The aim of this study was to evaluate the ability of Neutrophil Gelatinase-Associated Lipocalin (NGAL) to predict clinically relevant worsening renal function (WRF) in acute heart failure (AHF). Plasma NGAL and serum creatinine changes during the first 4 days of admission were investigated in 1447 patients hospitalized for AHF and enrolled in the Placebo-Controlled Randomized Study of the Selective A1Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) study. WRF was defined as serum creatinine rise ≥ 0.3 mg/dL through day 4. Biomarker patterns were described using linear mixed models. WRF developed in 325 patients (22%). Plasma NGAL did not rise earlier than creatinine in patients with WRF. After multivariable adjustment, baseline plasma NGAL, but not creatinine, predicted WRF. AUCs for WRF prediction were modest (<0.60) for all models. NGAL did not independently predict death or rehospitalization (p = n.s.). Patients with WRF and high baseline plasma NGAL had a greater risk of death, and renal or cardiovascular rehospitalization by 60 days than patients with WRF and a low baseline plasma NGAL (p for interaction = 0.024). A rise in plasma NGAL after baseline was associated with a worse outcome in patients with WRF, but not in patients without WRF (p = 0.007). On the basis of these results, plasma NGAL does not provide additional, clinically relevant information about the occurrence of WRF in patients with AHF. PMID:28698481

Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure.

PubMed

Damman, Kevin; Valente, Mattia A E; van Veldhuisen, Dirk J; Cleland, John G F; O'Connor, Christopher M; Metra, Marco; Ponikowski, Piotr; Cotter, Gad; Davison, Beth; Givertz, Michael M; Bloomfield, Daniel M; Hillege, Hans L; Voors, Adriaan A

2017-07-08

The aim of this study was to evaluate the ability of Neutrophil Gelatinase-Associated Lipocalin (NGAL) to predict clinically relevant worsening renal function (WRF) in acute heart failure (AHF). Plasma NGAL and serum creatinine changes during the first 4 days of admission were investigated in 1447 patients hospitalized for AHF and enrolled in the Placebo-Controlled Randomized Study of the Selective A₁Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) study. WRF was defined as serum creatinine rise ≥ 0.3 mg/dL through day 4. Biomarker patterns were described using linear mixed models. WRF developed in 325 patients (22%). Plasma NGAL did not rise earlier than creatinine in patients with WRF. After multivariable adjustment, baseline plasma NGAL, but not creatinine, predicted WRF. AUCs for WRF prediction were modest (<0.60) for all models. NGAL did not independently predict death or rehospitalization ( p = n.s.). Patients with WRF and high baseline plasma NGAL had a greater risk of death, and renal or cardiovascular rehospitalization by 60 days than patients with WRF and a low baseline plasma NGAL (p for interaction = 0.024). A rise in plasma NGAL after baseline was associated with a worse outcome in patients with WRF, but not in patients without WRF ( p = 0.007). On the basis of these results, plasma NGAL does not provide additional, clinically relevant information about the occurrence of WRF in patients with AHF.

Stent revascularization restores cortical blood flow and reverses tissue hypoxia in atherosclerotic renal artery stenosis but fails to reverse inflammatory pathways or glomerular filtration rate.

PubMed

Saad, Ahmed; Herrmann, Sandra M S; Crane, John; Glockner, James F; McKusick, Michael A; Misra, Sanjay; Eirin, Alfonso; Ebrahimi, Behzad; Lerman, Lilach O; Textor, Stephen C

2013-08-01

Atherosclerotic renal artery stenosis (ARAS) is known to reduce renal blood flow, glomerular filtration rate (GFR) and amplify kidney hypoxia, but the relationships between these factors and tubulointerstitial injury in the poststenotic kidney are poorly understood. The purpose of this study was to examine the effect of renal revascularization in ARAS on renal tissue hypoxia and renal injury. Inpatient studies were performed in patients with ARAS (n=17; >60% occlusion) before and 3 months after stent revascularization, or in patients with essential hypertension (n=32), during fixed Na(+) intake and angiotensin converting enzyme/angiotensin receptors blockers Rx. Single kidney cortical, medullary perfusion, and renal blood flow were measured using multidetector computed tomography, and GFR by iothalamate clearance. Tissue deoxyhemoglobin levels (R(2)*) were measured by blood oxygen level-dependent MRI at 3T, as was fractional kidney hypoxia (percentage of axial area with R(2)*>30/s). In addition, we measured renal vein levels of neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Pre-stent single kidney renal blood flow, perfusion, and GFR were reduced in the poststenotic kidney. Renal vein neutrophil gelatinase-associated lipocalin, tumor necrosis factor-α, monocyte chemoattractant protein-1, and fractional hypoxia were higher in untreated ARAS than in essential hypertension. After stent revascularization, fractional hypoxia fell (P<0.002) with increased cortical perfusion and blood flow, whereas GFR and neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α remained unchanged. These data demonstrate that despite reversal of renal hypoxia and partial restoration of renal blood flow after revascularization, inflammatory cytokines and injury biomarkers remained elevated and GFR failed to recover in ARAS. Restoration of vessel patency alone failed to reverse tubulointerstitial damage and partly explains the limited clinical benefit of renal stenting. These results identify potential therapeutic targets for recovery of kidney function in renovascular disease.

Late renal toxicity of treatment for childhood malignancy: risk factors, long-term outcomes, and surveillance.

PubMed

Skinner, Roderick

2018-02-01

Chronic glomerular and tubular nephrotoxicity is reported in 20-50% and 20-25%, respectively, of children and adolescents treated with ifosfamide and 60-80% and 10-30%, respectively, of those given cisplatin. Up to 20% of children display evidence of chronic glomerular damage after unilateral nephrectomy for a renal tumour. Overall, childhood cancer survivors have a ninefold higher risk of developing renal failure compared with their siblings. Such chronic nephrotoxicity may have multiple causes, including chemotherapy, radiotherapy exposure to kidneys, renal surgery, supportive care drugs and tumour-related factors. These cause a wide range of chronic glomerular and tubular toxicities, often with potentially severe clinical sequelae. Many risk factors for developing nephrotoxicity, mostly patient and treatment related, have been described, but we remain unable to predict all episodes of renal damage. This implies that other factors may be involved, such as genetic polymorphisms influencing drug metabolism. Although our knowledge of the long-term outcomes of chronic nephrotoxicity is increasing, there is still much to learn, including how we can optimally predict or achieve early detection of nephrotoxicity. Greater understanding of the pathogenesis of nephrotoxicity is needed before its occurrence can be prevented.

Estimating the Rate of Occurrence of Renal Stones in Astronauts

NASA Technical Reports Server (NTRS)

Myers, J.; Goodenow, D.; Gokoglu, S.; Kassemi, M.

2016-01-01

Changes in urine chemistry, during and post flight, potentially increases the risk of renal stones in astronauts. Although much is known about the effects of space flight on urine chemistry, no inflight incidence of renal stones in US astronauts exists and the question "How much does this risk change with space flight?" remains difficult to accurately quantify. In this discussion, we tackle this question utilizing a combination of deterministic and probabilistic modeling that implements the physics behind free stone growth and agglomeration, speciation of urine chemistry and published observations of population renal stone incidences to estimate changes in the rate of renal stone presentation. The modeling process utilizes a Population Balance Equation based model developed in the companion IWS abstract by Kassemi et al. (2016) to evaluate the maximum growth and agglomeration potential from a specified set of urine chemistry values. Changes in renal stone occurrence rates are obtained from this model in a probabilistic simulation that interrogates the range of possible urine chemistries using Monte Carlo techniques. Subsequently, each randomly sampled urine chemistry undergoes speciation analysis using the well-established Joint Expert Speciation System (JESS) code to calculate critical values, such as ionic strength and relative supersaturation. The Kassemi model utilizes this information to predict the mean and maximum stone size. We close the assessment loop by using a transfer function that estimates the rate of stone formation from combining the relative supersaturation and both the mean and maximum free stone growth sizes. The transfer function is established by a simulation analysis which combines population stone formation rates and Poisson regression. Training this transfer function requires using the output of the aforementioned assessment steps with inputs from known non-stone-former and known stone-former urine chemistries. Established in a Monte Carlo system, the entire renal stone analysis model produces a probability distribution of the stone formation rate and an expected uncertainty in the estimate. The utility of this analysis will be demonstrated by showing the change in renal stone occurrence predicted by this method using urine chemistry distributions published in Whitson et al. 2009. A comparison to the model predictions to previous assessments of renal stone risk will be used to illustrate initial validation of the model.

A Decline in Intraoperative Renal Near-Infrared Spectroscopy Is Associated With Adverse Outcomes in Children Following Cardiac Surgery.

PubMed

Gist, Katja M; Kaufman, Jonathan; da Cruz, Eduardo M; Friesen, Robert H; Crumback, Sheri L; Linders, Megan; Edelstein, Charles; Altmann, Christopher; Palmer, Claire; Jalal, Diana; Faubel, Sarah

2016-04-01

Renal near-infrared spectroscopy is known to be predictive of acute kidney injury in children following cardiac surgery using a series of complex equations and area under the curve. This study was performed to determine if a greater than or equal to 20% reduction in renal near-infrared spectroscopy for 20 consecutive minutes intraoperatively or within the first 24 postoperative hours is associated with 1) acute kidney injury, 2) increased acute kidney injury biomarkers, or 3) other adverse clinical outcomes in children following cardiac surgery. Prospective single center observational study. Pediatric cardiac ICU. Children less than or equal to age 4 years who underwent cardiac surgery with the use of cardiopulmonary bypass during the study period (June 2011-July 2012). None. A reduction in near-infrared spectroscopy was not associated with acute kidney injury. Nine of 12 patients (75%) with a reduction in renal near-infrared spectroscopy did not develop acute kidney injury. The remaining three patients had mild acute kidney injury (pediatric Risk, Injury, Failure, Loss, End stage-Risk). A reduction in renal near-infrared spectroscopy was associated with the following adverse clinical outcomes: 1) a longer duration of mechanical ventilation (p = 0.05), 2) longer intensive care length of stay (p = 0.05), and 3) longer hospital length of stay (p < 0.01). A decline in renal near-infrared spectroscopy in combination with an increase in serum interleukin-6 and serum interleukin-8 was associated with a longer intensive care length of stay, and the addition of urine interleukin-18 to this was associated with a longer hospital length of stay. In this cohort, the rate of acute kidney injury was much lower than anticipated thereby limiting the evaluation of a reduction in renal near-infrared spectroscopy as a predictor of acute kidney injury. A greater than or equal to 20% reduction in renal near-infrared spectroscopy was significantly associated with adverse outcomes in children following cardiac surgery. The addition of specific biomarkers to the model was predictive of worse outcomes in these patients. Thus, real-time evaluation of renal near-infrared spectroscopy using the specific levels of change of a 20% reduction for 20 minutes may be useful in predicting prolonged mechanical ventilation and other adverse outcomes in children undergoing cardiac surgery.

A Case of Left Renal Vein Ligation in a Patient with Solitary Left Kidney Undergoing Liver Transplantation to Control Splenorenal Shunt and Improve Portal Venous Flow.

PubMed

Martino, Rodrigo B; Júnior, Eserval Rocha; Manuel, Valdano; Rocha-Santos, Vinicius; D'Albuquerque, Luis Augusto C; Andraus, Wellington

2017-10-11

BACKGROUND Adequate portal venous flow is required for successful liver transplantation. Reduced venous flow and blood flow 'steal' by collateral vessels are a concern, and when there is a prominent splenorenal shunt present, ligation of the left renal vein has been recommended to improve portal venous blood flow. CASE REPORT A 51-year-old man who had undergone right nephrectomy in childhood required liver transplantation for liver cirrhosis and hepatocellular carcinoma due to hepatitis C virus (HCV) infection. The patient had no other comorbidity and no history of hepatorenal syndrome. At transplantation surgery, portal venous flow was poor and did not improve with ligation of shunt veins, but ligation of the left renal vein improved portal venous flow. On the first and fifth postoperative days, the patient was treated with basiliximab, a chimeric monoclonal antibody to the IL-2 receptor, and methylprednisolone. The calcineurin inhibitor, tacrolimus, was introduced on the fifth postoperative day. On the sixteenth postoperative day, renal color Doppler ultrasound showed normal left renal parenchyma; hepatic Doppler ultrasound showed good portal vein flow and preserved hepatic parenchyma in the liver transplant. CONCLUSIONS This case report has shown that in a patient with a single left kidney, left renal vein ligation is feasible and safe in a patient with no other risk factors for renal impairment following liver transplantation. Modification of postoperative immunosuppression to avoid calcineurin inhibitors in the very early postoperative phase may be important in promoting good recovery of renal function and to avoid the need for postoperative renal dialysis.

High-volume forced diuresis with matched hydration using the RenalGuard System to prevent contrast-induced nephropathy: A meta-analysis of randomized trials.

PubMed

Shah, Rahman; Wood, Sarah J; Khan, Sajjad A; Chaudhry, Amina; Rehan Khan, M; Morsy, Mohamed S

2017-12-01

Contrast-induced nephropathy (CIN) is a well-recognized complication of coronary angiography that is associated with poor outcomes. Several small randomized controlled trials (RCTs) have recently shown that in patients with chronic kidney disease (CKD), furosemide-induced forced diuresis with matched hydration using the RenalGuard system can prevent its occurrence. However, individual studies have been underpowered and thus cannot show significant differences in major clinical endpoints. Forced diuresis with matched hydration using the RenalGuard system improves clinical outcomes in patients undergoing coronary angiography. Scientific databases and websites were searched for relevant RCTs. The pooled risk ratios were calculated using random-effects models. The primary endpoint was CIN, and the secondary endpoints were major adverse clinical events (MACEs) and the need for renal replacement therapy. Data from 3 trials including 586 patients were analyzed. High-volume forced diuresis with matched hydration using the RenalGuard system decreased risk of CIN by 60% (risk ratio: 0.40, 95% confidence interval: 0.25 to 0.65, P < 0.001), MACE rate by 59%, and the need for renal replacement therapy by 78%, compared with the standard of care. In patients with CKD undergoing coronary angiography, high-volume forced diuresis with matched hydration using the RenalGuard system significantly reduces the risk of CIN, MACE rate, and the need for renal replacement therapy. Larger RCTs with sufficient power are needed to confirm these findings. © 2017 Wiley Periodicals, Inc.

Oxalate nephropathy associated with chronic pancreatitis.

PubMed

Cartery, Claire; Faguer, Stanislas; Karras, Alexandre; Cointault, Olivier; Buscail, Louis; Modesto, Anne; Ribes, David; Rostaing, Lionel; Chauveau, Dominique; Giraud, Patrick

2011-08-01

Enteric overabsorption of oxalate may lead to hyperoxaluria and subsequent acute oxalate nephritis (AON). AON related to chronic pancreatitis is a rare and poorly described condition precluding early recognition and treatment. We collected the clinical characteristics, treatment, and renal outcome of 12 patients with chronic pancreatitis-associated AON followed in four French renal units. Before AON, mild to moderate chronic kidney disease was present in all patients, diabetes mellitus in eight (insulin [n = 6]; oral antidiabetic drugs [n = 2]), and known chronic pancreatitis in only eight. At presentation, pancreas imaging showed gland atrophy/heterogeneity, Wirsung duct dilation, calcification, or pseudocyst. Renal findings consisted of rapidly progressive renal failure with tubulointerstitial profile. Acute modification of glomerular filtration preceded the AON (i.e., diarrhea and diuretics). Increase in urinary oxalate excretion was found in all tested patients and hypocalcemia in nine (<1.5 mmol/L in four patients). Renal biopsy showed diffuse crystal deposits, highly suggestive of oxalate crystals, with tubular necrosis and interstitial inflammatory cell infiltrates. Treatment consisted of pancreatic enzyme supplementation, oral calcium intake, and an oxalate-free diet in all patients and renal replacement therapy in five patients. After a median follow-up of 7 months, three of 12 patients reached end-stage renal disease. AON is an under-recognized severe crystal-induced renal disease with features of tubulointerstitial nephritis that may occur in patients with a long history of chronic pancreatitis or reveal the pancreatic disease. Extrinsic triggering factors should be prevented.

microRNA-21-induced dissociation of PDCD4 from rictor contributes to Akt-IKKβ-mTORC1 axis to regulate renal cancer cell invasion.

PubMed

Bera, Amit; Das, Falguni; Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S; Abboud, Hanna E; Choudhury, Goutam Ghosh

2014-10-15

Renal cancer metastasis may result from oncogenic forces that contribute to the primary tumor. We have recently identified microRNA-21 as an oncogenic driver of renal cancer cells. The mechanism by which miR-21 controls renal cancer cell invasion is poorly understood. We show that miR-21 directly downregulates the proapoptotic protein PDCD4 to increase migration and invasion of ACHN and 786-O renal cancer cells as a result of phosphorylation/activation of Akt and IKKβ, which activate NFκB-dependent transcription. Constitutively active (CA) Akt or CA IKKβ blocks PDCD4-mediated inhibition and restores renal cancer cell migration and invasion. PDCD4 inhibits mTORC1 activity, which was reversed by CA IKKβ. Moreover, CA mTORC1 restores cell migration and invasion inhibited by PDCD4 and dominant negative IKKβ. Moreover, PDCD4 negatively regulates mTORC2-dependent Akt phosphorylation upstream of this cascade. We show that PDCD4 forms a complex with rictor, an exclusive component of mTORC2, and that this complex formation is reduced in renal cancer cells due to increased miR-21 expression resulting in enhanced phosphorylation of Akt. Thus our results identify a previously unrecognized signaling node where high miR-21 levels reduce rictor-PDCD4 interaction to increase phosphorylation of Akt and contribute to metastatic fitness of renal cancer cells. Copyright © 2014 Elsevier Inc. All rights reserved.

microRNA-21-induced Dissociation of PDCD4 from Rictor Contributes to Akt-IKKβ-mTORC1 axis to Regulate Select Renal Cancer Cell Invasion

PubMed Central

Bera, Amit; Das, Falguni; Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh

2014-01-01

Renal cancer metastasis may result from oncogenic forces that contribute to the primary tumor. We have recently identified microRNA-21 as an oncogenic driver of renal cancer cells. The mechanism by which miR-21 controls renal cancer cell invasion is poorly understood. We show that miR-21 directly downregulates the proapoptotic protein PDCD4 to increase migration and invasion of ACHN and 786-O renal cancer cells as a result of phosphorylation/activation of Akt and IKKβ, which activate NFκB-dependent transcription. Constitutively active (CA) Akt or CA IKKβ blocks PDCD4-mediated inhibition and restores renal cancer cell migration and invasion. PDCD4 inhibits mTORC1 activity, which was reversed by CA IKKβ. Moreover, CA mTORC1 restores cell migration and invasion inhibited by PDCD4- and dominant negative IKKβ. Moreover, PDCD4 negatively regulates mTORC2-dependent Akt phosphorylation upstream of this cascade. We show that PDCD4 forms a complex with rictor, an exclusive component of mTORC2, and that this complex formation is reduced in renal cancer cells due to increased miR-21 expression resulting in enhanced phosphorylation of Akt. Thus our results identify a previously unrecognized signaling node where high miR-21 levels reduce rictor-PDCD4 interaction to increase phosphorylation of Akt and contribute to metastatic fitness of renal cancer cells. PMID:25016284

Sarcomatoid renal cell carcinoma: Biology and treatment advances.

PubMed

Mouallem, Nemer El; Smith, Steven C; Paul, Asit K

2018-06-01

Sarcomatoid transformation in renal cell carcinoma, so called sacromatoid RCC (sRCC), is associated with an aggressive behavior and a poor prognosis. Current therapeutic approaches are largely ineffective. Recent studies looking into the genomic and molecular characterization of sRCCs have provided insights into the biology and pathogenesis of this entity. These advances in molecular signatures may help development of effective treatment strategies. We herein present a review of recent developments in the pathology, biology, and treatment modalities in sRCC. Copyright © 2017 Elsevier Inc. All rights reserved.

[Breast carcinoma metastasis to the gastrointestinal tract and tumour-to-tumour metastasis to renal cell carcinoma].

PubMed

Mosholt, Karina Sif Søndergaard; Pilt, Anette Pedersen; Wittendorff, Hans-Erik

2015-04-06

Breast carcinoma metastasis to the gastrointestinal tract and tumour-to-tumour metastasis is rare. We describe a case of a 71-year-old woman with previous breast cancer presenting with dyspepsia, nausea and weight-loss. Biopsies from the pylorus revealed what appeared to be a gastric carcinoma. A CT scan showed large kidney mass and biopsies revealed clear cell renal cell carcinoma with areas of poorly differentiated adenocarcinoma. Subsequent immunohistochemical analysis revealed the presence of breast carcinoma in both locations.

INTERPRETING SPONTANEOUS RENAL LESIONS IN SAFETY AND RISK ASSESSMENT

EPA Science Inventory

Interpreting Spontaneous Renal Lesions in Safety and Risk Assessment
Douglas C. Wolf, D.V.M., Ph.D.

Introduction

Risk assessment is a process whereby the potential adverse health effects from exposure to a xenobiotic are predicted after evaluation of the availab...

Elevated cystatin C: is it a reflection for kidney or liver impairment in hepatic children?

PubMed

El-Sayed, Behairy; El-Araby, Hanaa; Adawy, Nermin; Hassona, Mona; El-Nady, Naglaa; Zakaria, Haidy; Khedr, Mohammed

2017-09-01

To assess if elevated serum cystatin C (Cyst-C) is an indicator for renal or hepatic dysfunction in presence of liver fibrosis. Data of 50 children with chronic liver diseases (CLDs), out of which 25 were without renal impairment, and 25 with renal impairment were analyzed. Twenty healthy children served as a healthy control group. Routine investigations, creatinine clearance, hepatitis viral markers, abdominal ultrasonography, and liver biopsy were performed for patients with CLDs. Measurement of serum Cyst-C concentration by particle induced immunonephelometry were completed for both patients and control group. Results showed that serum Cyst-C is not correlated with the degree of hepatic impairment ( p > 0.05). Cyst-C levels were significantly higher in patients with renal impairment (3.66 ± 0.85) than those without (0.71 ± 0.12), and healthy control group (0.63 ± 0.85). Cystatin-C showed significant elevation in patients with severe fibrosis with renal impairment (3.66 ± 0.85) than those without (0.76 ± 0.04) ( p < 0.0001). Cyst-C at cutoff levels of 1.65 mg/l showed 100% accuracy in discrimination between those with and those without renal impairment. Cyst-C > 2.34 mg/l predicting GFR < 40 ml/min with accuracy of 90%. Cyst-C > 2.73 mg/l predicting GFR < 20 ml/min with accuracy of 81.5%. Serum Cyst-C is a promising marker to estimate renal impairment in children with CLDs. Further studies are needed to estimate the accuracy of serum Cyst-C for early detection of renal impairment and close monitoring of the hepatic children.

Increasing Body Mass Index Predicts Rapid Decline in Renal Function: A 5 Year Retrospective Study.

PubMed

Ma, Xiaojing; Zhang, Chengyin; Su, Hong; Gong, Xiaojie; Kong, Xianglei

2018-05-02

While obesity is a recognized risk factor for chronic kidney disease, it remains unclear whether change in body mass index (ΔBMI ) is independently associated with decline in renal function (evaluated by the change in estimated glomerular filtration rate, ΔeGFR) over time. Accordingly, to help clarify this we conducted a retrospective study to measure the association of ΔBMI with decline in renal function in Chinese adult population. A total of 4007 adults (aged 45.3±13.7 years, 68.6% male) without chronic kidney disease at baseline were enrolled between 2008 and 2013. Logistic regression models were applied to explore the relationships between baseline BMI and ΔBMI, and rapid decline in renal function (defined as the lowest quartile of ΔeGFR ). During 5 years of follow-up, the ΔBMI and ΔeGFR were 0.47±1.6 (kg/m 2 ) and -3.0±8.8 (ml/min/1.73 m 2 ), respectively. After adjusted for potential confounders, ΔBMI (per 1 kg/m 2 increase) was independently associated with the rapid decline in renal function [with a fully adjusted OR of 1.12 (95% CI, 1.05 to 1.20). By contrast, the baseline BMI was not associated with rapid decline in renal function [OR=1.05 (95% CI, 0.98 to 1.13)]. The results were robust among 2948 hypertension-free and diabetes-free participants, the adjusted ORs of ΔBMI and baseline BMI were 1.14 (95% CI, 1.05 to 1.23) and 1.0 (95% CI, 0.96 to 1.04) for rapid decline in renal function, respectively. The study revealed that increasing ΔBMI predicts rapid decline in renal function. © Georg Thieme Verlag KG Stuttgart · New York.

Innovative use of novel biomarkers to improve the safety of renally-eliminated and nephrotoxic medications.

PubMed

Barreto, Erin F; Rule, Andrew D; Voils, Stacy A; Kane-Gill, Sandra L

2018-06-08

Over the last decade, the discovery and research into the application of novel renal biomarkers to improve medication efficacy and safety has expanded considerably. Pharmacists are uniquely positioned to leverage this new technology for renal assessment to improve medication dosing and monitoring. Serum cystatin C is a relatively new, inexpensive, functional renal biomarker that responds more quickly to changing renal function than creatinine and is not meaningfully affected by age, sex, skeletal muscle mass, dietary intake, or deconditioning. Cystatin C has been proposed as an adjunct or alternative to creatinine for glomerular filtration rate (GFR) assessment and estimation of drug clearance. Tissue inhibitor of metalloproteinase-2●insulin-like growth factor-binding protein 7 ([TIMP-2]●[IGFBP7]) is a composite of two damage biomarkers released into the urine at a checkpoint in mitosis when renal cells undergo stress or sense a future risk of damage. Concentrations of [TIMP-2]●[IGFBP7] increase before a rise in serum creatinine is evident, thus providing insightful information for evaluation in the context of other patient data to predict the risk for impending kidney injury. The purpose for this article is to provide a brief overview of novel renal biomarkers that are being used as a mechanism to improve medication safety, including discussion of cystatin C, as part of drug-dosing algorithms and specifically for vancomycin dosing, and use of [TIMP-2]●[IGFBP7] for risk prediction in acute kidney injury and drug-induced kidney disease. Select cases of clinical experience with use of novel renal biomarkers are outlined, and lessons learned and future applications are described. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model

PubMed Central

Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

2016-01-01

The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet–fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms of sublethal tubular cell injury. PMID:26752420

Dehydration upon admission is a risk factor for incomplete recovery of renal function in children with haemolytic uremic syndrome.

PubMed

Ojeda, José M; Kohout, Isolda; Cuestas, Eduardo

2013-01-01

Haemolytic uremic syndrome (HUS) is the most common cause of acute renal failure and the second leading cause of chronic renal failure in children. The factors that affect incomplete renal function recovery prior to hospital admission are poorly understood. To analyse the risk factors that determine incomplete recovery of renal function prior to hospitalisation in children with HUS. A retrospective case-control study. age, sex, duration of diarrhoea, bloody stools, vomiting, fever, dehydration, previous use of antibiotics, and incomplete recovery of renal function (proteinuria, hypertension, reduced creatinine clearance, and chronic renal failure during follow-up). Patients of both sexes under 15 years of age were included. Of 36 patients, 23 were males (65.3%; 95%CI: 45.8 to 80.9), with an average age of 2.5 ± 1.4 years. Twenty-one patients required dialysis (58%; 95% CI: 40.8 to 75.8), and 13 (36.1%; 95% CI: 19.0 to 53.1) did not recover renal function. In the bivariate model, the only significant risk factor was dehydration (defined as weight loss >5%) [(OR: 5.3; 95% CI: 1.4 to 12.3; P=.0220]. In the multivariate analysis (Cox multiple regression), only dehydration was marginally significant (HR: 95.823; 95% CI: 93.175 to 109.948; P=.085). Our data suggest that dehydration prior to admission may be a factor that increases the risk of incomplete recovery of renal function during long-term follow-up in children who develop HUS D+. Consequently, in patients with diarrhoea who are at risk of HUS, dehydration should be strongly avoided during outpatient care to preserve long-term renal function. These results must be confirmed by larger prospective studies.

Outcome of Renal Artery Reconstruction

PubMed Central

Darling, R. Clement; Kreienberg, Paul B.; Chang, Benjamin B.; Paty, Philip S. K.; Lloyd, William E.; Leather, Robert P.; Shah, Dhiraj M.

1999-01-01

Objective To evaluate the short- and long-term results of surgical reconstruction of the renal arteries, the authors review their experience with more than 600 reconstructions performed over a 12-year period. Summary Background Data Reconstruction of the renal arteries, whether for primary renal indications or concomitantly with aortic reconstruction, has evolved over the past 40 years. There is concern that renal artery reconstructions carry significant rates of mortality and morbidity and may fare poorly compared with less-invasive procedures. Methods From 1986 to 1998, 687 renal artery reconstructions were performed in 568 patients. Of these, 105 patients had simultaneous bilateral renal artery reconstructions. Fifty-six percent of the patients were male; 11% had diabetes; 35% admitted to smoking at the time of surgery. Mean age was 67 (range, 1 to 92). One hundred fifty-six (23%) were primary procedures and the remainder were adjunctive procedures with aortic reconstructions; 406 were abdominal aortic aneurysms and 125 were aortoiliac occlusive disease. Five hundred procedures were bypasses, 108 were endarterectomies, 72 were reimplantation, and 7 were patch angioplasties. There were 31 surgical deaths (elective and emergent) in the entire group for a mortality rate of 5.5%. Predictors of increased risk of death were patients with aortoiliac occlusive disease and patients undergoing bilateral simultaneous renal artery revascularization. Cause of death was primarily cardiac. Other nonfatal complications included bleeding (nine patients) and wound infection (three patients). There were 9 immediate occlusions (1.3%) and 10 late occlusions (1.5%). Thirty-three patients (4.8%) had temporary worsening of their renal function after surgery. Conclusion Renal artery revascularization is a safe and durable procedure. It can be performed in selected patients for primary renovascular pathology. It can also be an adjunct to aortic reconstruction with acceptable mortality and morbidity rates. PMID:10522722

A multi-centre qualitative study exploring the experiences of UK South Asian and white diabetic patients referred for renal care.

PubMed

Wilkinson, Emma; Randhawa, Gurch; Feehally, John; Farrington, Ken; Greenwood, Roger; Choi, Peter; Lightstone, Liz

2012-11-23

An exploration of renal complications of diabetes from the patient perspective is important for developing quality care through the diabetic renal disease care pathway. Newly referred South Asian and White diabetic renal patients over 16 years were recruited from nephrology outpatient clinics in three UK centres--Luton, West London and Leicester--and their experiences of the diabetes and renal care recorded.A semi-structured qualitative interview was conducted with 48 patients. Interview transcripts were analysed thematically and comparisons made between the White and South Asian groups. 23 South Asian patients and 25 White patients were interviewed. Patient experience of diabetes ranged from a few months to 35 years with a mean time since diagnosis of 12.1 years and 17.1 years for the South Asian and White patients respectively. Confusion emerged as a response to referral shared by both groups. This sense of confusion was associated with reported lack of information at the time of referral, but also before referral. Language barriers exacerbated confusion for South Asian patients. The diabetic renal patients who have been referred for specialist renal care and found the referral process confusing have poor of awareness of kidney complications of diabetes. Healthcare providers should be more aware of the ongoing information needs of long term diabetics as well as the context of any information exchange including language barriers.

Post-transplant HLA class II antibodies and high soluble CD30 levels are independently associated with poor kidney graft survival.

PubMed

Langan, L L; Park, L P; Hughes, T L; Irish, A; Luxton, G; Witt, C S; Christiansen, F T

2007-04-01

HLA-specific antibodies (HSA) and soluble CD30 (sCD30) were measured in 208 renal transplant recipients with functioning grafts at least 1 year after transplantation (median 8.2 years) to investigate the predictive value of HSA and sCD30 on subsequent graft outcome. HSA (class I and class II) were detected by both ELISA LAT-M and Luminex LabScreen assays. Data on graft outcome was collected with a median follow-up time of 3.5 years after antibody and sCD30 measurement. Recipients with post-transplant HLA class II antibodies had particularly poor graft outcome with a hazard ratio (HR) of 7.8 (p < 0.0001) when detected by ELISA, and a HR of 6.0 (p < 0.0001) when detected by Luminex. A high post-transplant sCD30 level >or=100 U/mL was associated with increased risk of subsequent graft failure (HR 2.7, p = 0.03). sCD30 and HSA had an independent and additive association with graft outcome. Recipients with HLA class II antibody and high sCD30 had the highest risk of subsequent graft failure (HR 43.4, p < 0.0001 and HR 18.1, p = 0.0008 for ELISA and Luminex, respectively). These data show that detection of HSA and serum sCD30 measured at least 1-year post-transplant provides valuable and predictive information regarding subsequent graft outcome.

NiaoDuQing granules relieve chronic kidney disease symptoms by decreasing renal fibrosis and anemia

PubMed Central

Wang, Xu; Yu, Suyun; Jia, Qi; Chen, Lichuan; Zhong, Jinqiu; Pan, Yanhong; Shen, Peiliang; Shen, Yin; Wang, Siliang; Wei, Zhonghong; Cao, Yuzhu; Lu, Yin

2017-01-01

NiaoDuQing (NDQ) granules, a traditional Chinese medicine, has been clinically used in China for over fourteen years to treat chronic kidney disease (CKD). To elucidate the mechanisms underlying the therapeutic benefits of NDQ, we designed an approach incorporating chemoinformatics, bioinformatics, network biology methods, and cellular and molecular biology experiments. A total of 182 active compounds were identified in NDQ granules, and 397 putative targets associated with different diseases were derived through ADME modelling and target prediction tools. Protein-protein interaction networks of CKD-related and putative NDQ targets were constructed, and 219 candidate targets were identified based on topological features. Pathway enrichment analysis showed that the candidate targets were mostly related to the TGF-β, the p38MAPK, and the erythropoietin (EPO) receptor signaling pathways, which are known contributors to renal fibrosis and/or renal anemia. A rat model of CKD was established to validate the drug-target mechanisms predicted by the systems pharmacology analysis. Experimental results confirmed that NDQ granules exerted therapeutic effects on CKD and its comorbidities, including renal anemia, mainly by modulating the TGF-β and EPO signaling pathways. Thus, the pharmacological actions of NDQ on CKD symptoms correlated well with in silico predictions. PMID:28915563

Application of HRV-CD for estimation of life expectancy in various clinical disorders.

PubMed

Almoznino-Sarafian, Dorit; Sarafian, Gideon; Zyssman, Itzhak; Shteinshnaider, Miriam; Tzur, Irma; Kaplan, Ben-Zion; Berman, Sylvia; Cohen, Natan; Gorelik, Oleg

2009-12-01

Low heart rate variability (HRV) was found in various medical conditions including heart failure and acute myocardial infarction. Decreased HRV in these conditions predicted poor prognosis. HRV was estimated in 133 unselected inpatients with relevant clinical bedside conditions by non-linear analysis derived from chaos theory, which calculates the correlation dimension (CD) of the cardiac electrophysiologic system (HRV-CD). Mean HRV-CD in the entire group was 3.75+/-0.45. Heart failure, coronary artery disease, cardiac arrhythmia, low serum potassium, renal dysfunction, and diabetes mellitus were significantly associated with reduced HRV-CD compared to their counterparts [3.6 vs. 3.9 (P<.001), 3.65 vs. 3.87 (P=.005), 3.58 vs. 3.8 (P=.01), 3.38 vs. 3.81 (P=.02), 3.59 vs. 3.8 (P=.04), and 3.66 vs. 3.82 (P=.04), respectively]. Stepwise logistic regression showed heart failure to be the condition most significantly associated with low HRV-CD (odds ratio 4.2, 95% confidence interval 1.90-9.28, P<.001). In the entire group, decreased HRV-CD (< or =3.75 vs. >3.75) was associated with lower survival (P=.01). Mortality of diabetic patients with HRV-CD < or =3.75 exceeded the mortality in patients with HRV-CD >3.75 (P=.02). Heart failure, renal dysfunction or age over 70 combined with HRV-CD < or =3.75 also appeared to be associated with augmented mortality. Diminished HRV-CD is associated with heart failure, coronary artery disease, cardiac arrhythmia, renal dysfunction, diabetes mellitus and low serum potassium. Among the latter, heart failure is most significantly associated with decreased HRV-CD. Decreased HRV-CD values, especially in diabetics, are also associated with lower survival.

Altered metabolic pathways in clear cell renal cell carcinoma: A meta-analysis and validation study focused on the deregulated genes and their associated networks

PubMed Central

Zaravinos, Apostolos; Pieri, Myrtani; Mourmouras, Nikos; Anastasiadou, Natassa; Zouvani, Ioanna; Delakas, Dimitris; Deltas, Constantinos

2014-01-01

Clear cell renal cell carcinoma (ccRCC) is the predominant subtype of renal cell carcinoma (RCC). It is one of the most therapy-resistant carcinomas, responding very poorly or not at all to radiotherapy, hormonal therapy and chemotherapy. A more comprehensive understanding of the deregulated pathways in ccRCC can lead to the development of new therapies and prognostic markers. We performed a meta- analysis of 5 publicly available gene expression datasets and identified a list of co- deregulated genes, for which we performed extensive bioinformatic analysis coupled with experimental validation on the mRNA level. Gene ontology enrichment showed that many proteins are involved in response to hypoxia/oxygen levels and positive regulation of the VEGFR signaling pathway. KEGG analysis revealed that metabolic pathways are mostly altered in ccRCC. Similarly, Ingenuity Pathway Analysis showed that the antigen presentation, inositol metabolism, pentose phosphate, glycolysis/gluconeogenesis and fructose/mannose metabolism pathways are altered in the disease. Cellular growth, proliferation and carbohydrate metabolism, were among the top molecular and cellular functions of the co-deregulated genes. qRT-PCR validated the deregulated expression of several genes in Caki-2 and ACHN cell lines and in a cohort of ccRCC tissues. NNMT and NR3C1 increased expression was evident in ccRCC biopsies from patients using immunohistochemistry. ROC curves evaluated the diagnostic performance of the top deregulated genes in each dataset. We show that metabolic pathways are mostly deregulated in ccRCC and we highlight those being most responsible in its formation. We suggest that these genes are candidate predictive markers of the disease. PMID:25594006

Prediction of human pharmacokinetics using physiologically based modeling: a retrospective analysis of 26 clinically tested drugs.

PubMed

De Buck, Stefan S; Sinha, Vikash K; Fenu, Luca A; Nijsen, Marjoleen J; Mackie, Claire E; Gilissen, Ron A H J

2007-10-01

The aim of this study was to evaluate different physiologically based modeling strategies for the prediction of human pharmacokinetics. Plasma profiles after intravenous and oral dosing were simulated for 26 clinically tested drugs. Two mechanism-based predictions of human tissue-to-plasma partitioning (P(tp)) from physicochemical input (method Vd1) were evaluated for their ability to describe human volume of distribution at steady state (V(ss)). This method was compared with a strategy that combined predicted and experimentally determined in vivo rat P(tp) data (method Vd2). Best V(ss) predictions were obtained using method Vd2, providing that rat P(tp) input was corrected for interspecies differences in plasma protein binding (84% within 2-fold). V(ss) predictions from physicochemical input alone were poor (32% within 2-fold). Total body clearance (CL) was predicted as the sum of scaled rat renal clearance and hepatic clearance projected from in vitro metabolism data. Best CL predictions were obtained by disregarding both blood and microsomal or hepatocyte binding (method CL2, 74% within 2-fold), whereas strong bias was seen using both blood and microsomal or hepatocyte binding (method CL1, 53% within 2-fold). The physiologically based pharmacokinetics (PBPK) model, which combined methods Vd2 and CL2 yielded the most accurate predictions of in vivo terminal half-life (69% within 2-fold). The Gastroplus advanced compartmental absorption and transit model was used to construct an absorption-disposition model and provided accurate predictions of area under the plasma concentration-time profile, oral apparent volume of distribution, and maximum plasma concentration after oral dosing, with 74%, 70%, and 65% within 2-fold, respectively. This evaluation demonstrates that PBPK models can lead to reasonable predictions of human pharmacokinetics.

High EphA2 protein expression in renal cell carcinoma is associated with a poor disease outcome.

PubMed

Xu, Jinsheng; Zhang, Junxia; Cui, Liwen; Zhang, Huiran; Zhang, Shenglei; Bai, Yaling

2014-08-01

The receptor tyrosine kinase, ephrin type-A receptor 2 (EphA2), is normally expressed at sites of cell-to-cell contact in adult epithelial tissues, however, recent studies have shown that it is also overexpressed in various types of epithelial carcinomas, with the greatest level of EphA2 expression observed in metastatic lesions. In the present study, the association between the expression of EphA2 and the outcome of RCC patients was assessed. The high expression level of EphA2 was identified by log-rank test for a statistically significant prediction of the RCC outcome. In an overall multivariate analysis, the high expression level of EphA2 was identified as an independent predictor of RCC outcome. The length of survival of the patients with high EphA2 expression was shorter than that of the patients with a low level of expression (relative risk, 2.304; 95% CI, 1.102-4.818; P=0.027). The analysis of the expression levels of EphA2 in tumor tissues may aid in the identification of the patient subgroup that are at a high risk of a poor disease outcome.

Trajectory of Estimated Glomerular Filtration Rate Predicts Renal Injury in Children with Multicystic Dysplastic Kidney.

PubMed

Matsumura, Kazuya; Sugii, Kyoko; Awazu, Midori

2018-06-07

Children with a solitary functioning kidney have a risk of renal injury caused by hyperfiltration. Timely intervention with renin-angiotensin inhibitors may be beneficial. We examined whether trajectory of estimated glomerular filtration rate (eGFR) would predict renal injury, defined as microalbuminuria/proteinuria, hypertension, and/or a decline in eGFR. Seventeen patients (male 7, female 10) with multicystic dysplastic kidney (MCDK; median age 13 years, range 6-19 years) followed in our clinic were examined retrospectively. An eGFR decline was defined as a fall to < 90 mL/min/1.73 m2 or a decline of > 5 mL/min/1.73 m2/year for those with baseline eGFR of ≥90 or < 90 mL/min/1.73 m2 respectively. Nine patients had renal injury at the time of investigation. Compared with 8 patients without renal injury, those with renal injury tended to be older (14.7 ± 4.2 vs. 11.4 ± 4.6 years) and the birth weight was smaller (2,538 ± 281 vs. 2,966 ± 361 g, p < 0.05). The frequency of contralateral congenital anomaly of kidney and urinary tract (cyst, hydronephrosis, or vesicoureteral reflux) were not different. The trajectory of eGFR in those without renal injury was either an increase (n = 3) or unidentifiable (n = 5), whereas that in the renal injury group was exclusively an increase followed by decline (p < 0.05). The average age of the onset of eGFR decline was 9.4 ± 4.2 years and that of the start of renal injury (albuminuria/proteinuria 5, eGFR decline 4, hypertension 1) was 12.5 ± 4.2 years. All the children with MCDK who developed renal injury had eGFR trajectory of increase followed by decline. Renal injury followed the peak eGFR by 3 years on average. This observation is in agreement with the hyperfiltration theory and underscores the importance of following eGFR trajectory closely. © 2018 S. Karger AG, Basel.

Aortic calcification burden predicts deterioration of renal function after radical nephrectomy.

PubMed

Fukushi, Ken; Hatakeyama, Shingo; Yamamoto, Hayato; Tobisawa, Yuki; Yoneyama, Tohru; Soma, Osamu; Matsumoto, Teppei; Hamano, Itsuto; Narita, Takuma; Imai, Atsushi; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Terayama, Yuriko; Funyu, Tomihisa; Ohyama, Chikara

2017-02-06

Radical nephrectomy for renal cell carcinoma (RCC) is a risk factor for the development of chronic kidney disease (CKD), and the possibility of postoperative deterioration of renal function must be considered before surgery. We investigated the contribution of the aortic calcification index (ACI) to the prediction of deterioration of renal function in patients undergoing radical nephrectomy. Between January 1995 and December 2012, we performed 511 consecutive radical nephrectomies for patients with RCC. We retrospectively studied data from 109 patients who had regular postoperative follow-up of renal function for at least five years. The patients were divided into non-CKD and pre-CKD based on a preoperative estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m 2 or <60 mL/min/1.73 m 2 , respectively. The ACI was quantitatively measured by abdominal computed tomography before surgery. The patients in each group were stratified between low and high ACIs. Variables such as age, sex, comorbidities, and pre- and postoperative renal function were compared between patients with a low or high ACI in each group. Renal function deterioration-free interval rates were evaluated by Kaplan-Meier analysis. Factors independently associated with deterioration of renal function were determined using multivariate analysis. The median age, preoperative eGFR, and ACI in this cohort were 65 years, 68 mL/min/1.73 m 2 , and 8.3%, respectively. Higher ACI (≥8.3%) was significantly associated with eGFR decline in both non-CKD and pre-CKD groups. Renal function deterioration-free interval rates were significantly lower in the ACI-high than ACI-low strata in both of the non-CKD and pre-CKD groups. Multivariate analysis showed that higher ACI was an independent risk factor for deterioration of renal function at 5 years after radical nephrectomy. Aortic calcification burden is a potential predictor of deterioration of renal function after radical nephrectomy. This study was registered as a clinical trial: UMIN000023577.

Renal pelvic anatomy is associated with incidence, grade, and need for intervention for urine leak following partial nephrectomy.

PubMed

Tomaszewski, Jeffrey J; Cung, Bic; Smaldone, Marc C; Mehrazin, Reza; Kutikov, Alexander; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

2014-11-01

Although the effect of tumor complexity on perioperative outcome measures is well established, the impact of renal pelvic anatomy on perioperative outcomes remains poorly defined. To evaluate renal pelvic anatomy as an independent predictor of urine leak in moderate- and high-complexity tumors undergoing nephron-sparing surgery. Patients undergoing open partial nephrectomy (PN) for localized RCC were stratified into intermediate- and high-complexity groups using a nephrometry score (7-9 and 10-12, respectively). A renal pelvic score (RPS) was defined by the percentage of renal pelvis contained inside the volume of the renal parenchyma. On this basis, patients were categorized as having an intraparenchymal (>50%) or extraparenchymal (<50%) renal pelvis. Characteristics of patients with and without an intraparenchymal renal pelvic anatomy were compared. Inclusion criteria were met by 255 patients undergoing PN for intermediate (73.6%) and complex (26.4%) localized renal tumors (mean size: 4.6±2.9cm). Twenty-four (9.6%) renal pelves were classified as completely intraparenchymal. Following stratification by RPS, groups differed with respect to Charlson comorbidity index, body mass index, and largest tumor size, while no differences were observed between hospital length of stay, nephrometry score, estimated blood loss, operative time, and age. Intrarenal pelvic anatomy was associated with a markedly increased risk of urine leak (75% vs 6.5%; p=0.001), secondary intervention (37.5% vs 3.9%; p<0.001), and prolonged duration of urine leak (93±62 d vs 56±29 d; p=0.025). Intraparenchymal renal pelvic anatomy is an uncommon anatomic variant associated with an increased rate of urine leak following PN. Elevated pressures within a small intraparenchymal renal pelvis might explain the increased risk. Preoperative imaging characteristics suggestive of increased risk for urine leak should be considered in perioperative management algorithms. Copyright © 2013. Published by Elsevier B.V.

Comparison of survival analysis and palliative care involvement in patients aged over 70 years choosing conservative management or renal replacement therapy in advanced chronic kidney disease.

PubMed

Hussain, Jamilla A; Mooney, Andrew; Russon, Lynne

2013-10-01

There are limited data on the outcomes of elderly patients with chronic kidney disease undergoing renal replacement therapy or conservative management. We aimed to compare survival, hospital admissions and palliative care access of patients aged over 70 years with chronic kidney disease stage 5 according to whether they chose renal replacement therapy or conservative management. Retrospective observational study. Patients aged over 70 years attending pre-dialysis clinic. In total, 172 patients chose conservative management and 269 chose renal replacement therapy. The renal replacement therapy group survived for longer when survival was taken from the time estimated glomerular filtration rate <20 mL/min (p < 0.0001), <15 mL/min (p < 0.0001) and <12 mL/min (p = 0.002). When factors influencing survival were stratified for both groups independently, renal replacement therapy failed to show a survival advantage over conservative management, in patients older than 80 years or with a World Health Organization performance score of 3 or more. There was also a significant reduction in the effect of renal replacement therapy on survival in patients with high Charlson's Comorbidity Index scores. The relative risk of an acute hospital admission (renal replacement therapy vs conservative management) was 1.6 (p < 0.05; 95% confidence interval = 1.14-2.13). A total of 47% of conservative management patients died in hospital, compared to 69% undergoing renal replacement therapy (Renal Registry data). Seventy-six percent of the conservative management group accessed community palliative care services compared to 0% of renal replacement therapy patients. For patients aged over 80 years, with a poor performance status or high co-morbidity scores, the survival advantage of renal replacement therapy over conservative management was lost at all levels of disease severity. Those accessing a conservative management pathway had greater access to palliative care services and were less likely to be admitted to or die in hospital.

Evolution of association between renal and liver functions while awaiting heart transplant: An application using a bivariate multiphase nonlinear mixed effects model.

PubMed

Rajeswaran, Jeevanantham; Blackstone, Eugene H; Barnard, John

2018-07-01

In many longitudinal follow-up studies, we observe more than one longitudinal outcome. Impaired renal and liver functions are indicators of poor clinical outcomes for patients who are on mechanical circulatory support and awaiting heart transplant. Hence, monitoring organ functions while waiting for heart transplant is an integral part of patient management. Longitudinal measurements of bilirubin can be used as a marker for liver function and glomerular filtration rate for renal function. We derive an approximation to evolution of association between these two organ functions using a bivariate nonlinear mixed effects model for continuous longitudinal measurements, where the two submodels are linked by a common distribution of time-dependent latent variables and a common distribution of measurement errors.

Value of adding the renal pathological score to the kidney failure risk equation in advanced diabetic nephropathy.

PubMed

Yamanouchi, Masayuki; Hoshino, Junichi; Ubara, Yoshifumi; Takaichi, Kenmei; Kinowaki, Keiichi; Fujii, Takeshi; Ohashi, Kenichi; Mise, Koki; Toyama, Tadashi; Hara, Akinori; Kitagawa, Kiyoki; Shimizu, Miho; Furuichi, Kengo; Wada, Takashi

2018-01-01

There have been a limited number of biopsy-based studies on diabetic nephropathy, and therefore the clinical importance of renal biopsy in patients with diabetes in late-stage chronic kidney disease (CKD) is still debated. We aimed to clarify the renal prognostic value of pathological information to clinical information in patients with diabetes and advanced CKD. We retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic nephropathy in four centers in Japan. 296 patients with stage 3-5 CKD at the time of biopsy were identified and assigned two risk prediction scores for end-stage renal disease (ESRD): the Kidney Failure Risk Equation (KFRE, a score composed of clinical parameters) and the Diabetic Nephropathy Score (D-score, a score integrated pathological parameters of the Diabetic Nephropathy Classification by the Renal Pathology Society (RPS DN Classification)). They were randomized 2:1 to development and validation cohort. Hazard Ratios (HR) of incident ESRD were reported with 95% confidence interval (CI) of the KFRE, D-score and KFRE+D-score in Cox regression model. Improvement of risk prediction with the addition of D-score to the KFRE was assessed using c-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During median follow-up of 1.9 years, 194 patients developed ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score were significant predictors of ESRD both in the development cohort and in the validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of the KFRE was good, but its predictive value was weaker than that in the miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90) and was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83). Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI: 0.0-0.8%). We found that the predict values of the KFRE and the D-score were not as good as reported, and combining the D-score with the KFRE did not significantly improve prediction of the risk of ESRD in advanced diabetic nephropathy. To improve prediction of renal prognosis for advanced diabetic nephropathy may require different approaches with combining clinical and pathological parameters that were not measured in the KFRE and the RPS DN Classification.

NSS for an RCC in a patient with renal insufficiency after heart transplant because of right ventricular tumor.

PubMed

Prokopowicz, Grzegorz; Zyczkowski, Marcin; Nowakowski, Krzysztof; Bryniarski, Piotr; Paradysz, Andrzej

2013-01-01

The effect of the immunosuppressive therapy on the development of neoplasms has become the object of an ever increasing interest for clinicians all over the world. The literature on neoplasms development in the course of therapy following transplants has confirmed a considerable increase in the incidence of neoplasms of the skin and lymph nodes. Organ neoplasms developing in patients after transplants are characterized by increased progression, poor cellular diversification and a more unfavorable prognosis than in the general population The aim of the study is to present the case of a nephron-sparing surgery of a renal tumor (NSS) without any intraoperative ischaemia in a 55-year-old female patient with an orthotopic heart transplant and renal insufficiency following a prolonged immune suppression. It is estimated that the patients at the highest risk of neoplasm development are those in the first months after transplant, especially heart transplant. They require maximum doses of immunosuppressive drugs. In the case of patients with initial renal insufficiency the duration of ischaemia of the organ operated on should be minimized, and if possible, surgery should be conducted without clamping the renal pedicle. The surgical treatment of RCC (renal cell carcinoma) in transplant patients does not require any reduction in the amount of the immunosuppressive drugs.

Primary Adult Renal Ewing's Sarcoma: A Rare Entity

PubMed Central

Mukkunda, Ravindra; Venkitaraman, Ramachandran; Thway, Khin; Min, Toon; Fisher, Cyril; Horwich, Alan; Judson, Ian

2009-01-01

Background. Ewing's sarcoma of extraskeletal origin is uncommon and that is of primary renal origin in adults are rare. There is no consensus on the optimal management of Ewing's tumors of renal origin. Methods. A retrospective review of the clinical features, treatment, and outcome of adult patients with primary renal extra-skeletal Ewing's sarcoma who were treated at the Royal Marsden hospital from January 1993–December 2007 is reported. Results. Seven adult patients with primary renal Ewing's sarcoma were identified. All four patients with nonmetastatic disease had radical nephrectomy and received adjuvant chemotherapy +/− radiotherapy. Two developed metastatic disease while on adjuvant chemotherapy, and one patient relapsed after 55 months. The three patients with metastatic disease at presentation did not have nephrectomy and were treated with chemotherapy. All three patients had disease progression with a dismal outcome. Only one patient in the whole group is alive and disease free. The median overall survival was 62.8 months, and the median disease-free survival in patients with nonmetastatic disease after combined modality treatment was 30.3 months. Conclusion. Primary adult renal Ewing's sarcoma is an aggressive tumor with a propensity for early metastasis. Radical nephrectomy with adjuvant combination chemotherapy produced the best results but the outlook remained poor with only one patient experiencing long disease-free survival. PMID:19478963

[Outcome of rapidly progressive glomerulonephritis post-streptococcal disease in children].

PubMed

Jellouli, Manel; Maghraoui, Sondos; Abidi, Kamel; Hammi, Yosra; Goucha, Rim; Naija, Ouns; Zarrouk, Chokri; Gargah, Tahar

2015-11-01

Rapidly progressive glomerulonephritis is a rare form of postinfectious glomerulonephritis. The aim of this study was to describe the outcome of our patients with severe post-streptococcal glomerulonephritis. This retrospective study was conducted in the department of pediatrics in Charles-Nicolle Hospital during a period of 13 years (1997-2009). Twenty-seven children were identified. The mean age was 8.7 years. All patients presented renal failure at presentation. The mean serum creatinine at presentation was 376.9 μmol/L. Six patients presented nephrotic syndrome. Twenty-six children had renal biopsies. Renal biopsies showed crescents in 24 cases. Eighteen children received pulse dose of corticosteroids (66.6%) and 6 children (22%) received pulse dose of corticosteroids and cyclophosphamide. Eleven patients required dialysis. At last follow-up, 22 patients (81.5%) had normal kidney function, 2 had renal dysfunction and 3 reached end stage renal disease. The only significant determinant for renal survival was the supportive dialysis (P=0.015). Rapidly progressive glomerulonephritis is uncommon. There have been significant advancements in supportive, as well as specific therapy, but the outcome continues to be poor. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Impact of estimated glomerular filtration rate based on plasma cystatin C and serum creatinine levels before allogeneic hematopoietic cell transplantation.

PubMed

Wada, Hidenori; Kanda, Junya; Akahoshi, Yu; Nakano, Hirofumi; Ugai, Tomotaka; Yamasaki, Ryoko; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Nakasone, Hideki; Yamazaki, Rie; Kako, Shinichi; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

2018-06-01

No standard method for measuring renal function has been established in allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed 80 patients with hematological diseases who underwent allo-HCT at our center. We assessed renal function using creatinine clearance (Ccr), estimated glomerular filtration rate (eGFR) based on creatinine (eGFRcre), eGFR based on cystatin C (eGFRcys), and the average of eGFRcre and eGFRcys (eGFRave). We then evaluated the impact of pre-transplant renal function on the exacerbation of renal function and non-relapse mortality after transplantation. There was a significant correlation between Ccr and eGFRcre, eGFRcys, and eGFRave. eGFRave best predicted the exacerbation of renal function according to the area under the receiver-operating characteristic curve. The cumulative incidence of renal function exacerbation at 1 year was higher in the lower eGFRave group (<90 ml/min/1.73 m 2 ) than in the higher eGFRave group (≥90 ml/min/1.73 m 2 ; 0.85 vs. 0.39, p < 0.001), which was confirmed by a multivariate analysis (HR 2.75, p = 0.001). A lower eGFRave value was a marginally significant factor for non-relapse mortality (HR 3.29, p = 0.076). Among the four parameters, eGFRave best predicted the exacerbation of renal function in allo-HCT. Further, the marginal association between low eGFRave and high non-relapse mortality warrants further study in a prospective study in allo-HCT.

Clinical value of natriuretic peptides in chronic kidney disease.

PubMed

Santos-Araújo, Carla; Leite-Moreira, Adelino; Pestana, Manuel

2015-01-01

According to several lines of evidence, natriuretic peptides (NP) are the main components of a cardiac-renal axis that operate in clinical conditions of decreased cardiac hemodynamic tolerance to regulate sodium homeostasis, blood pressure and vascular function. Even though it is reasonable to assume that NP may exert a relevant role in the adaptive response to renal mass ablation, evidence gathered so far suggest that this contribution is probably complex and dependent on the type and degree of the functional mass loss. In the last years NP have been increasingly used to diagnose, monitor treatment and define the prognosis of several cardiovascular (CV) diseases. However, in many clinical settings, like chronic kidney disease (CKD), the predictive value of these biomarkers has been questioned. In fact, it is now well established that renal function significantly affects the plasmatic levels of NP and that renal failure is the clinical condition associated with the highest plasmatic levels of these peptides. The complexity of the relation between NP plasmatic levels and CV and renal functions has obvious consequences, as it may limit the predictive value of NP in CV assessment of CKD patients and be a demanding exercise for clinicians involved in the daily management of these patients. This review describes the role of NP in the regulatory response to renal function loss and addresses the main factors involved in the clinical valorization of the peptides in the context of significant renal failure. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

Expression of lactate/H⁺ symporters MCT1 and MCT4 and their chaperone CD147 predicts tumor progression in clear cell renal cell carcinoma: immunohistochemical and The Cancer Genome Atlas data analyses.

PubMed

Kim, Younghye; Choi, Jung-Woo; Lee, Ju-Han; Kim, Young-Sik

2015-01-01

Clear cell renal cell carcinomas (ccRCCs) have inactivation of the von Hippel-Lindau protein, leading to the accumulation of hypoxia-inducible factor-α (HIF-α). HIF-1α induces aerobic glycolysis, the Warburg effect, whereas HIF-2α functions as an oncoprotein. Lactate transport through monocarboxylate transporters (MCTs) and the chaperone CD147 is essential for high glycolytic cancer cell survival. To elucidate the clinical significance of MCT1, MCT4, and CD147 expression, we investigated their expressions by immunohistochemistry in ccRCC specimens and validated the results by an open-access The Cancer Genome Atlas data analysis. Overexpression of MCT1, MCT4, and CD147 was observed in 49.4% (89/180), 39.4% (71/180), and 79.4% (143/180) of ccRCC patients, respectively. High MCT1 expression was associated with older age (P = .017), larger tumor size (P = .015), and advanced TNM stage (P = .012). However, MCT4 overexpression was not related to any variables. CD147 overexpression correlated with high grade (P = .005), tumor necrosis (P = .016), and larger tumor size (P = .038). In univariate analysis, high expression of MCT1 (P < .001), MCT4 (P = .016), and CD147 (P = .02) was linked to short progression-free survival. In multivariate analysis, high MCT1 expression was associated with worse progression-free survival (P = .001). In conclusion, high expression of MCT1 and CD147 is associated with poor prognostic factors. Overexpression of MCT1, MCT4, and CD147 predicts tumor progression. Reversing the Warburg effect by targeting the lactate transporters may be a useful strategy to prevent ccRCC progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Risk factors and pathogenic significance of severe sepsis and septic shock in 2286 patients with gram-negative bacteremia.

PubMed

Kang, Cheol-In; Song, Jae-Hoon; Chung, Doo Ryeon; Peck, Kyong Ran; Ko, Kwan Soo; Yeom, Joon-Sup; Ki, Hyun Kyun; Son, Jun Seong; Lee, Seung Soon; Kim, Yeon-Sook; Jung, Sook-In; Kim, Shin-Woo; Chang, Hyun-Ha; Ryu, Seong Yeol; Kwon, Ki Tae; Lee, Hyuck; Moon, Chisook

2011-01-01

The aim of this study was to identify risk factors for development of severe sepsis or septic shock and to evaluate the clinical impact of severe sepsis on outcome in patients with gram-negative bacteremia (GNB). From the database of a nationwide surveillance for bacteremia, patients with GNB were analyzed. Data of patients with severe sepsis or septic shock were compared with those of patient with sepsis. Of 2286 patients with GNB, 506 (22.1%) fulfilled the criteria of severe sepsis or septic shock. Factors associated with severe sepsis or septic shock in the multivariate analysis included renal disease, indwelling urinary catheter, hematologic malignancy, and neutropenia. The 30-day mortality of patients with severe sepsis or septic shock was significantly higher than that of patients with sepsis (39.5% [172/435] vs. 7.4% [86/1170]; P < 0.001). Multivariable analysis revealed that solid tumor, liver disease, pulmonary disease, pneumonia, and pathogens other than Escherichia coli, which were risk factors of development of severe sepsis or septic shock, were also found to be strong predictors of mortality. Severe sepsis or septic shock was a significant factor associated with mortality (OR, 3.34; 95% CI, 2.35-4.74), after adjustment for other variables predicting poor prognosis. Severe sepsis or septic shock was a common finding in patients with GNB, predicting a higher mortality rate. Renal disease and indwelling urinary catheter were the most important risk factors significantly associated with severe sepsis or septic shock among patients with GNB. Copyright © 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Prediction of Everolimus Toxicity and Prognostic Value of Skeletal Muscle Index in Patients With Metastatic Renal Cell Carcinoma.

PubMed

Auclin, Edouard; Bourillon, Camille; De Maio, Eleonora; By, Marie Agnes; Seddik, Sofiane; Fournier, Laure; Auvray, Marie; Dautruche, Antoine; Vano, Yann-Alexandre; Thibault, Constance; Joly, Florence; Brunereau, Laurent; Gomez-Roca, Carlos; Chevreau, Christine; Elaidi, Reza; Oudard, Stéphane

2017-06-01

The objective of the study was to assess the prognostic role of skeletal muscle index (SMI) in metastatic renal cell carcinoma (mRCC) patients treated with everolimus, and its effect of on everolimus-induced toxicity. Consecutive mRCC patients treated with everolimus between February 2007 and November 2014 underwent computed tomography scans at a single center performed by the same radiologist. SMI was assessed before everolimus treatment using the L3 cross-sectional area. Overall survival (OS) was analyzed according to SMI value. Results were adjusted using the International Metastatic Database Consortium (IMDC) prognostic group, body mass index (BMI), and/or number of previous tyrosine kinase inhibitor lines (NPL). One hundred twenty-four mRCC patients (mean age, 60.21 years) were treated with everolimus as second- or third-line (82.3%) or > third-line (17.7%) therapy. Most patients (87.9%) had clear cell carcinoma. IMDC prognostic group was "favorable" (32.3%), "intermediate" (50%), or "poor" (17.7%). Median SMI was 40.75. OS was longer in patients from the highest versus lowest SMI tercile: 21.9 versus 10 months (P = .002). Continuous SMI at baseline was not significantly associated with OS after adjustment for IMDC prognostic group, BMI, or NPL but the highest versus lowest SMI tercile was an independent prognostic factor in multivariate analysis (P = .025). There was no difference in everolimus toxicity between SMI tercile groups. SMI was an independent prognostic factor for mRCC patients treated with everolimus. Whether this provides additional prognostic value to IMDC criteria needs to be confirmed in a larger cohort. SMI does not seem to be predictive of everolimus-induced toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Hyperglycemic Stress Impairs the Stemness Capacity of Kidney Stem Cells in Rats.

PubMed

Yang, Guang; Jia, Yali; Li, Chunlin; Cheng, Qingli; Yue, Wen; Pei, Xuetao

2015-01-01

The incidence of acute kidney injury in patients with diabetes is significantly higher than that of patients without diabetes, and may be associated with the poor stemness capacity of kidney stem cells (KSCs) and limited recovery of injured renal tubules. To investigate the effects of hyperglycemic stress on KSC stemness, KSCs were isolated from the rat renal papilla and analyzed for their self-renewal and differentiation abilities. Our results showed that isolated KSCs expressed the mesenchymal stem cell markers N-cadherin, Nestin, CD133, CD29, CD90, and CD73. Moreover, KSCs co-cultured with hypoxia-injured renal tubular epithelial cell (RTECs) induced the expression of the mature epithelial cell marker CK18, suggesting that the KSCs could differentiate into RTECs in vitro. However, KSC proliferation, differentiation ability and tolerance to hypoxia were decreased in high-glucose cultures. Taken together, these results suggest the high-glucose microenvironment can damage the reparative ability of KSCs. It may result in a decreased of recovery capability of renal tubules from injury.

Long-term survival in a patient with node-positive adult-onset Xp11.2 translocation renal cell carcinoma.

PubMed

Aoyagi, Toshiki; Shinohara, Nobuo; Kubota-Chikai, Kanako; Kuroda, Naoto; Nonomura, Katsuya

2011-01-01

Adult-onset Xp11.2 translocation renal cell carcinoma is a rare malignancy that has an aggressive clinical course and poor prognosis. The reasons for this include the fact that most patients have an advanced clinical stage at diagnosis and also that there is a lack of effective systemic therapy. We herein present the case of a 32-year-old woman suffering from node-positive Xp11.2 translocation renal cell carcinoma who underwent radical nephrectomy with an extensive retroperitoneal lymph node dissection, followed by two times of surgical resection for recurrent nodal disease. The patient has experienced no recurrent disease 4.5 years after the last operation and remains free of disease. Surgical approach to recurrent disease, if the recurrent site can be judged to be limited, might be one of the feasible treatment options in patients with Xp11.2 translocation renal cell carcinoma. Copyright © 2011 S. Karger AG, Basel.

Ochratoxin a and mitotic disruption: mode of action analysis of renal tumor formation by ochratoxin A.

PubMed

Mally, Angela

2012-06-01

The mycotoxin and food contaminant ochratoxin A (OTA) is a potent renal carcinogen in rodents, but its mode of action (MoA) is still poorly defined. In 2006, the European Food Safety Authority concluded that there is a "lack of evidence for the existence of OTA-DNA adducts" and thus insufficient evidence to establish DNA reactivity as a MoA for tumor formation by OTA. In reviewing the available database on OTA toxicity, a MoA for renal carcinogenicity of OTA is developed that involves a combination of genetic instability and increased proliferative drive as consequences of OTA-mediated disruption of mitosis, whereby the organ- and site-specificity of tumor formation by OTA is determined by selective renal uptake of OTA into the proximal tubule epithelium. The proposed MoA is critically assessed with respect to concordance of dose-response of the suggested key events and tumor formation, their temporal association, consistency, and biological plausibility. Uncertainties, data gaps and needs for further research are highlighted.

Renal denervation for resistant hypertension and beyond.

PubMed

Laffin, Luke J; Bakris, George L

2015-03-01

Despite the availability of more than 125 approved antihypertensive medications, 36 million (48%) of 75 million people with hypertension, including 16 million treated with antihypertensive medications in the United States, do not achieve guideline blood pressure goals known to reduce cardiovascular morbidity and mortality and progression of kidney disease; 3% to 6% of these 75 million hypertensive individuals are estimated to have resistant hypertension. A major contributing factor for poor blood pressure control, besides inadequate diuretic therapy, is failure of antihypertensive agents to inhibit the sympathetic nervous system effectively. Consequently, alternative device-driven approaches have been developed. Recent technical advances targeting renal sympathetic nerves, that is, renal denervation therapy, are the focus of more invasive therapies to treat resistant hypertension. Encouraging results from the SYMPLICITY HTN-2 trial, regarding efficacy and safety of renal denervation therapy, were countered by disappointing efficacy results of SYMPLICITY HTN-3. Reasons for these divergent results and the future of the field are discussed. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

WT1 controls antagonistic FGF and BMP-pSMAD pathways in early renal progenitors.

PubMed

Motamedi, Fariba Jian; Badro, Danielle A; Clarkson, Michael; Lecca, M Rita; Bradford, Stephen T; Buske, Fabian A; Saar, Kathrin; Hübner, Norbert; Brändli, André W; Schedl, Andreas

2014-07-17

Kidney organogenesis requires the tight control of proliferation, differentiation and apoptosis of renal progenitor cells. How the balance between these cellular decisions is achieved remains elusive. The Wilms' tumour suppressor Wt1 is required for progenitor survival, but the molecular cause for renal agenesis in mutants is poorly understood. Here we demonstrate that lack of Wt1 abolishes fibroblast growth factor (FGF) and induces BMP/pSMAD signalling within the metanephric mesenchyme. Addition of recombinant FGFs or inhibition of pSMAD signalling rescues progenitor cell apoptosis induced by the loss of Wt1. We further show that recombinant BMP4, but not BMP7, induces an apoptotic response within the early kidney that can be suppressed by simultaneous addition of FGFs. These data reveal a hitherto unknown sensitivity of early renal progenitors to pSMAD signalling, establishes FGF and pSMAD signalling as antagonistic forces in early kidney development and places WT1 as a key regulator of pro-survival FGF signalling pathway genes.

Response of urinary liver-type fatty acid-binding protein to contrast media administration has a potential to predict one-year renal outcome in patients with ischemic heart disease.

PubMed

Fujita, Daishi; Takahashi, Masao; Doi, Kent; Abe, Mitsuru; Tazaki, Junichi; Kiyosue, Arihiro; Myojo, Masahiro; Ando, Jiro; Fujita, Hideo; Noiri, Eisei; Sugaya, Takeshi; Hirata, Yasunobu; Komuro, Issei

2015-05-01

Urinary liver-type fatty acid-binding proteins (uL-FABP) have recently been recognized as a useful biomarker for predicting contrast-induced nephropathy. Although accumulating studies have evaluated short-term outcomes, its prognostic value for long-term renal prognosis in patients undergoing coronary angiography (CAG) has not been fully examined. This study aimed to evaluate the predictive value of uL-FABP for long-term renal outcome in patients with ischemic heart disease (IHD). Consecutive 24 patients with impaired renal function (serum creatinine >1.2 mg/dL) who underwent CAG were enrolled. uL-FABP was measured before CAG, 24 and 48 h after CAG. The changes in estimated glomerular filtration rate (eGFR) throughout CAG and at 1 year later were compared with the uL-FABP levels. The patients with a greater decrease in eGFR 1 year later had higher uL-FABP levels at all points, but only the value at 48 h after CAG reached statistical significance (lower vs. higher decreased eGFR group, 4.61 ± 3.87 vs. 17.71 ± 12.96; P < 0.01). Measurement of uL-FABP at 48 h after CAG (48h-uL-FABP) showed better correlation with the change in eGFR (pre-CAG uL-FABP vs. 48h-uL-FABP: R = 0.27, P = 0.20 vs. R = 0.65, P < 0.01). Moreover, the high-pre and high-48h-uL-FABP group showed a significantly larger decrease in eGFR compared with the high-pre and low-48h-uL-FABP group (change in eGFR; 8.12 ± 4.06 vs. 1.25 ± 2.23 mL/min/1.73 m2, P < 0.01), although the baseline eGFR levels were similar between these two groups. In this pilot study, measurement of uL-FABP levels at 48 h after CAG may be useful in detecting renal damage, and in predicting 1-year renal outcome in IHD patients undergoing CAG.

Prognostic value of renal fractional flow reserve in blood pressure response after renal artery stenting (PREFER study).

PubMed

Kądziela, Jacek; Januszewicz, Andrzej; Prejbisz, Aleksander; Michałowska, Ilona; Januszewicz, Magdalena; Florczak, Elżbieta; Kalińczuk, Łukasz; Norwa-Otto, Bożena; Warchoł, Ewa; Witkowski, Adam

2013-01-01

The aim of our study was to determine a potential relationship between resting translesional pressures ratio (Pd/Pa ratio), renal fractional flow reserve (rFFR) and blood pressure response after renal artery stenting. Thirty five hypertensive patients (49% males, mean age 64 years) with at least 60% stenosis in angiography, underwent renal artery stenting. Translesional systolic pressure gradient (TSPG), Pd/Pa ratio (the ratio of mean distal to lesion and mean proximal pressures) and hyperemic rFFR - after intrarenal administration of papaverine - were measured before stent implantation. Ambulatory blood pressure measurements (ABPM) were recorded before the procedure and after 6 months. The ABPM results were presented as blood pressure changes in subgroups of patients with normal (≥ 0.9) vs. abnormal (< 0.9) Pd/Pa ratio and normal (≥ 0.8) vs. abnormal (< 0.8) rFFR. Median Pd/Pa ratio was 0.84 (interquartile range 0.79-0.91) and strongly correlated with TSPG (r = -0.89, p < 0.001), minimal lumen diameter (MLD; r = 0.53, p < 0.005) and diameter stenosis (DS; r = -0.51, p < 0.005). Median rFFR was 0.78 (0.72-0.82). Similarly, significant correlation between rFFR and TSPG (r = -0.86, p < 0.0001), as well as with MLD (r = 0.50, p < 0.005) and DS (r = -0.51, p < 0.005) was observed. Procedural success was obtained in all patients. Baseline Pd/Pa ratio and rFFR did not predict hypertension response after renal artery stenting. Median changes of 24-h systolic/diastolic blood pressure were comparable in patients with abnormal vs. normal Pd/Pa ratio (-4/-3 vs. 0/2 mm Hg; p = NS) and with abnormal vs. normal rFFR (-2/-1 vs. -2/-0.5 mm Hg, respectively). Physiological assessment of renal artery stenosis using Pd/Pa ratio and papaverine- induced renal fractional fl ow reserve did not predict hypertension response after renal artery stenting.

Deregulation of E2-EPF Ubiquitin Carrier Protein in Papillary Renal Cell Carcinoma

PubMed Central

Roos, Frederik C.; Evans, Andrew J.; Brenner, Walburgis; Wondergem, Bill; Klomp, Jeffery; Heir, Pardeep; Roche, Olga; Thomas, Christian; Schimmel, Heiko; Furge, Kyle A.; Teh, Bin T.; Thüroff, Joachim W.; Hampel, Christian; Ohh, Michael

2011-01-01

Molecular pathways associated with pathogenesis of sporadic papillary renal cell carcinoma (PRCC), the second most common form of kidney cancer, are poorly understood. We analyzed primary tumor specimens from 35 PRCC patients treated by nephrectomy via gene expression analysis and tissue microarrays constructed from an additional 57 paraffin-embedded PRCC samples via immunohistochemistry. Gene products were validated and further studied by Western blot analyses using primary PRCC tumor samples and established renal cell carcinoma cell lines, and potential associations with pathologic variables and survival in 27 patients with follow-up information were determined. We show that the expression of E2-EPF ubiquitin carrier protein, which targets the principal negative regulator of hypoxia-inducible factor (HIF), von Hippel-Lindau protein, for proteasome-dependent degradation, is markedly elevated in the majority of PRCC tumors exhibiting increased HIF1α expression, and is associated with poor prognosis. In addition, we identified multiple hypoxia-responsive elements within the E2-EPF promoter, and for the first time we demonstrated that E2-EPF is a hypoxia-inducible gene directly regulated via HIF1. These findings reveal deregulation of the oxygen-sensing pathway impinging on the positive feedback mechanism of HIF1-mediated regulation of E2-EPF in PRCC. PMID:21281817

Serotonin levels in platelet-poor plasma and whole blood in people with type 2 diabetes with chronic kidney disease.

PubMed

Hara, Katsuko; Hirowatari, Yuji; Shimura, Yuko; Takahashi, Hakuo

2011-11-01

Patients with diabetes mellitus (DM) are prone to atherosclerosis. Atherosclerosis activates platelets; activated platelets release serotonin, and therefore, evaluation of serotonin levels in blood could be a valuable biomarker for future risk of cardiovascular events. Plasma serotonin levels obtained from patients with DM complicated with chronic kidney disease were measured using HPLC and were compared to serotonin levels of healthy control subjects. Patients with DM were classified into 2 subgroups of mildly (group 1) and moderately/severely (group 2) impaired renal function. Serotonin concentration in platelet-poor plasma for group 1 was significantly higher than that of healthy control subjects (p < 0.01), and was significantly higher than that of patients from group 2 (p < 0.05). The concentration of serotonin in whole blood for group 2 patients was significantly lower than that measured from healthy control subjects (p < 0.01). The ratio of the plasma to whole blood level was significantly elevated in both groups 1 and 2 compared with healthy controls (p < 0.01). Our results indicate that platelets are activated to release serotonin into plasma in diabetic patients with mildly impaired renal function. When renal damage is advanced, platelets are over-activated to release serotonin. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Population pharmacokinetic–pharmacodynamic analysis for sugammadex-mediated reversal of rocuronium-induced neuromuscular blockade

PubMed Central

Kleijn, Huub J; Zollinger, Daniel P; van den Heuvel, Michiel W; Kerbusch, Thomas

2011-01-01

AIMS An integrated population pharmacokinetic–pharmacodynamic model was developed with the following aims: to simultaneously describe pharmacokinetic behaviour of sugammadex and rocuronium; to establish the pharmacokinetic–pharmacodynamic model for rocuronium-induced neuromuscular blockade and reversal by sugammadex; to evaluate covariate effects; and to explore, by simulation, typical covariate effects on reversal time. METHODS Data (n = 446) from eight sugammadex clinical studies covering men, women, non-Asians, Asians, paediatrics, adults and the elderly, with various degrees of renal impairment, were used. Modelling and simulation techniques based on physiological principles were applied to capture rocuronium and sugammadex pharmacokinetics and pharmacodynamics and to identify and quantify covariate effects. RESULTS Sugammadex pharmacokinetics were affected by renal function, bodyweight and race, and rocuronium pharmacokinetics were affected by age, renal function and race. Sevoflurane potentiated rocuronium-induced neuromuscular blockade. Posterior predictive checks and bootstrapping illustrated the accuracy and robustness of the model. External validation showed concordance between observed and predicted reversal times, but interindividual variability in reversal time was pronounced. Simulated reversal times in typical adults were 0.8, 1.5 and 1.4 min upon reversal with sugammadex 16 mg kg−1 3 min after rocuronium, sugammadex 4 mg kg−1 during deep neuromuscular blockade and sugammadex 2 mg kg−1 during moderate blockade, respectively. Simulations indicated that reversal times were faster in paediatric patients and slightly slower in elderly patients compared with adults. Renal function did not affect reversal time. CONCLUSIONS Simulations of the therapeutic dosing regimens demonstrated limited impact of age, renal function and sevoflurane use, as predicted reversal time in typical subjects was always <2 min. PMID:21535448

Soluble CD30 does not predict late acute rejection or safe tapering of immunosuppression in renal transplantation.

PubMed

Valke, Lars L F G; van Cranenbroek, Bram; Hilbrands, Luuk B; Joosten, Irma

2015-01-01

Previous reports revealed the potential value of the soluble CD30 level (sCD30) as biomarker for the risk of acute rejection and graft failure after renal transplantation, here we examined its use for the prediction of safe tapering of calcineurin inhibitors as well as late acute rejection. In a cohort of renal transplant patients receiving triple immunosuppressive therapy we examined whether sCD30 can be used as a marker for safe (rejection-free) discontinuation of tacrolimus at six months after transplantation (TDS cohort: 24 rejectors and 44 non-rejecting controls). Also, in a second cohort of patients (n=22, rejectors n=11 and non-rejectors n=11), participating in a clinical trial of rituximab as induction therapy after renal transplantation (RITS cohort), we examined whether sCD30 could predict the occurrence of late (>3months post-transplant) acute rejection episodes. sCD30 was measured by ELISA in serum taken before and at several time points after transplantation. Overall, in the TDS cohort sCD30 decreased after transplantation. No difference in sCD30 was observed between rejectors and non-rejecting controls at any of the time points measured. In addition, in the RITS cohort, sCD30 measured at three months after transplantation were not indicative for the occurrence of late acute rejection. In two prospectively followed cohorts of renal transplant patients we found no association between sCD30 and the occurrence of either late acute rejection or acute rejection after reduction of immunosuppression. Copyright © 2014 Elsevier B.V. All rights reserved.

Serum creatinine can be used as a surrogate for glomerular filtration rate in single renal unit models.

PubMed

Gofrit, Ofer N; Orvieto, Marcelo A; Zorn, Kevin C; Steinberg, Gary D; Zagaja, Gregory P; Shalhav, Arieh L

2009-02-01

Single renal unit models are invaluable for studies in renal physiology, transplantation and response to ischemic injury. Glomerular filtration rate (GFR) is commonly used for evaluation of renal function. Measuring the GFR involves relatively complicated and expensive systems. In this study we determined whether serum creatinine (Scr) can predict the GFR in this model. Right laparoscopic nephrectomy was performed in 46 female pigs weighing 25 kg-30 kg. Twelve days later the left kidney was exposed to various periods of warm ischemia (30, 60, 90, and 120 minutes). Scr and GFR (using the iohexol clearance method) were determined preoperatively and at postoperative days 1, 3, 8, 15, 22 and 29. A total of 244 pairs of Scr and GFR values were analyzed to determine a formula for predicting GFR (pGFR) from Scr. Scr range was 1.2 mg/dl -29 mg/dl and GFR range was 1.8 ml/min -180.5 ml/min. The empiric formula deduced from the database for calculating pGFR from Scr was: pGFR = (217 divided by Scr) minus 0.2. pGFR correlated well with the actual GFR (R(2) = 0.85). The graphs for pGFR were almost indistinguishable from the graphs for actual GFR in every single animal. The results and conclusions of the experiments using either actual or predicted GFR were identical. We conclude that in a single renal unit porcine model using ischemia as the insult to the kidney, expensive actual measurements of GFR can be reliably replaced by Scr based calculated GFR.

A quantitative systems physiology model of renal function and blood pressure regulation: Model description.

PubMed

Hallow, K M; Gebremichael, Y

2017-06-01

Renal function plays a central role in cardiovascular, kidney, and multiple other diseases, and many existing and novel therapies act through renal mechanisms. Even with decades of accumulated knowledge of renal physiology, pathophysiology, and pharmacology, the dynamics of renal function remain difficult to understand and predict, often resulting in unexpected or counterintuitive therapy responses. Quantitative systems pharmacology modeling of renal function integrates this accumulated knowledge into a quantitative framework, allowing evaluation of competing hypotheses, identification of knowledge gaps, and generation of new experimentally testable hypotheses. Here we present a model of renal physiology and control mechanisms involved in maintaining sodium and water homeostasis. This model represents the core renal physiological processes involved in many research questions in drug development. The model runs in R and the code is made available. In a companion article, we present a case study using the model to explore mechanisms and pharmacology of salt-sensitive hypertension. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

A survey of views and practice patterns of dialysis medical directors toward end-of-life decision making for patients with end-stage renal disease.

PubMed

Fung, Enrica; Slesnick, Nate; Kurella Tamura, Manjula; Schiller, Brigitte

2016-07-01

Patients with end-stage renal disease report infrequent end-of-life discussions, and nephrology trainees report feeling unprepared for end-of-life decision making, but the views of dialysis medical directors have not been studied. Our objective is to understand dialysis medical directors' views and practice patterns on end-of-life decision making for patients with ESRD. We administered questionnaires to dialysis medical directors during medical director meetings of three different dialysis organizations in 2013. Survey questions corresponded to recommendations from the Renal Physicians Association clinical practice guidelines on initiation and withdrawal of dialysis. There were 121 medical director respondents from 28 states. The majority of respondents felt "very prepared" (66%) or "somewhat prepared" (29%) to participate in end-of-life decisions and most (80%) endorsed a model of shared decision making. If asked to do so, 70% of the respondents provided prognostic information "often" or "nearly always." For patients with a poor prognosis, 36% of respondents would offer a time-limited trial of dialysis "often" or "nearly always", while 56% of respondents would suggest withdrawal from dialysis "often" or "nearly always" for those with a poor prognosis currently receiving dialysis therapy. Patient resistance and fear of taking away hope were the most commonly cited barriers to end-of-life discussions. Views and reported practice patterns of medical directors are consistent with clinical practice guidelines for end-of-life decision making for patients with end-stage renal disease but inconsistent with patient perceptions. © The Author(s) 2016.

Combined use of late phase dimercapto-succinic acid renal scintigraphy and ultrasound as first line screening after urinary tract infection in children.

PubMed

Quirino, Isabel G; Silva, Jose Maria P; Diniz, Jose S; Lima, Eleonora M; Rocha, Ana Cristina S; Simões e Silva, Ana Cristina; Oliveira, Eduardo A

2011-01-01

The aim of this study was to evaluate the diagnostic accuracy of dimercapto-succinic acid renal scintigraphy and renal ultrasound in identifying high grade vesicoureteral reflux in children after a first episode of urinary tract infection. A total of 533 children following a first urinary tract infection were included in the analysis. Patients were assessed by 3 diagnostic imaging studies, renal ultrasound, dimercapto-succinic acid scan and voiding cystourethrography. The main event of interest was the presence of high grade (III to V) vesicoureteral reflux. The combined and separate diagnostic accuracy of screening methods was assessed by calculation of diagnostic OR, sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio. A total of 246 patients had reflux, of whom 144 (27%) had high grade (III to V) disease. Sensitivity, negative predictive value and diagnostic OR of ultrasound for high grade reflux were 83.3%, 90.8% and 7.9, respectively. Dimercapto-succinic acid scan had the same sensitivity as ultrasound but a higher negative predictive value (91.7%) and diagnostic OR (10.9). If both tests were analyzed in parallel by using the OR rule, ie a negative diagnosis was established only when both test results were normal, sensitivity increased to 97%, negative predictive value to 97% and diagnostic OR to 25.3. Only 9 children (6.3%) with dilating reflux had an absence of alterations in both tests. Our findings support the idea that ultrasound and dimercapto-succinic acid scan used in combination are reliable predictors of dilating vesicoureteral reflux. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Severe post-renal acute kidney injury, post-obstructive diuresis and renal recovery.

PubMed

Hamdi, Aïcha; Hajage, David; Van Glabeke, Emmanuel; Belenfant, Xavier; Vincent, François; Gonzalez, Frédéric; Ciroldi, Magali; Obadia, Edouard; Chelha, Riad; Pallot, Jean-Louis; Das, Vincent

2012-12-01

Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The pathophysiology of post-renal acute kidney injury (PR-AKI), i.e. caused by urinary tract obstruction, has been extensively studied in animal models but clinical studies on this subject are outdated, and/or have focused on the mechanisms of 'post-obstructive diuresis' (POD), a potentially life-threatening polyuria that can develop after the release of obstruction. In severe PR-AKI, the risk of occurrence of POD is high. POD occurrence predicts renal recovery without the persistence of severe chronic kidney failure. In the present study, the occurrence of POD and the persistence of chronic renal sequelae could be predicted early from clinical variables at admission before the release of obstruction. • To identify predictors of post-obstructive diuresis (POD) occurrence or severe chronic renal failure (CRF) persistence after the release of urinary tract obstruction in the setting of post-renal acute kidney injury (PR-AKI). • Bi-centre retrospective observational study of all patients with PR-AKI treated in two intensive care units (ICUs) from 1998 to 2010. • Clinical, biological and imaging characteristics on admission and after the release of obstruction were analysed with univariate and, if possible, multivariate analysis to search for predictors of (i) occurrence of POD (diuresis >4 L/day) after the release of obstruction; (ii) persistence of severe CRF (estimated glomerular filtration rate <30 mL/min/1.73 m(2), including end-stage CRF) at 3 months. • On admission, median (range) serum creatinine was 866 (247-3119) µmol/L. • POD occurred in 34 (63%) of the 54 analysable patients. On admission, higher serum creatinine (Odds ratio [OR] 1.002 per 1 µmol/L, 95% confidence interval [CI] 1.000-1.004, P = 0.004), higher serum bicarbonate (OR 1.36 per 1 mmol/L, 95% CI 1.13-1.65, P < 0.001), and urinary retention (OR 6.96, 95% CI 1.34-36.23, P = 0.01) independently predicted POD occurrence. • Severe CRF persisted in seven (21%) of the 34 analysable patients, including two (6%) cases of end-stage CRF. Predictors of severe CRF persistence after univariate analysis were: lower blood haemoglobin (P < 0.001) and lower serum bicarbonate (P = 0.03) on admission, longer time from admission to the release of obstruction (P = 0.01) and absence of POD (P = 0.04) after the release of obstruction. • In severe PR-AKI treated in ICU, POD occurrence was a frequent event that predicted renal recovery without severe CRF. • POD occurrence or severe CRF persistence could be predicted early from clinical and biological variables at admission before the release of obstruction. © 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.

Quantitative computer-aided diagnostic algorithm for automated detection of peak lesion attenuation in differentiating clear cell from papillary and chromophobe renal cell carcinoma, oncocytoma, and fat-poor angiomyolipoma on multiphasic multidetector computed tomography.

PubMed

Coy, Heidi; Young, Jonathan R; Douek, Michael L; Brown, Matthew S; Sayre, James; Raman, Steven S

2017-07-01

To evaluate the performance of a novel, quantitative computer-aided diagnostic (CAD) algorithm on four-phase multidetector computed tomography (MDCT) to detect peak lesion attenuation to enable differentiation of clear cell renal cell carcinoma (ccRCC) from chromophobe RCC (chRCC), papillary RCC (pRCC), oncocytoma, and fat-poor angiomyolipoma (fp-AML). We queried our clinical databases to obtain a cohort of histologically proven renal masses with preoperative MDCT with four phases [unenhanced (U), corticomedullary (CM), nephrographic (NP), and excretory (E)]. A whole lesion 3D contour was obtained in all four phases. The CAD algorithm determined a region of interest (ROI) of peak lesion attenuation within the 3D lesion contour. For comparison, a manual ROI was separately placed in the most enhancing portion of the lesion by visual inspection for a reference standard, and in uninvolved renal cortex. Relative lesion attenuation for both CAD and manual methods was obtained by normalizing the CAD peak lesion attenuation ROI (and the reference standard manually placed ROI) to uninvolved renal cortex with the formula [(peak lesion attenuation ROI - cortex ROI)/cortex ROI] × 100%. ROC analysis and area under the curve (AUC) were used to assess diagnostic performance. Bland-Altman analysis was used to compare peak ROI between CAD and manual method. The study cohort comprised 200 patients with 200 unique renal masses: 106 (53%) ccRCC, 32 (16%) oncocytomas, 18 (9%) chRCCs, 34 (17%) pRCCs, and 10 (5%) fp-AMLs. In the CM phase, CAD-derived ROI enabled characterization of ccRCC from chRCC, pRCC, oncocytoma, and fp-AML with AUCs of 0.850 (95% CI 0.732-0.968), 0.959 (95% CI 0.930-0.989), 0.792 (95% CI 0.716-0.869), and 0.825 (95% CI 0.703-0.948), respectively. On Bland-Altman analysis, there was excellent agreement of CAD and manual methods with mean differences between 14 and 26 HU in each phase. A novel, quantitative CAD algorithm enabled robust peak HU lesion detection and discrimination of ccRCC from other renal lesions with similar performance compared to the manual method.

Serum creatinine role in predicting outcome after cardiac surgery beyond acute kidney injury

PubMed Central

Najafi, Mahdi

2014-01-01

Serum creatinine is still the most important determinant in the assessment of perioperative renal function and in the prediction of adverse outcome in cardiac surgery. Many biomarkers have been studied to date; still, there is no surrogate for serum creatinine measurement in clinical practice because it is feasible and inexpensive. High levels of serum creatinine and its equivalents have been the most important preoperative risk factor for postoperative renal injury. Moreover, creatinine is the mainstay in predicting risk models and risk factor reduction has enhanced its importance in outcome prediction. The future perspective is the development of new definitions and novel tools for the early diagnosis of acute kidney injury largely based on serum creatinine and a panel of novel biomarkers. PMID:25276301

ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse.

PubMed

Göçeroğlu, Arda; Berden, Annelies E; Fiocco, Marta; Floßmann, Oliver; Westman, Kerstin W; Ferrario, Franco; Gaskin, Gill; Pusey, Charles D; Hagen, E Christiaan; Noël, Laure-Hélène; Rasmussen, Niels; Waldherr, Rüdiger; Walsh, Michael; Bruijn, Jan A; Jayne, David R W; Bajema, Ingeborg M

2016-01-01

Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild-moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray's regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8-14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray's model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different.

ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse

PubMed Central

Göçeroğlu, Arda; Berden, Annelies E.; Fiocco, Marta; Floßmann, Oliver; Westman, Kerstin W.; Ferrario, Franco; Gaskin, Gill; Pusey, Charles D.; Hagen, E. Christiaan; Noël, Laure-Hélène; Rasmussen, Niels; Waldherr, Rüdiger; Walsh, Michael; Bruijn, Jan A.; Jayne, David R. W.; Bajema, Ingeborg M.

2016-01-01

Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild–moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray’s regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8–14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray’s model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different. PMID:27973575

What are the implications of the spontaneous spleno-renal shunts in liver cirrhosis?

PubMed Central

2009-01-01

Background Although significant advances are expected to be made in the assessment of the portal hypertension-related complications, the prognostic role of spleno-renal shunts has not been fully explored so far. Clarifying this aspect could help tackle the life-treating events occurring in patients suffering from liver cirrhosis. The aim of the study was to analyze the relationships between the spleno-renal shunts presence at doppler ultrasound and the liver cirrhosis complications. Methods Design: eighty one patients out of 129 formed the study population (35 females). Chronic liver damage in these patients was caused by HCV (66), HBV (2), alcohol abuse (2) or unknown etiology, likely non-alcoholic steatohepatitis (11). Setting: two Liver Units of university/primary hospitals in Southern Italy. Main outcome measures: grading of esofageal varices; detection of ascites: assessment of hepatic encephalopathy; evaluation of liver cirrhosis severity; tracking hepatocellular carcinoma; doppler features of spleno-renal shunts and splenic flow velocity; spleen longitudinal diameter at sonography. Results The prevalence of spleno-renal shunts was 18.5%, without no difference concerning the etiology (HCV versus non-HCV, p = 0.870); the prevalence of hepatocellular carcinoma in patients with spleno-renal shunts was superior to that of patients without them (Pearson Chi-square, p = 0.006, power of sample size 74%), also after adjustment for liver decompensation (p = 0.024). The median score of hepatic encephalopathy in patients with and without spleno-renal shunts was similar, i.e., 0 (range, 0-2) versus 0 (0 - 3), p = 0.67. The median splenic vein flow velocity in patients with spleno-renal shunts was significantly inferior to that of patients without them, i.e., 13 cm/sec (95% confidence intervals, 6-18) versus 21 cm/sec (17-24), p < 0.0001. By far the largest percentage of large esophageal varices was in patients without spleno-renal shunts (p = 0.005). In contrast, the frequency of ascites and hepatic encephalopathy severity was overlapping in the two groups. BMI values but not Child-Pugh's classification predicted spleno-renal shunts (Ors = 1.84, 95% confidence intervals = 1.28-2.64, p = 0.001 and 1.145, 95% confidence intervals = 0.77-1.51, p = 0.66). Conclusion Taking into consideration the relatively small sample size, patients with spleno-renal shunts are burdened by an increased incidence of hepatocellular carcinoma. BMI predicted the spleno-renal shunts presence. PMID:19930687

Can quantity of amniotic fluid reliably predict postnatal renal function in boys with posterior urethral valves: a decision curve analysis.

PubMed

Harper, Luke; Waubant, Alice; Vignes, Julien; Amat, Sara; Dobremez, Eric; Lefevre, Yan; Ferdynus, Cyril

2017-09-01

Prenatal management of male fetuses with suspected posterior urethral valves depends on reliable markers for postnatal long-term renal function. Whether ultrasound parameters, including the presence or absence of oligohydramnios, are reliable remains the subject of debate. We decided to evaluate the reliability of quantity of amniotic fluid to predict postnatal renal function using decision curve analysis (DCA), a method for evaluating the clinical utility of a diagnostic test. We analyzed retrospectively 51 male fetuses born with prenatally suspected posterior urethral valves between 2009 and 2012. We studied the relationship between quantity of amniotic fluid on prenatal ultrasound and the nadir creatinine during the first year of life as a proxy of postnatal renal function using DCA. Twelve fetuses presented with prenatal oligohydramnios. Thirty-one children had a normal nadir creatinine, of which one had prenatal oligohydramnios (3.2%). Thirteen had a nadir creatinine between 35 and 75 μmol/L, of which four had prenatal oligohydramnios (30.8%). Seven had a nadir creatinine >75 μmol/L, all of them had prenatal oligohydramnios. In this retrospective study, DCA confirms the relationship between prenatal quantity of amniotic fluid volume and postnatal renal function. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mann, S.J.; Pickering, T.G.; Sos, T.A.

The purpose of this study was to determine the sensitivity, specificity, and clinical usefulness of renography performed in combination with captopril administration (captopril renography) in diagnosing renal artery stenosis. Fifty-five patients with suspected renal artery stenosis underwent renography prior to performance of renal angiography. Renography was performed on two consecutive days using technetium-99m-diethylenetiamine pentaacetic acid (DTPA) as an index of glomerular filtration rate and iodine-131-orthoiodohippurate (OIH) as an index of renal blood flow. Captopril (25 mg orally, crushed) was administered 1 hour before the second study. Renal artery stenosis was defined as a stenosis exceeding 70%. Renographic criteria were thenmore » established, retrospectively, to differentiate renal artery stenosis from essential hypertension based on (1) asymmetry of function and (2) the presence of captopril-induced changes. Renal artery stenosis was detected in 35 of 55 patients (21 with unilateral and 14 with bilateral stenosis). Three criteria were established for diagnosing renal artery stenosis: (1) a percent uptake of DTPA by the affected kidney of less than 40% of the combined bilateral uptake, (2) a delayed time to peak uptake of DTPA, which was more than 5 minutes longer in the affected kidney than in the contralateral kidney, (3) a delayed excretion of DTPA, with retention at 15 minutes, as a fraction of peak activity, more than 20% greater than in the contralateral kidney. The presence of one or more of these criteria was diagnostic of renal artery stenosis, with a sensitivity and specificity of 71% and 75%, respectively before captopril administration, and 94% and 95% after captopril administration. Lesser degrees of asymmetry (i.e., uptake of 40% to 50%) had very poor diagnostic specificity.« less

Activated renal tubular Wnt/β-catenin signaling triggers renal inflammation during overload proteinuria.

PubMed

Wong, Dickson W L; Yiu, Wai Han; Chan, Kam Wa; Li, Ye; Li, Bin; Lok, Sarah W Y; Taketo, Makoto M; Igarashi, Peter; Chan, Loretta Y Y; Leung, Joseph C K; Lai, Kar Neng; Tang, Sydney C W

2018-06-01

Imbalance of Wnt/β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect. Therefore, to identify the definitive role of tubular Wnt/β-catenin, we generated a novel transgenic "Tubcat" mouse conditionally expressing stabilized β-catenin specifically in renal tubules following tamoxifen administration. Four weeks after tamoxifen injection, uninephrectomized Tubcat mice displayed proteinuria and elevated blood urea nitrogen levels compared to non-transgenic mice, implying a detrimental effect of the activated signaling. This was associated with infiltration of the tubulointerstitium predominantly by M1 macrophages and overexpression of the inflammatory chemocytokines CCL-2 and RANTES. Induction of overload proteinuria by intraperitoneal injection of low-endotoxin bovine serum albumin following uninephrectomy for four weeks aggravated proteinuria and increased blood urea nitrogen levels to a significantly greater extent in Tubcat mice. Renal dysfunction correlated with the degree of M1 macrophage infiltration in the tubulointerstitium and renal cortical up-regulation of CCL-2, IL-17A, IL-1β, CXCL1, and ICAM-1. There was overexpression of cortical TLR-4 and NLRP-3 in Tubcat mice, independent of bovine serum albumin injection. Finally, there was no fibrosis, activation of epithelial-mesenchymal transition or non-canonical Wnt pathways observed in the kidneys of Tubcat mice. Thus, conditional activation of renal tubular Wnt/β-catenin signaling in a novel transgenic mouse model demonstrates that this pathway enhances intrarenal inflammation via the TLR-4/NLRP-3 inflammasome axis in overload proteinuria. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Percutaneous renal sympathetic nerve ablation for loin pain haematuria syndrome.

PubMed

Gambaro, Giovanni; Fulignati, Pierluigi; Spinelli, Alessio; Rovella, Valentina; Di Daniele, Nicola

2013-09-01

Loin pain haematuria syndrome (LPHS) is a severe renal pain condition of uncertain origin and often resistant to treatment. Nephrectomy and renal autotrasplantation have occasionally been performed in very severe cases. Its pathogenesis is controversial. A 40-year-old hypertensive lady was diagnosed with LPHS after repeated diagnostic imaging procedures had ruled out any renal, abdominal or spinal conditions to justify pain. Notwithstanding treatment with three drugs, she had frequent hypertensive crises during which the loin pain was dramatically exacerbated. Vascular causes of the pain and hypertension were investigated and excluded. Her renal function was normal. The patient was referred to a multidisciplinary pain clinic, but had no significant improvement in her pain symptoms despite the use of non-steroidal anti-inflammatory drugs, adjuvant antidepressants and opioid-like agents. The pain and the discomfort were so severe that her quality of life was very poor, and her social and professional activities were compromised. Nephrectomy and renal autotransplantation have occasionally been performed in these cases. Since visceral pain signals flow through afferent sympathetic fibres, we felt that percutaneous catheter-based radiofrequency ablation of the renal sympathetic nerve fibres (recently introduced for the treatment of drug-resistant hypertension) could be valuable for pain relief. We treated the patient with radiofrequency ablation (Medtronic Symplicity Catheter) applied only to the right renal artery. After a 6-month follow-up, the patient is pain free and normotensive with all drugs withdrawn. She has experienced no hypertensive crises in the meantime. This observation suggests that percutaneous sympathetic denervation could prove to be an effective mini-invasive strategy for the treatment of chronic renal pain, and LPHS in particular.

Compliance in peritoneal dialysis: a qualitative study of renal nurses.

PubMed

McCarthy, Alexandra; Cook, Peta S; Fairweather, Carrie; Shaban, Ramon; Martin-McDonald, Kristine

2009-06-01

End-stage renal failure is a life-threatening condition, often treated with home-based peritoneal dialysis (PD). PD is a demanding regimen, and the patients who practise it must make numerous lifestyle changes and learn complicated biomedical techniques. In our experience, the renal nurses who provide most PD education frequently express concerns that patient compliance with their teaching is poor. These concerns are mirrored in the renal literature. It has been argued that the perceived failure of health professionals to improve compliance rates with PD regimens is because 'compliance' itself has never been adequately conceptualized or defined; thus, it is difficult to operationalize and quantify. This paper examines how a group of Australian renal nurses construct patient compliance with PD therapy. These empirical data illuminate how PD compliance operates in one practice setting; how it is characterized by multiple and often competing energies; and how ultimately it might be pointless to try to tame 'compliance' through rigid definitions and measurement, or to rigidly enforce it in PD patients. The energies involved are too fractious and might be better spent, as many of the more experienced nurses in this study argue, in augmenting the energies that do work well together to improve patient outcomes.

Construction of a model for predicting creatinine clearance in Japanese patients treated with Cisplatin therapy.

PubMed

Yajima, Airi; Uesawa, Yoshihiro; Ogawa, Chiaki; Yatabe, Megumi; Kondo, Naoki; Saito, Shinichiro; Suzuki, Yoshihiko; Atsuda, Kouichiro; Kagaya, Hajime

2015-05-01

There exist various useful predictive models, such as the Cockcroft-Gault model, for estimating creatinine clearance (CLcr). However, the prediction of renal function is difficult in patients with cancer treated with cisplatin. Therefore, we attempted to construct a new model for predicting CLcr in such patients. Japanese patients with head and neck cancer who had received cisplatin-based chemotherapy were used as subjects. A multiple regression equation was constructed as a model for predicting CLcr values based on background and laboratory data. A model for predicting CLcr, which included body surface area, serum creatinine and albumin, was constructed. The model exhibited good performance prior to cisplatin therapy. In addition, it performed better than previously reported models after cisplatin therapy. The predictive model constructed in the present study displayed excellent potential and was useful for estimating the renal function of patients treated with cisplatin therapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Mathematical model to estimate risk of calcium-containing renal stones

NASA Technical Reports Server (NTRS)

Pietrzyk, R. A.; Feiveson, A. H.; Whitson, P. A.

1999-01-01

BACKGROUND/AIMS: Astronauts exposed to microgravity during the course of spaceflight undergo physiologic changes that alter the urinary environment so as to increase the risk of renal stone formation. This study was undertaken to identify a simple method with which to evaluate the potential risk of renal stone development during spaceflight. METHOD: We used a large database of urinary risk factors obtained from 323 astronauts before and after spaceflight to generate a mathematical model with which to predict the urinary supersaturation of calcium stone forming salts. RESULT: This model, which involves the fewest possible analytical variables (urinary calcium, citrate, oxalate, phosphorus, and total volume), reliably and accurately predicted the urinary supersaturation of the calcium stone forming salts when compared to results obtained from a group of 6 astronauts who collected urine during flight. CONCLUSIONS: The use of this model will simplify both routine medical monitoring during spaceflight as well as the evaluation of countermeasures designed to minimize renal stone development. This model also can be used for Earth-based applications in which access to analytical resources is limited.

Presence of FoxP3+ regulatory T Cells predicts outcome of subclinical rejection of renal allografts.

PubMed

Bestard, Oriol; Cruzado, Josep M; Rama, Inés; Torras, Joan; Gomà, Montse; Serón, Daniel; Moreso, Francesc; Gil-Vernet, Salvador; Grinyó, Josep M

2008-10-01

Subclinical rejection (SCR) of renal allografts refers to histologic patterns of acute rejection despite stable renal function. The clinical approach to SCR is controversial; it would be helpful to identify biomarkers that could determine whether the identified cellular infiltrates were detrimental. For investigation of whether the presence of FoxP3+ regulatory T cells (Treg) could help determine the functional importance of tubulointerstitial infiltrates observed in 6-mo protocol biopsies, 37 cases of SCR were evaluated. The presence of FoxP3+ Treg discriminated harmless from injurious infiltrates, evidenced by independently predicting better graft function 2 and 3 yr after transplantation. Furthermore, the FoxP3+ Treg/CD3+ T cell ratio positively correlated with graft function at 2 yr after transplantation, suggesting that an increasing proportion of Treg within the global T cell infiltrate may facilitate renal engraftment; therefore, immunostaining for FoxP3+ Treg in patients with SCR on protocol biopsies may ultimately be useful to identify patients who may require alterations in their immunosuppressive regimens.

Presence of FoxP3+ Regulatory T Cells Predicts Outcome of Subclinical Rejection of Renal Allografts

PubMed Central

Bestard, Oriol; Cruzado, Josep M.; Rama, Inés; Torras, Joan; Gomà, Montse; Serón, Daniel; Moreso, Francesc; Gil-Vernet, Salvador; Grinyó, Josep M.

2008-01-01

Subclinical rejection (SCR) of renal allografts refers to histologic patterns of acute rejection despite stable renal function. The clinical approach to SCR is controversial; it would be helpful to identify biomarkers that could determine whether the identified cellular infiltrates were detrimental. For investigation of whether the presence of FoxP3+ regulatory T cells (Treg) could help determine the functional importance of tubulointerstitial infiltrates observed in 6-mo protocol biopsies, 37 cases of SCR were evaluated. The presence of FoxP3+ Treg discriminated harmless from injurious infiltrates, evidenced by independently predicting better graft function 2 and 3 yr after transplantation. Furthermore, the FoxP3+ Treg/CD3+ T cell ratio positively correlated with graft function at 2 yr after transplantation, suggesting that an increasing proportion of Treg within the global T cell infiltrate may facilitate renal engraftment; therefore, immunostaining for FoxP3+ Treg in patients with SCR on protocol biopsies may ultimately be useful to identify patients who may require alterations in their immunosuppressive regimens. PMID:18495961

Prediction of Clinical Outcomes in Prenatal Hydronephrosis: Importance of Gravity Assisted Drainage.

PubMed

Sussman, Rachael D; Blum, Emily S; Sprague, Bruce M; Majd, Massoud; Rushton, H Gil; Pohl, Hans G

2017-03-01

In infants with SFU (Society for Fetal Urology) grade 3-4 congenital hydronephrosis, 99m Tc-mercaptoacetyltriglycine diuretic renography assesses differential function and drainage half-time. We routinely also include the percent of radiotracer drained after 30 minutes of diuresis as well as after 15 minutes with the patient in the upright position. We investigated whether any 1 or more of these parameters on initial diuretic renography predicts persistent or worsening drainage parameters. Infants 6 months or younger with grade 3-4 congenital hydronephrosis who presented between January 2009 and December 2014 were identified from billing data and included in analysis if they underwent at least 1 baseline diuretic renography. Those with structural anomalies were excluded from study. Baseline and followup differential function, diuresis half-time, clearance at 30 minutes and clearance with the patient upright were abstracted and comparisons were made between those with initially indeterminate diuresis half-time who underwent pyeloplasty vs those showing spontaneous improvement. A total of 74 patients (82 renal units) with presumed ureteropelvic junction obstruction met inclusion/exclusion criteria. All 10 renal units with initial diuresis half-time less than 5 minutes resolved spontaneously and all 25 renal units with initial diuresis half-time greater than 75 minutes underwent pyeloplasty. Therefore, we defined the indeterminate group as the 47 renal units with initial half-time between 5 and 75 minutes. Of those 47 renal units with indeterminate initial diuresis half-time 23 (47%) underwent pyeloplasty and 25 (53%) resolved spontaneously. Indications for pyeloplasty included worsening in 17 cases, persistent obstruction in 4 and urinary tract infection in 1. Among renal units with indeterminate drainage clearance while upright and clearance at 30 minutes were the only variables that differed significantly between surgical cases and those that resolved spontaneously. Radiotracer clearance with the patient upright and clearance at 30 minutes are more predictive of surgical management than diuresis half-time or differential function for renal units with indeterminate drainage. They should be included in the standard assessment of ureteropelvic junction obstruction. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Renal impairment in HIV-infected patients initiating tenofovir-containing antiretroviral therapy regimens in a Primary Healthcare Setting in South Africa.

PubMed

Kamkuemah, Monika; Kaplan, Richard; Bekker, Linda-Gail; Little, Francesca; Myer, Landon

2015-04-01

Long-term use of tenofovir disoproxil fumarate is associated with declines in glomerular function and chronic kidney disease in HIV-infected patients. We aimed to assess the prevalence and incidence of renal impairment in a primary care setting in sub-Saharan Africa. We analysed data from 1092 HIV-infected patients initiating tenofovir at a primary care clinic in Cape Town, South Africa. Renal function was assessed for the first 12 months on ART by estimating glomerular filtration rate (eGFR) calculated using the Cockroft-Gault equation categorised into normal, mild, moderate and severe reduction in renal function based on values >90, 60-89, 30-59 and <30 ml/min/1.73 m(2) , respectively. Associations were assessed using logistic regression, and average GFR trajectory over time was modelled using linear mixed-effects models. The cohort consisted of 62% women; median age was 34 years (IQR 29; 41 years). The majority had normal renal function pre-ART (79%), 19% had mildly reduced GFR, and 2% had moderate renal impairment. Older age, more advanced WHO stage and anaemia were independently associated with prevalent renal impairment. On average, estimated glomerular function improved over the first year on tenofovir [1.10 ml/min/1.73 m(2) average increase over 12 months (95% CI: 0.80; 1.40)]. Male gender, anaemia and immunosuppression (WHO Stage III/IV and CD4 cell counts <100 cells/mm(3) ) were associated with lower average eGFR levels over time. Overall, 3% developed eGFR <50 ml/min/1.73 m(2) during this period. Serum creatinine tests conducted before 4 months on ART had low predictive value for predicting change in eGFR after a year on ART. Generally, renal function improved in HIV-infected adults initiating ART in this primary healthcare setting during the first year on ART. While monitoring of renal function is recommended in the first 4 months on ART, renal impairment appears uncommon during the first 12 months of tenofovir-containing ART in primary care populations. © 2014 John Wiley & Sons Ltd.

Measurement of arterial transit time and renal blood flow using pseudocontinuous ASL MRI with multiple post-labeling delays: Feasibility, reproducibility, and variation.

PubMed

Kim, Dong Won; Shim, Woo Hyun; Yoon, Seong Kuk; Oh, Jong Yeong; Kim, Jeong Kon; Jung, Hoesu; Matsuda, Tsuyoshi; Kim, Dongeun

2017-09-01

To evaluate the feasibility, reproducibility, and variation of renal perfusion and arterial transit time (ATT) using pseudocontinuous arterial spin labeling magnetic resonance imaging (PCASL MRI) in healthy volunteers. PCASL MRI at 3T was performed in 25 healthy volunteers on two different occasions. The ATT and ATT-corrected renal blood flow (ATT-cRBF) were calculated at four different post-labeling delay points (0.5, 1.0, 1.5, and 2.0 s) and evaluated for each kidney and subject. The intraclass correlation (ICC) and Bland-Altman plot were used to assess the reproducibility of the PCASL MRI technique. The within-subject coefficient of variance was determined. Results were obtained for 46 kidneys of 23 subjects with a mean age of 38.6 ± 9.8 years and estimated glomerular filtration rate (eGFR) of 89.1 ± 21.2 ml/min/1.73 m 2 . Two subjects failed in the ASL MRI examination. The mean cortical and medullary ATT-cRBF for the subjects were 215 ± 65 and 81 ± 21 ml/min/100 g, respectively, and the mean cortical and medullary ATT were 1141 ± 262 and 1123 ± 245 msec, correspondingly. The ICC for the cortical ATT-cRBF was 0.927 and the within-subject coefficient of variance was 14.4%. The ICCs for the medullary ATT-cRBF and the cortical and medullary ATT were poor. The Bland-Altman plot for cortical RBF showed good agreement between the two measurements. PCASL MRI is a feasible and reproducible method for measuring renal cortical perfusion. In contrast, ATT for the renal cortex and medulla has poor reproducibility and high variation. 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:813-819. © 2017 International Society for Magnetic Resonance in Medicine.

Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN

PubMed Central

Zaidan, Mohamad; Terrier, Benjamin; Pozdzik, Agnieszka; Frouget, Thierry; Rioux-Leclercq, Nathalie; Combe, Christian; Lepreux, Sébastien; Hummel, Aurélie; Noël, Laure-Hélène; Marie, Isabelle; Legallicier, Bruno; François, Arnaud; Huart, Antoine; Launay, David; Kaplanski, Gilles; Bridoux, Frank; Vanhille, Philippe; Makdassi, Raifah; Augusto, Jean-François; Rouvier, Philippe; Karras, Alexandre; Jouanneau, Chantal; Verpont, Marie-Christine; Callard, Patrice; Carrat, Fabrice; Hermine, Olivier; Léger, Jean-Marc; Mariette, Xavier; Senet, Patricia; Saadoun, David; Ronco, Pierre; Brochériou, Isabelle; Cacoub, Patrice

2016-01-01

Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m2. Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m2 with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death. PMID:26260165

Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN.

PubMed

Zaidan, Mohamad; Terrier, Benjamin; Pozdzik, Agnieszka; Frouget, Thierry; Rioux-Leclercq, Nathalie; Combe, Christian; Lepreux, Sébastien; Hummel, Aurélie; Noël, Laure-Hélène; Marie, Isabelle; Legallicier, Bruno; François, Arnaud; Huart, Antoine; Launay, David; Kaplanski, Gilles; Bridoux, Frank; Vanhille, Philippe; Makdassi, Raifah; Augusto, Jean-François; Rouvier, Philippe; Karras, Alexandre; Jouanneau, Chantal; Verpont, Marie-Christine; Callard, Patrice; Carrat, Fabrice; Hermine, Olivier; Léger, Jean-Marc; Mariette, Xavier; Senet, Patricia; Saadoun, David; Ronco, Pierre; Brochériou, Isabelle; Cacoub, Patrice; Plaisier, Emmanuelle

2016-04-01

Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m(2) Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m(2)with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death. Copyright © 2016 by the American Society of Nephrology.

The Predictive Role of Serum Triglyceride to High-Density Lipoprotein Cholesterol Ratio According to Renal Function in Patients with Acute Myocardial Infarction.

PubMed

Kim, Jin Sug; Kim, Weon; Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyoon; Moon, Joo Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

2016-01-01

A high serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported as an independent predictor for cardiovascular events in the general population. However, the prognostic value of this ratio in patients with renal dysfunction is unclear. We examined the association of the TG/HDL-C ratio with major adverse cardiovascular events (MACEs) according to renal function in patients with acute myocardial infarction (AMI). This study was based on the Korea Acute Myocardial Infarction Registry database. Of 13,897 patients who were diagnosed with AMI, the study population included the 7,016 patients with available TG/HDL-C ratio data. Patients were stratified into three groups according to their estimated glomerular filtration rate (eGFR), and the TG/HDL-C ratio was categorized into tertiles. We investigated 12-month MACEs, which included cardiac death, myocardial infarction, and repeated percutaneous coronary intervention or coronary artery bypass grafting. During the 12-month follow up period, 593 patients experienced MACEs. There was a significant association between the TG/HDL-C ratio and MACEs (p<0.001) in the entire study cohort. Having a TG/HDL-C ratio value in the highest tertile of TG/HDL-C ratio was an independent factor associated with increased risk of MACEs (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.26-1.93; p<0.001). Then we performed subgroup analyses according to renal function. In patients with normal renal function (eGFR ≥ 90 ml/min/1.73m2) and mild renal dysfunction (eGFR ≥ 60 to < 90ml/min/1.73m2), a higher TG/HDL-C ratio was significantly associated with increased risk of MACEs (HR, 1.64; 95% CI, 1.04-2.60; p = 0.035; and HR, 1.56; 95% CI, 1.14-2.12; p = 0.005, respectively). However, in patients with moderate renal dysfunction (eGFR < 60 ml/min/1.73m2), TG/HDL-C ratio lost its predictive value on the risk of MACEs (HR, 1.23; 95% CI, 0.82-1.83; p = 0.317). In patients with AMI, TG/HDL-C ratio is a useful independent predictor of 12-month MACEs. However, this ratio does not have predictive power in patients with moderate renal dysfunction.

A Population Pharmacokinetic Model for 51Cr EDTA to Estimate Renal Function.

PubMed

Kuan, Isabelle H S; Duffull, Stephen B; Putt, Tracey L; Schollum, John B W; Walker, Robert J; Wright, Daniel F B

2017-06-01

51 Cr EDTA clearance (CL) from plasma is used to estimate glomerular filtration rate (GFR). We propose that current methods for analysing the raw 51 Cr EDTA measurements over-simplifies the disposition of 51 Cr EDTA and therefore could produce biased GFR estimates. The aim of this study was to develop a population pharmacokinetic model for 51 Cr EDTA disposition and to compare model-predicted GFR to other methods of estimating renal function. Data from 40 individuals who received ~7.4 MBq of 51 Cr EDTA, as an intravenous bolus, were available for analysis. Plasma radioactivity (counts/min) was measured from timed collection points at 2, 4, 6 and 24 h after the dose. A population analysis was conducted using NONMEM ® version 7.2. Model-predicted GFR was compared with other methods for estimating renal function using mean prediction error (MPE). A two-compartment pharmacokinetic model with first-order elimination best fit the data. Compared with the model predictions, creatinine CL from 24 h urine data was unbiased. The commonly used 'slope-intercept' method for estimating isotopic GFR was positively biased compared with the model (MPE 15.5 mL/min/1.73 m 2 [95% confidence interval {CI} 8.9-22.2]. The Cockcroft Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations led to negatively biased GFR estimates (MPE -19.0 [95% CI -25.4 to -12.7], -20.1 [95% CI -27.2 to -13.1] and -16.5 [95% CI -22.2 to -10.1] mL/min/1.73 m 2 , respectively). The biased GFR estimates were most obvious in patients with relatively normal renal function. This may lead to inaccurate dosing in patients who are receiving drugs with a narrow therapeutic range where dosing is adjusted according to GFR estimates (e.g. carboplatin). The study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), number: ACTRN 12611000035921.

Comparison of ultrasound versus computed tomography for the detection of kidney stones in the pediatric population: a clinical effectiveness study.

PubMed

Roberson, Nathaniel P; Dillman, Jonathan R; O'Hara, Sara M; DeFoor, William R; Reddy, Pramod P; Giordano, Richard M; Trout, Andrew T

2018-07-01

The incidence of pediatric nephrolithiasis in the United States is increasing. There is a paucity of literature comparing the diagnostic performance of computed ultrasound (US) to tomography (CT) in the pediatric population. To determine the diagnostic performance of renal US for nephrolithiasis in children using a clinical effectiveness approach. Institutional review board approval with a waiver of informed consent was obtained for this retrospective, HIPAA-complaint investigation. Billing records and imaging reports were used to identify children (≤18 years old) evaluated for nephrolithiasis by both US and unenhanced CT within 24 h between March 2012 and March 2017. Imaging reports were reviewed for presence, number, size and location of kidney stones. Diagnostic performance of US (reference standard=CT) was calculated per renal unit (left/right kidney) and per renal sector (four sectors per kidney). For sector analysis, US was considered truly positive if a stone was identified at CT in the same or an adjacent sector. There were 68 renal stones identified by CT in 30/69 patients (43%). Mean patient age was 14.7±3.6 years, and 35 were boys. For detecting nephrolithiasis in any kidney, US was 66.7% (48.8-80.8%) sensitive and 97.4% (86.8-99.9%) specific (positive predictive value=95.2% [77.3-99.8%], negative predictive value=79.2% [65.7-88.3%], positive likelihood ratio=26.0). Per renal sector, US was 59.7% (46.7-71.4%) sensitive and 97.4% (95.5-98.5%) specific (positive predictive value=72.3% [58.2-83.1%], negative predictive value=95.4% [93.2-96.9%], positive likelihood ratio=22.5). Of the 30 stones not detected by US, only 3 were >3 mm at CT. In clinical practice, US has high specificity for detecting nephrolithiasis in children but only moderate sensitivity and false negatives are common.

Accessory renal arteries: Prevalence in resistant hypertension and an important role in nonresponse to radiofrequency renal denervation.

PubMed

VonAchen, Paige; Hamann, Jason; Houghland, Thomas; Lesser, John R; Wang, Yale; Caye, David; Rosenthal, Kristi; Garberich, Ross F; Daniels, Mary; Schwartz, Robert S

The aim of this study was to understand the role of accessory renal arteries in resistant hypertension, and to establish their role in nonresponse to radiofrequency renal denervation (RDN) procedures. Prior studies suggest a role for accessory renal arteries in hypertensive syndromes, and recent clinical trials of renal denervation report that these anomalies are highly prevalent in resistant hypertension. This study evaluated the relationships among resistant hypertension, accessory renal arteries, and the response to radiofrequency (RF) renal denervation. Computed Tomography Angiography (CTA) and magnetic resonance imaging (MRI) scans from 58 patients with resistant hypertension undergoing RF renal denervation (RDN) were evaluated. Results were compared with CT scans in 57 healthy, normotensive subjects undergoing screening as possible renal transplant donors. All scans were carefully studied for accessory renal arteries, and were correlated with long term blood pressure reduction. Accessory renal arteries were markedly more prevalent in the hypertensive patients than normotensive renal donors (59% vs 32% respectively, p=0.004). RDN had an overall nonresponse rate of 29% (response rate 71%). Patients without accessory vessels had a borderline higher response rate to RDN than those with at least one accessory vessel (83% vs 62% respectively, p=0.076) and a higher RDN response than patients with untreated accessory arteries (83% vs 55%; p=0.040). For accessory renal arteries and nonresponse, the sensitivity was 76%, specificity 49%, with positive and negative predictive values 38% and 83% respectively. Accessory renal arteries were markedly over-represented in resistant hypertensives compared with healthy controls. While not all patients with accessory arteries were nonresponders, nonresponse was related to both the presence and non-treatment of accessory arteries. Addressing accessory renal arteries in future clinical trials may improve RDN therapeutic efficacy. Copyright © 2016 Elsevier Inc. All rights reserved.

Fas expression in renal cell carcinoma accurately predicts patient survival after radical nephrectomy.

PubMed

Sejima, Takehiro; Morizane, Shuichi; Hinata, Nobuyuki; Yao, Akihisa; Isoyama, Tadahiro; Saito, Motoaki; Takenaka, Atsushi

2012-01-01

To investigate Fas, Fas ligand (FasL) and Bcl-2 expression, which are considered to be important apoptotic regulatory factors in renal cell carcinomas (RCCs). mRNA quantification and immunohistochemistry allowed for the determination of the expression of these three factors in surgically resected tumors from 82 patients with RCC. The correlation of protein and gene expression with more than 10 years of survival data following nephrectomy (along with clinical and pathologic parameters) was analyzed using uni- and multivariate statistical models. A significantly poorer outcome was observed in patients with tumors expressing high levels of Fas mRNA in the multivariate analysis (p = 0.0002). In addition, patient survival was significantly worse in FasL mRNA-positive tumor cases when compared with FasL mRNA-negative cases (p = 0.0345). Ten cases relapsed more than 5 years after nephrectomy. Among them, the tumors of 8 cases (80%) did not express FasL mRNA. Analysis of Bcl-2 did not show statistical significance of Bcl-2 expression as a prognostic indicator. The data suggest that pronounced Fas expression is a surrogate biomarker of active cancer cell proliferation. Given the FasL tumor counterattack theory, FasL overexpression in RCC may be one of the host immune deficiencies, consequently leading to poor prognosis. Copyright © 2012 S. Karger AG, Basel.

Evaluation of serum neutrophil gelatinase-associated lipocalin as a novel biomarker of cardiorenal syndrome in dogs.

PubMed

Jung, Han-Byeol; Kang, Min-Hee; Park, Hee-Myung

2018-05-01

Worsening renal function and azotemia in patients with heart failure (HF) are strongly associated with disease severity and poor prognosis. Increasing interest in this correlation led to the description and classification of cardiorenal syndrome (CRS). We evaluated the role of neutrophil gelatinase-associated lipocalin (NGAL) in the early detection of CRS in dogs with HF. Ten healthy dogs and 31 dogs admitted with HF were included in our study. NGAL and troponin-I were measured on samples collected on the day of admission; creatinine was measured on admission and again on day 7. The CRS group was defined as subsequently developing renal azotemia. Of 31 dogs with HF, 20 were included in the HF group, and 11 were included in the CRS group. The admission NGAL concentrations of the CRS group were significantly higher than those of other groups ( p < 0.001). The severity of HF evaluation based on the modified New York Heart Association classification showed significant correlation with NGAL ( p < 0.001) and troponin-I ( p = 0.009) concentration. However, only serum NGAL concentration at admission was significantly associated with the development of CRS in dogs with HF ( p = 0.021). The admission serum NGAL ≥ 16.0 ng/mL (optimal cutoff value) had a sensitivity of 90.9% and specificity of 90.0% in predicting the development of CRS.

Methotrexate-induced epidermal necrosis: A case series of 24 patients.

PubMed

Chen, Ting-Jui; Chung, Wen-Hung; Chen, Chun-Bing; Hui, Rosaline Chung-Yee; Huang, Yu-Huei; Lu, Yueh-Tsung; Wang, Chang-Wei; Wang, Kuo-Hsien; Yang, Li-Cheng; Hung, Shuen-Iu

2017-08-01

Methotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To investigate the clinicopathology, risk factors, and prognostic factors of MEN. We enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX). Patients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN. The study was limited by the small sample size. MEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A multi-centre qualitative study exploring the experiences of UK South Asian and White Diabetic Patients referred for renal care

PubMed Central

2012-01-01

Background An exploration of renal complications of diabetes from the patient perspective is important for developing quality care through the diabetic renal disease care pathway. Methods Newly referred South Asian and White diabetic renal patients over 16 years were recruited from nephrology outpatient clinics in three UK centres - Luton, West London and Leicester – and their experiences of the diabetes and renal care recorded. A semi-structured qualitative interview was conducted with 48 patients. Interview transcripts were analysed thematically and comparisons made between the White and South Asian groups. Results 23 South Asian patients and 25 White patients were interviewed. Patient experience of diabetes ranged from a few months to 35 years with a mean time since diagnosis of 12.1 years and 17.1 years for the South Asian and White patients respectively. Confusion emerged as a response to referral shared by both groups. This sense of confusion was associated with reported lack of information at the time of referral, but also before referral. Language barriers exacerbated confusion for South Asian patients. Conclusions The diabetic renal patients who have been referred for specialist renal care and found the referral process confusing have poor of awareness of kidney complications of diabetes. Healthcare providers should be more aware of the ongoing information needs of long term diabetics as well as the context of any information exchange including language barriers. PMID:23176053

Effect of Dietary Countermeasures and Impact of Gravity on Renal Calculi Size Distributions Predicted by PBE-System and PBE-CFD Models

NASA Technical Reports Server (NTRS)

Kassemi, M.; Thompson, D.; Goodenow, D.; Gokoglu, S.; Myers, J.

2016-01-01

Renal stone disease is not only a concern on earth but can conceivably pose a serious risk to the astronauts health and safety in Space. In this work, two different deterministic models based on a Population Balance Equation (PBE) analysis of renal stone formation are developed to assess the risks of critical renal stone incidence for astronauts during space travel. In the first model, the nephron is treated as a continuous mixed suspension mixed product removal crystallizer and the PBE for the nucleating, growing and agglomerating renal calculi is coupled to speciation calculations performed by JESS. Predictions of stone size distributions in the kidney using this model indicate that the astronaut in microgravity is at noticeably greater but still subcritical risk and recommend administration of citrate and augmented hydration as effective means of minimizing and containing this risk. In the second model, the PBE analysis is coupled to a Computational Fluid Dynamics (CFD) model for flow of urine and transport of Calcium and Oxalate in the nephron to predict the impact of gravity on the stone size distributions. Results presented for realistic 3D tubule and collecting duct geometries, clearly indicate that agglomeration is the primary mode of size enhancement in both 1g and microgravity. 3D numerical simulations seem to further indicate that there will be an increased number of smaller stones developed in microgravity that will likely pass through the nephron in the absence of wall adhesion. However, upon reentry to a 1g (Earth) or 38g (Mars) partial gravitational fields, the renal calculi can lag behind the urinary flow in tubules that are adversely oriented with respect to the gravitational field and grow agglomerate to large sizes that are sedimented near the wall with increased propensity for wall adhesion, plaque formation, and risk to the astronauts.

Predictors of long-term renal outcome in lupus nephritis trials: lessons learned from the Euro-Lupus Nephritis cohort.

PubMed

Dall'Era, Maria; Cisternas, Miriam G; Smilek, Dawn E; Straub, Laura; Houssiau, Frédéric A; Cervera, Ricard; Rovin, Brad H; Mackay, Meggan

2015-05-01

There is a need to determine which response measures in lupus nephritis trials are most predictive of good long-term renal function. We used data from the Euro-Lupus Nephritis Trial to evaluate the performance of proteinuria, serum creatinine (Cr), and urinary red blood cells (RBCs) as predictors of good long-term renal outcome. Patients from the Euro-Lupus Nephritis Trial with proteinuria, serum Cr, and urinary RBC measurements at 3, 6, or 12 months and with a minimum of 7 years of followup were included (n = 76). We assessed the ability of these clinical biomarkers at 3, 6, and 12 months after randomization to predict good long-term renal outcome (defined as a serum Cr value ≤1.0 mg/dl) at 7 years. Receiver operating characteristic curves were generated to assess parameter performance at these time points and to select the best cutoff for individual parameters. Sensitivity and specificity were calculated for the parameters alone and in combination. A proteinuria value of <0.8 gm/day at 12 months after randomization was the single best predictor of good long-term renal function (sensitivity 81% and specificity 78%). The addition of serum Cr to proteinuria as a composite predictor did not improve the performance of the outcome measure; addition of urinary RBCs as a predictor significantly decreased the sensitivity to 47%. This study demonstrates that the level of proteinuria at 12 months is the individual best predictor of long-term renal outcome in patients with lupus nephritis. Inclusion of urinary RBCs as part of a composite outcome measure actually undermined the predictive value of the trial data. We therefore suggest that urinary RBCs should not be included as a component of clinical trial response criteria in lupus nephritis. © 2015, American College of Rheumatology.

Application of physiologically-based pharmacokinetic modeling to explore the role of kidney transporters in renal reabsorption of perfluorooctanoic acid in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Worley, Rachel Rogers, E-mail: idz7@cdc.gov; Interdisciplinary Toxicology Program, University of Georgia, 341 Pharmacy South, Athens, GA 30602; Fisher, Jeffrey

ABSTRACT: Renal elimination and the resulting clearance of perfluorooctanoic acid (PFOA) from the serum exhibit pronounced sex differences in the adult rat. The literature suggests that this is largely due to hormonally regulated expression of organic anion transporters (OATs) on the apical and basolateral membranes of the proximal tubule cells that facilitate excretion and reabsorption of PFOA from the filtrate into the blood. Previously developed PBPK models of PFOA exposure in the rat have not been parameterized to specifically account for transporter-mediated renal elimination. We developed a PBPK model for PFOA in male and female rats to explore the rolemore » of Oat1, Oat3, and Oatp1a1 in sex-specific renal reabsorption and excretion of PFOA. Descriptions of the kinetic behavior of these transporters were extrapolated from in vitro studies and the model was used to simulate time-course serum, liver, and urine data for intravenous (IV) and oral exposures in both sexes. Model predicted concentrations of PFOA in the liver, serum, and urine showed good agreement with experimental data for both male and female rats indicating that in vitro derived physiological descriptions of transporter-mediated renal reabsorption can successfully predict sex-dependent excretion of PFOA in the rat. This study supports the hypothesis that sex-specific serum half-lives for PFOA are largely driven by expression of transporters in the kidney and contribute to the development of PBPK modeling as a tool for evaluating the role of transporters in renal clearance. - Highlights: • The PBPK model for PFOA in the rat explores the role of OATs in sex-specific clearance. • Descriptions of OAT kinetics were extrapolated from in vitro studies. • Model predictions showed good fit with experimental data for male and female rats.« less

Transforming Growth Factor-β1 as a Novel Marker of Response to Therapy for Renal Cell Carcinoma.

PubMed

Adler, H L

2001-01-01

Renal cell carcinoma is expected to account for 30,000 new cancer cases and 11,900 cancer deaths in the United States in 1999 (1). At the time of initial presentation, up to one-third of patients with renal cell carcinoma (RCC) have metastatic disease; furthermore, almost half of the patients resected for cure will relapse (2). Due to the poor results of cytotoxic chemotherapy in the management of metastatic RCC (3), physicians have explored the use of new therapies including immunotherapy and gene therapy. Some of these therapies are discussed in other chapters of this textbook. The use of these new therapies allows for the identification and utilization of new tumor markers that may allow investigators to identify patients at risk for advanced disease as well as establish new definitions of tumor response.

Predictive features of chronic kidney disease in atypical haemolytic uremic syndrome

PubMed Central

Jamme, Matthieu; Raimbourg, Quentin; Chauveau, Dominique; Seguin, Amélie; Presne, Claire; Perez, Pierre; Gobert, Pierre; Wynckel, Alain; Provôt, François; Delmas, Yahsou; Mousson, Christiane; Servais, Aude; Vrigneaud, Laurence; Veyradier, Agnès

2017-01-01

Chronic kidney disease (CKD) is a frequent and serious complication of atypical haemolytic uremic syndrome (aHUS). We aimed to develop a simple accurate model to predict the risk of renal dysfunction in aHUS based on clinical and biological features available at hospital admission. Renal function at 1-year follow-up, based on an estimated glomerular filtration rate < 60mL/min/1.73m2 as assessed by the Modification of Diet in Renal Disease equation, was used as an indicator of significant CKD. Prospectively collected data from a cohort of 156 aHUS patients who did not receive eculizumab were used to identify predictors of CKD. Covariates associated with renal impairment were identified by multivariate analysis. The model performance was assessed and a scoring system for clinical practice was constructed from the regression coefficient. Multivariate analyses identified three predictors of CKD: a high serum creatinine level, a high mean arterial pressure and a mildly decreased platelet count. The prognostic model had a good discriminative ability (area under the curve = .84). The scoring system ranged from 0 to 5, with corresponding risks of CKD ranging from 18% to 100%. This model accurately predicts development of 1-year CKD in patients with aHUS using clinical and biological features available on admission. After further validation, this model may assist in clinical decision making. PMID:28542627

The Development of Brain Metastases in Patients with Renal Cell Carcinoma: Epidemiologic Trends, Survival, and Clinical Risk Factors Using a Population-based Cohort.

PubMed

Sun, Maxine; De Velasco, Guillermo; Brastianos, Priscilla K; Aizer, Ayal A; Martin, Allison; Moreira, Raphael; Nguyen, Paul L; Trinh, Quoc-Dien; Choueiri, Toni K

2018-01-05

The incidence of brain metastases (BM) in patients with renal cell carcinoma (RCC) is hypothesized to have increased in the last 2 decades. To define incidence trends according to patient and clinical characteristics, to identify risk factors, and to describe outcomes of patients with BM for RCC. Patients diagnosed with RCC between the years 2010 and 2013 within the Surveillance, Epidemiology, and End Results database. An external validation was also considered using patients diagnosed with RCC between 2010 and 2012 within the National Cancer Database. Incidence proportions of BM were calculated. Risk factors correlated with BM at diagnosis were identified via a 1000-bootstrap corrected multivariable logistic regression model. A risk model was then developed and evaluated using measures of predictive accuracy. Overall survival was examined using Cox regression analyses. The overall incidence proportions of BM at RCC diagnosis was 1.51% (95% confidence interval: 1.39-1.64%). White/other race, clear cell histology, and sarcomatoid differentiation, T2-4 disease, tumor dimension >10 cm, and N+ disease were significantly associated with BM at RCC diagnosis, and retained within the final prediction model. A risk score was created based on these variables (c-index: 0.803). BM at RCC diagnosis occurred in 0.5%, 3.6%, and 7.7% of patients categorized as low risk, intermediate risk, and high risk. Patients with BM were more likely to succumb to any death than those without BM at diagnosis (median overall survival: 6.4 mo vs not reached, respectively, adjusted hazard ratio: 1.87, 95% confidence interval: 1.67-2.08, p < 0.001). The real incidence of BM at RCC diagnosis is likely underestimated given that the observed rate likely reflects patients who presented with symptoms. Patients with BM at RCC have poor oncological outcomes. We have characterized the epidemiology of BM at RCC diagnosis and developed a clinical risk model for the purpose of predicting the development of BMs in patients diagnosed with a cortical renal mass. In this report we examined recent proportions of patients with brain metastases at kidney cancer diagnosis in a large community database originating from the US. We developed a model that may be used during routine clinical practice to predict brain metastases. The urologic-oncological community may consider baseline imaging for brain metastases in patients without any symptoms but at high risk of having brain metastases according to the risk model. However, the proposed model certainly needs further testing and validation in the clinical setting. Future studies on brain metastases survival and treatment options are also needed. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Fluid dynamic modelling of renal pelvic pressure during endoscopic stone removal

NASA Astrophysics Data System (ADS)

Oratis, Alexandros; Subasic, John; Bird, James; Eisner, Brian

2015-11-01

Endoscopic kidney stone removal procedures are known to increase internal pressure in the renal pelvis, the kidney's urinary collecting system. High renal pelvic pressure incites systemic absorption of irrigation fluid, which can increase the risk of postoperative fever and sepsis or the unwanted absorption of electrolytes. Urologists choose the appropriate surgical procedure based on patient history and kidney stone size. However, no study has been conducted to compare the pressure profiles of each procedure, nor is there a precise sense of how the renal pelvic pressure scales with various operational parameters. Here we develop physical models for the flow rates and renal pelvic pressure for various procedures. We show that the results of our models are consistent with existing urological data on each procedure and that the models can predict pressure profiles where data is unavailable.

Predictive factors for renal failure and a control and treatment algorithm

PubMed Central

Cerqueira, Denise de Paula; Tavares, José Roberto; Machado, Regimar Carla

2014-01-01

Objectives to evaluate the renal function of patients in an intensive care unit, to identify the predisposing factors for the development of renal failure, and to develop an algorithm to help in the control of the disease. Method exploratory, descriptive, prospective study with a quantitative approach. Results a total of 30 patients (75.0%) were diagnosed with kidney failure and the main factors associated with this disease were: advanced age, systemic arterial hypertension, diabetes mellitus, lung diseases, and antibiotic use. Of these, 23 patients (76.6%) showed a reduction in creatinine clearance in the first 24 hours of hospitalization. Conclusion a decline in renal function was observed in a significant number of subjects, therefore, an algorithm was developed with the aim of helping in the control of renal failure in a practical and functional way. PMID:26107827

Delta-like ligand 4: A predictor of poor prognosis in clear cell renal cell carcinoma

PubMed Central

WANG, WEI; YU, YI; WANG, YA; LI, XIAOMING; BAO, JUNSHENG; WU, GONGJIN; CHANG, HONG; SHI, TINGKAI; YUE, ZHONGJIN

2014-01-01

Delta-like ligand 4 (Dll4)-Notch signaling is important in tumor angiogenesis; however, the prognostic value of D114 detection in patients with clear cell renal cell carcinoma (CCRCC) remains unclear. The present study aimed to determine whether the presence of high Dll4 expression levels was correlated with poor prognosis in CCRCC following curative resection. The D114 expression levels in four paired samples of CCRCC tissues and adjacent normal renal tissues were assayed by western blotting. Surgical specimens comprised 121 CCRCC tissue samples and 65 normal renal tissue samples, obtained from patients with CCRCC. The specimens were immunohistochemically assessed to determine Dll4 and vascular endothelial growth factor receptor 2 (VEGFR-2) expression levels. The prognostic significance of Dll4 expression levels was evaluated by the Kaplan-Meier method and Cox regression analysis. The correlation between Dll4 expression levels and VEGFR-2 expression levels, tumor stage, tumor grade and metastasis, was examined by χ2 test and multivariate logistic regression. As determined by the western blotting results, Dll4 protein expression levels were significantly increased in CCRCC tissues compared with those in adjacent non-cancerous tissues. From the analysis of the surgical specimens, 53 (43.8%) CCRCC patients exhibited immunohistochemically high Dll4 expression levels and 68 (56.2%) patients exhibited low Dll4 expression levels. The survival curves revealed that the patients with high Dll4 expression levels had significantly shorter survival times than the patients with low Dll4 expression levels (P<0.001). Multivariate survival analysis demonstrated that the presence of high Dll4 expression levels was independently associated with reduced overall survival and progression-free survival times (P=0.021 and 0.034, respectively). A positive correlation was also identified between Dll4 and VEGFR-2 expression levels (P=0.001). In conclusion, the results show that the presence of high Dll4 expression levels was clearly associated with high VEGFR-2 expression levels, tumor grade, tumor stage and poor prognosis in CCRCC patients. Therefore, inhibition of Dll4 may exert potent growth inhibitory effects on tumors resistant to anti-VEGF therapies for CCRCC. PMID:25364440

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa.

PubMed

Lewandowski, L B; Schanberg, L E; Thielman, N; Phuti, A; Kalla, A A; Okpechi, I; Nourse, P; Gajjar, P; Faller, G; Ambaram, P; Reuter, H; Spittal, G; Scott, C

2017-02-01

Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrolment in the South African registry. South African patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study revealed a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

The assessment of renal cortex and parenchymal volume using automated CT volumetry for predicting renal function after donor nephrectomy.

PubMed

Mitsui, Yosuke; Sadahira, Takuya; Araki, Motoo; Wada, Koichiro; Tanimoto, Ryuta; Ariyoshi, Yuichi; Kobayashi, Yasuyuki; Watanabe, Masami; Watanabe, Toyohiko; Nasu, Yasutomo

2018-04-01

Contrast-enhanced CT is necessary before donor nephrectomy and is usually combined with a Tc-99m-mercapto-acetyltriglycine (MAG3) scan to check split renal function (SRF). However, all transplant programs do not use MAG3 because of its high cost and exposure to radiation. We examined whether CT volumetry of the kidney can be a new tool for evaluating SRF. Sixty-three patients underwent live donor nephrectomy. Patients without a 1.0 mm slice CT or follow-up for <12 months were excluded leaving 34 patients' data being analyzed. SRF was measured by MAG3. Split renal volume (SRV) was calculated automatically using volume analyzer software. The correlation between SRF and SRV was examined. The association between the donor's postoperative estimated glomerular filtration rate (eGFR) and predicted eGFR calculated by MAG3 or CT volumetry was analyzed at 1, 3, and 12 months post nephrectomy. Strong correlations were observed preoperatively in a Bland-Altman plot between SRF measured by MAG3 and either CT cortex or parenchymal volumetry. In addition, eGFR after donation correlated with SRF measured by MAG3 or CT volumetry. The correlation coefficients (R) for eGFR Mag3 split were 0.755, 0.615, and 0.763 at 1, 3 and 12 months, respectively. The corresponding R values for cortex volume split were 0.679, 0.638, and 0.747. Those for parenchymal volume split were 0.806, 0.592, and 0.764. Measuring kidney by CT volumetry is a cost-effective alternative to MAG3 for evaluating SRF and predicting postoperative donor renal function. Both cortex and parenchymal volumetry were similarly effective.

Kidney disease in heart failure: the importance of novel biomarkers for type 1 cardio-renal syndrome detection.

PubMed

Palazzuoli, Alberto; McCullough, Peter A; Ronco, Claudio; Nuti, Ranuccio

2015-08-01

Chronic kidney disease (CKD) in heart failure (HF) has been recognized as an independent risk factor for adverse outcome, although the most important clinical trials tend to exclude patients with moderate and severe renal insufficiency. Despite this common association, the precise pathophysiological connection and liaison between heart and kidney is partially understood. Moreover, is it not enough considering how much cardio-renal syndrome type 1 is attributable to previous CKD, and how much to new-onset acute kidney injury (AKI). Neither development of AKI, its progression and time nor duration is related to an adverse outcome. An AKI definition is not universally recognized, and many confounding terms have been used in literature: "worsening renal function", "renal impairment", "renal dysfunction", etc., are all names that contribute to misunderstanding, and do not facilitate an universal classification. Therefore, AKI development should be the consequence of the basal clinical characteristics of patients, different primitive kidney disease and hemodynamic status. AKI could also be the mirror of several underlying associated diseases poorly controlled. Finally, it is not clear which is the optimal laboratory tool for identifying patients with an increased risk of AKI. In the current report, we review the different kidney diseases' impact in HF, and we analyze the modalities for AKI recognition during HF focusing our attention about some new biomarkers with potential application in the current setting.

Phosphorylation of ribosomal protein S6 mediates compensatory renal hypertrophy

PubMed Central

Xu, Jinxian; Chen, Jianchun; Dong, Zheng; Meyuhas, Oded; Chen, Jian-Kang

2014-01-01

The molecular mechanism underlying renal hypertrophy and progressive nephron damage remains poorly understood. Here we generated congenic ribosomal protein S6 (rpS6) knockin mice expressing non-phosphorylatable rpS6 and found that uninephrectomy-induced renal hypertrophy was significantly blunted in these knockin mice. Uninephrectomy-induced increases in cyclin D1 and decreases in cyclin E in the remaining kidney were attenuated in the knockin mice compared to their wild-type littermates. Uninephrectomy induced rpS6 phosphorylation in the wild type mice; however, no rpS6 phosphorylation was detected in uninephrectomized or sham-operated knockin mice. Nonetheless, uninephrectomy stimulated comparable 4E-BP1 phosphorylation in both knockin and wild type mice, indicating that mTORC1 was still activated in the knockin mice. Moreover, the mTORC1 inhibitor rapamycin prevented both rpS6 and 4E-BP1 phosphorylation, significantly blunted uninephrectomy-induced renal hypertrophy in wild type mice, but did not prevent residual renal hypertrophy despite inhibiting 4E-BP1 phosphorylation in uninephrectomized knockin mice. Thus, both genetic and pharmacological approaches unequivocally demonstrate that phosphorylated rpS6 is a downstream effector of the mTORC1-S6K1 signaling pathway mediating renal hypertrophy. Hence, rpS6 phosphorylation facilitates the increase in cyclin D1 and decrease in cyclin E1 that underlie the hypertrophic nature of uninephrectomy-induced kidney growth. PMID:25229342

Arterial Stiffness and Renal Replacement Therapy: A Controversial Topic

PubMed Central

Fischer, Edmundo Cabrera; Zócalo, Yanina; Galli, Cintia; Bia, Daniel

2015-01-01

The increase of arterial stiffness has been to have a significant impact on predicting mortality in end-stage renal disease patients. Pulse wave velocity (PWV) is a noninvasive, reliable parameter of regional arterial stiffness that integrates the vascular geometry and arterial wall intrinsic elasticity and is capable of predicting cardiovascular mortality in this patient population. Nevertheless, reports on PWV in dialyzed patients are contradictory and sometimes inconsistent: some reports claim the arterial wall stiffness increases (i.e., PWV increase), others claim that it is reduced, and some even state that it augments in the aorta while it simultaneously decreases in the brachial artery pathway. The purpose of this study was to analyze the literature in which longitudinal or transversal studies were performed in hemodialysis and/or peritoneal dialysis patients, in order to characterize arterial stiffness and the responsiveness to renal replacement therapy. PMID:26064684

Etiology of the protein-energy wasting syndrome in chronic kidney disease: a consensus statement from the International Society of Renal Nutrition and Metabolism (ISRNM).

PubMed

Carrero, Juan Jesús; Stenvinkel, Peter; Cuppari, Lilian; Ikizler, T Alp; Kalantar-Zadeh, Kamyar; Kaysen, George; Mitch, William E; Price, S Russ; Wanner, Christoph; Wang, Angela Y M; ter Wee, Pieter; Franch, Harold A

2013-03-01

Protein-energy wasting (PEW), a term proposed by the International Society of Renal Nutrition and Metabolism (ISRNM), refers to the multiple nutritional and catabolic alterations that occur in chronic kidney disease (CKD) and associate with morbidity and mortality. To increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contribute, other highly prevalent factors are required for the full syndrome to develop. These include uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and multiple endocrine disorders that render a state of hypermetabolism leading to excess catabolism of muscle and fat. In addition, comorbid conditions associated with CKD, poor physical activity, frailty, and the dialysis procedure per se further contribute to PEW. Published by Elsevier Inc.

Achievement of trifecta in minimally invasive partial nephrectomy correlates with functional preservation of operated kidney: a multi-institutional assessment using MAG3 renal scan.

PubMed

Zargar, Homayoun; Porpiglia, Francesco; Porter, James; Quarto, Giuseppe; Perdona, Sisto; Bertolo, Riccardo; Autorino, Riccardo; Kaouk, Jihad H

2016-07-01

To validate and compare the values of "MIC" and "trifecta" as predictors of operated kidney functional preservation in a multi-institutional cohort of patients undergoing minimally invasive PN. We retrospectively reviewed records of consecutive cases of minimally invasive PN performed for cT1 renal masses in 4 centers from 2009 to 2013. Inclusion criteria consisted of availability of a renal scan obtained within 2 weeks prior to surgery and follow-up renal scan 3-6 months after the surgery. The primary endpoint of the study was to compare the degree of ipsilateral renal function preservation assessed by MAG3 renal scan in relation to achievement of MIC and trifecta. Total of 351 patients met our inclusion criteria. The rates of trifecta achievement for cT1a and cT1b tumors were 78.9 and 60.6 %, respectively. The rate of MIC achievement for cT1a tumors and cT1b tumors was 60.3 and 31.7 %, respectively. On multivariable linear regression model, only the degree of tumor complexity assessed by R.E.N.A.L nephrometry score [coefficient B -1.8 (-2.7, -0.9); p < 0.0001] and the achievement of trifecta [coefficient B 6.1 (2.4,9.8); p = 0.014] or MIC (coefficient B 7.2 (3.8,0.6); p < 0.0001) were significant clinical factors predicting ipsilateral split function preservation. Achievement of both MIC and "trifecta" is associated with higher proportion of split renal function preservation for cT1 tumors after minimally invasive PN. Thus, these outcome measures can be regarded not only as markers of surgical quality, but also as reliable surrogates for predicting functional outcome in the operated kidney.

Renal mass anatomic characteristics and perioperative outcomes of laparoscopic partial nephrectomy: a critical analysis.

PubMed

Tsivian, Matvey; Ulusoy, Said; Abern, Michael; Wandel, Ayelet; Sidi, A Ami; Tsivian, Alexander

2012-10-01

Anatomic parameters determining renal mass complexity have been used in a number of proposed scoring systems despite lack of a critical analysis of their independent contributions. We sought to assess the independent contribution of anatomic parameters on perioperative outcomes of laparoscopic partial nephrectomy (LPN). Preoperative imaging studies were reviewed for 147 consecutive patients undergoing LPN for a single renal mass. Renal mass anatomy was recorded: Size, growth pattern (endo-/meso-/exophytic), centrality (central/hilar/peripheral), anterior/posterior, lateral/medial, polar location. Multivariable models were used to determine associations of anatomic parameters with warm ischemia time (WIT), operative time (OT), estimated blood loss (EBL), intra- and postoperative complications, as well as renal function. All models were adjusted for the learning curve and relevant confounders. Median (range) tumor size was 3.3 cm (1.5-11 cm); 52% were central and 14% hilar. While 44% were exophytic, 23% and 33% were mesophytic and endophytic, respectively. Anatomic parameters did not uniformly predict perioperative outcomes. WIT was associated with tumor size (P=0.068), centrality (central, P=0.016; hilar, P=0.073), and endophytic growth pattern (P=0.017). OT was only associated with tumor size (P<0.001). No anatomic parameter predicted EBL. Tumor centrality increased the odds of overall and intraoperative complications, without reaching statistical significance. Postoperative renal function was not associated with any of the anatomic parameters considered after adjustment for baseline function and WIT. Learning curve, considered as a confounder, was independently associated with reduced WIT and OT as well as reduced odds of intraoperative complications. This study provides a detailed analysis of the independent impact of renal mass anatomic parameters on perioperative outcomes. Our findings suggest diverse independent contributions of the anatomic parameters to the different measures of outcomes (WIT, OT, EBL, complications, and renal function) emphasizing the importance of the learning curve.

Validation of the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) prognostic model for first-line pazopanib in metastatic renal carcinoma: the Spanish Oncologic Genitourinary Group (SOGUG) SPAZO study.

PubMed

Pérez-Valderrama, B; Arranz Arija, J A; Rodríguez Sánchez, A; Pinto Marín, A; Borrega García, P; Castellano Gaunas, D E; Rubio Romero, G; Maximiano Alonso, C; Villa Guzmán, J C; Puertas Álvarez, J L; Chirivella González, I; Méndez Vidal, M J; Juan Fita, M J; León-Mateos, L; Lázaro Quintela, M; García Domínguez, R; Jurado García, J M; Vélez de Mendizábal, E; Lambea Sorrosal, J J; García Carbonero, I; González del Alba, A; Suárez Rodríguez, C; Jiménez Gallego, P; Meana García, J A; García Marrero, R D; Gajate Borau, P; Santander Lobera, C; Molins Palau, C; López Brea, M; Fernández Parra, E M; Reig Torras, O; Basterretxea Badiola, L; Vázquez Estévez, S; González Larriba, J L

2016-04-01

Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice. Data of 278 patients, treated with first-line pazopanib for mRCC in 34 centres in Spain, were locally recorded and externally validated. Mean age was 66 years, there were 68.3% male, 93.5% clear-cell type, 74.8% nephrectomized, and 81.3% had ECOG 0-1. Metastatic sites were: lung 70.9%, lymph node 43.9%, bone 26.3%, soft tissue/skin 20.1%, liver 15.1%, CNS 7.2%, adrenal gland 6.5%, pleura/peritoneum 5.8%, pancreas 5%, and kidney 2.2%. After median follow-up of 23 months, 76.4% had discontinued pazopanib (57.2% due to progression), 47.9% had received second-line targeted therapy, and 48.9% had died. According to IMDC prognostic model, 19.4% had favourable risk (FR), 57.2% intermediate risk (IR), and 23.4% poor risk (PR). No unexpected toxicities were recorded. Response rate was 30.3% (FR: 44%, IR: 30% PR: 17.3%). Median progression-free survival (whole population) was 11 months (32 in FR, 11 in IR, 4 in PR). Median and 2-year overall survival (whole population) were 22 months and 48.1%, respectively (FR: not reached and 81.6%, IR: 22 and 48.7%, PR: 7 and 18.8%). These estimations and their 95% confidence intervals are fully consistent with the outcomes predicted by the IMDC prognostic model. Our results validate the IMDC model for first-line pazopanib in mRCC and confirm the effectiveness and safety of this treatment. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Anemia and Long-Term Renal Prognosis in Patients with Post-Renal Acute Kidney Injury of Nonmalignant Cause.

PubMed

Sasaki, Sho; Kawarazaki, Hiroo; Hasegawa, Takeshi; Shima, Hideaki; Naganuma, Toshihide; Shibagaki, Yugo

2017-01-01

The renal prognosis of post-renal acute kidney injury (PoR-AKI) has not been verified so far. The objective of this study was to assess the association of baseline anemia with long-term renal prognosis in patients with PoR-AKI. We performed a multicenter retrospective cohort study. Consecutive adult patients from December 2006 to February 2010, who met the requirements as mentioned in the definition of PoR-AKI, were included. Patients without data on baseline renal function and at 6 months after PoR-AKI were excluded. We set baseline hemoglobin (Hb) level (g/dl) as the main exposure to be tested. The main outcome measure was long-term renal prognosis as determined by the difference between proximate estimated glomerular filtration rate (eGFR) at 6 months after diagnosis of PoR-AKI and baseline eGFR prior to the occurrence of the present PoR-AKI (ΔeGFR after 6 months) using the general linear model. We included 136 patients with PoR-AKI. The most frequent cause of PoR-AKI was malignancy, accounting for 39.0% (n = 53) of cases. Multivariate analysis adjusted for possible confounders showed that ΔeGFR after 6 months significantly changed by -4.28 ml/min/1.73 m2 for every 1 g/dl lower Hb at diagnosis (95% CI 1.86-6.69, p < 0.01). An additional multivariate analysis that was stratified by the presence or absence of malignancy as the cause of PoR-AKI yielded the same significant result only in the stratum of the nonmalignant cause of PoR-AKI. Patients with a nonmalignant cause of PoR-AKI who have baseline anemia may have poor long-term renal prognosis. In these cases, close observation of renal function after renal recovery may be required. © 2016 S. Karger AG, Basel.

Are gatekeepers to renal services referring patients equitably?

PubMed

Kee, Frank; Reaney, Elizabeth; Savage, Gerard; O'Reilly, Dermot; Patterson, Chris; Maxwell, Peter; Fogarty, Damian

2007-01-01

Patients with chronic kidney disease (CKD) benefit from specialist interventions to retard progression of renal failure and prevent cardiovascular events. Certain patient groups have poor access to specialist renal services when dialysis is required. This study used a population-based laboratory database to investigate access to and timeliness of referral to renal specialists relatively early in the course of the disease. All tests for serum creatinine and haemoglobin (Hb) A(1)c in Northern Ireland in a two-year period (2001 and 2002) were retrieved for 345,441 adults. Of these, 16,856 patients had at least one serum creatinine level above 150 micromol/L in 2001 not deemed to be due to acute renal failure (crude prevalence 1.42%). This cohort was followed until the end of 2002 and the differences in the time to referral to a specialist were assessed using Cox's proportional hazards regression. Diabetic patients, older patients and those living in deprived areas were significantly more likely to have serum creatinine testing, compared with non-diabetic, younger and those living in more affluent areas. Delays in referral to renal specialists for patients with raised serum creatinine levels were significantly shorter among diabetic patients, women, younger individuals, those living in rural areas, those living close to renal centres and those living in deprived areas. Overall, only 19% of diabetic patients and 6% of non-diabetic patients who had CKD had seen a renal specialist within 12 months of their index creatinine test. Contrary to other diseases, disadvantaged patients do not seem to be under-investigated for renal disease compared with their more affluent neighbours and are generally referred earlier for specialist assessment. However, the absolute rate of timely specialist assessment is low. Recent changes in referral criteria for CKD will result in more referrals and will have serious resource implications. Opportunities for health gain among patients with declining renal function are being missed, particularly among the old and those living furthest from specialist centres.

Follow-up imaging of the urinary tract in spinal injury patients: is a KUB necessary with every ultrasound?

PubMed

Tins, B; Teo, H-G; Popuri, R; Cassar-Pullicino, V; Tyrrell, P

2005-04-01

Prospective study of 100 consecutive patients. To evaluate the diagnostic usefulness of the urinary tract (KUB) radiograph routinely performed as part of spinal injury patient urinary tract screening with ultrasound (US) and the KUB radiograph. Orthopaedic and District General Hospital with spinal injuries unit, UK. Prospective study of the urinary tract of 100 consecutive routine follow-up spinal injury patients with KUB (kidneys, ureters, bladder) radiograph and US of the urinary tract. The percentage of the visualised area of kidneys and urinary bladder and relevant abnormal findings were recorded. Relevant patient history was recorded. In all, 80 men 20 women were examined (average age 46 years, average time since injury 11 years). A total of 199 kidneys and 99 urinary bladders were examined. On average, less than 50% of the renal area and about 70-75% of the urinary bladder area were visualised. Five patients had renal stones identified on the KUB radiograph, and of these two were seen on US. There were no stones seen on US only. The patient history was not helpful to identify patients with renal stones. Significant further renal abnormalities were identified with US in 14 patients, and with the KUB radiograph in 0 patients. Significant urinary bladder abnormalities were identified with US in 20 patients, and with the KUB radiograph in 0 patients. On average, less than 50% of the kidney area is visualised on the KUB due to overlying bowel markings making the KUB radiograph a poor tool to assess the kidneys. The KUB radiograph and US are poor tools to assess urinary tract stones. In the absence of a therapeutic consequence, the KUB radiograph does not seem justified in the routine follow-up of the urinary tract in spinal injury patients.

Cardiovascular disease in live related renal transplantation.

PubMed

Kaul, A; Sharm, R K; Gupta, A; Sinha, N; Singh, U

2011-11-01

Cardiovascular disease has become the leading cause of morbidity and mortality in renal transplant recipients, although its pathogenesis and treatment are poorly understood. Modifiable cardiovascular risk factors and graft dysfunction both play an important role in development of post transplant cardiovascular events. Prevalence of cardiovascular disease was studied in stable kidney transplant patients on cyclosporine based triple immunosuppression in relation to the various risk factors and post transplant cardiovascular events. Analysis of 562 post transplant patients with stable graft function for 6 months, the patients were evaluated for cardiovascular events in post transplant period. Pre and post transplant risk factors were analyzed using the COX proportional hazard model. 174 patients had undergone pre transplant coronary angiography, 15 of these patients underwent coronary revascularization (angioplasty in 12, CABG in 3). The prevalence of CAD was 7.2% in transplant recipients. Of 42 patients with CAD 31 (73.8%) had cardiovascular event in post transplant period. Age > or = 40 yrs, male sex, graft dysfunction, diabetes as primary renal disease, pre transplant cardiovascular event, chronic rejection showed significant correlation in univariate analysis and there was significant between age > or = 40 years (OR = 2.16 with 95% CI, 0.977-4.78) S creatinine > or = 1.4 mg % (OR = 2.40 with 95% CI, 1.20 - 4.82), diabetes as primary disease (OR with 95% CI 3.67, 3.2-14.82), PTDM (OR 3.67, 95% CI 1.45-9.40), pre-transplant cardiovascular disease (OR 4.14, 95% CI .38-13.15) with post transplant cardiovascular event on multivariate analysis. There was poor patient and graft survival among those who suffered post transplant cardiovascular event. The incidence of cardiovascular disease continues to be high after renal transplantation and modifiable risk factors should be identified to prevent occurrence of events in post transplant period.

When health systems are barriers to health care: challenges faced by uninsured Mexican kidney patients.

PubMed

Kierans, Ciara; Padilla-Altamira, Cesar; Garcia-Garcia, Guillermo; Ibarra-Hernandez, Margarita; Mercado, Francisco J

2013-01-01

Chronic Kidney Disease disproportionately affects the poor in Low and Middle Income Countries (LMICs). Mexico exemplifies the difficulties faced in supporting Renal Replacement Therapy (RRT) and providing equitable patient care, despite recent attempts at health reform. The objective of this study is to document the challenges faced by uninsured, poor Mexican families when attempting to access RRT. The article takes an ethnographic approach, using interviewing and observation to generate detailed accounts of the problems that accompany attempts to secure care. The study, based in the state of Jalisco, comprised interviews with patients, their caregivers, health and social care professionals, among others. Observations were carried out in both clinical and social settings. In the absence of organised health information and stable pathways to renal care, patients and their families work extraordinarily hard and at great expense to secure care in a mixed public-private healthcare system. As part of this work, they must navigate challenging health and social care environments, negotiate treatments and costs, resource and finance healthcare and manage a wide range of formal and informal health information. Examining commonalities across pathways to adequate healthcare reveals major failings in the Mexican system. These systemic problems serve to reproduce and deepen health inequalities. A system, in which the costs of renal care are disproportionately borne by those who can least afford them, faces major difficulties around the sustainability and resourcing of RRTs. Attempts to increase access to renal therapies, therefore, need to take into account the complex social and economic demands this places on those who need access most. This paper further shows that ethnographic studies of the concrete ways in which healthcare is accessed in practice provide important insights into the plight of CKD patients and so constitute an important source of evidence in that effort.

How good are we at managing acute kidney injury in hospital?

PubMed

Meran, Soma; Wonnacott, Alexa; Amphlett, Bethan; Phillips, Aled

2014-04-01

Acute kidney injury (AKI) is a common clinical problem associated with adverse outcomes. This study identifies the incidence of AKI in two UK district general hospitals' without on-site renal services and assesses AKI management and level of nephrologist input. The AKIN classification was used to identify 1020 AKI patients over 6 months. Data were collated on patient demographics, AKI management and referral to nephrology and intensive care services. Short/long-term renal outcomes were investigated. Patients were followed up for 14 months post-discharge. Incidence of hospital-based AKI was 6.4%. Mean patient age was 73 years. There was 28.1% acute in-hospital mortality with a further 21.6% 14-month mortality. Only 8.3% of patients were referred to nephrology services for in-hospital review, and only 8.1% had outpatient nephrology follow-up. Compliance with the AKI National Confidential Enquiry into Patient Outcomes and Deaths (NCEPOD) recommendations was poor with 32.8% of patients having renal imaging and 15% of patients having acid-base status assessed. NCEPOD compliance improved with nephrology input. Patients referred to nephrology were likely to be younger with pre-existing CKD and severe AKI. 10.5% of AKI episodes were unrecognized. Forty percent of those with unrecognized AKI, (compared with 15% of recognized AKI) developed de novo or progression of pre-existing CKD. AKI in DGHs is mostly managed without nephrology input. There are significant shortcomings in AKI recognition and management in this setting. This is associated with poor mortality and long-term CKD. This study supports a need to improve the teaching and training of front-line medical staff in identifying AKI. Additionally, implementation of AKI e-alert systems may encourage early recognition and provide a prompt for renal referral.

Readmission for dehydration or renal failure after ileostomy creation.

PubMed

Paquette, Ian M; Solan, Patrick; Rafferty, Janice F; Ferguson, Martha A; Davis, Bradley R

2013-08-01

Ileostomy creation is a commonly performed operation in colorectal surgery; however, many patients develop complications such as dehydration postoperatively. Dehydration is often severe enough to warrant hospital readmission and may result in renal failure. The true incidence of this complication has not been well described. The aim of this study was to identify the rate of hospital readmission secondary to dehydration or renal failure within 30 days of ileostomy creation. Retrospective review of all patients undergoing ileostomy creation from 2007 to 2011 in a single colorectal practice of 4 surgeons was performed. Charts were reviewed to identify patients readmitted for dehydration or renal failure within 30 days of operation. Data were then analyzed to identify predictors of readmission, dehydration, and renal failure. Subset analysis compared patients readmitted with simple dehydration versus patients with renal failure. Two hundred one patients undergoing colorectal operations that included ileostomy creation within a 4-year period at a single institution for a variety of indications were included. The primary outcome measured was readmission for dehydration or renal failure. We observed a 17% 30-day readmission rate for dehydration or renal failure following ileostomy creation. Age greater than 50 was identified as an independent predictor of readmission with renal failure, whereas IPAA was predictive of readmission for simple dehydration, but not renal failure. Patients admitted with renal failure had significantly longer hospital stays and median hospital charges after readmission in comparison with patients admitted with simple dehydration. This study was limited by its retrospective nature and its limited sample size. Hospital readmission due to dehydration or renal failure following ileostomy creation is common, with age >50 being the strongest predictor for renal failure. Appropriate strategies to decrease dehydration and renal failure following ileostomy creation need to be investigated.

Blocking rpS6 Phosphorylation Exacerbates Tsc1 Deletion–Induced Kidney Growth

PubMed Central

Wu, Huijuan; Chen, Jianchun; Xu, Jinxian; Dong, Zheng; Meyuhas, Oded

2016-01-01

The molecular mechanisms underlying renal growth and renal growth–induced nephron damage remain poorly understood. Here, we report that in murine models, deletion of the tuberous sclerosis complex protein 1 (Tsc1) in renal proximal tubules induced strikingly enlarged kidneys, with minimal cystogenesis and occasional microscopic tumorigenesis. Signaling studies revealed hyperphosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and increased phosphorylation of ribosomal protein S6 (rpS6) in activated renal tubules. Notably, knockin of a nonphosphorylatable rpS6 in these Tsc1-mutant mice exacerbated cystogenesis and caused drastic nephron damage and renal fibrosis, leading to kidney failure and a premature death rate of 67% by 9 weeks of age. In contrast, Tsc1 single-mutant mice were all alive and had far fewer renal cysts at this age. Mechanistic studies revealed persistent activation of mammalian target of rapamycin complex 1 (mTORC1) signaling causing hyperphosphorylation and consequent accumulation of 4E-BP1, along with greater cell proliferation, in the renal tubules of Tsc1 and rpS6 double-mutant mice. Furthermore, pharmacologic treatment of Tsc1 single-mutant mice with rapamycin reduced hyperphosphorylation and accumulation of 4E-BP1 but also inhibited phosphorylation of rpS6. Rapamycin also exacerbated cystic and fibrotic lesions and impaired kidney function in these mice, consequently leading to a premature death rate of 40% within 2 weeks of treatment, despite destroying tumors and decreasing kidney size. These findings indicate that Tsc1 prevents aberrant renal growth and tumorigenesis by inhibiting mTORC1 signaling, whereas phosphorylated rpS6 suppresses cystogenesis and fibrosis in Tsc1-deleted kidneys. PMID:26296742

Effect of renal function status on the prognostic value of heart rate in acute ischemic stroke patients.

PubMed

Zhu, Zhengbao; Zhong, Chongke; Xu, Tian; Wang, Aili; Peng, Yanbo; Xu, Tan; Peng, Hao; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Geng, Deqin; Sun, Yingxian; Du, Qingjuan; Li, Yongqiu; Chen, Jing; Zhang, Yonghong; He, Jiang

2017-08-01

The association between heart rate and prognosis of ischemic stroke remains debatable, and whether renal function status influences the relationship between them is still not elucidated. A total of 3923 ischemic stroke patients were included in this prospective multicenter study from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes were, separately, death and major disability. The association between heart rate tertiles and primary outcome was appreciably modified by renal function status (p interaction  = 0.037). After multivariate adjustment, high heart rate was associated with increased risk of primary outcome in patients with abnormal renal function (odds ratio, 1.61; 95% confidence interval, 1.02-2.54; p trend  = 0.039) but not in patients with normal renal function (odds ratio, 0.96; 95% confidence interval, 0.75-1.23; p trend  = 0.741), when two extreme tertiles were compared. Each 10 bpm increase of heart rate was associated with 21% (95% CI: 1%-44%) increased risk of primary outcome, and a linear association between heart rate and risk of primary outcome was observed among patients with abnormal renal function (p for linearity = 0.002). High heart rate may be merely a strong predictor of poor prognosis in acute ischemic stroke patients with abnormal renal function, suggesting that heart rate reduction should be applied to ischemic stroke patients with abnormal renal function to improve their prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

[Sarcomatoid renal cell carcinoma].

PubMed

Arnoux, V; Lechevallier, E; Pamela, A; Long, J-A; Rambeaud, J-J

2013-06-01

The objective was to perform a systematic review of literature concerning epidemiology, clinical and biological data, prognosis and therapy of sarcomatoid renal cell carcinomas. Data on sarcomatoid renal cell carcinomas have been sought by querying the server Medline with MeSH terms following or combination of them: "renal carcinoma", "renal cell carcinoma," "renal cancer", "sarcomatoid" "sarcomatoid transformation" and "sarcomatoid differentiation." The articles obtained were selected according to their methodology, the language in English or French, the relevance and the date of publication. Twenty papers were selected. According to the literature, a sarcomatoid contingent can be observed in all subtypes of renal cell carcinomas, with a frequency of 1 to 15% of cases. The median age at diagnosis was 60 years with a majority of symptomatic patients (90%), mainly with abdominal pain and hematuria. These tumors were often found in patients with locally advanced or metastatic (45-77%). The imaging was not specific for the diagnosis and biopsy had a low sensitivity for identifying a sarcomatoid contingent. The treatment was based on a combination of maximal surgical resection whenever possible and systemic therapy for metastastic disease. Pathological data often showed large tumors, Furhman 4 grades, combined biphasic carcinomatous contingent (clear cell carcinoma in most cases) and sarcomatoid. Genetically, there was no specific abnormality but a complex association of chromosomal additions and deletions. The prognosis was pejorative with a specific median survival of 5 to 19 months without any impact of the sarcomatoid contingent rate. Sarcomatoid renal cell carcinoma is a form not to ignore despite its rarity. Mainly symptomatic and discovered at an advanced stage, it has a poor prognosis, requiring multidisciplinary management quickly and correctly. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Long-term prognosis of AL and AA renal amyloidosis: a Japanese single-center experience.

PubMed

Ozawa, Masatoyo; Komatsuda, Atsushi; Ohtani, Hiroshi; Nara, Mizuho; Sato, Ryuta; Togashi, Masaru; Takahashi, Naoto; Wakui, Hideki

2017-04-01

Few studies have been conducted on the long-term prognosis of patients with amyloid light chain (AL) and amyloid A (AA) renal amyloidosis in the same cohort. We retrospectively examined 68 patients with biopsy-proven renal amyloidosis (38 AL and 30 AA). Clinicopathological findings at the diagnosis and follow-up data were evaluated in each patient. We analyzed the relationship between clinicopathological parameters and survival data. Significant differences were observed in several clinicopathological features, such as proteinuria levels, between the AL and AA groups. Among all patients, 84.2 % of the AL group and 93.3 % of the AA group received treatments for the underlying diseases of amyloidosis. During the follow-up period (median 18 months in AL and 61 months in AA), 36.8 % of the AL group and 36.7 % of the AA group developed end-stage renal failure requiring dialysis, while 71.1 % of the AL group and 56.7 % of the AA group died. Patient and renal survivals were significantly longer in the AA group than in the AL group. eGFR of >60 mL/min/1.73 m 2 at biopsy and an early histological stage of glomerular amyloid deposition were identified as low-risk factors. A multivariate analysis showed that cardiac amyloidosis and steroid therapy significantly influenced patient and renal survivals. Our results showed that heart involvement was the major predictor of poor outcomes in renal amyloidosis, and that the prognosis of AA renal amyloidosis was markedly better than that in previously reported cohorts. Therapeutic advances in inflammatory diseases are expected to improve the prognosis of AA amyloidosis.

A novel angiotensin II type 1 receptor-associated protein induces cellular hypertrophy in rat vascular smooth muscle and renal proximal tubular cells.

PubMed

Guo, Deng-Fu; Tardif, Valerie; Ghelima, Karin; Chan, John S D; Ingelfinger, Julie R; Chen, XiangMei; Chenier, Isabelle

2004-05-14

Angiotensin II stimulates cellular hypertrophy in cultured vascular smooth muscle and renal proximal tubular cells. This effect is believed to be one of earliest morphological changes of heart and renal failure. However, the precise molecular mechanism involved in angiotensin II-induced hypertrophy is poorly understood. In the present study we report the isolation of a novel angiotensin II type 1 receptor-associated protein. It encodes a 531-amino acid protein. Its mRNA is detected in all human tissues examined but highly expressed in the human kidney, pancreas, heart, and human embryonic kidney cells as well as rat vascular smooth muscle and renal proximal tubular cells. Protein synthesis and relative cell size analyzed by flow cytometry studies indicate that overexpression of the novel angiotensin II type 1 receptor-associated protein induces cellular hypertrophy in cultured rat vascular smooth muscle and renal proximal tubular cells. In contrast, the hypertrophic effects was reversed in renal proximal tubular cell lines expressing the novel gene in the antisense orientation and its dominant negative mutant, which lacks the last 101 amino acids in its carboxyl-terminal tail. The hypertrophic effects are at least in part mediated via protein kinase B activation or cyclin-dependent kinase inhibitor, p27(kip1) protein expression level in vascular smooth muscle, and renal proximal tubular cells. Moreover, angiotensin II could not stimulate cellular hypertrophy in renal proximal tubular cells expressing the novel gene in the antisense orientation and its mutant. These findings may provide new molecular mechanisms to understand hypertrophic agents such as angiotensin II-induced cellular hypertrophy.

Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition.

PubMed

Sciacovelli, Marco; Gonçalves, Emanuel; Johnson, Timothy Isaac; Zecchini, Vincent Roberto; da Costa, Ana Sofia Henriques; Gaude, Edoardo; Drubbel, Alizee Vercauteren; Theobald, Sebastian Julian; Abbo, Sandra Riekje; Tran, Maxine Gia Binh; Rajeeve, Vinothini; Cardaci, Simone; Foster, Sarah; Yun, Haiyang; Cutillas, Pedro; Warren, Anne; Gnanapragasam, Vincent; Gottlieb, Eyal; Franze, Kristian; Huntly, Brian; Maher, Eamonn Richard; Maxwell, Patrick Henry; Saez-Rodriguez, Julio; Frezza, Christian

2016-08-31

Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer. Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor clinical outcome. Fumarate, a small molecule metabolite that accumulates in fumarate hydratase-deficient cells, plays a key role in cell transformation, making it a bona fide oncometabolite. Fumarate has been shown to inhibit α-ketoglutarate-dependent dioxygenases that are involved in DNA and histone demethylation. However, the link between fumarate accumulation, epigenetic changes, and tumorigenesis is unclear. Here we show that loss of fumarate hydratase and the subsequent accumulation of fumarate in mouse and human cells elicits an epithelial-to-mesenchymal-transition (EMT), a phenotypic switch associated with cancer initiation, invasion, and metastasis. We demonstrate that fumarate inhibits Tet-mediated demethylation of a regulatory region of the antimetastatic miRNA cluster mir-200ba429, leading to the expression of EMT-related transcription factors and enhanced migratory properties. These epigenetic and phenotypic changes are recapitulated by the incubation of fumarate hydratase-proficient cells with cell-permeable fumarate. Loss of fumarate hydratase is associated with suppression of miR-200 and the EMT signature in renal cancer and is associated with poor clinical outcome. These results imply that loss of fumarate hydratase and fumarate accumulation contribute to the aggressive features of fumarate hydratase-deficient tumours.

Factors Associated with Uncontrolled Hypertension among Renal Transplant Recipients Attending Nephrology Clinics in Nairobi, Kenya

PubMed Central

Kubo, Mary N.; Kayima, Joshua K.; Were, Anthony J.; McLigeyo, Seth O.; Ogola, Elijah N.

2015-01-01

Objective. To determine the factors associated with poor blood pressure control among renal transplant recipients in a resource-limited setting. Methods. A cross-sectional study was carried out on renal transplant recipients at the Kenyatta National Hospital. Sociodemographic details, blood pressure, urine albumin : creatinine ratio, and adherence using the MMAS-8 questionnaire were noted. Independent factors associated with uncontrolled hypertension were determined using logistic regression analysis. Results. 85 subjects were evaluated. Mean age was 42.4 (SD ± 12.2) years, with a male : female ratio of 1.9 : 1. Fifty-five patients (64.7%) had uncontrolled hypertension (BP ≥ 130/80 mmHg). On univariate analysis, male sex (OR 3.7, 95% CI 1.4–9.5, p = 0.006), higher levels of proteinuria (p = 0.042), and nonadherence to antihypertensives (OR 18, 95% CI 5.2–65.7, p < 0.001) were associated with uncontrolled hypertension. On logistic regression analysis, male sex (adjusted OR 4.6, 95% CI 1.1–19.0, p = 0.034) and nonadherence (adjusted OR 33.8, 95% CI 8.6–73.0, p < 0.001) were independently associated with uncontrolled hypertension. Conclusion. Factors associated with poor blood pressure control in this cohort were male sex and nonadherence to antihypertensives. Emphasis on adherence to antihypertensive therapy must be pursued within this population. PMID:26257920

Deregulation of E2-EPF ubiquitin carrier protein in papillary renal cell carcinoma.

PubMed

Roos, Frederik C; Evans, Andrew J; Brenner, Walburgis; Wondergem, Bill; Klomp, Jeffery; Heir, Pardeep; Roche, Olga; Thomas, Christian; Schimmel, Heiko; Furge, Kyle A; Teh, Bin T; Thüroff, Joachim W; Hampel, Christian; Ohh, Michael

2011-02-01

Molecular pathways associated with pathogenesis of sporadic papillary renal cell carcinoma (PRCC), the second most common form of kidney cancer, are poorly understood. We analyzed primary tumor specimens from 35 PRCC patients treated by nephrectomy via gene expression analysis and tissue microarrays constructed from an additional 57 paraffin-embedded PRCC samples via immunohistochemistry. Gene products were validated and further studied by Western blot analyses using primary PRCC tumor samples and established renal cell carcinoma cell lines, and potential associations with pathologic variables and survival in 27 patients with follow-up information were determined. We show that the expression of E2-EPF ubiquitin carrier protein, which targets the principal negative regulator of hypoxia-inducible factor (HIF), von Hippel-Lindau protein, for proteasome-dependent degradation, is markedly elevated in the majority of PRCC tumors exhibiting increased HIF1α expression, and is associated with poor prognosis. In addition, we identified multiple hypoxia-responsive elements within the E2-EPF promoter, and for the first time we demonstrated that E2-EPF is a hypoxia-inducible gene directly regulated via HIF1. These findings reveal deregulation of the oxygen-sensing pathway impinging on the positive feedback mechanism of HIF1-mediated regulation of E2-EPF in PRCC. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Comorbid renal tubular damage and hypoalbuminemia exacerbate cardiac prognosis in patients with chronic heart failure.

PubMed

Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Funayama, Akira; Kinoshita, Daisuke; Yokoyama, Miyuki; Takahashi, Tetsuya; Nishiyama, Satoshi; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

2016-02-01

Renal tubular damage (RTD) and hypoalbuminemia are risks for poor prognosis in patients with chronic heart failure (CHF). Renal tubules play a pivotal role in amino acid and albumin reabsorption, which maintain serum albumin levels. The aims of the present study were to (1) examine the association of RTD with hypoalbuminemia, and (2) assess the prognostic importance of comorbid RTD and hypoalbuminemia in patients with CHF. We measured N-acetyl-β-D-glucosamidase (NAG) levels and the urinary β2-microglobulin to creatinine ratio (UBCR) in 456 patients with CHF. RTD was defined as UBCR ≥ 300 μg/g or NAG ≥ 14.2 U/g. There were moderate correlations between RTD markers and serum albumin (NAG, r = -0.428, P < 0.0001; UBCR, r = -0.399, P < 0.0001). Multivariate logistic analysis showed that RTD was significantly related to hypoalbuminemia in patients with CHF. There were 134 cardiac events during a median period of 808 days. The comorbidity of RTD and hypoalbuminemia was increased with advancing New York Heart Association functional class. Multivariate Cox proportional hazard regression analysis showed that the presence of RTD and hypoalbuminemia was associated with cardiac events. The net reclassification index was significantly improved by adding RTD and hypoalbuminemia to the basic risk factors. Comorbid RTD and hypoalbuminemia are frequently observed and increase the risk for extremely poor outcome in patients with CHF.

Long-term survival in an adolescent with widely metastatic renal cell carcinoma with rhabdoid features.

PubMed

Ettinger, L J; Goodell, L A; Javidian, P; Hsieh, Y; Amenta, P

2000-01-01

Renal cell carcinoma is rarely seen in children and adolescents. Patients with widespread disease at diagnosis have a particularly poor survival rate. Currently, all known chemotherapy has been ineffective in improving the median survival in patients with advanced disease. A 13-year-old black boy with stage IV renal cell carcinoma with rhabdoid features is a long-term disease-free survivor after aggressive multiagent chemotherapy. After the initial evaluation and histologic diagnosis of renal cell carcinoma, the patient received three courses of an aggressive chemotherapy regimen consisting of vincristine, doxorubicin, cyclophosphamide with mesna uroprotection, granulocyte colony-stimulating factor and erythropoietin (Epogen). After an almost complete response, a radical nephrectomy was performed and results demonstrated a solitary small nodule with viable tumor. After surgery, he received floxuridine infusion for 14 days by circadian schedule at 28-day intervals for a total of 1 year. The patient is well and free of disease 5 years after initial presentation. The dramatic response to treatment and long-term disease-free survival of this patient suggest this chemotherapeutic approach warrants additional investigation.

Curcumin alleviates ischemia reperfusion-induced late kidney fibrosis through the APPL1/Akt signaling pathway.

PubMed

Hongtao, Chen; Youling, Fan; Fang, Huang; Huihua, Peng; Jiying, Zhong; Jun, Zhou

2018-05-09

As a major cause of renal failure, transient renal ischemia and reperfusion induce both acute kidney injury and late fibrosis, which are the common pathological manifestations of end-stage renal disease. Curcumin is a biologically active polyphenolic compound found in turmeric. Increasing evidence has demonstrated that curcumin has a protective action against renal fibrosis, whereas mechanisms underlying the anti-fibrosis role of curcumin remain poorly defined. Here, we found that APPL1, an important intracellular binding partner for AdipoR, was involved in the pathogenesis of acute injury or fibrosis and was significantly upregulated by curcumin in a mouse model of ischemia reperfusion-induced late kidney fibrosis. Moreover, Akt signaling was the specific signaling pathway identified downstream of APPL1 in the pathogenesis of fibrosis. Our in vitro experiment demonstrated that curcumin alleviates ischemia reperfusion-induced late kidney fibrosis via the APPL1/Akt pathway. These data are helpful for understanding the anti-fibrosis mechanism of curcumin in the pathogenesis of AKI-induced late fibrosis. © 2018 Wiley Periodicals, Inc.

Long-term Renal Function in Living Kidney Donors Who Had Histological Abnormalities at Donation.

PubMed

Fahmy, Lara M; Massie, Allan B; Muzaale, Abimereki D; Bagnasco, Serena M; Orandi, Babak J; Alejo, Jennifer L; Boyarsky, Brian J; Anjum, Saad K; Montgomery, Robert A; Dagher, Nabil N; Segev, Dorry L

2016-06-01

Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5-8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73 m decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (P < 0.01). In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, whereas no other subclinical histological abnormalities provided additional information.

Long-Term Renal Function in Living Kidney Donors who had Histological Abnormalities at Donation

PubMed Central

Fahmy, Lara M.; Massie, Allan B.; Muzaale, Abimereki D.; Bagnasco, Serena M.; Orandi, Babak J.; Alejo, Jennifer L.; Boyarsky, Brian J.; Anjum, Saad K.; Montgomery, Robert A.; Dagher, Nabil N.; Segev, Dorry L.

2016-01-01

Background Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. Methods We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Results Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5–8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73m2 decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (p<0.01). Conclusions In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, while no other subclinical histological abnormalities provided additional information. PMID:27152920

A Prospective Observational Study on the Predictive Value of Serum Cystatin C for Successful Weaning from Continuous Renal Replacement Therapy.

PubMed

Kim, Chang Seong; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

2018-05-30

There is a paucity of literature that investigates a biomarker associated with successful renal recovery following continuous renal replacement therapy (CRRT). Our study aimed to identify potential renal biomarkers or clinical indicators that could predict the successful weaning from CRRT. We conducted a prospective, observational study of 110 patients who had received CRRT and were weaned after renal recovery. Patients were considered to have successfully weaned from CRRT once there was no need for renal replacement therapy (RRT) for at least 14 days. For patients who had to restart dialysis within 14 days were considered unsuccessful. Of the 110 patients evaluated, 89 (80.9%) were successfully weaned from CRRT. These patients had lower serum cystatin C (CysC) levels and higher urine output than the group that restarted RRT at the time of CRRT cessation. However, the levels of serum creatinine and neutrophil gelatinase-associated lipocalin were not significantly lower in the successful group compared to the restart-RRT group. A multivariable logistic regression showed that serum CysC was an independent predictor for the successful weaning from CRRT. Furthermore, in a multivariable Cox proportional hazards analysis, the group that was successfully weaned from CRRT had a lower in-hospital mortality compared to the restarted RRT group. Serum CysC, at the time of CRRT cessation, is an independent predictor of the successful weaning from CRRT in critically ill patients with acute kidney injury. © 2018 The Author(s). Published by S. Karger AG, Basel.

Organisation of lymphocytic infiltrates in ANCA-associated glomerulonephritis.

PubMed

Brix, Silke R; Noriega, Mercedes; Herden, Elisabeth M; Goldmann, Birgit; Langbehn, Ulrike; Busch, Martin; Jabs, Wolfram J; Steinmetz, Oliver M; Panzer, Ulf; Huber, Tobias B; Stahl, Rolf A K; Wiech, Thorsten

2018-06-01

Renal involvement in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis contributes to significant morbidity and mortality in patients. In chronic inflammation, B cells are recruited to the inflamed tissue and organised lymphoid structures have been described in several autoimmune diseases. The aim of this study was to correlate the lymphoid organisation in renal biopsies with renal outcome in ANCA-associated glomerulonephritis (GN). We investigated 112 renal biopsies from patients with newly diagnosed ANCA-associated necrotising GN. We identified four different levels of the intrarenal organisation of lymphocytes: T cells without B cells, scattered B and T cells, clustered lymphocytic infiltrates and nodular compartmentally arranged B and T cell aggregates. Almost half the patients showed clusters of B and T lymphocytes in their biopsies. In 15 of these biopsies, a higher degree of organisation with lymphocytic compartments was detected. Inflammatory cell organisation was associated with renal failure, but not with tubular atrophy and interstitial fibrosis. Patients with organised lymphocytic infiltrates in their biopsy had worse renal function during follow-up and were more likely to develop end stage renal disease. In the present study, we show that the renal lymphocytic organisation is associated with renal outcome in ANCA-associated GN. The organisation of the lymphocytic infiltrate may be a morphological correlate of a perpetual and exaggerated inflammation in renal ANCA disease. Classifying the lymphocytic infiltrate could help to predict renal outcome, and might therefore be used for individualised adjustments in the intensity and duration of immunosuppressive therapy. © 2018 John Wiley & Sons Ltd.

Functional MRI detects perfusion impairment in renal allografts with delayed graft function.

PubMed

Hueper, Katja; Gueler, Faikah; Bräsen, Jan Hinrich; Gutberlet, Marcel; Jang, Mi-Sun; Lehner, Frank; Richter, Nicolas; Hanke, Nils; Peperhove, Matti; Martirosian, Petros; Tewes, Susanne; Vo Chieu, Van Dai; Großhennig, Anika; Haller, Hermann; Wacker, Frank; Gwinner, Wilfried; Hartung, Dagmar

2015-06-15

Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF. Copyright © 2015 the American Physiological Society.

Biological mechanism analysis of acute renal allograft rejection: integrated of mRNA and microRNA expression profiles.

PubMed

Huang, Shi-Ming; Zhao, Xia; Zhao, Xue-Mei; Wang, Xiao-Ying; Li, Shan-Shan; Zhu, Yu-Hui

2014-01-01

Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may be related to acute renal allograft rejection.

Biological mechanism analysis of acute renal allograft rejection: integrated of mRNA and microRNA expression profiles

PubMed Central

Huang, Shi-Ming; Zhao, Xia; Zhao, Xue-Mei; Wang, Xiao-Ying; Li, Shan-Shan; Zhu, Yu-Hui

2014-01-01

Objectives: Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. Methods: MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. Results: A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. Conclusions: We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may be related to acute renal allograft rejection. PMID:25664019

Scleroderma renal crisis in a case of mixed connective tissue disease.

PubMed

Vij, Mukul; Agrawal, Vinita; Jain, Manoj

2014-07-01

Mixed connective tissue disease (MCTD) is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma) and polymyositis. Scleroderma renal crisis (SRC) is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

Biochemical markers of acute limb ischemia, rhabdomyolysis, and impact on limb salvage.

PubMed

Watson, J Devin B; Gifford, Shaun M; Clouse, W Darrin

2014-12-01

Biochemical markers of ischemia reperfusion injury have been of interest to vascular surgeons and researchers for many years. Acute limb ischemia is the quintessential clinical scenario where these markers would seem relevant. The use of biomarkers to preoperatively or perioperatively predict which patients will not tolerate limb-salvage efforts or who will have poor functional outcomes after salvage is of immense interest. Creatinine phosphokinase, myoglobin, lactate, lactate dehydrogenase, potassium, bicarbonate, and neutrophil/leukocyte ratios are a few of the studied biomarkers available. Currently, the most well-studied aspect of ischemia reperfusion injury is rhabdomyolysis leading to acute kidney injury. The last 10 years have seen significant progression and improvement in the treatment of rhabdomyolysis, from minor supportive care to use of continuous renal replacement therapy. Identification of specific biomarkers with predictive outcome characteristics in the setting of ischemia reperfusion injury will help guide therapeutic development and potentially mitigate pathophysiologic changes in acute limb ischemia, including rhabdomyolysis. These may further lead to improvements in short- and long-term surgical outcomes and limb salvage, as well as a better understanding of the timing and selection of intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

Metastatic Neuroendocrine Tumour in a Renal Transplant Recipient: Dual-Tracer PET-CT with (18)F-FDG and (68)Ga-DOTANOC in This Rare Setting.

PubMed

Karunanithi, Sellam; Roy, Shambo Guha; Sharma, Punit; Yadav, Rajni; Bal, Chandrasekhar; Kumar, Rakesh

2015-03-01

Recipients of renal transplant are at increased risk of developing various malignancies, especially post-transplant lymphoproliferative disorder (PTLD) and skin cancers. Neuroendocrine tumours (NET) of the gastrointestinal tract have not been reported in this setting. Here we describe the case of a 75-year-old male who had undergone renal transplant 8 years back and now presented with significant weight loss and backache, clinically suspected as PTLD. (18)F-Fluordeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) showed hypermetabolic lesions in the liver and rectum, raising the suspicion of PTLD. However, biopsy from the liver lesion showed poorly differentiated NET. (68)Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI(3)-octreotide ((68)Ga-DOTANOC) PET-CT was then done, which confirmed the primary lesion in the rectum with liver metastases.

A case of rhabdomyolysis after kidney transplantation successfully managed with intensive continuous dialysis.

PubMed

Shahbazov, Rauf; Fox, Michael; Alejo, Jennifer L; Anjum, Malik A; Azari, Feredun; Doyle, Alden; Agarwal, Avinash; Brayman, Kenneth L

2018-04-01

Rhabdomyolysis is characterized by muscle cell death which can result in acute kidney injury from pigment nephropathy. We present a patient who developed rhabdomyolysis immediately after deceased donor kidney transplantation surgery and was managed with continuous renal replacement therapy that resulted in successful salvage of the kidney allograft. Patients who develop acute kidney failure requiring renal replacement therapy generally have a poor prognosis. It is worth noting that while continuous veno-venous hemofiltration (CVVHF) offers greater volume support and continuous clearance compared to hemodialysis (HD), recent studies have demonstrated no clinically significant improvement in clinical outcome between the two. Perhaps CVVHF is a better modality compared to HD in this setting to prevent further insult from pigment nephropathy to an allograft. A combination of early diagnosis and intensive continuous renal replacement therapy can be used for allograft salvage in a patient with rhabdomyolysis in the immediate post-kidney transplant period.

Nutrition in children with CRF and on dialysis

PubMed Central

Shaw, Vanessa

2007-01-01

The objectives of this study are: (1) to understand the importance of nutrition in normal growth; (2) to review the methods of assessing nutritional status; (3) to review the dietary requirements of normal children throughout childhood, including protein, energy, vitamins and minerals; (4) to review recommendations for the nutritional requirements of children with chronic renal failure (CRF) and on dialysis; (5) to review reports of spontaneous nutritional intake in children with CRF and on dialysis; (6) to review the epidemiology of nutritional disturbances in renal disease, including height, weight and body composition; (7) to review the pathological mechanisms underlying poor appetite, abnormal metabolic rate and endocrine disturbances in renal disease; (8) to review the evidence for the benefit of dietetic input, dietary supplementation, nasogastric and gastrostomy feeds and intradialytic nutrition; (9) to review the effect of dialysis adequacy on nutrition; (10) to review the effect of nutrition on outcome. PMID:17216263

Value of Nephrometry Score Constituents on Perioperative Outcomes and Split Renal Function in Patients Undergoing Minimally Invasive Partial Nephrectomy.

PubMed

Watts, Kara L; Ghosh, Propa; Stein, Solomon; Ghavamian, Reza

2017-01-01

To assess the relationship between individual nephrometry score (NS) constituents (RENAL) on perioperative outcomes and renal function of the surgical kidney in patients undergoing laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy. Two hundred forty-five patients who underwent laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Each renal mass' NS was calculated from preoperative computed tomography imaging. Multivariate regression analysis was used to evaluate the effect of NS variables on perioperative outcomes and change in overall renal function (as estimated by glomerular filtration rate) from preoperative to 1-year postoperative. A cohort analysis assessed the effect of NS variables on change in split renal function of the surgical kidney from pre- to postoperative based on nuclear medicine renal scintigraphy. Tumor radius (R), endophytic nature (E), and nearness to collecting system (N) variables significantly and incrementally predicted a longer operative time and warm ischemia time. Overall renal function based on glomerular filtration rate was not affected by any NS variable. However, percent function of the surgical kidney by renal scintigraphy significantly decreased postoperatively as R and E values increased. R, E, and N were associated with significant changes in warm ischemia time and operative time. R and E were associated with a significant decrease in split renal function of the surgical kidney at 1 year after surgery but not with overall renal function. R, E, and N are the NS constituents most relevant to perioperative outcomes and postoperative differential renal function after partial nephrectomy. Copyright © 2016. Published by Elsevier Inc.

Zinc restriction during different periods of life: influence in renal and cardiovascular diseases.

PubMed

Tomat, Analía Lorena; Costa, María de los Ángeles; Arranz, Cristina Teresa

2011-04-01

Micronutrient undernutrition during critical periods of growth has become an important health issue in developing and developed countries, particularly among pregnant women and children having an imbalanced diet. Zinc is a widely studied microelement in infant feeding because it is a component of several enzymes involved in intermediary metabolism ranging from growth to cell differentiation and metabolism of proteins, carbohydrates, and lipids. Human and experimental studies have reported an association between zinc deficiency and the etiopathogenesis of cardiovascular and renal diseases like hypertension, atherosclerosis, congestive heart failure, coronary heart disease, and diabetes. The main links between the development of these pathologies and zinc deficiency are multiple mechanisms involving oxidative stress damage, apoptosis, and inflammation. A substantial body of evidence suggests that a poor in utero environment elicited by maternal dietary or placental insufficiency may "programme" susceptibility in the fetus to later development of cardiovascular, renal, metabolic, and endocrine diseases. Zinc deficiency in rats during intrauterine and postnatal growth can also be considered a model of fetal programming of cardiovascular and renal diseases in adult life. Dietary zinc restriction during fetal life, lactation, and/or postweaning induces an increase in arterial blood pressure and impairs renal function in adult life. This review focuses on the contributions of experimental and clinical studies to current knowledge of the physiologic role of zinc in the cardiovascular and renal systems. Moreover, this review examines the relationship between zinc deficiency during different periods of life and the development of cardiovascular and renal diseases in adult life. Copyright © 2011 Elsevier Inc. All rights reserved.

Anti-neutrophil cytoplasmic antibody-associated vasculitis with renal involvement: Analysis of 89 cases.

PubMed

Caravaca-Fontán, Fernando; Yerovi, Estefanía; Delgado-Yagu E, María; Galeano, Cristina; Pampa-Saico, Saúl; Tenorio, Maria Teresa; Liaño, Fernando

2017-01-06

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement are associated with high morbi-mortality. In this study we analyse if the prognosis of these diseases have improved in recent years, and which factors influence the outcomes. Retrospective single-centre observational study, which included all patients diagnosed with microscopic polyangiitis and granulomatosis with polyangiitis with renal involvement in the last 25 years. Demographic, clinical and biochemical parameters of prognostic interest were recorded. The differences between four chronological periods were analysed, along with the determinants of a poor outcome (death or end-stage renal disease). Eighty-nine patients were included (mean age 64±15 years). Sixty-four patients (72%) had microscopic polyangiitis and 25 (28%) granulomatosis with polyangiitis. During the study period, 37 (42%) patients died. Through Cox regression analysis, the best determinants of mortality were the initial glomerular filtration rate (HR 0.911; P=.003), Charlson comorbidity index (HR 1.513; P<.0001) and tobacco smoking (HR 1.816; P=.003). 35% developed end-stage renal disease, and the best determinants (by competing-risk regression) were: initial glomerular filtration rate (sub-hazard ratio [SHR]: 0.791; P<.0001), proteinuria (SHR: 1.313; P<.0001), and smoking status (SHR: 1.848; P=.023). No differences were found in patients' mortality or renal survival between the different study periods. Prognosis of anti-neutrophil cytoplasm antibodies vasculitis with renal involvement treated with conventional immunosuppressive therapy remains unsatisfactory, and continues to have increased long-term complications and mortality. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Multislice CT Angiography in Renal Artery Stent Evaluation: Prospective Comparison with Intra-Arterial Digital Subtraction Angiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raza, Syed A.; Chughtai, Aamer R.; Wahba, Mona

2004-01-15

Purpose: To assess the role of multislice computed tomography angiography (MCTA) in the evaluation of renal artery stents, using intra-arterial digital subtraction angiography (DSA) as the gold standard. Methods: Twenty consecutive patients (15 men, 5 women) with 23 renal artery stents prospectively underwent both MCTA and DSA. Axial images, multiplanar reconstructions and maximum intensity projection images were used for diagnosis. The MCTA and DSA images were each interpreted without reference to the result of the other investigation. Results:The three cases of restenosis on DSA were detected correctly by MCTA; in 19 cases where MCTA showed a fully patent stent, themore » DSA was also negative. Sensitivity and negative predictive value (NPV) of MCTA were therefore 100%. In four cases, MCTA showed apparently minimal disease which was not shown on DSA. These cases are taken as false positive giving a specificity of 80% and a positive predictive value of 43%. Conclusion: The high sensitivity and NPV suggest MCTA may be useful as a noninvasive screen for renal artery stentrestenosis. MCTA detected mild disease in a few patients which was not confirmed on angiography.« less

Estimation of Daily Proteinuria in Patients with Amyloidosis by Using the Protein-To-Creatinine ratio in Random Urine Samples.

PubMed

Talamo, Giampaolo; Mir Muhammad, A; Pandey, Manoj K; Zhu, Junjia; Creer, Michael H; Malysz, Jozef

2015-02-11

Measurement of daily proteinuria in patients with amyloidosis is recommended at the time of diagnosis for assessing renal involvement, and for monitoring disease activity. Renal involvement is usually defined by proteinuria >500 mg/day. We evaluated the accuracy of the random urine protein-to-creatinine ratio (Pr/Cr) in predicting 24 hour proteinuria in patient with amyloidosis. We compared results of random urine Pr/Cr ratio and concomitant 24-hour urine collections in 44 patients with amyloidosis. We found a strong correlation (Spearman's ρ=0.874) between the Pr/Cr ratio and the 24 hour urine protein excretion. For predicting renal involvement, the optimal cut-off point of the Pr/Cr ratio was 715 mg/g. The sensitivity and specificity for this point were 91.8% and 95.5%, respectively, and the area under the curve value was 97.4%. We conclude that the random urine Pr/Cr ratio could be useful in the screening of renal involvement in patients with amyloidosis. If validated in a prospective study, the random urine Pr/Cr ratio could replace the 24 hour urine collection for the assessment of daily proteinuria and presence of nephrotic syndrome in patients with amyloidosis.

Rhabdomyolysis after sleeve gastrectomy: increase in muscle enzymes does not predict fatal outcome.

PubMed

Foresteri, Pietro; Pietro, Forestieri; Formato, Antonio; Antonio, Formato; Pilone, Vincenzo; Vincenzo, Pilone; Romano, Antonietta; Antonietta, Romano; Monda, Antonietta; Angela, Monda; Tramontano, Salvatore; Salvatore, Tramontano

2008-03-01

Rhabdomyolysis (RML) is a clinical and biochemical syndrome caused by destruction of skeletal muscles and constitutes a complication of bariatric surgery, with an incidence near to 22%. It is accompanied by increase in serum of intracellular enzymes. Laboratory data as predictive of prognosis have been evaluated by some authors. We report a case of RML after a sleeve gastrectomy, with good prognosis despite a very extensive muscle damage and very high seric and urinary peaks of intracellular enzymes. We describe a 34-years-old super-obese male (body mass index, 54.3 kg/m2) who underwent to laparoscopic sleeve gastrectomy. After 24 h, patient complained of pain in gluteal region, oliguria, and high levels of creatine phosphokinase that reached to 58,395 IU/l. Acute renal failure related to RML was diagnosed. Dialysis was not necessary. Ambulatorial control of renal function after dimission did not reveal a permanent damage. RML is a biochemical syndrome recently associated with bariatric surgery. Early diagnosis is ever necessary. Laboratory data represent markers for diagnosis and prognostic indicator of renal failure. There is no clear relation between seric levels of intracellular enzymes and irreversible renal damage and RML-related mortality.

Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects.

PubMed

Kusuhara, H; Ito, S; Kumagai, Y; Jiang, M; Shiroshita, T; Moriyama, Y; Inoue, K; Yuasa, H; Sugiyama, Y

2011-06-01

A microdose study of metformin was conducted to investigate the predictability of drug-drug interactions at the therapeutic dose (ThD). Healthy subjects received a microdose (100 µg) or ThD (250 mg) of metformin orally, with or without a potent and competitive multidrug and toxin extrusion (MATE) inhibitor, pyrimethamine (50 mg, p.o.), in a crossover fashion. Pyrimethamine significantly reduced the renal clearance of metformin by 23 and 35% at the microdose and ThD, respectively. At ThD, but not at microdose, it caused significant increases in the maximum concentration (C(max)) and area under the plasma concentration-time curve (AUC) of metformin (142 and 139% of control values, respectively). Human canalicular membrane vesicles showed pyrimethamine-inhibitable metformin uptake. Pyrimethamine did not affect plasma lactate/pyruvate after ThD of metformin but significantly reduced the renal clearance of creatinine, thereby causing elevation of plasma creatinine level. This microdose study quantitatively predicted a drug-drug interaction involving the renal clearance of metformin at ThD by pyrimethamine. Pyrimethamine is a useful in vivo inhibitor of MATE proteins.

MicroRNA profiling of human kidney cancer subtypes.

PubMed

Petillo, David; Kort, Eric J; Anema, John; Furge, Kyle A; Yang, Ximing J; Teh, Bin Tean

2009-07-01

Although the functions of most of the identified microRNAs (miRNAs) have yet to be determined, their use as potential biomarkers has been considered in several human diseases and cancers. In order to understand their role in renal tumorigenesis, we screened the expression levels of miRNAs in four subtypes of human renal neoplasms: clear cell, papillary, and chromophobe renal cell carcinomas (RCC) as well as benign renal oncocytomas. We found a unique miRNA signature for each subtype of renal tumor. Furthermore, we identified unique patterns of miRNA expression distinguishing clear cell RCC cases with favorable vs. unfavorable outcome. Specifically, we documented the overexpression of miRs 424 and 203 in clear cell RCC relative to papillary RCC, as well as the inversion of expression of miR-203 in the benign oncocytomas (where it is underexpressed relative to normal kidney) as compared to the malignant chromophobe RCC (where it is overexpressed relative to normal kidney). Our results further suggest that overexpression of S-has-miR-32 is associated with poor outcome. While previous studies have identified unique miRNA expression pattern distinguishing tumors from different anatomical locations, here we extend this principle to demonstrate the utility of miRNA expression profiling to identify a signature unique to various tumor subtypes at a single anatomic locus.

Dual Paraneoplastic Syndromes: Small Cell Lung Carcinoma-related Oncogenic Osteomalacia, and Syndrome of Inappropriate Antidiuretic Hormone Secretion: Report of a Case and Review of the Literature

PubMed Central

Ng, Roland CK

2011-01-01

Acquired isolated renal phosphate wasting associated with a tumor, known as oncogenic osteomalacia or tumor-induced osteomalacia, is a rare paraneoplastic syndrome caused by overproduction of fibroblast growth factor 23. Oncogenic osteomalacia is usually associated with benign mesenchymal tumors. Syndrome of inappropriate antidiuretic hormone secretion (SIADH), on the other hand, is a common paraneoplastic syndrome caused by small cell carcinoma (SCC). Concomitant oncogenic osteomalacia and SIADH associated with SCC is very rare with only 4 other cases reported in the literature. The authors report a case of small cell lung cancer (SCLC)-related renal wasting hypophosphatemia and concurrent SIADH, and review the literature reporting 9 other cases of SCC associated with oncogenic osteomalacia. Almost half of reported cases of renal phosphate wasting associated with SCC concomitantly presented with SIADH. These cases had initial serum phosphorus level lower and survival periods shorter than those without SIADH. This rare combination of a dual paraneoplastic syndrome and low serum phosphorus may be a poor prognostic sign. In addition, both renal phosphate wasting and SIADH usually occur in a short period of time before identification of SCC. Therefore, renal wasting hypophosphatemia with concomitant SIADH/hyponatremia should prompt a search for SCC rather than a benign mesenchymal tumor. PMID:21886301

Dual paraneoplastic syndromes: small cell lung carcinoma-related oncogenic osteomalacia, and syndrome of inappropriate antidiuretic hormone secretion: report of a case and review of the literature.

PubMed

Tantisattamo, Ekamol; Ng, Roland C K

2011-07-01

Acquired isolated renal phosphate wasting associated with a tumor, known as oncogenic osteomalacia or tumor-induced osteomalacia, is a rare paraneoplastic syndrome caused by overproduction of fibroblast growth factor 23. Oncogenic osteomalacia is usually associated with benign mesenchymal tumors. Syndrome of inappropriate antidiuretic hormone secretion (SIADH), on the other hand, is a common paraneoplastic syndrome caused by small cell carcinoma (SCC). Concomitant oncogenic osteomalacia and SIADH associated with SCC is very rare with only 4 other cases reported in the literature. The authors report a case of small cell lung cancer (SCLC)-related renal wasting hypophosphatemia and concurrent SIADH, and review the literature reporting 9 other cases of SCC associated with oncogenic osteomalacia. Almost half of reported cases of renal phosphate wasting associated with SCC concomitantly presented with SIADH. These cases had initial serum phosphorus level lower and survival periods shorter than those without SIADH. This rare combination of a dual paraneoplastic syndrome and low serum phosphorus may be a poor prognostic sign. In addition, both renal phosphate wasting and SIADH usually occur in a short period of time before identification of SCC. Therefore, renal wasting hypophosphatemia with concomitant SIADH/hyponatremia should prompt a search for SCC rather than a benign mesenchymal tumor.

Inflammation and metabolic disorders.

PubMed

Navab, Mohamad; Gharavi, Nima; Watson, Andrew D

2008-07-01

Poor nutrition, overweight and obesity have increasingly become a public health concern as they affect many metabolic disorders, including heart disease, diabetes, digestive system disorders, and renal failure. Study of the effects of life style including healthy nutrition will help further elucidate the mechanisms involved in the adverse effects of poor nutrition. Unhealthy life style including poor nutrition can result in imbalance in our oxidation/redox systems. Lipids can undergo oxidative modification by lipoxygenases, cyclooxygenases, myeloperoxidase, and other enzymes. Oxidized phospholipids can induce inflammatory molecules in the liver and other organs. This can contribute to inflammation, leading to coronary heart disease, stroke, renal failure, inflammatory bowl disease, metabolic syndrome, bone and joint disorders, and even certain types of cancer. Our antioxidant and antiinflammatory defense mechanisms contribute to a balance between the stimulators and the inhibitors of inflammation. Beyond a point, however, these systems might be overwhelmed and eventually fail. High-density lipoprotein is a potent inhibitor of the formation of toxic oxidized lipids. High-density lipoprotein is also an effective system for stimulating the genes whose products are active in the removal, inactivation, and elimination of toxic lipids. Supporting the high-density lipoprotein function should help maintain the balance in these systems. It is hoped that the present report would elucidate some of the ongoing work toward this goal.

The reproducibility and predictive value on outcome of renal biopsies from expanded criteria donors.

PubMed

Azancot, M Antonieta; Moreso, Francesc; Salcedo, Maite; Cantarell, Carme; Perello, Manel; Torres, Irina B; Montero, Angeles; Trilla, Enric; Sellarés, Joana; Morote, Joan; Seron, Daniel

2014-05-01

Reproducibility and predictive value on outcome are the main criteria to evaluate the utility of histological scores. Here we analyze the reproducibility of donor biopsy assessment by different on-call pathologists and the retrospective evaluation by a single renal pathologist blinded to clinical outcomes. We also evaluate the predictive value on graft outcome of both evaluations. A biopsy was performed in donors with any of the following: age≥55 years, hypertension, diabetes, creatinine>1.5 mg/dl, or stroke. Glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal thickening, and arteriolar hyalinosis evaluated according to the Banff criteria were added to obtain a chronic score. Biopsies were classified as mild (≥3), intermediate (4-5), or advanced (6-7) damage, and unacceptable (≥8) for transplantation of 127 kidneys biopsied. Weighted κ value between both readings was 0.41 (95% CI: 0.28-0.54). Evaluation of biopsies by the renal pathologist was significantly and independently associated with estimated 12-month glomerular filtration rate and a significant composite outcome variable, including death-censored graft survival and time to reach an estimated glomerular filtration rate<30 ml/min per 1.73 m2. Thus, there was no association between readings of on-call pathologists and outcome. The lack of association between histological scores obtained by the on-call pathologists and graft outcome suggests that a specific training on renal pathology is recommended to optimize the use of kidneys retrieved from expanded criteria donors.

Systemic lupus erythematosus and thrombotic thrombocytopenia purpura: a refractory case without lupus activity.

PubMed

Garcia Boyero, Raimundo; Mas Esteve, Eva; Mas Esteve, Maria; Millá Perseguer, M Magdalena; Marco Buades, Josefa; Beltran Fabregat, Juan; Cañigral Ferrando, Guillermo; Belmonte Serrano, Miguel Angel

2013-01-01

The association between systemic lupus erythematosus (SLE) and thrombotic thrombocytopenic purpura (TTP) has been infrequently reported. Usually, patients with TTP have more SLE activity and frequent renal involvement. Here we present a case of TTP associated to low-activity SLE. The absence of renal and major organ involvement increased the difficulty in making the initial diagnosis. ADAMTS13 activity in plasma in this patient was very low, as seen in other similar cases. The evolution of the patient was poor, needing plasma exchanges and immunosuppressive therapy, including the use of rituximab. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Bilateral renal milk of calcium masquerading as nephrolithiasis in patients with spinal cord injury.

PubMed

Vaidyanathan, Subramanian; Hughes, Peter L; Soni, Bakul M

2007-01-01

Milk of calcium is a viscous colloidal suspension of calcium carbonate, calcium phosphate, or calcium oxalate, or a mixture of these compounds. The calcific material gravitates to the dependent portion of a cystic cavity. Crescent- or hemisphere-shaped calcium density with a sharp horizontal upper border at the milk of calcium-clear fluid interface confirms the diagnosis. Bilateral milk of calcium in the renal pelvis or in dilated calyces is very rare and has not been reported in patients with spinal cord injury. A 63-year-old male patient with T-10 paraplegia presented with recurrent urinary tract infections. X-ray of the kidneys, taken with the vertical beam while the patient lay supine, revealed a poorly defined opacity overlying the lower pole of the right kidney. Findings on ultrasonography of the kidneys were interpreted as a large, staghorn-type calculus in the dilated lower pole calyx of the right kidney. Because x-ray of the kidneys showed a poorly defined opacity overlying the lower pole of the right kidney, milk of calcium was suspected, and computed tomography (CT) of the kidneys was performed. Calcific debris with horizontal layering in the lower pole calyces of both kidneys was seen; this confirmed the diagnosis of milk of calcium. A 62-year-old female patient with C-7 tetraplegia underwent ileal conduit urinary diversion. Subsequently, she developed calculi in the right kidney, which were treated with shock wave lithotripsy. Follow-up x-ray revealed faintly opaque shadows with indistinct margins in the region of both kidneys. Intravenous urography showed cortical thinning at the upper poles and blunting of the calyces, suggestive of chronic pyelonephritis. The right renal pelvis was bulky, and bilateral renal calculi were diagnosed during ultrasonography; however, the presence of faintly radio-opaque shadows with indistinct margins raised suspicions of renal milk of calcium. A CT scan of the kidneys, which was performed in the supine and subsequently in the prone position, revealed gravity-dependent layering of calcific material in the pelves of both kidneys and in the midpole calyces of the right kidney, thus confirming the diagnosis of milk of calcium. In conclusion, CT scan of the kidneys confirmed the diagnosis of bilateral renal milk of calcium, a very rare entity in patients with spinal cord injury. Awareness of typical and unique features of milk of calcium during imaging enables physicians to recognize renal milk of calcium and to differentiate it from nephrolithiasis, thereby avoiding unwarranted interventions such as shock wave lithotripsy or endoscopic procedures.

Validation of a Postoperative Nomogram Predicting Recurrence in Patients with Conventional Clear Cell Renal Cell Carcinoma.

PubMed

Lee, Byron H; Feifer, Andrew; Feuerstein, Michael A; Benfante, Nicole E; Kou, Lei; Yu, Changhong; Kattan, Michael W; Russo, Paul

2018-01-01

Clear cell renal cell carcinoma (RCC) continues to be the most commonly diagnosed subtype and is associated with more aggressive behavior than papillary and chromophobe RCC. Predicting disease recurrence after surgical extirpation is important for counseling and targeting those at high risk for adjuvant therapy clinical trials. To validate a postoperative nomogram predicting 5-yr recurrence-free probability (RFP) for clinically localized clear cell RCC. We identified all patients who underwent nephrectomy for clinically localized clear cell RCC from 1990 to 2009 at Memorial Sloan Kettering Cancer Center. After excluding patients with bilateral renal masses, familial RCC syndromes, and T3c or T4 tumors due to the limited number, 1642 participants were available for analysis. Partial or radical nephrectomy. Disease recurrence was defined as any new tumor after nephrectomy or kidney cancer-specific mortality, whichever occurred first. A postoperative nomogram was used to calculate the predicted 5-yr RFP, and these values were compared with the actual 5-yr RFP. Nomogram performance was evaluated by concordance index and calibration plot. Median follow-up was 39 mo (interquartile range: 14-79 mo), and disease recurrence was observed in 50 patients. The nomogram concordance index was 0.81. The calibration curve showed that the nomogram underestimated the actual 5-yr RFP. We updated the nomogram by including the entire patient population, which maintained performance and significantly improved calibration. The updated clear cell RCC postoperative nomogram performed well in the combined cohort. Underestimation of actual 5-yr RFP by the original nomogram may be due to increased surgeon experience and other unknown variables. We updated a valuable prediction tool used for assessing the disease recurrence probability after nephrectomy for clear cell renal cell carcinoma. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The Predictive Role of Serum Triglyceride to High-Density Lipoprotein Cholesterol Ratio According to Renal Function in Patients with Acute Myocardial Infarction

PubMed Central

Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyoon; Moon, Joo Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

2016-01-01

Objective A high serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported as an independent predictor for cardiovascular events in the general population. However, the prognostic value of this ratio in patients with renal dysfunction is unclear. We examined the association of the TG/HDL-C ratio with major adverse cardiovascular events (MACEs) according to renal function in patients with acute myocardial infarction (AMI). Method This study was based on the Korea Acute Myocardial Infarction Registry database. Of 13,897 patients who were diagnosed with AMI, the study population included the 7,016 patients with available TG/HDL-C ratio data. Patients were stratified into three groups according to their estimated glomerular filtration rate (eGFR), and the TG/HDL-C ratio was categorized into tertiles. We investigated 12-month MACEs, which included cardiac death, myocardial infarction, and repeated percutaneous coronary intervention or coronary artery bypass grafting. Results During the 12-month follow up period, 593 patients experienced MACEs. There was a significant association between the TG/HDL-C ratio and MACEs (p<0.001) in the entire study cohort. Having a TG/HDL-C ratio value in the highest tertile of TG/HDL-C ratio was an independent factor associated with increased risk of MACEs (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.26–1.93; p<0.001). Then we performed subgroup analyses according to renal function. In patients with normal renal function (eGFR ≥ 90 ml/min/1.73m2) and mild renal dysfunction (eGFR ≥ 60 to < 90ml/min/1.73m2), a higher TG/HDL-C ratio was significantly associated with increased risk of MACEs (HR, 1.64; 95% CI, 1.04–2.60; p = 0.035; and HR, 1.56; 95% CI, 1.14–2.12; p = 0.005, respectively). However, in patients with moderate renal dysfunction (eGFR < 60 ml/min/1.73m2), TG/HDL-C ratio lost its predictive value on the risk of MACEs (HR, 1.23; 95% CI, 0.82–1.83; p = 0.317). Conclusions In patients with AMI, TG/HDL-C ratio is a useful independent predictor of 12-month MACEs. However, this ratio does not have predictive power in patients with moderate renal dysfunction. PMID:27788233

[Renal denervation a treatment for resistant hypertension: a French experience].

PubMed

Benamer, H; Mylotte, D; Garcia-Alonso, C; Unterseeh, T; Garot, P; Louvard, Y; Lefevre, T; Morice, M-C

2013-12-01

Arterial hypertension is the largest single contributor to global mortality, and is poorly controlled in approximately 50% of patients despite lifestyle and pharmacologic interventions. Randomized clinical trials have demonstrated that catheter-based renal sympathetic denervation reduces blood pressure (BP) in patients with resistant hypertension. We sought to evaluate the efficacy of this novel therapy in "Real World" clinical practice. Consecutive patients with treatment-resistant primary hypertension, as defined as home BP>160 mmHg despite treatment with ≥3 antihypertensive drugs, were selected for denervation following renal artery screening. Ambulatory and home BP monitoring was performed in all patients prior to and following percutaneous renal sympathetic denervation. In total, 35 patients were selected for catheter-based renal sympathetic denervation. The mean age was 63.6 ± 11.7 years, 37.1% were women, 37.1% were diabetic, and 11.4% had renal impairment (GFR<45 mL/min). The basal BP (home or ambulatory) was 179.1 ± 20.75/99.66 ± 19.76 mmHg, despite an average of 4.91 ± 0.98 medications per patient. Successful bilateral sympathetic denervation was performed in 33/35 patients (1 renal artery stenosis on angiography [not ablated], 1 patient with renal artery spasm [unilateral denervation]), with an average 5.9 ± 1.6 ablations per renal artery. No procedural complications occurred. At 6 months, blood pressure was 15.5 ± 22.37/87.76 ± 13.97 mmHg (P<0.01). At 2 years follow-up, systolic blood pressure (ABPM or Home BP) was 143.8 ± 15.30 mmHg (P<0.0001) and diastolic 83.42 ± 12.80 mmHg (P=0.0004). There were no adverse events during follow-up, and no deterioration in renal function was observed. Catheter-based renal denervation is safe and efficacious treatment, which results in significant reductions in blood pressure in patients with treatment-resistant hypertension, stable at 2 years follow-up. These results are applicable to real-world patient populations. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Quantifying and estimating the predictive accuracy for censored time-to-event data with competing risks.

PubMed

Wu, Cai; Li, Liang

2018-05-15

This paper focuses on quantifying and estimating the predictive accuracy of prognostic models for time-to-event outcomes with competing events. We consider the time-dependent discrimination and calibration metrics, including the receiver operating characteristics curve and the Brier score, in the context of competing risks. To address censoring, we propose a unified nonparametric estimation framework for both discrimination and calibration measures, by weighting the censored subjects with the conditional probability of the event of interest given the observed data. The proposed method can be extended to time-dependent predictive accuracy metrics constructed from a general class of loss functions. We apply the methodology to a data set from the African American Study of Kidney Disease and Hypertension to evaluate the predictive accuracy of a prognostic risk score in predicting end-stage renal disease, accounting for the competing risk of pre-end-stage renal disease death, and evaluate its numerical performance in extensive simulation studies. Copyright © 2018 John Wiley & Sons, Ltd.

Influence of Acute Kidney Injury Defined by the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease Score on the Clinical Course of PICU Patients.

PubMed

Cabral, Felipe Cezar; Ramos Garcia, Pedro Celiny; Mattiello, Rita; Dresser, Daiane; Fiori, Humberto Holmer; Korb, Cecilia; Dalcin, Tiago Chagas; Piva, Jefferson Pedro

2015-10-01

To evaluate the predictive value of the pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease criteria for disease course severity in patients with or without acute kidney injury admitted to a PICU. Retrospective cohort study. A 12-bed PICU at a tertiary referral center in Southern Brazil. All patients admitted to the study unit over a 1-year period. A database of all eligible patients was analyzed retrospectively. Patients were classified by pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease score at admission and worst pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease score during PICU hospitalization. The outcomes of interest were length of PICU stay, duration of mechanical ventilation, duration of vasoactive drug therapy, and mortality. The Pediatric Index of Mortality 2 was used to assess overall disease severity at the time of PICU admission. Of 375 patients, 169 (45%) presented acute kidney injury at the time of admission and 37 developed acute kidney injury during PICU stay, for a total of 206 of 375 patients (55%) diagnosed with acute kidney injury during the study period. The median Pediatric Index of Mortality 2 score predicted a mortality rate of 9% among non-acute kidney injury patients versus a mortality rate of 16% among acute kidney injury patients (p = 0.006). The mortality of patients classified as pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease F was double that predicted by Pediatric Index of Mortality 2 (7 vs 3.2). Patients classified as having severe acute kidney injury (pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease I + F) exhibited higher mortality (14.1%; p = 0.001) and prolonged PICU length of stay (median, 7 d; p = 0.001) when compared with other patients. Acute kidney injury is a very frequent occurrence among patients admitted to PICUs. The degree of acute kidney injury severity, as assessed by the pediatric-modified Risk, Injury, Failure, Loss, End-stage renal disease criteria, is a good predictor of morbidity and mortality in this population. Pediatric Index of Mortality 2 tends to underestimate mortality in pediatric patients with severe acute kidney injury.

Urine peptidome analysis predicts risk of end-stage renal disease and reveals proteolytic pathways involved in autosomal dominant polycystic kidney disease progression.

PubMed

Pejchinovski, Martin; Siwy, Justyna; Metzger, Jochen; Dakna, Mohammed; Mischak, Harald; Klein, Julie; Jankowski, Vera; Bae, Kyongtae T; Chapman, Arlene B; Kistler, Andreas D

2017-03-01

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by slowly progressive bilateral renal cyst growth ultimately resulting in loss of kidney function and end-stage renal disease (ESRD). Disease progression rate and age at ESRD are highly variable. Therapeutic interventions therefore require early risk stratification of patients and monitoring of disease progression in response to treatment. We used a urine peptidomic approach based on capillary electrophoresis-mass-spectrometry (CE-MS) to identify potential biomarkers reflecting the risk for early progression to ESRD in the Consortium of Radiologic Imaging in Polycystic Kidney Disease (CRISP) cohort. A biomarker-based classifier consisting of 20 urinary peptides allowed the prediction of ESRD within 10-13 years of follow-up in patients 24-46 years of age at baseline. The performance of the biomarker score approached that of height-adjusted total kidney volume (htTKV) and the combination of the biomarker panel with htTKV improved prediction over either one alone. In young patients (<24 years at baseline), the same biomarker model predicted a 30 mL/min/1.73 m 2 glomerular filtration rate decline over 8 years. Sequence analysis of the altered urinary peptides and the prediction of the involved proteases by in silico analysis revealed alterations in distinct proteolytic pathways, in particular matrix metalloproteinases and cathepsins. We developed a urinary test that accurately predicts relevant clinical outcomes in ADPKD patients and suggests altered proteolytic pathways involved in disease progression. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Expression of receptor-type protein tyrosine phosphatase in developing and adult renal vasculature

PubMed Central

Takahashi, Keiko; Kim, Rachel; Lauhan, Colette; Park, Yuna; Nguyen, Nghiep G.; Vestweber, Dietmar; Dominguez, Melissa G.; Valenzuela, David M.; Murphy, Andrew J.; Yancopoulos, George D.; Gale, Nicholas W.; Takahashi, Takamune

2017-01-01

Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs) in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs) in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems. In this study, we evaluated the promoter activity and immunolocalization of two endothelial RPTPs, VE-PTP and PTPμ, in developing and adult renal vasculature using the heterozygous LacZ knock-in mice and specific antibodies. In adult kidneys, both VE-PTP and PTPμ were expressed in the endothelium of arterial, glomerular, and medullary vessels, while their expression was highly limited in peritubular capillaries and venous endothelium. VE-PTP and PTPμ promoter activity was also observed in medullary tubular segments in adult kidneys. In embryonic (E12.5, E13.5, E15.5, E17.5) and postnatal (P0, P3, P7) kidneys, these RPTPs were expressed in ingrowing renal arteries, developing glomerular microvasculature (as early as the S-shaped stage), and medullary vessels. Their expression became more evident as the vasculatures matured. Peritubular capillary expression of VE-PTP was also noted in embryonic and postnatal kidneys. Compared to VE-PTP, PTPμ immunoreactivity was relatively limited in embryonic and neonatal renal vasculature and evident immunoreactivity was observed from the P3 stage. These findings indicate 1) VE-PTP and PTPμ are expressed in endothelium of arterial, glomerular, and medullary renal vasculature, 2) their expression increases as renal vascular development proceeds, suggesting that these RPTPs play a role in maturation and maintenance of these vasculatures, and 3) peritubular capillary VE-PTP expression is down-regulated in adult kidneys, suggesting a role of VE-PTP in the development of peritubular capillaries. PMID:28542220

Candidacy for Kidney Transplantation of Older Adults

PubMed Central

Grams, Morgan E.; Kucirka, Lauren M.; Hanrahan, Colleen F.; Montgomery, Robert A.; Massie, Allan B.; Segev, Dorry L.

2013-01-01

OBJECTIVES To develop a prediction model for kidney transplantation (KT) outcomes specific to older adults with end-stage renal disease (ESRD) and to use this model to estimate the number of excellent older KT candidates who lack access to KT. DESIGN Secondary analysis of data collected by the United Network for Organ Sharing and U.S. Renal Disease System. SETTING Retrospective analysis of national registry data. PARTICIPANTS Model development: Medicare-primary older recipients (aged ≥ 65) of a first KT between 1999 and 2006 (N = 6,988). Model application: incident Medicare-primary older adults with ESRD between 1999 and 2006 without an absolute or relative contraindication to transplantation (N = 128,850). MEASUREMENTS Comorbid conditions were extracted from U.S. Renal Disease System Form 2728 data and Medicare claims. RESULTS The prediction model used 19 variables to estimate post-KT outcome and showed good calibration (Hosmer–Lemeshow P = .44) and better prediction than previous population-average models (P < .001). Application of the model to the population with incident ESRD identified 11,756 excellent older transplant candidates (defined as >87% predicted 3-year post-KT survival, corresponding to the top 20% of transplanted older adults used in model development), of whom 76.3% (n = 8,966) lacked access. It was estimated that 11% of these candidates would have identified a suitable live donor had they been referred for KT. CONCLUSION A risk-prediction model specific to older adults can identify excellent KT candidates. Appropriate referral could result in significantly greater rates of KT in older adults. PMID:22239290

Does bone measurement on the radius indicate skeletal status. Concise communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazess, R.B.; Peppler, W.W.; Chesney, R.W.

1984-03-01

Single-photon (I-125) absorptiometry was used to measure bone mineral content (BMC) of the distal third of the radius, and dual-photon absorptiometry (Gd-153) was used to measure total-body bone mineral (TBBM), as well as the BMC of major skeletal regions. Measurements were done in normal females, normal males, osteoporotic females, osteoporotic males, and renal patients. The BMC of the radius predicted TBBM well in normal subjects, but was less satisfactory in the patient groups. The spinal BMC was predicted with even lower accuracy from radius measurement. The error in predicting areal density (bone mass per unit projected skeletal area) of themore » lumbar and thoracic spine from the radius BMC divided by its width was smaller, but the regressions differed significantly among normals, osteoporotics, and renal patients. There was a preferential spinal osteopenia in the osteoporotic group and in about half of the renal patients. Bone measurements on the radius can indicate overall skeletal status in normal subjects and to a lesser degree in patients, but these radius measurements are inaccurate, even on the average, as an indicator of spinal state.« less

Ultrasound evaluation of valsartan therapy for renal cortical perfusion.

PubMed

Kishimoto, Noriko; Mori, Yasukiyo; Nishiue, Takashi; Nose, Atsuko; Kijima, Yasuaki; Tokoro, Toshiko; Yamahara, Hideki; Okigaki, Mitsuhiko; Kosaki, Atsushi; Iwasaka, Toshiji

2004-05-01

An increase in renal blood flow with a concomitant decrease in filtration fraction at the onset of angiotensin II receptor blocker treatment has been shown to predict a long-term renoprotective effect. However, no studies are available regarding angiotensin receptor blocker-induced changes in renal cortical perfusion observed in the clinical setting. We have recently developed a convenient method of evaluating human renal cortical blood flow with contrast-enhanced harmonic ultrasonography. The goal of this study was to use this method to examine the effect of valsartan, an angiotensin II receptor blocker, on renal cortical perfusion. We performed intermittent second harmonic imaging with venous infusion of a microbubble contrast agent in 7 healthy volunteers. Contrast-enhanced harmonic ultrasonography performed after oral administration of valsartan (80mg) showed a significant increase in microbubble velocity, which correlated well with the increase in total renal blood flow determined by p-aminohippurate clearance (r=0.950, p < 0.001). Although fractional vascular volume was not significantly increased, alterations in renal cortical blood flow calculated by the product of microbubble velocity and fractional volume were also correlated with the change in total renal blood flow (r=0.756, p < 0.05). These results indicate that valsartan increases the renal cortical blood flow in normal kidneys, mainly by increasing blood flow velocity. Contrast-enhanced harmonic ultrasonography is a promising technique for evaluating the precise effect on renal cortical perfusion and optimal dose of valsartan in diseased kidneys.

Frequency of postnatal hydronephrosis in infants with a renal anterior-posterior pelvic diameter > 4 mm on midtrimester ultrasound.

PubMed

Chou, Ching-Yu; Chen, Li-Ching; Cheong, Mei-Leng; Tsai, Ming-Song

2015-10-01

To examine the association of antenatal renal pelvic dilatation observed on midtrimester ultrasound screening with the presence of hydronephrosis in newborn infants. The records of patients who received fetal ultrasound examination at 18-28 weeks' gestation from May 2008 to March 2012 were retrospectively reviewed. A fetal renal pelvic anterior-posterior (AP) diameter > 4 mm was considered abnormal and ≤ 4 mm was considered normal. On postnatal ultrasound, a renal pelvic AP diameter > 3 mm was considered to indicate hydronephrosis and ≤ 3 mm was considered normal. The association of postnatal hydronephrosis with prenatal pelvic AP diameter was determined using binary logistic regression analysis. The study comprised 1310 newborn infants: 684 (52.2%) male and 626 (47.8%) female. Multivariate analysis showed a right or left prenatal AP renal pelvic diameter > 4 mm was associated with a higher risk of postnatal hydronephrosis compared with a right and left prenatal AP renal pelvic diameter ≤ 4 mm. Boys had a higher risk for postnatal hydronephrosis than girls (odds ratio = 2.42, p < 0.05). An antenatal renal pelvic AP diameter > 4 mm on midtrimester ultrasound is predictive of postnatal hydronephrosis. Copyright © 2015. Published by Elsevier B.V.

Can preeclampsia be considered a renal compartment syndrome? A hypothesis and analysis of the literature.

PubMed

Reuter, David G; Law, Yuk; Levy, Wayne C; Seslar, Stephen P; Zierler, R Eugene; Ferguson, Mark; Chattra, James; McQuinn, Tim; Liu, Lenna L; Terry, Mark; Coffey, Patricia S; Dimer, Jane A; Hanevold, Coral; Flynn, Joseph T; Stapleton, F Bruder

2016-11-01

The morbidity and mortality associated with preeclampsia is staggering. The physiology of the Page kidney, a condition in which increased intrarenal pressure causes hypertension, appears to provide a unifying framework to explain the complex pathophysiology. Page kidney hypertension is renin-mediated acutely and ischemia-mediated chronically. Renal venous outflow obstruction also causes a Page kidney phenomenon, providing a hypothesis for the increased vulnerability of a subset of women who have what we are hypothesizing is a "renal compartment syndrome" due to inadequate ipsilateral collateral renal venous circulation consistent with well-known variation in normal venous anatomy. Dynamic changes in renal venous anatomy and physiology in pregnancy appear to correlate with disease onset, severity, and recurrence. Since maternal recumbent position is well known to affect renal perfusion and since chronic outflow obstruction makes women vulnerable to the ischemic/inflammatory sequelae, heightened awareness of renal compartment syndrome physiology is critical. The anatomic and physiologic insights provide immediate strategies to predict and prevent preeclampsia with straightforward, low-cost interventions that make renewed global advocacy for pregnant women a realistic goal. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Renal replacement therapy in patients with severe precapillary pulmonary hypertension with acute right heart failure.

PubMed

Sztrymf, Benjamin; Prat, Dominique; Jacobs, Frédéric M; Brivet, François G; O'Callaghan, Dermot S; Price, Laura C; Jais, Xavier; Sitbon, Olivier; Simonneau, Gérald; Humbert, Marc

2013-01-01

Renal replacement therapy has been suggested as a therapeutic option in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension. However, there are few data supporting this strategy. To describe the clinical course and the prognosis of pulmonary hypertensive patients undergoing renal replacement therapy in the setting of acute right heart failure. This was a single-center retrospective study over an 11-year period. Data were collected from all patients with chronic precapillary pulmonary hypertension requiring catecholamine infusions for clinical worsening and acute kidney injury that necessitated renal replacement therapy. Fourteen patients were included. At admission, patients had a blood urea of 28.2 mmol/l (22.3-41.2), a creatinine level of 496 µmol/l (304-590), and a mean urine output in the 24 h preceding hospitalization of 200 ml (0-650). Sixty-eight renal replacement therapy sessions were performed, 36 of which were continuous and 32 of which were intermittent. Systemic hypotension occurred in 16/32 intermittent and 16/36 continuous sessions (p = 0.9). Two patients died during a continuous session. The intensive care unit-related, 1-, and 3-month mortality was 46.7, 66.7, and 73.3%, respectively. Renal replacement therapy is feasible in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension but is associated with a poor prognosis. The best modality and timing in this population remain to be defined. Copyright © 2012 S. Karger AG, Basel.

Membranoproliferative glomerulonephritis and acute renal failure in a patient with chronic lymphocytic leukemia: Response to obinutuzumab.

PubMed

Jain, Punit; Kanagal-Shamanna, Rashmi; Wierda, William; Ferrajoli, Alessandra; Keating, Michael; Jain, Nitin

2017-09-01

Membranoproliferative glomerulonephritis (MPGN) is a common extramedullary renal presentation in chronic lymphocytic leukemia (CLL) and can present with either a frank renal failure or proteinuria. One of its etiologies has been attributed to a paraneoplastic, immune complex phenomenon occurring in CLL. Although there is no standard of care in such patients, use of anti-CD20 monoclonal antibodies like rituximab have been used before in such patients with variable responses. Obinutuzumab is a novel, type II, immunoglobulin-G1 monoclonal antibody with a higher efficacy than rituximab and has an established safely profile in patients with comorbidities and poor renal functions. There are no such reported cases of MPGN in CLL being treated with obinutuzumab. We used the standard doses of obinutuzumab in our elderly patient (78-year-old woman) with high-risk CLL due to an underlying TP53 mutation, along with a MPGN-related acute renal failure. The patient achieved complete remission after six cycles of obinutuzumab; however, she remained positive for minimal residual disease on flow cytometry. Her renal function improved completely, suggesting a complete response of her underlying MPGN. Obinutuzumab has an established safety profile in patients with CLL, but our case is the first reported case of a paraneoplastic, immune complex-mediated MPGN in CLL being treated with obinutuzumab. Obinutuzumab should be explored as a potential option in patients with CLL and MPGN. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Enhancing patient engagement and blood pressure management for renal transplant recipients via home electronic monitoring and web-enabled collaborative care.

PubMed

Aberger, Edward W; Migliozzi, Daniel; Follick, Michael J; Malick, Tom; Ahern, David K

2014-09-01

Effective management of hypertension in chronic kidney disease and renal transplantation is a clinical priority and has societal implications in terms of preserving and optimizing the value of scarce organs. However, hypertension is optimally managed in only 37% of people with chronic kidney disease, and poor control can contribute to premature graft loss in renal transplant recipients. This article describes a telehealth system that incorporates home electronic blood pressure (BP) monitoring and uploading to a patient portal coupled with a Web-based dashboard that enables clinical pharmacist collaborative care in a renal transplant clinic. The telehealth system was developed and implemented as a quality improvement initiative in a renal transplant clinic in a large, 700-bed, urban hospital with the aim of improving BP in posttransplant patients. A convenience sample of 66 posttransplant patients was recruited by the clinical pharmacist from consecutive referrals to the Transplant Clinic. Preliminary results show statistically significant reductions in average systolic and diastolic BP of 6.0 mm Hg and 3.0 mm Hg, respectively, at 30 days after enrollment. Two case reports describe the instrumental role of home BP monitoring in the context of medication therapy management. Optimizing BP control for both pre- and post-renal transplant patients is likely to benefit society in terms of preserving scarce resources and reducing healthcare costs due to premature graft failure. Connected health systems hold great promise for supporting team-based care and improved health outcomes.

Echocardiographic predictors of change in renal function with intravenous diuresis for decompensated heart failure.

PubMed

Gannon, Stephen A; Mukamal, Kenneth J; Chang, James D

2018-06-14

The aim of this study was to identify echocardiographic predictors of improved or worsening renal function during intravenous diuresis for decompensated heart failure. Secondary aim included defining the incidence and clinical risk factors for acute changes in renal function with decongestion. A retrospective review of 363 patients admitted to a single centre for decompensated heart failure who underwent intravenous diuresis and transthoracic echocardiography was conducted. Clinical, echocardiographic, and renal function data were retrospectively collected. A multinomial logistic regression model was created to determine relative risk ratios for improved renal function (IRF) or worsening renal function (WRF). Within this cohort, 36% of patients experienced WRF, 35% had stable renal function, and 29% had IRF. Patients with WRF were more likely to have a preserved left ventricular ejection fraction compared with those with stable renal function or IRF (P = 0.02). Patients with IRF were more likely to have a dilated, hypokinetic right ventricle compared with those with stable renal function or WRF (P ≤ 0.01), although this was not significant after adjustment for baseline characteristics. Left atrial size, left ventricular linear dimensions, and diastolic function did not significantly predict change in renal function. An acute change in renal function occurred in 65% of patients admitted with decompensated heart failure. WRF was statistically more likely in patients with a preserved left ventricular ejection fraction. A trend towards IRF was noted in patients with global right ventricular dysfunction. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Association of Circulating Biomarkers (Adrenomedullin, TNFR1, and NT-proBNP) With Renal Function Decline in Patients With Type 2 Diabetes: A French Prospective Cohort.

PubMed

Saulnier, Pierre-Jean; Gand, Elise; Velho, Gilberto; Mohammedi, Kamel; Zaoui, Philippe; Fraty, Mathilde; Halimi, Jean Michel; Roussel, Ronan; Ragot, Stéphanie; Hadjadj, Samy

2017-03-01

We explored the prognostic value of three circulating candidate biomarkers-midregional-proadrenomedullin (MR-proADM), soluble tumor necrosis factor receptor 1 (sTNFR1), and N-terminal prohormone brain natriuretic peptide (NT-proBNP)-for change in renal function in patients with type 2 diabetes. Outcomes were defined as renal function loss (RFL), ≥40% decline of estimated glomerular filtration rate (eGFR) from baseline, and rapid renal function decline (RRFD), absolute annual eGFR slope <-5 mL/min/year. We used a proportional hazard model for RFL and a logistic model for RRFD. Adjustments were performed for established risk factors (age, sex, diabetes duration, HbA 1c , blood pressure, baseline eGFR, and urinary albumin-to-creatinine ratio [uACR]). C-statistics were used to assess the incremental predictive value of the biomarkers to these risk factors. Among 1,135 participants (mean eGFR 76 mL/min, median uACR 2.6 mg/mmol, and median GFR slope -1.6 mL/min/year), RFL occurred in 397, RRFD developed in 233, and 292 died during follow-up. Each biomarker predicted RFL and RRFD. When combined, MR-proADM, sTNFR1, and NT-proBNP predicted RFL independently from the established risk factors (adjusted hazard ratio 1.59 [95% CI 1.34-1.89], P < 0.0001; 1.33 [1.14-1.55], P = 0.0003; and 1.22 [1.07-1.40], P = 0.004, respectively) and RRFD (adjusted odds ratio 1.56 [95% CI 1.7-2.09], P = 0.003; 1.72 [1.33-2.22], P < 0.0001; and 1.28 [1.03-1.59], P = 0.02, respectively). The combination of the three biomarkers yielded the highest discrimination (difference in C-statistic = 0.054, P < 0.0001; 0.067, P < 0.0001 for RFL; and 0.027, P < 0.0001 for RRFD). In addition to established risk factors, MR-proADM, sTNFR1, and NT-proBNP improve risk prediction of loss of renal function in patients with type 2 diabetes. © 2017 by the American Diabetes Association.

Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments

PubMed Central

Coppo, Rosanna; Troyanov, Stéphan; Bellur, Shubha; Cattran, Daniel; Cook, H Terence; Feehally, John; Roberts, Ian S D; Morando, Laura; Camilla, Roberta; Tesar, Vladimir; Lunberg, Sigrid; Gesualdo, Loreto; Emma, Francesco; Rollino, Cristiana; Amore, Alessandro; Praga, Manuel; Feriozzi, Sandro; Segoloni, Giuseppe; Pani, Antonello; Cancarini, Giovanni; Durlik, Magalena; Moggia, Elisabetta; Mazzucco, Gianna; Giannakakis, Costantinos; Honsova, Eva; Sundelin, B Brigitta; Di Palma, Anna Maria; Ferrario, Franco; Gutierrez, Eduardo; Asunis, Anna Maria; Barratt, Jonathan; Tardanico, Regina; Perkowska-Ptasinska, Agnieszka

2014-01-01

The Oxford Classification of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as independent predictors of outcome. Whether it applies to individuals excluded from the original study and how therapy influences the predictive value of pathology remain uncertain. The VALIGA study examined 1147 patients from 13 European countries that encompassed the whole spectrum of IgAN. Over a median follow-up of 4.7 years, 86% received renin–angiotensin system blockade and 42% glucocorticoid/immunosuppressive drugs. M, S, and T lesions independently predicted the loss of estimated glomerular filtration rate (eGFR) and a lower renal survival. Their value was also assessed in patients not represented in the Oxford cohort. In individuals with eGFR less than 30 ml/min per 1.73 m2, the M and T lesions independently predicted a poor survival. In those with proteinuria under 0.5 g/day, both M and E lesions were associated with a rise in proteinuria to 1 or 2 g/day or more. The addition of M, S, and T lesions to clinical variables significantly enhanced the ability to predict progression only in those who did not receive immunosuppression (net reclassification index 11.5%). The VALIGA study provides a validation of the Oxford classification in a large European cohort of IgAN patients across the whole spectrum of the disease. The independent predictive value of pathology MEST score is reduced by glucocorticoid/immunosuppressive therapy. PMID:24694989

Predictors for the need of surgery in antenatally detected hydronephrosis due to UPJ obstruction--a prospective multivariate analysis.

PubMed

Arora, S; Yadav, P; Kumar, M; Singh, S Kumar; Sureka, S Kumar; Mittal, V; Ansari, M S

2015-10-01

Disagreement exists over the ability of different diagnostic tests to define obstruction, indications and timing of surgery and which patients will benefit from surgical intervention in antenatal hydronephrosis (ANH) due to ureteropelvic junction obstruction (UPJO). We try to find a way to predict which patients of ANH due to UPJO will eventually need surgery during conservative management. Prospective single centre study involving 122 renal units at a referral centre in India. Patients on conservative management were followed using a standard protocol and operated for pre-defined indications defining failure of conservative management. Patients who underwent surgery were compared with the non-operated group in terms of sex, side, baseline grade of hydronephrosis, maximum anterioposterior diameter on first postnatal ultrasound and differential renal function on first renal scan. A total of 109 renal units qualified for conservative management. Of those, 23.9% required operative intervention during follow-up. Median time to failure of conservative management was 37 weeks. The median follow-up of non-operated cases was 54 months. Univariate analysis revealed that society of fetal urology (SFU) grade of hydronephrosis, anteroposterior diameter (APD), cortical thickness (CT), and pre-operative differential renal function (DRF) had a significant association with surgery (P < 0.05). Multivariate analysis revealed APD and pre-operative DRF as the only independent predictors for requiring surgery, while CT and initial SFU grade of hydronephrosis were not. Receiver operating curve analysis showed that an APD of 24.3 mm could predict the need for surgery, with a sensitivity of 73.1% and a specificity of 88.0%. APD and DRF are the predictive factors for surgery. We stop short of recommending surgery only on the basis of APD. Instead we recommend that efforts be made to improve the specificity of this criterion, or by using APD in perspective with the differential renal function. We can reduce the burden of investigations in those with APD <24 mm while those with APD >24 mm can be more comprehensively monitored. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Preoperative anemia versus blood transfusion: Which is the culprit for worse outcomes in cardiac surgery?

PubMed

LaPar, Damien J; Hawkins, Robert B; McMurry, Timothy L; Isbell, James M; Rich, Jeffrey B; Speir, Alan M; Quader, Mohammed A; Kron, Irving L; Kern, John A; Ailawadi, Gorav

2018-04-04

Reducing blood product utilization after cardiac surgery has become a focus of perioperative care as studies have suggested improved outcomes. The relative impact of preoperative anemia versus packed red blood cells (PRBC) transfusion on outcomes remains poorly understood, however. In this study, we investigated the relative association between preoperative hematocrit (Hct) level and PRBC transfusion on postoperative outcomes after coronary artery bypass grafting (CABG) surgery. Patient records for primary, isolated CABG operations performed between January 2007 and December 2017 at 19 cardiac surgery centers were evaluated. Hierarchical logistic regression modeling was used to estimate the relationship between baseline preoperative Hct level as well as PRBC transfusion and the likelihoods of postoperative mortality and morbidity, adjusted for baseline patient risk. Variable and model performance characteristics were compared to determine the relative strength of association between Hct level and PRBC transfusion and primary outcomes. A total of 33,411 patients (median patient age, 65 years; interquartile range [IQR], 57-72 years; 26% females) were evaluated. The median preoperative Hct value was 39% (IQR, 36%-42%), and the mean Society of Thoracic Surgeons (STS) predicted risk of mortality was 1.8 ± 3.1%. Complications included PRBC transfusion in 31% of patients, renal failure in 2.8%, stroke in 1.3%, and operative mortality in 2.0%. A strong association was observed between preoperative Hct value and the likelihood of PRBC transfusion (P < .001). After risk adjustment, PRBC transfusion, but not Hct value, demonstrated stronger associations with postoperative mortality (odds ratio [OR], 4.3; P < .0001), renal failure (OR 6.3; P < .0001), and stroke (OR, 2.4; P < .0001). A 1-point increase in preoperative Hct was associated with decreased probabilities of mortality (OR, 0.97; P = .0001) and renal failure (OR, 0.94; P < .0001). The models with PRBC had superior predictive power, with a larger area under the curve, compared with Hct for all outcomes (all P < .01). Preoperative anemia was associated with up to a 4-fold increase in the probability of PRBC transfusion, a 3-fold increase in renal failure, and almost double the mortality. PRBC transfusion appears to be more closely associated with risk-adjusted morbidity and mortality compared with preoperative Hct level alone, supporting efforts to reduce unnecessary PRBC transfusions. Preoperative anemia independently increases the risk of postoperative morbidity and mortality. These data suggest that preoperative Hct should be included in the STS risk calculators. Finally, efforts to optimize preoperative hematocrit should be investigated as a potentially modifiable risk factor for mortality and morbidity. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

AGXT2 rs37369 polymorphism predicts the renal function in patients with chronic heart failure.

PubMed

Hu, Xiao-Lei; Zeng, Wen-Jing; Li, Mu-Peng; Yang, Yong-Long; Kuang, Da-Bin; Li, He; Zhang, Yan-Jiao; Jiang, Chun; Peng, Li-Ming; Qi, Hong; Zhang, Ke; Chen, Xiao-Ping

2017-12-30

Patients with chronic heart failure (CHF) are often accompanied with varying degrees of renal diseases. The purpose of this study was to identify rs37369 polymorphism of AGXT2 specific to the renal function of CHF patients. A total of 1012 southern Chinese participants, including 487 CHF patients without history of renal diseases and 525 healthy volunteers, were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes of AGXT2 rs37369 polymorphism. Levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected to indicate the renal function of the participants. BUN level was significantly higher in CHF patients without history of renal diseases compared with healthy volunteers (p=0.000). And the similar result was also obtained for SCr (p=0.000). Besides, our results indicated that the level of BUN correlated significantly with SCr in both the CHF patients without renal diseases (r=0.4533, p<0.0001) and volunteers (r=0.2489, p<0.0001). Furthermore, we found that the AGXT2 rs37369 polymorphism could significantly affect the level of BUN in CHF patients without history of renal diseases (p=0.036, AA+AG vs GG). Patients with rs37369 GG genotype showed a significantly reduced level of BUN compared to those with the AA genotype (p=0.024), and the significant difference was still observed in the smokers of CHF patients without renal diseases (p=0.023). In conclusion, we found that CHF might induce the impairment of kidney and cause deterioration of renal function. AGXT2 rs37369 polymorphism might affect the renal function of CHF patients free from renal diseases, especially in patients with cigarette smoking. Copyright © 2017. Published by Elsevier B.V.

Post-Discharge Worsening Renal Function in Patients with Type 2 Diabetes and Recent Acute Coronary Syndrome.

PubMed

Morici, Nuccia; Savonitto, Stefano; Ponticelli, Claudio; Schrieks, Ilse C; Nozza, Anna; Cosentino, Francesco; Stähli, Barbara E; Perrone Filardi, Pasquale; Schwartz, Gregory G; Mellbin, Linda; Lincoff, A Michael; Tardif, Jean-Claude; Grobbee, Diederick E

2017-09-01

Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge worsening renal function has never been investigated in this setting. We considered the placebo cohort of the AleCardio trial comparing aleglitazar with standard medical therapy among patients with type 2 diabetes mellitus and a recent acute coronary syndrome. Patients who had died or had been admitted to hospital for heart failure before the 6-month follow-up, as well as patients without complete renal function data, were excluded, leaving 2776 patients for the analysis. Worsening renal function was defined as a >20% reduction in estimated glomerular filtration rate from discharge to 6 months, or progression to macroalbuminuria. The Cox regression analysis was used to determine the prognostic impact of 6-month renal deterioration on the composite of all-cause death and hospitalization for heart failure. Worsening renal function occurred in 204 patients (7.34%). At a median follow-up of 2 years the estimated rates of death and hospitalization for heart failure per 100 person-years were 3.45 (95% confidence interval [CI], 2.46-6.36) for those with worsening renal function, versus 1.43 (95% CI, 1.14-1.79) for patients with stable renal function. At the adjusted analysis worsening renal function was associated with the composite endpoint (hazard ratio 2.65; 95% CI, 1.57-4.49; P <.001). Post-discharge worsening renal function is not infrequent among patients with type 2 diabetes and acute coronary syndromes with normal or mildly depressed renal function, and is a strong predictor of adverse cardiovascular events. Copyright © 2017 Elsevier Inc. All rights reserved.

Decreased GFR estimated by MDRD or Cockcroft-Gault equation predicts incident CVD: the strong heart study.

PubMed

Shara, Nawar M; Resnick, Helaine E; Lu, Li; Xu, Jiaqiong; Vupputuri, Suma; Howard, Barbara V; Umans, Jason G

2009-01-01

Kidney function, expressed as glomerular filtration rate (GFR), is commonly estimated from serum creatinine (Scr) and, when decreased, may serve as a nonclassical risk factor for incident cardiovascular disease (CVD). The ability of estimated GFR (eGFR) to predict CVD events during 5-10 years of follow-up is assessed using data from the Strong Heart Study (SHS), a large cohort with a high prevalence of diabetes. eGFRs were calculated with the abbreviated Modification of Diet in Renal Disease study (MDRD) and the Cockcroft-Gault (CG) equations. These estimates were compared in participants with normal and abnormal Scr. The association between eGFR and incident CVD was assessed. More subjects were labeled as having low eGFR (<60 ml/min per 1.73 m2) by the MDRD or CG equation, than by Scr alone. When Scr was in the normal range, both equations labeled similar numbers of participants as having low eGFRs, although concordance between the equations was poor. However, when Scr was elevated, the MDRD equation labeled more subjects as having low eGFR. Persons with low eGFR had increased risk of CVD. The MDRD and CG equations labeled more participants as having decreased GFR than did Scr alone. Decreased eGFR was predictive of CVD in this American Indian population with a high prevalence of obesity and type 2 diabetes mellitus.

GCRBS score: a new scoring system for predicting outcome in severe falciparum malaria.

PubMed

Mohapatra, Biranchi Narayan; Jangid, Sanjay Kumar; Mohanty, Rina

2014-01-01

Severe falciparum malaria is a critical illness resulting in multi-organ dysfunction and death. Severe malaria is defined by the World Health Organisation as a qualitative variable. The purpose of this study is to devise a scoring system for predicting outcome in severe falciparum malaria. 112 cases of severe falciparum malaria diagnosed as per the WHO criteria, were evaluated to determine the parameters which were significantly associated with mortality. Of all the parameters studied, five variables namely cerebral malaria (GCS < 11), Renal failure (Creatinine > 3 mg/dl), Respiratory distress (Respiratory rate > 24/min), Jaundice (Bilirubin >10 mg/dl) and Shock (Systolic BP < 90 mm of Hg) were all found to be associated with a poor prognosis. The five selected parameters were analysed using the Odds ratio and a new scoring system named as GCRBS score was designed with a possible score from 0-10. With a cut-off score of 5, the GCRBS score predicted mortality with a sensitivity of 85.3% and a specificity of 95.6%. The GCRBS score is easy to calculate and apply. Of the 5 parameters, 3 are clinical which can be determined at bedside and only 2 are biochemical which can be done in any laboratory.The most important advantage of this scoring system is that all the 5 parameters are to be assessed quantitatively for allotting a score, which would eliminate the possibility of observer bias.

The role of procalcitonin for acute pyelonephritis and subsequent renal scarring in infants and young children.

PubMed

Sheu, Ji-Nan; Chang, Hung-Ming; Chen, Shan-Ming; Hung, Tung-Wei; Lue, Ko-Huang

2011-11-01

We assessed the usefulness of procalcitonin as a biological marker in diagnosing acute pyelonephritis and for predicting subsequent renal scarring in young children with a first febrile urinary tract infection. Children 2 years old or younger with a first febrile urinary tract infection were prospectively studied. Renal parenchymal involvement was assessed by (99m)Tc-dimercaptosuccinic acid scan within 5 days of admission and after 6 months. Serum samples from all patients were tested for procalcitonin, C-reactive protein and white blood cell count measurements. The 112 enrolled patients (age range 24 days to 24 months old) were divided into acute pyelonephritis (76) and lower urinary tract infection (36) groups according to the results of (99m)Tc-dimercaptosuccinic acid scans. Median values of procalcitonin, C-reactive protein and white blood cell count at hospitalization were significantly higher in patients with acute pyelonephritis than in those with lower urinary tract infection. The area under receiver operating characteristic curves showed that procalcitonin was superior to C-reactive protein and white blood cell count as a marker for diagnosing acute pyelonephritis. Initial and post-antibiotic treatment procalcitonin values were significantly higher in children with renal scarring than in those without scarring (p <0.001). Procalcitonin values at hospitalization and after treatment were independent predictors of later renal scarring on logistic regression analysis. Our results indicate the superior diagnostic accuracy of procalcitonin for predicting acute pyelonephritis in children 2 years old or younger. Higher initial and posttreatment procalcitonin values are independent risk factors for later renal scarring. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Can computerized tomography accurately stage childhood renal tumors?

PubMed

Abdelhalim, Ahmed; Helmy, Tamer E; Harraz, Ahmed M; Abou-El-Ghar, Mohamed E; Dawaba, Mohamed E; Hafez, Ashraf T

2014-07-01

Staging of childhood renal tumors is crucial for treatment planning and outcome prediction. We sought to identify whether computerized tomography could accurately predict the local stage of childhood renal tumors. We retrospectively reviewed our database for patients diagnosed with childhood renal tumors and treated surgically between 1990 and 2013. Inability to retrieve preoperative computerized tomography, intraoperative tumor spillage and nonWilms childhood renal tumors were exclusion criteria. Local computerized tomography stage was assigned by a single experienced pediatric radiologist blinded to the pathological stage, using a consensus similar to the Children's Oncology Group Wilms tumor staging system. Tumors were stratified into up-front surgery and preoperative chemotherapy groups. The radiological stage of each tumor was compared to the pathological stage. A total of 189 tumors in 179 patients met inclusion criteria. Computerized tomography staging matched pathological staging in 68% of up-front surgery (70 of 103), 31.8% of pre-chemotherapy (21 of 66) and 48.8% of post-chemotherapy scans (42 of 86). Computerized tomography over staged 21.4%, 65.2% and 46.5% of tumors in the up-front surgery, pre-chemotherapy and post-chemotherapy scans, respectively, and under staged 10.7%, 3% and 4.7%. Computerized tomography staging was more accurate in tumors managed by up-front surgery (p <0.001) and those without extracapsular extension (p <0.001). The validity of computerized tomography staging of childhood renal tumors remains doubtful. This staging is more accurate for tumors treated with up-front surgery and those without extracapsular extension. Preoperative computerized tomography can help to exclude capsular breach. Treatment strategy should be based on surgical and pathological staging to avoid the hazards of inaccurate staging. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Non-metastatic clear cell renal cancer: dependence of the tumour stage on clinico-anatomic and morphologic factors; prognostic value of macro- and karyometric characteristics].

PubMed

Iurin, A G

2010-01-01

Non-metastatic clear-cell renal cancer: dependence of the tumour stage on clinico-anatomic and morphologic factors; prognostic value of macro- and karyometric characteristics Sankt Peterburg Pathology Bureau, Sankt Peterburg It was shown based on multivariate regression analysis that pT1a3bN0MO stages of non-metastatic clear-cell renal cancer significantly correlate not only with the tumor size and invasion into the fatty tissue and/or renal vein but also with the invasion into the renal capsule and with the mean maximum diameter and mean nucleus area of tumor cells. There was no correlation of clear-cell renal cancer stages with tumor proliferative activity, gene p53 mutation, oncosuppressor gene PTEN expression, fraction of tumour clear-cell component, and such clinical characteristics as patients' sex, age, and body mass index. Taking into account statistically significant differences between the patients' survival rates, the regression equations developed in this work may be used for the prediction of disease outcome.

High-Throughput Sequencing Reveals Circulating miRNAs as Potential Biomarkers of Kidney Damage in Patients with Systemic Lupus Erythematosus.

PubMed

Navarro-Quiroz, Elkin; Pacheco-Lugo, Lisandro; Lorenzi, Hernan; Díaz-Olmos, Yirys; Almendrales, Lisneth; Rico, Edwin; Navarro, Roberto; España-Puccini, Pierine; Iglesias, Antonio; Egea, Eduardo; Aroca, Gustavo

2016-01-01

Renal involvement is one of the most severe manifestations of systemic lupus erythematosus (SLE). Renal biopsy is the gold standard when it comes to knowing whether a patient has lupus nephritis, and the degree of renal disease present. However, the biopsy has various complications, bleeding being the most common. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with SLE is a priority. Micro RNAs (miRNAs) are differentially expressed in various tissues, and changes in their expression have been associated with several pathological processes. The aim of this study was to identify changes in the abundance of miRNAs in plasma samples from patients with lupus nephritis that could potentially allow the diagnosis of renal damage in SLE patients. This is an observational case-control cross-sectional study, in which we characterized the differential abundance profiles of miRNAs among patients with different degrees of lupus compared with SLE patients without renal involvement and healthy control individuals. We found 89 miRNAs with changes in their abundance between lupus nephritis patients and healthy controls, and 17 miRNAs that showed significant variations between SLE patients with or without renal involvement. Validation for qPCR of a group of miRNAs on additional samples from lupus patients with or without nephritis, and from healthy individuals, showed that five miRNAs presented an average detection sensitivity of 97%, a specificity of 70.3%, a positive predictive value of 82.5%, a negative predictive value of 96% and a diagnosis efficiency of 87.9%. These results strongly suggest that miR-221-5p, miR-380-3p, miR-556-5p, miR-758-3p and miR-3074-3p are potential diagnostic biomarkers of lupus nephritis in patients with SLE. The observed differential pattern of miRNA abundance may have functional implications in the pathophysiology of SLE renal damage.

[Sequential monitoring of renal transplant with aspiration cytology].

PubMed

Manfro, R C; Gonçalves, L F; de Moura, L A

1998-01-01

To evaluate the utility of kidney aspiration cytology in the sequential monitorization of acute rejection in renal transplant patients. Thirty patients were submitted to 376 aspirations. The clinical diagnoses were independently established. The representativity of the samples reached 82.7%. The total corrected increment index and the number of immunoactivated cells were higher during acute rejection as compared to normal allograft function, acute tubular necrosis, and cyclosporine nephrotoxicity. The parameters to the diagnosis of acute rejection were sensitivity: 71.8%, specificity: 87.3%, positive predictive value: 50.9%, negative predictive value: 94.9% and accuracy 84.9%. The false positive results were mainly related to cytomegalovirus infection or to the administration of OKT3. In 10 out of 11 false negative results incipient immunoactivation was present alerting to the possibility of acute rejection. Kidney aspiration cytology is a useful tool for the sequential monitorization of acute rejection in renal transplant patients. The best results are reached when the results of aspiration cytology are analyzed with the clinical data.

Effects of a renal rehabilitation exercise program in patients with CKD: a randomized, controlled trial.

PubMed

Rossi, Ana P; Burris, Debra D; Lucas, F Leslie; Crocker, Gail A; Wasserman, James C

2014-12-05

Patients with CKD have a high prevalence of cardiovascular disease associated with or exacerbated by inactivity. This randomized, controlled study investigated whether a renal rehabilitation exercise program for patients with stages 3 or 4 CKD would improve their physical function and quality of life. In total, 119 adults with CKD stages 3 and 4 were randomized, and 107 of these patients proceeded to usual care or the renal rehabilitation exercise intervention consisting of usual care plus guided exercise two times per week for 12 weeks (24 sessions). Physical function was determined by three well established performance-based tests: 6-minute walk test, sit-to-stand test, and gait-speed test. Health-related quality of life was assessed by the RAND 36-Item Short Form Health Survey. At baseline, no differences in self-reported level of activity, 6-minute walk test, and sit-to-stand test scores were observed between the usual care (n=48) and renal rehabilitation exercise (n=59) groups, although baseline gait-speed test score was higher in the renal rehabilitation exercise group (P<0.001). At follow-up, the renal rehabilitation exercise group but not the usual care group showed significant improvements in the 6-minute walk test (+210.4±266.0 ft [19% improvement] versus -10±219.9 ft; P<0.001), the sit-to-stand test (+26.9±27% of age prediction [29% improvement] versus +0.7±12.1% of age prediction; P<0.001), and the RAND-36 physical measures of role functioning (P<0.01), physical functioning (P<0.01), energy/fatigue levels (P=0.01), and general health (P=0.03) and mental measure of pain scale (P=0.04). The renal rehabilitation exercise regimen was generally well tolerated. A 12-week/24-session renal rehabilitation exercise program improved physical capacity and quality of life in patients with CKD stages 3 and 4. Longer follow-up is needed to determine if these findings will translate into decreased mortality rates. Copyright © 2014 by the American Society of Nephrology.

Renal function changes after percutaneous nephrolithotomy in patients with renal calculi with a solitary kidney compared to bilateral kidneys.

PubMed

Shi, Xiaolei; Peng, Yonghan; Li, Ling; Li, Xiao; Wang, Qi; Zhang, Wei; Dong, Hao; Shen, Rong; Lu, Chaoyue; Liu, Min; Gao, Xiaofeng; Sun, Yinghao

2018-05-26

To evaluate renal function changes and risk factors for acute kidney injury (AKI) after percutaneous nephrolithotomy (PCNL) in patients with renal calculi with a solitary kidney (SK) or normal bilateral kidneys (BKs). Between 2012 and 2016, 859 patients undergoing PCNL were retrospectively reviewed at Changhai Hospital. In all, 53 patients with a SK were paired with 53 patients with normal BKs via a propensity score-matched analysis. Data for the following variables were collected: age, sex, body mass index, stone size, distribution, operation time, perioperative outcomes, and complications. The complications were graded according to the modified Clavien-Dindo system. Univariable and multivariable logistic regression models were constructed to evaluate risk factors for predicting AKI. The SK and BKs groups were comparable in terms of age, sex ratio, stone size, stone location distribution, comorbidities, and American Society of Anesthesiologists Physical Status classification. The initial and final stone-free rates were comparable between the SK and BKs groups (initial: 52.83% vs 58.49%, P = 0.696; final: 84.91% vs 92.45%, P = 0.359). There was no difference between the two groups for complications, according to the Clavien-Dindo grades. The estimated glomerular filtration rate (eGFR) increased dramatically after the stone burden was immediately relieved, and during the 6-month follow-up eGFR was lower in the SK group compared with the BKs group. We found a modest improvement in renal function immediately after PCNL in the BKs group, and renal function gain was delayed in the SK group. Through logistic regression analysis, we discovered that a SK, preoperative creatinine and diabetes were independent risk factors for predicting AKI after PCNL. Considering the overall complication rates, PCNL is generally a safe procedure for treating renal calculi amongst patients with a SK or normal BKs. Follow-up renal function analysis showed a modest improvement in patients of both groups. Compared to patients with normal BKs, patients with a SK were more likely to develop AKI after PCNL. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Mechanism of intracellular signal transduction during injury of renal tubular cells induced by postasphyxial serum in neonates with asphyxia.

PubMed

Zhao, Jin; Dong, Wen-Bin; Li, Peng-yun; Deng, Chun-liang

2009-01-01

Renal injury is a severe and extremely common complication that occurs early in neonates with asphyxia. Reperfusion injury has been suggested as the cause of kidney damage during resuscitation of neonatal asphyxia. Previous studies have demonstrated that postasphyxial serum from neonates with asphyxia may result in apoptosis of renal tubular cells. However, the mechanisms that mediate renal tubular cell apoptosis induced by postasphyxial serum remain poorly understood. In this report we investigate the intracellular signal transduction mechanisms that operate during injury of renal tubular cells induced by postasphyxial serum in neonates. Cultured human renal proximal tubular cells HK-2 cell were exposed to 10% fetal calf serum (normal control), 20% postasphyxial serum or 20% postasphyxial serum with pyrrolidine dithiocarbamate (PDTC). The expression of both BAD and BAX in the cytoplasm was detected by immunohistochemistry. The mitochondria membrane potential (Deltapsim) was examined by confocal microscopy, and the release of the apoptogenic mitochondrial proteins cytochrome C and AIF was assessed by Western blot analysis. Loss of mitochondria membrane potential was detected in HK-2 cells treated with 20% postasphyxial serum as compared to cells in normal serum or PTDC-pretreated cells in 20% postasphyxial serum. A significant increase of Bad and Bax protein expression was also detected, along with the release of cytochrome C and AIF from mitochondria to cytosol in the postasphyxial serum treated cells, but not in the normal or PTDC-pretreated control cells. Our findings suggest that postasphyxial serum may induce renal tubular cell apoptosis through the mitochondrial pathway, and its intracellular signal transduction mechanism includes the activation of nuclear factor-kappaB. Copyright 2009 S. Karger AG, Basel.

Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers.

PubMed

Pruijm, Menno; Hofmann, Lucie; Charollais-Thoenig, Julie; Forni, Valentina; Maillard, Marc; Coristine, Andrew; Stuber, Matthias; Burnier, Michel; Vogt, Bruno

2013-09-01

Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

Retroperitoneal teratoma with somatic malignant transformation: a papillary renal cell carcinoma in a testicular germ cell tumour metastasis following platinum-based chemotherapy.

PubMed

Zeh, Nina; Wild, Peter J; Bode, Peter K; Kristiansen, Glen; Moch, Holger; Sulser, Tullio; Hermanns, Thomas

2013-02-12

Malignant transformation describes the phenomenon in which a somatic component of a germ cell teratoma undergoes malignant differentiation. A variety of different types of sarcoma and carcinoma, all non-germ cell, have been described as a result of malignant transformation. A 33-year-old man presented with a left testicular mass and elevated tumour markers. Staging investigations revealed retroperitoneal lymphadenopathy with obstruction of the left ureter and distant metastases. Histopathology from the left radical orchiectomy showed a mixed germ cell tumour (Stage III, poor prognosis). The ureter was stented and four cycles of cisplatin, etoposide and bleomycin chemotherapy administered. After initial remission, the patient recurred four years later with a large retroperitoneal mass involving the renal vessels and the left ureter. Left retroperitoneal lymph node dissection with en-bloc resection of the left kidney was performed.Histopathology revealed a germ cell tumour metastasis consisting mainly of mature teratoma. Additionally, within the teratoma a papillary renal cell carcinoma was found. The diagnosis was supported by immunohistochemistry showing positivity for AMACR, CD10 and focal expression of RCC and CK7. There was no radiological or histo-pathological evidence of a primary renal cell cancer. To the best of our knowledge, malignant transformation into a papillary renal cell carcinoma has not been reported in a testicular germ cell tumour metastasis following platinum-based chemotherapy. This histological diagnosis might have implications for potential future therapies. In the case of disease recurrence, renal cell cancer as origin of the recurrent tumour has to be excluded because renal cell carcinoma metastases would not respond well to the classical germ cell tumour chemotherapy regimens.

Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

PubMed Central

Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y.; Castoldi, Ângela; Gonçalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco José; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Império-Lima, Maria Regina; Figueiredo-Neto, Antônio Martins; Reis, Marlene Antônia; Marinho, Cláudio Romero Farias; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

2012-01-01

Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA. PMID:22952850

The impact of renal protection clinics on prescription of and adherence to cardioprotective drug therapy in chronic kidney disease patients.

PubMed

Lepeytre, Fanny; Cardinal, Héloise; Fradette, Lorraine; Verhave, Jacobien; Dorais, Marc; LeLorier, Jacques; Pichette, Vincent; Madore, François

2017-06-01

Background: The aim of this study was to assess the impact of follow-up in renal protection clinics on the prescription of and adherence to cardioprotective drugs in patients with chronic kidney disease (CKD). Methods: We studied stage 4 and 5 CKD patients who initiated follow-up in three renal protection clinics. The prescription pattern of antihypertensive agents (AHA) and lipid-lowering agents (LLAs) was measured as the percentage of patients who are prescribed the agents of interest at a given time. Adherence to drug therapy was defined as the percentage of days, during a pre-defined observation period, in which patients have an on-hand supply of their prescribed medications. Results: A total of 259 CKD patients were enrolled and followed for up to 1 year after referral to renal protection clinics. There was a significant increase in the prescription of angiotensin-converting enzyme inhibitors (34-39%), angiotensin II receptor blockers (11-14%), beta-blockers (40-51%), calcium channel blockers (62-74%), diuretics (66-78%) and LLAs (39-47%) during follow-up in the renal protection clinic compared with baseline (P-values <0.01 for all comparisons). The proportions of patients with good (≥ 80%) and poor (< 80%) adherence to AHA (P = 0.41) and LLAs (P = 0.11) were similar in the year preceding and the year following the first visit to the renal protection clinics. Conclusion: Our results suggest that referral and follow-up in a renal protection clinic may increase the prescription of cardioprotective agents in CKD patients, but does not appear to improve adherence to these medications.

Transcatheter Arterial Embolization with a Mixture of Absolute Ethanol and Iodized Oil for Poorly Visualized Endophytic Renal Masses Prior to CT-Guided Percutaneous Cryoablation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michimoto, Kenkichi, E-mail: michikoo@jikei.ac.jp; Shimizu, Kanichiro; Kameoka, Yoshihiko

PurposeTo retrospectively evaluate the feasibility of transcatheter arterial embolization (TAE) using a mixture of absolute ethanol and iodized oil to improve localization of endophytic renal masses on unenhanced computed tomography (CT) prior to CT-guided percutaneous cryoablation (PCA).Materials and MethodsOur institutional review board approved this retrospective study. From September 2011 to June 2015, 17 patients (mean age, 66.8 years) with stage T1a endophytic renal masses (mean diameter, 26.5 mm) underwent TAE using a mixture of absolute ethanol and iodized oil to improve visualization of small and endophytic renal masses on unenhanced CT prior to CT-guided PCA. TAE was considered successful that accumulated iodizedmore » oil depicted whole of the tumor edge on CT. PCA was considered successful when the iceball covered the entire tumor with over a 5 mm margin. Oncological and renal functional outcomes and complications were also evaluated.ResultsTAE was successfully performed in 16 of 17 endophytic tumors. The 16 tumors were performed under CT-guided PCA with their distinct visualization of localization and safe ablated margin. During the mean follow-up period of 15.4 ± 5.1 months, one patient developed local recurrence. Estimated glomerular filtration rate declined by 8 % with statistical significance (P = 0.01). There was no procedure-related significant complication.ConclusionTAE using a mixture of absolute ethanol and iodized oil to improve visualization of endophytic renal masses facilitated tumor localization on unenhanced CT, permitting depiction of the tumor edge as well as a safe margin for ablation during CT-guided PCA, with an acceptable decline in renal function.« less

Epidemiology of kidney cancer.

PubMed

Dayal, H; Kinman, J

1983-12-01

Renal-cell carcinoma usually affects those over 40 years old, and, in any age group, the disease occurs about twice as frequently among men as it does among women. The incidence of the disease has been steadily increasing over the years. In the United States, the probability of surviving after diagnosis of renal cancer has been improving since 1940 regardless of race, sex, and age at diagnosis. The relationship between SES and the chance of developing the disease is sporadic with an indication of a slightly higher risk in the upper socioeconomic classes. Urbanrural comparisons consistently suggest that a higher risk is associated with urban residence. Tobacco use is probably the only environmental factor that could be considered to be etiologically related to cancer of the kidney. A variety of studies point to a moderate but consistent association with tobacco use in the form of cigarette, cigar, or pipe smoking. The excess of the disease in males compared to females and the lower incidence in Mormons may partly be due to the confounding effect of smoking. Dietary vitamin A or vitamin A supplements may have an antipromoting effect in the development of kidney cancer. Hypotheses implicating fat and/or cholesterol intake in the etiology of cancer of the kidney appear to be too tenuous. The evidence of a relationship between concentrations of certain trace metals in drinking water and incidence of renal cancer is weak. Similarly, there is no strong indication of an increased risk among individuals exposed to radiation. In general, with the exception of the observation of an unusually high risk among coke-oven workers, occupational studies have not identified any high-risk groups. Familial aggregation, though rare, occurs with peculiar disease characteristics that may predict similar cancers in the proband's relatives with a high degree of accuracy. In conclusion, the etiology of cancer of the kidney is poorly understood. The descriptive epidemiology of the disease provides some interesting insights into the correlates of the distribution of the disease.(ABSTRACT TRUNCATED AT 400 WORDS)

The usefulness of administrative databases for identifying disease cohorts is increased with a multivariate model.

PubMed

van Walraven, Carl; Austin, Peter C; Manuel, Douglas; Knoll, Greg; Jennings, Allison; Forster, Alan J

2010-12-01

Administrative databases commonly use codes to indicate diagnoses. These codes alone are often inadequate to accurately identify patients with particular conditions. In this study, we determined whether we could quantify the probability that a person has a particular disease-in this case renal failure-using other routinely collected information available in an administrative data set. This would allow the accurate identification of a disease cohort in an administrative database. We determined whether patients in a randomly selected 100,000 hospitalizations had kidney disease (defined as two or more sequential serum creatinines or the single admission creatinine indicating a calculated glomerular filtration rate less than 60 mL/min/1.73 m²). The independent association of patient- and hospitalization-level variables with renal failure was measured using a multivariate logistic regression model in a random 50% sample of the patients. The model was validated in the remaining patients. Twenty thousand seven hundred thirteen patients had kidney disease (20.7%). A diagnostic code of kidney disease was strongly associated with kidney disease (relative risk: 34.4), but the accuracy of the code was poor (sensitivity: 37.9%; specificity: 98.9%). Twenty-nine patient- and hospitalization-level variables entered the kidney disease model. This model had excellent discrimination (c-statistic: 90.1%) and accurately predicted the probability of true renal failure. The probability threshold that maximized sensitivity and specificity for the identification of true kidney disease was 21.3% (sensitivity: 80.0%; specificity: 82.2%). Multiple variables available in administrative databases can be combined to quantify the probability that a person has a particular disease. This process permits accurate identification of a disease cohort in an administrative database. These methods may be extended to other diagnoses or procedures and could both facilitate and clarify the use of administrative databases for research and quality improvement. Copyright © 2010 Elsevier Inc. All rights reserved.

External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study

PubMed Central

Heng, Daniel Y C; Xie, Wanling; Regan, Meredith M; Harshman, Lauren C; Bjarnason, Georg A; Vaishampayan, Ulka N; Mackenzie, Mary; Wood, Lori; Donskov, Frede; Tan, Min-Han; Rha, Sun-Young; Agarwal, Neeraj; Kollmannsberger, Christian; Rini, Brian I; Choueiri, Toni K

2014-01-01

Summary Background The International Metastatic Renal-Cell Carcinoma Database Consortium model offers prognostic information for patients with metastatic renal-cell carcinoma. We tested the accuracy of the model in an external population and compared it with other prognostic models. Methods We included patients with metastatic renal-cell carcinoma who were treated with first-line VEGF-targeted treatment at 13 international cancer centres and who were registered in the Consortium’s database but had not contributed to the initial development of the Consortium Database model. The primary endpoint was overall survival. We compared the Database Consortium model with the Cleveland Clinic Foundation (CCF) model, the International Kidney Cancer Working Group (IKCWG) model, the French model, and the Memorial Sloan-Kettering Cancer Center (MSKCC) model by concordance indices and other measures of model fit. Findings Overall, 1028 patients were included in this study, of whom 849 had complete data to assess the Database Consortium model. Median overall survival was 18·8 months (95% 17·6–21·4). The predefined Database Consortium risk factors (anaemia, thrombocytosis, neutrophilia, hypercalcaemia, Karnofsky performance status <80%, and <1 year from diagnosis to treatment) were independent predictors of poor overall survival in the external validation set (hazard ratios ranged between 1·27 and 2·08, concordance index 0·71, 95% CI 0·68–0·73). When patients were segregated into three risk categories, median overall survival was 43·2 months (95% CI 31·4–50·1) in the favourable risk group (no risk factors; 157 patients), 22·5 months (18·7–25·1) in the intermediate risk group (one to two risk factors; 440 patients), and 7·8 months (6·5–9·7) in the poor risk group (three or more risk factors; 252 patients; p<0·0001; concordance index 0·664, 95% CI 0·639–0·689). 672 patients had complete data to test all five models. The concordance index of the CCF model was 0·662 (95% CI 0·636–0·687), of the French model 0·640 (0·614–0·665), of the IKCWG model 0·668 (0·645–0·692), and of the MSKCC model 0·657 (0·632–0·682). The reported versus predicted number of deaths at 2 years was most similar in the Database Consortium model compared with the other models. Interpretation The Database Consortium model is now externally validated and can be applied to stratify patients by risk in clinical trials and to counsel patients about prognosis. PMID:23312463

MicroRNA-214 Reduces Insulin-like Growth Factor-1 (IGF-1) Receptor Expression and Downstream mTORC1 Signaling in Renal Carcinoma Cells*

PubMed Central

Das, Falguni; Dey, Nirmalya; Bera, Amit; Kasinath, Balakuntalam S.; Ghosh-Choudhury, Nandini; Choudhury, Goutam Ghosh

2016-01-01

Elevated IGF-1/insulin-like growth factor-1 receptor (IGF-1R) autocrine/paracrine signaling in patients with renal cell carcinoma is associated with poor prognosis of the disease independent of their von Hippel-Lindau (VHL) status. Increased expression of IGF-1R in renal cancer cells correlates with their potency of tumor development and progression. The mechanism by which expression of IGF-1R is increased in renal carcinoma is not known. We report that VHL-deficient and VHL-positive renal cancer cells possess significantly decreased levels of mature, pre-, and pri-miR-214 than normal proximal tubular epithelial cells. We identified an miR-214 recognition element in the 3′UTR of IGF-1R mRNA and confirmed its responsiveness to miR-214. Overexpression of miR-214 decreased the IGF-1R protein levels, resulting in the inhibition of Akt kinase activity in both types of renal cancer cells. IGF-1 provoked phosphorylation and inactivation of PRAS40 in an Akt-dependent manner, leading to the activation of mTORC1 signal transduction to increase phosphorylation of S6 kinase and 4EBP-1. Phosphorylation-deficient mutants of PRAS40 and 4EBP-1 significantly inhibited IGF-1R-driven proliferation of renal cancer cells. Expression of miR-214 suppressed IGF-1R-induced phosphorylation of PRAS40, S6 kinase, and 4EBP-1, indicating inhibition of mTORC1 activity. Finally, miR-214 significantly blocked IGF-1R-forced renal cancer cell proliferation, which was reversed by expression of 3′UTR-less IGF-1R and constitutively active mTORC1. Together, our results identify a reciprocal regulation of IGF-1R levels and miR-214 expression in renal cancer cells independent of VHL status. Our data provide evidence for a novel mechanism for IGF-1R-driven renal cancer cell proliferation involving miR-214 and mTORC1. PMID:27226530

Tumor Mutational Load and Immune Parameters across Metastatic Renal Cell Carcinoma Risk Groups.

PubMed

de Velasco, Guillermo; Miao, Diana; Voss, Martin H; Hakimi, A Ari; Hsieh, James J; Tannir, Nizar M; Tamboli, Pheroze; Appleman, Leonard J; Rathmell, W Kimryn; Van Allen, Eliezer M; Choueiri, Toni K

2016-10-01

Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared with patients with favorable or intermediate risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here, we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole-exome transcriptome data in renal cell carcinoma patients (n = 54) included in The Cancer Genome Atlas who ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Nonsynonymous mutational load did not differ significantly by the MSKCC risk group, nor was the expression of cytolytic genes-granzyme A and perforin-or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis revealed that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. Cancer Immunol Res; 4(10); 820-2. ©2016 AACR. ©2016 American Association for Cancer Research.

[Selective preimplantation pathological evaluation in renal transplantation: a single center's experience].

PubMed

Peng, F H; Chen, J J; Peng, L K; Xie, X B; Lan, G B; Yu, S J; Wang, Y; Tang, X T; Dai, H L; Gao, C; Fang, C H

2018-01-16

Objective: To summarize the clinical data of pre-implantation biopsy donors in our hospital and explore the clinical characteristics of those donors in pathological high-risk, and to provide references for the selective histological evaluation of extended criteria donor kidneys. Methods: We retrospectively reviewed the clinical data and pre-implantation renal pathologic score of donors from January 1, 2015 to May 1, 2017.During this period, 247 cases of donation after citizen's death (DCD) occurred.After clinical evaluation and selective machine perfusion( Lifeport) evaluation, 30 cases of pre-implantation pathological evaluation were performed.According to Remuzzi scores, donors were divided into low-risk and high-risk group.Nine cases of low-risk group (bilateral kidney's Remuzzi score ≤3) and 16 cases of high-risk group (bilateral or unilateral kidney's Remuzzi score ≥4, severe glomerular micro-thrombi or severe tubular necrosis) were included.Five cases of donors were excluded due to only unilateral renal pathological result available.Both high-risk and low-risk groups' clinical data, including sex, age, height, body weight, body mass index, proteinuria, hematuria, urinary glucose, baseline or admission serum creatinine, serum creatinine before procurement, history of hypertension and/or diabetes mellitus, cardiopulmonary resuscitation or not, with or without the history of shock, urine output prior to acquisition, macroscopical manifestations of donor kidney, cause of death were statistically analyzed. Results: The donors' baseline serum creatinine/upper limit of normal serum creatinine range in high-risk group were significantly higher than that in low-risk group [(129.8±42.2)% vs(92.4±30.5)%, P =0.029]. The poor macroscopical manifestations of donor kidneys were significantly more frequent in high-risk group than that in low-risk group (12/16 vs 0/9, P = 0). No significant differences between two groups were found regarding their age, height, weight, BMI, proteinuria, hematuria, urine glucose, pre-procure creatinine level, history of hypertension and/or diabetes mellitus, cause of death and so on ( P >0.05). Conclusions: After clinical evaluation and selective Lifeport evaluation, donor grafts of whose baseline serum creatinine levels increased beyond normal range and of whose grafts' macroscopical manifestations were poor, should undergo pre-implantation pathological evaluation further.Also, it is reasonable to perform pre-implantation biopsy in cases of equivocal results after Lifeport evaluation.This will be beneficial to identify histological high-risk donors and also be predictive to allocate the grafts.

Case study: the link between hypertension and diabetes.

PubMed

Bakris, George L; Gonzalez, Edgar R

2007-06-01

Many diabetics develop hypertension, and it is a major risk factor for cardiovascular and microvascular complications. To review a case study of a patient with poorly controlled hypertension and diabetes. Further assessment of this case study shows that the patient has poorly controlled hypertension, despite multiple medications. The patient also has metabolic syndrome complicated.by diabetes, microalbuminuria and peripheral arterial disease. The patient's hypertensive treatment options must be evaluated in light of the fact that polypharmacy has made it more difficult for her to achieve glycemic control. A panoply of drugs and drug classes are available from which to choose: diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and aldosterone antagonists. New vasodilatory betablockers reduce adverse drug reactions and produce beneficial effects on arterial vasculature. Various beta~blockers' effects on insulin sensitivity are compared. Older beta-blockers have been shown to have detrimental effects on glucose or lipid parameters. Newer agents such as nebivolol do not impact lipid, glucose, insulin, or high-density lipoproteins. Instead, nebivolol stimulates endothelial nitric oxide release in renal arteries and improves renal function.

Long non-coding RNA GAS5 sensitizes renal cell carcinoma to sorafenib via miR-21/SOX5 pathway.

PubMed

Liu, Lei; Pang, Xinlu; Shang, Wenjin; Xie, Hongchang; Feng, Yonghua; Feng, Guiwen

2018-06-12

Although the use of sorafenib appears to increase the survival rate of renal cell carcinoma (RCC) patients, there is also a proportion of patients who exhibit a poor primary response to sorafenib treatment. Therefore, it is critical to elucidate the mechanisms underlying sorafenib resistance and find representative biomarkers for sorafenib treatment in RCC patients. Herein, we identified that a long noncoding RNA GAS5 was downregulated in sorafenib nonresponsive RCCs. GAS5 overexpression conferred sorafenib sensitive to nonresponsive RCC cells, whereas knockdown of GAS5 promoted responsive RCC cells resistant to sorafenib treatment in vitro and in vivo. Mechanistically, GAS5 functioned as competing endogenous RNA to repress miR-21, which controlled its down-stream target SOX5. We proposed that GAS5 was responsible for sorafenib resistance in RCC cells and GAS5 exerted its function through the miR-21/ SOX5 axis. Our findings suggested that GAS5 downregulation may be a new marker of poor response to sorafenib and GAS5 could be a potential therapeutic target for sorafenib treatment in RCC.

Acute Kidney Injury Predicts Major Adverse Outcomes in Diabetes: Synergic Impact With Low Glomerular Filtration Rate and Albuminuria.

PubMed

Monseu, Mathilde; Gand, Elise; Saulnier, Pierre-Jean; Ragot, Stéphanie; Piguel, Xavier; Zaoui, Philippe; Rigalleau, Vincent; Marechaud, Richard; Roussel, Ronan; Hadjadj, Samy; Halimi, Jean-Michel

2015-12-01

Subjects with diabetes are prone to the development of cardiovascular and noncardiovascular complications. In separate studies, acute kidney injury (AKI), albuminuria, and low estimated glomerular filtration rate (eGFR) were shown to predict adverse outcomes, but, when considered together, their respective prognostic value is unknown. Patients with type 2 diabetes consecutively recruited in the SURDIAGENE cohort were prospectively followed up for major diabetes-related events, as adjudicated by an independent committee: death (with cause), major cardiovascular events (myocardial infarction, stroke, congestive heart failure, amputation, and arterial revascularization), and renal failure (i.e., sustained doubling of serum creatinine level or end-stage renal disease). Intrahospital AKI occurred in 411 of 1,371 patients during the median follow-up period of 69 months. In multivariate analyses, AKI was significantly associated with cardiovascular and noncardiovascular death, including cancer-related death. In multivariate analyses, AKI was a powerful predictor of major adverse cardiovascular events, heart failure requiring hospitalization, myocardial infarction, stroke, lower-limb amputation or revascularization, and carotid artery revascularization. AKI, eGFR, and albuminuria, even when simultaneously considered in multivariate models, predicted all-cause and cardiovascular deaths. All three renal biomarkers were also prognostic of most adverse outcomes and of the risk of renal failure. AKI, low eGFR, and elevated albuminuria, separately or together, are compelling biomarkers of major adverse outcomes and death in diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients

PubMed Central

Caroli, Anna; Antiga, Luca; Conti, Sara; Sonzogni, Aurelio; Fasolini, Giorgio; Ondei, Patrizia; Perico, Norberto; Remuzzi, Giuseppe; Remuzzi, Andrea

2011-01-01

Total kidney and cyst volumes have been used to quantify disease progression in autosomal dominant polycystic kidney disease (ADPKD), but a causal relationship with progression to renal failure has not been demonstrated. Advanced image processing recently allowed to quantify extracystic tissue, and to identify an additional tissue component named “intermediate,” appearing hypoenhanced on contrast-enhanced computed tomography (CT). The aim of this study is to provide a histological characterization of intermediate volume, investigate its relation with renal function, and provide preliminary evidence of its role in long-term prediction of functional loss. Three ADPKD patients underwent contrast-enhanced CT scans before nephrectomy. Histological samples of intermediate volume were drawn from the excised kidneys, and stained with hematoxylin and eosin and with saturated picrosirius solution for histological analysis. Intermediate volume showed major structural changes, characterized by tubular dilation and atrophy, microcysts, inflammatory cell infiltrate, vascular sclerosis, and extended peritubular interstitial fibrosis. A significant correlation (r = −0.69, P < 0.001) between relative intermediate volume and baseline renal function was found in 21 ADPKD patients. Long-term prediction of renal functional loss was investigated in an independent cohort of 13 ADPKD patients, followed for 3 to 8 years. Intermediate volume, but not total kidney or cyst volume, significantly correlated with glomerular filtration rate decline (r = −0.79, P < 0.005). These findings suggest that intermediate volume may represent a suitable surrogate marker of ADPKD progression and a novel therapeutic target. PMID:21683674

Severe manifestation of Bartter syndrome Type IV caused by a novel insertion mutation in the BSND gene.

PubMed

de Pablos, Augusto Luque; García-Nieto, Victor; López-Menchero, Jesús C; Ramos-Trujillo, Elena; González-Acosta, Hilaria; Claverie-Martín, Félix

2014-05-01

Bartter syndrome Type IV is a rare subtype of the Bartter syndromes that leads to both severe renal salt wasting and sensorineural deafness. This autosomal recessive disease is caused by mutations in the gene encoding barttin, BSND, an essential subunit of the ClC-K chloride channels expressed in renal and inner ear epithelia. Patients differ in the severity of renal symptoms, which appears to depend on the modification of channel function by the mutant barttin. To date, only a few BSND mutations have been reported, most of which are missense or nonsense mutations. In this study, we report the identification of the first insertion mutation, p.W102Vfs*7, in the BSND gene of a newborn girl with acute clinical symptoms including early-onset chronic renal failure. The results support previous data indicating that mutations that are predicted to abolish barttin expression are associated with a severe phenotype and early onset renal failure.

Fluid Overload is Associated with Late Poor Outcomes in Neonates Following Cardiac Surgery

PubMed Central

Wilder, Nicole S; Yu, Sunkyung; Donohue, Janet E; Goldberg, Caren S; Blatt, Neal B

2016-01-01

Objective Acute kidney injury (AKI) is a severe complication of cardiac surgery associated with increased morbidity and mortality, yet AKI classification for neonates remains challenging. We characterized patterns of post-operative fluid overload (FO) as a surrogate marker for AKI and as a risk factor of poor post-operative outcomes in neonates undergoing cardiac surgery. Design Retrospective cohort study. Setting Single, congenital heart center destination program. Patients 435 neonates undergoing cardiac surgery with cardiopulmonary bypass from January 2006 through December 2010. Interventions None Measurements and Main Results Demographics, diagnosis, and perioperative clinical variables were collected, including daily weights and serum creatinine (SCr) levels. A composite poor clinical outcome (death, need for renal replacement therapy (RRT), or extracorporeal life support (ECLS) within 30 post-operative days) was considered the primary outcome measure. Twenty-one neonates (5%) had a composite poor outcome with 7 (2%) requiring RRT, 8 (2%) requiring ECLS, and 14 (3%) dying between 3 and 30 days post-surgery. Neonates with a composite poor outcome had significantly higher maximum FO (>20%) and were slower to diurese. A receiver-operating characteristic curve determined that FO ≥ 16% and SCr ≥ 0.9 on post-operative day 3 were the optimal cutoffs for significant discrimination on the primary outcome (area under the curve = 0.71 and 0.76, respectively). In multivariable analysis, FO ≥ 16% (adjusted odds ratio [AOR] = 3.7) and SCr ≥ 0.9 (AOR = 6.6) on post-operative day 3 remained an independent risk factor for poor outcome. FO ≥ 16% was also significantly associated with cardiac arrest requiring cardiopulmonary resuscitation, prolonged intensive care unit stay, and chest re-exploration. Conclusions This study highlights the importance of monitoring fluid balance in the neonatal cardiac surgical population, and suggests that daily FO, a readily-available, non-invasive marker of renal function, may be a sensitive and specific predictor of adverse outcomes. PMID:27028790

Captain Lord's uremia.

PubMed

Wyner, Lawrence Michael

2013-06-01

The hundredth anniversary of the worst ever civilian maritime disaster was also the fiftieth anniversary of the death of arguably its most controversial character, Captain Stanley Lord, skipper of the Californian, a "tramp" steamer that became entrapped in ice just off the Grand Banks of Newfoundland on April 14, 1912. Although Lord was faulted in two widely publicized inquiries for failing to respond to Titanic's distress signals, there may have actually been a medical reason for his behavior because he suffered from chronic renal disease and most likely had some secondary cognitive impairment due to this disease. An assessment of Lord's health history shows that he fractured his leg as a young man; suffered from poor eyesight, which led to his premature retirement from the sea by the age of 50; and eventually died from renal failure. Furthermore, his death certificate alludes to previous uremic episodes, perhaps encompassing the time period of the Titanic accident. Lord may have been under some pressure not to reveal his infirmity because doing so could have further jeopardized his career. The literature abounds with evidence that renal insufficiency negatively affects cognition, often years before progression to end-stage renal disease. Captain Lord's failure to act in a crisis situation may serve as a case in point.

Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function.

PubMed

Perco, Paul; Heinzel, Andreas; Leierer, Johannes; Schneeberger, Stefan; Bösmüller, Claudia; Oberhuber, Rupert; Wagner, Silvia; Engler, Franziska; Mayer, Gert

2018-05-03

Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.

Estimation of Daily Proteinuria in Patients with Amyloidosis by Using the Protein-To-Creatinine ratio in Random Urine Samples

PubMed Central

Talamo, Giampaolo; Mir Muhammad, A.; Pandey, Manoj K.; Zhu, Junjia; Creer, Michael H.; Malysz, Jozef

2015-01-01

Measurement of daily proteinuria in patients with amyloidosis is recommended at the time of diagnosis for assessing renal involvement, and for monitoring disease activity. Renal involvement is usually defined by proteinuria >500 mg/day. We evaluated the accuracy of the random urine protein-to-creatinine ratio (Pr/Cr) in predicting 24 hour proteinuria in patient with amyloidosis. We compared results of random urine Pr/Cr ratio and concomitant 24-hour urine collections in 44 patients with amyloidosis. We found a strong correlation (Spearman’s ρ=0.874) between the Pr/Cr ratio and the 24 hour urine protein excretion. For predicting renal involvement, the optimal cut-off point of the Pr/Cr ratio was 715 mg/g. The sensitivity and specificity for this point were 91.8% and 95.5%, respectively, and the area under the curve value was 97.4%. We conclude that the random urine Pr/Cr ratio could be useful in the screening of renal involvement in patients with amyloidosis. If validated in a prospective study, the random urine Pr/Cr ratio could replace the 24 hour urine collection for the assessment of daily proteinuria and presence of nephrotic syndrome in patients with amyloidosis. PMID:25918613