Preoperative dipstick albuminuria and other urine abnormalities predict acute kidney injury and patient outcomes.

PubMed

Park, Sehoon; Lee, Soojin; Lee, Anna; Paek, Jin Hyuk; Chin, Ho Jun; Na, Ki Young; Chae, Dong-Wan; Kim, Sejoong

2018-05-01

It is unclear whether pathologic findings on preoperative urinalysis are associated with the risk of postoperative acute kidney injury (AKI). Therefore, we performed a retrospective review to investigate this association. We assessed the clinical significance of preoperative dipstick urinalysis in a 10-year surgery cohort from a tertiary hospital in Korea. Patients without available information on perioperative serum creatinine levels or kidney injury prior to surgery were excluded. Preoperative dipstick urinalysis parameters, including albuminuria, hematuria, pyuria, and others were studied. The primary outcome was postoperative acute kidney injury. Secondary outcomes were postoperative 1-year mortality and progression of poor kidney function parameters. We enrolled 40,090 patients. The presence of dipstick albuminuria was associated with an increased risk of postoperative AKI (adjusted odds ratio 1.47 [1.29-1.66], P < .001), and the association showed a dose-response relationship. High specific gravity was significantly associated with increased risk of AKI (adjusted odds ratio 1.30 [1.04-1.63], P = .02). Furthermore, in patients with postoperative AKI, those with baseline albuminuria had a worse prognosis with regard to 1-year mortality (adjusted hazard ratio 2.81 [1.56-5.09], P < .001) and persistent renal function impairment (adjusted odds ratio 2.07 [1.21-3.46], P = .007), independent of estimated glomerular filtration rate values. Patients with baseline hematuria and pyuria also had an inferior postoperative AKI prognosis when compared to those without the urinalysis abnormalities. Baseline dipstick urinalysis may predict postoperative AKI and may be significantly associated with prognosis after surgery. (Surgery 2017;160:XXX-XXX.). Copyright © 2017 Elsevier Inc. All rights reserved.

[Acute kidney injury after pediatric cardiac surgery: risk factors and outcomes. Proposal for a predictive model].

PubMed

Cardoso, Bárbara; Laranjo, Sérgio; Gomes, Inês; Freitas, Isabel; Trigo, Conceição; Fragata, Isabel; Fragata, José; Pinto, Fátima

2016-02-01

To characterize the epidemiology and risk factors for acute kidney injury (AKI) after pediatric cardiac surgery in our center, to determine its association with poor short-term outcomes, and to develop a logistic regression model that will predict the risk of AKI for the study population. This single-center, retrospective study included consecutive pediatric patients with congenital heart disease who underwent cardiac surgery between January 2010 and December 2012. Exclusion criteria were a history of renal disease, dialysis or renal transplantation. Of the 325 patients included, median age three years (1 day-18 years), AKI occurred in 40 (12.3%) on the first postoperative day. Overall mortality was 13 (4%), nine of whom were in the AKI group. AKI was significantly associated with length of intensive care unit stay, length of mechanical ventilation and in-hospital death (p<0.01). Patients' age and postoperative serum creatinine, blood urea nitrogen and lactate levels were included in the logistic regression model as predictor variables. The model accurately predicted AKI in this population, with a maximum combined sensitivity of 82.1% and specificity of 75.4%. AKI is common and is associated with poor short-term outcomes in this setting. Younger age and higher postoperative serum creatinine, blood urea nitrogen and lactate levels were powerful predictors of renal injury in this population. The proposed model could be a useful tool for risk stratification of these patients. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study.

PubMed

Nickolas, Thomas L; Schmidt-Ott, Kai M; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C; Barasch, Jonathan

2012-01-17

This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Diagnostic and Prognostic Stratification in the Emergency Department Using Urinary Biomarkers of Nephron Damage

PubMed Central

Nickolas, Thomas L.; Schmidt-Ott, Kai M.; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J.; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C.; Barasch, Jonathan

2012-01-01

Objectives This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Background Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. Methods In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase–associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. Results All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Conclusion Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. PMID:22240130

Regulated compensated donation in Pakistan and Iran.

PubMed

Rizvi, Adibul Hasan S; Naqvi, Anwar S A; Zafar, Naqi M; Ahmed, Ejaz

2009-04-01

Paid living unrelated kidney donor transplantation has flourished in Pakistan and Iran. This review discusses the dynamics and consequences of organ trade in Pakistan and of a regulated paid donor model in Iran on transplant activities in these countries. In 2007, over 2500 renal transplants were performed in Pakistan, where more than 70% were from socioeconomic disadvantaged kidney vendors. More than half of recipients were foreigners who paid US$20,000-30,000. Recipients of vendor kidneys had poor outcome and high infectious complications. Regulated paid donor kidney transplant in Iran number around 1500 per year and constitute 70% of the total transplants. Graft survival rates are similar to those for living related donors. The donors are paid US$1200 and additional monies are negotiated between the recipient-donor pair. This model claims to have abolished waiting lists, although many poor patients wait for deceased donors. In both countries, recipients are relatively rich and vendors are the poor of the society who sell kidneys for quick money or to repay debts. Paid donation, regulated or commercial, leads to coercion and exploitation of the poor and benefits the rich. This situation has forestalled deceased donor program and hence other solid-organ transplants. The way forward is to promote deceased donors by making transplant available to all who need it.

The Natural History of Kidney Graft Cortical Microcirculation Determined by Real-Time Contrast-Enhanced Sonography (RT-CES).

PubMed

Jiménez, Carlos; López, María Ovidia; Ros, Amaia; Aguilar, Ana; Menendez, David; Rivas, Begoña; Santana, María José; Vaca, Marco Antonio; Escuin, Fernando; Madero, Rosario; Selgas, Rafael

2016-01-01

Kidney transplantation is the therapy of choice for end-stage kidney disease. Graft's life span is shorter than expected due in part to the delayed diagnosis of various complications, specifically those related to silent progression. It is recognized that serum creatinine levels and proteinuria are poor markers of mild kidney lesions, which results in delayed clinical information. There are many investigation looking for early markers of graft damage. Decreasing kidney graft cortical microcirculation has been related to poor prognosis in kidney transplantation. Cortical capillary blood flow (CCBF) can be measured by real-time contrast-enhanced sonography (RT-CES). Our aim was to describe the natural history of CCBF over time under diverse conditions of kidney transplantation, to explore the influence of donor conditions and recipient events, and to determine the capacity of CCBF for predicting renal function in medium term. RT-CES was performed in 79 consecutive kidney transplant recipients during the first year under regular clinical practice. Cortical capillary blood flow was measured. Clinical variables were analyzed. The influence of CCBF has been determined by univariate and multivariate analysis using mixed regression models based on sequential measurements for each patient over time. We used a first-order autoregression model as the structure of the covariation between measures. The post-hoc comparisons were considered using the Bonferroni correction. The CCBF values varied significantly over the study periods and were significantly lower at 48 h and day 7. Brain-death donor age and CCBF levels showed an inverse relationship (r: -0.62, p<0.001). Living donors showed higher mean CCBF levels than brain-death donors at each point in the study. These significant differences persisted at month 12 (54.5 ± 28.2 vs 33.7 ± 30 dB/sec, living vs brain-death donor, respectively, p = 0.004) despite similar serum creatinine levels (1.5 ± 0.3 and 1.5 ± 0.5 mg/dL). A sole rejection episode was associated with lower overall CCBF values over the first year. CCBF defined better than level of serum creatinine the graft function status at medium-term. RT-CES is a non-invasive tool that can quantify and iteratively estimate cortical microcirculation. We have described the natural history of cortical capillary blood flow under regular clinical conditions.

Kidney biopsy

MedlinePlus

... normal structure. What Abnormal Results Mean An abnormal result means there are changes in the kidney tissue. This may be due to: Infection Poor blood flow through the kidney Connective tissue diseases such as systemic lupus erythematosus Other diseases that may be affecting the ...

Drug transporter expression profiling in a three-dimensional kidney proximal tubule in vitro nephrotoxicity model.

PubMed

Diekjürgen, Dorina; Grainger, David W

2018-05-09

Given currently poor toxicity translational predictions for drug candidates, improved mechanistic understanding underlying nephrotoxicity and drug renal clearance is needed to improve drug development and safety screening. Therefore, better relevant and well-characterized in vitro screening models are required to reliably predict human nephrotoxicity. Because kidney proximal tubules are central to active drug uptake and secretion processes and therefore to nephrotoxicity, this study acquired regio-specific expression data from recently reported primary proximal tubule three-dimensional (3D) hyaluronic acid gel culture and non-gel embedded cultured murine proximal tubule suspensions used in nephrotoxicity assays. Quantitative assessment of the mRNA expression of 21 known kidney tubule markers and important proximal tubule transporters with known roles in drug transport was obtained. Asserting superior gene expression levels over current commonly used two-dimensional (2D) kidney cell culture lines was the study objective. Hence, we compare previously published gel-based 3D proximal tubule fragment culture and their non-gel suspensions for up to 1 week. We demonstrate that 3D tubule culture exhibits superior gene expression levels and profiles compared to published commonly used 2D kidney cell lines (Caki-1 and HK-2) in plastic plate monocultures. Additionally, nearly all tested genes retain mRNA expression after 7 days in both proximal tubule cultures, a limitation of 2D cell culture lines. Importantly, gel presence is shown not to interfere with the gene expression assay. Western blots confirm protein expression of OAT1 and 3 and OCT2. Functional transport assays confirm their respective transporter functions in vitro. Overall, results validate retention of essential toxicity-relevant transporters in this published 3D proximal tubule model over conventional 2D kidney cell cultures, producing opportunities for more reliable, sensitive, and comprehensive drug toxicity studies relevant to drug development and nephrotoxicity goals.

The prediction of drug metabolism, tissue distribution, and bioavailability of 50 structurally diverse compounds in rat using mechanism-based absorption, distribution, and metabolism prediction tools.

PubMed

De Buck, Stefan S; Sinha, Vikash K; Fenu, Luca A; Gilissen, Ron A; Mackie, Claire E; Nijsen, Marjoleen J

2007-04-01

The aim of this study was to assess a physiologically based modeling approach for predicting drug metabolism, tissue distribution, and bioavailability in rat for a structurally diverse set of neutral and moderate-to-strong basic compounds (n = 50). Hepatic blood clearance (CL(h)) was projected using microsomal data and shown to be well predicted, irrespective of the type of hepatic extraction model (80% within 2-fold). Best predictions of CL(h) were obtained disregarding both plasma and microsomal protein binding, whereas strong bias was seen using either blood binding only or both plasma and microsomal protein binding. Two mechanistic tissue composition-based equations were evaluated for predicting volume of distribution (V(dss)) and tissue-to-plasma partitioning (P(tp)). A first approach, which accounted for ionic interactions with acidic phospholipids, resulted in accurate predictions of V(dss) (80% within 2-fold). In contrast, a second approach, which disregarded ionic interactions, was a poor predictor of V(dss) (60% within 2-fold). The first approach also yielded accurate predictions of P(tp) in muscle, heart, and kidney (80% within 3-fold), whereas in lung, liver, and brain, predictions ranged from 47% to 62% within 3-fold. Using the second approach, P(tp) prediction accuracy in muscle, heart, and kidney was on average 70% within 3-fold, and ranged from 24% to 54% in all other tissues. Combining all methods for predicting V(dss) and CL(h) resulted in accurate predictions of the in vivo half-life (70% within 2-fold). Oral bioavailability was well predicted using CL(h) data and Gastroplus Software (80% within 2-fold). These results illustrate that physiologically based prediction tools can provide accurate predictions of rat pharmacokinetics.

Association between Delayed graft function (DGF) biomarkers and long-term outcomes after living donor kidney transplantation.

PubMed

Sahraei, Zahra; Mehdizadeh, Mona; Salamzadeh, Jamshid; Nafar, Mohsen; Eshraghi, Azadeh

2018-05-21

The Association between preoperative Urine Neutrophil Gelatinase-associated Lipocalin (uNGAL) and interlukin-18 (uIL-18) with poor 1-year allograft function has been shown in deceased-donor kidney transplant recipients previously, and also these markers could predict 3-month allograft function. However, it is unknown whether there is any association between these postoperative biomarkers with important recipient outcomes beyond this time in live-donor transplants. NGAL and IL-18 four and 24 hours were measured in live-donor kidney transplant recipients after transplantation. The relationships between changes in these markers with clinical outcomes as well as kidney function were examined at 1 month and 2 years. Also, the association between delayed graft function with clinical outcome and serum creatinine (SrCr) were evaluated during this period. The Mean age for kidney recipients was 23.9 years. There was significant interaction between uNGAL 24 hr (pvalue=0.01) and uIL-18 four and 24 hr after transplantation (pvalue=0.04, 0.03; respectively) with patients' outcome after 1 month and changes in uNGAL with outcomes after 2 years (pvalue= 0.04). Changes in urine NGAL postoperative is associated with worse outcome 2 years after kidney transplantation, suggesting its potential role for identifying patients that are at high risk for diminished allograft function, outcome and survival. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Leveraging Big Data and Electronic Health Records to Enhance Novel Approaches to Acute Kidney Injury Research and Care.

PubMed

Sutherland, Scott M; Goldstein, Stuart L; Bagshaw, Sean M

2017-01-01

While acute kidney injury (AKI) has been poorly defined historically, a decade of effort has culminated in a standardized, consensus definition. In parallel, electronic health records (EHRs) have been adopted with greater regularity, clinical informatics approaches have been refined, and the field of EHR-enabled care improvement and research has burgeoned. Although both fields have matured in isolation, uniting the 2 has the capacity to redefine AKI-related care and research. This article describes how the application of a consistent AKI definition to the EHR dataset can accurately and rapidly diagnose and identify AKI events. Furthermore, this electronic, automated diagnostic strategy creates the opportunity to develop predictive approaches, optimize AKI alerts, and trace AKI events across institutions, care platforms, and administrative datasets. © 2017 S. Karger AG, Basel.

The Association Between Urine Output, Creatinine Elevation, and Death.

PubMed

Engoren, Milo; Maile, Michael D; Heung, Michael; Jewell, Elizabeth S; Vahabzadeh, Christie; Haft, Jonathan W; Kheterpal, Sachin

2017-04-01

Acute kidney injury can be defined by a fall in urine output, and urine output criteria may be more sensitive in identifying acute kidney injury than traditional serum creatinine criteria. However, as pointed out in the Kidney Disease Improving Global Outcome guidelines, the association of urine output with subsequent creatinine elevations and death is poorly characterized. The purpose of this study was to determine what degrees of reduced urine output are associated with subsequent creatinine elevation and death. This was a retrospective cohort study of adult patients (age ≥18 years) cared for in a cardiovascular intensive care unit after undergoing cardiac operations in a tertiary care university medical center. All adult patients who underwent cardiac operations and were not receiving dialysis preoperatively were studied. The development of acute kidney injury was defined as an increase in creatinine of more than 0.3 mg/dL or by more than 50% above baseline by postoperative day 3. Acute kidney injury developed in 1,061 of 4,195 patients (25%). Urine output had moderate discrimination in predicting subsequent acute kidney injury (C statistic = .637 ± .054). Lower urine output and longer duration of low urine output were associated with greater odds of developing acute kidney injury and death. We found that there is similar accuracy in using urine output corrected for actual, ideal, or adjusted weight to discriminate future acute kidney injury by creatinine elevation and recommend using actual weight for its simplicity. We also found that low urine output is associated with subsequent acute kidney injury and that the association is greater for lower urine output and for low urine output of longer durations. Low urine output (<0.2 mL · kg -1 · h -1 ), even in the absence of acute kidney injury by creatinine elevation, is independently associated with mortality. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

[Membranous nephropathy: Pathophysiology and natural history].

PubMed

Seitz-Polski, Barbara; Lambeau, Gérard; Esnault, Vincent

2017-04-01

Membranous nephropathy is a major cause of nephrotic syndrome in adults, with various etiologies and outcomes. One third of patients enter spontaneous remission with blockade of the renin-angiotensin system, one third develop a persistent nephrotic syndrome, while another third of patients develop end-stage kidney disease and 40% of them relapse after kidney transplantation. Treatment of membranous nephropathy remains controversial. Immunosuppressive therapy is only recommended in case of renal function deterioration or persistent nephrotic syndrome after 6months of renin-angiotensin system blockade. Therefore, delayed immunosuppressive treatments may lead to significant and potentially irreversible complications. For long, no biological markers could predict clinical outcome and guide therapy. The discovery of autoantibodies to the phospholipase A2 receptor (PLA2R1) in 2009, and to the thrombospondin type 1 domain containing 7A (THSD7A) in 2014 in respectively 70 and 5% of patients with membranous nephropathy were major breakthroughs. The passive infusion of human anti-THSD7A antibodies in mouse induces proteinuria and membranous nephropathy. The identification of these antigens has allowed developing diagnostic and prognostic tests. High anti-PLA2R1 titers at time of diagnosis predict a poor renal outcome. Anti-PLA2R1 antibodies can bind at least three different domains of PLA2R1. Epitope spreading with binding of two or three of these antigenic domains is associated with active membranous nephropathy and poor renal survival. These new tools could help us to monitor disease severity and to predict renal prognosis for a better selection of patients that should benefit of early immunosuppressive therapy. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Diagnosing obesity by body mass index in chronic kidney disease: an explanation for the "obesity paradox?".

PubMed

Agarwal, Rajiv; Bills, Jennifer E; Light, Robert P

2010-11-01

Although obesity is associated with poor outcomes, among patients with chronic kidney disease (CKD), obesity is related to improved survival. These results may be related to poor diagnostic performance of body mass index (BMI) in assessing body fat content. Accordingly, among 77 patients with CKD and 20 controls, body fat percentage was estimated by air displacement plethysmography (ADP), skinfold thickness, and body impedance analysis. Defined by BMI ≥30 kg/m(2), the prevalence of obesity was 20% in controls and 65% in patients with CKD. Defined by ADP, the prevalence increased to 60% among controls and to 90% among patients with CKD. Although sensitivity and positive predictive value of BMI to diagnose obesity were 100%, specificity was 72%, but the negative predictive value was only 30%. BMI correctly classified adiposity in 75%. Regardless of the presence or absence of CKD, subclinical obesity (defined as BMI <30 kg/m(2) but excess body fat by ADP) was often missed in people with low lean body mass. The adjusted odds ratio for subclinical obesity per 1 kg of reduced lean body mass by ADP was 1.14 (95% CI: 1.06 to 1.23; P<0.001). Skinfold thickness measurements correctly classified 94% of CKD patients, but bioelectrical impedance analyzer-assessed body fat estimation did so in only 65%. Air displacement plethysmography-, skinfold thickness-, and bioelectrical impedance analyzer-assessed body fat all provided reproducible estimates of adiposity. Skinfold thickness measurements may be a better test to classify obesity among those with CKD. Given the low negative predictive value of BMI for obesity, our study may provide an explanation of the "obesity paradox."

Type-1 hepatorenal syndrome associated with infections in cirrhosis: natural history, outcome of kidney function, and survival.

PubMed

Barreto, Rogelio; Fagundes, Claudia; Guevara, Mónica; Solà, Elsa; Pereira, Gustavo; Rodríguez, Ezequiel; Graupera, Isabel; Martín-Llahí, Marta; Ariza, Xavier; Cárdenas, Andrés; Fernández, Javier; Rodés, Juan; Arroyo, Vicente; Ginès, Pere

2014-04-01

Type-1 hepatorenal syndrome (HRS) is a common complication of bacterial infections in cirrhosis, but its natural history remains undefined. To assess the outcome of kidney function and survival of patients with type-1 HRS associated with infections, 70 patients diagnosed during a 6-year period were evaluated prospectively. Main outcomes were no reversibility of type-1 HRS during treatment of the infection and 3-month survival. Forty-seven (67%) of the 70 patients had no reversibility of type-1 HRS during treatment of the infection. [Correction to previous sentence added March 10, 2014, after first online publication: "Twenty-three (33%)" was changed to "Forty-seven (67%)."] The main predictive factor of no reversibility of type-1 HRS was absence of infection resolution (no reversibility: 96% versus 48% in patients without and with resolution of the infection; P < 0.001). Independent predictive factors of no reversibility of type-1 HRS were age, high baseline serum bilirubin, nosocomial infection, and reduction in serum creatinine <0.3 mg/dL at day 3 of antibiotic treatment. No reversibility was also associated with severity of circulatory dysfunction, as indicated by more marked activity of the vasoconstrictor systems. In the whole series, 3-month probability of survival was only 21%. Factors associated with poor prognosis were baseline serum bilirubin, no reversibility of type-1 HRS, lack of resolution of the infection, and development of septic shock after diagnosis of type-1 HRS. Type-1 HRS associated with infections is not reversible in two-thirds of patients with treatment of infection only. No reversibility of type-1 HRS is associated with lack of resolution of the infection, age, high bilirubin, and no early improvement of kidney function and implies a poor prognosis. These results may help advance the management of patients with type-1 HRS associated with infections. © 2014 by the American Association for the Study of Liver Diseases.

Kidney allograft survival of African American and Caucasian American recipients with lupus.

PubMed

Contreras, G; Li, H; Gonzalez-Suarez, M; Isakova, T; Scialla, J J; Pedraza, F; Mattiazzi, A; Diaz-Wong, R; Sageshima, J; Brito, Y; Guerra, G; Acevedo, B; Sajid Ali, A; Kershaw, T J; Chen, L; Burke, G W; Kupin, W; Ciancio, G; Roth, D

2014-02-01

African Americans with lupus who receive kidney transplants have high prevalence of predictors of allograft failure, which can explain their poor outcomes. Of 1223 African Americans and 1029 Caucasian Americans with lupus who received kidney transplants from deceased donors between 1987 and 2006 with complete records in the UNOS program, 741 pairs were matched in 16 predictors employing a predicted probability of group membership. The primary outcome was allograft failure. Main secondary outcomes were rejection, allograft failure due to rejection, and mortality. Matched pairs were predominantly women (82%) with a mean age of 39 years. Twenty-four percent of recipients received kidneys from expanded criteria donors. African Americans and Caucasian Americans matched well (p ≥ 0.05): donor age, gender and race; recipient age, gender, education and insurance; dialysis prior to transplant, kidneys from expanded criteria donors, cold ischemia time, history of prior kidney transplant, panel reactive antibodies, human leukocyte antigens mismatch, blood type compatibility, transplant Era, and follow-up time. Contrary to the unmatched cohort with significantly higher allograft failure rate (events per 100 patient-years) in African Americans compared to Caucasian Americans (10.49 vs 6.18, p<0.001), matched pairs had similar allograft failure rates (8.41 vs 7.81, p=0.418). Matched pairs also had similar rates of rejections (9.82 vs 9.39, p=0.602), allograft failure due to rejection (6.19 vs 5.71, p=0.453), and mortality (2.79 vs 3.52, p=0.097). In lupus recipients of kidney transplants from deceased donors, African American and Caucasian Americans have similar allograft failure rates when predictors are matched between groups.

Urinary microbiome of kidney transplant patients reveals dysbiosis with potential for antibiotic resistance

PubMed Central

Rani, Asha; Ranjan, Ravi; McGee, Halvor S.; Andropolis, Kalista E.; Panchal, Dipti V.; Hajjiri, Zahraa; Brennan, Daniel C.; Finn, Patricia W.; Perkins, David L.

2016-01-01

Recent studies have established that a complex community of microbes colonize the human urinary tract; however their role in kidney transplant patients treated with prophylactic antibiotics remains poorly investigated. Our aim was to investigate the urinary microbiome of kidney transplant recipients. Urine samples from 21 patients following kidney transplantation and 8 healthy controls, were collected. All patients received prophylactic treatment with the antibiotic trimethoprim/sulfamethoxazole. Metagenomic DNA was isolated from urine samples, sequenced using metagenomics shotgun sequencing approach on Illumina HiSeq2000 platform, and analyzed for microbial taxonomic and functional annotations. Our results demonstrate that the urine microbiome of kidney transplants was markedly different at all taxonomic levels from phyla to species, had decreased microbial diversity and increased abundance of potentially pathogenic species compared to healthy controls. Specifically, at the phylum level we detected a significant decrease in Actinobacteria and increase in Firmicutes due to increases in Enterococcus faecalis. In addition, there was an increase in the Proteobacteria due to increases in E. coli. Analysis of predicted functions of the urinary metagenome revealed increased abundance of enzymes in the folate pathway including dihydrofolate synthase that are not inhibited by trimethoprim/sulfamethoxazole, but can augment folate metabolism. This report characterizes the urinary microbiome of kidney transplants using shotgun metagenomics approach. Our results indicate that the urinary microbiota may be modified in the context of prophylactic antibiotics, indicating that a therapeutic intervention may shift the urinary microbiota to select bacterial species with increased resistance to antibiotics. The evaluation and development of optimal prophylactic regimens that do not promote antibiotic resistance is an important future goal. PMID:27669488

Comparison of conventional versus three-dimensional ultrasound in fetal renal pelvis measurement and their potential prediction of neonatal uropathies.

PubMed

Duin, L K; Nijhuis, J G; Scherjon, S A; Vossen, M; Willekes, C

2016-01-01

To establish a threshold value for fetal renal pelvis dilatation measured by automatic volume calculation (SonoAVC) in the third trimester of pregnancy to predict neonatal uropathies, and to compare these results with conventional antero-posterior (AP) measurement, fetal kidney 3D volume and renal parenchymal thickness. In a prospective cohort study, 125 fetuses with renal pelvis AP diameter of ≥5 mm both at 20 weeks of gestation and in the third trimester, underwent an additional 3D volume measurement of the fetal kidney in the third trimester. Receiver operating characteristic (ROC) curves for establishing threshold values for fetal renal pelvis volume, AP measurement, fetal kidney volume and renal parenchymal thickness to predict neonatal uropathies were analyzed. Also, sensitivity, specificity, area under the curve (AUC) and likelihood ratios were calculated. A cut-off point of 1.58 cm³ was identified in the third trimester of pregnancy (AUC 0.865 (95% CI 0.789-0.940), sensitivity 76.3%, specificity 87.4%, LR+ 6.06, LR- 0.27) for measurements with SonoAVC. A cut-off value of 11.5 mm was established in the third trimester of pregnancy (AUC 0.828 (95% CI 0.737-0.918), sensitivity 71.1%, specificity 85.1%, LR+ 4.77, LR- 0.34) for the conventional AP measurement. A cut-off point for fetal kidney volume was calculated at 13.29 cm³ (AUC 0.769 (95% CI 0.657-0.881), sensitivity 71%, specificity 66%, LR+ 2.09, LR- 0.44). For renal parenchymal thickness, a cut-off point of 8.4 mm was established (AUC 0.216 (95% CI 0.117-0.315), sensitivity 31.6%, specificity 32.6%, LR+ 0.47, LR- 2.10). This study demonstrates that 3D fetal renal pelvis volume measurements and AP measurements both have a good and comparable diagnostic performance, fetal renal volume a fair accuracy and renal parenchymal thickness a poor accuracy in predicting postnatal renal outcome.

Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.

PubMed

Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy

2018-06-01

The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Circulating Kidney Injury Molecule 1 Predicts Prognosis and Poor Outcome in Patients With Acetaminophen‐Induced Liver Injury

PubMed Central

Sabbisetti, Venkata S.; Francis, Ben; Jorgensen, Andrea L.; Craig, Darren G.N.; Simpson, Kenneth J.; Bonventre, Joseph V.; Park, B. Kevin; Dear, James W.

2015-01-01

Acute kidney injury in the context of acetaminophen (APAP; paracetamol)‐induced liver injury is an important predictor of the requirement for urgent liver transplantation (LT) to avoid death. However, the prognostic biomarker used to report kidney dysfunction (serum creatinine concentration) has suboptimal sensitivity and specificity. Kidney injury molecule 1 (KIM‐1) can be quantified in plasma as a sensitive and specific biomarker of kidney injury in both clinical and preclinical studies. Therefore, plasma KIM‐1 has potential as a sensitive prognostic biomarker of patient outcome post‐APAP overdose. In a cohort of APAP overdose patients (N = 74) with and without established liver injury, we quantified plasma KIM‐1 by immunoassay on the first day of admission to a LT unit and assessed its diagnostic performance to predict outcome compared with serum creatinine concentration. Day 1 plasma KIM‐1 was significantly elevated in patients that died or required LT, compared to spontaneous survivors (1,182 ± 251 vs. 214 ± 45 pg/mL; P < 0.005). Receiver operator characteristic analysis demonstrated the superiority of KIM‐1 (area under the curve [AUC]: 0.87; 95% confidence interval [CI]: 0.78‐0.95; 0.56 sensitivity at 0.95 specificity), compared with serum creatinine (AUC, 0.76; 95% CI: 0.64‐0.87; 0.08 sensitivity at 0.95 specificity) and other current prognostic indicators, when measured on the first day of enrollment into the study. Furthermore, KIM‐1 was found to be a statistically significant independent predictor of outcome at the 5% level (P < 0.0386) in a multivariable logistic regression model that considered all measured factors (pseudo‐R^2 = 0.895). Conclusion: Early measurement of plasma KIM‐1 represents a more sensitive predictor of patient outcome than serum creatinine concentration post‐APAP overdose. With further development, plasma KIM‐1 could significantly improve prognostic stratification. (Hepatology 2015;62:591–599 PMID:25891479

CT volumetry is superior to nuclear renography for prediction of residual kidney function in living donors.

PubMed

Barbas, Andrew S; Li, Yanhong; Zair, Murtuza; Van, Julie A; Famure, Olusegun; Dib, Martin J; Laurence, Jerome M; Kim, S Joseph; Ghanekar, Anand

2016-09-01

Living kidney donor evaluation commonly includes nuclear renography to assess split kidney function and computed tomography (CT) scan to evaluate anatomy. To streamline donor workup and minimize exposure to radioisotopes, we sought to assess the feasibility of using proportional kidney volume from CT volumetry in lieu of nuclear renography. We examined the correlation between techniques and assessed their ability to predict residual postoperative kidney function following live donor nephrectomy. In a cohort of 224 live kidney donors, we compared proportional kidney volume derived by CT volumetry with split kidney function derived from nuclear renography and found only modest correlation (left kidney R(2) =26.2%, right kidney R(2) =26.7%). In a subset of 88 live kidney donors with serum creatinine measured 6 months postoperatively, we compared observed estimated glomerular filtration rate (eGFR) at 6 months with predicted eGFR from preoperative imaging. Compared to nuclear renography, CT volumetry more closely approximated actual observed postoperative eGFR for Chronic Kidney Disease Epidemiology Collaboration (J-test: P=.02, Cox-Pesaran test: P=.01) and Mayo formulas (J-test: P=.004, Cox-Pesaran test: P<.001). These observations support the use of CT volumetry for estimation of split kidney function in healthy individuals with normal kidney function and morphology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pretransplant soluble CD30 serum concentration does not affect kidney graft outcomes 3 years after transplantation.

PubMed

Kovač, J; Arnol, M; Vidan Jeras, B; Bren, A F; Kandus, A

2010-12-01

An elevated serum concentration of soluble the form of CD30 (sCD30), an activation marker of mainly T(H)2-type cytokines producing T lymphocytes, has been reported as a predictive factor for acute cellular rejection episodes and poor graft outcomes in kidney transplantation. This historic cohort study investigated the association of a pretransplant sCD30 serum concentrations with kidney graft function and graft survival 3 years posttransplantation in adult recipients of deceased donor kidney grafts, treated with monoclonal anti-CD25 antibodies as an induction treatment combined with a cyclosporine (CsA)-based maintenance triple therapy. The pretransplant sera of 296 recipients were tested for sCD30 content using a microsphere flow-cytometry assay. The estimated glomerular filtration rate (eGFR) was determined by the 4-variable Modification of Diet in Renal Disease equation. The incidences of graft loss were calculated with the use of Kaplan-Meier survival analysis and compared using the log-rank test. According to the distribution of the pretransplant sCD30 levels concentration ≥2700 pg/mL was defined as high (n = 146) and concentration <2700 pg/mL as low (n = 150). Three years posttransplantation, the eGFR was not significantly different in the recipients in high and low sCD30 groups (65 ± 24 vs 67 ± 21 mL/min/1.73 m(2); P = .43); there was no association between the eGFR 3 years after transplantation and the pretransplant sCD30 levels (r(2) = 0.002; P = .49). Graft survival 3 years after transplantation was also not different in the recipients in high and low sCD30 groups (P = .52). In our adult deceased-donor kidney graft recipients, the pretransplant sCD30 serum concentration was not a predictive factor of immunologic risk associated with the kidney graft function 3 years posttransplantation; neither did it affect graft survival 3 years after transplantation. The immunosuppression with anti-CD25 antibodies as an induction treatment combined with the CsA-based maintenance triple therapy could possibly be decisive for our findings. Copyright © 2010 Elsevier Inc. All rights reserved.

Blood urea nitrogen to serum creatinine ratio is an accurate predictor of outcome in diarrhea-associated hemolytic uremic syndrome, a preliminary study.

PubMed

Keenswijk, Werner; Vanmassenhove, Jill; Raes, Ann; Dhont, Evelyn; Vande Walle, Johan

2017-03-01

Diarrhea-associated hemolytic uremic syndrome (D+HUS) is a common thrombotic microangiopathy during childhood and early identification of parameters predicting poor outcome could enable timely intervention. This study aims to establish the accuracy of BUN-to-serum creatinine ratio at admission, in addition to other parameters in predicting the clinical course and outcome. Records were searched for children between 1 January 2008 and 1 January 2015 admitted with D+HUS. A complicated course was defined as developing one or more of the following: neurological dysfunction, pancreatitis, cardiac or pulmonary involvement, hemodynamic instability, and hematologic complications while poor outcome was defined by death or development of chronic kidney disease. Thirty-four children were included from which 11 with a complicated disease course/poor outcome. Risk of a complicated course/poor outcome was strongly associated with oliguria (p = 0.000006) and hypertension (p = 0.00003) at presentation. In addition, higher serum creatinine (p = 0.000006) and sLDH (p = 0.02) with lower BUN-to-serum creatinine ratio (p = 0.000007) were significantly associated with development of complications. A BUN-to-sCreatinine ratio ≤40 at admission was a sensitive and highly specific predictor of a complicated disease course/poor outcome. A BUN-to-serum Creatinine ratio can accurately identify children with D+HUS at risk for a complicated course and poor outcome. What is Known: • Oliguria is a predictor of poor long-term outcome in D+HUS What is New: • BUN-to-serum Creatinine ratio at admission is an entirely novel and accurate predictor of poor outcome and complicated clinical outcome in D+HUS • Early detection of the high risk group in D+HUS enabling early treatment and adequate monitoring.

Specific regions of the brain are capable of fructose metabolism.

PubMed

Oppelt, Sarah A; Zhang, Wanming; Tolan, Dean R

2017-02-15

High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and non-alcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40-60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase. Bioinformatic analysis of gene expression encoding these proteins (glut5, glut9, khk, and aldoC, respectively) identifies other organs capable of this fructose metabolism. This analysis predicts brain, lymphoreticular tissue, placenta, and reproductive tissues as possible additional organs for fructose metabolism. While expression of these genes is highest in liver, the brain is predicted to have expression levels of these genes similar to kidney. RNA in situ hybridization of coronal slices of adult mouse brains validate the in silico expression of glut5, glut9, khk, and aldoC, and show expression across many regions of the brain, with the most notable expression in the cerebellum, hippocampus, cortex, and olfactory bulb. Dissected samples of these brain regions show KHK and aldolase enzyme activity 5-10 times the concentration of that in liver. Furthermore, rates of fructose oxidation in these brain regions are 15-150 times that of liver slices, confirming the bioinformatics prediction and in situ hybridization data. This suggests that previously unappreciated regions across the brain can use fructose, in addition to glucose, for energy production. Copyright © 2016 Elsevier B.V. All rights reserved.

Specific regions of the brain are capable of fructose metabolism

PubMed Central

Oppelt, Sarah A.; Zhang, Wanming; Tolan, Dean R.

2017-01-01

High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and nonalcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40–60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase. Bioinformatic analysis of gene expression encoding these proteins (glut5, glut9, khk, and aldoC, respectively) identifies other organs capable of this fructose metabolism. This analysis predicts brain, lymphoreticular tissue, placenta, and reproductive tissues as possible additional organs for fructose metabolism. While expression of these genes is highest in liver, the brain is predicted to have expression levels of these genes similar to kidney. RNA in situ hybridization of coronal slices of adult mouse brains validate the in silico expression of glut5, glut9, khk, and aldoC, and show expression across many regions of the brain, with the most notable expression in the cerebellum, hippocampus, cortex, and olfactory bulb. Dissected samples of these brain regions show KHK and aldolase enzyme activity 5–10 times the concentration of that in liver. Furthermore, rates of fructose oxidation in these brain regions are 15–150 times that of liver slices, confirming the bioinformatics prediction and in situ hybridization data. This suggests that previously unappreciated regions across the brain can use fructose, in addition to glucose, for energy production. PMID:28034722

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.

Preimplant Histologic Acute Tubular Necrosis and Allograft Outcomes

PubMed Central

Hall, Isaac E.; Reese, Peter P.; Weng, Francis L.; Schröppel, Bernd; Doshi, Mona D.; Hasz, Rick D.; Reitsma, William; Goldstein, Michael J.; Hong, Kwangik

2014-01-01

Background and objectives The influence of deceased-donor AKI on post-transplant outcomes is poorly understood. The few published studies about deceased-donor preimplant biopsy have reported conflicting results regarding associations between AKI and recipient outcomes. Design, setting, participants, & measurements This multicenter study aimed to evaluate associations between deceased-donor biopsy reports of acute tubular necrosis (ATN) and delayed graft function (DGF), and secondarily for death-censored graft failure, first adjusting for the kidney donor risk index and then stratifying by donation after cardiac death (DCD) status. Results Between March 2010 and April 2012, 651 kidneys (369 donors, 4 organ procurement organizations) were biopsied and subsequently transplanted, with ATN reported in 110 (17%). There were 262 recipients (40%) who experienced DGF and 38 (6%) who experienced graft failure. DGF occurred in 45% of kidneys with reported ATN compared with 39% without ATN (P=0.31) resulting in a relative risk (RR) of 1.13 (95% confidence interval [95% CI], 0.9 to 1.43) and a kidney donor risk index–adjusted RR of 1.11 (95% CI, 0.88 to 1.41). There was no significant difference in graft failure for kidneys with versus without ATN (8% versus 5%). In stratified analyses, the adjusted RR for DGF with ATN was 0.97 (95% CI, 0.7 to 1.34) for non-DCD kidneys and 1.59 (95% CI, 1.23 to 2.06) for DCD kidneys (P=0.02 for the interaction between ATN and DCD on the development of DGF). Conclusions Despite a modest association with DGF for DCD kidneys, this study reveals no significant associations overall between preimplant biopsy-reported ATN and the outcomes of DGF or graft failure. The potential benefit of more rigorous ATN reporting is unclear, but these findings provide little evidence to suggest that current ATN reports are useful for predicting graft outcomes or deciding to accept or reject allograft offers. PMID:24558049

Latest consensus and update on protein-energy wasting in chronic kidney disease.

PubMed

Obi, Yoshitsugu; Qader, Hemn; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2015-05-01

Protein-energy wasting (PEW) is a state of metabolic and nutritional derangements in chronic disease states including chronic kidney disease (CKD). Cumulative evidence suggests that PEW, muscle wasting and cachexia are common and strongly associated with mortality in CKD, which is reviewed here. The malnutrition-inflammation score (KALANTAR Score) is among the comprehensive and outcome-predicting nutritional scoring tools. The association of obesity with poor outcomes is attenuated across more advanced CKD stages and eventually reverses in the form of obesity paradox. Frailty is closely associated with PEW, muscle wasting and cachexia. Muscle loss shows stronger associations with unfavorable outcomes than fat loss. Adequate energy supplementation combined with low-protein diet for the management of CKD may prevent the development of PEW and can improve adherence to low-protein diet, but dietary protein requirement may increase with aging and is higher under dialysis therapy. Phosphorus burden may lead to poor outcomes. The target serum bicarbonate concentration is normal range and at least 23 mEq/l for nondialysis-dependent and dialysis-dependent CKD patients, respectively. A benefit of exercise is suggested but not yet conclusively proven. Prevention and treatment of PEW should involve individualized and integrated approaches to modulate identified risk factors and contributing comorbidities.

Prognostic Value of Urinary Neutrophil Gelatinase-Associated Lipocalin on the First Day of Admission for Adverse Events in Patients With Acute Decompensated Heart Failure.

PubMed

Nakada, Yasuki; Kawakami, Rika; Matsui, Masaru; Ueda, Tomoya; Nakano, Tomoya; Takitsume, Akihiro; Nakagawa, Hitoshi; Nishida, Taku; Onoue, Kenji; Soeda, Tsunenari; Okayama, Satoshi; Watanabe, Makoto; Kawata, Hiroyuki; Okura, Hiroyuki; Saito, Yoshihiko

2017-05-18

Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) is an early predictor of acute kidney injury and adverse events in various diseases; however, in acute decompensated heart failure patients, its significance remains poorly understood. This study aimed to investigate the prognostic value of U-NGAL on the first day of admission for the occurrence of acute kidney injury and long-term outcomes in acute decompensated heart failure patients. We studied 260 acute decompensated heart failure patients admitted to our department between 2011 and 2014 by measuring U-NGAL in 24-hour urine samples collected on the first day of admission. Primary end points were all-cause death, cardiovascular death, and heart failure admission. Patients were divided into 2 groups according to their median U-NGAL levels (32.5 μg/gCr). The high-U-NGAL group had a significantly higher occurrence of acute kidney injury during hospitalization than the low-U-NGAL group ( P =0.0012). Kaplan-Meier analysis revealed that the high-U-NGAL group exhibited a worse prognosis than the low-U-NGAL group in all-cause death (hazard ratio 2.07; 95%CI 1.38-3.12, P =0.0004), cardiovascular death (hazard ratio 2.29; 95%CI 1.28-4.24, P =0.0052), and heart failure admission (hazard ratio 1.77; 95%CI 1.13-2.77, P =0.0119). The addition of U-NGAL to the estimated glomerular filtration rate significantly improved the predictive accuracy of all-cause mortality ( P =0.0083). In acute decompensated heart failure patients, an elevated U-NGAL level on the first day of admission was related to the development of clinical acute kidney injury and independently associated with poor prognosis. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Pancreas retransplantation: a second chance for diabetic patients?

PubMed

Buron, Fanny; Thaunat, Olivier; Demuylder-Mischler, Sandrine; Badet, Lionel; Brunet, Maria; Ber, Charles-Eric; Thivolet, Charles; Martin, Xavier; Berney, Thierry; Morelon, Emmanuel

2013-01-27

If pancreas transplantation is a validated alternative for type 1 diabetic patients with end-stage renal disease, the management of patients who have lost their primary graft is poorly defined. This study aims at evaluating pancreas retransplantation outcome. Between 1976 and 2008, 569 pancreas transplantations were performed in Lyon and Geneva, including 37 second transplantations. Second graft survival was compared with primary graft survival of the same patients and the whole population. Predictive factors of second graft survival were sought. Patient survival and impact on kidney graft function and survival were evaluated. Second pancreas survival of the 17 patients transplanted from 1995 was close to primary graft survival of the whole population (71% vs. 79% at 1 year and 59% vs. 69% at 5 years; P=0.5075) and significantly better than their first pancreas survival (71% vs. 29% at 1 year and 59% vs. 7% at 5 years; P=0.0008) regardless of the cause of first pancreas loss. The same results were observed with all 37 retransplantations. Survival of second simultaneous pancreas and kidney transplantations was better than survival of second pancreas after kidney. Patient survival was excellent (89% at 5 years). Pancreas retransplantation had no impact on kidney graft function and survival (100% at 5 years). Pancreas retransplantation is a safe procedure with acceptable graft survival that should be proposed to diabetic patients who have lost their primary graft.

YKL-40 Associates with Renal Recovery in Deceased Donor Kidney Transplantation

PubMed Central

Puthumana, Jeremy; Hall, Isaac E.; Reese, Peter P.; Schröppel, Bernd; Weng, Francis L.; Thiessen-Philbrook, Heather; Doshi, Mona D.; Rao, Veena; Lee, Chun Geun; Elias, Jack A.; Cantley, Lloyd G.

2017-01-01

Deceased donor kidneys with AKI are often discarded for fear of poor transplant outcomes. Donor biomarkers that predict post-transplant renal recovery could improve organ selection and reduce discard. We tested whether higher levels of donor urinary YKL-40, a repair phase protein, associate with improved recipient outcomes in a prospective cohort study involving deceased kidney donors from five organ procurement organizations. We measured urinary YKL-40 concentration in 1301 donors (111 had AKI, defined as doubling of serum creatinine) and ascertained outcomes in the corresponding 2435 recipients, 756 of whom experienced delayed graft function (DGF). Donors with AKI had higher urinary YKL-40 concentration (P<0.001) and acute tubular necrosis on procurement biopsies (P=0.05). In fully adjusted analyses, elevated donor urinary YKL-40 concentration associated with reduced risk of DGF in both recipients of AKI donor kidneys (adjusted relative risk, 0.51 [95% confidence interval (95% CI), 0.32 to 0.80] for highest versus lowest YKL-40 tertile) and recipients of non-AKI donor kidneys (adjusted relative risk, 0.79 [95% CI, 0.65 to 0.97]). Furthermore, in the event of DGF, elevated donor urinary YKL-40 concentration associated with higher 6-month eGFR (6.75 [95% CI, 1.49 to 12.02] ml/min per 1.73 m2) and lower risk of graft failure (adjusted hazard ratio, 0.50 [95% CI, 0.27 to 0.94]). These findings suggest that YKL-40 is produced in response to tubular injury and is independently associated with recovery from AKI and DGF. If ultimately validated as a prognostic biomarker, urinary YKL-40 should be considered in determining the suitability of donor kidneys for transplant. PMID:27451287

The Development of a Machine Learning Inpatient Acute Kidney Injury Prediction Model.

PubMed

Koyner, Jay L; Carey, Kyle A; Edelson, Dana P; Churpek, Matthew M

2018-07-01

To develop an acute kidney injury risk prediction model using electronic health record data for longitudinal use in hospitalized patients. Observational cohort study. Tertiary, urban, academic medical center from November 2008 to January 2016. All adult inpatients without pre-existing renal failure at admission, defined as first serum creatinine greater than or equal to 3.0 mg/dL, International Classification of Diseases, 9th Edition, code for chronic kidney disease stage 4 or higher or having received renal replacement therapy within 48 hours of first serum creatinine measurement. None. Demographics, vital signs, diagnostics, and interventions were used in a Gradient Boosting Machine algorithm to predict serum creatinine-based Kidney Disease Improving Global Outcomes stage 2 acute kidney injury, with 60% of the data used for derivation and 40% for validation. Area under the receiver operator characteristic curve (AUC) was calculated in the validation cohort, and subgroup analyses were conducted across admission serum creatinine, acute kidney injury severity, and hospital location. Among the 121,158 included patients, 17,482 (14.4%) developed any Kidney Disease Improving Global Outcomes acute kidney injury, with 4,251 (3.5%) developing stage 2. The AUC (95% CI) was 0.90 (0.90-0.90) for predicting stage 2 acute kidney injury within 24 hours and 0.87 (0.87-0.87) within 48 hours. The AUC was 0.96 (0.96-0.96) for receipt of renal replacement therapy (n = 821) in the next 48 hours. Accuracy was similar across hospital settings (ICU, wards, and emergency department) and admitting serum creatinine groupings. At a probability threshold of greater than or equal to 0.022, the algorithm had a sensitivity of 84% and a specificity of 85% for stage 2 acute kidney injury and predicted the development of stage 2 a median of 41 hours (interquartile range, 12-141 hr) prior to the development of stage 2 acute kidney injury. Readily available electronic health record data can be used to predict impending acute kidney injury prior to changes in serum creatinine with excellent accuracy across different patient locations and admission serum creatinine. Real-time use of this model would allow early interventions for those at high risk of acute kidney injury.

Chronic kidney disease and diabetes in the national health service: a cross-sectional survey of the U.K. national diabetes audit.

PubMed

Hill, C J; Cardwell, C R; Patterson, C C; Maxwell, A P; Magee, G M; Young, R J; Matthews, B; O'Donoghue, D J; Fogarty, D G

2014-04-01

We investigated the prevalence of chronic kidney disease and attainment of therapeutic targets for HbA1c and blood pressure in a large U.K.-based diabetes population. The U.K. National Diabetes Audit provided data from 1 January 2007 to 31 March 2008. Inclusion criteria were a documented urinary albumin:creatinine ratio and serum creatinine. Patients were stratified according to chronic kidney disease stage and albuminuria status. Chronic kidney disease was defined as an estimated glomerular filtration rate < 60 ml min(-1) 1.73 m(-2) , albuminuria or both. The proportions of patients achieving nationally defined glycaemic and systolic blood pressure targets were determined. The cohort comprised 1,423,669 patients, of whom 868,616 (61%) met inclusion criteria. Of the patients analysed, 92.2% had Type 2 diabetes. A higher proportion of people with Type 2 diabetes (42.3%) had renal dysfunction compared with those with Type 1 diabetes (32.4%). Achievement of systolic blood pressure and HbA1c targets was poor. Among people with Type 1 diabetes, 67.8% failed to achieve an HbA1c < 58 mmol/mol (7.5%). Of all people with diabetes, 37.8% failed to achieve a systolic blood pressure < 140 mmHg. Blood pressure control was poor in advanced chronic kidney disease. For example, mean (standard deviation) systolic blood pressure rose from 128.6 (15.4) mmHg among people with Type 1 diabetes and normal renal function to 141.0 (23.6) mmHg in those with chronic kidney disease stage 5 and macroalbuminuria. The high prevalence of chronic kidney disease and poor attainment of treatment targets highlights a large subset of the diabetes population at increased risk of cardiovascular mortality or progressive kidney disease. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

A Score for Predicting Acute Kidney Injury After Coronary Artery Bypass Graft Surgery in an Asian Population.

PubMed

Mithiran, Harish; Kunnath Bonney, Glenn; Bose, Saideep; Subramanian, Srinivas; Zhe Yan, Zan Ng; Zong En, Seth Yeak; Papadimas, Evangelos; Chauhan, Ishaan; MacLaren, Graeme; Kofidis, Theodoros

2016-10-01

To develop a scoring system to predict acute kidney injury in Asian patients after coronary artery bypass grafting. A retrospective analysis of data collected in an institutional cardiac database. A tertiary academic hospital in a large metropolitan city. The study comprised 954 patients with coronary artery disease. All patients underwent coronary artery bypass surgery with cardiopulmonary bypass but did not undergo any other concomitant procedures. The main outcome measured was acute kidney injury as defined by the Acute Kidney Injury Network criteria. The following 6 clinical variables were independent predictors of kidney injury: age>60 years, diabetes requiring insulin, estimated glomerular filtration rate<60 mL/min/1.73 m(2), ejection fraction<40%, cardiopulmonary bypass time>140 minutes, and aortic cross-clamp time>100 minutes. These variables were used to develop the Singapore Acute Kidney Injury score. The Singapore Acute Kidney Injury score is a simple way to predict, at the time of admission to the intensive care unit, an Asian patient's risk of developing acute kidney injury after coronary artery bypass surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

The mechanisms of intrarenal hemodynamic changes following acute arterial occlusion.

DOT National Transportation Integrated Search

1963-10-01

The hemodynamic response of the kidney to acute arterial occlusion is poorly understood. The purpose of the present study was to determine intrarenal hemodynamic changes in intact and isolated kidneys following arterial occlusion. : The relative role...

Temporal and geographical external validation study and extension of the Mayo Clinic prediction model to predict eGFR in the younger population of Swiss ADPKD patients.

PubMed

Girardat-Rotar, Laura; Braun, Julia; Puhan, Milo A; Abraham, Alison G; Serra, Andreas L

2017-07-17

Prediction models in autosomal dominant polycystic kidney disease (ADPKD) are useful in clinical settings to identify patients with greater risk of a rapid disease progression in whom a treatment may have more benefits than harms. Mayo Clinic investigators developed a risk prediction tool for ADPKD patients using a single kidney value. Our aim was to perform an independent geographical and temporal external validation as well as evaluate the potential for improving the predictive performance by including additional information on total kidney volume. We used data from the on-going Swiss ADPKD study from 2006 to 2016. The main analysis included a sample size of 214 patients with Typical ADPKD (Class 1). We evaluated the Mayo Clinic model performance calibration and discrimination in our external sample and assessed whether predictive performance could be improved through the addition of subsequent kidney volume measurements beyond the baseline assessment. The calibration of both versions of the Mayo Clinic prediction model using continuous Height adjusted total kidney volume (HtTKV) and using risk subclasses was good, with R 2 of 78% and 70%, respectively. Accuracy was also good with 91.5% and 88.7% of the predicted within 30% of the observed, respectively. Additional information regarding kidney volume did not substantially improve the model performance. The Mayo Clinic prediction models are generalizable to other clinical settings and provide an accurate tool based on available predictors to identify patients at high risk for rapid disease progression.

Sirolimus and everolimus clearance in maintenance kidney and liver transplant recipients: Diagnostic efficiency of the concentration/dose ratio for the prediction of trough steady-state concentrations

PubMed Central

Bouzas, Lorena; Hermida, Jesús

2010-01-01

Objectives Therapeutic monitoring of sirolimus and everolimus is necessary in order to minimize adverse side-effects and to ensure effective immunosuppression. A sirolimus-dosing model using the concentration/dose ratio has been previously proposed for kidney transplant patients, and the aim of our study was the evaluation of this single model for the prediction of trough sirolimus and everolimus concentrations. Methods Trough steady-state sirolimus concentrations were determined in several blood samples from each of 7 kidney and 9 liver maintenance transplant recipients, and everolimus concentrations from 20 kidney, 17 liver, and 3 kidney/liver maintenance transplant recipients. Predicted sirolimus and everolimus concentrations (Css), corresponding to the doses (D), were calculated using the measured concentrations (Css0) and corresponding doses (D0) on starting the study: Css = (Css0)(D)/D0. Results The diagnostic efficiency of the predicting model for the correct classification as subtherapeutic, therapeutic, and supratherapeutic values with respect to the experimentally obtained concentrations was 91.3% for sirolimus and 81.4% for everolimus in the kidney transplant patients. In the liver transplant patients the efficiency was 69.2% for sirolimus and 72.6% for everolimus, and in the kidney/liver transplant recipients the efficiency for everolimus was 67.9%. Conclusions The model has an acceptable diagnostic efficiency (>80%) for the prediction of sirolimus and everolimus concentrations in kidney transplant recipients, but not in liver transplant recipients. However, considering the wide ranges found for the prediction error of sirolimus and everolimus concentrations, the clinical relevance of this dosing model is weak. PMID:19943816

Prediction of Fat-Free Mass in Kidney Transplant Recipients.

PubMed

Størset, Elisabet; von Düring, Marit Elizabeth; Godang, Kristin; Bergan, Stein; Midtvedt, Karsten; Åsberg, Anders

2016-08-01

Individualization of drug doses is essential in kidney transplant recipients. For many drugs, the individual dose is better predicted when using fat-free mass (FFM) as a scaling factor. Multiple equations have been developed to predict FFM based on healthy subjects. These equations have not been evaluated in kidney transplant recipients. The objectives of this study were to develop a kidney transplant specific equation for FFM prediction and to evaluate its predictive performance compared with previously published equations. Ten weeks after transplantation, FFM was measured by dual-energy X-ray absorptiometry. Data from a consecutive cohort of 369 kidney transplant recipients were randomly assigned to an equation development data set (n = 245) or an evaluation data set (n = 124). Prediction equations were developed using linear and nonlinear regression analysis. The predictive performance of the developed equation and previously published equations in the evaluation data set was assessed. The following equation was developed: FFM (kg) = {FFMmax × body weight (kg)/[81.3 + body weight (kg)]} × [1 + height (cm) × 0.052] × [1-age (years) × 0.0007], where FFMmax was estimated to be 11.4 in males and 10.2 in females. This equation provided an unbiased, precise prediction of FFM in the evaluation data set: mean error (ME) (95% CI), -0.71 kg (-1.60 to 0.19 kg) in males and -0.36 kg (-1.52 to 0.80 kg) in females, root mean squared error 4.21 kg (1.65-6.77 kg) in males and 3.49 kg (1.15-5.84 kg) in females. Using previously published equations, FFM was systematically overpredicted in kidney-transplanted males [ME +1.33 kg (0.40-2.25 kg) to +5.01 kg (4.06-5.95 kg)], but not in females [ME -2.99 kg (-4.07 to -1.90 kg) to +3.45 kg (2.29-4.61) kg]. A new equation for FFM prediction in kidney transplant recipients has been developed. The equation may be used for population pharmacokinetic modeling and clinical dose selection in kidney transplant recipients.

Symptomatic BK Virus Infection Is Associated with Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients

PubMed Central

Abudayyeh, Ala; Hamdi, Amir; Lin, Heather; Abdelrahim, Maen; Rondon, Gabriela; Andersson, Borje S; Afrough, Aimaz; Martinez, Charles S; Tarrand, Jeffrey J; Kontoyiannis, Dimitrios P.; Marin, David; Gaber, A. Osama; Salahudeen, Abdulla; Oran, Betul; Chemaly, Roy F.; Olson, Amanda; Jones, Roy; Popat, Uday; Champlin, Richard E; Shpall, Elizabeth J.; Winkelmayer, Wolfgang C.; Rezvani, Katayoun

2017-01-01

Nephropathy due to BK virus infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation. We hypothesized that BKV infection was a marker of Kidney Function Decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic hematopoietic stem cell transplantation at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the CKD-EPI equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline and Fine and Gray’s method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic hematopoietic stem cell transplantation, BK viruria was detected in 25% (n=629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease, chronic graft versus host disease, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (P <0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. Post-allogeneic hematopoietic stem cell transplantation, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT. PMID:26608093

Circulating AST, H-FABP, and NGAL are early and accurate biomarkers of graft injury and dysfunction in a preclinical model of kidney transplantation.

PubMed

Jochmans, Ina; Lerut, Evelyne; van Pelt, Jos; Monbaliu, Diethard; Pirenne, Jacques

2011-11-01

To investigate circulating biomarkers of initial graft injury in a porcine kidney autotransplant model. Injury endured by kidney grafts early posttransplant determines their outcome. However, creatinine (clearance) is a poor surrogate of tissue injury and urinary biomarkers are limited by graft anuria or persistent native kidney diuresis. No validated circulating biomarkers quantifying initial graft injury exist. Minimally injured porcine kidney grafts (n = 6) were cold stored (18 hours) and autotransplanted. Moderately (n = 6) and severely injured grafts (n = 7) were exposed to 30 or 60 minutes warm ischemia before storage and autotransplantation. Four biomarkers [aspartate transaminase (AST), heart-type fatty acid-binding protein (H-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-β-glucosaminidase (NAG)] were measured posttransplant and compared with creatinine (clearance) and histology. Diuresis was delayed in moderately [2.5 days (2-3)] and severely [4 days (4-5)] versus minimally injured grafts (P < 0.001). Creatinine peaked later than AST, H-FABP, and NGAL [4 days (3-5) vs 3 hours (3-6), 6 hours (6-24), 2 days (1-3), respectively] and only differentiated minimally from severely injured grafts. Peak AST and H-FABP distinguished all injury grades. Neutrophil gelatinase-associated lipocalin discriminated initial graft injury 2 days posttransplant. Peak AST, H-FABP, and NGAL correlated with peak creatinine [Pearson coefficients: 0.70 (P = 0.001), 0.85 (P < 0.0001), 0.80 (P < 0.0001)]. N-acetyl-β-glucosaminidase was not different. Decreased clearance accounted for a small percentage of H-FABP and NGAL increase. Histology was not different among transplanted groups. Plasma AST, H-FABP, and NGAL reflect the severity of initial kidney graft injury and predict graft dysfunction earlier and more accurately than creatinine (clearance) and histology. They represent promising tools to improve patient care after kidney transplantation.

Hyponatremia Predicts Poor Outcomes in Patients with Chronic Kidney Disease Undergoing Heart Surgery.

PubMed

Shavit, Linda; Merin, Ofer; Grenader, Tal; Jacobson, Ehud; Waldenberg, Chani; Bitran, Daniel; Fink, Daniel; Silberman, Shuli

2018-05-08

Preoperative hyponatremia adversely impacts outcomes of cardiothoracic surgery. However, in patients with chronic kidney disease, the association of sodium levels on postoperative events has never been evaluated. We investigated the impact of preoperative hyponatremia on outcomes after cardiac surgery in patients with non-dialysis-dependent chronic kidney disease. Primary endpoints were operative mortality and acute kidney injury requiring dialysis. Secondary endpoints were major infection and long-term survival. The study is observational and includes all patients with stage III-IV chronic kidney disease (non-dialysis) undergoing cardiac surgery between February 2000-January 2016. Patients were stratified into 2 groups by preoperative sodium levels: Na <135 mEq/L; Na ≥135 mEq/L. There were 1008 patients (mean eGFR 43 ± 14 mL/min/1.73 m 2 ): 92 (9%) in the low sodium group. Patients with low sodium had higher operative mortality (p=0.0004), need for new dialysis (p=0.0008), and infection (p=0.002). Predictors of operative mortality were: EuroSCORE (HR1.03; CI 1.02-1.05 ; p<0.0001); Decreasing values of sodium (HR 1.14; CI 1.07-1.2; p=0.0002); and decreasing values of GFR (HR1.01; CI 1.003-1.03; p=0.007). Sodium below 135 mEq/L was independently associated with increased need for dialysis (HR1.3; CI 1.1-1.7; p= 0.0008). By linear regression, decreasing values of preoperative sodium were proportionate to the incidence of operative mortality (p<0.0001) and need for dialysis (p<0.0001). Preoperative hyponatremia is a predictor of increased mortality as well as other adverse events in patients with non- dialysis dependent chronic kidney disease undergoing cardiac surgery. These findings are similar to those in hyponatremic patients without kidney disease. Copyright © 2018. Published by Elsevier Inc.

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.

Annual literature review of donor-specific HLA antibodies after organ transplantation.

PubMed

Kaneku, Hugo

2011-01-01

The literature review of post-transplant DSA published in 2011 shows: Observations after kidney and lung transplant in non-sensitized transplant recipients show that monitoring post-transplant HLA antibodies offers limited benefit in predicting acute rejection episodes. It remains to be seen if a different monitoring schedule and/ or studying other organs may show otherwise. Nevertheless, others have shown that monitoring post-transplant antibodies does identify patients at higher risk for chronic rejection. Studies in kidney, heart, and liver patients transplanted in the presence of preformed DSA show that detecting these antibodies early after transplant identifies a group of patients with greater risk for allograft dysfunction. New and larger studies using bortezomib and eculizumab to treat acute antibody-mediated rejection confirm earlier observations that these two therapies are effective in treating and preventing rejections. In general, identification of HLAantibodies and DSA after transplant is associated with higher rates of rejection and poor allograft survival in all organs examined. IgM antibodies appear to play an important role after lung transplants.

The Kidney Outcomes Prediction and Evaluation (KOPE) study: a prospective cohort investigation of patients undergoing hemodialysis. Study design and baseline characteristics.

PubMed

Sevick, M A; Tell, G S; Shumaker, S A; Rocco, M V; Burkart, J M; Rushing, J T; Levine, D W; Chen, J; Bradham, D D; Pierce, J J; James, M K

1998-04-01

The purpose of the Kidney Outcomes Prediction and Evaluation (KOPE) study, was to more fully characterize the end-stage renal disease (ESRD) population with respect to social, psychological, and clinical characteristics, and to prospectively study the biomedical, social, and psychological factors that influence a range of ESRD outcomes in a large observational study of black and white patients on hemodialysis. This paper focuses on the KOPE study design as well as characteristics of patients at baseline. KOPE was a prospective cohort investigation of patients treated at four dialysis centers in Forsyth County, North Carolina. Participants were interviewed at the dialysis centers, semi-annually over a 3 1/2 year period. Prevalent cases who were being treated with hemodialysis at the initiation of the study were enrolled into KOPE. Incident cases were subsequently enrolled as they presented to the participating units for hemodialysis. A total of 304 prevalent and 162 incident cases were enrolled into the study. The baseline health and sociodemographic characteristics of KOPE participants reported in this paper were obtained from medical records and Southeast Kidney Council data. Laboratory values taken within a 30-day interval around the baseline interview are also reported. KOPE participants differ from national statistics on race, age, and gender. Differences between KOPE participants and patients living in the region, but who did not participate in the study, can be explained by our recruitment criteria. KOPE will enable the characterization of the ESRD population, identification of factors related to poor outcomes, and identification of opportunities for interventions to prevent death and morbidity.

Novel Approach to Estimate Kidney and Cyst Volumes using Mid-Slice Magnetic Resonance Images in Polycystic Kidney Disease

PubMed Central

Bae, Kyongtae T; Tao, Cheng; Wang, Jinhong; Kaya, Diana; Wu, Zhiyuan; Bae, Junu T; Chapman, Arlene B; Torres, Vicente E; Grantham, Jared J; Mrug, Michal; Bennett, William M; Flessner, Michael F; Landsittel, Doug P

2013-01-01

Objective To evaluate whether kidney and cyst volumes can be accurately estimated based on limited area measurements from MR images of patients with autosomal dominant polycystic kidney disease (ADPKD). Materials and Methods MR coronal images of 178 ADPKD participants from the Consortium for Radiologic Imaging Studies of ADPKD (CRISP) were analyzed. For each MR image slice, we measured kidney and renal cyst areas using stereology and region-based thresholding methods, respectively. The kidney and cyst ‘observed’ volumes were calculated by summing up the area measurements of all the slices covering the kidney. To estimate the volume, we selected a coronal mid-slice in each kidney and multiplied its area by the total number of slices (‘PANK2’ for kidney and ‘PANC2’ for cyst). We then compared the kidney and cyst volumes predicted from PANK2 and PANC2, respectively, to the corresponding observed volumes, using a linear regression analysis. Results The kidney volume predicted from PANK2 correlated extremely well with the observed kidney volume: R2=0.994 for right and 0.991 for left kidney. The linear regression coefficient multiplier to PANK2 that best fit the kidney volume was 0.637 (95%CI: 0.629–0.644) for right and 0.624 (95%CI: 0.616–0.633) for left kidney. The correlation between the cyst volume predicted from PANC2 and the observed cyst volume was also very high: R2=0.984 for right and 0.967 for left kidney. The least squares linear regression coefficient for PANC2 was 0.637 (95%CI: 0.624–0.649) for right and 0.608 (95%CI: 0.591–0.625) for left kidney. Conclusion Kidney and cyst volumes can be closely approximated by multiplying the product of the mid-slice area measurement and the total number of slices in the coronal MR images of ADPKD kidneys by 0.61–0.64. This information will help save processing time needed to estimate total kidney and cyst volumes of ADPKD kidneys. PMID:24107679

Role of Magnetic Resonance Elastography as a Noninvasive Measurement Tool of Fibrosis in a Renal Allograft: A Case Report.

PubMed

Kim, J K; Yuen, D A; Leung, G; Jothy, S; Zaltzman, J; Ramesh Prasad, G V; Prabhudesai, V; Mnatzakanian, G; Kirpalani, A

2017-09-01

A major reason for poor long-term kidney transplant outcomes is the development of chronic allograft injury, characterized by interstitial fibrosis and tubular atrophy. Currently, an invasive biopsy that samples only <1% of the kidney is the gold standard for detecting kidney allograft fibrosis. We report the use of magnetic resonance elastography (MRE) to quantify tissue stiffness as a noninvasive and whole-kidney measurement tool of allograft fibrosis in a kidney transplant patient at 2 time points. The MRE whole-kidney stiffness values reflected the changes in fibrosis of the kidney allograft as assessed by histologic examination. To our knowledge, this technique is the first observation of change over time in MRE-derived whole-kidney stiffness in an allograft that is consistent with changes in histology-derived fibrosis scores in a single patient. Copyright © 2017 Elsevier Inc. All rights reserved.

Age and treatment of kidney failure.

PubMed

Elliott, Meghan J; Tam-Tham, Helen; Hemmelgarn, Brenda R

2013-05-01

This review discusses issues related to treatment of chronic kidney disease, and kidney failure in particular, among older adults. A substantial proportion of older adults have chronic kidney disease and progress to kidney failure. There is considerable variability in treatment practices for advanced kidney disease among older adults, and evidence that treatment decisions such as dialysis initiation may be made without adequate preparation. When initiated, survival among older adults on chronic dialysis remains poor, and is associated with a significant decline in functional status. There is also evidence to suggest that dialysis initiation may not reflect overall treatment goals of elderly patients, but rather a lack of clear communication between patients and health practitioners, and underdeveloped conservative care programs in many centers. Kidney failure is common among older adults. When considering treatment options for kidney failure, patient priorities, preferences, and symptoms should be taken into account, using a shared decision-making approach.

Ex Vivo Perfusion Characteristics of Donation After Cardiac Death Kidneys Predict Long-Term Graft Survival.

PubMed

Sevinc, M; Stamp, S; Ling, J; Carter, N; Talbot, D; Sheerin, N

2016-12-01

Ex vivo perfusion is used in our unit for kidneys donated after cardiac death (DCD). Perfusion flow index (PFI), resistance, and perfusate glutathione S-transferase (GST) can be measured to assess graft viability. We assessed whether measurements taken during perfusion could predict long-term outcome after transplantation. All DCD kidney transplants performed from 2002 to 2014 were included in this study. The exclusion criteria were: incomplete data, kidneys not machine perfused, kidneys perfused in continuous mode, and dual transplantation. There were 155 kidney transplantations included in the final analysis. Demographic data, ischemia times, donor hypertension, graft function, survival and machine perfusion parameters after 3 hours were analyzed. Each perfusion parameter was divided into 3 groups as high, medium, and low. Estimated glomerular filtration rate was calculated at 12 months and then yearly after transplantation. There was a significant association between graft survival and PFI and GST (P values, .020 and .022, respectively). PFI was the only independent parameter to predict graft survival. A low PFI during ex vivo hypothermic perfusion is associated with inferior graft survival after DCD kidney transplantation. We propose that PFI is a measure of the health of the graft vasculature and that a low PFI indicates vascular disease and therefore predicts a worse long-term outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Kidney transplant tourism: cases from Canada.

PubMed

Wright, L; Zaltzman, J S; Gill, J; Prasad, G V R

2013-11-01

Canada has a marked shortfall between the supply and demand for kidneys for transplantation. Median wait times for deceased donor kidney transplantation vary from 5.8 years in British Columbia, 5.2 years in Manitoba and 4.5 years in Ontario to a little over 2 years in Quebec and Nova Scotia. Living donation provides a viable option for some, but not all people. Consequently, a small number of people travel abroad to undergo kidney transplantation by commercial means. The extent to which they are aware of the potential risks to their health and the health of the kidney vendors is unclear. Travel abroad to obtain a kidney commercially i.e. transplant tourism (TT), raises ethical issues which include the exploitation of the poor, uncertainty of donor informed consent to nephrectomy, poor clinical care and lack of follow up for the donor, commodification of the body and inequity of access to medical care for donors. Also, TT widens socioeconomic disparities in access to transplantation, differing from the Canadian system of universal coverage for healthcare. The Canadian transplant community has discussed how to respond to patients who plan to travel abroad for TT or return with a purchased kidney. Unease rests in the tension between the duty to care for legitimate Canadian residents and the unwillingness to enable TT. This paper discusses three anonymized cases and the Canadian responses to TT as recorded in academic literature and a formal statement by relevant professional bodies.

Utility of screening ultrasound after first febrile UTI among patients with clinically significant vesicoureteral reflux.

PubMed

Massanyi, Eric Z; Preece, Janae; Gupta, Angela; Lin, Susan M; Wang, Ming-Hsien

2013-10-01

To assess the sensitivity and negative predictive value (NPV) of screening renal and bladder ultrasound (RBUS) after initial febrile urinary tract infection (UTI) among patients with clinically significant vesicoureteral reflux (VUR). A retrospective review was performed of all children <2 years of age who presented with a febrile UTI between 2004 and 2011. The sensitivity and NPV of initial RBUS was calculated among patients who were found to have high-grade (IV-V) VUR. Additionally, initial RBUS among patients with evidence of photopenia on dimercaptosuccinic acid (DMSA) scan or who underwent surgical intervention were reviewed. One hundred forty-four patients with febrile UTI were identified; available RBUS, voiding cystourethrogram (VCUG), and DMSA results for each kidney were reviewed. One hundred fifty-eight kidneys had evidence of VUR on VCUG, and initial RBUS demonstrated abnormality in 25 (sensitivity 0.17). Forty-five kidneys had high-grade VUR and RBUS revealed abnormality in 16 (sensitivity 0.36). One hundred seventy-eight kidneys had no evidence of abnormality on initial RBUS, and 136 (76%) were found to have VUR (NPV 0.24), of which 31 had high-grade VUR (NPV 0.83). Seven kidneys had scarring on DMSA and initial RBUS was normal in 4 (57%). Twelve of 19 patients (63%) who eventually underwent surgical intervention had a normal initial RBUS. RBUS has poor sensitivity and NPV for detecting high-grade VUR in patients <2 years who present with a febrile UTI. A significant number of patients who were diagnosed with high-grade VUR, renal scarring, or underwent surgical correction of VUR had a negative screening RBUS. Copyright © 2013 Elsevier Inc. All rights reserved.

Time-in-a-bottle (TIAB): a longitudinal, correlational study of patterns, potential predictors, and outcomes of immunosuppressive medication adherence in adult kidney transplant recipients.

PubMed

Russell, Cynthia L; Ashbaugh, Catherine; Peace, Leanne; Cetingok, Muammer; Hamburger, Karen Q; Owens, Sarah; Coffey, Deanna; Webb, Andrew W; Hathaway, Donna; Winsett, Rebecca P; Madsen, Richard; Wakefield, Mark R

2013-01-01

This study examined patterns, potential predictors, and outcomes of immunosuppressive medication adherence in a convenience sample of 121 kidney transplant recipients aged 21 yr or older from three kidney transplant centers using a theory-based, descriptive, correlational, longitudinal design. Electronic monitoring was conducted for 12 months using electronic monitoring. Participants were persistent in taking their immunosuppressive medications, but execution, which includes both taking and timing, was poor. Older age was the only demographic variable associated with medication adherence (r = 0.25; p = 0.005). Of the potential predictors examined, only medication self-efficacy was associated with medication non-adherence, explaining about 9% of the variance (r = 0.31, p = 0.0006). The few poor outcomes that occurred were not significantly associated with medication non-adherence, although the small number of poor outcomes may have limited our ability to detect a link. Future research should test fully powered, theory-based, experimental interventions that include a medication self-efficacy component. © 2013 John Wiley & Sons A/S.

Time-in-a-Bottle (TIAB): A Longitudinal, Correlational Study of Patterns, Potential Predictors, and Outcomes of Immunosuppressive Medication Adherence in Adult Kidney Transplant Recipients

PubMed Central

Russell, Cynthia L.; Ashbaugh, Catherine; Peace, Leanne; Cetingok, Muammer; Hamburger, Karen Q.; Owens, Sarah; Coffey, Deanna; Webb, Andrew; Hathaway, Donna; Winsett, Rebecca P.; Madsen, Richard; Wakefield, Mark R.

2013-01-01

This study examined patterns, potential predictors, and outcomes of immunosuppressive medication adherence in a convenience sample of 121 kidney transplant recipients aged 21 years or older from three kidney transplant centers using a theory-based, descriptive, correlational, longitudinal design. Electronic monitoring was conducted for 12 months using the Medication Event Monitoring System. Participants were persistent in taking their immunosuppressive medications, but execution, which includes both taking and timing, was poor. Older age was the only demographic variable associated with medication adherence (r = 0.25; p = 0.005). Of the potential predictors examined, only medication self-efficacy was associated with medication non-adherence, explaining about 9% of the variance (r = 0.31, p = 0.0006). The few poor outcomes that occurred were not significantly associated with medication non-adherence, although the small number of poor outcomes may have limited our ability to detect a link. Future research should test fully powered, theory-based, experimental interventions that include a medication self-efficacy component. PMID:24093614

"Living cadavers" in Bangladesh: bioviolence in the human organ bazaar.

PubMed

Moniruzzaman, Monir

2012-03-01

The technology-driven demand for the extraction of human organs--mainly kidneys, but also liver lobes and single corneas--has created an illegal market in body parts. Based on ethnographic fieldwork, in this article I examine the body bazaar in Bangladesh: in particular, the process of selling organs and the experiences of 33 kidney sellers who are victims of this trade. The sellers' narratives reveal how wealthy buyers (both recipients and brokers) tricked Bangladeshi poor into selling their kidneys; in the end, these sellers were brutally deceived and their suffering was extreme. I therefore argue that the current practice of organ commodification is both exploitative and unethical, as organs are removed from the bodies of the poor by inflicting a novel form of bioviolence against them. This bioviolence is deliberately silenced by vested interest groups for their personal gain.

Polycystic kidneys in the red panda (Ailurus fulgens).

PubMed

Makungu, Modesta; du Plessis, Wencke M; Barrows, Michelle; Koeppel, Katja N; Groenewald, Hermanus B

2013-09-01

An intact adult male 14.3-yr-old red panda (Ailurus fulgens) presented for health examination with a history of slowly progressing loss of body condition. Abdominal radiographs revealed a truncated abdomen with poor serosal abdominal detail and multiple areas of spondylosis with some collapsed intervertebral disc spaces. On computed tomography, multiple ovoid hypoattenuating lesions were seen in the left and right kidneys. Gross pathology and histopathology revealed multiple cystic lesions in the kidneys concurrent with pancreatic cysts on histopathology. To the best of the authors' knowledge, polycystic kidneys have not been reported in this species.

Depression and kidney transplantation.

PubMed

Chilcot, Joseph; Spencer, Benjamin Walter Jack; Maple, Hannah; Mamode, Nizam

2014-04-15

While kidney transplantation offers several advantages in terms of improved clinical outcomes and quality of life compared to dialysis modalities, depressive symptoms are still present in approximately 25% of patients, rates comparable to that of the hemodialysis population. Correlates of depressive symptoms include marital status, income, kidney function, history of affective illness, malnutrition, and inflammation. Depressive symptoms are also associated with poor outcomes following kidney transplantation including nonadherence to immunosuppressant medication, graft failure, and all-cause mortality. Efforts to detect and treat depression should be a priority if one is to improve treatment adherence, quality of life, and outcomes in transplant recipients.

Optimizing SGLT inhibitor treatment for diabetes with chronic kidney diseases.

PubMed

Layton, Anita T

2018-06-28

Diabetes induces glomerular hyperfiltration, affects kidney function, and may lead to chronic kidney diseases. A novel therapeutic treatment for diabetic patients targets the sodium-glucose cotransporter isoform 2 (SGLT2) in the kidney. SGLT2 inhibitors enhance urinary glucose, [Formula: see text] and fluid excretion and lower hyperglycemia in diabetes by inhibiting [Formula: see text] and glucose reabsorption along the proximal convoluted tubule. A goal of this study is to predict the effects of SGLT2 inhibitors in diabetic patients with and without chronic kidney diseases. To that end, we applied computational rat kidney models to assess how SGLT2 inhibition affects renal solute transport and metabolism when nephron population are normal or reduced (the latter simulates chronic kidney disease). The model predicts that SGLT2 inhibition induces glucosuria and natriuresis, with those effects enhanced in a remnant kidney. The model also predicts that the [Formula: see text] transport load and thus oxygen consumption of the S3 segment are increased under SGLT2 inhibition, a consequence that may increase the risk of hypoxia for that segment. To protect the vulnerable S3 segment, we explore dual SGLT2/SGLT1 inhibition and seek to determine the optimal combination that would yield sufficient urinary glucose excretion while limiting the metabolic load on the S3 segment. The model predicts that the optimal combination of SGLT2/SGLT1 inhibition lowers the oxygen requirements of key tubular segments, but decreases urine flow and [Formula: see text] excretion; the latter effect may limit the cardiovascular protection of the treatment.

Risk prediction models for graft failure in kidney transplantation: a systematic review.

PubMed

Kaboré, Rémi; Haller, Maria C; Harambat, Jérôme; Heinze, Georg; Leffondré, Karen

2017-04-01

Risk prediction models are useful for identifying kidney recipients at high risk of graft failure, thus optimizing clinical care. Our objective was to systematically review the models that have been recently developed and validated to predict graft failure in kidney transplantation recipients. We used PubMed and Scopus to search for English, German and French language articles published in 2005-15. We selected studies that developed and validated a new risk prediction model for graft failure after kidney transplantation, or validated an existing model with or without updating the model. Data on recipient characteristics and predictors, as well as modelling and validation methods were extracted. In total, 39 articles met the inclusion criteria. Of these, 34 developed and validated a new risk prediction model and 5 validated an existing one with or without updating the model. The most frequently predicted outcome was graft failure, defined as dialysis, re-transplantation or death with functioning graft. Most studies used the Cox model. There was substantial variability in predictors used. In total, 25 studies used predictors measured at transplantation only, and 14 studies used predictors also measured after transplantation. Discrimination performance was reported in 87% of studies, while calibration was reported in 56%. Performance indicators were estimated using both internal and external validation in 13 studies, and using external validation only in 6 studies. Several prediction models for kidney graft failure in adults have been published. Our study highlights the need to better account for competing risks when applicable in such studies, and to adequately account for post-transplant measures of predictors in studies aiming at improving monitoring of kidney transplant recipients. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Endogenous Antiangiogenic Factors in Chronic Kidney Disease: Potential Biomarkers of Progression.

PubMed

Tanabe, Katsuyuki; Sato, Yasufumi; Wada, Jun

2018-06-24

Chronic kidney disease (CKD) is a major global health problem. Unless intensive intervention is initiated, some patients can rapidly progress to end-stage kidney disease. However, it is often difficult to predict renal outcomes using conventional laboratory tests in individuals with CKD. Therefore, many researchers have been searching for novel biomarkers to predict the progression of CKD. Angiogenesis is involved in physiological and pathological processes in the kidney and is regulated by the balance between a proangiogenic factor, vascular endothelial growth factor (VEGF)-A, and various endogenous antiangiogenic factors. In recent reports using genetically engineered mice, the roles of these antiangiogenic factors in the pathogenesis of kidney disease have become increasingly clear. In addition, recent clinical studies have demonstrated associations between circulating levels of antiangiogenic factors and renal dysfunction in CKD patients. In this review, we summarize recent advances in the study of representative endogenous antiangiogenic factors, including soluble fms-related tyrosine kinase 1, soluble endoglin, pigment epithelium-derived factor, VEGF-A 165 b, endostatin, and vasohibin-1, in associations with kidney diseases and discuss their predictive potentials as biomarkers of progression of CKD.

Profile, risk factors and outcome of acute kidney injury in paediatric acute-on-chronic liver failure.

PubMed

Lal, Bikrant B; Alam, Seema; Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev

2018-01-11

There are no studies on acute kidney injury in paediatric acute-on-chronic liver failure. This study was planned with aim to describe the clinical presentation and outcome of acute kidney injury among paediatric acute-on-chronic liver failure patients. Data of all children 1-18 years of age presenting with acute chronic liver failure (Asia pacific association for the study of the liver definition) was reviewed. Acute kidney injury was defined as per Kidney Diseases-Improving Global Outcomes guidelines. Poor outcome was defined as death or need for liver transplant within 3 months of development of acute kidney injury. A total of 84 children with acute-on-chronic liver failure were presented to us in the study period. Acute kidney injury developed in 22.6% of patients with acute-on-chronic liver failure. The median duration from acute-on-chronic liver failure to development of acute kidney injury was 4 weeks (Range: 2-10 weeks). The causes of acute kidney injury were hepatorenal syndrome (31.6%), sepsis (31.6%), nephrotoxic drugs (21%), dehydration (10.5%) and bile pigment related acute tubular necrosis in one patient. On univariate analysis, higher baseline bilirubin, higher international normalized ratio, higher paediatric end stage liver disease, presence of systemic inflammatory response syndrome and presence of spontaneous bacterial peritonitis had significant association with presence of acute kidney injury. On logistic regression analysis, presence of systemic inflammatory response syndrome (adjusted OR: 8.659, 95% CI: 2.18-34.37, P = .002) and higher baseline bilirubin (adjusted OR: 1.07, 95% CI: 1.008-1.135, P = .025) were independently associated with presence of acute kidney injury. Of the patients with acute kidney injury, 5(26.3%) survived with native liver, 10(52.6%) died and 4 (21.1%) underwent liver transplantation. Acute kidney injury developed in 22.6% of children with acute-on-chronic liver failure. Bilirubin more than 17.7 mg/dL and presence of systemic inflammatory response syndrome were high risk factors for acute kidney injury. Development of acute kidney injury in a child with acute-on-chronic liver failure suggests poor outcome and need for early intervention. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reduced expression of IQGAP2 and higher expression of IQGAP3 correlates with poor prognosis in cancers

PubMed Central

Kumar, Dinesh; Hassan, Md. Khurshidul; Pattnaik, Niharika; Mohapatra, Nachiketa

2017-01-01

IQGAPs is a family of proteins which comprises three members, in humans. The expression pattern and role of IQGAP1 has been well established in many cancers, whereas those of IQGAP2 and IQGAP3, have mostly remained unexplored. We used available large datasets, to explore the pan-cancer status of these two genes in-silico. Here we have analysed their mRNA expression and correlation with survivability in eight different cancers, including lung, breast, gastric, brain, colorectal, prostate, liver and kidney cancers and, their subtypes. The mRNA expression of IQGAP2 and IQGAP3 in individual cancers were analysed in two different publicly available databases viz. Oncomine and TCGA. The prognostic value of these genes in lung, breast and gastric cancer was analysed using Kaplan-Meier Plotter database, whereas for brain, colorectal, liver, prostate and kidney cancers, SurvExpress database was used. These results were validated by immunohistochemistry in cancer tissues (stomach, prostate, brain, colorectal). Moreover, we did IQGAP2 and IQGAP3 genomic alteration and, promoter methylation analysis using cBioportal and Wanderer web tool, respectively. Most of the cancer types (lung, breast, prostate, brain, gastric, liver, kidney and colorectal) showed increased IQGAP3 mRNA expression. In contrast, the IQGAP2 transcript levels were reduced across different cancers viz. lung, breast, gastric, liver, kidney and colorectal cancer. IQGAP2 expression correlated positively with survivability, on the contrary, IQGAP3 expression levels correlated inversely with survivability, in most of the cancers. Collectively, enhanced IQGAP3 and reduced IQGAP2 levels were frequently observed in multiple cancers with the former predicting poor survivability and the later opposite. Methylation pattern was significantly altered in most of the cancer types. We found copy no. variation and mutations in specific cancers, for IQGAP2 and IQGAP3. Our in-vivo (IHC) data confirmed the in-silico findings completely. Hence, IQGAP2 and IQGAP3 have potential to be used as prognostic markers or therapeutic targets in specific cancers. PMID:29073199

Reduced expression of IQGAP2 and higher expression of IQGAP3 correlates with poor prognosis in cancers.

PubMed

Kumar, Dinesh; Hassan, Md Khurshidul; Pattnaik, Niharika; Mohapatra, Nachiketa; Dixit, Manjusha

2017-01-01

IQGAPs is a family of proteins which comprises three members, in humans. The expression pattern and role of IQGAP1 has been well established in many cancers, whereas those of IQGAP2 and IQGAP3, have mostly remained unexplored. We used available large datasets, to explore the pan-cancer status of these two genes in-silico. Here we have analysed their mRNA expression and correlation with survivability in eight different cancers, including lung, breast, gastric, brain, colorectal, prostate, liver and kidney cancers and, their subtypes. The mRNA expression of IQGAP2 and IQGAP3 in individual cancers were analysed in two different publicly available databases viz. Oncomine and TCGA. The prognostic value of these genes in lung, breast and gastric cancer was analysed using Kaplan-Meier Plotter database, whereas for brain, colorectal, liver, prostate and kidney cancers, SurvExpress database was used. These results were validated by immunohistochemistry in cancer tissues (stomach, prostate, brain, colorectal). Moreover, we did IQGAP2 and IQGAP3 genomic alteration and, promoter methylation analysis using cBioportal and Wanderer web tool, respectively. Most of the cancer types (lung, breast, prostate, brain, gastric, liver, kidney and colorectal) showed increased IQGAP3 mRNA expression. In contrast, the IQGAP2 transcript levels were reduced across different cancers viz. lung, breast, gastric, liver, kidney and colorectal cancer. IQGAP2 expression correlated positively with survivability, on the contrary, IQGAP3 expression levels correlated inversely with survivability, in most of the cancers. Collectively, enhanced IQGAP3 and reduced IQGAP2 levels were frequently observed in multiple cancers with the former predicting poor survivability and the later opposite. Methylation pattern was significantly altered in most of the cancer types. We found copy no. variation and mutations in specific cancers, for IQGAP2 and IQGAP3. Our in-vivo (IHC) data confirmed the in-silico findings completely. Hence, IQGAP2 and IQGAP3 have potential to be used as prognostic markers or therapeutic targets in specific cancers.

Organ quality metrics are a poor predictor of costs and resource utilization in deceased donor kidney transplantation.

PubMed

Stahl, Christopher C; Wima, Koffi; Hanseman, Dennis J; Hoehn, Richard S; Ertel, Audrey; Midura, Emily F; Hohmann, Samuel F; Paquette, Ian M; Shah, Shimul A; Abbott, Daniel E

2015-12-01

The desire to provide cost-effective care has lead to an investigation of the costs of therapy for end-stage renal disease. Organ quality metrics are one way to attempt to stratify kidney transplants, although the ability of these metrics to predict costs and resource use is undetermined. The Scientific Registry of Transplant Recipients database was linked to the University HealthSystem Consortium Database to identify adult deceased donor kidney transplant recipients from 2009 to 2012. Patients were divided into cohorts by kidney criteria (standard vs expanded) or kidney donor profile index (KDPI) score (<85 vs 85+). Length of stay, 30-day readmission, discharge disposition, and delayed graft function were used as indicators of resource use. Cost was defined as reimbursement based on Medicare cost/charge ratios and included the costs of readmission when applicable. More than 19,500 patients populated the final dataset. Lower-quality kidneys (expanded criteria donor or KDPI 85+) were more likely to be transplanted in older (both P < .001) and diabetic recipients (both P < .001). After multivariable analysis controlling for recipient characteristics, we found that expanded criteria donor transplants were not associated with increased costs compared with standard criteria donor transplants (risk ratio [RR] 0.97, 95% confidence interval [CI] 0.93-1.00, P = .07). KDPI 85+ was associated with slightly lower costs than KDPI <85 transplants (RR 0.95, 95% CI 0.91-0.99, P = .02). When KDPI was considered as a continuous variable, the association was maintained (RR 0.9993, 95% CI 0.999-0.9998, P = .01). Organ quality metrics are less influential predictors of short-term costs than recipient factors. Future studies should focus on recipient characteristics as a way to discern high versus low cost transplantation procedures. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Yonsei nomogram: A predictive model of new-onset chronic kidney disease after on-clamp partial nephrectomy in patients with T1 renal tumors.

PubMed

Abdel Raheem, Ali; Shin, Tae Young; Chang, Ki Don; Santok, Glen Denmer R; Alenzi, Mohamed Jayed; Yoon, Young Eun; Ham, Won Sik; Han, Woong Kyu; Choi, Young Deuk; Rha, Koon Ho

2018-06-19

To develop a predictive nomogram for chronic kidney disease-free survival probability in the long term after partial nephrectomy. A retrospective analysis was carried out of 698 patients with T1 renal tumors undergoing partial nephrectomy at a tertiary academic institution. A multivariable Cox regression analysis was carried out based on parameters proven to have an impact on postoperative renal function. Patients with incomplete data, <12 months follow up and preoperative chronic kidney disease stage III or greater were excluded. The study end-points were to identify independent risk factors for new-onset chronic kidney disease development, as well as to construct a predictive model for chronic kidney disease-free survival probability after partial nephrectomy. The median age was 52 years, median tumor size was 2.5 cm and mean warm ischemia time was 28 min. A total of 91 patients (13.1%) developed new-onset chronic kidney disease at a median follow up of 60 months. The chronic kidney disease-free survival rates at 1, 3, 5 and 10 year were 97.1%, 94.4%, 85.3% and 70.6%, respectively. On multivariable Cox regression analysis, age (1.041, P = 0.001), male sex (hazard ratio 1.653, P < 0.001), diabetes mellitus (hazard ratio 1.921, P = 0.046), tumor size (hazard ratio 1.331, P < 0.001) and preoperative estimated glomerular filtration rate (hazard ratio 0.937, P < 0.001) were independent predictors for new-onset chronic kidney disease. The C-index for chronic kidney disease-free survival was 0.853 (95% confidence interval 0.815-0.895). We developed a novel nomogram for predicting the 5-year chronic kidney disease-free survival probability after on-clamp partial nephrectomy. This model might have an important role in partial nephrectomy decision-making and follow-up plan after surgery. External validation of our nomogram in a larger cohort of patients should be considered. © 2018 The Japanese Urological Association.

Early post-transplant immune monitoring can predict long-term kidney graft survival: soluble CD30 levels, anti-HLA antibodies and IgA-anti-Fab autoantibodies.

PubMed

Amirzargar, Mohammad Ali; Amirzargar, Aliakbar; Basiri, Abbas; Hajilooi, Mehrdad; Roshanaei, Ghodratollah; Rajabi, Gholamreza; Mohammadiazar, Sina; Solgi, Ghasem

2014-01-01

This study aimed to investigate the predictive power of anti-HLA antibodies, sCD30 levels and IgA-anti-Fab autoantibody before and early after transplantation in relation to long-term kidney allograft survival. Pre- and post-transplant sera samples of 59 living-unrelated donor kidney recipients were tested for above risk factors by enzyme-linked immunoabsorbent assay. 15 out of 59 cases experienced rejection episodes (failure group). Pre- and post-transplant high sCD30 levels were significantly associated with graft failure (P=0.02 and P=0.004) and decreased 4 year graft survival (P = 0.009 and P = 0.001). Higher frequency of post-transplant HLA class-II antibody in the absence of class-I antibody was observed in failure group (P=0.007). Patients with post-transplant HLA class-I and class-II antibodies either alone or in combination showed significant lower 4 year graft survival. Recipients with high sCD30 levels in the presence of HLA class-I or class-II antibodies within 2 weeks post-transplant had poor graft survival (P = 0.004 and P = 0.002, respectively). High levels of post-transplant IgA-anti-Fab antibody was more frequent in functioning-graft patients (P = 0.00001), correlated with decreased serum creatinine levels (P = 0.01) and associated with improved graft survival (P = 0.008). Our findings indicate the deleterious effect of early post-transplant HLA antibodies and increased sCD30 levels dependently and protective effect of IgA-anti-Fab antibodies on long-term renal graft outcomes. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

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%.

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

Study of Acute Kidney Injury on 309 Hypertensive Inpatients with ACEI/ARB - Diuretic Treatment.

PubMed

Chen, Qiaochao; Zhu, Shaofang; Liao, Jianjun; He, Wen

2018-06-01

The present study investigated risk factors for acute kidney injury (AKI) in patients found to be hypertensive during hospitalization who were prescribed angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists (ARB) + diuretic combinations, in order to determine which type of diuretic or combination of diuretics used in ACE/ARB-treated patients leads to a higher risk of acute kidney injury. Data on basic information, medical history, diagnostic information and medications prescribed were obtained from the patients' medical records. Retrospective analysis of potential risk factors and ACEI/ARB + diuretic use with AKI was performed. Multivariate analysis showed initial risk factors for AKI to be chronic kidney disease and poor cardiac function. In univariate analysis, patients whose baseline serum creatinine was between 115 and 265 μmol/L also had a higher risk of AKI. The combination of furosemide and spironolactone produced only approximately a third of the risk of AKI as the combination of hydrochlorothiazide and spironolactone. Chronic kidney disease and poor cardiac function are major risk factors for AKI in hypertensive inpatients using ACEI/ARB + diuretic therapy. The combination of thiazide diuretic and aldosterone antagonist had a higher risk of AKI than other single diuretics or diuretic combinations. Copyright © 2017 National Medical Association. Published by Elsevier Inc. All rights reserved.

Kidney transplantation in the elderly.

PubMed

Singh, Neeraj; Nori, Uday; Pesavento, Todd

2009-08-01

Recent outcome data, ongoing organ shortage and proposed changes in allocation policies are driving the need to review current practices and possible future course of kidney transplantation in the elderly patients. A proposed new kidney allocation system based on matching donor and recipient characteristics to enable 'age-matched' kidney allocation is currently being discussed in the USA. While this system benefits younger recipients, implications for elderly recipients receiving older grafts remain a matter of debate. Despite improved outcomes, there remain significant challenges to kidney transplantation in the elderly, including organ shortage, poor transplant rate, evolving allocation policies, high wait-list mortality and nonstandardized immunosuppression. Prospective studies are needed to evaluate the strategies to meet these challenges and to study the impact of proposed new allocation system.

Self-rated appetite as a predictor of mortality in patients with stage 5 chronic kidney disease.

PubMed

Gama-Axelsson, Thiane; Lindholm, Bengt; Bárány, Peter; Heimbürger, Olof; Stenvinkel, Peter; Qureshi, Abdul Rashid

2013-03-01

To investigate the level of anorexia and its correlation with mortality in chronic kidney disease stage 5 patients not yet on dialysis (CKD5-ND) and in those with stage 5 chronic kidney disease undergoing dialysis (CKD5-D). In an observational study, self-rated appetite (as part of a subjective global assessment of nutritional status), along with anthropometrics and biochemical markers of nutritional status, was analyzed in relation to survival. In a subgroup of patients, appetite change after start of dialysis was studied prospectively. Two hundred eighty CKD5-ND (40% female; age 54 ± 12 years; glomerular filtration rate 7 ± 2 mL/minute) and 243 CKD5-D patients (116 hemodialysis and 127 peritoneal dialysis [PD]; 44% female; age 54 ± 12 years; dialysis vintage time 12 ± 2 months) who had been on dialysis for about 1 year were studied. CKD5-ND patients with poor appetite (50%) had a higher prevalence of cardiovascular disease, lower body weight and serum creatinine level, and higher C-reactive protein. CKD5-D patients with poor appetite (33%) had impaired subjective global assessment of nutritional status and lower body weight, fat body mass, handgrip strength, hemoglobin, and serum albumin level. In a Kaplan-Meier analysis, appetite was not associated with survival difference, whereas in the Cox proportional hazards model with competing risk analysis, poor appetite increased mortality risk in PD patients but not in hemodialysis and CKD5-ND patients. In CKD5-ND patients, self-rated appetite was not an independent predictor of 48-months survival, whereas there was a significant increase in mortality risk in PD patients with poor appetite. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Role of renal biomarkers as predictors of acute kidney injury in cardiac surgery.

PubMed

Ghatanatti, Ravi; Teli, Anita; Tirkey, Sundeep Sanjivan; Bhattacharya, Subhankar; Sengupta, Gautam; Mondal, Ansuman

2014-02-01

Cardiac surgery is unique in using cardiopulmonary bypass in various clinical scenarios. Injury of vital organs is unavoidable in the perioperative period. Acute kidney injury is a consequence of the systemic inflammatory response after bypass, emboli, ischemia, and low cardiac output states, reportedly occurring in 30%-40% of open heart surgeries. Acute kidney injury is associated with increased morbidity, mortality, and cost. Many preventive measures (off-pump procedures, decreased crossclamp time, pulsatile flow, adequate hydration) are taken in the perioperative period to avoid organ injury, but in vain. Traditionally, blood urea, serum creatinine, and creatinine clearance rate were applied for prediction of acute kidney injury. The recent emergence of biomarkers such as neutrophil gelatinase-associated lipocalin, cystatin C, liver-type fatty acid binding protein, interleukin-18, kidney injury molecule-1, and tetrahydrobiopterin have helped in detecting acute kidney injury long before the rise of serum creatinine. These biomarkers can also be used as tools for predicting therapeutic effects in acute kidney injury and for monitoring drug toxicity. This review consolidates the knowledge of biomarkers and their application in acute kidney injury management.

[Towards the development of living donor kidney transplantation].

PubMed

Macher, Marie-Alice

2016-12-01

Living donor kidney transplantation has been increasing since 2008. Living donors represent a significant potential for organ transplants, in a context where the needs outstrip the availability of organs from deceased donors. However, patients are still poorly informed regarding the conditions in which these transplants are possible. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Predonation Volume of Future Remnant Cortical Kidney Helps Predict Postdonation Renal Function in Live Kidney Donors.

PubMed

Fananapazir, Ghaneh; Benzl, Robert; Corwin, Michael T; Chen, Ling-Xin; Sageshima, Junichiro; Stewart, Susan L; Troppmann, Christoph

2018-07-01

Purpose To determine whether the predonation computed tomography (CT)-based volume of the future remnant kidney is predictive of postdonation renal function in living kidney donors. Materials and Methods This institutional review board-approved, retrospective, HIPAA-compliant study included 126 live kidney donors who had undergone predonation renal CT between January 2007 and December 2014 as well as 2-year postdonation measurement of estimated glomerular filtration rate (eGFR). The whole kidney volume and cortical volume of the future remnant kidney were measured and standardized for body surface area (BSA). Bivariate linear associations between the ratios of whole kidney volume to BSA and cortical volume to BSA were obtained. A linear regression model for 2-year postdonation eGFR that incorporated donor age, sex, and either whole kidney volume-to-BSA ratio or cortical volume-to-BSA ratio was created, and the coefficient of determination (R 2 ) for the model was calculated. Factors not statistically additive in assessing 2-year eGFR were removed by using backward elimination, and the coefficient of determination for this parsimonious model was calculated. Results Correlation was slightly better for cortical volume-to-BSA ratio than for whole kidney volume-to-BSA ratio (r = 0.48 vs r = 0.44, respectively). The linear regression model incorporating all donor factors had an R 2 of 0.66. The only factors that were significantly additive to the equation were cortical volume-to-BSA ratio and predonation eGFR (P = .01 and P < .01, respectively), and the final parsimonious linear regression model incorporating these two variables explained almost the same amount of variance (R 2 = 0.65) as did the full model. Conclusion The cortical volume of the future remnant kidney helped predict postdonation eGFR at 2 years. The cortical volume-to-BSA ratio should thus be considered for addition as an important variable to living kidney donor evaluation and selection guidelines. © RSNA, 2018.

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

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.

Prediction of acute kidney injury within 30 days of cardiac surgery.

PubMed

Ng, Shu Yi; Sanagou, Masoumeh; Wolfe, Rory; Cochrane, Andrew; Smith, Julian A; Reid, Christopher Michael

2014-06-01

To predict acute kidney injury after cardiac surgery. The study included 28,422 cardiac surgery patients who had had no preoperative renal dialysis from June 2001 to June 2009 in 18 hospitals. Logistic regression analyses were undertaken to identify the best combination of risk factors for predicting acute kidney injury. Two models were developed, one including the preoperative risk factors and another including the pre-, peri-, and early postoperative risk factors. The area under the receiver operating characteristic curve was calculated, using split-sample internal validation, to assess model discrimination. The incidence of acute kidney injury was 5.8% (1642 patients). The mortality for patients who experienced acute kidney injury was 17.4% versus 1.6% for patients who did not. On validation, the area under the curve for the preoperative model was 0.77, and the Hosmer-Lemeshow goodness-of-fit P value was .06. For the postoperative model area under the curve was 0.81 and the Hosmer-Lemeshow P value was .6. Both models had good discrimination and acceptable calibration. Acute kidney injury after cardiac surgery can be predicted using preoperative risk factors alone or, with greater accuracy, using pre-, peri-, and early postoperative risk factors. The ability to identify high-risk individuals can be useful in preoperative patient management and for recruitment of appropriate patients to clinical trials. Prediction in the early stages of postoperative care can guide subsequent intensive care of patients and could also be the basis of a retrospective performance audit tool. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

External Validation of a Tool Predicting 7-Year Risk of Developing Cardiovascular Disease, Type 2 Diabetes or Chronic Kidney Disease.

PubMed

Rauh, Simone P; Rutters, Femke; van der Heijden, Amber A W A; Luimes, Thomas; Alssema, Marjan; Heymans, Martijn W; Magliano, Dianna J; Shaw, Jonathan E; Beulens, Joline W; Dekker, Jacqueline M

2018-02-01

Chronic cardiometabolic diseases, including cardiovascular disease (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD), share many modifiable risk factors and can be prevented using combined prevention programs. Valid risk prediction tools are needed to accurately identify individuals at risk. We aimed to validate a previously developed non-invasive risk prediction tool for predicting the combined 7-year-risk for chronic cardiometabolic diseases. The previously developed tool is stratified for sex and contains the predictors age, BMI, waist circumference, use of antihypertensives, smoking, family history of myocardial infarction/stroke, and family history of diabetes. This tool was externally validated, evaluating model performance using area under the receiver operating characteristic curve (AUC)-assessing discrimination-and Hosmer-Lemeshow goodness-of-fit (HL) statistics-assessing calibration. The intercept was recalibrated to improve calibration performance. The risk prediction tool was validated in 3544 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Discrimination was acceptable, with an AUC of 0.78 (95% CI 0.75-0.81) in men and 0.78 (95% CI 0.74-0.81) in women. Calibration was poor (HL statistic: p < 0.001), but improved considerably after intercept recalibration. Examination of individual outcomes showed that in men, AUC was highest for CKD (0.85 [95% CI 0.78-0.91]) and lowest for T2D (0.69 [95% CI 0.65-0.74]). In women, AUC was highest for CVD (0.88 [95% CI 0.83-0.94)]) and lowest for T2D (0.71 [95% CI 0.66-0.75]). Validation of our previously developed tool showed robust discriminative performance across populations. Model recalibration is recommended to account for different disease rates. Our risk prediction tool can be useful in large-scale prevention programs for identifying those in need of further risk profiling because of their increased risk for chronic cardiometabolic diseases.

Risk, Predictors, and Outcomes of Acute Kidney Injury in Patients Admitted to Intensive Care Units in Egypt.

PubMed

Abd ElHafeez, Samar; Tripepi, Giovanni; Quinn, Robert; Naga, Yasmine; Abdelmonem, Sherif; AbdelHady, Mohamed; Liu, Ping; James, Matthew; Zoccali, Carmine; Ravani, Pietro

2017-12-07

Epidemiology of acute kidney injury (AKI) in developing countries is under-studied. We evaluated the risk and prognosis of AKI in patients admitted to intensive care units (ICUs) in Egypt. We recruited consecutive adults admitted to ICUs in Alexandria Teaching Hospitals over six months. We used the KDIGO criteria for AKI. We followed participants until the earliest of ICU discharge, death, day 30 from entry or study end. Of the 532 participants (median age 45 (Interquartile range [IQR]: 30-62) years, 41.7% male, 23.7% diabetics), 39.6% had AKI at ICU admission and 37.4% developed AKI after 24 hours of ICU admission. Previous need of diuretics, sepsis and low education were associated with AKI at ICU admission; APACHE II score independently predicted AKI after ICU admission. A total of 120 (22.6%) patients died during 30-day follow-up. Compared to patients who remained AKI-free, mortality was significantly higher in patients who had AKI at study entry (Hazard Ratio [HR] 2.14; 95% Confidence Interval [CI] 1.02-4.48) or developed AKI in ICU (HR 2.74; 95% CI 1.45-5.17). The risk of AKI is high in critically ill people and predicts poor outcomes. Further studies are needed to estimate the burden of AKI among patients before ICU admission.

Evaluation of a prognostic scoring system for dogs managed with hemodialysis.

PubMed

Perondi, Francesca; Lippi, Ilaria; Ceccherini, Gianila; Marchetti, Veronica; Bernicchi, Lucrezia; Guidi, Grazia

2018-06-24

To investigate prognostic models in a cohort of dogs with acute kidney injury (AKI) and acute on chronic kidney disease (AKI/CKD) managed by hemodialysis. Retrospective study from July 2011 to November 2014. University Veterinary Teaching Hospital. Forty dogs with historical, clinical, imaging, and laboratory findings consistent with AKI or AKI/CKD managed with intermittent hemodialysis were included. Scoring system models previously established by Segev et al for outcome prediction in dogs with AKI were applied to all dogs. Models A, B, and C correctly classified outcomes in 68%, 83%, and 85% of cases, respectively. In our cohort Model A showed sensitivity of 58% and specificity of 86%, Model B showed sensitivity of 79% and specificity of 87%, Model C showed sensitivity of 86% and specificity of 84%. The presence of anuria (P < 0.0002), respiratory complications (P < 0.0001), disseminated intravascular coagulation (DIC) (P = 0.0004), grade of AKI (P = 0.0023), pancreatitis (P = 0.0001), and systemic inflammatory response syndrome (SIRS) (P = 0.0001) was significantly higher in nonsurvivors compared with survivors. In our cohort of patients, Segev's model C showed the best sensitivity and specificity for predicting prognosis, while model A had lower sensitivity. In our cohort of dialysis patients, the presence of respiratory complications, DIC, SIRS, and pancreatitis at hospitalization, were correlated with a poor prognosis. © Veterinary Emergency and Critical Care Society 2018.

Assessing barriers to adherence in routine clinical care for pediatric kidney transplant patients.

PubMed

Varnell, Charles D; Rich, Kristin L; Nichols, Melissa; Dahale, Devesh; Goebel, Jens W; Pai, Ahna L H; Hooper, David K; Modi, Avani C

2017-11-01

Patient-identified barriers to immunosuppressive medications are associated with poor adherence and negative clinical outcomes in transplant patients. Assessment of adherence barriers is not part of routine post-transplant care, and studies regarding implementing such a process in a reliable way are lacking. Using the Model for Improvement and PDSA cycles, we implemented a system to identify adherence barriers, including patient-centered design of a barriers assessment tool, identification of eligible patients, clear roles for clinic staff, and creating a culture of non-judgmental discussion around adherence. We performed time-series analysis of our process measure. Secondary analyses examined the endorsement and concordance of adherence barriers between patient-caregiver dyads. After three methods of testing, the most reliable delivery system was an EHR-integrated tablet that alerted staff of patient eligibility for assessment. Barriers were endorsed by 35% of caregivers (n=85) and 43% of patients (n=60). The most frequently patient-endorsed barriers were forgetting, poor taste, and side effects. Caregivers endorsed forgetting and side effects. Concordance between patient-caregiver dyads was fair (k=0.299). Standardized adherence barriers assessment is feasible in the clinical care of pediatric kidney transplant patients. Features necessary for success included automation, redundant systems with designated staff to identify and mitigate failures, aligned reporting structures, and reliable measurement approaches. Future studies will examine whether barriers predict clinical outcomes (eg, organ rejection, graft loss). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury

PubMed Central

Pannu, Neesh; Hemmelgarn, Brenda R.; Austin, Peter C.; Tan, Zhi; McArthur, Eric; Manns, Braden J.; Tonelli, Marcello; Wald, Ron; Quinn, Robert R.; Ravani, Pietro; Garg, Amit X.

2017-01-01

Importance Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up. Objective To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease. Design, Setting, and Participants Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013). Exposures Demographic, laboratory, and comorbidity variables measured prior to discharge. Main Outcomes and Measures Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year. Results The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%). Conclusions and Relevance A multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research. PMID:29136443

Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury.

PubMed

James, Matthew T; Pannu, Neesh; Hemmelgarn, Brenda R; Austin, Peter C; Tan, Zhi; McArthur, Eric; Manns, Braden J; Tonelli, Marcello; Wald, Ron; Quinn, Robert R; Ravani, Pietro; Garg, Amit X

2017-11-14

Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up. To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease. Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013). Demographic, laboratory, and comorbidity variables measured prior to discharge. Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year. The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%). A multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research.

Nonadherence to immunosuppressive therapy in kidney transplant recipients: can technology help?

PubMed

Nerini, Erika; Bruno, Fulvio; Citterio, Franco; Schena, Francesco P

2016-10-01

End-stage kidney disease is a life-threatening condition that compels patients to accept either dialysis or transplant. Kidney transplantation is the best choice for patients with end-stage kidney disease because it ensures higher quality of life and longer survival rates than other choices, with less cost for the healthcare system. However, in order for renal recipients to maintain the functioning graft they must take lifelong immunosuppressive medications, with possible side effects and low medication adherence. It is known that low medication adherence in kidney transplant recipients may cause poor outcomes, chronic graft rejection, and graft failure. In this review, the authors give an overview of nonadherence in the transplant setting. In addition, they analyze the role of different technologies as an aid to improve adherence, with a focus on mobile-phone based solutions to monitor and enhance kidney transplant recipient compliance.

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.

Pantoprazole-induced acute kidney injury: A case report.

PubMed

Peng, Tao; Hu, Zhao; Zheng, Hongnan; Zhen, Junhui; Ma, Chengjun; Yang, Xiangdong

2018-06-01

The present study reports a case of pantoprazole-induced acute kidney disease. The patient was diagnosed with acute kidney injury with wide interstitial inflammation and eosinophil infiltration. Following 1 month of glucocorticoid therapy, the patient's serum creatinine and urea nitrogen decreased to within normal ranges. The presentation, clinical course, diagnosis and prognosis of pantoprazole-induced acute kidney injury are discussed herein to highlight the importance of early and correct diagnosis for good prognosis. Disease characteristics include short-term increased serum creatinine levels that respond to glucocorticoid treatment. The patient had no history of chronic kidney disease or proteinuria and presented with increased serum creatinine following treatment with pantoprazole. Following the end of pantoprazole treatment, short-term RRT and long-term prednisolone was administered, then serum creatinine returned to normal. Pantoprazole-induced acute kidney injury is commonly misdiagnosed and late diagnosis results in poor patient prognoses. Misdiagnosis leads to the administration of treatments that may exacerbate the condition, so appropriate diagnosis and treatment for pantoprazole-induced acute kidney injury is necessary.

Computed Tomography Volumetry in Preoperative Living Kidney Donor Assessment for Prediction of Split Renal Function.

PubMed

Wahba, Roger; Franke, Mareike; Hellmich, Martin; Kleinert, Robert; Cingöz, Tülay; Schmidt, Matthias C; Stippel, Dirk L; Bangard, Christopher

2016-06-01

Transplant centers commonly evaluate split renal function (SRF) with Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy in living kidney donation. Alternatively, the kidney volume can be measured based on predonation CT scans. The aim of this study was to identify the most accurate CT volumetry technique for SRF and the prediction of postdonation kidney function (PDKF). Three CT volumetry techniques (modified ellipsoid volume [MELV], smart region of interest [ROI] volume, renal cortex volume [RCV]) were performed in 101 living kidney donors. Preoperation CT volumetric SRF was determined and compared with MAG3-SRF, postoperation donor kidney function, and graft function. The correlation between donors predonation total kidney volume and predonation kidney function was the highest for RCV (0.58 with creatine clearance, 0.54 with estimated glomerular filtration rate-Cockcroft-Gault). The predonation volume of the preserved kidney was (ROI, MELV, RCV) 148.0 ± 29.1 cm, 151.2 ± 35.4 and 93.9 ± 25.2 (P < 0.005 MELV vs RCV and ROI vs RCV). Bland-Altman analysis showed agreement between CT volumetry SRF and MAG3-SRF (bias, 95% limits of agreement: ROI vs MAG3 0.4%, -7.7% to 8.6%; MELV vs MAG3 0.4%, -8.9% to 9.7%; RCV vs MAG3 0.8%, -9.1% to 10.7%). The correlation between predonation CT volumetric SRF of the preserved kidney and PDKF at day 3 was r = 0.85 to 0.88, between MAG3-SRF and PDKF (r = 0.84). The difference of predonation SRF between preserved and donated kidney was the lowest for ROI and RCV (median, 3% and 4%; 95th percentile, 9% and 13%). Overall renal cortex volumetry seems to be the most accurate technique for the evaluation of predonation SRF and allows a reliable prediction of donor's PDKF.

Hepatitis A complicated with acute renal failure and high hepatocyte growth factor: A case report.

PubMed

Oe, Shinji; Shibata, Michihiko; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

2015-08-28

A 58-year-old man was admitted to our hospital. Laboratory data showed severe liver injury and that the patient was positive for immunoglobulin M anti-hepatitis A virus (HAV) antibodies. He was also complicated with severe renal dysfunction and had an extremely high level of serum hepatocyte growth factor (HGF). Therefore, he was diagnosed with severe acute liver failure with acute renal failure (ARF) caused by HAV infection. Prognosis was expected to be poor because of complications by ARF and high serum HGF. However, liver and renal functions both improved rapidly without intensive treatment, and he was subsequently discharged from our hospital on the 21(st) hospital day. Although complication with ARF and high levels of serum HGF are both important factors predicting poor prognosis in acute liver failure patients, the present case achieved a favorable outcome. Endogenous HGF might play an important role as a regenerative effector in injured livers and kidneys.

[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.

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.

Use of Readily Accessible Inflammatory Markers to Predict Diabetic Kidney Disease.

PubMed

Winter, Lauren; Wong, Lydia A; Jerums, George; Seah, Jas-Mine; Clarke, Michele; Tan, Sih Min; Coughlan, Melinda T; MacIsaac, Richard J; Ekinci, Elif I

2018-01-01

Diabetic kidney disease is a common complication of type 1 and type 2 diabetes and is the primary cause of end-stage renal disease in developed countries. Early detection of diabetic kidney disease will facilitate early intervention aimed at reducing the rate of progression to end-stage renal disease. Diabetic kidney disease has been traditionally classified based on the presence of albuminuria. More recently estimated glomerular filtration rate has also been incorporated into the staging of diabetic kidney disease. While albuminuric diabetic kidney disease is well described, the phenotype of non-albuminuric diabetic kidney disease is now widely accepted. An association between markers of inflammation and diabetic kidney disease has previously been demonstrated. Effector molecules of the innate immune system including C-reactive protein, interleukin-6, and tumor necrosis factor-α are increased in patients with diabetic kidney disease. Furthermore, renal infiltration of neutrophils, macrophages, and lymphocytes are observed in renal biopsies of patients with diabetic kidney disease. Similarly high serum neutrophil and low serum lymphocyte counts have been shown to be associated with diabetic kidney disease. The neutrophil-lymphocyte ratio is considered a robust measure of systemic inflammation and is associated with the presence of inflammatory conditions including the metabolic syndrome and insulin resistance. Cross-sectional studies have demonstrated a link between high levels of the above inflammatory biomarkers and diabetic kidney disease. Further longitudinal studies will be required to determine if these readily available inflammatory biomarkers can accurately predict the presence and prognosis of diabetic kidney disease, above and beyond albuminuria, and estimated glomerular filtration rate.

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.

Classification Models to Predict Survival of Kidney Transplant Recipients Using Two Intelligent Techniques of Data Mining and Logistic Regression.

PubMed

Nematollahi, M; Akbari, R; Nikeghbalian, S; Salehnasab, C

2017-01-01

Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD). Prediction of the transplant survival is of paramount importance. The objective of this study was to develop a model for predicting survival in kidney transplant recipients. In a cross-sectional study, 717 patients with ESRD admitted to Nemazee Hospital during 2008-2012 for renal transplantation were studied and the transplant survival was predicted for 5 years. The multilayer perceptron of artificial neural networks (MLP-ANN), logistic regression (LR), Support Vector Machine (SVM), and evaluation tools were used to verify the determinant models of the predictions and determine the independent predictors. The accuracy, area under curve (AUC), sensitivity, and specificity of SVM, MLP-ANN, and LR models were 90.4%, 86.5%, 98.2%, and 49.6%; 85.9%, 76.9%, 97.3%, and 26.1%; and 84.7%, 77.4%, 97.5%, and 17.4%, respectively. Meanwhile, the independent predictors were discharge time creatinine level, recipient age, donor age, donor blood group, cause of ESRD, recipient hypertension after transplantation, and duration of dialysis before transplantation. SVM and MLP-ANN models could efficiently be used for determining survival prediction in kidney transplant recipients.

Assessment of Plasma and NGAL for the Early Prediction of Acute Kidney Injury After Cardiac Surgery in Adults Study

ClinicalTrials.gov

2017-04-24

Acute Kidney Injury (AKI); Chronic Kidney Disease (CKD); End Stage Renal Disease (ESRD); Estimated Glomerular Filtration Rate (eGFR); Neutrophil Gelatinase-associated Lipocalin (NGAL); Serum Creatinine (SCr); Urine Creatinine (UCr); Urine Albumin (UAlb)

Optical Coherence Tomography in Kidney Transplantation

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Wierwille, Jeremiah; Chen, Yu

End-stage renal disease (ESRD) is associated with both high mortality rates and an enormous economic burden [1]. The preferred treatment option for ESRD that can extend patients' lives and improve their quality of life is kidney transplantation. However, organ shortages continue to pose a major problem in kidney transplantation. Most kidneys for transplantation come from heart-beating cadavers. Although non-heart-beating cadavers represent a potentially large pool of donor kidneys, these kidneys are not often used due to the unknown extent of damage to the renal tubules (i.e., acute tubular necrosis or "ATN") induced by ischemia (i.e., lack of blood flow). Also, ischemic insult suffered by kidneys awaiting transplantation frequently causes ATN that leads to varying degrees of delayed graft function (DGF) after transplantation. Finally, ATN represents a significant risk for eventual graft and patient survival [2, 3] and can be difficult to discern from rejection. In present clinical practice, there is no reliable real-time test to determine the viability of donor kidneys and whether or not donor kidneys might exhibit ATN. Therefore, there is a critical need for an objective and reliable real-time test to predict ATN to use these organs safely and utilize the donor pool optimally. In this review, we provided preliminary data indicating that OCT can be used to predict the post-transplant function of kidneys used in transplantation.

Level of soluble CD30 after kidney transplantation correlates with acute rejection episodes.

PubMed

Yang, J L; Hao, H J; Zhang, B; Liu, Y X; Chen, S; Na, Y Q

2008-12-01

Measurement of soluble CD30 (sCD30) levels may predict acute rejection episodes (ARE). To explore the value of sCD30 after transplantation, we tested serum sCD30 levels in 58 kidney transplant cases at 1 day before and 7 and 28 days after transplantation by enzyme-linked immunosorbent assay (ELISA). The incidences of ARE after kidney transplantation were recorded simultaneously. Meanwhile, 31 healthy individuals were selected as a control group. The results showed a relationship between sCD30 level in serum before kidney transplantation and the incidence of ARE. However, the relationship was more significant between serum sCD30 levels at day 7 after kidney transplantation and the incidence of ARE. There was no obvious relationship between serum sCD30 levels at day 28 after kidney transplantation and the incidence of ARE. These results suggested that the level of sCD30 at day 7 posttransplantation provides valuable data to predict ARE.

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.

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

B-mode Ultrasound Versus Color Doppler Twinkling Artifact in Detecting Kidney Stones

PubMed Central

Harper, Jonathan D.; Hsi, Ryan S.; Shah, Anup R.; Dighe, Manjiri K.; Carter, Stephen J.; Moshiri, Mariam; Paun, Marla; Lu, Wei; Bailey, Michael R.

2013-01-01

Abstract Purpose To compare color Doppler twinkling artifact and B-mode ultrasonography in detecting kidney stones. Patients and Methods Nine patients with recent CT scans prospectively underwent B-mode and twinkling artifact color Doppler ultrasonography on a commercial ultrasound machine. Video segments of the upper pole, interpolar area, and lower pole were created, randomized, and independently reviewed by three radiologists. Receiver operator characteristics were determined. Results There were 32 stones in 18 kidneys with a mean stone size of 8.9±7.5 mm. B-mode ultrasonography had 71% sensitivity, 48% specificity, 52% positive predictive value, and 68% negative predictive value, while twinkling artifact Doppler ultrasonography had 56% sensitivity, 74% specificity, 62% positive predictive value, and 68% negative predictive value. Conclusions When used alone, B-mode is more sensitive, but twinkling artifact is more specific in detecting kidney stones. This information may help users employ twinkling and B-mode to identify stones and developers to improve signal processing to harness the fundamental acoustic differences to ultimately improve stone detection. PMID:23067207

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.

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)

Quality of care in patients with diabetic kidney disease in Asia: The Joint Asia Diabetes Evaluation (JADE) Registry.

PubMed

Luk, A O; Li, X; Zhang, Y; Guo, X; Jia, W; Li, W; Weng, J; Yang, W; Chan, W B; Ozaki, R; Tsang, C C; Mukhopadhyay, M; Ojha, A K; Hong, E G; Yoon, K H; Sobrepena, L; Toledo, R M; Duran, M; Sheu, W; Q Do, T; Nguyen, T K; Ma, R C; Kong, A P; Chow, C C; Tong, P C; So, W Y; Chan, J C

2016-09-01

Diabetic kidney disease independently predicts cardiovascular disease and premature death. We examined the burden of chronic kidney disease (CKD, defined as an estimated GFR < 60 ml/min/1.73 m(2) ) and quality of care in a cross-sectional survey of adults (age ≥ 18 years) with Type 2 diabetes across Asia. The Joint Asia Diabetes Evaluation programme is a disease-management programme implemented using an electronic portal that systematically captures clinical characteristics of all patients enrolled. Between July 2007 and December 2012, data on 28 110 consecutively enrolled patients (China: 3415, Hong Kong: 15 196, India: 3714, Korea: 1651, Philippines: 3364, Vietnam: 692, Taiwan: 78) were analysed. In this survey, 15.9% of patients had CKD, 25.0% had microalbuminuria and 12.5% had macroalbuminuria. Patients with CKD were less likely to achieve HbA1c < 53 mmol/mol (7.0%) (36.0% vs. 42.3%) and blood pressure < 130/80 mmHg (20.8% vs. 35.3%), and were more likely to have retinopathy (26.2% vs. 8.7%), sensory neuropathy (29.0% vs. 7.7%), cardiovascular disease (26.6% vs. 8.7%) and self-reported hypoglycaemia (18.9% vs. 8.2%). Despite high frequencies of albuminuria (74.8%) and dyslipidaemia (93.0%) among CKD patients, only 49.0% were using renin-angiotensin system inhibitors and 53.6% were on statins. On logistic regression, old age, male gender, tobacco use, long disease duration, high HbA1c , blood pressure and BMI, and low LDL cholesterol were independently associated with CKD (all P < 0.05). The poor control of risk factors, suboptimal use of organ-protective drugs and high frequencies of hypoglycaemia highlight major treatment gaps in patients with diabetic kidney disease in Asia. © 2015 Diabetes UK.

Clinical outcomes associated with albuminuria in central Australia: a cohort study.

PubMed

Ritte, Rebecca; Luke, Joanne; Nelson, Craig; Brown, Alex; O'Dea, Kerin; Jenkins, Alicia; Best, James D; McDermott, Robyn; Daniel, Mark; Rowley, Kevin

2016-08-05

Chronic kidney disease (CKD) and end-stage-kidney disease (ESKD) continue to be under-diagnosed and a major burden for Aboriginal communities in central Australia. The aim of this study was to examine the risk of poor clinical outcomes associated with elevated albumin-to-creatinine ratio (ACR) among Aboriginal people in central Australia. Cox proportional hazards models were used to estimate the risk of end stage kidney disease (ESKD), dialysis, CVD (cardiovascular disease) and mortality associated with participants' baseline albuminuria reading from a 10-year cohort study of Aboriginal people (n = 623) from three communities in central Australia. Predictors of progression of albuminuria were also examined in the context of the Kidney Health Australia (KHA) Risk Matrix. A baseline ACR level of ≥3.5 mg/mmol was associated with an almost 10-fold increased risk of ESKD (95%CI 2.07-43.8) and a 15-fold risk of dialysis (95%CI 1.89-121). Albuminuria ≥3.5 mg/mmol was also associated with a borderline 63 % increased risk of CVD (95%CI 0.98-2.71). No significant association was observed with mortality from all-causes or chronic disease. Diabetes and a waist-to-hip ratio ≥0.90 independently predicted a two-fold increased risk of a progression to higher ACR levels. A single measure of moderately increased albuminuria was a strong predictor of renal failure in this population. A single spot urine ACR analysis in conjunction with the KHA Risk Matrix may be a useful and efficient strategy to screen for risk of CKD and progression to dialysis in remote communities. A focus on individuals with diabetes and/or central obesity for strategies to avoid increases in albuminuria may also prevent future CKD and CVD complications.

Preoperative predictive model for acute kidney injury after elective cardiac surgery: a prospective multicentre cohort study.

PubMed

Callejas, Raquel; Panadero, Alfredo; Vives, Marc; Duque, Paula; Echarri, Gemma; Monedero, Pablo

2018-05-11

Predictive models of CS-AKI include emergency surgery and patients with haemodynamic instability. Our objective was to evaluate the performance of validated predictive models (Thakar and Demirjian) in elective cardiac surgery and to propose a better score in the case of poor performance. A prospective, multicentre, observational study was designed. Data were collected from 942 patients undergoing cardiac surgery, after excluding emergency surgery and patients with an intraaortic balloon pump. The main outcome measure was CS-AKI defined by the composite of requiring dialysis or doubling baseline creatinine values. Both models showed poor discrimination in elective surgery (Thakar's model, AUROC = 0.57, 95% CI = 0.50-0.64 and Demirjian's model, AUROC= 0.64, 95% CI = 0.58-0.71). We generated a new model whose significant independent predictors were: anaemia, age, hypertension, obesity, congestive heart failure, previous cardiac surgery and type of surgery. It classifies patients with scores 0-3 as low risk (< 5%), scores 4-7 as medium risk (up to 15%) and scores > 8 as high risk (>30%) of developing CS-AKI with a statistically significant correlation (p <0.001). Our model reflects acceptable discriminatory ability (AUC = 0.72, 95% CI = 0.66-0.78) which is significantly better than Thakar and Demirjian's models (p<0.01). We developed a new simple predictive model of CS-AKI in elective surgery based on available preoperative information. Our new model is easy to calculate and can be an effective tool for communicating risk to patients and guiding decision-making in the perioperative period. The study requires external validation.

TCF21 hypermethylation in genetically quiescent clear cell sarcoma of the kidney | Office of Cancer Genomics

Cancer.gov

Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood tumor whose molecular pathogenesis remains poorly understood. We analyzed a discovery set of 13 CCSKs for changes in chromosome copy number, mutations, rearrangements, global gene expression and global DNA methylation. No recurrent segmental chromosomal copy number changes or somatic variants (single nucleotide or small insertion/deletion) were identified.

Simultaneous Expression from Both the Sense and Antisense Strand of the Erythropoietin Receptor Gene Mitigates Acute Lung Injury

DTIC Science & Technology

2017-09-01

Toronto) which immunoprecipitates EpoR but works poorly in immunoblots and not at in immunohistochemistry (Hu et al., Kidney Int. 2013 Sep;84(3):468-81...DAPI EpoR/GFP/DAPIGFP/DAPI C.. Ba/F32EpoR2Flag2GFP.cells 9 Figure 4. Screening the new MAbs to human RopE. Human embryonic kidney -293 (HEK-293) cells...ontogeny of EpoR and RopE expression Figure 7. Concordant RopE and EpoR expression was observed in the lung (left) and the kidney (right) that increase

Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock.

PubMed

Deep, Akash; Sagar, Hiremath; Goonasekera, Chulananda; Karthikeyan, Palaniswamy; Brierley, Joe; Douiri, Abdel

2018-07-01

There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock. Prospective cohort study. PICU of a tertiary care hospital. All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014. Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury. Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52-6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3-99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury. Manifestations of sepsis-associated acute kidney injury often occur early after PICU admission and is associated with increased morbidity and mortality. There is a need to develop a predictive model in septic shock which could facilitate early detection of acute kidney injury.

Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection.

PubMed

Weng, Shuo-Chun; Shu, Kuo-Hsiung; Wu, Ming-Ju; Wen, Mei-Chin; Hsieh, Shie-Liang; Chen, Nien-Jung; Tarng, Der-Cherng

2015-09-03

Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation.

Renal oxygenation and hemodynamics in acute kidney injury and chronic kidney disease

PubMed Central

Singh, Prabhleen; Ricksten, Sven-Erik; Bragadottir, Gudrun; Redfors, Bengt; Nordquist, Lina

2013-01-01

Summary 1. Acute kidney injury (AKI) puts a major burden on health systems that may arise from multiple initiating insults, including ischemia-reperfusion injury, cardiovascular surgery, radio-contrast administration as well as sepsis. Similarly, the incidence and prevalence of chronic kidney disease (CKD) continues to increase with significant morbidity and mortality. Moreover, an increasing number of AKI patients survive to develop CKD and end-stage kidney disease (ESRD). 2. Although the mechanisms for development of AKI and progression of CKD remain poorly understood, initial impairment of oxygen balance is likely to constitute a common pathway, causing renal tissue hypoxia and ATP starvation that will in turn induce extracellular matrix production, collagen deposition and fibrosis. Thus, possible future strategies for one or both conditions may involve dopamine, loop-diuretics, inducible nitric oxide synthase inhibitors and atrial natriuretic peptide, substances that target kidney oxygen consumption and regulators of renal oxygenation such as nitric oxide and heme oxygenase-1. PMID:23360244

Dietary sodium in chronic kidney disease: a comprehensive approach.

PubMed

Wright, Julie A; Cavanaugh, Kerri L

2010-01-01

Despite existing guidelines, dietary sodium intake among people worldwide often exceeds recommended limits. Research evidence is growing in both animal and human studies showing indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have important effects on proteinuria, efficacy of antiproteinuric pharmacologic therapy, hypertension control, maintaining an optimal volume status, and immunosuppressant therapy. Dietary sodium intake is an important consideration in patients with all stages of chronic kidney disease, including those receiving dialysis therapy or those who have received a kidney transplant. We review in detail the dietary sodium recommendations suggested by various organizations for patients with kidney disease. Potential barriers to successfully translating current sodium intake guidelines into practice include poor knowledge about the sodium content of food among both patients and providers, complex labeling information, patient preferences related to taste, and limited support for modifications in public policy. Finally, we offer existing and potential solutions that may assist providers in educating and empowering patients to effectively manage their dietary sodium intake.

Time-integrated activity coefficient estimation for radionuclide therapy using PET and a pharmacokinetic model: A simulation study on the effect of sampling schedule and noise

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

Hardiansyah, Deni

2016-09-15

Purpose: The aim of this study was to investigate the accuracy of PET-based treatment planning for predicting the time-integrated activity coefficients (TIACs). Methods: The parameters of a physiologically based pharmacokinetic (PBPK) model were fitted to the biokinetic data of 15 patients to derive assumed true parameters and were used to construct true mathematical patient phantoms (MPPs). Biokinetics of 150 MBq {sup 68}Ga-DOTATATE-PET was simulated with different noise levels [fractional standard deviation (FSD) 10%, 1%, 0.1%, and 0.01%], and seven combinations of measurements at 30 min, 1 h, and 4 h p.i. PBPK model parameters were fitted to the simulated noisymore » PET data using population-based Bayesian parameters to construct predicted MPPs. Therapy simulations were performed as 30 min infusion of {sup 90}Y-DOTATATE of 3.3 GBq in both true and predicted MPPs. Prediction accuracy was then calculated as relative variability v{sub organ} between TIACs from both MPPs. Results: Large variability values of one time-point protocols [e.g., FSD = 1%, 240 min p.i., v{sub kidneys} = (9 ± 6)%, and v{sub tumor} = (27 ± 26)%] show inaccurate prediction. Accurate TIAC prediction of the kidneys was obtained for the case of two measurements (1 and 4 h p.i.), e.g., FSD = 1%, v{sub kidneys} = (7 ± 3)%, and v{sub tumor} = (22 ± 10)%, or three measurements, e.g., FSD = 1%, v{sub kidneys} = (7 ± 3)%, and v{sub tumor} = (22 ± 9)%. Conclusions: {sup 68}Ga-DOTATATE-PET measurements could possibly be used to predict the TIACs of {sup 90}Y-DOTATATE when using a PBPK model and population-based Bayesian parameters. The two time-point measurement at 1 and 4 h p.i. with a noise up to FSD = 1% allows an accurate prediction of the TIACs in kidneys.« less

Regulated compensation for kidney donors in the Philippines.

PubMed

Padilla, Benita S

2009-04-01

The purpose of this review is to discuss the recent events and experiences in the Philippines related to compensated kidney donation. Between 2002 and 2008, the Philippine government, through the Department of Health, administered a program called the Philippine Organ Donation Program that allowed prospective kidney providers to sign up, be allocated to prospective recipients and receive gratuities for their kidney. Transplant tourism flourished during this period because of rampant disregard for the regulation limiting foreign recipients to 10% of total kidney transplants. There is evidence of inadequate donor care. Efforts to curb the problem included a ban on foreigners coming to the Philippines to have kidney transplants with Filipinos as donors as well as strengthening of the implementing rules and regulations of both the antihuman trafficking law and the organ donation law that allowed donation after brain death. The experience in the Philippines mirrored those in India and Pakistan where paid donors reported poor outcomes. An effective national kidney disease prevention program and the deceased donor program for transplantation should be aggressively promoted. Legislation against transplant commercialism is needed.

Predictive Factors of Chronic Kidney Disease in Patients with Vesicoureteral Reflux Treated Surgically and Followed after Puberty.

PubMed

Kang, Minyong; Lee, Jung Keun; Im, Young Jae; Choi, Hwang; Park, Kwanjin

2016-04-01

We delineated clinical features and determined predictors of chronic kidney disease during long-term postpubertal followup in patients with vesicoureteral reflux treated surgically. We analyzed the data of 101 patients who were surgically treated for vesicoureteral reflux and had gone through puberty. Patients underwent preoperative and postoperative voiding cystourethrography to assess reflux status, and dimercaptosuccinic acid scan to assess renal cortical defects. We compared several variables preoperatively and postpubertally, including body mass index; blood urea nitrogen, creatinine and uric acid levels; estimated glomerular filtration rate; microalbuminuria; blood pressure; renal function and renal scarring. Kaplan-Meier analysis was used to predict chronic kidney disease-free survival rates throughout the followup periods. Cox regression model was adopted to identify independent predictors of chronic kidney disease. We defined chronic kidney disease as estimated glomerular filtration rate less than 60 ml/minute/1.73 m(2). Median followup was 100.0 months (IQR 69.0 to 136.5). Median age was 16 years at last followup (IQR 14 to 18). A total of 11 patients (10.9%) were diagnosed with de novo chronic kidney disease during postpubertal followup. It is noteworthy that serum uric acid levels (HR 1.96) and presence of high grade reflux (HR 7.40) were significant predictors of chronic kidney disease on multivariate analysis. In children who were treated surgically for vesicoureteral reflux preoperative uric acid levels and high grade reflux were independent predictors of de novo chronic kidney disease during postpubertal followup. Our results offer valuable information for predicting long-term renal outcomes in patients with vesicoureteral reflux treated surgically. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Ascites and acute kidney injury].

PubMed

Piano, Salvatore; Tonon, Marta; Angeli, Paolo

2016-07-01

Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years.

Linking acute kidney injury to chronic kidney disease: the missing links.

PubMed

Kaballo, Mohammed A; Elsayed, Mohamed E; Stack, Austin G

2017-08-01

Acute kidney injury (AKI) is considered to be a major public health problem around the globe, and it is associated with major adverse clinical outcomes and significant health care costs. There is growing evidence suggesting that AKI is associated with the subsequent development of chronic kidney disease (CKD). While recovery of kidney function occurs in the majority of patients surviving an AKI episode, a large number of patients do not recover completely. Similarly, CKD is a well-known risk factor for the development of AKI. Recent studies suggest that both AKI and CKD are not separate disease entities but are in fact components of a far more closely interconnected disease continuum. However, the true nature of this relationship is complex and poorly understood. This review explores potential relationships between AKI and CKD, and seeks to uncover a number of "missing links" in this tentative emerging relationship.

Assessing the likely harms to kidney vendors in regulated organ markets.

PubMed

Koplin, Julian

2014-01-01

Advocates of paid living kidney donation frequently argue that kidney sellers would benefit from paid donation under a properly regulated kidney market. The poor outcomes experienced by participants in existing markets are often entirely attributed to harmful black-market practices. This article reviews the medical and anthropological literature on the physical, psychological, social, and financial harms experienced by vendors under Iran's regulated system of donor compensation and black markets throughout the world and argues that this body of research not only documents significant harms to vendors, but also provides reasons to believe that such harms would persist under a regulated system. This does not settle the question of whether or not a regulated market should be introduced, but it does strengthen the case against markets in kidneys while suggesting that those advocating such a system cannot appeal to the purported benefits to vendors to support their case.

Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics.

PubMed

Yerramilli, Murthy; Farace, Giosi; Quinn, John; Yerramilli, Maha

2016-11-01

Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and the presence of one is a risk for the other. CKD is an important predictor of AKI after exposure to nephrotoxic drugs or major surgery, whereas persistent or repetitive injury could result in the progression of CKD. This brings new perspectives to the diagnosis and monitoring of kidney diseases highlighting the need for a panel of kidney-specific biomarkers that reflect functional as well as structural damage and recovery, predict potential risk and provide prognosis. This article discusses the kidney-specific biomarkers, symmetric dimethylarginine (SDMA), clusterin, cystatin B, and inosine. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute kidney injury following peripheral angiography and endovascular therapy: A systematic review of the literature.

PubMed

Prasad, Anand; Ortiz-Lopez, Carolina; Khan, Aazib; Levin, Daniel; Kaye, David M

2016-08-01

Radiographic contrast administration is a major cause of acute kidney injury (AKI), worldwide. Currently, contrast induced acute kidney injury (CI-AKI) is the third leading cause of hospital acquired renal failure in the United States. Over 50% of these cases are the result of contrast exposure during cardiac catheterization. The predictive risk factors for and clinical impact of AKI following coronary procedures have been extensively studied and documented in the literature. Similar data, however, are lacking for AKI following angiography or endovascular interventions for lower extremity peripheral artery disease (PAD). The present review examined the published data available for AKI in patients undergoing peripheral procedures using MEDLINE searches. Specific data on number of peripheral cases, subject characteristics, hydration strategies, and AKI incidence rates was recorded. The systematic review resulted in 50 potentially relevant studies and ultimately 15 studies were selected for detailed analysis that included AKI incidence data on patients undergoing peripheral angiography or interventions. The summated studies included 11,311 patients and 10,316 peripheral procedures. The median incidence of AKI in the studies was 10%. The retrieved publications demonstrated significant variations in patient risk factors, definitions of AKI, and specificity of description of endovascular therapies. The incidence, risk factors, and outcomes related to AKI in the context of peripheral angiography or endovascular therapy remain poorly described in the literature and warrant further study in a prospective, systematic fashion. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

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.

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

Emotional and Financial Experiences of Kidney Donors over the Past 50 Years: The RELIVE Study.

PubMed

Jacobs, Cheryl L; Gross, Cynthia R; Messersmith, Emily E; Hong, Barry A; Gillespie, Brenda W; Hill-Callahan, Peg; Taler, Sandra J; Jowsey, Sheila G; Beebe, Tim J; Matas, Arthur J; Odim, Jonah; Ibrahim, Hassan N

2015-12-07

Most kidney donors view their experience positively, but some may experience psychosocial and financial burdens. We hypothesized that certain donor characteristics, poor outcome of the recipient, negative perceptions of care, and lack of support may be associated with poor psychosocial outcomes for donors. The Renal and Lung Living Donors Evaluation Study (RELIVE) examined long-term medical and psychosocial outcomes for kidney donors (at three U.S. transplant centers) who donated between 1963 and 2005. Standardized questionnaires evaluated donor perspectives, recovery time, social support, motivation, financial impact, insurability after donation, and current psychological status. Questionnaires were mailed to 6909 donors. Questionnaires were returned by 2455 donors, who had donated 17 ± 10 years earlier (range, 5-48 years), a response rate of 36%. Most (95%) rated their overall donation experience as good to excellent. Rating the overall donor experience more negatively was associated with donor complications, psychological difficulties, recipient graft failure, and longer time since donation. Nine percent (n=231) reported one or more of the following poor psychosocial outcomes: fair or poor overall donor experience, financial burden, regret or discomfort with decision to donate, or psychological difficulties since donation. Recipient graft failure was the only predictor for reporting one or more of these poor psychosocial outcomes (odds ratio, 1.77; 95% confidence interval, 1.33 to 2.34). Donors with lower educational attainment experienced greater financial burden. One of five employed donors took unpaid leave; 2% reported health and life insurability concerns. Although the majority of donors viewed their overall donation experience positively, almost 1 in 10 donors reported at least one negative consequence related to donation. Recipient graft failure was associated with poor psychosocial outcome, defined as one or more of these negative consequences. Some donors were financially disadvantaged, and some experienced insurance difficulties. Interventions to avoid negative psychosocial and financial consequences are warranted. Copyright © 2015 by the American Society of Nephrology.

Emotional and Financial Experiences of Kidney Donors over the Past 50 Years: The RELIVE Study

PubMed Central

Gross, Cynthia R.; Messersmith, Emily E.; Hong, Barry A.; Gillespie, Brenda W.; Hill-Callahan, Peg; Taler, Sandra J.; Jowsey, Sheila G.; Beebe, Tim J.; Matas, Arthur J.; Odim, Jonah; Ibrahim, Hassan N.

2015-01-01

Background and objectives Most kidney donors view their experience positively, but some may experience psychosocial and financial burdens. We hypothesized that certain donor characteristics, poor outcome of the recipient, negative perceptions of care, and lack of support may be associated with poor psychosocial outcomes for donors. Design, setting, participants, & measurements The Renal and Lung Living Donors Evaluation Study (RELIVE) examined long-term medical and psychosocial outcomes for kidney donors (at three U.S. transplant centers) who donated between 1963 and 2005. Standardized questionnaires evaluated donor perspectives, recovery time, social support, motivation, financial impact, insurability after donation, and current psychological status. Questionnaires were mailed to 6909 donors. Results Questionnaires were returned by 2455 donors, who had donated 17±10 years earlier (range, 5–48 years), a response rate of 36%. Most (95%) rated their overall donation experience as good to excellent. Rating the overall donor experience more negatively was associated with donor complications, psychological difficulties, recipient graft failure, and longer time since donation. Nine percent (n=231) reported one or more of the following poor psychosocial outcomes: fair or poor overall donor experience, financial burden, regret or discomfort with decision to donate, or psychological difficulties since donation. Recipient graft failure was the only predictor for reporting one or more of these poor psychosocial outcomes (odds ratio, 1.77; 95% confidence interval, 1.33 to 2.34). Donors with lower educational attainment experienced greater financial burden. One of five employed donors took unpaid leave; 2% reported health and life insurability concerns. Conclusions Although the majority of donors viewed their overall donation experience positively, almost 1 in 10 donors reported at least one negative consequence related to donation. Recipient graft failure was associated with poor psychosocial outcome, defined as one or more of these negative consequences. Some donors were financially disadvantaged, and some experienced insurance difficulties. Interventions to avoid negative psychosocial and financial consequences are warranted. PMID:26463883

Acute Kidney Injury and Big Data.

PubMed

Sutherland, Scott M; Goldstein, Stuart L; Bagshaw, Sean M

2018-01-01

The recognition of a standardized, consensus definition for acute kidney injury (AKI) has been an important milestone in critical care nephrology, which has facilitated innovation in prevention, quality of care, and outcomes research among the growing population of hospitalized patients susceptible to AKI. Concomitantly, there have been substantial advances in "big data" technologies in medicine, including electronic health records (EHR), data registries and repositories, and data management and analytic methodologies. EHRs are increasingly being adopted, clinical informatics is constantly being refined, and the field of EHR-enabled care improvement and research has grown exponentially. While these fields have matured independently, integrating the two has the potential to redefine and integrate AKI-related care and research. AKI is an ideal condition to exploit big data health care innovation for several reasons: AKI is common, increasingly encountered in hospitalized settings, imposes meaningful risk for adverse events and poor outcomes, has incremental cost implications, and has been plagued by suboptimal quality of care. In this concise review, we discuss the potential applications of big data technologies, particularly modern EHR platforms and health data repositories, to transform our capacity for AKI prediction, detection, and care quality. © 2018 S. Karger AG, Basel.

Does size matter? Kidney transplant donor size determines kidney function among living donors

PubMed Central

Narasimhamurthy, Meenakshi; Smith, Lachlan M.; Machan, Jason T.; Reinert, Steven E.; Gohh, Reginald Y.; Dworkin, Lance D.; Merhi, Basma; Patel, Nikunjkumar; Beland, Michael D.

2017-01-01

Background Kidney donor outcomes are gaining attention, particularly as donor eligibility criteria continue to expand. Kidney size, a useful predictor of recipient kidney function, also likely correlates with donor outcomes. Although donor evaluation includes donor kidney size measurements, the association between kidney size and outcomes are poorly defined. Methods We examined the relationship between kidney size (body surface area-adjusted total volume, cortical volume and length) and renal outcomes (post-operative recovery and longer-term kidney function) among 85 kidney donors using general linear models and time-to-chronic kidney disease data. Results Donors with the largest adjusted cortical volume were more likely to achieve an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 over a median 24-month follow-up than those with smaller cortical volumes (P <0.001), had a shorter duration of renal recovery (1.3–2.2 versus 32.5 days) and started with a higher eGFR at pre-donation (107–110 versus 91 mL/min/1.73 m2) and immediately post-nephrectomy (∼63 versus 50–51 mL/min/1.73 m2). Similar findings were seen with adjusted total volume and length. Conclusions Larger kidney donors were more likely to achieve an eGFR ≥60 mL/min/1.73 m2 with renal recovery over a shorter duration due to higher pre-donation and initial post-nephrectomy eGFRs. PMID:28638611

Anatomy guided automated SPECT renal seed point estimation

NASA Astrophysics Data System (ADS)

Dwivedi, Shekhar; Kumar, Sailendra

2010-04-01

Quantification of SPECT(Single Photon Emission Computed Tomography) images can be more accurate if correct segmentation of region of interest (ROI) is achieved. Segmenting ROI from SPECT images is challenging due to poor image resolution. SPECT is utilized to study the kidney function, though the challenge involved is to accurately locate the kidneys and bladder for analysis. This paper presents an automated method for generating seed point location of both kidneys using anatomical location of kidneys and bladder. The motivation for this work is based on the premise that the anatomical location of the bladder relative to the kidneys will not differ much. A model is generated based on manual segmentation of the bladder and both the kidneys on 10 patient datasets (including sum and max images). Centroid is estimated for manually segmented bladder and kidneys. Relatively easier bladder segmentation is followed by feeding bladder centroid coordinates into the model to generate seed point for kidneys. Percentage error observed in centroid coordinates of organs from ground truth to estimated values from our approach are acceptable. Percentage error of approximately 1%, 6% and 2% is observed in X coordinates and approximately 2%, 5% and 8% is observed in Y coordinates of bladder, left kidney and right kidney respectively. Using a regression model and the location of the bladder, the ROI generation for kidneys is facilitated. The model based seed point estimation will enhance the robustness of kidney ROI estimation for noisy cases.

Approaches to ascertaining comorbidity information: validation of routine hospital episode data with clinician-based case note review.

PubMed

Soo, Martin; Robertson, Lynn M; Ali, Tariq; Clark, Laura E; Fluck, Nicholas; Johnston, Marjorie; Marks, Angharad; Prescott, Gordon J; Smith, William Cairns S; Black, Corri

2014-04-21

In clinical practice, research, and increasingly health surveillance, planning and costing, there is a need for high quality information to determine comorbidity information about patients. Electronic, routinely collected healthcare data is capturing increasing amounts of clinical information as part of routine care. The aim of this study was to assess the validity of routine hospital administrative data to determine comorbidity, as compared with clinician-based case note review, in a large cohort of patients with chronic kidney disease. A validation study using record linkage. Routine hospital administrative data were compared with clinician-based case note review comorbidity data in a cohort of 3219 patients with chronic kidney disease. To assess agreement, we calculated prevalence, kappa statistic, sensitivity, specificity, positive predictive value and negative predictive value. Subgroup analyses were also performed. Median age at index date was 76.3 years, 44% were male, 67% had stage 3 chronic kidney disease and 31% had at least three comorbidities. For most comorbidities, we found a higher prevalence recorded from case notes compared with administrative data. The best agreement was found for cerebrovascular disease (κ = 0.80) ischaemic heart disease (κ = 0.63) and diabetes (κ = 0.65). Hypertension, peripheral vascular disease and dementia showed only fair agreement (κ = 0.28, 0.39, 0.38 respectively) and smoking status was found to be poorly recorded in administrative data. The patterns of prevalence across subgroups were as expected and for most comorbidities, agreement between case note and administrative data was similar. Agreement was less, however, in older ages and for those with three or more comorbidities for some conditions. This study demonstrates that hospital administrative comorbidity data compared moderately well with case note review data for cerebrovascular disease, ischaemic heart disease and diabetes, however there was significant under-recording of some other comorbid conditions, and particularly common risk factors.

Plasma Proenkephalin and Poor Long-Term Outcome in Renal Transplant Recipients

PubMed Central

Kieneker, Lyanne M.; Hartmann, Oliver; Struck, Joachim; Bergmann, Andreas; Gansevoort, Ron T.; Joosten, Michel M.; van den Berg, Else; de Boer, Rudolf A.; Bakker, Stephan J.L.

2017-01-01

Background Proenkephalin (pro-ENK), a stable and reliable surrogate marker for unstable enkephalins, was found to be associated with acute kidney injury and chronic renal failure in previous studies. We aimed to investigate whether pro-ENK is linked to chronic kidney injury and poor long-term outcome in renal transplant recipients (RTR). Methods We included 664 stable RTR and 95 healthy kidney donors. Pro-ENK was measured in plasma with a double monoclonal sandwich immunoassay. Graft failure was defined as return to dialysis therapy or retransplantation. Results Median pro-ENK was 110 pmol/L (interquartile range [IQR], 85-148 pmol/L) in RTR and 48 pmol/L (IQR, 42-55 pmol/L) in kidney donors. Pro-ENK was correlated with estimated glomerular filtration rate (GFR) (rs = −0.80, P < 0.001) in RTR and with measured GFR (rs = −0.74, P < 0.001) in kidney donors. During a median follow-up of 3.1 years (IQR, 2.7-3.9 years), 45 RTR developed graft failure and 76 died. Pro-ENK was positively associated with risk (hazard ratio [HR] per standard deviation increment of the logarithm of pro-ENK; 95% confidence interval [CI]) of graft failure (HR, 4.80; 95% CI, 3.55-6.48) and mortality (HR, 1.50; 95% CI, 1.22-1.85). After adjustment of age, sex, and estimated GFR, the association of pro-ENK with graft failure remained significant (HR, 2.36; 95% CI, 1.37-4.06), whereas no significant association of pro-ENK with risk of all-cause mortality was observed (HR, 1.34; 95% CI, 0.90-2.09). Conclusions Plasma pro-ENK is associated with kidney function as reflected by correlations with measured GFR in both RTR and kidney donors. In addition, pro-ENK was independently associated with increased risk of graft failure in RTR. Pro-ENK may aid in identification of RTR at risk for late graft failure. PMID:28795142

Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate.

PubMed

Grams, Morgan E; Sang, Yingying; Ballew, Shoshana H; Carrero, Juan Jesus; Djurdjev, Ognjenka; Heerspink, Hiddo J L; Ho, Kevin; Ito, Sadayoshi; Marks, Angharad; Naimark, David; Nash, Danielle M; Navaneethan, Sankar D; Sarnak, Mark; Stengel, Benedicte; Visseren, Frank L J; Wang, Angela Yee-Moon; Köttgen, Anna; Levey, Andrew S; Woodward, Mark; Eckardt, Kai-Uwe; Hemmelgarn, Brenda; Coresh, Josef

2018-06-01

Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m 2 . Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m 2 and 168 mg/g, respectively. Using competing-risk regression, random-effect meta-analysis, and Markov processes with Monte Carlo simulations, we developed two- and four-year models of the probability and timing of kidney failure requiring kidney replacement therapy (KRT), a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD. Hypothetically applied to a 60-year-old white male with a history of CVD, a systolic blood pressure of 140 mmHg, an eGFR of 25 ml/min/1.73m 2 and a urine albumin-to-creatinine ratio of 1000 mg/g, the four-year model predicted a 17% chance of survival after KRT, a 17% chance of survival after a CVD event, a 4% chance of survival after both, and a 28% chance of death (9% as a first event, and 19% after another CVD event or KRT). Risk predictions for KRT showed good overall agreement with the published kidney failure risk equation, and both models were well calibrated with observed risk. Thus, commonly-measured clinical characteristics can predict the timing and occurrence of clinical outcomes in patients with severely decreased GFR. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Renal Resistance Trend During Hypothermic Machine Perfusion Is More Predictive of Postoperative Outcome Than Biopsy Score: Preliminary Experience in 35 Consecutive Kidney Transplantations.

PubMed

Bissolati, Massimiliano; Gazzetta, Paolo Giovanni; Caldara, Rossana; Guarneri, Giovanni; Adamenko, Olga; Giannone, Fabio; Mazza, Michele; Maggi, Giulia; Tomanin, Deborah; Rosati, Riccardo; Secchi, Antonio; Socci, Carlo

2018-03-30

Hypothermic machine perfusion (HPM) grants a better postoperative outcome in transplantation of organs procured from extended criteria donors (ECDs) and donors after cardiac death (DCD). So far, the only available parameter for outcome prediction concerning those organs is pretransplant biopsy score. The aim of this study is to evaluate whether renal resistance (RR) trend during HPM may be used as a predictive marker for post-transplantation outcome. From December 2015 to present, HMP has been systematically applied to all organs from ECDs and DCD. All grafts underwent pretransplantation biopsy evaluation using Karpinski's histological score. Only organs that reached RR value ≤1.0 within 3 hours of perfusion were transplanted. Single kidney transplantation (SKT) or double kidney transplantation (DKT) were performed according to biopsy score results. Sixty-five HMPs were performed (58 from ECDs and 7 from DCD/ECMO donors). Fifteen kidneys were insufficiently reconditioned (RR > 1) and were therefore discarded. Forty-nine kidneys were transplanted, divided between 21 SKT and 14 DKT. Overall primary nonfunction (PNF) and delayed graft function (DGF) rate were 2.9 and 17.1%, respectively. DGF were more common in kidneys from DCD (67 vs. 7%; P = 0.004). Biopsy score did not correlate with PNF/DGF rate (P = 0.870) and postoperative creatinine trend (P = 0.796). Recipients of kidneys that reached RR ≤ 1.0 within 1 hour of HMP had a lower PNF/DGF rate (11 vs. 44%; P = 0.033) and faster serum creatinine decrease (POD10 creatinine: 1.79 mg/dL vs. 4.33 mg/dL; P = 0.019). RR trend is more predictive of post-transplantation outcome than biopsy score. Hence, RR trend should be taken into account in the pretransplantation evaluation of the organs. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival

PubMed Central

De Serres, Sacha A.; Safa, Kassem; Bijol, Vanesa; Ueno, Takuya; Onozato, Maristela L.; Iafrate, A. John; Herter, Jan M.; Lichtman, Andrew H.; Mayadas, Tanya N.; Guleria, Indira; Rennke, Helmut G.; Najafian, Nader; Chandraker, Anil

2015-01-01

Progress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival. PMID:25855773

Reassessing marketing of kidneys from the 2008 perspective.

PubMed

Friedman, Eli A; Friedman, Amy L

2009-01-01

Progressive improvements in all aspects of the kidney transplant regimen establish this form of renal replacement therapy as superior to peritoneal or hemodialysis in terms of extent of rehabilitation and long-term recipient survival. Continuous growth in the number of patients with kidney failure sustained by dialytic therapy has not been associated with substantially increased deceased donor kidney contributions, causing intensified stressful waiting periods for potential recipients lacking a live kidney donor. Neither public relation campaigns nor local government efforts have substantially increased kidney donation. Buying a donor kidney is illegal and condemned as fostering exploitation of poor people by the wealthy. Widely publicized examples of coercion of unwilling donors create a negative image of harmful, inhumane conduct deployed to obtain kidneys sold and transplanted under unsavory circumstances. Yet efforts to establish and test governmental programs to supervise and sustain acceptable standards for the sale and implantation of kidneys from fully informed, medically evaluated and protected, fairly compensated donors have been resisted and frustrated by those who consider such compensation loathsome. Accordingly, while selling kidneys is prohibited by law, pressure from those wanting to quench the number of deaths of wait-listed dialysis patients continues forcing reexamination of an issue that, like prohibition of the possession and sale of alcohol in the United States in 1920, places the will of a people in opposition to unreasonably restrictive laws. The debate continues.

Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation.

PubMed

Rees, M A; Dunn, T B; Kuhr, C S; Marsh, C L; Rogers, J; Rees, S E; Cicero, A; Reece, L J; Roth, A E; Ekwenna, O; Fumo, D E; Krawiec, K D; Kopke, J E; Jain, S; Tan, M; Paloyo, S R

2017-03-01

Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end-stage renal disease die because they cannot afford renal replacement therapy-even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed-world patient-donor pairs with immunological barriers and developing-world patient-donor pairs with financial barriers. By making developed-world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange-a modality equally benefitting rich and poor. We report the 1-year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow-up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Respiratory motion prediction and prospective correction for free-breathing arterial spin-labeled perfusion MRI of the kidneys.

PubMed

Song, Hao; Ruan, Dan; Liu, Wenyang; Stenger, V Andrew; Pohmann, Rolf; Fernández-Seara, Maria A; Nair, Tejas; Jung, Sungkyu; Luo, Jingqin; Motai, Yuichi; Ma, Jingfei; Hazle, John D; Gach, H Michael

2017-03-01

Respiratory motion prediction using an artificial neural network (ANN) was integrated with pseudocontinuous arterial spin labeling (pCASL) MRI to allow free-breathing perfusion measurements in the kidney. In this study, we evaluated the performance of the ANN to accurately predict the location of the kidneys during image acquisition. A pencil-beam navigator was integrated with a pCASL sequence to measure lung/diaphragm motion during ANN training and the pCASL transit delay. The ANN algorithm ran concurrently in the background to predict organ location during the 0.7-s 15-slice acquisition based on the navigator data. The predictions were supplied to the pulse sequence to prospectively adjust the axial slice acquisition to match the predicted organ location. Additional navigators were acquired immediately after the multislice acquisition to assess the performance and accuracy of the ANN. The technique was tested in eight healthy volunteers. The root-mean-square error (RMSE) and mean absolute error (MAE) for the eight volunteers were 1.91 ± 0.17 mm and 1.43 ± 0.17 mm, respectively, for the ANN. The RMSE increased with transit delay. The MAE typically increased from the first to last prediction in the image acquisition. The overshoot was 23.58% ± 3.05% using the target prediction accuracy of ± 1 mm. Respiratory motion prediction with prospective motion correction was successfully demonstrated for free-breathing perfusion MRI of the kidney. The method serves as an alternative to multiple breathholds and requires minimal effort from the patient. © 2017 American Association of Physicists in Medicine.

Early Outcomes of the New UK Deceased Donor Kidney Fast-Track Offering Scheme.

PubMed

Callaghan, Chris J; Mumford, Lisa; Pankhurst, Laura; Baker, Richard J; Bradley, J Andrew; Watson, Christopher J E

2017-12-01

The UK Kidney Fast-Track Scheme (KFTS) was introduced in 2012 to identify kidneys at high risk of discard and to rapidly facilitate transplantation. A retrospective analysis of kidneys transplanted through the KFTS was undertaken. UK Transplant Registry data were collected on deceased donor kidneys implanted between November 1, 2012, and April 30, 2015, (donation after brain death [DBD] donors) and March 1, 2013, and April 30, 2015 (donation after circulatory death [DCD] donors). Posttransplant outcomes included 1-year estimated glomerular filtration rate and death-censored graft survival (DCGS). Over the study period, 523 deceased donor kidneys were transplanted through the KFTS and 4174 via the standard National Kidney Allocation Scheme (NKAS). Kidneys in the KFTS were more likely to be from older diabetic donors, had a higher frequency of poor ex vivo perfusion, had longer cold ischemic times, and were transplanted into older recipients. One-year DCGS of KFTS and NKAS DBD donor kidneys was similar (94% vs 95%; P = 0.70), but for DCD donor kidneys, DCGS was lower in those allocated via the KFTS (91% versus 95%; P = 0.04). Median 1-year estimated glomerular filtration rate for DBD donor kidneys was lower in those allocated via the KFTS (49 vs 52 mL/min per 1.73 m; P = 0.01), but for DCD kidneys, there was no difference (45 vs 48 mL/min per 1.73 m; P = 0.10). Although KFTS kidneys have less favorable donor, graft, and recipient risk factors than NKAS kidneys, short-term graft and patient outcomes are acceptable. National schemes that identify and rapidly offer kidneys at high risk of discard may contribute to minimizing the unnecessary discard of organs.

Mortality prediction in patients with acute kidney injury requiring renal replacement therapy after cardiac surgery.

PubMed

Skarupskienė, Inga; Adukauskienė, Dalia; Kuzminskienė, Jurgita; Rimkutė, Laima; Balčiuvienė, Vilma; Žiginskienė, Edita; Kuzminskis, Vytautas; Adukauskaitė, Agnė; Pentiokinienė, Daiva; Bumblytė, Inga Arūnė

2017-01-01

Acute kidney injury (AKI) is a common and potentially serious postoperative complication after cardiac surgery, and it remains a cause of major morbidity and mortality. The aim of our study was to assess the prognostic illness severity score and to estimate the significant risk factors for poor outcome of patients with AKI requiring renal replacement therapy (RRT) after cardiac surgery. We retrospectively analyzed data of adult (>18 years) patients (n=111) who underwent open heart surgery and had developed AKI with need for RRT. Prognostic illness severity scores were calculated and perioperative risk factors of lethal outcome were assessed at the RRT initiation time. We defined three illness severity scores: Acute Physiology and Chronic Health Evaluation (APACHE II) as a general score, Sequential Organ Failure Assessment (SOFA) as an organ failure score, and Liano score as a kidney-specific disease severity score. Logistic regression was also used for the multivariate analysis of mortality risk factors. Hospital mortality was 76.5%. More than 7% of patients remained dialysis-dependent after their discharge from the hospital. The prognostic abilities of the scores were assessed for their discriminatory power. The area under the receiver-operating characteristic (ROC) curve of SOFA score was 0.719 (95% CI, 0.598-0.841), of Liano was 0.661 (95% CI, 0.535-0.787) and 0.668 (95% CI, 0.550-0.785) of APACHE II scores. From 16 variables analyzed for model selection, we reached a final logistic regression model, which demonstrated four variables significantly associated with patients' mortality. Glasgow coma score<14 points (OR=3.304; 95% CI, 1.130-9.662; P=0.003), mean arterial blood pressure (MAP)<63.5mmHg (OR=3.872; 95% CI, 1.011-13.616; P=0.035), serum creatinine>108.5μmol/L (OR=0.347; 95% CI, 0.123-0.998; P=0.046) and platelet count<115×10 9 /L (OR=3.731; 95% CI, 1.259-11.054; P=0.018) were independent risk factors for poor patient outcome. Our study demonstrated that SOFA score estimation is the most accurate to predict the fatal outcome in patients with AKI requiring RRT after cardiac surgery. Lethal patient outcome is related to Glasgow coma score, mean arterial blood pressure, preoperative serum creatinine and postoperative platelet count. Copyright © 2017 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Sp. z o.o. All rights reserved.

Impact of chronic kidney disease stage on lower-extremity arthroplasty.

PubMed

Deegan, Brian F; Richard, Raveesh D; Bowen, Thomas R; Perkins, Robert M; Graham, Jove H; Foltzer, Michael A

2014-07-01

End-stage renal disease and dialysis is commonly associated with poor outcomes after joint replacement surgery. The goal of this study was to evaluate postoperative complications in patients with less advanced chronic kidney disease undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Patients who underwent THA or TKA between 2004 and 2011 with stage 1, 2, or 3 chronic kidney disease were retrospectively reviewed via an electronic medical record. The authors compared 377 patients who had stage 1 to 2 chronic kidney disease with 402 patients who had stage 3 chronic kidney disease. No significant differences in 90-day readmission or revision rates were found between the stage 1 to 2 and stage 3 patient groups. For patients with stage 3 chronic kidney disease, the overall mortality rate was greater than that in patients with stage 1 to 2 chronic kidney disease. However, when adjusted for comorbid disease, no significant increases were seen in joint infection, readmission, or early revision between patients with stage 1 to 2 chronic kidney disease vs patients with stage 3 chronic kidney disease. The overall incidence of infection was high (3.5%) but far less than reported for patients with end-stage renal disease, dialysis, and kidney transplant. In conclusion, patients with stage 1, 2, or 3 chronic kidney disease may have a higher than expected rate of prosthetic joint infection (3.5%) after total joint arthroplasty. Patients with stage 3 chronic kidney disease are at higher risk for postoperative mortality compared with those with lesser stages of kidney disease. Copyright 2014, SLACK Incorporated.

Natural killer cell function predicts severe infection in kidney transplant recipients.

PubMed

Dendle, Claire; Gan, Poh-Yi; Polkinghorne, Kevan R; Ngui, James; Stuart, Rhonda L; Kanellis, John; Thursky, Karin; Mulley, William R; Holdsworth, Stephen

2018-04-30

The aim of this study was to determine if natural killer cell number (CD3 - /CD16 ± /CD56 ± ) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty-nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P = .018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.90; P < .0001) but not natural killer number (OR 0.96, 95% CI 0.93-1.00; P = .051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

Stochastic Petri Net Modeling of Hypoxia Pathway Predicts a Novel Incoherent Feed-Forward Loop Controlling SDF-1 Expression in Acute Kidney Injury.

PubMed

Heidary, Zarifeh; Ghaisari, Jafar; Moein, Shiva; Naderi, Mahmood; Gheisari, Yousof

2016-01-01

Homing of stem cells to the sites of injury is crucial for tissue regeneration. Stromal derived factor 1 (SDF-1) is among the most important chemokines recruiting these cells. Unexpectedly, our previous experimental data on mouse models of acute kidney injury showed that SDF-1 has a declining trend following ischemic kidney insult. To describe this unforeseen observation, a stochastic Petri net model of SDF-1 regulation in the hypoxia pathway was constructed based on main related components extracted from literature. Using this strategy, predictions regarding the underlying mechanisms of SDF-1 kinetics are generated and a novel incoherent feed forward loop regulating SDF-1 expression is proposed. The computational approach suggested here can be exploited to propose novel therapies for debilitating disorders such as kidney injury.

Quality of Vitamin K Antagonist Anticoagulation in Spain: Prevalence of Poor Control and Associated Factors.

PubMed

Anguita Sánchez, Manuel; Bertomeu Martínez, Vicente; Cequier Fillat, Ángel

2015-09-01

To study the prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain in patients with nonvalvular atrial fibrillation, and to identify associated factors. We studied 1056 consecutive patients seen at 120 cardiology clinics in Spain between November 2013 and March 2014. We analyzed the international normalized ratio from the 6 months prior to the patient's visit, calculating the prevalence of poorly controlled anticoagulation, defined as < 65% time in therapeutic range using the Rosendaal method. Mean age was 73.6 years (standard deviation, 9.8 years); women accounted for 42% of patients. The prevalence of poorly controlled anticoagulation was 47.3%. Mean time in therapeutic range was 63.8% (25.9%). The following factors were independently associated with poorly controlled anticoagulation: kidney disease (odds ratio = 1.53; 95% confidence interval, 1.08-2.18; P = .018), routine nonsteroidal anti-inflammatory drugs (odds ratio = 1.79; 95% confidence interval, 1.20-2.79; P = .004), antiplatelet therapy (odds ratio = 2.16; 95% confidence interval, 1.49-3.12; P < .0001) and absence of angiotensin receptor blockers (odds ratio = 1.39; 95% confidence interval, 1.08-1.79; P = .011). There is a high prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain. Factors associated with poor control are kidney disease, routine nonsteroidal anti-inflammatory drugs, antiplatelet use, and absence of angiotensin receptor blockers. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

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.

Dietary sugar and artificial sweetener intake and chronic kidney disease: a review.

PubMed

Karalius, Vytas P; Shoham, David A

2013-03-01

Sugar consumption, especially in the form of fructose, has been hypothesized to cause kidney disease. This review provides an overview of the epidemiologic evidence that sugar consumption increases CKD risk. Research supports a causal role of sugar in several kidney disease risk factors, including increasing serum uric acid levels, diabetes, and obesity. Sugar may also harm the kidney via other mechanisms. There is no evidence that sucrose is any safer for the kidney than high fructose corn syrup (HFCS) because both are similar in composition. To date, 5 epidemiologic studies have directly evaluated the relationship between sugar consumption (in the form of sugar-sweetened beverages) and CKD. Although most studies suggest that the risk of CKD is elevated among consumers of sugar-sweetened beverages, only 2 studies report statistically significant associations. Three studies have also examined diet soda consumption, with two reporting positive and significant associations. Confounding by unmeasured lifestyle factors may play a role in the positive results whereas poor measurement of sugar and artificial sweetener intake could explain null results. Nevertheless, the hypothesis that sugar causes kidney disease remains plausible, and alternative research designs may be needed. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The need for kidney transplantation in low- and middle-income countries in 2012: an epidemiological perspective.

PubMed

Muralidharan, Aditya; White, Sarah

2015-03-01

Epidemiological and demographic transitions are shifting the burden of modifiable risk factors for chronic and end-stage kidney disease to low- and middle-income countries (LMIC). This shifting burden of disease--combined with economic transitions and health system reforms--has led to the rapid growth of dialysis populations in LMIC including Malaysia, Tunisia, Turkey, Chile, Mexico, and Uruguay. Yet, compared to 1.5 million on dialysis in LMIC, only approximately 33,000 kidney transplants were performed in 2012. Reasons include health system factors (personnel, infrastructure, system coordination, and financing) and cultural factors (public and professional attitudes and the legal environment). The size of the dialysis populations, however, is generally a poor indicator of the potential need for kidney transplantation in LMIC. Population needs for kidney transplantation should instead be assessed based on the epidemiology of the actual underlying burden of disease (both treated and untreated), and the costs and benefits of treatment as well as prevention strategies relative to existing service provision. Here, we review current data on the global burden of end-stage kidney disease and the distribution of major risk factors, and compare this to access to kidney transplantation in 2012.

Folate deficiency

MedlinePlus

... as phenytoin, sulfasalazine, or trimethoprim-sulfamethoxazole) Eating an unhealthy diet that does not include enough fruits and vegetables Kidney dialysis Symptoms Folic acid deficiency may cause: Fatigue, irritability, or diarrhea Poor growth Smooth and ...

Transcript profiling of Wilms tumors reveals connections to kidney morphogenesis and expression patterns associated with anaplasia.

PubMed

Li, Wenliang; Kessler, Patricia; Williams, Bryan R G

2005-01-13

Anaplasia (unfavorable histology) is associated with therapy resistance and poor prognosis of Wilms tumor, but the molecular basis for this phenotype is unclear. Here, we used a cDNA array with 9240 clones relevant to cancer biology and/or kidney development to examine the expression profiles of 54 Wilms tumors, five normal kidneys and fetal kidney. By linking genes differentially expressed between fetal kidney and Wilms tumors to kidney morphogenesis, we found that genes expressed at a higher level in Wilms tumors tend to be expressed more in uninduced metanephrogenic mesenchyme or blastema than in their differentiated structures. Conversely, genes expressed at a lower level in Wilms tumors tend to be expressed less in uninduced metanephrogenic mesenchyme or blastema. We also identified 97 clones representing 76 Unigenes or unclustered ESTs that clearly separate anaplastic Wilms tumors from tumors with favorable histology. Genes in this set provide insight into the nature of the abnormal nuclear morphology of anaplastic tumors and may facilitate identification of molecular targets to improve their responsiveness to treatment.

Dietary Sodium in Chronic Kidney Disease: A Comprehensive Approach

PubMed Central

Wright, Julie A.; Cavanaugh, Kerri L.

2010-01-01

Despite existing guidelines, dietary sodium intake among people worldwide often exceeds recommended limits. Research evidence is growing in both animal and human studies showing indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have important effects on proteinuria, efficacy of antiproteinuric pharmacologic therapy, hypertension control, maintaining an optimal volume status, and immunosuppressant therapy. Dietary sodium intake is an important consideration in patients with all stages of chronic kidney disease, including those receiving dialysis therapy or those who have received a kidney transplant. We review in detail the dietary sodium recommendations suggested by various organizations for patients with kidney disease. Potential barriers to successfully translating current sodium intake guidelines into practice include poor knowledge about the sodium content of food among both patients and providers, complex labeling information, patient preferences related to taste, and limited support for modifications in public policy. Finally, we offer existing and potential solutions that may assist providers in educating and empowering patients to effectively manage their dietary sodium intake. PMID:20557489

Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of Exercise to Prevent and Treat Physical Impairments in CKD.

PubMed

Roshanravan, Baback; Gamboa, Jorge; Wilund, Kenneth

2017-06-01

Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high risk for mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment that includes rehabilitative therapies and counseling on physical activity. Exercise has beneficial effects on systemic inflammation, muscle, and physical performance in chronic kidney disease. Kidney health providers need to identify patient and care delivery barriers to exercise in order to effectively counsel patients on physical activity. A thorough medical evaluation and assessment of baseline function using self-reported and objective function assessment is essential to guide an effective individualized exercise prescription to prevent function decline in persons with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disablement process and reviews screening and treatment strategies that kidney health professionals can use in clinical practice to prevent functional decline and disability. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Awareness level of kidney functions and diseases among adults in a Nigerian population

PubMed Central

Okwuonu, C. G.; Chukwuonye, I. I.; Ogah, S. O.; Abali, C.; Adejumo, O. A.; Oviasu, E.

2015-01-01

The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher – administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18–78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria. PMID:26060365

Pharmacological strategies for kidney function preservation: are there differences by ethnicity?

PubMed

Lakkis, Jay; Weir, Matthew R

2004-01-01

The prevalence of chronic kidney disease (CKD) is on the rise in all ethnic groups. This is because of the increased prevalence of obesity, diabetes mellitus, the metabolic syndrome, and the inadequate control of elevated blood pressure and other cardiovascular-renal risk factors, especially in ethnic minority populations. The implications of the aforementioned trends in risk factor prevalence and control are profound. Moreover, these trends negatively impact patient quality of life and place an enormous financial burden on the health care system for the provision of care to patients with CKD, end-stage renal disease (ESRD), and/or cardiovascular disease (CVD). Thus, it is of utmost importance to devise strategies that prevent kidney disease and delay progressive loss of kidney function in persons with CKD. Proven strategies include pharmacological interventions that lower blood pressure to less than target levels (<130/80 mm Hg), attainment of optimal glycemic control (Hb A1c <7%), and reducing urinary protein excretion. It is also possible, although yet unproven, that correction of anemia and aggressive treatment of dyslipidemia may forestall the loss of kidney function. In general, ethnic minorities are underrepresented in most large trials. Recently, a few outcome clinical trials in blacks have reinforced the lessons of kidney function preservation already learned in nonblack populations. That is, the reversible risk factors for CKD appear to be virtually identical and, at least in nondiabetic CKD, pharmacological targeting of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers preserves kidney function better than non-RAAS blood pressure-lowering regimens, especially when significant proteinuria exists. Although more CKD studies in ethnic minorities are needed, until they become available, the best available evidence from the existing clinical trial database should be applied to minorities with CKD-even when specific data are not available for a specific racial or ethnic group. Why this approach? First, there are no known unique risk factors for kidney disease in any ethnic group. Second, poor control of reversible risk factors for CKD is universal, particularly in blacks and other ethnic minorities. Thus, it is logical to predict that more efficient use of strategies proven to forestall loss of kidney function will reduce the excess of CKD and ESRD in ethnic minorities relative to non-minority populations. However, medical-based strategies alone are probably not enough. The global epidemic of obesity will fuel the growing population of persons, especially among ethnic minorities, with diabetes, the main cause of CKD, ESRD, and CVD. The obesity and diabetes epidemics are unlikely to abate without innovative and ultimately effective public health approaches.

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

Non-Integrated Information and Communication Technologies in the Kidney Transplantation Process in Brazil.

PubMed

Peres Penteado, Alissa; Fábio Maciel, Rafael; Erbs, João; Feijó Ortolani, Cristina Lucia; Aguiar Roza, Bartira; Torres Pisa, Ivan

2015-01-01

The entire kidney transplantation process in Brazil is defined through laws, decrees, ordinances, and resolutions, but there is no defined theoretical map describing this process. From this representation it's possible to perform analysis, such as the identification of bottlenecks and information and communication technologies (ICTs) that support this process. The aim of this study was to analyze and represent the kidney transplantation workflow using business process modeling notation (BPMN) and then to identify the ICTs involved in the process. This study was conducted in eight steps, including document analysis and professional evaluation. The results include the BPMN model of the kidney transplantation process in Brazil and the identification of ICTs. We discovered that there are great delays in the process due to there being many different ICTs involved, which can cause information to be poorly integrated.

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.

Treatment and prevention of kidney stones: an update.

PubMed

Frassetto, Lynda; Kohlstadt, Ingrid

2011-12-01

The incidence of nephrolithiasis (kidney stones) is rising worldwide, especially in women and with increasing age. Kidney stones are associated with chronic kidney disease. Preventing recurrence is largely specific to the type of stone (e.g., calcium oxalate, calcium phosphate, cystine, struvite [magnesium ammonium phosphate]), and uric acid stones); however, even when the stone cannot be retrieved, urine pH and 24-hour urine assessment provide information about stone-forming factors that can guide prevention. Medications, such as protease inhibitors, antibiotics, and some diuretics, increase the risk of some types of kidney stones, and patients should be counseled about the risks of using these medications. Managing diet, medication use, and nutrient intake can help prevent the formation of kidney stones. Obesity increases the risk of kidney stones. However, weight loss could undermine prevention of kidney stones if associated with a high animal protein intake, laxative abuse, rapid loss of lean tissue, or poor hydration. For prevention of calcium oxalate, cystine, and uric acid stones, urine should be alkalinized by eating a diet high in fruits and vegetables, taking supplemental or prescription citrate, or drinking alkaline mineral waters. For prevention of calcium phosphate and struvite stones, urine should be acidified; cranberry juice or betaine can lower urine pH. Antispasmodic medications, ureteroscopy, and metabolic testing are increasingly being used to augment fluid and pain medications in the acute management of kidney stones.

Pretransplant Tacrolimus Dose Requirements Predict Early Posttransplant Dose Requirements in Blood Group AB0-Incompatible Kidney Transplant Recipients.

PubMed

Shuker, Nauras; de Man, Femke M; de Weerd, Annelies E; van Agteren, Madelon; Weimar, Willem; Betjes, Michiel G H; van Gelder, Teun; Hesselink, Dennis A

2016-04-01

The aim of this study was to investigate whether pretransplant tacrolimus (Tac) dose requirements of patients scheduled to undergo living donor kidney transplantation correlate with posttransplantation dose requirements. The predictive value of Tac dose requirements (defined as the ratio of the Tac predose concentration, C0, divided by the total daily Tac dose, D) pretransplantation on this same parameter posttransplantation was assessed retrospectively in a cohort of 57 AB0-incompatible kidney transplant recipients. These patients started immunosuppressive therapy 14 days before transplant surgery. All patients were using a stable dose of glucocorticoids and were at steady-state Tac exposure before transplantation. Tac dose requirements immediately before transplantation (C0/Dbefore) explained 63% of the Tac dose requirements on day 3 after transplantation: r = 0.633 [F (1, 44) = 75.97, P < 0.01]. No other clinical and demographic variables predicted Tac dose requirements early after transplantation. Steady-state Tac dose requirement before transplantation largely predicted posttransplantation Tac dose requirements in AB0-incompatible kidney transplant recipients. The importance of this finding is that the posttransplantation Tac dose can be individualized based on a patient's pretransplantation Tac concentration/dose ratio. Pretransplant Tac phenotyping therefore has the potential to improve transplantation outcomes.

Reliability of CKD-EPI predictive equation in estimating chronic kidney disease prevalence in the Croatian endemic nephropathy area.

PubMed

Fuček, Mirjana; Dika, Živka; Karanović, Sandra; Vuković Brinar, Ivana; Premužić, Vedran; Kos, Jelena; Cvitković, Ante; Mišić, Maja; Samardžić, Josip; Rogić, Dunja; Jelaković, Bojan

2018-02-15

Chronic kidney disease (CKD) is a significant public health problem and it is not possible to precisely predict its progression to terminal renal failure. According to current guidelines, CKD stages are classified based on the estimated glomerular filtration rate (eGFR) and albuminuria. Aims of this study were to determine the reliability of predictive equation in estimation of CKD prevalence in Croatian areas with endemic nephropathy (EN), compare the results with non-endemic areas, and to determine if the prevalence of CKD stages 3-5 was increased in subjects with EN. A total of 1573 inhabitants of the Croatian Posavina rural area from 6 endemic and 3 non-endemic villages were enrolled. Participants were classified according to the modified criteria of the World Health Organization for EN. Estimated GFR was calculated using Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). The results showed a very high CKD prevalence in the Croatian rural area (19%). CKD prevalence was significantly higher in EN then in non EN villages with the lowest eGFR value in diseased subgroup. eGFR correlated significantly with the diagnosis of EN. Kidney function assessment using CKD-EPI predictive equation proved to be a good marker in differentiating the study subgroups, remained as one of the diagnostic criteria for EN.

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

The exciting "bench to bedside" journey of cell therapies for acute kidney injury and renal transplantation.

PubMed

Dellepiane, Sergio; Medica, Davide; Quercia, Alessandro Domenico; Cantaluppi, Vincenzo

2017-06-01

Acute kidney injury (AKI) is characterized by an increasing incidence and poor outcomes in both developed and undeveloped countries. AKI is also acquiring importance in the setting of kidney transplantation (KT): besides all the classical forms of AKI that KT patients may undergo, several transplant-specific injuries can also lead to the loss of graft function. The mechanisms of tissue damage in native and grafted kidneys share several common pathogenic elements. Since appropriate therapeutic treatments are still lacking-probably due to the disease complexity-clinicians are forced to provide only supportive care. In this composite scenario, cell therapies represent an evolving frontier for AKI treatment in native and transplanted kidneys: ex-vivo manipulated stem or immune cells are able to counteract renal dysfunction by a wide range of biological mechanisms. In this review, we will discuss the potential applications of cell therapies in AKI and KT by analyzing the available clinical data and the most promising experimental prospects from a "bench to bedside" perspective.

Pleomorphic leiomyosarcoma with a dedifferentiation-like appearance in the kidney: case report and literature review.

PubMed

Tajima, Shogo; Waki, Michihiko; Fukuyama, Masashi

2016-12-01

Although primary leiomyosarcoma of the kidney is extremely rare, it is the most common sarcoma of the kidney. Leiomyosarcoma with a large pleomorphic component is designated as pleomorphic leiomyosarcoma. The pleomorphic component is usually similar to undifferentiated high-grade pleomorphic sarcoma, although it variably expresses smooth muscle markers on immunohistochemistry. In the few reported cases of pleomorphic leiomyosarcoma of the kidney, cases with the pleomorphic component showing distinct nodularity similar to dedifferentiated leiomyosarcoma have not been described, to the best of our knowledge. Herein, we present a case of a 49-year-old woman with pleomorphic leiomyosarcoma in the kidney showing distinct nodularity of smooth muscle marker-expressing pleomorphic cells within a background of classic leiomyosarcoma. Along with the classification as a pleomorphic leiomyosarcoma, suggesting aggressive clinical behavior, the renal origin itself might also be a predictor of poor prognosis, as shown in a previous study. This case also involved concomitant distant metastases, already present during the initial detection of the renal tumor.

Uranium XAFS analysis of kidney from rats exposed to uranium

PubMed Central

Kitahara, Keisuke; Numako, Chiya; Terada, Yasuko; Nitta, Kiyohumi; Homma-Takeda, Shino

2017-01-01

The kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine-structure (µXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The U L III-edge X-ray absorption near-edge structure spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175 keV) although the peak widths for some kidney specimens were slightly narrowed. µXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate. PMID:28244440

Uranium XAFS analysis of kidney from rats exposed to uranium.

PubMed

Kitahara, Keisuke; Numako, Chiya; Terada, Yasuko; Nitta, Kiyohumi; Shimada, Yoshiya; Homma-Takeda, Shino

2017-03-01

The kidney is the critical target of uranium exposure because uranium accumulates in the proximal tubules and causes tubular damage, but the chemical nature of uranium in kidney, such as its chemical status in the toxic target site, is poorly understood. Micro-X-ray absorption fine-structure (µXAFS) analysis was used to examine renal thin sections of rats exposed to uranyl acetate. The U L III -edge X-ray absorption near-edge structure spectra of bulk renal specimens obtained at various toxicological phases were similar to that of uranyl acetate: their edge position did not shift compared with that of uranyl acetate (17.175 keV) although the peak widths for some kidney specimens were slightly narrowed. µXAFS measurements of spots of concentrated uranium in the micro-regions of the proximal tubules showed that the edge jump slightly shifted to lower energy. The results suggest that most uranium accumulated in kidney was uranium (VI) but a portion might have been biotransformed in rats exposed to uranyl acetate.

Adaptive functional change of the contralateral kidney after partial nephrectomy.

PubMed

Choi, Se Young; Yoo, Sangjun; You, Dalsan; Jeong, In Gab; Song, Cheryn; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

2017-08-01

Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1 : <30 ml·min -1 ·1.73 m -2 , group 2 : 30-45 ml·min -1 ·1.73 m -2 , and group 3 : ≥45 ml·min -1 ·1.73 m -2 ). Multiple-regression analysis was used to identify the factors associated with increased GFR of the contralateral kidney over a 4-yr postoperative period. Patients in group 1 had a higher mean age and hypertension history, worse American Society of Anesthesiologists score, and larger tumor size than in the other two groups. The ipsilateral GFR changes at 4 yr after partial nephrectomy were -18.9, -3.6, and 3.9% in groups 1 , 2 , and 3 , respectively, whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [β: -0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative contralateral GFR (β: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were significant predictive factors for increased GFR of the contralateral kidney after 4 yr. The contralateral kidney compensated for the functional loss of the ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in younger patients with decreased contralateral renal function. Copyright © 2017 the American Physiological Society.

Abrupt Decline in Kidney Function Before Initiating Hemodialysis and All-Cause Mortality: The Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Hsu, Raymond K; Chai, Boyang; Roy, Jason A; Anderson, Amanda H; Bansal, Nisha; Feldman, Harold I; Go, Alan S; He, Jiang; Horwitz, Edward J; Kusek, John W; Lash, James P; Ojo, Akinlolu; Sondheimer, James H; Townsend, Raymond R; Zhan, Min; Hsu, Chi-Yuan

2016-08-01

It is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy. Prospective cohort study. The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation. The primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point. All-cause mortality within 1 year after initiating hemodialysis therapy. Multivariable Cox proportional hazards. Among 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76). Relatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data. Abrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

Periodontitis associated with chronic kidney disease among Mexican Americans.

PubMed

Ioannidou, Effie; Hall, Yoshio; Swede, Helen; Himmelfarb, Jonathan

2013-01-01

In comparison to non-Hispanic whites, a number of health-care disparities, including poor oral health, have been identified among Hispanics in general and Mexican Americans in particular. We hypothesized that Mexican Americans with chronic kidney disease (CKD) would have higher prevalence of chronic periodontitis compared with Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. We examined this hypothesis using the National Health and Nutrition Examination Survey 1988-1994 (NHANES III) data set. We followed the American Academy of Periodontology/Center for Disease Control and Prevention case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (P<0.001). Mexican Americans with reduced kidney function were twofold more likely to have periodontitis compared with Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes, and socioeconomic status. Multivariate adjusted odds ratio for periodontitis significantly increased with 1, 5, and 10 mL/minute estimated glomerular filtration rate reduction from the mean. This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. © 2012 American Association of Public Health Dentistry.

Periodontitis associated with Chronic Kidney Disease among Mexican Americans

PubMed Central

Ioannidou, Effie; Hall, Yoshio; Swede, Helen; Himmelfarb, Jonathan

2012-01-01

Objective In comparison to non-Hispanic whites, a number of healthcare disparities, including poor oral health, have been identified among Hispanics in general and Mexican-Americans in particular. We hypothesized that Mexican-Americans with Chronic Kidney disease (CKD) would have higher prevalence of chronic periodontitis compared to Mexican Americans with normal kidney function, and that the level of kidney function would be inversely related to the prevalence of periodontal disease. Method We examined this hypothesis using the National Health and Nutrition Examination Survey 1988–1994 (NHANES III) dataset. We followed the American Academy of Periodontology (AAP)/Center for Disease Control and Prevention (CDC) case definition for periodontitis. Glomerular filtration rate was estimated using the CKD-Epidemiology (EPI) equation for Hispanic populations. The classification to CKD stages was based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Results Periodontitis prevalence increased across the kidney function groups showing a statistically significant dose-response association (p<0.001). Mexican Americans with reduced kidney function were 2-fold more likely to have periodontitis compared to Mexican Americans with normal kidney function after adjusting for potential confounders such as smoking, diabetes and socioeconomic status. Multivariate adjusted Odds Ratio for periodontitis significantly increased with 1, 5 and 10 mL/minute eGFR reduction from the mean. Conclusion This is the first report, to the best our knowledge, that showed an increase of periodontitis prevalence with decreased kidney function in this population. PMID:22775287

Change of sleep quality from pre- to 3 years post-solid organ transplantation: The Swiss Transplant Cohort Study

PubMed Central

Denhaerynck, Kris; Huynh-Do, Uyen; Binet, Isabelle; Hadaya, Karine; De Geest, Sabina

2017-01-01

Background Poor sleep quality (SQ) is common after solid organ transplantation; however, very little is known about its natural history. We assessed the changes in SQ from pre- to 3 years post-transplant in adult heart, kidney, liver and lung recipients included in the prospective nation-wide Swiss Transplant Cohort Study. We explored associations with selected variables in patients suffering persistent poor SQ compared to those with good or variable SQ. Methods Adult single organ transplant recipients enrolled in the Swiss Transplant Cohort Study with pre-transplant and at least 3 post-transplant SQ assessment data were included. SQ was self-reported pre-transplant (at listing), then at 6, 12, 24 and 36 months post-transplant. A single SQ item was used to identify poor (0–5) and good sleepers (6–10). Between organ groups, SQ was compared via logistic regression analysis with generalized estimating equations. Within the group reporting persistently poor SQ, we used logistic regression or Kaplan-Meier analysis as appropriate to check for differences in global quality of life and survival. Results In a sample of 1173 transplant patients (age: 52.1±13.2 years; 65% males; 66% kidney, 17% liver, 10% lung, 7% heart) transplanted between 2008 and 2012, pre- transplant poor SQ was highest in liver (50%) and heart (49%) recipients. Overall, poor SQ decreased significantly from pre-transplant (38%) to 24 months post-transplant (26%) and remained stable at 3 years (29%). Patients reporting persistently poor SQ had significantly more depressive symptomatology and lower global quality of life. Conclusion Because self-reported poor SQ is related to poorer global quality of life, these results emphasize the need for further studies to find suitable treatment options for poor SQ in transplant recipients. PMID:29020112

Aortic PWV in Chronic Kidney Disease: A CRIC Ancillary Study

PubMed Central

Townsend, Raymond R.; Wimmer, Neil J.; Chirinos, Julio A.; Parsa, Afshin; Weir, Matthew; Perumal, Kalyani; Lash, James P.; Chen, Jing; Steigerwalt, Susan P.; Flack, John; Go, Alan S.; Rafey, Mohammed; Rahman, Mahboob; Sheridan, Angela; Gadegbeku, Crystal A.; Robinson, Nancy A.; Joffe, Marshall

2009-01-01

Background Aortic PWV is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV. Methods We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in chronic kidney disease. Results PWV measurements were obtained in 2564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were < 7.7 m/sec, 7.7–10.2 m/sec and > 10.2 m/sec with an overall mean (± S.D.) value of 9.48 ± 3.03 m/sec [95% CI = 9.35–9.61 m/sec]. Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function. Conclusions The large size of this unique cohort, and the targeted enrollment of chronic kidney disease participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure. PMID:20019670

Renal Allograft Outcome After Simultaneous Heart and Kidney Transplantation.

PubMed

Grupper, Avishay; Grupper, Ayelet; Daly, Richard C; Pereira, Naveen L; Hathcock, Matthew A; Kremers, Walter K; Cosio, Fernando G; Edwards, Brooks S; Kushwaha, Sudhir S

2017-08-01

Chronic kidney disease frequently accompanies end-stage heart failure and may result in consideration of simultaneous heart and kidney transplantation (SHKT). In recent years, there has been a significant increase in SHKT. This single-center cohort consisted of 35 patients who underwent SHKT during 1996 to 2015. The aim of this study was to review factors that may predict better long-term outcome after SKHT. Thirteen patients (37%) had delayed graft function (DGF) after transplant (defined as the need for dialysis during the first 7 days after transplant), which was significantly associated with mechanical circulatory support device therapy and high right ventricular systolic pressure before transplant. Most of the recipients had glomerular filtration rate (GFR) ≥50 ml/min/1.73 m 2 at 1 and 3 years after transplant (21 of 26 [81%] and 20 of 21 [95%], respectively). Higher donor age was associated with reduced 1-year GFR (p = 0.017), and higher recipient pretransplant body mass index was associated with reduced 3-year GFR (p = 0.008). There was a significant association between DGF and reduced median GFR at 1 and 3 years after transplant (p <0.005). Patient survival rates at 6 months, 1, and 3 years after transplant were 97%, 91%, and 86% respectively. In conclusions, our data support good outcomes after SHKT. Mechanical circulatory support device therapy and pulmonary hypertension before transplant are associated with DGF, which is a risk factor for poor long-term renal allograft function. Copyright © 2017 Elsevier Inc. All rights reserved.

The weekend effect alters the procurement and discard rates of deceased donor kidneys in the United States

PubMed Central

Mohan, Sumit; Foley, Karl; Chiles, Mariana C; Dube, Geoffrey K; Patzer, Rachel E; Pastan, Stephen; Crew, R John; Cohen, David; Ratner, Lloyd

2016-01-01

Factors contributing to the high rate of discard among deceased donor kidneys remain poorly understood and the influence of resource limitations of weekends on kidney transplantation is unknown. To quantify this we used data from the Scientific Registry of Transplant Recipients and assembled a retrospective cohort of 181,799 deceased donor kidneys recovered for transplantation from 2000-2013. We identified the impact of the day of the week on the procurement and subsequent utilization or discard of deceased donor kidneys in the United States, as well as report the geographic variation on the impact of weekends on transplantation. Compared to weekday kidneys, organs procured on weekends were significantly more likely to be discarded than transplanted (odds ratio: 1.16; 95% confidence interval 1.13 – 1.19), even after adjusting for organ quality (adjusted odds ratio: 1.13; 95% confidence interval 1.10 – 1.17). Weekend discards were of a significantly higher quality than weekday discards (kidney donor profile index: 76.5 vs 77.3%). Considerable geographic variation was noted in the proportion of transplants that occurred over the weekend. Kidneys available for transplant over the weekend were significantly more likely to be used at larger transplant centers, be shared without payback, and experienced shorter cold ischemia times. Thus, factors other than kidney quality are contributing to the discard of deceased donor kidneys, particularly during weekends. Policy prescriptions, administrative or organizational solutions within transplant programs may potentially mitigate against the recent increase in kidney discards. PMID:27182001

Perioperative change in creatinine following cardiac surgery with cardiopulmonary bypass is useful in predicting acute kidney injury: a single-centre retrospective cohort study.

PubMed

Takaki, Shunsuke; Shehabi, Yahya; Pickering, John W; Endre, Zoltan; Miyashita, Tetsuya; Goto, Takahisa

2015-10-01

Acute kidney injury is common following cardiac surgery. Experimental models of acute kidney injury suggest that successful therapy should be implemented within 24-48 h of renal injury. However, it is difficult to detect acute kidney injury shortly after cardiac surgery, because creatinine concentration is diluted by cardiopulmonary bypass. We hypothesized that, following cardiopulmonary bypass, creatinine reduction ratios would correlate with haematocrit reduction ratios and would be associated with the incidence of acute kidney injury. We collected demographic and blood test data from consecutive patients (n = 1137) who had undergone cardiac surgery with cardiopulmonary bypass. The creatinine reduction ratio was calculated as follows: (preoperative creatinine-postoperative creatinine)/preoperative creatinine. Patients were assigned to either of two groups. The first group (Group 1) was used to determine the threshold for acute kidney injury, and the second group (Group 2) was used to assess diagnostic performance. Acute kidney injury was defined as an increase in serum creatinine level >0.3 mg/dl or >150% from baseline. The incidence of acute kidney injury was 14.5% (79/545) in Group 1 and 15.5% (92/592) in Group 2. Postoperatively, creatinine concentration correlated strongly with haematocrit concentration (Pearson's r(2): 0.91). In Group 1, the area under the receiver operating characteristic curve, sensitivity and specificity were 0.71, 64.1 and 66.4%, respectively, for creatinine reduction ratios of <20%. In Group 2, the odds ratio, positive predictive value, negative predictive value and relative risk for creatinine reduction ratio performance were 4.3 (95% confidence interval 2.6-7.0), 0.27 (0.21-0.32), 0.92 (0.89-0.95) and 3.42 (2.22-5.27), respectively. The creatinine reduction ratio may be associated with perioperative renal injury. Therefore, it is a good diagnostic indicator with high performance, and may be useful in detecting acute kidney injury at an earlier stage relative to conventional means. In addition, using creatinine reduction ratios in this manner is financially feasible. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. 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.

Effect of Replacing Race with Apolipoprotein L1 Genotype in Calculation of Kidney Donor Risk Index

PubMed Central

Julian, B. A.; Gaston, R. S.; Brown, W. M.; Reeves-Daniel, A. M.; Israni, A. K.; Schladt, D. P.; Pastan, S. O.; Mohan, S.; Freedman, B. I.; Divers, J.

2016-01-01

Renal allografts from deceased African Americans with two apolipoprotein L1 gene (APOL1) renal-risk variants fail sooner than kidneys from donors with fewer variants. Kidney Donor Risk Index (KDRI) was developed to evaluate organ offers by predicting allograft longevity and includes African American race as a risk factor. Substituting APOL1 genotype for race may refine the KDRI. For 622 deceased African American kidney donors, we applied 10-fold cross-validation approach to estimate contribution of APOL1 variants to a revised KDRI. Cross-validation was repeated 10,000 times to generate distribution of effect size associated with APOL1 genotype. Average effect size was used to derive the revised KDRI weighting. Mean current-KDRI score for all donors was 1.4930 versus mean revised-KDRI score 1.2518 for 529 donors with 0/1 variant and 1.8527 for 93 donors with 2 variants. Original and revised KDRIs had comparable survival prediction errors after transplantation, but the spread in Kidney Donor Profile Index based on presence/absence of 2 APOL1 variants was 37 percentage points. Replacing donor race with APOL1 genotype in KDRI better defines risk associated with kidneys transplanted from deceased African American donors, substantially improves KDRI score for 85-90% of kidneys offered, and enhances the link between donor quality and recipient need. PMID:27862962

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.

Methodological issues in current practice may lead to bias in the development of biomarker combinations for predicting acute kidney injury.

PubMed

Meisner, Allison; Kerr, Kathleen F; Thiessen-Philbrook, Heather; Coca, Steven G; Parikh, Chirag R

2016-02-01

Individual biomarkers of renal injury are only modestly predictive of acute kidney injury (AKI). Using multiple biomarkers has the potential to improve predictive capacity. In this systematic review, statistical methods of articles developing biomarker combinations to predict AKI were assessed. We identified and described three potential sources of bias (resubstitution bias, model selection bias, and bias due to center differences) that may compromise the development of biomarker combinations. Fifteen studies reported developing kidney injury biomarker combinations for the prediction of AKI after cardiac surgery (8 articles), in the intensive care unit (4 articles), or other settings (3 articles). All studies were susceptible to at least one source of bias and did not account for or acknowledge the bias. Inadequate reporting often hindered our assessment of the articles. We then evaluated, when possible (7 articles), the performance of published biomarker combinations in the TRIBE-AKI cardiac surgery cohort. Predictive performance was markedly attenuated in six out of seven cases. Thus, deficiencies in analysis and reporting are avoidable, and care should be taken to provide accurate estimates of risk prediction model performance. Hence, rigorous design, analysis, and reporting of biomarker combination studies are essential to realizing the promise of biomarkers in clinical practice.

Cognitive Performance Is Highly Stable over a 2-Year-Follow-Up in Chronic Kidney Disease Patients in a Dedicated Medical Environment.

PubMed

Gronewold, Janine; Todica, Olga; Seidel, Ulla K; Volsek, Michaela; Kribben, Andreas; Bruck, Heike; Hermann, Dirk M

2016-01-01

As kidney and brain functions decline with aging, chronic kidney disease (CKD) and dementia are becoming increasing health burdens worldwide. Among the risk factors for cognitive impairment, CKD is increasingly recognized. The precise impact of CKD on the development of cognitive impairment is poorly understood. In the New Tools for the Prevention of Cardiovascular Disease in Chronic Kidney Disease (NTCVD) cohort, which was recruited in a dedicated nephrology department, we examined the 2-year course of cognitive performance in 120 patients (73 patients with CKD stages 3-5D, 47 control patients without CKD with similar vascular risk profile) using a comprehensive battery of 10 neuropsychological tests. Kidney function, vascular risk factors and cognitive performance were highly stable both in CKD and control patients. The summary score of cognitive performance in CKD patients was very similar at baseline (z = -0.63±0.76) and follow-up (z = -0.54±0.79, p = 0.113), as was cognitive performance in control patients (z = -0.01±0.59 and 0.01±0.70, p = 0.862, at baseline and follow-up, respectively). Total serum cholesterol (199.6±36.0 and 186.0±32.9, p = 0.005 in controls; 194.4±46.1 and 181.2±41.2, p = 0.008 in CKD) and common carotid intima-media thickness (0.87±0.18 and 0.84±0.17, p = 0.351 in controls; 0.88±0.21 and 0.82±0.16, p = 0.002 in CKD) moderately but significantly decreased during the follow-up. In multivariable regression analyses, high age (β = -0.28, 95%CI = -0.48 to 0.08, p = 0.007) predicted decrease in cognitive performance. In this well-defined cohort receiving state-of-the-art therapy, cognitive performance did not decrease over 2 years. Our data emphasize the aspect of risk factor control, suggesting that dedicated medical care might prevent cognitive decline in CKD patients.

Endothelial sirtuin 1 inactivation enhances capillary rarefaction and fibrosis following kidney injury through Notch activation

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

Kida, Yujiro; Zullo, Joseph A.; Renal Research Institute, Department of Physiology, New York Medical College, Valhalla, NY

Peritubular capillary (PTC) rarefaction along with tissue fibrosis is a hallmark of chronic kidney disease (CKD). However, molecular mechanisms of PTC loss have been poorly understood. Previous studies have demonstrated that functional loss of endothelial sirtuin 1 (SIRT1) impairs angiogenesis during development and tissue damage. Here, we found that endothelial SIRT1 dysfunction causes activation of endothelial Notch1 signaling, which leads to PTC rarefaction and fibrosis following kidney injury. In mice lacking functional SIRT1 in the endothelium (Sirt1 mutant), kidney injury enhanced apoptosis and senescence of PTC endothelial cells with impaired endothelial proliferation and expanded myofibroblast population and collagen deposition. Comparedmore » to wild-type kidneys, Sirt1 mutant kidneys up-regulated expression of Delta-like 4 (DLL4, a potent Notch1 ligand), Hey1 and Hes1 (Notch target genes), and Notch intracellular domain-1 (NICD1, active form of Notch1) in microvascular endothelial cells (MVECs) post-injury. Sirt1 mutant primary kidney MVECs reduced motility and vascular assembly and enhanced senescence compared to wild-type kidney MVECs. This difference in the phenotype was negated with Notch inhibition. Concurrent stimulation of DLL4 and transforming growth factor (TGF)-β1 increased trans-differentiation of primary kidney pericytes into myofibroblast more than TGF-β1 treatment alone. Collectively, these results indicate that endothelial SIRT1 counteracts PTC rarefaction by repression of Notch1 signaling and antagonizes fibrosis via suppression of endothelial DLL4 expression. - Highlights: • SIRT1 represses Notch1 signaling in capillary endothelial cells in the kidney. • Endothelial SIRT1 is depleted in the kidney following injury. • Activation of endothelial Notch impairs angiogenesis in the kidney. • Increased expression of endothelial DLL4 enhances renal fibrosis.« less

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.

Delayed Consequences of Acute Kidney Injury

PubMed Central

Parr, Sharidan K; Siew, Edward D

2016-01-01

Acute kidney injury (AKI) is an increasingly common complication of hospitalization and acute illness. Experimental data indicate that AKI may cause permanent kidney damage through tubulointerstitial fibrosis and progressive nephron loss, while also lowering the threshold for subsequent injury. Furthermore, preclinical data suggest that AKI may also cause distant organ dysfunction. The extension of these findings to human studies suggests long-term consequences of AKI including, but not limited to recurrent AKI, progressive kidney disease, elevated blood pressure, cardiovascular events, and mortality. As the number of AKI survivors increases, the need to better understand the mechanisms driving these processes becomes paramount. Optimizing care for AKI survivors will require understanding the short- and long-term risks associated with AKI, identifying patients at highest risk for poor outcomes, and testing interventions that target modifiable risk factors. In this review, we examine the literature describing the association between AKI and long-term outcomes and highlight opportunities for further research and potential intervention. PMID:27113695

The Epigenetics of Kidney Cancer and Bladder Cancer

PubMed Central

Hoffman, Amanda M.; Cairns, Paul

2012-01-01

Summary This review focuses on the epigenetic alterations of aberrant promoter hypermethylation of genes, histone modifications or RNA interference in cancer cells. The current knowledge of hypermethylation of allele(s) in classical tumor suppressor genes in inherited and sporadic cancer, candidate tumor suppressor and other cancer genes is summarized gene by gene. Global and array-based studies of tumor cell hypermethylation are discussed. The importance of standardization of scoring of the methylation status of a gene is highlighted. The histone marks associated with hypermethylated genes, and the microRNAs with dysregulated expression, in kidney or bladder tumor cells are also discussed. Kidney cancer has the highest mortality rate of the genitourinary cancers. There are management issues with the high recurrence rate of superficial bladder cancer while muscle invasive bladder cancer has a poor prognosis. These clinical problems are the basis for translational application of gene hypermethylation to the diagnosis and prognosis of kidney and bladder cancer. PMID:22126150

Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates

PubMed Central

Yabu, Julie M.; Siebert, Janet C.; Maecker, Holden T.

2016-01-01

Background Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Methods and Findings Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Conclusions Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize medicine to ultimately improve overall outcomes in highly sensitized kidney transplant candidates. PMID:27078882

Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates.

PubMed

Yabu, Julie M; Siebert, Janet C; Maecker, Holden T

2016-01-01

Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize medicine to ultimately improve overall outcomes in highly sensitized kidney transplant candidates.

Extension of a PBPK model for ethylene glycol and glycolic acid to include the competitive formation and clearance of metabolites associated with kidney toxicity in rats and humans

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

Corley, R.A., E-mail: rick.corley@pnl.gov; Saghir, S.A.; Bartels, M.J.

2011-02-01

A previously developed PBPK model for ethylene glycol and glycolic acid was extended to include glyoxylic acid, oxalic acid, and the precipitation of calcium oxalate that is associated with kidney toxicity in rats and humans. The development and evaluation of the PBPK model was based upon previously published pharmacokinetic studies coupled with measured blood and tissue partition coefficients and rates of in vitro metabolism of glyoxylic acid to oxalic acid, glycine and other metabolites using primary hepatocytes isolated from male Wistar rats and humans. Precipitation of oxalic acid with calcium in the kidneys was assumed to occur only at concentrationsmore » exceeding the thermodynamic solubility product for calcium oxalate. This solubility product can be affected by local concentrations of calcium and other ions that are expressed in the model using an ion activity product estimated from toxicity studies such that calcium oxalate precipitation would be minimal at dietary exposures below the NOAEL for kidney toxicity in the sensitive male Wistar rat. The resulting integrated PBPK predicts that bolus oral or dietary exposures to ethylene glycol would result in typically 1.4-1.6-fold higher peak oxalate levels and 1.6-2-fold higher AUC's for calcium oxalate in kidneys of humans as compared with comparably exposed male Wistar rats over a dose range of 1-1000 mg/kg. The converse (male Wistar rats predicted to have greater oxalate levels in the kidneys than humans) was found for inhalation exposures although no accumulation of calcium oxalate is predicted to occur until exposures are well in excess of the theoretical saturated vapor concentration of 200 mg/m{sup 3}. While the current model is capable of such cross-species, dose, and route-of-exposure comparisons, it also highlights several areas of potential research that will improve confidence in such predictions, especially at low doses relevant for most human exposures.« less

Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection.

PubMed

Nafar, Mohsen; Farrokhi, Farhat; Vaezi, Mohammad; Entezari, Amir-Ebrahim; Pour-Reza-Gholi, Fatemeh; Firoozan, Ahmad; Eniollahi, Behzad

2009-01-01

Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. Pre-transplant and post-operative levels of serum sCD30 were 58.10 +/- 52.55 and 51.55 +/- 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P < 0.001). The relative changes of sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.

The value of Doppler ultrasound in predicting delayed graft function occurrence after kidney transplantation.

PubMed

Mocny, Grzegorz; Bachul, Piotr; Chang, Ea-Sle; Kulig, Piotr

The aim of this study was to assess the predictive value of blood flow velocity and vascular resistance measured by Doppler ultrasound in terms of pulsatility index (PI) and resistive index (RI) respectively, in the occurrence of delayed graft function (DGF) after kidney transplantation. This prospective study enrolled kidney transplant recipients operated from January 2005 to April 2009 in the 1st Department of General, Oncological and Gastroenterological Surgery, Jagiellonian University Medical College, Kraków, Poland. The medical records of 53 kidney transplant recipients from deceased donors were reviewed. PI and RI values of the graft arcuate artery were calculated immediately after blood flow restoration and on the 1st, 2nd, 4th and 8th post-operative day. DGF was observed in 20 patients (37.7%), while 33 patients (62.3%) had immediate restoration of the kidney function. The mean intraoperative values of RI and PI from patients with DGF were significantly higher in comparison to patients without DGF (0.9 vs. 0.74, p <0.001; 1.76 vs. 1.54, p = 0.019, respectively). Post-operatively, the RI and PI values remained stable and significantly higher in DGF group. The highest sensitivity of RI to predict DGF occurrence was observed intraoperatively and on the first postoperative day, with values of 77.8% and 72.2%, respectively. The risk of DGF occurrence with intraoperative RI value ≥0.9 increased by 13-fold, and with intraoperative PI value ≥1.9 by 12-fold. This increase was even more prominent during the first post-operative day with RI value ≥0.9 or PI value ≥1.9 with 19-fold increase in the risk of DGF occurrence. According to our study, the utilization of Doppler ultrasound with measurement of hemodynamic parameters (PI, RI), play a crucial role in predicting the outcomes of kidney transplantation.

Predictors of liver donation without kidney recovery in a cohort of expanded criteria donors: identifying opportunities to improve expanded criteria donor kidney utilization.

PubMed

White, S L; Leichtman, A B; O'Connor, K; Lipkowitz, G; Pietroski, R; Stoff, J S; Luskin, R S; Belcher, J; Meyer, K; Merion, R M; Port, F K; Delmonico, F L

2012-09-01

To maximize deceased donation, it is necessary to facilitate organ recovery from expanded criteria donors (ECDs). Utilization of donors meeting the kidney definition for ECDs increases access to kidney transplantation and reduces waiting times; however, ECDs often do not proceed to kidney recovery. Based on a prospective study of three Organ Procurement Organizations in the United States, we describe the characteristics of donors meeting the Organ Procurement and Transplant Network (OPTN) ECD kidney definition (donor age 60+ or donor age 50-60 years with two of the following: final serum creatinine > 1.5 mg/dL, history of hypertension, or death from cerebral vascular accident) who donated a liver without kidney recovery. ECDs with organs recovered between February 2003 and September 2005 by New England Organ Bank, Gift of Life Michigan, and LifeChoice Donor Services were studied (n = 324). All donors were declared dead by neurological criteria. Data on a wide range of donor characteristics were collected, including donor demographics, medical history, cause of death, donor status during hospitalization, serological status, and donor kidney quality. Logistic regression models were used to identify donor characteristics predictive of liver-alone donation. Seventy-four of the 324 donors fulfilling the ECD definition for kidneys donated a liver alone (23%). History of diabetes, final serum creatinine > 1.5 mg/dL, age 70+, and presence of proteinuria were associated with liver-alone donation in univariate models. On multivariate analysis, only final serum creatinine > 1.5 mg/dL and age 70+ were independently predictive of liver donation alone. Older age and elevated serum creatinine may be perceived as stronger contraindications to kidney donation than the remaining elements of the ECD definition. It is likely that at least a proportion of these liver-alone donors represent missed opportunities for kidney transplantation. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

Efficacy of Cordyceps sinensis as an adjunctive treatment in kidney transplant patients: A systematic-review and meta-analysis.

PubMed

Ong, Bee Yean; Aziz, Zoriah

2017-02-01

Cordyceps sinensis (cordyceps) is a fungus used in traditional Chinese medicine as adjuvant immunosuppressive agent in patients with kidney transplant. This review evaluates current evidence on the efficacy and safety of natural and fermented cordyceps preparations in patients with kidney transplant. English and Chinese electronic databases including The Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and CNKI (China National Knowledge Infrastructure) were searched up to December 2015 for relevant randomized controlled trials. Journals and conference proceedings were also searched. Two review authors independently selected trials for inclusion, extracted data, and assessed methodological quality. The primary outcome measures were incidence of acute graft rejection in the first year post-transplantation, one-year graft survival rate (defined as the percentage of patients with functioning grafts) and patient survival rate (or all-cause mortality). Nine studies were eligible for inclusion. These studies were considered to be at moderate risk of bias due to poor reporting of methods. Four studies that compared cordyceps-based therapy with azathioprine-based therapy gave comparable acute rejection rates, and graft and patient survival. The cordyceps-treated group however showed better kidney function and lower incidences of hyperuricemia, hyperlipidemia, hyperglycemia and liver injury. Cordyceps used with different combinations of immunosuppressant therapy showed significant reduction in proteinuria after 6-12 months. Compared to the group receiving cyclosporine A monotherapy, treatment with a combination of cordyceps and cyclosporine A showed less treatment-induced nephrotoxicity. Adverse events were either not monitored or poorly documented in most trials. Current evidence shows that cordyceps as an adjuvant to routine immunosuppressant therapy may benefit kidney transplant patient, however, better quality evidence is still required. Copyright © 2016 Elsevier Ltd. All rights reserved.

A qualitative assessment of personal and social responsibility for kidney disease: the Increasing Kidney Disease Awareness Network Transplant Project.

PubMed

Spigner, Clarence; Lyles, Courtney Rees; Galvin, Georgia; Sabin, Janice; Davis, Connie; Dick, Andre; Young, Bessie A

2011-01-01

Limited qualitative research has explored opinions of kidney disease health care providers regarding racial and ethnic disparities in access to and receipt of kidney transplantation. Key informant interviews were conducted among transplant nephrologists, nephrologists, transplant social workers, and transplant coordinators to determine barriers to transplantation among African Americans compared to whites with end-stage renal disease (ESRD). Thirty-eight interviews were audio recorded and transcribed to hardcopy for content analysis. Grounded theory was used to determine dominant themes within the interviews. Reliability and validity were ensured by several coinvestigators independently sorting verbatim responses used for generating themes and subsequent explanations. Several major categories arose from analysis of the transcripts. Under the category of personal and social responsibility for kidney transplantation, interviews revealed 4 major themes: negative personal behaviors, acquisition of and lack of self-treatment of comorbid conditions, lack of individual responsibility, and the need for more social responsibility. Many providers perceived patients as being largely responsible for the development of ESRD, while some providers expressed the idea that more social responsibility was needed to improve poor health status and disparities in kidney transplantation rates. Kidney disease health providers seemed torn between notions of patients' accountability and social responsibility for racial disparities in chronic kidney disease and ESRD. Further research is needed to clarify which aspects contribute most to disparities in access to transplantation.

Risk profile, quality of life and care of patients with moderate and advanced CKD : The French CKD-REIN Cohort Study.

PubMed

Stengel, Bénédicte; Metzger, Marie; Combe, Christian; Jacquelinet, Christian; Briançon, Serge; Ayav, Carole; Fouque, Denis; Laville, Maurice; Frimat, Luc; Pascal, Christophe; Herpe, Yves-Edouard; Morel, Pascal; Deleuze, Jean-François; Schanstra, Joost P; Lange, Céline; Legrand, Karine; Speyer, Elodie; Liabeuf, Sophie; Robinson, Bruce M; Massy, Ziad A

2018-04-09

The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study was designed to investigate the determinants of prognosis and care of patients referred to nephrologists with moderate and advanced chronic kidney disease (CKD). We examined their baseline risk profile and experience. We collected bioclinical and patient-reported information from 3033 outpatients with CKD and estimated glomerular filtration rates (eGFRs) of 15-60 mL/min/1.73 m2 treated at 40 nationally representative public and private facilities. The patients' median age was 69 (60-76) years, 65% were men, their mean eGFR was 33 mL/min/1.73 m2, 43% had diabetes, 24% had a history of acute kidney injury (AKI) and 57% had uncontrolled blood pressure (BP; >140/90 mmHg). Men had worse risk profiles than women and were more likely to be past or current smokers (73% versus 34%) and have cardiovascular disease (59% versus 42%), albuminuria >30 mg/mmol (or proteinuria > 50) (40% versus 30%) (all P < 0.001) and a higher median risk of end-stage renal disease within 5 years, predicted by the kidney failure risk equation {12% [interquartile range (IQR) 3-37%] versus 9% [3-31%], P = 0.008}. During the previous year, 60% of patients reported one-to-two nephrologist visits and four or more general practitioner visits; only 25% saw a dietician and 75% were prescribed five or more medications daily. Physical and mental quality of life (QoL) were poor, with scores <50/100. The CKD-REIN study highlights high-risk profiles of cohort members and identifies several priorities, including improving BP control and dietary counselling and increasing doctors' awareness of AKI, polypharmacy and QoL. ClinicalTrials.gov identifier: NCT03381950.

Incidence, care quality and outcomes of patients with acute kidney injury in admitted hospital care.

PubMed

Medcalf, J F; Davies, C; Hollinshead, J; Matthews, B; O'Donoghue, D

2016-12-01

Acute kidney injury (AKI) is common in acute hospital admission and associated with worse patient outcomes. To measure incidence, care quality and outcome of AKI in admitted hospital care. Forty-six of 168 acute NHS healthcare trusts in UK caring for 2 million acute hospital admissions per annum collected information on adults identified with AKI stage 3 (3-fold rise in serum creatinine or creatinine >354 µmol/l) through routine biochemical testing over a 5-month period in 2012. Information was collected on patient and care characteristics. Primary outcomes were survival and recovery of kidney function at 1 month. A total of 15 647 patients were identified with biochemical AKI stage 3. Case note reviews were available for 7726 patients. In 80%, biochemical AKI stage 3 was confirmed clinically. Among this group, median age was 75 years, median length of stay was 12 days and the overall mortality within 1 month was 38%. Significant factors in a multivariable model predicting survival included age and some causes of AKI. Dipstick urinalysis, medication review, discussion with a nephrologist and acceptance for transfer to a renal unit were also associated with higher survival, but not early review by a senior doctor, acceptance for transfer to critical care or requirement for renal replacement therapy. Eighteen percent of people did not have their kidney function checked 1 month after the episode had resolved. This large study of in-hospital AKI supports the efficacy of biochemical detection of AKI in common usage. AKI mortality remains substantial, length of stay comparable with single-centre studies, and much of the variation is poorly explained (model Cox and Snell R 2  =   0.131) from current predictors. © The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Tenascin-C Is a Major Component of the Fibrogenic Niche in Kidney Fibrosis

PubMed Central

Fu, Haiyan; Tian, Yuan; Zhou, Lili; Zhou, Dong; Tan, Roderick J.; Stolz, Donna B.

2017-01-01

Kidney fibrosis initiates at certain focal sites in which the fibrogenic niche provides a specialized microenvironment that facilitates fibroblast activation and proliferation. However, the molecular identity of these fibrogenic niches is poorly characterized. Here, we determined whether tenascin-C (TNC), an extracellular matrix glycoprotein, is a component of the fibrogenic niche in kidney fibrosis. In vivo, TNC expression increased rapidly in kidneys subjected to unilateral ureteral obstruction or ischemia/reperfusion injury and predominantly localized at the foci rich in fibroblasts in renal interstitium. In vitro, TNC selectively promoted renal interstitial fibroblast proliferation, bromodeoxyuridine incorporation, and the expression of proliferation-related genes. The mitogenic activity of TNC required the integrin/focal adhesion kinase/mitogen-activated protein kinase signaling cascade. Using decellularized extracellular matrix scaffolds, we found that TNC-enriched scaffolds facilitated fibroblast proliferation, whereas TNC-deprived scaffolds inhibited proliferation. Matrix scaffold prepared from fibrotic kidney also promoted greater ex vivo fibroblast proliferation than did scaffolds prepared from healthy kidney. Conversely, small interfering RNA-mediated knockdown of TNC in vivo repressed injury-induced fibroblast expansion and renal fibrosis. These studies identify TNC as a major constituent of the fibrogenic niche that promotes fibroblast proliferation, and illustrate a pivotal role for the TNC-enriched microenvironment in kidney fibrogenesis. PMID:27612995

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.

Zero-Time Renal Transplant Biopsies: A Comprehensive Review.

PubMed

Naesens, Maarten

2016-07-01

Zero-time kidney biopsies, obtained at time of transplantation, are performed in many transplant centers worldwide. Decisions on kidney discard, kidney allocation, and choice of peritransplant and posttransplant treatment are sometimes based on the histological information obtained from these biopsies. This comprehensive review evaluates the practical considerations of performing zero-time biopsies, the predictive performance of zero-time histology and composite histological scores, and the clinical utility of these biopsies. The predictive performance of individual histological lesions and of composite scores for posttransplant outcome is at best moderate. No single histological lesion or composite score is sufficiently robust to be included in algorithms for kidney discard. Dual kidney transplantation has been based on histological assessment of zero-time biopsies and improves outcome in individual patients, but the waitlist effects of this strategy remain obscure. Zero-time biopsies are valuable for clinical and translational research purposes, providing insight in risk factors for posttransplant events, and as baseline for comparison with posttransplant histology. The molecular phenotype of zero-time biopsies yields novel therapeutic targets for improvement of donor selection, peritransplant management and kidney preservation. It remains however highly unclear whether the molecular expression variation in zero-time biopsies could become a better predictor for posttransplant outcome than donor/recipient baseline demographic factors.

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.

CD146(+) cells are essential for kidney vasculature development.

PubMed

Halt, Kimmo J; Pärssinen, Heikki E; Junttila, Sanna M; Saarela, Ulla; Sims-Lucas, Sunder; Koivunen, Peppi; Myllyharju, Johanna; Quaggin, Susan; Skovorodkin, Ilya N; Vainio, Seppo J

2016-08-01

The kidney vasculature is critical for renal function, but its developmental assembly mechanisms remain poorly understood and models for studying its assembly dynamics are limited. Here, we tested whether the embryonic kidney contains endothelial cells (ECs) that are heterogeneous with respect to VEGFR2/Flk1/KDR, CD31/PECAM, and CD146/MCAM markers. Tie1Cre;R26R(YFP)-based fate mapping with a time-lapse in embryonic kidney organ culture successfully depicted the dynamics of kidney vasculature development and the correlation of the process with the CD31(+) EC network. Depletion of Tie1(+) or CD31(+) ECs from embryonic kidneys, with either Tie1Cre-induced diphtheria toxin susceptibility or cell surface marker-based sorting in a novel dissociation and reaggregation technology, illustrated substantial EC network regeneration. Depletion of the CD146(+) cells abolished this EC regeneration. Fate mapping of green fluorescent protein (GFP)-marked CD146(+)/CD31(-) cells indicated that they became CD31(+) cells, which took part in EC structures with CD31(+) wild-type ECs. EC network development depends on VEGF signaling, and VEGF and erythropoietin are expressed in the embryonic kidney even in the absence of any external hypoxic stimulus. Thus, the ex vivo embryonic kidney culture models adopted here provided novel ways for targeting renal EC development and demonstrated that CD146(+) cells are critical for kidney vasculature development. Copyright © 2016 International Society of Nephrology. All rights reserved.

Reliability of CKD-EPI predictive equation in estimating chronic kidney disease prevalence in the Croatian endemic nephropathy area

PubMed Central

Fuček, Mirjana; Dika, Živka; Karanović, Sandra; Vuković Brinar, Ivana; Premužić, Vedran; Kos, Jelena; Cvitković, Ante; Mišić, Maja; Samardžić, Josip; Rogić, Dunja; Jelaković, Bojan

2017-01-01

Introduction Chronic kidney disease (CKD) is a significant public health problem and it is not possible to precisely predict its progression to terminal renal failure. According to current guidelines, CKD stages are classified based on the estimated glomerular filtration rate (eGFR) and albuminuria. Aims of this study were to determine the reliability of predictive equation in estimation of CKD prevalence in Croatian areas with endemic nephropathy (EN), compare the results with non-endemic areas, and to determine if the prevalence of CKD stages 3-5 was increased in subjects with EN. Materials and methods A total of 1573 inhabitants of the Croatian Posavina rural area from 6 endemic and 3 non-endemic villages were enrolled. Participants were classified according to the modified criteria of the World Health Organization for EN. Estimated GFR was calculated using Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). Results The results showed a very high CKD prevalence in the Croatian rural area (19%). CKD prevalence was significantly higher in EN then in non EN villages with the lowest eGFR value in diseased subgroup. Conclusions eGFR correlated significantly with the diagnosis of EN. Kidney function assessment using CKD-EPI predictive equation proved to be a good marker in differentiating the study subgroups, remained as one of the diagnostic criteria for EN. PMID:29187794

Pericytes in kidney fibrosis.

PubMed

Ren, Shuyu; Duffield, Jeremy S

2013-07-01

Pericytes and perivascular fibroblasts have emerged as poorly appreciated yet extensive populations of mesenchymal cells in the kidney that play important roles in homeostasis and responses to injury. This review will update readers on the evolving understanding of the biology of these cells. Fate mapping has identified pericytes and perivascular fibroblasts as the major source of pathological fibrillar matrix-forming cells in interstitial kidney disease. In other organs similar cells have been described and independent fate mapping indicates that pericytes or perivascular cells are myofibroblast progenitors in multiple organs. Over the last year, new insights into the function of pericytes in kidney homeostasis has been uncovered and new molecular pathways that regulate detachment and their transdifferentiation into pathological myofibroblasts, including Wingless/Int, ephrin, transforming growth factor β, platelet derived growth factor, and Hedgehog signaling pathways, have been reported. In addition provocative studies indicate that microRNAs, which regulate posttranscriptional gene expression, may also play important roles in their transdifferentiation. Pericytes and perivascular fibroblasts are the major source of pathological collagen fiber-forming cells in interstitial kidney diseases. New avenues of research into their activation and differentiation has identified new drug candidates for the treatment of interstitial kidney disease.

Living Donor Kidney Transplantation: Overcoming Disparities in Live Kidney Donation in the US—Recommendations from a Consensus Conference

PubMed Central

Rodrigue, James R.; Kazley, Abby Swanson; Mandelbrot, Didier A.; Hays, Rebecca; LaPointe Rudow, Dianne

2015-01-01

Despite its superior outcomes relative to chronic dialysis and deceased donor kidney transplantation, live donor kidney transplantation (LDKT) is less likely to occur in minorities, older adults, and poor patients than in those who are white, younger, and have higher household income. In addition, there is considerable geographic variability in LDKT rates. Concomitantly, in recent years, the rate of living kidney donation (LKD) has stopped increasing and is declining, after decades of consistent growth. Particularly noteworthy is the decline in LKD among black, younger, male, and lower-income adults. The Live Donor Community of Practice within the American Society of Transplantation, with financial support from 10 other organizations, held a Consensus Conference on Best Practices in Live Kidney Donation in June 2014. The purpose of this meeting was to identify LKD best practices and knowledge gaps that might influence LDKT, with a focus on patient and donor education, evaluation efficiencies, disparities, and systemic barriers to LKD. In this article, we discuss trends in LDKT/LKD and emerging novel strategies for attenuating disparities, and we offer specific recommendations for future clinical practice, education, research, and policy from the Consensus Conference Workgroup focused on disparities. PMID:25883072

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.

Cerebral Small Vessel Disease and Chronic Kidney Disease

PubMed Central

2015-01-01

Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small artery diseases, kidney impairment can be predictive of the presence and severity of cerebral small vessel diseases. Chronic kidney disease has been reported to be associated with silent brain infarcts, cerebral white matter lesions, and cerebral microbleeds, independently of vascular risk factors. In addition, chronic kidney disease affects cognitive function, partly via the high prevalence of cerebral small vessel diseases. Retinal artery disease also has an independent relationship with chronic kidney disease and cognitive impairment. Stroke experts are no longer allowed to be ignorant of chronic kidney disease. Close liaison between neurologists and nephrologists can improve the management of cerebral small vessel diseases in kidney patients. PMID:25692105

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

ExplorinG frailty and mild cognitive impairmEnt in kidney tRansplantation to predict biomedicAl, psychosocial and health cost outcomeS (GERAS): protocol of a nationwide prospective cohort study.

PubMed

Mauthner, Oliver; Claes, Veerle; Walston, Jeremy; Engberg, Sandra; Binet, Isabelle; Dickenmann, Michael; Golshayan, Déla; Hadaya, Karine; Huynh-Do, Uyen; Calciolari, Stefano; De Geest, Sabina

2017-03-01

To present the rationale, design and methodology of the GERAS project, which examines whether assessment of frailty and mild cognitive impairment could enhance risk prediction for biomedical, psychosocial outcomes and foster efficient resource allocation in kidney transplantation. For the burgeoning cohort of older patients considered for kidney transplantation, evidence gaps regarding frailty and mild cognitive impairment limit clinical decision-making and medical management. As known risk factors for 'hard' clinical outcomes in chronic illness, both require further study in transplantation. Integrating these and other bio-psychosocial factors into a comprehensive pre-transplant patient assessment will provide insights regarding economic implications and may improve risk prediction. A nation-wide multi-centre prospective cohort study nested in the Swiss Transplant Cohort Study. Our nationally representative convenience sample includes 250 adult kidney transplant recipients. Data sources include the Swiss Transplant Cohort Study and primary data collected at time of transplantation, 6 months, 1 and 2 years post-transplant via established measures (the Montreal Cognitive Assessment, Psychosocial Questionnaire, Fried Frailty Instrument and a blood analysis), investigator-developed instruments and datasets compiled by hospitals' management control units, sickness funds, the Swiss Federal Statistical Office and the European Renal Association. Descriptive, competing risk survival and mixed effects analyses will be performed. Research Ethics Committee approval was obtained in January 2016. This pioneering project jointly examines frailty and mild cognitive impairment from bio-psychosocial and health economic perspectives. Results may significantly inform risk prediction, care tailoring and resource optimization to improve health outcomes in the ageing kidney transplant cohort. © 2016 John Wiley & Sons Ltd.

Determination of cadmium relative bioavailability in contaminated soils and its prediction using in vitro methodologies.

PubMed

Juhasz, Albert L; Weber, John; Naidu, Ravi; Gancarz, Dorota; Rofe, Allan; Todor, Damian; Smith, Euan

2010-07-01

In this study, cadmium (Cd) relative bioavailability in contaminated (n = 5) and spiked (n = 2) soils was assessed using an in vivo mouse model following administration of feed containing soil or Cd acetate (reference material) over a 15 day exposure period. Cadmium relative bioavailability varied depending on whether the accumulation of Cd in the kidneys, liver, or kidney plus liver was used for relative bioavailability calculations. When kidney plus liver Cd concentrations were used, Cd relative bioavailability ranged from 10.1 to 92.1%. Cadmium relative bioavailability was higher (14.4-115.2%) when kidney Cd concentrations were used, whereas lower values (7.2-76.5%) were derived when liver Cd concentrations were employed in calculations. Following in vivo studies, four in vitro methodologies (SBRC, IVG, PBET, and DIN), encompassing both gastric and intestinal phases, were assessed for their ability to predict Cd relative bioavailability. Pearson correlations demonstrated a strong linear relationship between Cd relative bioavailability and Cd bioaccessibility (0.62-0.91), however, stronger in vivo-in vitro relationships were observed when Cd relative bioavailability was calculated using kidney plus liver Cd concentrations. Whereas all in vitro assays could predict Cd relative bioavailability with varying degrees of confidence (r(2) = 0.348-0.835), large y intercepts were calculated for a number of in vitro assays which is undesirable for in vivo-in vitro predictive models. However, determination of Cd bioaccessibility using the intestinal phase of the PBET assay resulted in a small y intercept (5.14; slope =1.091) and the best estimate of in vivo Cd relative bioavailability (r(2) = 0.835).

Long-term outcomes of acute kidney injury.

PubMed

Coca, Steven G

2010-05-01

The goal of this review is to summarize the recent plethora of data that relate to long-term outcomes after acute kidney injury (AKI). Surviving patients with AKI are still at high risk for long-term adverse outcomes, even if serum creatinine returns to normal. After adjusting for potential confounders, many recent studies have demonstrated that AKI is independently associated with chronic kidney disease, end-stage renal disease, and premature death. Unfortunately, definitive evidence from randomized controlled trials demonstrating that prevention or treatment of AKI prevents long-term adverse outcomes is not yet available. AKI is clearly a prognostic marker for poor long-term outcomes, but more studies will be needed to determine whether AKI is truly causal and whether or not the risk is modifiable.

Predicting Severity of Acute Kidney Injury in Term Neonates with Perinatal Asphyxia Using Urinary Neutrophil Gelatinase Associated Lipocalin.

PubMed

Tanigasalam, Vasanthan; Bhat, Ballambattu Vishnu; Adhisivam, Bethou; Sridhar, Magadi Gopalakrishna; Harichandrakumar, Kottyen Thazath

2016-11-01

To evaluate the utility of urinary Neutrophil Gelatinase Associated Lipocalin (NGAL) as a biomarker for predicting Acute Kidney Injury (AKI) and its severity among neonates with perinatal asphyxia. This descriptive study included 120 term neonates with perinatal asphyxia. Renal parameters of neonates were monitored and AKI was ascertained as per Acute Kidney Injury Network criteria. Urinary NGAL was estimated and correlated with severity of AKI. Among the 120 neonates with perinatal asphyxia, 55(46 %) had AKI. The median urinary NGAL level was 165 ng/ml (88.8-245.8) in neonates with AKI compared to 58.97(42.8-74.7) in those without AKI. The median NGAL was 134.45(112.2-162.5), 301.2(255.5-361.2), 416.2(412.2-465.5) in AKI stages 1, 2 and 3 respectively. An NGAL cut off value of 86.82 ng/ml had 87 % sensitivity and 87.7 % specificity in predicting AKI. Urinary NGAL is a useful biomarker for predicting AKI and its severity among neonates with perinatal asphyxia.

Complete staghorn calculus in polycystic kidney disease: infection is still the cause

PubMed Central

2013-01-01

Background Kidney stones in patients with autosomal dominant polycystic kidney disease are common, regarded as the consequence of the combination of anatomic abnormality and metabolic risk factors. However, complete staghorn calculus is rare in polycystic kidney disease and predicts a gloomy prognosis of kidney. For general population, recent data showed metabolic factors were the dominant causes for staghorn calculus, but for polycystic kidney disease patients, the cause for staghorn calculus remained elusive. Case presentation We report a case of complete staghorm calculus in a polycystic kidney disease patient induced by repeatedly urinary tract infections. This 37-year-old autosomal dominant polycystic kidney disease female with positive family history was admitted in this hospital for repeatedly upper urinary tract infection for 3 years. CT scan revealed the existence of a complete staghorn calculus in her right kidney, while there was no kidney stone 3 years before, and the urinary stone component analysis showed the composition of calculus was magnesium ammonium phosphate. Conclusion UTI is an important complication for polycystic kidney disease and will facilitate the formation of staghorn calculi. As staghorn calculi are associated with kidney fibrosis and high long-term renal deterioration rate, prompt control of urinary tract infection in polycystic kidney disease patient will be beneficial in preventing staghorn calculus formation. PMID:24070202

Complete staghorn calculus in polycystic kidney disease: infection is still the cause.

PubMed

Mao, Zhiguo; Xu, Jing; Ye, Chaoyang; Chen, Dongping; Mei, Changlin

2013-08-01

Kidney stones in patients with autosomal dominant polycystic kidney disease are common, regarded as the consequence of the combination of anatomic abnormality and metabolic risk factors. However, complete staghorn calculus is rare in polycystic kidney disease and predicts a gloomy prognosis of kidney. For general population, recent data showed metabolic factors were the dominant causes for staghorn calculus, but for polycystic kidney disease patients, the cause for staghorn calculus remained elusive. We report a case of complete staghorm calculus in a polycystic kidney disease patient induced by repeatedly urinary tract infections. This 37-year-old autosomal dominant polycystic kidney disease female with positive family history was admitted in this hospital for repeatedly upper urinary tract infection for 3 years. CT scan revealed the existence of a complete staghorn calculus in her right kidney, while there was no kidney stone 3 years before, and the urinary stone component analysis showed the composition of calculus was magnesium ammonium phosphate. UTI is an important complication for polycystic kidney disease and will facilitate the formation of staghorn calculi. As staghorn calculi are associated with kidney fibrosis and high long-term renal deterioration rate, prompt control of urinary tract infection in polycystic kidney disease patient will be beneficial in preventing staghorn calculus formation.

Integration of multimodal RNA-seq data for prediction of kidney cancer survival

PubMed Central

Schwartzi, Matt; Parkl, Martin; Phanl, John H.; Wang., May D.

2016-01-01

Kidney cancer is of prominent concern in modern medicine. Predicting patient survival is critical to patient awareness and developing a proper treatment regimens. Previous prediction models built upon molecular feature analysis are limited to just gene expression data. In this study we investigate the difference in predicting five year survival between unimodal and multimodal analysis of RNA-seq data from gene, exon, junction, and isoform modalities. Our preliminary findings report higher predictive accuracy-as measured by area under the ROC curve (AUC)-for multimodal learning when compared to unimodal learning with both support vector machine (SVM) and k-nearest neighbor (KNN) methods. The results of this study justify further research on the use of multimodal RNA-seq data to predict survival for other cancer types using a larger sample size and additional machine learning methods. PMID:27532026

Allocating Deceased Donor Kidneys to Candidates with High Panel-Reactive Antibodies.

PubMed

Gebel, Howard M; Kasiske, Bertram L; Gustafson, Sally K; Pyke, Joshua; Shteyn, Eugene; Israni, Ajay K; Bray, Robert A; Snyder, Jon J; Friedewald, John J; Segev, Dorry L

2016-03-07

In December of 2014, the Organ Procurement and Transplant Network implemented a new Kidney Allocation System (KAS) for deceased donor transplant, with increased priority for highly sensitized candidates (calculated panel-reactive antibody [cPRA] >99%). We used a modified version of the new KAS to address issues of access and equity for these candidates. In a simulation, 10,988 deceased donor kidneys transplanted into waitlisted recipients in 2010 were instead allocated to candidates with cPRA≥80% (n=18,004). Each candidate's unacceptable donor HLA antigens had been entered into the allocation system by the transplant center. In simulated match runs, kidneys were allocated sequentially to adult ABO identical or permissible candidates with cPRA 100%, 99%, 98%, etc. to 80%. Allocations were restricted to donor/recipient pairs with negative virtual crossmatches. The simulation indicated that 2111 of 10,988 kidneys (19.2%) would have been allocated to patients with cPRA 100% versus 74 of 10,988 (0.7%) that were actually transplanted. Of cPRA 100% candidates, 74% were predicted to be compatible with an average of six deceased donors; the remaining 26% seemed to be incompatible with every deceased donor organ that entered the system. Of kidneys actually allocated to cPRA 100% candidates in 2010, 66% (49 of 74) were six-antigen HLA matched/zero-antigen mismatched (HLA-A, -B, and -DR) with their recipients versus only 11% (237 of 2111) in the simulation. The simulation predicted that 10,356 of 14,433 (72%) candidates with cPRA 90%-100% could be allocated an organ compared with 7.3% who actually underwent transplant. Data in this simulation are consistent with early results of the new KAS; specifically, nearly 20% of deceased donor kidneys were (virtually) compatible with cPRA 100% candidates. Although most of these candidates were predicted to be compatible with multiple donors, approximately one-quarter are unlikely to receive a single offer. Copyright © 2016 by the American Society of Nephrology.

Hypothermic machine perfusion permits extended cold ischemia times with improved early graft function.

PubMed

Guy, Alison; McGrogan, Damian; Inston, Nicholas; Ready, Andrew

2015-04-01

The logistics of deceased-donor renal transplants are largely affected by cold ischemia time. However, to attain successful outcomes, other issues must be considered. Extending cold ischemia time to accommodate these issues would be valuable. We investigated the role of hypothermic machine perfusion to extend cold ischaemia time. Deceased-donor kidneys were allocated to a storage method, depending on predicted time to operation. Kidneys to be transplanted from 8:00 AM to 8:00 PM in the transplant room remained in static cold storage. If predicted operating time was out of hours, the kidney was transferred to hypothermic machine perfusion and transplanted at the earliest opportunity on the dedicated transplant list. There were 74 kidneys transplanted from hypothermic machine perfusion and 101 kidneys from static cold storage. Median cold ischemia time was 23.85 hours in the hypothermic machine perfusion group, compared with 13 hours in the static cold storage group (P ≤ .0001). There were 20 kidneys (27%) from hypothermic machine perfusion that had delayed graft function, compared with 47 kidneys (47%) in the static cold storage group (P = .012). There were no other significant differences in graft or postoperative complications. This study demonstrated that improved early graft outcomes can be achieved following longer cold ischemia time by using hypothermic machine perfusion rather than static cold storage. This effect is likely multifactorial including the inherent effects of hypothermic machine perfusion, improved recipient preparation, and possibly better perioperative conditions.

Biomarkers and surrogate endpoints in kidney disease.

PubMed

Hartung, Erum A

2016-03-01

Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. "Hard" endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease.

Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm

PubMed Central

Perens, Elliot A; Garavito-Aguilar, Zayra V; Guio-Vega, Gina P; Peña, Karen T; Schindler, Yocheved L; Yelon, Deborah

2016-01-01

Proper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidney by restricting IM dimensions. The IM is expanded in zebrafish hand2 mutants and is diminished when hand2 is overexpressed. Within the posterior mesoderm, hand2 is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, and hand2 promotes venous development while inhibiting IM formation at this interface. Furthermore, hand2 and the co-expressed zinc-finger transcription factor osr1 have functionally antagonistic influences on kidney development. Together, our data suggest that hand2 functions in opposition to osr1 to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM. DOI: http://dx.doi.org/10.7554/eLife.19941.001 PMID:27805568

Understanding the influence of educational attainment on kidney health and opportunities for improved care.

PubMed

Green, Jamie A; Cavanaugh, Kerri L

2015-01-01

Educational attainment is an important but often overlooked contributor to health outcomes in patients with kidney disease. Those with lower levels of education have an increased risk of ESRD, complications of peritoneal dialysis, worse transplant outcomes, and mortality. Mediators of these associations are poorly understood but involve a complex interplay between health knowledge, behaviors, and socioeconomic and psychosocial factors. Interventions targeting these aspects of care have the potential to reduce disparities related to educational attainment; however, few programs have been described that specifically address this issue. Future research efforts should not only systematically assess level of educational attainment but also report the differential impact of interventions across educational strata. In addition, routine measurement of health literacy may be useful to identify high-risk patients independent of years of schooling. A better understanding of the influence of educational attainment on kidney health provides an opportunity to improve the care and outcomes of vulnerable patients with kidney disease. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Pretransplantation recipient regulatory T cell suppressive function predicts delayed and slow graft function after kidney transplantation.

PubMed

Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Michel, Rene P; Lipman, Mark L; Mucsi, Istvan; Cantarovich, Marcelo; Tchervenkov, Jean I; Paraskevas, Steven

2014-10-15

Delayed graft function (DGF) and slow graft function (SGF) are a continuous spectrum of ischemia-reperfusion-related acute kidney injury (AKI) that increases the risk for acute rejection and graft loss after kidney transplantation. Regulatory T cells (Tregs) are critical in transplant tolerance and attenuate murine AKI. In this prospective observational cohort study, we evaluated whether pretransplantation peripheral blood recipient Treg frequency and suppressive function are predictors of DGF and SGF after kidney transplantation. Deceased donor kidney transplant recipients (n=53) were divided into AKI (n=37; DGF, n=10; SGF, n=27) and immediate graft function (n=16) groups. Pretransplantation peripheral blood CD4CD25FoxP3 Treg frequency was quantified by flow cytometry. Regulatory T-cell suppressive function was measured by suppression of autologous effector T-cell proliferation by Treg in co-culture. Pretransplantation Treg suppressive function, but not frequency, was decreased in AKI recipients (P<0.01). In univariate and multivariate analyses accounting for the effects of cold ischemic time and donor age, Treg suppressive function discriminated DGF from immediate graft function recipients in multinomial logistic regression (odds ratio, 0.77; P<0.01), accurately predicted AKI in receiver operating characteristic curve (area under the curve, 0.82; P<0.01), and predicted 14-day estimated glomerular filtration rate in linear regression (P<0.01). Our results indicate that recipient peripheral blood Treg suppressive function is a potential independent pretransplantation predictor of DGF and SGF.

Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

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

Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra

Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy

DOE PAGES

Raman, Rajesh N.; Pivetti, Christopher D.; Ramsamooj, Rajendra; ...

2017-05-03

Functional changes in rat kidneys during the induced ischemic injury and recovery phases were explored using multimodal autofluorescence and light scattering imaging. We aim to evaluate the use of noncontact optical signatures for rapid assessment of tissue function and viability. Specifically, autofluorescence images were acquired in vivo under 355, 325, and 266 nm illumination while light scattering images were collected at the excitation wavelengths as well as using relatively narrowband light centered at 500 nm. The images were simultaneously recorded using a multimodal optical imaging system. We also analyzed to obtain time constants, which were correlated to kidney dysfunction asmore » determined by a subsequent survival study and histopathological analysis. This analysis of both the light scattering and autofluorescence images suggests that changes in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, coupled with vascular response, contribute to the behavior of the observed signal, which may be used to obtain tissue functional information and offer the ability to predict posttransplant kidney function.« less

Prognostic Value of Improved Kidney Function After Transcatheter Aortic Valve Implantation for Aortic Stenosis.

PubMed

Nijenhuis, Vincent Johan; Peper, Joyce; Vorselaars, Veronique M M; Swaans, Martin J; De Kroon, Thom; Van der Heyden, Jan A S; Rensing, Benno J W M; Heijmen, Robin; Bos, Willem-Jan W; Ten Berg, Jurrien M

2018-05-15

Transcatheter aortic valve implantation (TAVI) is associated with acute kidney injury (AKI), but can also improve the kidney function (IKF). We assessed the effects of kidney function changes in relation to baseline kidney function on 2-year clinical outcomes after TAVI. In total, 639 consecutive patients with aortic stenosis who underwent TAVI were stratified into 3 groups according to the ratio of serum creatinine post- to pre-TAVI: IKF (≤0.80; n = 95 [15%]), stable kidney function (0.80 to 1.5; n = 477 [75%]), and AKI (≥1.5; n = 67 [10%]). Different AKI risk scores were compared using receiving-operator characteristics. Median follow-up was 24 (8 to 44) months. At 3 months, the increase in estimated glomerular filtration rate in the IKF group remained, and the decreased estimated glomerular filtration rate in the AKI group recovered. Compared with a stable kidney function, AKI showed a higher 2-year mortality rate (adjusted hazard ratio [HR] 3.69, 95% confidence interval [CI] 2.43 to 5.62) and IKF a lower mortality rate (adjusted hazard ratio 0.53, 95% CI 0.30 to 0.93). AKI also predicted major and life-threatening bleeding (adjusted odds ratio 2.94, 95% CI 1.27 to 6.78). Independent predictors of AKI were chronic kidney disease and pulmonary hypertension. Independent predictors of IKF were female gender, a preserved kidney function, absence of atrial fibrillation, and hemoglobin level. Established AKI risk scores performed moderately and did not differentiate between AKI and IKF. In conclusion, AKI is transient and is independently associated with a higher mortality rate, whereas IKF is sustained and is associated with a lower mortality rate. These effects are independent of baseline kidney function. Further studies are warranted to investigate the role of IKF and generate a dedicated prediction model. Copyright © 2018 Elsevier Inc. All rights reserved.

Paid donation: a global view.

PubMed

Ghahramani, Nasrollah; Rizvi, S Adibul Hasan; Padilla, Benita

2012-07-01

Paying for kidney or other organ donation has lead to heated debates about donor and recipient welfare. Many have argued that paying for donation leads to coercion and exploitation of the poor, and, in the end, produces more harm than good. Others have said that payment helps the poor, and we should all have sovereignty over our bodies and, thus, should be allowed to donate for remuneration. Although World Health Organizations and governments in many countries have now banned the process of paying for donation, there is still ongoing payment legally and illegally. Thus, this timely set of three articles from Iran, Pakistan, and the Philippines, where paid donation has been extensively performed, will allow the reader to decide for themselves whether the benefits and/or harms of this practice are now clear. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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.

Microvascular pericytes in healthy and diseased kidneys

PubMed Central

Pan, Szu-Yu; Chang, Yu-Ting; Lin, Shuei-Liong

2014-01-01

Pericytes are interstitial mesenchymal cells found in many major organs. In the kidney, microvascular pericytes are defined anatomically as extensively branched, collagen-producing cells in close contact with endothelial cells. Although many molecular markers have been proposed, none of them can identify the pericytes with satisfactory specificity or sensitivity. The roles of microvascular pericytes in kidneys were poorly understood in the past. Recently, by using genetic lineage tracing to label collagen-producing cells or mesenchymal cells, the elusive characteristics of the pericytes have been illuminated. The purpose of this article is to review recent advances in the understanding of microvascular pericytes in the kidneys. In healthy kidney, the pericytes are found to take part in the maintenance of microvascular stability. Detachment of the pericytes from the microvasculature and loss of the close contact with endothelial cells have been observed during renal insult. Renal microvascular pericytes have been shown to be the major source of scar-forming myofibroblasts in fibrogenic kidney disease. Targeting the crosstalk between pericytes and neighboring endothelial cells or tubular epithelial cells may inhibit the pericyte–myofibroblast transition, prevent peritubular capillary rarefaction, and attenuate renal fibrosis. In addition, renal pericytes deserve attention for their potential to produce erythropoietin in healthy kidneys as pericytes stand in the front line, sensing the change of oxygenation and hemoglobin concentration. Further delineation of the mechanisms underlying the reduced erythropoietin production occurring during pericyte–myofibroblast transition may be promising for the development of new treatment strategies for anemia in chronic kidney disease. PMID:24465134

Elevated Endothelial Hypoxia-Inducible Factor-1α Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease.

PubMed

Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K; Tao, Lijian; Kellems, Rodney E; Xia, Yang

2015-07-01

Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1α (HIF-1α) is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis, we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1α and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with reverse transcription polymerase chain reaction profiling revealed that elevated endothelial HIF-1α is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1α gene expression was induced by angiotensin II in a nuclear factor-κB-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1α and Nf-κb genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1α gene expression in endothelial cells is detrimental to induce kidney injury, hypertension, and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease. © 2015 American Heart Association, Inc.

Global trends and challenges in deceased donor kidney allocation.

PubMed

Wu, Diana A; Watson, Christopher J; Bradley, J Andrew; Johnson, Rachel J; Forsythe, John L; Oniscu, Gabriel C

2017-06-01

Worldwide, the number of patients able to benefit from kidney transplantation is greatly restricted by the severe shortage of deceased donor organs. Allocation of this scarce resource is increasingly challenging and complex. Striking an acceptable balance between efficient use of (utility) and fair access to (equity) the limited supply of donated kidneys raises controversial but important debates at ethical, medical, and social levels. There is no international consensus on the recipient and donor factors that should be considered in the kidney allocation process. There is a general trend toward a reduction in the influence of human leukocyte antigen mismatch and an increase in the importance of other factors shown to affect posttransplant outcomes, such as cold ischemia, duration of dialysis, donor and recipient age, and comorbidity. Increased consideration of equity has led to improved access to transplantation for disadvantaged patient groups. There has been an overall improvement in the transparency and accountability of allocation policies. Novel and contentious approaches in kidney allocation include the use of survival prediction scores as a criterion for accessing the waiting list and at the point of organ offering with matching of predicted graft and recipient survival. This review compares the diverse international approaches to deceased donor kidney allocation and their evolution over the last decade. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.

PubMed

Lentine, Krista L; Kasiske, Bertram L; Levey, Andrew S; Adams, Patricia L; Alberú, Josefina; Bakr, Mohamed A; Gallon, Lorenzo; Garvey, Catherine A; Guleria, Sandeep; Li, Philip Kam-Tao; Segev, Dorry L; Taler, Sandra J; Tanabe, Kazunari; Wright, Linda; Zeier, Martin G; Cheung, Michael; Garg, Amit X

2017-08-01

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, many recommendations, for which there was no evidence or no systematic search for evidence was undertaken by the Evidence Review Team, were issued as ungraded expert opinion recommendations. The guideline work group concluded that a comprehensive approach to risk assessment should replace decisions based on assessments of single risk factors in isolation. Original data analyses were undertaken to produce a "proof-in-concept" risk-prediction model for kidney failure to support a framework for quantitative risk assessment in the donor candidate evaluation and defensible shared decision making. This framework is grounded in the simultaneous consideration of each candidate's profile of demographic and health characteristics. The processes and framework for the donor candidate evaluation are presented, along with recommendations for optimal care before, during, and after donation. Limitations of the evidence are discussed, especially regarding the lack of definitive prospective studies and clinical outcome trials. Suggestions for future research, including the need for continued refinement of long-term risk prediction and novel approaches to estimating donation-attributable risks, are also provided.In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Living Kidney Donor Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017;101(Suppl 8S):S1-S109.

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

Quality of Sleep and its Relationship to Quality of Life in Hemodialysis Patients

PubMed Central

Parvan, Kobra; lakdizaji, Sima; Roshangar, Fariborz; Mostofi, Mahtab

2013-01-01

Introduction: Despite many advances in the treatment of chronic renal failure, the quality of sleep in patients who suffer from this disease is at the risk. The high prevalence of sleep disorders in hemodialysis patients, which is concomitant with physical, behavioral, and psychological problems, has always affected these patients' quality of life (QOL). This study aimed to determine the relationship between quality of sleep and quality of life in hemodialysis patients. Methods: By using a descriptive and correlational design, this study was conducted on 245 hemodialysis patients in 2012. Patients were selected by convenience sampling from the hemodialysis ward of four training hospitals of Tabriz and Maragheh. Quality of sleep was measured by the Pittsburgh Sleep Quality Index (PSQI), and the quality of life for patients was measured by the Kidney Disease Quality Of Life questionnaire (KDQOL-SF). Results: 83.3% of hemodialysis patients had poor quality of sleep. Poor quality of life was significantly associated with poor quality of sleep. There was a significant negative correlation between global PSQI and important aspects of quality of life including physical health, symptoms and problems, the impact of kidney disease on daily life, burden of kidney disease, mental health, social support, and sexual function. Conclusion: The low quality of sleep in hemodialysis patients has an effect on the deterioration of their quality of life. Therefore, training, counseling, and advocacy programs should be developed to improve the patients' quality of sleep and quality of life, especially those with lower education level and income, and older people. PMID:25276738

Interleukin-1β Activates a MYC-Dependent Metabolic Switch in Kidney Stromal Cells Necessary for Progressive Tubulointerstitial Fibrosis.

PubMed

Lemos, Dario R; McMurdo, Michael; Karaca, Gamze; Wilflingseder, Julia; Leaf, Irina A; Gupta, Navin; Miyoshi, Tomoya; Susa, Koichiro; Johnson, Bryce G; Soliman, Kirolous; Wang, Guanghai; Morizane, Ryuji; Bonventre, Joseph V; Duffield, Jeremy S

2018-06-01

Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1 α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo , in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids. Results In mice, MYC and the target genes thereof became activated in resident SCs early after kidney injury, suggesting that acute innate immune signals regulate this transcriptional switch. In vitro , stimulation of purified human kidney SCs and human kidney organoids with IL-1 β recapitulated the molecular events observed in vivo , inducing functional metabolic derangement characterized by increased MYC-dependent glycolysis, the latter proving necessary to drive proliferation and matrix production. MYC interacted directly with sequestosome 1/p62, which is involved in proteasomal degradation, and modulation of p62 expression caused inverse effects on MYC expression. IL-1 β stimulated autophagy flux, causing degradation of p62 and accumulation of MYC. Inhibition of the IL-1R signal transducer kinase IRAK4 in vivo or inhibition of MYC in vivo as well as in human kidney organoids in vitro abrogated fibrosis and reduced tubular injury. Conclusions Our findings define a connection between IL-1 β and metabolic switch in fibrosis initiation and progression and highlight IL-1 β and MYC as potential therapeutic targets in tubulointerstitial diseases. Copyright © 2018 by the American Society of Nephrology.

Waiting for a kidney transplant: the experience of patients with end-stage renal disease in South Korea.

PubMed

Chong, Hye Jin; Kim, Hyun Kyung; Kim, Sung Reul; Lee, Sik

2016-04-01

To explore the experiences of Korean patients with end-stage renal disease awaiting kidney transplantation. The need for kidney transplantation has increased worldwide, while the number of kidney donors has not increased commensurately. This mismatch is a serious issue in South Korea. Prolonged waits for transplantation may cause physical and psychosocial issues and lead to poor outcomes. Nevertheless, the experience of waiting for kidney transplantation in South Korea has never been explored in depth. A qualitative descriptive design was used. The participants were eight patients diagnosed with end-stage renal disease on the waiting list for kidney transplantation in South Korea. Data were collected through individual in-depth interviews. All conversations during interviews were recorded and transcribed verbatim. Transcribed data were analysed using conventional content analysis. The experience of waiting for kidney transplantation consisted of six categories: (1) the light at the end of the tunnel, (2) being on call without any promise, (3) a tough tug of war between excitement and frustration, (4) doubts in the complexity, (5) A companion on the hard journey and (6) getting ready for D-day. Kidney transplantation candidates experience psychosocial difficulties and concerns while waiting for long periods of time without any assurance of resolution. Systematic education and psychosocial support from health care professionals and family members help patients get through what they describe as a difficult journey. Comprehensive management programs for kidney transplantation candidates are needed. Health care professionals need to recognise the psychosocial concerns of patients awaiting kidney transplantation. Clinicians should provide patients with information and support throughout the waiting period. © 2016 John Wiley & Sons Ltd.

Severe vitamin D deficiency upon admission in critically ill patients is related to acute kidney injury and a poor prognosis.

PubMed

Zapatero, A; Dot, I; Diaz, Y; Gracia, M P; Pérez-Terán, P; Climent, C; Masclans, J R; Nolla, J

2018-05-01

To evaluate the prevalence of vitamin D deficiency in critically ill patients upon admission to an Intensive Care Unit (ICU) and its prognostic implications. A single-center, prospective observational study was carried out from January to November 2015. Patients were followed-up on until death or hospital discharge. The department of Critical Care Medicine of a university hospital. All adults admitted to the ICU during the study period, without known factors capable of altering serum 25(OH)D concentration. Determination of serum 25(OH)D levels within the first 24h following admission to the ICU. Prevalence and mortality at 28 days. The study included 135 patients, of which 74% presented deficient serum 25(OH)D levels upon admission to the ICU. Non-survivors showed significantly lower levels than survivors (8.14ng/ml [6.17-11.53] vs. 12ng/ml [7.1-20.30]; P=.04], and the serum 25(OH)D levels were independently associated to mortality (OR 2.86; 95% CI 1.05-7.86; P=.04]. The area under the ROC curve was 0.61 (95% CI 0.51-0.75), and the best cut-off point for predicting mortality was 10.9ng/ml. Patients with serum 25(OH)D<10.9ng/ml also showed higher acute kidney injury rates (13 vs. 29%; P=.02). Vitamin D deficiency is highly prevalent upon admission to the ICU. Severe Vitamin D deficiency (25[OH]D<10.9ng/ml) upon admission to the ICU is associated to acute kidney injury and mortality. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Prevention of contrast-induced nephropathy with single bolus erythropoietin in patients with diabetic kidney disease: A randomized controlled trial.

PubMed

Shema-Didi, Lilach; Kristal, Batya; Eizenberg, Sarit; Marzuq, Nabil; Sussan, Majdy; Feldman-Idov, Yulie; Ofir, Pnina; Atar, Shaul

2016-04-01

Contrast-induced-nephropathy (CIN) is associated with poor outcomes, thus prevention of CIN may be of clinical value. Erythropoietin (EPO) has been shown to elicit tissue-protective effects in experimental models and in clinical studies of acute kidney injury. We therefore evaluated its effectiveness for prevention of CIN after coronary angiography (CA) ± percutaneous coronary intervention (PCI) in diabetic patients with chronic kidney disease. A prospective, randomized, controlled trial was carried out in 138 diabetic patients with eGFR <60 mL/min who underwent non-urgent CA ± PCI. Patients received normal saline and n-acetyl cysteine before CA, with or without 50,000 U of EPO administered 30 min prior to CA. CIN was defined as an increase in serum creatinine of at least 0.5 mg/dL during the first 2 days after exposure to contrast media. Primary outcome was the incidence of CIN. Secondary outcomes were the sensitivity and positive predictive value (PPV) of Cystatin C (CC) and Neutrophil-gelatinase-associated-lipocalin (NGAL) for diagnosis of CIN. The observed incidence of CIN was 8.7%, significantly lower than the expected for such high-risk population. The administration of EPO prior to CA did not reduce the incidence of CIN (9.7% vs. 7.6%, P = 0.65). CC and NGAL demonstrated a low sensitivity (16.6%) and low PPV (6.7 and 33.3%, respectively) for detecting CIN. The administration of EPO prior to CA did not reduce the incidence of CIN. Additional prospective research with a larger sample size and in other patient categories is essential to further define the potential protective effect of EPO on prevention of CIN. © 2015 Asian Pacific Society of Nephrology.

Gist of medicinal plants of Pakistan having ethnobotanical evidences to crush renal calculi (kidney stones).

PubMed

Nasim, Muhammad Jawad; Bin Asad, Muhammad Hassham Hassan; Durr-e-Sabih; Ikram, Raja Muhammad; Hussain, Muhammad Sikandar; Khan, Muhammad Tajammal; Ahamad, Ghafoor; Karim, Sabiha; Khan, Shujaat Ali; Murtaza, Ghulam

2014-01-01

Human civilization is facing the problem of kidney stones since ancient ages. Although mortality rate is not so high, yet it affects the victim's quality of life. The patient suffers from intense pain and many other symptoms modifying his life style and affecting his socioeconomic status. Many drugs and invasive methods have also been developed for the treatment, but these are highly costly and unaffordable for poor people and the rate of reoccurrence is also high. The use of medicinal plants is both affordable and effective in this respect. In this article, 35 medicinal plants of Pakistan origin and their crucial information have been enumerated in alphabetical order of plant's scientific name, family, place (distribution), part used, local name, habit, major constituents and references. It can also be seen that all parts are used for the treatment of kidney stones. Leaves represent 28% contribution, whole plants and seeds 12%, fruits and roots 11% contribution in this respect. Flowers contribute 8% in the treatment of kidney stone while branches, bark, bushes, buds, milk and shoots contribute only 3% in the removal of kidney stones. Habits of plants were also taken under consideration. It was noticed that herbs are the most useful life form in this regard which contributed 63% for the removal of kidney stone. Shrubs contributed 20%, trees 11% while bushes and weeds contributed 3% for the removal of kidney stones.

Serum Uromodulin Levels in Prediction of Acute Kidney Injury in the Early Phase of Acute Pancreatitis.

PubMed

Kuśnierz-Cabala, Beata; Gala-Błądzińska, Agnieszka; Mazur-Laskowska, Małgorzata; Dumnicka, Paulina; Sporek, Mateusz; Matuszyk, Aleksandra; Gil, Krzysztof; Ceranowicz, Piotr; Walocha, Jerzy; Kucharz, Jakub; Pędziwiatr, Michał; Bartuś, Krzysztof; Trąbka, Rafał; Kuźniewski, Marek

2017-06-14

In health, uromodulin is the main protein of urine. Serum uromodulin concentrations (sUMOD) have been shown to correlate with kidney function. Acute kidney injury (AKI) is among the main complications of severe acute pancreatitis (AP). No reports exist on sUMOD in patients with AP, including the diagnostic usefulness for early prediction of AP severity. We measured sUMOD during first 72 h of AP. Sixty-six adult patients with AP were recruited at the surgical ward of the District Hospital in Sucha Beskidzka, Poland. AP was diagnosed according to the Revised Atlanta Classification. Blood samples were collected at 24, 48 and 72 h of AP, and sUMOD concentrations were measured with enzyme-linked immunosorbent test. sUMOD decreased non-significantly during the study. Patients with severe AP had non-significantly lower sUMOD concentrations than those with mild disease. Significant positive correlation was observed between sUMOD and estimated glomerular filtration rate on each day of the study and negative correlations were shown between sUMOD and age, serum creatinine, cystatin C and urea. Patients with AKI tended to have lower sUMOD. Although sUMOD correlated significantly with kidney function in the early phase of AP, measuring sUMOD did not allow to reliably predict AP severity or development of AKI.

Newborn screening: A disease-changing intervention for glutaric aciduria type 1.

PubMed

Boy, Nikolas; Mengler, Katharina; Thimm, Eva; Schiergens, Katharina A; Marquardt, Thorsten; Weinhold, Natalie; Marquardt, Iris; Das, Anibh M; Freisinger, Peter; Grünert, Sarah C; Vossbeck, Judith; Steinfeld, Robert; Baumgartner, Matthias R; Beblo, Skadi; Dieckmann, Andrea; Näke, Andrea; Lindner, Martin; Heringer, Jana; Hoffmann, Georg F; Mühlhausen, Chris; Maier, Esther M; Ensenauer, Regina; Garbade, Sven F; Kölker, Stefan

2018-05-01

Untreated individuals with glutaric aciduria type 1 (GA1) commonly present with a complex, predominantly dystonic movement disorder (MD) following acute or insidious onset striatal damage. Implementation of GA1 into newborn screening (NBS) programs has improved the short-term outcome. It remains unclear, however, whether NBS changes the long-term outcome and which variables are predictive. This prospective, observational, multicenter study includes 87 patients identified by NBS, 4 patients missed by NBS, and 3 women with GA1 identified by positive NBS results of their unaffected children. The study population comprises 98.3% of individuals with GA1 identified by NBS in Germany during 1999-2016. Overall, cumulative sensitivity of NBS is 95.6%, but it is lower (84%) for patients with low excreter phenotype. The neurologic outcome of patients missed by NBS is as poor as in the pre-NBS era, and the clinical phenotype of diagnosed patients depends on the quality of therapeutic interventions rather than noninterventional variables. Presymptomatic start of treatment according to current guideline recommendations clearly improves the neurologic outcome (MD: 7% of patients), whereas delayed emergency treatment results in acute onset MD (100%), and deviations from maintenance treatment increase the risk of insidious onset MD (50%). Independent of the neurologic phenotype, kidney function tends to decline with age, a nonneurologic manifestation not predicted by any variable included in this study. NBS is a beneficial, disease-changing intervention for GA1. However, improved neurologic outcome critically depends on adherence to recommended therapy, whereas kidney dysfunction does not appear to be impacted by recommended therapy. Ann Neurol 2018;83:970-979. © 2018 American Neurological Association.

Detailed kinetics of EBV-specific CD4+ and CD8+ T cells during primary EBV infection in a kidney transplant patient.

PubMed

Piriou, Erwan R W A N; van Dort, Karel; Weel, Jan F L; Bemelman, Frederike J; Gamadia, Laila E; van Oers, Marinus H J; van Baarle, Debbie

2006-04-01

The etiology of infectious mononucleosis is poorly understood and usually detected many weeks after infection. Here, we present a unique case of primary symptomatic EBV infection after kidney transplantation, in whom we analyzed both EBV-specific CD4+ and CD8+ T cells in detail from the moment of infection up to latency. We show that EBV-specific T-cell responses in peripheral blood during primary EBV infection after kidney transplantation peaked early after the appearance of viral load, but well before onset of IM symptoms, suggesting that IM in this case is not caused by high numbers of CD8+ T cells per se but may be caused by lack of homing to lymph nodes or tonsils.

The Role of Procurement Biopsies in Acceptance Decisions for Kidneys Retrieved for Transplant

PubMed Central

Stewart, Darren E.; Bista, Bipin R.; Salkowski, Nicholas; Snyder, Jon J.; Israni, Ajay K.; Crary, Gretchen S.; Rosendale, John D.; Matas, Arthur J.; Delmonico, Francis L.

2014-01-01

Background and objectives There is a shortage of kidneys for transplant, and many patients on the deceased donor kidney transplant waiting list would likely benefit from kidneys that are currently being discarded. In the United States, the most common reason given for discarding kidneys retrieved for transplant is procurement biopsy results. This study aimed to compare biopsy results from discarded kidneys with discard attributed to biopsy findings, with biopsy results from comparable kidneys that were successfully transplanted. Design, setting, participants, & measurements In this retrospective, observational, case-control study, biopsy reports were examined from 83 kidneys discarded in 2010 due to biopsy findings (cases), 83 contralateral transplanted kidneys from the same donor (contralateral controls), and 83 deceased donors randomly matched to cases by donor risk profile (randomly matched controls). A second procurement biopsy was obtained in 64 of 332 kidneys (19.3%). Results The quality of biopsy reports was low, with amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, and acute tubular necrosis often not indicated; 69% were wedge biopsies and 94% used frozen tissue. The correlation between first and second procurement biopsies was poor; only 25% of the variability (R2) in glomerulosclerosis was explained by biopsies being from the same kidney. The percentages of glomerulosclerosis overlapped substantially between cases, contralateral controls, and randomly matched controls: 17.1%±15.3%, 9.0%±6.6%, and 5.0%±5.9%, respectively. Of all biopsy findings, only glomerulosclerosis>20% was independently correlated with discard (cases versus contralateral controls; odds ratio, 15.09; 95% confidence interval, 2.47 to 92.41; P=0.003), suggesting that only this biopsy result was used in acceptance decisions. One-year graft survival was 79.5% and 90.7% in contralateral and randomly matched controls, respectively, versus 91.6% among all deceased donor transplants in the Scientific Registry of Transplant Recipients. Conclusions Routine use of biopsies could lead to unnecessary kidney discards. PMID:24558053

Successful Management of New-Onset Diabetes Mellitus and Obesity With the Use of Laparoscopic Sleeve Gastrectomy After Kidney Transplantation-A Case Report.

PubMed

Chen, J H; Lee, C H; Chang, C M; Yin, W Y

2016-04-01

In kidney transplantation, obesity is associated with poorer graft survival and patient survival. Bariatric surgery may provide benefit for these patients, not only by inducing weight loss, but also via reduction of diabetes. We report a case of morbid obesity, poorly controlled new-onset diabetes mellitus, and gout after kidney transplantation that was treated with laparoscopic sleeve gastrectomy 3 years after kidney transplantation. After 1 year of follow-up, 76% excessive body weight loss was attained. No complications were noted. The operation also provided total remission of diabetes and gout as well as good graft survival. Based on our experience, laparoscopic sleeve gastrectomy may be a feasible treatment for obese patients after renal transplantation to help resolve obesity and control new-onset diabetes. However, the timing of operation and the long-term potential for graft and patient survivals with this operation require further study. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of bortezomib in heavy-chain deposition disease: a report of 3 cases.

PubMed

Patel, Kinjal; Dillon, John J; Leung, Nelson; Bomback, Andrew S; Appel, Gerald B; D'Agati, Vivette; Canetta, Pietro A

2014-07-01

Heavy-chain deposition disease (HCDD) is a rare complication of plasma cell dyscrasia in which monoclonal heavy chains deposit in glomerular and tubular basement membranes of the kidney. Clinical and pathologic features of HCDD have been well described in case reports and series, but evidence supporting specific therapies is sparse. Historically, the disease has had a poor prognosis, intensifying the need to clarify optimal treatments. We describe 3 cases of HCDD with biopsy-proven glomerular involvement, severe nephrotic syndrome, and decline in kidney function that were treated successfully with bortezomib, a proteasome inhibitor. None of these patients had multiple myeloma. In all cases, bortezomib-based therapy resulted in sustained resolution of nephrotic syndrome and improvement in kidney function. All 3 patients developed peripheral neuropathy; otherwise, treatment was well tolerated. To our knowledge, this is the first description of the clinical effectiveness of bortezomib against HCDD. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Functional principal component analysis of glomerular filtration rate curves after kidney transplant.

PubMed

Dong, Jianghu J; Wang, Liangliang; Gill, Jagbir; Cao, Jiguo

2017-01-01

This article is motivated by some longitudinal clinical data of kidney transplant recipients, where kidney function progression is recorded as the estimated glomerular filtration rates at multiple time points post kidney transplantation. We propose to use the functional principal component analysis method to explore the major source of variations of glomerular filtration rate curves. We find that the estimated functional principal component scores can be used to cluster glomerular filtration rate curves. Ordering functional principal component scores can detect abnormal glomerular filtration rate curves. Finally, functional principal component analysis can effectively estimate missing glomerular filtration rate values and predict future glomerular filtration rate values.

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

Simultaneous Liver-Kidney Transplantation: Impact on Liver Transplant Patients and the Kidney Transplant Waiting List.

PubMed

Miles, Clifford D; Westphal, Scott; Liapakis, AnnMarie; Formica, Richard

2018-01-01

The number of simultaneous liver-kidney transplants (SLKT) performed in the USA has been rising. The Organ Procurement and Transplantation Network implemented a new policy governing SLKT that specifies eligibility criteria for candidates to receive a kidney with a liver, and creates a kidney waitlist "safety net" for liver recipients with persistent renal failure after transplant. This review explores potential impacts for liver patients and the kidney waitlist. Factors that have contributed to the rise in SLKT including Model for End-stage Liver Disease (MELD)-based allocation, regional sharing for high MELD candidates, and the rising incidence of non-alcoholic steatohepatitis will continue to increase the number of liver transplant candidates with concurrent renal insufficiency. The effect of center behavior based on the new policy is harder to predict, given wide historic variability in SLKT practice. Continued increase in combined liver/kidney failure is likely, and SLKT and kidney after liver transplant may both increase. Impact of the new policy should be carefully monitored, but influences beyond the policy need to be accounted for.

Biomarkers and surrogate endpoints in kidney disease

PubMed Central

2015-01-01

Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. “Hard” endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease. PMID:25980469

Antibody-Mediated Rejection of the Kidney after Simultaneous Pancreas-Kidney Transplantation

PubMed Central

Pascual, Julio; Samaniego, Milagros D.; Torrealba, José R.; Odorico, Jon S.; Djamali, Arjang; Becker, Yolanda T.; Voss, Barbara; Leverson, Glen E.; Knechtle, Stuart J.; Sollinger, Hans W.; Pirsch, John D.

2008-01-01

The prevalence, risk factors, and outcome of antibody-mediated rejection (AMR) of the kidney after simultaneous pancreas-kidney transplantation are unknown. In 136 simultaneous pancreas-kidney recipients who were followed for an average of 3.1 yr, 21 episodes of AMR of the kidney allograft were identified. Eight episodes occurred early (≤90 d) after transplantation, and 13 occurred later. Histologic evidence of concomitant acute cellular rejection was noted in 12 cases; the other nine had evidence only of humoral rejection. In 13 cases, clinical rejection of the pancreas was diagnosed simultaneously, and two of these were biopsy proven and were positive for C4d immunostaining. Multivariate analysis identified only one significant risk factor: Female patients were three times more likely to experience AMR. Nearly all early episodes resolved with treatment and did not predict graft loss, but multivariate Cox models revealed that late AMR episodes more than tripled the risk for kidney and pancreas graft loss; therefore, new strategies are needed to prevent and to treat late AMR in simultaneous pancreas-kidney transplant recipients. PMID:18235091

Experimental lead poisoning in Turkey Vultures, Cathartes aura

USGS Publications Warehouse

Carpenter, J.W.; Pattee, O.H.; Fritts, S.H.; Rattner, B.A.; Wiemeyer, Stanley N.; Royle, J. Andrew; Smith, M.R.

2003-01-01

Lead-induced mortality appears to have been a major factor in the decline of the California condor, Gymnogyps californianus. We orally dosed turkey vultures (Cathartes aura) with BB-sized lead shot from January 1988 through July 1988 to determine physiological response (delta-aminolevulinic acid dehydratase inhibition, erythrocyte protoporphyrin levels, anemia), diagnostic tissue lead concentrations (blood, liver, and kidney), and comparative sensitivity of this species. Two turkey vultures died and two became so intoxicated they were euthanized. Overall, responses of measured parameters were comparable to other species exposed to lead although there was considerable individual variation. Survival time (143-211 days), even with the large number of shot and constant redosing, was much longer than reported for other species of birds, suggesting considerable tolerance by turkey vultures to the deleterious effects of lead ingestion. Based on these observations, turkey vultures appear to be poor models for assessing the risk of lead poisoning to California condors or predicting their physiological response.

Complete genome sequence of the fish pathogen Flavobacterium psychrophilum ATCC 49418(T.).

PubMed

Wu, Anson Kk; Kropinski, Andrew M; Lumsden, John S; Dixon, Brian; MacInnes, Janet I

2015-01-01

Flavobacterium psychrophilum is the causative agent of bacterial cold water disease and rainbow trout fry mortality syndrome in salmonid fishes and is associated with significant losses in the aquaculture industry. The virulence factors and molecular mechanisms of pathogenesis of F. psychrophilum are poorly understood. Moreover, at the present time, there are no effective vaccines and control using antimicrobial agents is problematic due to growing antimicrobial resistance and the fact that sick fish don't eat. In the hopes of identifying vaccine and therapeutic targets, we sequenced the genome of the type strain ATCC 49418 which was isolated from the kidney of a Coho salmon (Oncorhychus kisutch) in Washington State (U.S.A.) in 1989. The genome is 2,715,909 bp with a G+C content of 32.75%. It contains 6 rRNA operons, 49 tRNA genes, and is predicted to encode 2,329 proteins.

Complete genome sequence of the fish pathogen Flavobacterium psychrophilum ATCC 49418T

PubMed Central

2015-01-01

Flavobacterium psychrophilum is the causative agent of bacterial cold water disease and rainbow trout fry mortality syndrome in salmonid fishes and is associated with significant losses in the aquaculture industry. The virulence factors and molecular mechanisms of pathogenesis of F. psychrophilum are poorly understood. Moreover, at the present time, there are no effective vaccines and control using antimicrobial agents is problematic due to growing antimicrobial resistance and the fact that sick fish don’t eat. In the hopes of identifying vaccine and therapeutic targets, we sequenced the genome of the type strain ATCC 49418 which was isolated from the kidney of a Coho salmon (Oncorhychus kisutch) in Washington State (U.S.A.) in 1989. The genome is 2,715,909 bp with a G+C content of 32.75%. It contains 6 rRNA operons, 49 tRNA genes, and is predicted to encode 2,329 proteins. PMID:25685258

A kidney from hell? A nephrological view of the Whitechapel murders in 1888.

PubMed

Wolf, Gunter

2008-10-01

In the poor Whitechapel district of the East End of London in the fall of 1888, at least five prostitutes were brutally murdered, and in all but one case, also mutilated. The murderer was never caught and became known by his nickname 'Jack the Ripper'. The left kidney and the uterus were cut out and taken away from one of the victims named Catherine Eddowes. A kidney was also cut out of the body from another victim, but not taken away. Two weeks later, George Lusk, president of the Whitechapel Vigilance Committee, received a small cardboard box with half of a longitudinally divided kidney and a letter entitled 'From hell' claiming that the kidney inside the box was taken from the victim. The kidney was brought to Dr Thomas Horrocks Openshaw, the Curator of the London Pathological Museum, where the kidney could be microscopically examined. The press jumped on the topic and made a circumstantial case that this kidney had been indeed torn from the body of Catherine Eddowes. According to the later memoirs of Major Henry Smith of the City Police published more than 20 years after the incident, the kidney left in the corpse of Catherine Eddowes was in an advanced stage of Bright's disease and the kidney sent to George Lusk was in exactly a similar stage. Today, the majority of criminologists believe that the kidney sent to Mr Lusk was a hoax as were other letters signed with Jack the Ripper. However, the murderer took organs from his victims, and in the case of Catherine Eddowes, the kidney. Serial killers often mutilate their victims and abscond with the removed body parts as trophies. By removing the kidney from Catherine Eddowes, Jack the Ripper may have tried to take possession of the conscience, emotions and desires of one of his victims, attributes residing in the kidney as described in the Bible. Jack the Ripper was never caught; many suspects have been suggested, and the murder series ended as suddenly as it had begun. We will never know who this mentally disturbed 'nephrophilic' was. Today, the story of Jack the Ripper is part of contemporary culture.

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

Skin autofluorescence as a measure of advanced glycation endproduct deposition: a novel risk marker in chronic kidney disease.

PubMed

Smit, Andries J; Gerrits, Esther G

2010-11-01

Skin autofluorescence (SAF) is a new method to noninvasively assess accumulation of advanced glycation endproducts (AGEs) in a tissue with low turnover. Recent progress in the clinical application of SAF as a risk marker for diabetic nephropathy as well as cardiovascular disease in nondiabetic end-stage kidney disease, less advanced chronic kidney disease, and renal transplant recipients is reviewed. Experimental studies highlight the fundamental role of the interaction of AGEs with the receptor for AGEs (RAGEs), also called the AGE-RAGE axis, in the pathogenesis of vascular and chronic kidney disease. SAF predicts (cardiovascular) mortality in renal failure and also chronic renal transplant dysfunction. Long-term follow-up results from the Diabetes Control and Complications Trial and UK Prospective Diabetes Study suggest that AGE accumulation is a key carrier of metabolic memory and oxidative stress. Short-term intervention studies in diabetic nephropathy with thiamine, benfotiamine and angiotensin-receptor blockers aimed at reducing AGE formation have reported mixed results. SAF is a noninvasive marker of AGE accumulation in a tissue with low turnover, and thereby of metabolic memory and oxidative stress. SAF independently predicts cardiovascular and renal risk in diabetes, as well as in chronic kidney disease. Further long-term studies are required to assess the potential benefits of interventions to reduce AGE accumulation.

Black Americans' Perspectives of Barriers and Facilitators of Community Screening for Kidney Disease.

PubMed

Umeukeje, Ebele M; Wild, Marcus G; Maripuri, Saugar; Davidson, Teresa; Rutherford, Margaret; Abdel-Kader, Khaled; Lewis, Julia; Wilkins, Consuelo H; Cavanaugh, Kerri

2018-04-06

Incidence of ESKD is three times higher in black Americans than in whites, and CKD prevalence continues to rise among black Americans. Community-based kidney disease screening may increase early identification and awareness of black Americans at risk, but it is challenging to implement. This study aimed to identify participants' perspectives of community kidney disease screening. The Health Belief Model provides a theoretic framework for conceptualization of these perspectives and optimization of community kidney disease screening activities. Researchers in collaboration with the Tennessee Kidney Foundation conducted three focus groups of adults in black American churches in Nashville, Tennessee. Questions examined views on CKD information, access to care, and priorities of kidney disease health. Content analysis was used. Guided by the Health Belief Model, a priori themes were generated, and additional themes were derived from the data using an inductive approach. Thirty-two black Americans completed the study in 2014. Participants were mostly women (79%) with a mean age of 56 years old (range, 24-78). Two major categories of barriers to kidney disease screening were identified: ( 1 ) participant factors, including limited kidney disease knowledge, spiritual/religious beliefs, emotions, and culture of the individual; and ( 2 ) logistic factors, including lack of convenience and incentives and poor advertisement. Potential facilitators of CKD screening included provision of CKD education, convenience of screening activities, and use of culturally sensitive and enhanced communication strategies. Program recommendations included partnering with trusted community members, selecting convenient locations, tailored advertising, and provision of compensation. Findings of this study suggest that provider-delivered culturally sensitive education and stakeholder engagement are critical to increase trust, decrease fear, and maximize participation and early identification of kidney disease among black Americans considering community screening. Copyright © 2018 by the American Society of Nephrology.

Antibody-mediated rejection in kidney transplantation: a review of pathophysiology, diagnosis, and treatment options.

PubMed

Kim, Miae; Martin, Spencer T; Townsend, Keri R; Gabardi, Steven

2014-07-01

Antibody-mediated rejection (AMR), also known as B-cell-mediated or humoral rejection, is a significant complication after kidney transplantation that carries a poor prognosis. Although fewer than 10% of kidney transplant patients experience AMR, as many as 30% of these patients experience graft loss as a consequence. Although AMR is mediated by antibodies against an allograft and results in histologic changes in allograft vasculature that differ from cellular rejection, it has not been recognized as a separate disease process until recently. With an improved understanding about the importance of the development of antibodies against allografts as well as complement activation, significant advances have occurred in the treatment of AMR. The standard of care for AMR includes plasmapheresis and intravenous immunoglobulin that remove and neutralize antibodies, respectively. Agents targeting B cells (rituximab and alemtuzumab), plasma cells (bortezomib), and the complement system (eculizumab) have also been used successfully to treat AMR in kidney transplant recipients. However, the high cost of these medications, their use for unlabeled indications, and a lack of prospective studies evaluating their efficacy and safety limit the routine use of these agents in the treatment of AMR in kidney transplant recipients. © 2014 Pharmacotherapy Publications, Inc.

B-type natriuretic peptide and cardiac troponin I are associated with adverse outcomes in stable kidney transplant recipients

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Approximately 200 000 kidney transplant recipients are living in the United States; they are at increased risk for cardiovascular and other adverse outcomes. Biomarkers predicting these outcomes are needed. Using specimens collected during the Folic Acid for Vascular Outcome Reduction in...

Implications of dynamic changes in miR-192 expression in ischemic acute kidney injury.

PubMed

Zhang, Lulu; Xu, Yuan; Xue, Song; Wang, Xudong; Dai, Huili; Qian, Jiaqi; Ni, Zhaohui; Yan, Yucheng

2017-03-01

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) with poor outcomes. While many important functions of microRNAs (miRNAs) have been identified in various diseases, few studies reported miRNAs in acute kidney IRI, especially the dynamic changes in their expression and their implications during disease progression. The expression of miR-192, a specific kidney-enriched miRNA, was assessed in both the plasma and kidney of IRI rats at different time points after kidney injury and compared to renal function and kidney histological changes. The results were validated in the plasma of the selected patients with AKI after cardiac surgery compared with those matched patients without AKI. The performance characteristics of miR-192 were summarized using area under the receiver operator characteristic (ROC) curves (AUC-ROC). MiRNA profiling in plasma led to the identification of 42 differentially expressed miRNAs in the IRI group compared to the sham group. MiR-192 was kidney-enriched and chosen for further validation. Real-time PCR showed that miR-192 levels increased by fourfold in the plasma and decreased by about 40% in the kidney of IRI rats. Plasma miR-192 expression started increasing at 3 h and peaked at 12 h, while kidney miR-192 expression started decreasing at 6 h and remained at a low level for 7 days after reperfusion. Plasma miR-192 level in patients with AKI increased at the time of ICU admission, was stable for 2 h and decreased after 24 h. AUC-ROC was 0.673 (95% CI: 0.540-0.806, p = 0.014). Plasma miR-192 expression was induced in a time-dependent manner after IRI in rats and patients with AKI after cardiac surgery, comparably to the kidney injury development and recovery process, and may be useful for the detection of AKI.

Incidence and Risk Factors for Leukopenia in Kidney Transplant Recipients Receiving Valganciclovir for Cytomegalovirus Prophylaxis.

PubMed

Liang, Xinyun; Famure, Olusegun; Li, Yanhong; Kim, S Joseph

2018-06-01

Valganciclovir is used not only for cytomegalovirus prophylaxis after kidney transplantation but can also induce leukopenia, thereby making patients more susceptible to other infections. The epidemiology of leukopenia in patients on valganciclovir remains poorly understood. To determine the incidence and risk factors for leukopenia in patients receiving valganciclovir for cytomegalovirus prophylaxis after kidney transplantation. In this single-center, retrospective, cohort study, we included kidney recipients transplanted from January 1, 2003, to December 31, 2010, to determine the incidence and risk factors for leukopenia in patients who received valganciclovir for cytomegalovirus prophylaxis. The Kaplan-Meier product limit method was used to graphically assess time to leukopenia, and risk factors were assessed using Cox proportional hazards models. A total of 542 kidney transplant recipients were included in the study cohort. The cumulative incidence of leukopenia at 6 months posttransplant was 39.3% (11.0% for neutropenia). Low baseline white blood cell count (hazard ratio [HR] 2.34 [95% confidence interval [CI], 1.37-4.00]) and high baseline body mass index (HR 1.05 [95% CI, 1.02-1.09]) were independently associated with an increased risk of leukopenia, while higher Cockcroft-Gault creatinine clearance (HR 0.87 [95% CI, 0.78-0.97]) was significantly associated with a decreased risk of leukopenia. These data suggest that recipient baseline white blood cell count, baseline body mass index, and kidney function are clinical predictors of new-onset leukopenia after kidney transplantation. Our results may inform the approach to cytomegalovirus prophylaxis to reduce the risk of valganciclovir-induced leukopenia in kidney transplant recipients.

Apelin/APJ system: A novel potential therapy target for kidney disease.

PubMed

Huang, Zhen; Wu, Lele; Chen, Linxi

2018-05-01

Apelin is an endogenous ligand of seven-transmembrane G protein-coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, kidney, and even in tumor tissues. Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important role in process of water and sodium balance. Additionally, more studies also indicate that apelin/APJ system exerts a broad range of activities in kidney. Therefore, we review the role of apelin/APJ system in kidney diseases such as renal fibrosis, renal ischemia/reperfusion injury, diabetic nephropathy, polycystic kidney disease, and hemodialysis (HD). Apelin/APJ system can improve renal interstitial fibrosis by reducing the deposition of extracellular matrix. Apelin/APJ system significantly reduces renal ischemia/reperfusion injury by inhibiting renal cell death. Apelin/APJ system involves the progression of diabetic nephropathy (DN). Apelin/APJ system also predicts the process of polycystic kidney disease. Besides, apelin/APJ system prevents some dialysis complications in HD patients. And apelin/APJ system alleviates chronic kidney disease (CKD) by inhibiting vascular calcification (VC). Overall, apelin/APJ system plays diversified roles in kidney disease and may be a potential target for the treatment of kidney disease. © 2017 Wiley Periodicals, Inc.

Kidney damage in extracorporeal shock wave lithotripsy: a numerical approach for different shock profiles.

PubMed

Weinberg, Kerstin; Ortiz, Michael

2009-08-01

In shock-wave lithotripsy--a medical procedure to fragment kidney stones--the patient is subjected to hypersonic waves focused at the kidney stone. Although this procedure is widely applied, the physics behind this medical treatment, in particular the question of how the injuries to the surrounding kidney tissue arise, is still under investigation. To contribute to the solution of this problem, two- and three-dimensional numerical simulations of a human kidney under shock-wave loading are presented. For this purpose a constitutive model of the bio-mechanical system kidney is introduced, which is able to map large visco-elastic deformations and, in particular, material damage. The specific phenomena of cavitation induced oscillating bubbles is modeled here as an evolution of spherical pores within the soft kidney tissue. By means of large scale finite element simulations, we study the shock-wave propagation into the kidney tissue, adapt unknown material parameters and analyze the resulting stress states. The simulations predict localized damage in the human kidney in the same regions as observed in animal experiments. Furthermore, the numerical results suggest that in first instance the pressure amplitude of the shock wave impulse (and not so much its exact time-pressure profile) is responsible for damaging the kidney tissue.

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.

Aortic PWV in chronic kidney disease: a CRIC ancillary study.

PubMed

Townsend, Raymond R; Wimmer, Neil J; Chirinos, Julio A; Parsa, Afshin; Weir, Matthew; Perumal, Kalyani; Lash, James P; Chen, Jing; Steigerwalt, Susan P; Flack, John; Go, Alan S; Rafey, Mohammed; Rahman, Mahboob; Sheridan, Angela; Gadegbeku, Crystal A; Robinson, Nancy A; Joffe, Marshall

2010-03-01

Aortic pulse wave velocity (PWV) is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end-stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease (CKD) who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV. We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in CKD. PWV measurements were obtained in 2,564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were <7.7 m/s, 7.7-10.2 m/s, and >10.2 m/s with an overall mean (+/- s.d.) value of 9.48 +/- 3.03 m/s (95% confidence interval = 9.35-9.61 m/s). Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function. The large size of this unique cohort, and the targeted enrollment of CKD participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure.

Difficult conversations: Australian Indigenous patients' views on kidney transplantation.

PubMed

Devitt, Jeannie; Anderson, Kate; Cunningham, Joan; Preece, Cilla; Snelling, Paul; Cass, Alan

2017-10-11

Indigenous Australians suffer a disproportionate burden of end stage kidney disease (ESKD) but are significantly less likely to receive a transplant. This study explores Indigenous ESKD patients' views on transplantation as a treatment option. The Improving Access to Kidney Transplants (IMPAKT) research program investigated barriers to kidney transplantation for Indigenous Australians. An interview study, conducted in 2005-2006, elicited illness experience narratives from 146 Indigenous patients, including views on transplant. Interviews were conducted at 26 sites that collectively treat the majority of Indigenous ESKD patients. Key themes were identified via team consensus meetings, providing a flexible framework and focus for continued coding. Four inter-related themes were identified in patient commentary: a very high level (90% of respondents) of positive interest in transplantation; patients experienced a range of communication difficulties and felt uninformed about transplant; family involvement in decision-making was constrained by inadequate information; and patients needed to negotiate cultural and social sensitivities around transplantation. Indigenous ESKD patients demonstrated an intense interest in transplantation preferring deceased over living kidney donation. Patients believe transplant is the path most likely to support the re-establishment of their 'normal' family life. Patients described themselves as poorly informed; most had only a rudimentary knowledge of the notion of transplant but no understanding of eligibility criteria, the transplant procedure and associated risks. Patients experienced multiple communication barriers that - taken together - undermine their engagement in treatment decision-making. Families and communities are disempowered because they also lack information to reach a shared understanding of transplantation. Cultural sensitivities associated with transplantation were described but these did not appear to constrain patients in making choices about their own health. Transplant units and local treatment providers should collaborate to develop user-friendly, culturally informed and region-specific patient education programs. Quality improvement cycles should underpin the development of national guidelines for patient education. Noting Indigenous patients' intense interest in transplantation, and nephrologists' concerns regarding poor transplant outcomes, research should prioritise exploring the predictors of transplant outcomes for Indigenous Australians.

Utilizing electronic health records to predict acute kidney injury risk and outcomes: workgroup statements from the 15(th) ADQI Consensus Conference.

PubMed

Sutherland, Scott M; Chawla, Lakhmir S; Kane-Gill, Sandra L; Hsu, Raymond K; Kramer, Andrew A; Goldstein, Stuart L; Kellum, John A; Ronco, Claudio; Bagshaw, Sean M

2016-01-01

The data contained within the electronic health record (EHR) is "big" from the standpoint of volume, velocity, and variety. These circumstances and the pervasive trend towards EHR adoption have sparked interest in applying big data predictive analytic techniques to EHR data. Acute kidney injury (AKI) is a condition well suited to prediction and risk forecasting; not only does the consensus definition for AKI allow temporal anchoring of events, but no treatments exist once AKI develops, underscoring the importance of early identification and prevention. The Acute Dialysis Quality Initiative (ADQI) convened a group of key opinion leaders and stakeholders to consider how best to approach AKI research and care in the "Big Data" era. This manuscript addresses the core elements of AKI risk prediction and outlines potential pathways and processes. We describe AKI prediction targets, feature selection, model development, and data display.

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.

Pretransplant Recipient Circulating CD4+CD127lo/- Tumor Necrosis Factor Receptor 2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and Predictor of Delayed and Slow Graft Function After Kidney Transplantation.

PubMed

Nguyen, Minh-Tri J P; Fryml, Elise; Sahakian, Sossy K; Liu, Shuqing; Cantarovich, Marcelo; Lipman, Mark; Tchervenkov, Jean I; Paraskevas, Steven

2016-02-01

Delayed graft function (DGF) and slow graft function (SGF) are ischemia-reperfusion-associated acute kidney injuries (AKI) that decrease long-term graft survival after kidney transplantation. Regulatory T (Treg) cells are protective in murine AKI, and their suppressive function predictive of AKI in kidney transplantation. The conventional Treg cell function coculture assay is however time-consuming and labor intensive. We sought a simpler alternative to measure Treg cell function and predict AKI. In this prospective observational cohort study, pretransplant recipient circulating CD4+CD25+CD127lo/- and CD4+CD127lo/- tumor necrosis factor receptor 2 (TNFR2)+ Treg cells were measured by flow cytometry in 76 deceased donor kidney transplant recipients (DGF, n = 18; SGF, n = 34; immediate graft function [IGF], n = 24). In a subset of 37 recipients, pretransplant circulating Treg cell-suppressive function was also quantified by measuring the suppression of autologous effector T-cell proliferation by Treg cell in coculture. The TNFR2+ expression on CD4+CD127lo/- T cells correlated with Treg cell-suppressive function (r = 0.63, P < 0.01). In receiver operating characteristic curves, percentage and absolute number of CD4+CD127lo/-TNFR2+ Treg cell predicted DGF from non-DGF (IGF + SGF) with area under the curves of 0.75 and 0.77, respectively, and also AKI (DGF + SGF) from IGF with area under the curves of 0.76 and 0.72, respectively (P < 0.01). Prediction of AKI (DGF + SGF) from IGF remained significant in multivariate logistic regression accounting for cold ischemic time, donor age, previous transplant, and pretransplant dialysis modality. Pretransplant recipient circulating CD4+CD127lo/-TNFR2+ Treg cell is potentially a simpler alternative to Treg cell function as a pretransplant recipient immune marker for AKI (DGF + SGF), independent from donor and organ procurement characteristics.

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.

Organ trafficking and transplant tourism: a commentary on the global realities.

PubMed

Budiani-Saberi, D A; Delmonico, F L

2008-05-01

The extent of organ sales from commercial living donors (CLDs) or vendors has now become evident. At the Second Global Consultation on Human Transplantation of the World Health Organization's (WHO) in March 2007, it was estimated that organ trafficking accounts for 5-10% of the kidney transplants performed annually throughout the world. Patients with sufficient resources in need of organs may travel from one country to another to purchase a kidney (or liver) mainly from a poor person. Transplant centers in 'destination' countries have been well known to encourage the sale of organs to 'tourist' recipients from the 'client' countries.

Timely Diagnosis of Acute Kidney Injury Using Kinetic eGFR and the Creatinine Excretion to Production Ratio, E/eG - Creatinine Can Be Useful!

PubMed

Endre, Zoltán H; Pianta, Timothy J; Pickering, John W

2016-01-01

Post transplant repeated measurements of urine volume and serum creatinine (sCr) are used to assess kidney function. Under non-steady state conditions, repeated measurement of sCr allows calculation of the kinetic estimated GFR (KeGFR). Additional measurement of urinary creatinine allows the calculation of the creatinine excretion to (estimated) production ratio (E/eG). We hypothesized that post-transplant KeGFR and E/eG would predict delayed graft function (DGF), as early as 4 h and outperform a validated clinical model at 12 h. This was a retrospective analysis of prospectively acquired data in a study of 56 recipients of deceased-donor kidney transplant. We assessed predictive performance with the area under the receiver operator characteristic curve (AUC) and the added value to a clinical model with integrated discrimination improvement analysis. At 4 h, the AUC for E/eG was 0.87 (95% CI 0.77-0.96) and for KeGFR 0.69 (95% CI 0.56-0.83). Both E/eG and KeGFR improved the risk prediction of a clinical model for DGF by 32 and 18%, and for non-DGF by 17 and 10%, respectively. While E/eG had better predictive performance of DGF than KeGFR, KeGFR might also facilitate perioperative management including drug dosing after kidney transplantation. Together these measurements may facilitate the possibility of conducting trials of early intervention to ameliorate the adverse effects of ischaemia-reperfusion injury on long-term DGF. © 2016 S. Karger AG, Basel.

Urinary biomarkers predict advanced acute kidney injury after cardiovascular surgery.

PubMed

Wang, Jian-Jhong; Chi, Nai-Hsin; Huang, Tao-Min; Connolly, Rory; Chen, Liang Wen; Chueh, Shih-Chieh Jeff; Kan, Wei-Chih; Lai, Chih-Cheng; Wu, Vin-Cent; Fang, Ji-Tseng; Chu, Tzong-Shinn; Wu, Kwan-Dun

2018-04-26

Acute kidney injury (AKI) after cardiovascular surgery is a serious complication. Little is known about the ability of novel biomarkers in combination with clinical risk scores for prediction of advanced AKI. In this prospectively conducted multicenter study, urine samples were collected from 149 adults at 0, 3, 6, 12 and 24 h after cardiovascular surgery. We measured urinary hemojuvelin (uHJV), kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), α-glutathione S-transferase (uα-GST) and π-glutathione S-transferase (uπ-GST). The primary outcome was advanced AKI, under the definition of Kidney Disease: Improving Global Outcomes (KDIGO) stage 2, 3 and composite outcomes were KDIGO stage 2, 3 or 90-day mortality after hospital discharge. Patients with advanced AKI had significantly higher levels of uHJV and uKIM-1 at 3, 6 and 12 h after surgery. When normalized by urinary creatinine level, uKIM-1 in combination with uHJV at 3 h post-surgery had a high predictive ability for advanced AKI and composite outcome (AUC = 0.898 and 0.905, respectively). The combination of this biomarker panel (normalized uKIM-1, uHJV at 3 h post-operation) and Liano's score was superior in predicting advanced AKI (AUC = 0.931, category-free net reclassification improvement of 1.149, and p <  0.001). When added to Liano's score, normalized uHJV and uKIM-1 levels at 3 h after cardiovascular surgery enhanced the identification of patients at higher risk of progression to advanced AKI and composite outcomes.

NMR-based urine analysis in rats: prediction of proximal tubule kidney toxicity and phospholipidosis.

PubMed

Lienemann, Kai; Plötz, Thomas; Pestel, Sabine

2008-01-01

The aim of safety pharmacology is early detection of compound-induced side-effects. NMR-based urine analysis followed by multivariate data analysis (metabonomics) identifies efficiently differences between toxic and non-toxic compounds; but in most cases multiple administrations of the test compound are necessary. We tested the feasibility of detecting proximal tubule kidney toxicity and phospholipidosis with metabonomics techniques after single compound administration as an early safety pharmacology approach. Rats were treated orally, intravenously, inhalatively or intraperitoneally with different test compounds. Urine was collected at 0-8 h and 8-24 h after compound administration, and (1)H NMR-patterns were recorded from the samples. Variation of post-processing and feature extraction methods led to different views on the data. Support Vector Machines were trained on these different data sets and then aggregated as experts in an Ensemble. Finally, validity was monitored with a cross-validation study using a training, validation, and test data set. Proximal tubule kidney toxicity could be predicted with reasonable total classification accuracy (85%), specificity (88%) and sensitivity (78%). In comparison to alternative histological studies, results were obtained quicker, compound need was reduced, and very importantly fewer animals were needed. In contrast, the induction of phospholipidosis by the test compounds could not be predicted using NMR-based urine analysis or the previously published biomarker PAG. NMR-based urine analysis was shown to effectively predict proximal tubule kidney toxicity after single compound administration in rats. Thus, this experimental design allows early detection of toxicity risks with relatively low amounts of compound in a reasonably short period of time.

Assessment of triglyceride and cholesterol in overweight people based on multiple linear regression and artificial intelligence model.

PubMed

Ma, Jing; Yu, Jiong; Hao, Guangshu; Wang, Dan; Sun, Yanni; Lu, Jianxin; Cao, Hongcui; Lin, Feiyan

2017-02-20

The prevalence of high hyperlipemia is increasing around the world. Our aims are to analyze the relationship of triglyceride (TG) and cholesterol (TC) with indexes of liver function and kidney function, and to develop a prediction model of TG, TC in overweight people. A total of 302 adult healthy subjects and 273 overweight subjects were enrolled in this study. The levels of fasting indexes of TG (fs-TG), TC (fs-TC), blood glucose, liver function, and kidney function were measured and analyzed by correlation analysis and multiple linear regression (MRL). The back propagation artificial neural network (BP-ANN) was applied to develop prediction models of fs-TG and fs-TC. The results showed there was significant difference in biochemical indexes between healthy people and overweight people. The correlation analysis showed fs-TG was related to weight, height, blood glucose, and indexes of liver and kidney function; while fs-TC was correlated with age, indexes of liver function (P < 0.01). The MRL analysis indicated regression equations of fs-TG and fs-TC both had statistic significant (P < 0.01) when included independent indexes. The BP-ANN model of fs-TG reached training goal at 59 epoch, while fs-TC model achieved high prediction accuracy after training 1000 epoch. In conclusions, there was high relationship of fs-TG and fs-TC with weight, height, age, blood glucose, indexes of liver function and kidney function. Based on related variables, the indexes of fs-TG and fs-TC can be predicted by BP-ANN models in overweight people.

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)

Plasma protein biomarkers enhance the clinical prediction of kidney injury recovery in patients undergoing liver transplantation.

PubMed

Levitsky, Josh; Baker, Talia B; Jie, Chunfa; Ahya, Shubhada; Levin, Murray; Friedewald, John; Al-Saden, Patrice; Salomon, Daniel R; Abecassis, Michael M

2014-12-01

Biomarkers predictive of recovery from acute kidney injury (AKI) after liver transplantation (LT) could enhance decision algorithms regarding the need for liver-kidney transplantation or renal sparing regimens. Multianalyte plasma/urine kidney injury protein panels were performed immediately before and 1 month post-LT in an initial test group divided by reversible pre-LT AKI (rAKI = post-LT renal recovery) versus no AKI (nAKI). This was followed by a larger validation set that included an additional group: irreversible pre-LT AKI (iAKI = no post-LT renal recovery). In the test group (n = 16), six pre-LT plasma (not urine) kidney injury proteins (osteopontin [OPN], neutrophil gelatinase-associated lipocalin, cystatin C, trefoil factor 3, tissue inhibitor of metalloproteinase [TIMP]-1, and β-2-microglobulin) were higher in rAKI versus nAKI (P < 0.05) and returned to normal values with renal recovery post-LT. In the validation set (n = 46), a number of proteins were significantly higher in both rAKI and iAKI versus nAKI. However, only pre-LT plasma OPN (P = 0.009) and TIMP-1 (P = 0.019) levels were significantly higher in rAKI versus iAKI. Logistic regression modeling was used to correlate the probability of post-LT rAKI, factoring in both pre-LT protein markers and clinical variables. A combined model including elevated OPN and TIMP-1 levels, age <57, and absence of diabetes had the highest area under the curve of 0.82, compared to protein-only and clinical variable-only models. These data suggest that plasma protein profiles might improve the prediction of pre-LT kidney injury recovery after LT. However, multicenter, prospective studies are needed to validate these findings and ultimately test the value of such protein panels in perioperative management and decision making. © 2014 by the American Association for the Study of Liver Diseases.

Chemokine Receptor Ccr1 Drives Neutrophil-Mediated Kidney Immunopathology and Mortality in Invasive Candidiasis

PubMed Central

Lionakis, Michail S.; Swamydas, Muthulekha; Wan, Wuzhou; Richard Lee, Chyi-Chia; Cohen, Jeffrey I.; Scheinberg, Phillip; Gao, Ji-Liang; Murphy, Philip M.

2012-01-01

Invasive candidiasis is the 4th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1lo to Ccr1high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1+/+ and Ccr1−/− donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ. PMID:22916017

Association of U.S. Dialysis Facility Neighborhood Characteristics with Facility-Level Kidney Transplantation

PubMed Central

Plantinga, Laura; Pastan, Stephen; Kramer, Michael; McClellan, Ann; Krisher, Jenna; Patzer, Rachel E.

2014-01-01

Background Improving access to optimal healthcare may depend on attributes of neighborhoods where patients receive healthcare services. We investigated whether characteristics of dialysis facility neighborhoods—where most patients with end-stage renal disease are treated—were associated with facility-level kidney transplantation. Methods We examined the association between census tract (neighborhood)-level sociodemographic factors and facility-level kidney transplantation rate in 3,983 U.S. dialysis facilities with reported kidney transplantation rates. Number of kidney transplants and total person-years contributed at the facility level in 2007-2010 were obtained from the Dialysis Facility Report and linked to census tract data on sociodemographic characteristics from the American Community Survey 2006-2010 by dialysis facility location. We used multivariable Poisson models with generalized estimating equations to estimate associations between neighborhood characteristics and transplant incidence. Results U.S. dialysis facilities were located in neighborhoods with substantially greater proportions of black and poor residents, relative to the national average. Most facility neighborhood characteristics were associated with transplant, with incidence rate ratios (95% CI) for standardized increments (in percentage) of neighborhood exposures of: living in poverty, 0.88 (0.84-0.92), black race, 0.83 (0.78-0.89); high school graduates, 1.22 (1.17-1.26); and unemployed, 0.90 (0.85-0.95). Conclusion Dialysis facility neighborhood characteristics may be modestly associated with facility rates of kidney transplantation. The success of dialysis facility interventions to improve access to kidney transplantation may partially depend on reducing neighborhood-level barriers. PMID:25196018

Molecular Classifiers for Acute Kidney Transplant Rejection in Peripheral Blood by Whole Genome Gene Expression Profiling

PubMed Central

Kurian, S. M.; Williams, A. N.; Gelbart, T.; Campbell, D.; Mondala, T. S.; Head, S. R.; Horvath, S.; Gaber, L.; Thompson, R.; Whisenant, T.; Lin, W.; Langfelder, P.; Robison, E. H.; Schaffer, R. L.; Fisher, J. S.; Friedewald, J.; Flechner, S. M.; Chan, L. K.; Wiseman, A. C.; Shidban, H.; Mendez, R.; Heilman, R.; Abecassis, M. M.; Marsh, C. L.; Salomon, D. R.

2015-01-01

There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi-array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one-by-one analysis strategy to model the real clinical application of this test. Multiple three-way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction. PMID:24725967

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.

[Spleen, liver and kidney-strengthening formula combined with polyethylene glycol interferon in treatment of chronic hepatitis B].

PubMed

Chen, Wei

2016-02-01

To observe the clinical efficacy of spleen, liver and kidney-strengthening formula combined with polyethylene glycol interferon in the treatment of HBeAg positive chronic hepatitis B(HP-HBV).One hundred and twenty-six patients with HP-HBV, who were treated in the hospital from June 2012 to December 2014, were selected and injected with polyethylene glycol interferon α-2a(or α-2b). The treatment course for the patients lasted for 24 weeks. Base on the level of HBV-DNA, patients are divided into response group and poor response group. According to random number table, the poor response group were randomized into control group and test group. Patients in the control group were injected with polyethylene glycol interferon α-2a(or α-2b), and patients in the test group were treated with spleen, liver and kidney-strengthening formula combined with polyethylene glycol interferon. Clinical efficacies of the 2 groups were observed, and changes in the level of HBeAg, ALT and HBV-DNA were observed before treatment and at the 24th week after treatment, and virological and serological response, biochemical responses, integral clinical symptoms and signs, adverse reactions were observed after 48 weeks of treatment.After 24 weeks of treatment, the response group was significantly better than the poor response group in HBeAg, ALT and the level of HBV-DNA(P<0.05). After 48 weeks of treatment, there was statistical significance in HBV-DNA negative conversion rate, HBeAg negative conversion rate between the 2 groups(P<0.05), and the test group was better in the two indicators. And the test group was significantly lower than the control group in clinical symptoms and signs score at the 48th week after treatment(P<0.05), with a significantly lower adverse reaction rate than the control group(P<0.05).Combination of spleen, liver and kidney-strengthening formula and polyethylene glycol interferon α-2a was effective and safe in the treatment of chronic hepatitis B, and so worth promoting in clinic. Copyright© by the Chinese Pharmaceutical Association.

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.

Improved prediction of tacrolimus concentrations early after kidney transplantation using theory-based pharmacokinetic modelling.

PubMed

Størset, Elisabet; Holford, Nick; Hennig, Stefanie; Bergmann, Troels K; Bergan, Stein; Bremer, Sara; Åsberg, Anders; Midtvedt, Karsten; Staatz, Christine E

2014-09-01

The aim was to develop a theory-based population pharmacokinetic model of tacrolimus in adult kidney transplant recipients and to externally evaluate this model and two previous empirical models. Data were obtained from 242 patients with 3100 tacrolimus whole blood concentrations. External evaluation was performed by examining model predictive performance using Bayesian forecasting. Pharmacokinetic disposition parameters were estimated based on tacrolimus plasma concentrations, predicted from whole blood concentrations, haematocrit and literature values for tacrolimus binding to red blood cells. Disposition parameters were allometrically scaled to fat free mass. Tacrolimus whole blood clearance/bioavailability standardized to haematocrit of 45% and fat free mass of 60 kg was estimated to be 16.1 l h−1 [95% CI 12.6, 18.0 l h−1]. Tacrolimus clearance was 30% higher (95% CI 13, 46%) and bioavailability 18% lower (95% CI 2, 29%) in CYP3A5 expressers compared with non-expressers. An Emax model described decreasing tacrolimus bioavailability with increasing prednisolone dose. The theory-based model was superior to the empirical models during external evaluation displaying a median prediction error of −1.2% (95% CI −3.0, 0.1%). Based on simulation, Bayesian forecasting led to 65% (95% CI 62, 68%) of patients achieving a tacrolimus average steady-state concentration within a suggested acceptable range. A theory-based population pharmacokinetic model was superior to two empirical models for prediction of tacrolimus concentrations and seemed suitable for Bayesian prediction of tacrolimus doses early after kidney transplantation.

Predicting long-term graft survival in adult kidney transplant recipients.

PubMed

Pinsky, Brett W; Lentine, Krista L; Ercole, Patrick R; Salvalaggio, Paolo R; Burroughs, Thomas E; Schnitzler, Mark A

2012-07-01

The ability to accurately predict a population's long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population's long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS) projections were calculated and compared with the population's actual graft survival. The projection curves were created using a two-part estimation model that (1) fits a Kaplan-Meier survival curve immediately after transplant (Part A) and (2) uses truncated observational data to model a survival function for long-term projection (Part B). Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted survival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%). Excellent predictability (41.3%) can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population's long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.

Health and Nutrition Literacy and Adherence to Treatment in Children, Adolescents, and Young Adults With Chronic Kidney Disease and Hypertension, North Carolina, 2015

PubMed Central

Ferris, Maria; Rak, Eniko

2016-01-01

Introduction Adherence to treatment and dietary restrictions is important for health outcomes of patients with chronic/end-stage kidney disease and hypertension. The relationship of adherence with nutritional and health literacy in children, adolescents, and young adults is not well understood. The current study examined the relationship of health literacy, nutrition knowledge, nutrition knowledge–behavior concordance, and medication adherence in a sample of children and young people with chronic/end-stage kidney disease and hypertension. Methods We enrolled 74 patients (aged 7–29 y) with a diagnosis of chronic/end-stage kidney disease and hypertension from the University of North Carolina Kidney Center. Participants completed instruments of nutrition literacy (Disease-Specific Nutrition Knowledge Test), health literacy (Newest Vital Sign), nutrition behavior (Nutrition Knowledge–Behavior Concordance Scale), and medication adherence (Morisky Medication Adherence Scale). Linear and binary logistic regressions were used to test the associations. Results In univariate comparisons, nutrition knowledge was significantly higher in people with adequate health literacy. Medication adherence was related to nutrition knowledge and nutrition knowledge–behavior concordance. Multivariate regression models demonstrated that knowledge of disease-specific nutrition restrictions did not significantly predict nutrition knowledge–behavior concordance scores. In logistic regression, knowledge of nutrition restrictions did not significantly predict medication adherence. Lastly, health literacy and nutrition knowledge–behavior concordance were significant predictors of medication adherence. Conclusion Nutrition knowledge and health literacy skills are positively associated. Nutrition knowledge, health literacy, and nutrition knowledge–behavior concordance are positively related to medication adherence. Future research should focus on additional factors that may predict disease-specific nutrition behavior (adherence to dietary restrictions) in children and young people with chronic conditions. PMID:27490366

A mouse diversity panel approach reveals the potential for clinical kidney injury due to DB289 not predicted by classical rodent models.

PubMed

Harrill, Alison H; Desmet, Kristina D; Wolf, Kristina K; Bridges, Arlene S; Eaddy, J Scott; Kurtz, C Lisa; Hall, J Ed; Paine, Mary F; Tidwell, Richard R; Watkins, Paul B

2012-12-01

DB289 is the first oral drug shown in clinical trials to have efficacy in treating African trypanosomiasis (African sleeping sickness). Mild liver toxicity was noted but was not treatment limiting. However, development of DB289 was terminated when several treated subjects developed severe kidney injury, a liability not predicted from preclinical testing. We tested the hypothesis that the kidney safety liability of DB289 would be detected in a mouse diversity panel (MDP) comprised of 34 genetically diverse inbred mouse strains. MDP mice received 10 days of oral treatment with DB289 or vehicle and classical renal biomarkers blood urea nitrogen (BUN) and serum creatinine (sCr), as well as urine biomarkers of kidney injury were measured. While BUN and sCr remained within reference ranges, marked elevations were observed for kidney injury molecule-1 (KIM-1) in the urine of sensitive mouse strains. KIM-1 elevations were not always coincident with elevations in alanine aminotransferase (ALT), suggesting that renal injury was not linked to hepatic injury. Genome-wide association analyses of KIM-1 elevations indicated that genes participating in cholesterol and lipid biosynthesis and transport, oxidative stress, and cytokine release may play a role in DB289 renal injury. Taken together, the data resulting from this study highlight the utility of using an MDP to predict clinically relevant toxicities, to identify relevant toxicity biomarkers that may translate into the clinic, and to identify potential mechanisms underlying toxicities. In addition, the sensitive mouse strains identified in this study may be useful in screening next-in-class compounds for renal injury.

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.

Herpes virus infection associated with interstitial nephritis in a beaked whale (Mesoplodon densirostris)

PubMed Central

2012-01-01

Background The capacity for herpesvirus to cause disease in cetaceans is unclear and may be varied depending on the different conditions of individuals and between different species. Kidney pathology and intralesional virus-associated infection have been rarely reported in cetaceans. Result On April 2004, an old adult male Blainville’s beaked whale (Mesoplodon densirostris) 420 cm long with a poor body condition was stranded on Tenerife Island. During necropsy, no gross lesions were observed in the kidneys. However, membranous glomerulonephritis, multifocal interstitial lymphoplasmacytic nephritis and acute multifocal necrotizing tubulointerstitial nephritis with intranuclear inclusion bodies was diagnosed by histological analysis. Tissue samples were submitted for bacteriological analysis and molecular viral screening. Conclusion A novel alpha herpesvirus associated with interstitial nephritis was identified in an old adult male Blainville's beaked whale (M. densirostris) with a poor body condition stranded in the Canary Islands. This report suggests that identification of herpesvirus infection could be used as a differential diagnosis for interstitial nephritis in cetaceans. PMID:23237059

Non-proteinuric rather than proteinuric renal diseases are the leading cause of end-stage kidney disease.

PubMed

Bolignano, Davide; Zoccali, Carmine

2017-04-01

Proteinuria is a distinguishing feature in primary and secondary forms of chronic glomerulonephritis, which contribute to no more than the 20% of the end-stage kidney disease (ESKD) population. The contribution of non-proteinuric nephropathies to the global ESKD burden is still poorly focused and scarce research efforts are dedicated to the elucidation of risk factors and mechanistic pathways triggering ESKD in these diseases. We abstracted information on proteinuria in the main renal diseases other than glomerulonephritides that may evolve into ESKD. In type 2 diabetes, non-proteinuric diabetic kidney disease (DKD) is more frequent than proteinuric DKD, and risk factors for non-proteinuric forms of DKD now receive increasing attention. Similarly, proteinuria is most often inconspicuous or absent in the most frequent cause of ESKD, i.e. hypertension-related chronic kidney disease (CKD), as well as in progressive cystic diseases like autosomal dominant polycystic kidney disease and in pyelonephritis/tubulo-interstitial diseases. Maintaining a high degree of attention in the care of CKD patients with proteinuria is fundamental to effectively retard progression toward kidney failure. However, substantial research efforts are still needed to develop treatment strategies that may help the vast majority of CKD patients who eventually develop ESKD via mechanistic pathways other than proteinuria. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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.

Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis.

PubMed

Lindström, Nils O; De Sena Brandine, Guilherme; Tran, Tracy; Ransick, Andrew; Suh, Gio; Guo, Jinjin; Kim, Albert D; Parvez, Riana K; Ruffins, Seth W; Rutledge, Elisabeth A; Thornton, Matthew E; Grubbs, Brendan; McMahon, Jill A; Smith, Andrew D; McMahon, Andrew P

2018-06-04

Mammalian nephrons arise from a limited nephron progenitor pool through a reiterative inductive process extending over days (mouse) or weeks (human) of kidney development. Here, we present evidence that human nephron patterning reflects a time-dependent process of recruitment of mesenchymal progenitors into an epithelial nephron precursor. Progressive recruitment predicted from high-resolution image analysis and three-dimensional reconstruction of human nephrogenesis was confirmed through direct visualization and cell fate analysis of mouse kidney organ cultures. Single-cell RNA sequencing of the human nephrogenic niche provided molecular insights into these early patterning processes and predicted developmental trajectories adopted by nephron progenitor cells in forming segment-specific domains of the human nephron. The temporal-recruitment model for nephron polarity and patterning suggested by direct analysis of human kidney development provides a framework for integrating signaling pathways driving mammalian nephrogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes.

PubMed

Greifenhagen, Uta; Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

2016-04-29

Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. α-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Estimated GFR and the Effect of Intensive Blood Pressure Lowering After Acute Intracerebral Hemorrhage.

PubMed

Zheng, Danni; Sato, Shoichiro; Arima, Hisatomi; Heeley, Emma; Delcourt, Candice; Cao, Yongjun; Chalmers, John; Anderson, Craig S

2016-07-01

The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP<140mmHg) or contemporaneous guideline-based (target SBP<180mmHg) BP management. 2,823 patients from 144 clinical hospitals in 21 countries. Admission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and <60mL/min/1.73m(2), respectively). The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P=0.5 for homogeneity). Generalizability issues arising from a clinical trial population. Decreased eGFR predicts poor outcome in acute ICH. Early intensive BP lowering provides similar treatment effects in patients with ICH with decreased eGFRs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Kidneys for sale: who disapproves, and why?

PubMed

Leider, S; Roth, A E

2010-05-01

The shortage of transplant kidneys has spurred debate about legalizing monetary payments to donors to increase the number of available kidneys. However, buying and selling organs faces widespread disapproval. We survey a representative sample of Americans to assess disapproval for several forms of kidney market, and to understand why individuals disapprove by identifying factors that predict disapproval, including disapproval of markets for other body parts, dislike of increased scope for markets and distrust of markets generally. Our results suggest that while the public is potentially receptive to compensating kidney donors, among those who oppose it, general disapproval toward certain kinds of transactions is at least as important as concern about specific policy details. Between 51% and 63% of respondents approve of the various potential kidney markets we investigate, and between 42% and 58% want such markets to be legal. A total of 38% of respondents disapprove of at least one market. Respondents who distrust markets generally are not more disapproving of kidney markets; however we find significant correlations between kidney market disapproval and attitudes reflecting disapproval toward certain transactions-including both other body markets and market encroachment into traditionally nonmarket exchanges, such as food preparation.

Formula Feeding Is Independently Associated With Acute Kidney Injury in Very Low Birth Weight Infants.

PubMed

Ginovart, Gemma; Gich, Ignasi; Verd, Sergio

2016-11-01

Successful strategies to prevent neonatal acute kidney injury are lacking. Nevertheless, it is well known that in breastfed babies the excretory needs of the kidney are low because the intake of most nutrients is just above the nutritional requirement. This study aimed to determine whether feeding type predicts acute kidney injury in the very low birth weight infant. One hundred and eighty-six infants were enrolled in this pre-post cohort study (114 infants were included in the only human milk-fed group and 72 in the formula-fed group). Routine biological markers of acute kidney injury were collected in both groups from birth to discharge. Compared with formula feeding, human milk feeding was associated with almost 80% lower odds of acute kidney injury (odds ratio [OR] = 0.2; 95% confidence interval [CI], 0.05-0.77). After confounding variables had been controlled for, formula feeding was independently associated with acute kidney injury in very low birth weight infants. The study showed that, at our institution, acute kidney injury in the neonatal period is frequently associated with the avoidable procedure of formula feeding. Further prospective multicenter studies are needed to determine the generality of this association.

Fetal kidney length as a useful adjunct parameter for better determination of gestational age.

PubMed

Ugur, Mete G; Mustafa, Aynur; Ozcan, Huseyin C; Tepe, Neslihan B; Kurt, Huseyin; Akcil, Emre; Gunduz, Reyhan

2016-05-01

To determine the validity of fetal kidney length and amniotic fluid index (AFI) in labor dating.  This prospective study included 180 pregnant women followed up in the outpatient clinic at the Department of Obstetrics and Gynecology, Gaziantep University, Turkey, between January 2014 and January 2015. The gestational age (GA) was estimated by early fetal ultrasound measures and last menstrual period. Routine fetal biometric parameters, fetal kidney length, and amniotic fluid index were measured. We studied the correlation between fetal kidney length, amniotic fluid index, and gestational age.  The mean gestational age depending on last menstrual period and early ultrasound was 31.98±4.29 (24-39 weeks). The mean kidney length was 35.66±6.61 (19-49 mm). There was a significant correlation between gestational age and fetal kidney length (r=0.947, p=0.001). However, there was a moderate negative correlation between GA and AFI. Adding fetal kidney length to the routine biometrics improved the effectiveness of the model used to estimate GA (R2=0.965 to R2=0.987).  Gestational age can be better predicted by adding fetal kidney length to other routine parameters.

Systematic review of kidney transplantation functional predictors.

PubMed

Miret Alomar, E; Trilla Herrera, E; Lorente Garcia, D; Regis Placido, L; López Del Campo, R; Cuadras Solé, M; Pont Castellana, T; Moreso Mateos, F; Serón Micas, D; Morote Robles, J

2018-05-01

Kidney transplantation from donors with expanded criteria has increased the pool of kidneys at the cost of a higher risk of short and long-term graft dysfunction. The main issue lies in determining which kidneys will offer acceptable function and survival compared with the risk represented by surgery and subsequent immunosuppression. The objective of our article is to review the current evidence on the tools for predicting the functionality of kidney transplantation from cadaveric donors with expanded criteria and determining the validity for their use in standard practice. We conducted a systematic literature review according to the PRISM criteria, through Medline (http://www.ncbi.nlm.nih.gov) and using the keywords (in isolation or in conjunction) "cadaveric renal transplantation; kidney graft function appraisal, graft function predictors". We selected prospective and retrospective series and review articles. A total of 375 articles were analysed, 39 of which were ultimately selected for review. The predictors of functionality include the following: The donor risk indices; the calculation of the renal functional weight or the assessment of the nephronic mass; the measurement of vascular resistances during perfusion in hypothermia; the measurement of the donor's biomarkers in urine and in the perfusion liquid; the measurement of functional and reperfusion parameters in normothermia; and the measurement of morphological parameters (microscopic and macroscopic) of the target organ. In this article, we present an explanatory summary of each of these parameters, as well as their most recent evidence on this issue. None of the reviewed parameters in isolation could reliably predict renal function and graft survival. There is a significant void in terms of the macroscopic assessment of kidney transplantation. We need to continue developing predictors of renal functionality to accurately define the distribution of each currently available donor kidney. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors

PubMed Central

Lentine, Krista L.; Kasiske, Bertram L.; Levey, Andrew S.; Adams, Patricia L.; Alberú, Josefina; Bakr, Mohamed A.; Gallon, Lorenzo; Garvey, Catherine A.; Guleria, Sandeep; Li, Philip Kam-Tao; Segev, Dorry L.; Taler, Sandra J.; Tanabe, Kazunari; Wright, Linda; Zeier, Martin G.; Cheung, Michael; Garg, Amit X.

2017-01-01

Abstract The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, many recommendations, for which there was no evidence or no systematic search for evidence was undertaken by the Evidence Review Team, were issued as ungraded expert opinion recommendations. The guideline work group concluded that a comprehensive approach to risk assessment should replace decisions based on assessments of single risk factors in isolation. Original data analyses were undertaken to produce a “proof-in-concept” risk-prediction model for kidney failure to support a framework for quantitative risk assessment in the donor candidate evaluation and defensible shared decision making. This framework is grounded in the simultaneous consideration of each candidate's profile of demographic and health characteristics. The processes and framework for the donor candidate evaluation are presented, along with recommendations for optimal care before, during, and after donation. Limitations of the evidence are discussed, especially regarding the lack of definitive prospective studies and clinical outcome trials. Suggestions for future research, including the need for continued refinement of long-term risk prediction and novel approaches to estimating donation-attributable risks, are also provided. In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Living Kidney Donor Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017;101(Suppl 8S):S1–S109. PMID:28742762

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.

Exploring metabolic dysfunction in chronic kidney disease

PubMed Central

2012-01-01

Impaired kidney function and chronic kidney disease (CKD) leading to kidney failure and end-stage renal disease (ESRD) is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD) risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabolic factors may play key roles in CKD development and pathogenesis. These include raised proinflammatory cytokines, such as interleukin-1 and −6, tumor necrosis factor, altered hepatic acute phase proteins, including reduced albumin, increased C-reactive protein, and perturbations in normal anabolic hormone responses with reduced growth hormone-insulin-like growth factor-1 axis activity. Others include hyperactivation of the renin-angiotensin aldosterone system (RAAS), with angiotensin II and aldosterone implicated in hypertension and the promotion of insulin resistance, and subsequent pharmacological blockade shown to improve blood pressure, metabolic control and offer reno-protective effects. Abnormal adipocytokine levels including leptin and adiponectin may further promote the insulin resistant, and proinflammatory state in CKD. Ghrelin may be also implicated and controversial studies suggest activities may be reduced in human CKD, and may provide a rationale for administration of acyl-ghrelin. Poor vitamin D status has also been associated with patient outcome and CVD risk and may indicate a role for supplementation. Glucocorticoid activities traditionally known for their involvement in the pathogenesis of a number of disease states are increased and may be implicated in CKD-associated hypertension, insulin resistance, diabetes risk and cachexia, both directly and indirectly through effects on other systems including activation of the mineralcorticoid receptor. Insight into the multiple factors altered in CKD may provide useful information on disease pathogenesis, clinical assessment and treatment rationale such as potential pharmacological, nutritional and exercise therapies. PMID:22537670

Characterization of Mineralocorticoid Receptor Antagonist Therapy Initiation in High-Risk Patients With Heart Failure.

PubMed

Cooper, Lauren B; Hammill, Bradley G; Peterson, Eric D; Pitt, Bertram; Maciejewski, Matthew L; Curtis, Lesley H; Hernandez, Adrian F

2017-01-01

Heart failure guidelines recommend routine monitoring of serum potassium, and renal function in patients treated with a mineralocorticoid receptor antagonist (MRA). How these recommendations are implemented in high-risk patients or according to setting of drug initiation is poorly characterized. We conducted a retrospective cohort study of Medicare beneficiaries linked to laboratory data in 10 states with prevalent heart failure as of July 1, 2011, and incident MRA use between May 1 and September 30, 2011. Outcomes included laboratory testing before MRA initiation and in the early (days 1-10) and extended (days 11-90) post-initiation periods, based on setting of drug initiation and the presence of renal insufficiency. Additional outcomes included abnormal laboratory results and adverse events proximate to MRA initiation. Of 10 443 Medicare beneficiaries with heart failure started on an MRA, 19.7% were initiated during a hospitalization. Appropriate follow-up laboratory testing across all time periods occurred in 25.2% of patients with inpatient initiation compared with 2.8% of patients begun as an outpatient. Patients with chronic kidney disease had higher rates of both hyperkalemia and acute kidney failure in the early (1.3% and 2.7%, respectively) and extended (5.6% and 9.8%, respectively) post-initiation periods compared with those without chronic kidney disease. Patients initiated on MRA therapy as an outpatient had extremely poor rates of guideline indicated follow-up laboratory monitoring after drug initiation. In particular, patients with chronic kidney disease are at high risk for adverse events after MRA initiation. Quality improvement initiatives focused on systems to improve appropriate laboratory monitoring are needed. © 2017 American Heart Association, Inc.

The Kidney and Periodontal Disease (KAPD) study: A pilot randomized controlled trial testing the effect of non-surgical periodontal therapy on chronic kidney disease.

PubMed

Grubbs, Vanessa; Garcia, Faviola; Jue, Bonnie L; Vittinghoff, Eric; Ryder, Mark; Lovett, David; Carrillo, Jacqueline; Offenbacher, Steven; Ganz, Peter; Bibbins-Domingo, Kirsten; Powe, Neil R

2017-02-01

Chronic kidney disease (CKD) remains a prevalent public health problem that disproportionately affects minorities and the poor, despite intense efforts targeting traditional risk factors. Periodontal diseases are common bacterial plaque-induced inflammatory conditions that can respond to treatment and have been implicated as a CKD risk factor. However there is limited evidence that treatment of periodontal disease slows the progression of CKD. We describe the protocol of the Kidney and Periodontal Disease (KAPD) study, a 12-month un-blinded, randomized, controlled pilot trial with two intent-to-treat treatment arms: 1. immediate intensive non-surgical periodontal treatment or 2. rescue treatment with delayed intensive treatment. The goals of this pilot study are to test the feasibility of conducting a larger trial in an ethnically and racially diverse, underserved population (mostly poor and/or low literacy) with both CKD and significant periodontal disease to determine the effect of intensive periodontal treatment on renal and inflammatory biomarkers over a 12-month period. To date, KAPD has identified 634 potentially eligible patients who were invited to in-person screening. Of the 83 (13.1%) of potentially eligible patients who attended in-person screening, 51 (61.4%) were eligible for participation and 46 enrolled in the study. The mean age of participants is 59.2years (range 34 to 73). Twenty of the participants (43.5%) are Black and 22 (47.8%) are Hispanic. Results from the KAPD study will provide needed preliminary evidence of the effectiveness of non-surgical periodontal treatment to slow CKD progression and inform the design future clinical research trials. Copyright © 2016. Published by Elsevier Inc.

Simultaneous Liver-Kidney Allocation Policy: A Proposal to Optimize Appropriate Utilization of Scarce Resources.

PubMed

Formica, R N; Aeder, M; Boyle, G; Kucheryavaya, A; Stewart, D; Hirose, R; Mulligan, D

2016-03-01

The introduction of the Mayo End-Stage Liver Disease score into the Organ Procurement and Transplantation Network (OPTN) deceased donor liver allocation policy in 2002 has led to a significant increase in the number of simultaneous liver-kidney transplants in the United States. Despite multiple attempts, clinical science has not been able to reliably predict which liver candidates with renal insufficiency will recover renal function or need a concurrent kidney transplant. The problem facing the transplant community is that currently there are almost no medical criteria for candidacy for simultaneous liver-kidney allocation in the United States, and this lack of standardized rules and medical eligibility criteria for kidney allocation with a liver is counter to OPTN's Final Rule. Moreover, almost 50% of simultaneous liver-kidney organs come from a donor with a kidney donor profile index of ≤0.35. The kidneys from these donors could otherwise be allocated to pediatric recipients, young adults or prior organ donors. This paper presents the new OPTN and United Network of Organ Sharing simultaneous liver-kidney allocation policy, provides the supporting evidence and explains the rationale on which the policy was based. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Using optical coherence tomography (OCT) to evaluate the status of human donor kidneys (Conference Presentation)

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Konkel, Brandon; Anderson, Erik; Stein, Matthew; Cooper, Matthew; Verbesey, Jennifer E.; Ghasemian, Seyed; Chen, Yu

2016-02-01

The main cause of delayed renal function following the transplant of donor kidneys is ischemic induced acute tubular necrosis (ATN). The ability to determine the degree of ATN suffered by donor kidneys prior to their transplant would enable transplant surgeons to use kidneys that might otherwise be discarded and better predict post-transplant renal function. Currently, there are no reliable tests to determine the extent of ATN of donor kidneys prior to their transplant. In ongoing clinical trials, we have been using optical coherence tomography (OCT) to non-invasively image the superficial proximal tubules of human donor kidneys prior to and following transplant, and correlate these observations with post-transplant renal function. Thus far we have studied over 40 living donor kidneys and 10 cadaver donor kidneys, and demonstrated that this imaging can be performed in a sterile and expeditious fashion in the operating room (OR). Because of many variables associated with a diverse population of donors/recipients and transplant operation parameters, more transplant data must be collected prior to drawing definite conclusions. Nevertheless, our observations have thus far mirrored our previously published laboratory results indicating that damage to the kidney proximal tubules as indicated by tubule swelling is a good measure of post-transplant ATN and delayed graft function. We conclude that OCT is a useful procedure for analyzing human donor kidneys.

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.

Market competition influences renal transplantation risk and outcomes.

PubMed

Adler, Joel T; Sethi, Rosh K V; Yeh, Heidi; Markmann, James F; Nguyen, Louis L

2014-09-01

To evaluate the impact of market competition on patient mortality and graft failure after kidney transplantation. Kidneys are initially allocated within 58 donation service areas (DSAs), which have varying numbers of transplant centers. Market competition is generally considered beneficial. The Scientific Registry of Transplant Recipients database was queried and the Herfindahl-Hirschman index (HHI), a measure of market competition, was calculated for each DSA from 2003 to 2012. Receipt of low-quality kidneys (Kidney Donor Profile Index ≥ 85) was modeled with multivariable logistic regression, and Cox proportional hazards models were created for graft failure and patient mortality. A total of 127,355 adult renal transplants were performed. DSAs were categorized as 7 no (HHI = 1), 17 low (HHI = 0.52-0.97), 17 medium (HHI = 0.33-0.51), or 17 high (HHI = 0.09-0.32) competition. For deceased donor kidney transplantation, increasing market competition was significantly associated with mortality [hazard ratio (HR): 1.11, P = 0.01], graft failure (HR: 1.18, P = 0.0001), and greater use of low-quality kidneys (odds ratio = 1.39, P < 0.0001). This was not true for living donor kidney transplantation (mortality HR: 0.94, P = 0.48; graft failure HR: 0.99, P = 0.89). Competition was associated with longer waitlists (P = 0.04) but not with the number of transplants per capita in a DSA (P = 0.21). Increasing market competition is associated with increased patient mortality and graft failure and the use of riskier kidneys. These results may represent more aggressive transplantation and tolerance of greater risk for patients who otherwise have poor alternatives. Market competition should be better studied to ensure optimal outcomes.

Effect of a Mobile Web App on Kidney Transplant Candidates' Knowledge About Increased Risk Donor Kidneys: A Randomized Controlled Trial.

PubMed

Gordon, Elisa J; Sohn, Min-Woong; Chang, Chih-Hung; McNatt, Gwen; Vera, Karina; Beauvais, Nicole; Warren, Emily; Mannon, Roslyn B; Ison, Michael G

2017-06-01

Kidney transplant candidates (KTCs) must provide informed consent to accept kidneys from increased risk donors (IRD), but poorly understand them. We conducted a multisite, randomized controlled trial to evaluate the efficacy of a mobile Web application, Inform Me, for increasing knowledge about IRDs. Kidney transplant candidates undergoing transplant evaluation at 2 transplant centers were randomized to use Inform Me after routine transplant education (intervention) or routine transplant education alone (control). Computer adaptive learning method reinforced learning by embedding educational material, and initial (test 1) and additional test questions (test 2) into each chapter. Knowledge (primary outcome) was assessed in person after education (tests 1 and 2), and 1 week later by telephone (test 3). Controls did not receive test 2. Willingness to accept an IRD kidney (secondary outcome) was assessed after tests 1 and 3. Linear regression test 1 knowledge scores were used to test the significance of Inform Me exposure after controlling for covariates. Multiple imputation was used for intention-to-treat analysis. Two hundred eighty-eight KTCs participated. Intervention participants had higher test 1 knowledge scores (mean difference, 6.61; 95% confidence interval [95% CI], 5.37-7.86) than control participants, representing a 44% higher score than control participants' scores. Intervention participants' knowledge scores increased with educational reinforcement (test 2) compared with control arm test 1 scores (mean difference, 9.50; 95% CI, 8.27-10.73). After 1 week, intervention participants' knowledge remained greater than controls' knowledge (mean difference, 3.63; 95% CI, 2.49-4.78) (test 3). Willingness to accept an IRD kidney did not differ between study arms at tests 1 and 3. Inform Me use was associated with greater KTC knowledge about IRD kidneys above routine transplant education alone.

Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation.

PubMed

Mai, Hoa Le; Treilhaud, Michèle; Ben-Arye, Shani Leviatan; Yu, Hai; Perreault, Hélène; Ang, Evelyn; Trébern-Launay, Katy; Laurent, Julie; Malard-Castagnet, Stéphanie; Cesbron, Anne; Nguyen, Thi Van Ha; Brouard, Sophie; Rostaing, Lionel; Houssel-Debry, Pauline; Legendre, Christophe; Girerd, Sophie; Kessler, Michèle; Morelon, Emmanuel; Sicard, Antoine; Garrigue, Valérie; Karam, Georges; Chen, Xi; Giral, Magali; Padler-Karavani, Vered; Soulillou, Jean Paul

2018-04-01

End-stage renal failure occurs in a substantial number of patients having received a nonrenal transplantation (NRT), for whom a kidney transplantation is needed. The medical strategy regarding the use of immunosuppression (IS) for a kidney graft in patients after an NRT is not well established. The prekidney grafts long-term IS advocates for a mild induction, such as using anti-IL-2R antibodies, whereas addition of new incompatibilities and anti-HLA preimmunization may suggest using stronger IS such as induction by polyclonal antithymocyte globulins (ATG). We performed Cox multivariate and propensity score analysis of our validated transplant database to study the impact of the type of induction therapy on kidney graft survival of recipients of a kidney graft after NRT. We report here that kidney transplantation after NRT treated with an ATG induction has a poorer outcome (kidney and recipient survival) than that with an anti-IL-2R induction. After accounting for potential baseline differences with a multivariate Cox model, or by adjusting on a propensity score, we found that despite patients having received ATG cumulate more risk factors, ATG appears independently involved. As animal-derived biotherapeutics induce antiglycan antibodies and particularly anti-N-glycolylneuraminic acid (Neu5Gc) IgGs which may activate endothelial cells in patients and grafts, we also investigated the magnitude and the nature of the anti-Neu5Gc elicited by the induction and showed that induction was associated with a shift in anti-Neu5Gc IgG repertoire. Possible reasons and mechanisms of a deleterious ATG usage in these patients are discussed. Our study suggests that ATG induction after a kidney transplantation in recipients already under maintenance IS for a NRT should be used cautiously.

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

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.

Epidemiology and outcome of the cardio-renal syndrome.

PubMed

Cruz, Dinna N; Gheorghiade, Mihai; Palazzuoli, Alberto; Palazuolli, Alberto; Ronco, Claudio; Bagshaw, Sean M

2011-11-01

Cardiac and kidney disease are common, increasingly encountered and often co-exist. Recently, the Acute Dialysis Quality Initiative (ADQI) Working Group convened a consensus conference to develop a classification scheme for the CRS and for five discrete subtypes. These CRS subtypes likely share pathophysiologic mechanisms, however, also have distinguishing clinical features, in terms of precipitating events, risk identification, natural history and outcomes. Knowledge of the epidemiology of heart-kidney interaction stratified by the proposed CRS subtypes is increasingly important for understanding the overall burden of disease for each CRS subtype, along with associated morbidity, mortality and health resource utilization. Likewise, an understanding of the epidemiology of CRS is necessary for characterizing whether there exists important knowledge gaps and to aid the in the design of clinical studies. In the most recent European and American guidelines for heart failure management, acute kidney injury and dysfunction were considered an index of poor prognosis. Paradoxically, however, in many randomized trials of interventions for patients with heart failure, those with kidney injury or dysfunction are often excluded. This review will provide a summary of the epidemiology of the cardio-renal syndrome and its subtypes.

Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury

PubMed Central

Vilay, A Mary; Churchwell, Mariann D; Mueller, Bruce A

2008-01-01

Decreased renal drug clearance is an obvious consequence of acute kidney injury (AKI). However, there is growing evidence to suggest that nonrenal drug clearance is also affected. Data derived from human and animal studies suggest that hepatic drug metabolism and transporter function are components of nonrenal clearance affected by AKI. Acute kidney injury may also impair the clearance of formed metabolites. The fact that AKI does not solely influence kidney function may have important implications for drug dosing, not only of renally eliminated drugs but also of those that are hepatically cleared. A review of the literature addressing the topic of drug metabolism and clearance alterations in AKI reveals that changes in nonrenal clearance are highly complicated and poorly studied, but they may be quite common. At present, our understanding of how AKI affects drug metabolism and nonrenal clearance is limited. However, based on the available evidence, clinicians should be cognizant that even hepatically eliminated drugs and formed drug metabolites may accumulate during AKI, and renal replacement therapy may affect nonrenal clearance as well as drug metabolite clearance. PMID:19040780

How to grow a kidney: patient-specific kidney organoids come of age.

PubMed

Schmidt-Ott, Kai M

2017-01-01

The notion of regrowing a patient's kidney in a dish has fascinated researchers for decades and has spurred visions of revolutionary clinical applications. Recently, this option has come closer to reality. Key technologies have been developed to generate patient-specific pluripotent stem cells and to edit their genome. Several laboratories have devised protocols to differentiate patient-specific pluripotent stem cells into kidney cells or into in vitro organoids that resemble the kidney with respect to cell types, tissue architecture and disease pathology. This was possible because of rapidly expanding knowledge regarding the cellular and molecular basis of embryonic kidney development. Generating kidney cells or organoids from patient-specific stem cells may prove to be clinically useful in several ways. First, patient-specific kidney cells or organoids could be used to predict an individual's response to stressors, toxins or medications and thereby develop personalized treatment decisions. Second, patient-specific stem cells harbour the individual's genetic defects. This may potentially enable genetic rescue attempts to establish the significance of a genetic defect in a stem cell-derived organoid or it may allow testing of patient-specific targeted therapies for kidney disease in vitro. From a tissue engineering perspective, patient-specific kidney organoids might provide a key advance towards engineering immunocompatible transplantable kidneys. This review article summarizes recent developments in the field and discusses its current limitations and future perspectives. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Correlates of Physical Functioning and Performance Across the Spectrum of Kidney Function.

PubMed

Segura-Ortí, E; Gordon, P L; Doyle, J W; Johansen, K L

2018-06-01

The aim of this study was to determine the extent to which poor physical functioning, low participation in physical activity, and muscle atrophy observed among patients on hemodialysis are evident in the earlier stages of chronic kidney disease (CKD). We enrolled adults in three groups: no CKD, Stages 3 to 4 CKD, and hemodialysis. Outcomes measured were physical activity, muscle size, thigh muscle strength, physical performance, and self-reported physical function. Patients with CKD had muscle area intermediate between the no CKD and hemodialysis groups, but they had low levels of physical activity that were similar to the hemodialysis group. Physical activity and muscle size were significantly associated with all outcomes. Kidney function was not significantly associated with muscle strength or physical performance after adjustment for physical activity and muscle size. In conclusion, interventions aimed to increase muscle mass and energy expenditure might have an impact on improving physical function of CKD patients.

Stroke and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Management Across Kidney Disease Stages

PubMed Central

Weiner, Daniel E.; Dad, Taimur

2015-01-01

Summary Cerebrovascular disease and stroke are very common at all stages of chronic kidney disease (CKD), likely representing both shared risk factors as well as synergy among risk factors. More subtle ischemic brain lesions may be particularly common in the CKD population, with subtle manifestations including cognitive impairment. For individuals with nondialysis CKD, the prevention, approach to, diagnosis, and management of stroke is similar to the general, non-CKD population. For individuals with end-stage renal disease, far less is known regarding the prevention of stroke. Stroke prophylaxis using warfarin in dialysis patients with atrial fibrillation in particular remains of uncertain benefit. End-stage renal disease patients can be managed aggressively in the setting of acute stroke. Outcomes after stroke at all stages of CKD are poor, and improving these outcomes should be the subject of future clinical trials. PMID:26355250

Research of human kidney thermal properties for the purpose of cryosurgery

NASA Astrophysics Data System (ADS)

Ponomarev, D. E.; Pushkarev, A. V.

2017-11-01

Calculation of the heat transfer is required to correctly predict the results of cryosurgery, cryopreservation, etc. One of the important initial parameters are the thermophysical properties of biological tissues. In the present study, the values of the heat capacity, cryoscopic temperature and enthalpy of the phase transition of the kidney samples in vitro were obtained by differential scanning calorimetry.

Fluid accumulation during acute kidney injury in the intensive care unit.

PubMed

Berthelsen, R E; Perner, A; Jensen, A K; Jensen, J-U; Bestle, M H

2018-07-01

Fluid therapy is a ubiquitous intervention in patients admitted to the intensive care unit, but positive fluid balance may be associated with poor outcomes and particular in patients with acute kidney injury. Studies describing this have defined fluid overload either at specific time points or considered patients with a positive mean daily fluid balance as fluid overloaded. We wished to detail this further and performed joint model analyses of the association between daily fluid balance and outcome represented by mortality and renal recovery in patients admitted with acute kidney injury. We did a retrospective cohort study of patients admitted to the intensive care unit with acute kidney injury during a 2-year observation period. We used serum creatinine measurements to identify patients with acute kidney injury and collected sequential daily fluid balance during the first 5 days of admission to the intensive care unit. We used joint modelling techniques to correlate the development of fluid overload with survival and renal recovery adjusted for age, gender and disease severity. The cohort contained 863 patients with acute kidney injury of whom 460 (53%) and 254 (29%) developed 5% and 10% fluid overload, respectively. We found that both 5% and 10% fluid overload was correlated with reduced survival and renal recovery. Joint model analyses of fluid accumulation in patients admitted to the intensive care unit with acute kidney injury confirm that even a modest degree of fluid overload (5%) may be negatively associated with both survival and renal recovery. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Papillary necrosis with invasive fungal infections: a case series of 29 patients

PubMed Central

Gupta, Krishan L.; Muthukumar, Thangamani; Joshi, Kusum; Chakrbarti, Arunaloke; Kohli, Harbir S.; Jha, Vivekanand; Sakhuja, Vinay

2013-01-01

Background Renal papillary necrosis (RPN) is associated with a number of comorbid conditions. However, it has been rarely reported in patients with fungal infections of the kidney. Methods We analyzed medical records of our hospital for the last two decades and identified 29 patients with fungal infections and RPN. Results Among the 29 patients, there were 24 men and 5 women. The median (range) age at presentation was 31.2 years (2 days–73 years). Three patients (10%) were kidney transplant recipients. The remaining had varied co-existing medical conditions that included diabetes mellitus in 16 (55%) and septicemia in 4 (14%). Clinical features at presentation were fever and oliguric kidney failure in 17 patients and loin pain accompanied by passage of fleshy material per urethra in 11 (38%). Diagnosis was made ante-mortem in 17 (59%) patients. Twenty patients (69%) had infection limited to the kidneys, while in the rest, it was disseminated. Kidney involvement was bilateral in 17 patients (59%). Urinalysis showed pyuria in 23 (79%) and microhematuria in 8 (28%) patients. Fungal infections included candidiasis (69%), aspergillosis (21%) and zygomycosis (10%). Of the 17 patients in whom the diagnoses was made ante-mortem, 12 survived and 5 died. Overall mortality was observed in 48% of cases. Conclusions We herein report a series of patients with RPN associated with fungal infections of the kidney. Presentation varies from asymptomatic urinary tract infection to severe kidney failure with poor outcome. High index of suspicion is necessary to reduce the associated high mortality in these patients. PMID:27293566

A national program toward improving renal health: advancing organ donation awareness.

PubMed

Uriarte, R D B; Amarillo, M L; Ampil, R S; Manauis, M N T; Danguilan, R A; Ona, E T

2010-01-01

Despite the national advocacy campaign for kidney transplantation from deceased donors in the Philippines 96% of kidneys transplanted into 721 kidney transplants from 1999 to 2001 came from living donors. A national survey on the knowledge, attitudes and perceptions of Filipinos on organ donation in 2001 showed factors that disadvantaged deceased organ donation to be poor understanding of "brain death," religion, and fear of the operation. These concerns were addressed and another survey was conducted in 2005. To compare knowledge, attitudes, and perceptions of Filipinos on organ donation between 2001 and 2005, and compare the number of kidney transplants from deceased donors between 2001 until 2008. Two surveys in 15 regions of the Philippines were conducted using multistage sampling. Using a structured questionnaire there were 2000 respondents in 2001, and 2140 in 2005. Analysis was performed using chi-square analysis. The majority of respondents knew about kidney donation. Between 2001 and 2005, there was increased awareness that transplants came from both living and deceased donors (37% to 41%) and a decline in those believing transplants came only from deceased donors (14% to 9%). Willingness to become a living (59% to 87%) or a deceased donor (35% to 49%) increased. The increase in transplantation from deceased donors from an average of 10 per year from 1999 to 2001 to 31 per year from 2006 to 2008. Increased awareness about kidney donation among Filipinos, improved consent to become an organ donor, and an increase in kidney transplantation from deceased donors occurred from 2001 to 2008.

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

Rare cause of adult female incontinence: complete duplication of the collecting system and ectopic ureter of the kidney draining into the vagina treated by laparoscopic upper pole heminephrectomy and ureterectomy.

PubMed

Alkan, Ilter; Özveri, Hakan; Taş, Selim; Ipekçi, Tümay; Yılmaz, Serdar

2014-08-01

A 38-year-old woman presented with a lifelong history of involuntary urinary leakage. The patient reported that she had been operated for her urinary leakage with the diagnosis of stress incontinence with transobturator tape two times at two different institutions. Preoperative computed tomography scan showed complete duplication of the left kidney with poorly functioning upper pole and a tortuous left dilated ureter running down and opening into the vagina. Laparoscopic left upper pole heminephrectomy and ureterectomy were performed uneventfully. Her incontinence improved immediately after surgery.

Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy

PubMed Central

2014-01-01

Background Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0). Methods In 38 patients, standard activity of 177Lu-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated. Results At 4 h, HK (≥5.0) was present in 94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK. Increases in K+ were significantly correlated with decreases in phosphate (r = −0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of >28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37). Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK >6.0 (accuracy = 81.6%). Conclusions A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining its potential utility for identifying ‘high-risk’ patients prone to PRRT. PMID:25977880

Estimated glomerular filtration rate is an early biomarker of cardiac surgery-associated acute kidney injury.

PubMed

Candela-Toha, Ángel; Pardo, María Carmen; Pérez, Teresa; Muriel, Alfonso; Zamora, Javier

2018-04-20

and objective Acute kidney injury (AKI) diagnosis is still based on serum creatinine and diuresis. However, increases in creatinine are typically delayed 48h or longer after injury. Our aim was to determine the utility of routine postoperative renal function blood tests, to predict AKI one or 2days in advance in a cohort of cardiac surgery patients. Using a prospective database, we selected a sample of patients who had undergone major cardiac surgery between January 2002 and December 2013. The ability of the parameters to predict AKI was based on Acute Kidney Injury Network serum creatinine criteria. A cohort of 3,962 cases was divided into 2groups of similar size, one being exploratory and the other a validation sample. The exploratory group was used to show primary objectives and the validation group to confirm results. The ability to predict AKI of several kidney function parameters measured in routine postoperative blood tests, was measured with time-dependent ROC curves. The primary endpoint was time from measurement to AKI diagnosis. AKI developed in 610 (30.8%) and 623 (31.4%) patients in the exploratory and validation samples, respectively. Estimated glomerular filtration rate using the MDRD-4 equation showed the best AKI prediction capacity, with values for the AUC ROC curves between 0.700 and 0.946. We obtained different cut-off values for estimated glomerular filtration rate depending on the degree of AKI severity and on the time elapsed between surgery and parameter measurement. Results were confirmed in the validation sample. Postoperative estimated glomerular filtration rate using the MDRD-4 equation showed good ability to predict AKI following cardiac surgery one or 2days in advance. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Risk factors for CKD in persons with kidney stones: a case-control study in Olmsted County, Minnesota.

PubMed

Saucier, Nathan A; Sinha, Mukesh K; Liang, Kelly V; Krambeck, Amy E; Weaver, Amy L; Bergstralh, Eric J; Li, Xujian; Rule, Andrew D; Lieske, John C

2010-01-01

Kidney stones are associated with increased risk of chronic kidney disease (CKD); however, risk factors in the general community are poorly defined. A nested case-control study was performed in residents of Olmsted County, MN, who presented with a kidney stone at the Mayo Clinic in 1980-1994 to contrast patients with kidney stones who developed CKD with a group that did not. Participants were selected from the Rochester Epidemiology Project, an electronic linkage system among health care providers in Olmsted County, MN. Cases were identified by diagnostic code for CKD and confirmed to have an estimated glomerular filtration rate < 60 mL/min/1.73 m(2). Controls were matched 2:1 to cases for age, sex, date of first kidney stone, and length of medical record. Charts were abstracted to characterize stone disease, hypertension, diabetes, obesity, tobacco use, ileal conduit, symptomatic stones, type and number of stones, urinary tract infections, number and type of surgical procedures, and medical therapy. Kidney stone patients with CKD were compared with matched stone patients without CKD. There were 53 cases and 106 controls with a mean age of 57 years at first stone event and 59% men. In kidney stone patients, cases with CKD were significantly more likely (P < 0.05) than controls to have had a history of diabetes (41.5% vs 17.0%), hypertension (71.7% vs 49.1%), frequent urinary tract infections (22.6% vs 6.6%), struvite stones (7.5% vs 0%), and allopurinol use (32.1% vs 4.7%) based on univariate analysis. Potential limitations include limited statistical power to detect associations, incomplete data from 24-hour urine studies, and that stone composition was not always available. As in the general population, hypertension and diabetes are associated with increased risk of CKD in patients with kidney stones. However, other unique predictors were identified in patients with kidney stones that increased the possibility of CKD. Further studies are warranted to elucidate the nature of these associations. Copyright 2009 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Thermal therapy in urologic systems: a comparison of arrhenius and thermal isoeffective dose models in predicting hyperthermic injury.

PubMed

He, Xiaoming; Bhowmick, Sankha; Bischof, John C

2009-07-01

The Arrhenius and thermal isoeffective dose (TID) models are the two most commonly used models for predicting hyperthermic injury. The TID model is essentially derived from the Arrhenius model, but due to a variety of assumptions and simplifications now leads to different predictions, particularly at temperatures higher than 50 degrees C. In the present study, the two models are compared and their appropriateness tested for predicting hyperthermic injury in both the traditional hyperthermia (usually, 43-50 degrees C) and thermal surgery (or thermal therapy/thermal ablation, usually, >50 degrees C) regime. The kinetic parameters of thermal injury in both models were obtained from the literature (or literature data), tabulated, and analyzed for various prostate and kidney systems. It was found that the kinetic parameters vary widely, and were particularly dependent on the cell or tissue type, injury assay used, and the time when the injury assessment was performed. In order to compare the capability of the two models for thermal injury prediction, thermal thresholds for complete killing (i.e., 99% cell or tissue injury) were predicted using the models in two important urologic systems, viz., the benign prostatic hyperplasia tissue and the normal porcine kidney tissue. The predictions of the two models matched well at temperatures below 50 degrees C. At higher temperatures, however, the thermal thresholds predicted using the TID model with a constant R value of 0.5, the value commonly used in the traditional hyperthermia literature, are much lower than those predicted using the Arrhenius model. This suggests that traditional use of the TID model (i.e., R=0.5) is inappropriate for predicting hyperthermic injury in the thermal surgery regime (>50 degrees C). Finally, the time-temperature relationships for complete killing (i.e., 99% injury) were calculated and analyzed using the Arrhenius model for the various prostate and kidney systems.

Association of kidney stones with atherosclerotic cardiovascular disease among adults in the United States: Considerations by race-ethnicity.

PubMed

Glover, LaShaunta M; Bass, Martha Ann; Carithers, Teresa; Loprinzi, Paul D

2016-04-01

There is a paucity of research examining the relationship between kidney stones and risk of cardiovascular disease while considering individuals of different race-ethnicities. The purpose of this study was to examine the association between history of kidney stones and increased odds of atherosclerotic cardiovascular disease (via the Pooled Cohort Equations) across race-ethnicity groups. 5571 participants aged 40-79 from the 2007-2012 cycles of the NHANES were used for this study. A history of kidney stones was collected from survey data. Predicted odds of having a 10-year atherosclerotic cardiovascular disease (ASCVD) event was assessed from the Pooled Cohort Equations. After adjustments, having kidney stones was not associated with an increase odds of having an ASCVD event within the next 10-years (OR 1.03; 95% CI: 0.58-1.82, P=0.91). However, among non-Hispanic blacks, those with kidney stones had a 2.24 increased odds (OR 2.24; 95% CI: 1.08-4.66; P=0.03) of having an ASCVD event within the next 10-years when compared to non-Hispanic blacks with no history of a kidney stone. Kidney stones were associated with 10-year risk of a future ASCVD event among non-Hispanic blacks. Copyright © 2016 Elsevier Inc. All rights reserved.

Diabetes and Kidney Disease in American Indians: Potential Role of Sugar-Sweetened Beverages.

PubMed

Yracheta, Joseph M; Lanaspa, Miguel A; Le, MyPhuong T; Abdelmalak, Manal F; Alfonso, Javier; Sánchez-Lozada, Laura G; Johnson, Richard J

2015-06-01

Since the early 20th century, a marked increase in obesity, diabetes, and chronic kidney disease has occurred in the American Indian population, especially the Pima Indians of the Southwest. Here, we review the current epidemic and attempt to identify remediable causes. A search was performed using PubMed and the search terms American Indian and obesity, American Indian and diabetes, American Indian and chronic kidney disease, and American Indian and sugar or fructose, Native American, Alaska Native, First Nations, Aboriginal, Amerind, and Amerindian for American Indian for articles linking American Indians with diabetes, obesity, chronic kidney disease, and sugar; additional references were identified in these publications traced to 1900 and articles were reviewed if they were directly discussing these topics. Multiple factors are involved in the increased risk for diabetes and kidney disease in the American Indian population, including poverty, overnutrition, poor health care, high intake of sugar, and genetic mechanisms. Genetic factors may be especially important in the Pima, as historical records suggest that this group was predisposed to obesity before exposure to Western culture and diet. Exposure to sugar-sweetened beverages may also be involved in the increased risk for chronic kidney disease. In these small populations in severe health crisis, we recommend further studies to investigate the role of excess added sugar, especially sugar-sweetened beverages, as a potentially remediable risk factor. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Imperfect Gold Standards for Kidney Injury Biomarker Evaluation

PubMed Central

Betensky, Rebecca A.; Emerson, Sarah C.; Bonventre, Joseph V.

2012-01-01

Clinicians have used serum creatinine in diagnostic testing for acute kidney injury for decades, despite its imperfect sensitivity and specificity. Novel tubular injury biomarkers may revolutionize the diagnosis of acute kidney injury; however, even if a novel tubular injury biomarker is 100% sensitive and 100% specific, it may appear inaccurate when using serum creatinine as the gold standard. Acute kidney injury, as defined by serum creatinine, may not reflect tubular injury, and the absence of changes in serum creatinine does not assure the absence of tubular injury. In general, the apparent diagnostic performance of a biomarker depends not only on its ability to detect injury, but also on disease prevalence and the sensitivity and specificity of the imperfect gold standard. Assuming that, at a certain cutoff value, serum creatinine is 80% sensitive and 90% specific and disease prevalence is 10%, a new perfect biomarker with a true 100% sensitivity may seem to have only 47% sensitivity compared with serum creatinine as the gold standard. Minimizing misclassification by using more strict criteria to diagnose acute kidney injury will reduce the error when evaluating the performance of a biomarker under investigation. Apparent diagnostic errors using a new biomarker may be a reflection of errors in the imperfect gold standard itself, rather than poor performance of the biomarker. The results of this study suggest that small changes in serum creatinine alone should not be used to define acute kidney injury in biomarker or interventional studies. PMID:22021710

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.

Novel pathologic scoring tools predict end-stage kidney disease in light chain (AL) amyloidosis.

PubMed

Rubinstein, Samuel; Cornell, Robert F; Du, Liping; Concepcion, Beatrice; Goodman, Stacey; Harrell, Shelton; Horst, Sara; Lenihan, Daniel; Slosky, David; Fogo, Agnes; Langone, Anthony

2017-09-01

Light chain (AL) amyloidosis frequently involves the kidney, causing significant morbidity and mortality. A pathologic scoring system with prognostic utility has not been developed. We hypothesized that the extent of amyloid deposition and degree of scarring injury on kidney biopsy, could provide prognostic value, and aimed to develop pathologic scoring tools based on these features. This is a case-control study of 39 patients treated for AL amyloidosis with biopsy-proven kidney involvement at a large academic medical center. Our novel scoring tools, composite scarring injury score (CSIS) and amyloid score (AS) were applied to each kidney biopsy. The primary outcome was progression to dialysis-dependent end-stage kidney disease (ESKD) using a 12-month landmark analysis. At 12 months, nine patients had progressed to ESKD. Patients with an AS ≥7.5 had a significantly higher cumulative incidence of ESKD than those with AS <7.5 (p = .04, 95% CI 0.13-0.64). Using a 12-month landmark analysis, AS correlated with progression to ESKD. These data suggest that a kidney biopsy, in addition to providing diagnostic information, can be the basis for a pathologic scoring system with prognostic significance.

Physical, cognitive and emotional factors contributing to quality of life, functional health and participation in community dwelling in chronic kidney disease.

PubMed

Seidel, Ulla K; Gronewold, Janine; Volsek, Michaela; Todica, Olga; Kribben, Andreas; Bruck, Heike; Hermann, Dirk M

2014-01-01

Quality of life (QoL) impairment is a well-known consequence of chronic kidney disease (CKD). The factors influencing QoL and late life functional health are poorly examined. Using questionnaires combined with neuropsychological examinations, we prospectively evaluated physical, cognitive, and emotional factors influencing QoL, functional health and participation in community dwelling in 119 patients with CKD stages 3-5 including hemodialysis (61.5±15.7years; 63% men) and 54 control patients of the same age without CKD but with similar cardiovascular risk profile. Compared with control patients, CKD patients showed impairment of the physical component of QoL and overall function, assessed by the SF-36 and LLFDI, whereas disability, assessed by LLFDI, was selectively impaired in CKD patients on hemodialysis. Multivariable linear regressions (forced entry) confirmed earlier findings that CKD stage (β = -0.24; p = 0.012) and depression (β = -0.30; p = 0.009) predicted the QoL physical component. Hitherto unknown, CKD stage (β = -0.23; p = 0.007), cognition (β = 0.20; p = 0.018), and depression (β = -0.51; <0.001) predicted disability assessed by the LLFDI, while age (β = -0.20; p = 0.023), male gender (B = 5.01; p = 0.004), CKD stage (β = -0.23; p = 0.005), stroke history (B = -9.00; p = 0.034), and depression (β = -0.41; p<0.001) predicted overall function. Interestingly, functional health deficits, cognitive disturbances, depression, and anxiety were evident almost only in CKD patients with coronary heart disease (found in 34.2% of CKD patients). The physical component of QoL and functional health decreased with age and depressive symptoms, and increased with cognitive abilities. In CKD, QoL, functional health, and participation in community dwelling are influenced by physical, cognitive, and emotional factors, most prominently in coronary heart disease patients.

Clinicopathological analysis of biopsy-proven diabetic nephropathy based on the Japanese classification of diabetic nephropathy.

PubMed

Furuichi, Kengo; Shimizu, Miho; Yuzawa, Yukio; Hara, Akinori; Toyama, Tadashi; Kitamura, Hiroshi; Suzuki, Yoshiki; Sato, Hiroshi; Uesugi, Noriko; Ubara, Yoshifumi; Hohino, Junichi; Hisano, Satoshi; Ueda, Yoshihiko; Nishi, Shinichi; Yokoyama, Hitoshi; Nishino, Tomoya; Kohagura, Kentaro; Ogawa, Daisuke; Mise, Koki; Shibagaki, Yugo; Makino, Hirofumi; Matsuo, Seiichi; Wada, Takashi

2018-06-01

The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis. The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy. The median observation period was 70.4 (IQR 20.9-101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m 2 /year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%. This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.

Serum uric acid is a GFR-independent long-term predictor of acute and chronic renal insufficiency: the Jerusalem Lipid Research Clinic cohort study

PubMed Central

Kark, Jeremy D.

2011-01-01

Background. Kidney disease is commonly accompanied by hyperuricemia. However, the contribution of serum uric acid (SUA) to kidney injury is debated. Our objective was to assess the long-term prediction of renal failure by SUA. Methods. Visit 2 participants in the Jerusalem Lipid Research Clinic cohort with normal baseline kidney function were followed for 24–28 years. SUA levels were assessed for associations with acute renal failure (ARF) and chronic renal failure (CRF) as defined by hospital discharge records, and mortality, ascertained through linkage with the national population registry. Results. Among 2449 eligible participants (1470 men, 979 women aged 35–78 years in 1976–79), SUA was positively linked with male sex, serum creatinine and components of the metabolic syndrome but was lower in smokers and in diabetic subjects. The 22- to 25-year incidence of hospital-diagnosed kidney failure (145 first events, 67% CRF) and the 24- to 28-year mortality (587 events) were higher in subject with hyperuricemia (>6.5 mg/dL in men and >5.3 mg/dL in women, reflecting the upper quintiles), independent of baseline kidney function and covariates. Hyperuricemia conferred adjusted hazard ratios of 1.36 (P = 0.003), 2.14 (P < 0.001) and 2.87 (P = 0.003) for mortality, CRF and ARF, respectively. Conclusions. SUA predicts renal failure incidence and all-cause mortality independently of demographic and clinical covariates. These results lend support to the undertaking of clinical trials to examine the effect of uric acid-lowering strategies on kidney outcomes. PMID:21220750

Best single time point correlations with AUC for cyclosporine and tacrolimus in HIV-infected kidney and liver transplant recipients.

PubMed

Frassetto, Lynda A; Tan-Tam, Clara C; Barin, Burc; Browne, Matt; Wolfe, Alan R; Stock, Peter G; Roland, Michelle; Benet, Leslie Z

2014-03-27

Interactions between antiretrovirals (ARVs) and transplant immunosuppressant agents (IS) among HIV-infected transplant recipients may lead to lack of efficacy or toxicity. In transplant recipients not infected with HIV, tacrolimus (TAC) trough levels (C0) or cyclosporine (CsA) drawn at C0 or 2 hours after dosing (C2) correlate with drug exposure (area under the curve [AUC]/dose) and outcomes. Because of ARV-IS interactions in HIV-infected individuals, and the high rate of rejection in these subjects, this study investigated the correlations between IS concentrations and exposure to determine the best method to monitor immunosuppressant levels. This study prospectively studied 50 HIV-infected transplant recipients undergoing kidney or liver transplantation evaluating the pharmacokinetics of the IS in 150 studies over time after transplantation (weeks 2 to 4, 12, 28, 52, and 104). IS levels were measured with liquid chromatography-tandem mass spectrometry and AUC calculated using WinNonlin 9.0. Correlation analyses were run on SAS 9.2. CsA concentration at C4 correlated better with AUC than C0 or C2, and over time TAC concentration correlated better at C0 or C2. It is suggested that C0 is acceptable for TAC monitoring, but poor predictability will occur at C0 with CsA. The low correlation of C0 with CsA AUC could be responsible for the higher rejection rates on CsA that has been reported in these subjects.

Practical use of home blood pressure monitoring in chronic kidney disease.

PubMed

Sanghavi, Sarah; Vassalotti, Joseph A

2014-08-01

Despite the availability of blood pressure (BP)-lowering medications and dietary education, hypertension is still poorly controlled in the chronic kidney disease (CKD) population. As glomerular filtration rate declines, the number of medications required to achieve BP targets increases, which may lead to reduced patient adherence and therapeutic inertia by the clinician. Home BP monitoring (HBPM) has emerged as a means of improving diagnostic accuracy, risk stratification, patient adherence, and therapeutic intervention. The definition of hypertension by HBPM is an average BP >135/85 mm Hg. Twelve readings over the course of 3-5 days are sufficient for clinical decision making. Diagnostic accuracy is especially important in the CKD population as approximately half of these patients have either white coat hypertension or masked hypertension. Preliminary data suggest that HBPM outperforms office BP monitoring in predicting progression to end-stage renal disease or death. When combined with additional support such as telemonitoring, medication titration, or behavioral therapy, HBPM results in a sustained improvement in BP control. HBPM must be adapted to provide information on the phenomena of nondipping (absence of nocturnal fall in BP) and reverse dipping (paradoxical increase in BP at night). These diurnal patterns are more prevalent in the CKD population and are important cardiovascular risk factors. Ambulatory BP monitoring provides nocturnal BP readings and unlike HBPM may be reimbursed by Medicare when certain criteria are met. Further studies are needed to determine whether HBPM is cost-effective in the current US healthcare system.

Small renal masses: The molecular markers associated with outcome of patients with kidney tumors 7 cm or less

NASA Astrophysics Data System (ADS)

Spirina, L. V.; Usynin, Y. A.; Kondakova, I. V.; Yurmazov, Z. A.; Slonimskaya, E. M.; Pikalova, L. V.

2016-08-01

The investigation of molecular mechanisms of tumor cell behavior in small renal masses is required to achieve the better cancer survival. The aim of the study is to find molecular markers associated with outcome of patients with kidney tumors 7 cm or less. A homogenous group of 20 patients T1N0M0-1 (mean age 57.6 ± 2.2 years) with kidney cancer was selected for the present analysis. The content of transcription and growth factors was determined by ELISA. The levels of AKT-mTOR signaling pathway components were measured by Western blotting analysis. The molecular markers associated with unfavorable outcome of patients with kidney tumors 7 cm or less were high levels of NF-kB p50, NF-kB p65, HIF-1, HIF-2, VEGF and CAIX. AKT activation with PTEN loss also correlated with the unfavorable outcome of kidney cancer patients with tumor size 7 cm or less. It is observed that the biological features of kidney cancer could predict the outcome of patients.

Multiple high-intensity focused ultrasound probes for kidney-tissue ablation.

PubMed

Häcker, Axel; Chauhan, Sunita; Peters, Kristina; Hildenbrand, Ralf; Marlinghaus, Ernst; Alken, Peter; Michel, Maurice Stephan

2005-10-01

To investigate kidney-tissue ablation by high-intensity focused ultrasound (HIFU) using multiple and single probes. Ultrasound beams (1.75 MHz) produced by a piezoceramic element (focal distance 80 mm) were focused at the center of renal parenchyma. One of the three probes (mounted on a jig) could also be used for comparison with a single probe at comparable power ratings. Lesion dimensions were examined in perfused and unperfused ex vivo porcine kidneys at different power levels (40, 60, and 80 W) and treatment times (4, 6, and 8 seconds). At identical power levels, the lesions induced by multiple probes were larger than those induced by a single probe. Lesion size increased with increasing pulse duration and generator power. The sizes and shapes of the lesions were predictably repeatable in all samples. Lesions in perfused kidneys were smaller than those in unperfused kidneys. Ex vivo, kidney-tissue ablation by means of multiple HIFU probes offers significant advantages over single HIFU probes in respect of lesion size and formation. These advantages need to be confirmed by tests in vivo at higher energy levels.

Relationship of fibroblast growth factor 21 with kidney function and albuminuria: multi-ethnic study of atherosclerosis.

PubMed

Anuwatmatee, Sahapab; Allison, Matthew A; Shlipak, Michael G; McClelland, Robyn L; Kramer, Holly; Tang, Shudi; Hou, Liming; Rye, Kerry-Anne; Ong, Kwok Leung

2018-05-15

Fibroblast growth factor 21 (FGF21) may play a role in the development of chronic kidney disease (CKD). We therefore investigated the relationship of plasma FGF21 levels with kidney function and albuminuria in the Multi-Ethnic Study of Atherosclerosis (MESA). The analysis included 5724 MESA participants ages 45-84 years between 2000 and 2002, free of clinically apparent cardiovascular disease (CVD). Participants were followed up in person at four additional clinic visits over 10 years. Plasma FGF21 levels were measured at baseline examination by enzyme-linked immunosorbent assay. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Outcomes were urinary albumin:creatinine ratio (UACR) progression, incident CKD by eGFR (reaching eGFR <60 mL/min/1.73 m2 with eGFR loss rate ≥1 mL/min/1.73 m2 per year) and rapid kidney function decline (eGFR decline >5%/year). At baseline, higher FGF21 levels, assessed as both continuous and categorical quartile variables, were significantly associated with lower eGFR and higher UACR, after adjusting for demographic, socioeconomic and other confounding factors [adjusted mean differences of -2.63 mL/min/1.73 m2 in eGFR and 0.134 in log normally transformed UACR (mg/g) for the highest FGF21 quartile compared with the lowest quartile, all P < 0.001]. However, in longitudinal analyses, baseline FGF21 levels did not predict incident CKD by eGFR, rapid kidney function decline or UACR progression. No significant interaction with sex and race/ethnicity was found (all P > 0.05). Our study does not support a role of FGF21 as a biomarker for predicting kidney function decline or albuminuria in adults free of clinically apparent CVD at baseline.

The quality of information about kidney transplantation on the World Wide Web.

PubMed

Hanif, Faisal; Abayasekara, Kumar; Willcocks, Lisa; Jolly, Elaine C; Jamieson, Neville V; Praseedom, Raaj K; Goodacre, John A; Read, Janet C; Chaudhry, Afzal; Gibbs, Paul

2007-01-01

Websites on the Internet are used increasingly by patients and those caring for them as a source of medical information. This study investigated the nature and quality of the kidney transplant-related information currently available on the World Wide Web (WWW). Four common search engines were used to explore the Internet using the keywords "kidney transplantation." Each website was assessed on the following categories: source, language, accessibility, presence of kitemarks, and quality/depth of information. Websites were scored independently by four transplant clinicians (two surgeons and two physicians), and a weighted Information Score (IS) was created to assess the overall clinical and educational value of the site. A total of 200 potential websites were identified of which 94 websites were suitable for scoring. The remaining 106 were repetitions or non-accessible links. The overall median weighted IS for the sites assessed was 21 (IQR 0-61). Median weighted IS of sites originating from Europe and USA were 47 (IQR = 21-61) and 45 (IQR = 15-61) respectively (p = 0.27). Websites belonging to academic institutions scored higher with a median weighted IS of 49 (IQR = 20-61) when compared with kitemarked websites (median 21, IQR = 5-45, p = 0.01). However, there was no statistically significant difference in weighted IS of kitemarked, professional (median 22, IQR = 2-53), commercial (median 20, IQR = 0-45), and individual websites (median 9, IQR 3-12). There was a good agreement between the observers who scored the websites with an intraclass correlation coefficient (ICC) of 0.79 and an associated 95% CI (0.73-0.90) for the four observers on the 94 websites. The educational material currently available on the WWW about kidney transplantation is often of poor quality and more input is required from transplant clinicians. Quality seals in the form of kitemarks may give a false sense of security. The gaps in validity and accuracy of the information available on complex topics such as kidney transplantation should be filled; otherwise poor quality information will continue to be the norm rather than the exception.

Cloning and preliminary functional studies of the JAM-A gene in grass carp (Ctenopharyngodon idellus).

PubMed

Du, Fukuan; Su, Jianguo; Huang, Rong; Liao, Lanjie; Zhu, Zuoyan; Wang, Yaping

2013-06-01

Grass carp (Ctenopharyngodon idellus) is a very important aquaculture species in China and other South-East Asian countries; however, disease outbreaks in this species are frequent, resulting in huge economic losses. Grass carp hemorrhage caused by grass carp reovirus (GCRV) is one of the most serious diseases. Junction adhesion molecule A (JAM-A) is the mammalian receptor for reovirus, and has been well studied. However, the JAM-A gene in grass carp has not been studied so far. In this study, we cloned and elucidated the structure of the JAM-A gene in grass carp (GcJAM-A) and then studied its functions during grass carp hemorrhage. GcJAM-A is composed of 10 exons and 9 introns, and its full-length cDNA is 1833 bp long, with an 888 bp open reading frame (ORF) that encodes a 295 amino acid protein. The GcJAM-A protein is predicted to contain a typical transmembrane domain. Maternal expression pattern of GcJAM-A is observed during early embryogenesis, while zygote expression occurs at 8 h after hatching. GcJAM-A is expressed strongly in the gill, liver, intestine and kidney, while it is expressed poorly in the blood, brain, spleen and head kidney. Moreover, lower expression is observed in the gill, liver, intestine, brain, spleen and kidney of 30-month-old individuals, compared with 6-month-old. In a GcJAM-A-knockdown cell line (CIK) infected with GCRV, the expression of genes involved in the interferon and apoptosis pathways was significantly inhibited. These results suggest that GcJAM-A could be a receptor for GCRV. We have therefore managed to characterize the GcJAM-A gene and provide evidence for its role as a receptor for GCRV. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Serum Bicarbonate and Structural and Functional Cardiac Abnormalities in Chronic Kidney Disease - A Report from the Chronic Renal Insufficiency Cohort Study.

PubMed

Dobre, Mirela; Roy, Jason; Tao, Kaixiang; Anderson, Amanda H; Bansal, Nisha; Chen, Jing; Deo, Rajat; Drawz, Paul; Feldman, Harold I; Hamm, L Lee; Hostetter, Thomas; Kusek, John W; Lora, Claudia; Ojo, Akinlolu O; Shrama, Kumar; Rahman, Mahboob

2016-01-01

Heart failure (HF) is a frequent occurrence in chronic kidney disease (CKD) patients and predicts poor survival. Serum bicarbonate is associated with increased rates of HF in CKD; however, the mechanisms leading to this association are incompletely understood. This study aims to assess whether serum bicarbonate is independently associated with structural and functional cardiac abnormalities in CKD. The association between serum bicarbonate and left ventricular (LV) hypertrophy (LVH), LV mass indexed to height2.7, LV geometry, ejection fraction (EF) and diastolic dysfunction was assessed in 3,483 participants without NYHA class III/IV HF, enrolled in the Chronic Renal Insufficiency Cohort study. The mean estimated glomerular filtration rate was 42.5 ± 17 ml/min/1.73 m2. The overall prevalence of LVH was 51.2%, with 57.8, 50.9 and 47.7% for bicarbonate categories <22, 22-26 and >26 mmol/l, respectively. Participants with low bicarbonate were more likely to have LVH and abnormal LV geometry (OR 1.32; 95% CI 1.07-1.64, and OR 1.57; 95% CI 1.14-2.16, respectively). However, the association was not statistically significant after adjustment for demographics, traditional cardiovascular risk factors, medications and kidney function (OR 1.07; 95% CI 0.66-1.72, and OR 1.27; 95% CI 0.64-2.51, respectively). No association was found between bicarbonate and systolic or diastolic dysfunction. During follow-up, no significant changes in LV mass or EF were observed in any bicarbonate strata. In a large CKD study, serum bicarbonate was associated with LV mass and concentric LVH; however, this association was attenuated after adjustment for clinical factors suggesting that the observed cardiac effects are mediated through yet unknown mechanisms. © 2016 Published by S. Karger AG, Basel.

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.

Photoacoustic imaging for assessing ischemic kidney damage in vivo

NASA Astrophysics Data System (ADS)

Berndl, Elizabeth S. L.; He, Xiaolin; Yuen, Darren A.; Kolios, Michael C.

2018-02-01

Ischemic reperfusion injuries (IRIs) occur after blood returns to a tissue or organ after a period without oxygen or nutrients, which causes an inflammatory response leading to heterogeneous scarring of the nearby tissue and vasculature. This is associated with long-term decreases blood flow, and necrosis. Although most commonly associated with heart attacks and strokes, IRIs are also a side effect of organ transplants, when the organ is reperfused in the recipient's body after being transported from the donor to the transplant hospital. Currently, the optimal method of monitoring for IRI is limited to biopsies, which are invasive and poorly monitor the spatial heterogeneity of the damage. To non-invasively identify changes in kidneys, the left renal artery in mice (n=3) was clamped for 45 minutes to create an IRI event. Both kidneys of each animal were monitored using photoacoustics (PA) with the VevoLAZR system (Fujifilm-VisualSonics, Toronto) three, four and eight weeks after surgery. IRI-treated kidneys show increased picosirius red staining, indicative of collagen (0.601 vs 0.042, p < 0.0001), decreased size as assessed by cross-sectional area (7.8 mm2 vs 35.9 mm2 , p < 0.0001), and decreased oxygen saturation (sO2; 62% vs 77%, p = 0.02). Analysis of the photoacoustic data shows that a two-point metric, the 715:930 nm ratio of the whole kidney (1.05 vs 0.57, p = 0.049) and the optical spectral slope (OSS) (0.8 * 10-3 vs 3.0 * 10-3, p = 0.013) are both able to differentiate between IRI-treated and healthy kidneys. These data suggest that photoacoustics can be used as a non-invasive method to observe in vivo changes in the kidney due to IRI.

Low-level cadmium exposure and effects on kidney function

PubMed Central

Wallin, Maria; Sallsten, Gerd; Lundh, Thomas; Barregard, Lars

2014-01-01

Objectives The nephrotoxicity of cadmium at low levels of exposure, measured by urinary cadmium, has recently been questioned since co-excretion of cadmium and proteins may have causes other than cadmium toxicity. The aim of this study was to explore the relation between kidney function and low or moderate cadmium levels, measured directly in kidney biopsies. Methods We analysed cadmium in kidney biopsies (K-Cd), blood (B-Cd) and urine (U-Cd) from 109 living kidney donors in a cross-sectional study. We measured glomerular filtration rate (GFR), cystatin C in serum, albumin, β-2-microglobulin (B2M), retinol-binding protein (RBP), α-1-microglobulin (A1M), N-acetyl-β-d-glucosaminidase and kidney injury molecule 1 (KIM-1) in 24 h and overnight urine. Results We found significant positive associations between A1M excretion and K-Cd in multiple regression models including age, sex, weight, smoking and urinary flow rate. This association was also present in never-smokers. A1M was also positively associated with B-Cd and U-Cd. GFR and the other biomarkers of kidney function were not associated with K-Cd. GFR estimated from serum cystatin C showed a very poor correlation with measured GFR. KIM-1, RBP and possibly albumin were positively associated with U-Cd, but only in overnight urine. No associations were found with B2M. Conclusions Our results suggest that A1M in urine is a sensitive biomarker for effects of low-level cadmium exposure. A few associations between other renal biomarkers and U-Cd, but not K-Cd, were probably caused by physiological co-excretion or chance. PMID:25286916

Immune cells and type 1 IFN in urine of SLE patients correlate with immunopathology in the kidney.

PubMed

Scott, Eric; Dooley, Mary Anne; Vilen, Barbara J; Clarke, Stephen H

2016-07-01

The immunopathological events in the kidneys of lupus nephritis (LN) patients are poorly understood due in part to the difficulty in acquiring serial biopsies and the inherent limitations in their analysis. To identify a means to circumvent these limitations, we investigated whether immune cells of kidney origin are present in patient urine and whether they correlate with kidney pathology. Flow cytometry analysis was performed on peripheral blood and urine cells of 69 SLE patients, of whom 41 were LN patients. In addition, type I IFN (IFNα/β) levels were determined in plasma and urine by bioassay. Approximately 60% of non-LN patients had urine lymphocytes. In these patients, T cells were always present and predominantly CD8(+), while B cells were either absent or a mixture of naïve and memory B cells. In contrast, >90% of LN patients had urine lymphocytes. In half, the B and T cells resembled those in non-LN patient urine; however, in the remaining patients, the B cells were exclusively Ig-secreting plasmablasts or plasma cells (PB/PCs) and the T cells were predominantly CD4(+). In addition, pDCs and IFNα/β frequently accompanied PB/PCs. The majority of patients with urine PB/PCs presented with proliferative nephritis and a significant loss of kidney function, which in some cases had progressed to end stage renal disease (ESRD). In conclusion, urine can provide access to cells of kidney resident populations for phenotypic and functional characterization. Analysis of these cells provides insight into the kidney immunopathology and may serve as biomarkers to identify patients at risk for developing LN and progressing to ESRD. Copyright © 2016 Elsevier Inc. All rights reserved.

Adenine phosphoribosyltransferase deficiency in the United Kingdom: two novel mutations and a cross-sectional survey

PubMed Central

Arenas-Hernandez, Monica; Escuredo, Emilia; Fairbanks, Lynette; Marinaki, Tony; Mapplebeck, Sarah; Sheaff, Michael; Almond, Michael K.

2016-01-01

Background Adenine phosphoribosyltransferase deficiency is an inborn error of metabolism that can cause kidney disease from crystalline nephropathy or kidney stones. Methods We present three cases from a single centre with varied presentations to illustrate how increasing awareness led to better patient identification. We then undertook a cross-sectional survey of all the patients identified from the Purine Research Laboratory in the UK since 1974. Results Our index case presented with recurrent nephrolithiasis and was diagnosed on stone analysis, the second case presented with acute kidney injury and the third case was identified from a biopsy undertaken for acute on chronic kidney injury. Genetic studies identified two novel mutations. Twenty patients were retrospectively identified. The mean age at diagnosis was 25 years (range 2–70); eight were <20 years, seven were 20–40 years and five were >40 years. Five of the 20 patients were deceased, 3 after end-stage renal disease (ESRD). Twelve have normal renal function, one had CKD stage 3, one had severe kidney disease and one was on dialysis. Conclusions Adenine phosphoribosyltransferase deficiency presents in a wide spectrum in all age groups. Patients can be completely asymptomatic and kidney disease may be incorrectly attributed to other conditions. Outcome is poor in late diagnosis and there is a high prevalence of ESRD. Patients with unexplained renal stone disease or deterioration in kidney function should be considered for screening. Identification and surveillance of patients in the UK can improve. There is now a rare disease registry with meetings organized that include patients, families and health care providers to improve awareness. PMID:27994857

Drug management in the elderly adult with chronic kidney disease: a review for the primary care physician.

PubMed

Ponticelli, Claudio; Sala, Gabriele; Glassock, Richard J

2015-05-01

With advancing age, the functional reserve of many organs tends to decrease. In particular, the lean body mass, the levels of serum albumin, the blood flow to the liver, and the glomerular filtration rate are reduced in elderly individuals and can be further impaired by the concomitant presence of acute or chronic kidney disease. Moreover, patients with kidney disease are often affected by comorbid processes and are prescribed multiple medications. The aging process also modifies some drug interactions, including the affinity of some drugs for their receptor, the number of receptors, and the cell responses upon receptor activation. Therefore, older patients with kidney disease are particularly susceptible to the risks of adverse drug reactions. Planning a pharmacological regimen in such patients is confounded by the paucity of information available on the pharmacokinetic and pharmacodynamic profiles of a large number of drugs commonly used in this group of patients. Finally, many aged patients suffer from unintentional poor compliance. In this review, the problems physicians face in designing safe and effective medication management in elderly individuals are discussed, paying attention to those more frequently used, which may be potentially harmful in patients with kidney disease. The risks of overdosing and underdosing are outlined, and some recommendations to reduce the risk of adverse drug reactions are provided. A review of the literature covering the field of drug management in older patients with kidney disease was performed by selecting those articles published between January 1, 1990, and December 1, 2014, using PubMed as a search engine with the keywords elderly, kidney disease, drugs, drug interaction, and renal function. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Influence of the Method of Definition on the Prevalence of Left-Ventricular Hypertrophy in Children with Chronic Kidney Disease: Data from the Know-Ped CKD Study.

PubMed

Cho, Heeyeon; Choi, Hyun Jin; Kang, Hee Gyung; Ha, Il-Soo; Cheong, Hae Il; Han, Kyung Hee; Kim, Seong Heon; Cho, Min Hyun; Shin, Jae Il; Lee, Joo Hoon; Park, Young Seo

2017-01-01

Children with chronic kidney disease (CKD) have a high risk of cardiovascular disease. Left-ventricular (LV) hypertrophy (LVH) is an early marker of cardiovascular disease in pediatric CKD, and the prevalence of LVH in pediatric CKD is approximately 20-30% in pre-dialysis CKD patients. However, there is no consensus on the ideal method of defining LVH in pediatric CKD patients. Previous studies have typically used the LV mass index (LVMI), which is calculated as LV mass in grams divided by height in meters to the 2.7th power ≥ 38 g/m2.7, to diagnose LVH in children with CKD. Recently, age-specific reference values for LVMI ≥ 95th percentile and LV wall-thickness z-score > 1.64 in children were addressed. The aim of this study was to assess the prevalence and contributing factors of LVH in pediatric CKD patients according to each measurement and evaluate the concordance between each measurement. We used the baseline data of the KoreaN cohort study for Outcome in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD), which is a nationwide, 10-year, prospective, observational cohort study of pediatric CKD. A total of 469 patients were enrolled, and 458 patients were included in the final analysis. Univariate and multiple logistic regression analysis were performed to evaluate the association of the variables with LVH. Kappa statistics were used to analyze the concordance. According to an LVH diagnosis of LVMI ≥ 38 g/m2.7, 188 patients (41.0%) were diagnosed with LVH, and the prevalence of LVH was high in younger patients (< 2 years of age). Using the age-specific reference values, 116 patients (25.3%) were diagnosed with LVH, and there was no difference in the prevalence of LVH according to age. Thirty-one patients (6.8%) were diagnosed with LVH using an LV wall-thickness z-score > 1.64. There is poor concordance between the diagnosis of LVH using the LV wall-thickness z-score and the LVMI method. The results of this study show that there is poor concordance between the diagnosis of LVH using the wall-thickness z-score and the LVMI2.7 criteria. Further investigation is needed to estimate the correlation between LVH and cardiac dysfunction and to find a better method for defining LVH in the pediatric CKD cohort and thereby predicting cardiac dysfunction. © 2017 The Author(s). Published by S. Karger AG, Basel.

CXCR1-mediated Neutrophil Degranulation and Fungal Killing Promotes Candida Clearance and Host Survival

PubMed Central

Swamydas, Muthulekha; Gao, Ji-Liang; Break, Timothy J.; Johnson, Melissa D.; Jaeger, Martin; Rodriguez, Carlos A.; Lim, Jean K.; Green, Nathaniel M.; Collar, Amanda L.; Fischer, Brett G.; Lee, Chyi-Chia Richard; Perfect, John R.; Alexander, Barbara D.; Kullberg, Bart-Jan; Netea, Mihai G.; Murphy, Philip M.; Lionakis, Michail S.

2016-01-01

Systemic Candida albicans infection causes high morbidity and mortality and is now the leading cause of nosocomial bloodstream infection in the US. Neutropenia is a major risk factor for poor outcome in infected patients; however, the molecular factors that mediate neutrophil trafficking and effector function during infection are poorly defined. Here, using a mouse model of systemic candidiasis, we found that the neutrophil-selective CXC chemokine receptor Cxcr1 and its ligand, Cxcl5, are highly induced in the Candida-infected kidney, the target organ in the model. To investigate the role of Cxcr1 in antifungal host defense in vivo, we generated Cxcr1−/− mice and analyzed their immune response to Candida. Mice lacking Cxcr1 exhibited decreased survival with enhanced Candida growth in the kidney and renal failure. Surprisingly, increased susceptibility of Cxcr1−/− mice to systemic candidiasis was not due to impaired neutrophil trafficking from the blood into the infected kidney but was the result of defective killing of the fungus by neutrophils that exhibited a cell-intrinsic decrease in degranulation. In humans, the mutant CXCR1 allele CXCR1-T276 results in impaired neutrophil degranulation and fungal killing and was associated with increased risk of disseminated candidiasis in infected patients. Together, our data demonstrate a biological function for mouse Cxcr1 in vivo and indicate that CXCR1-dependent neutrophil effector function is a critical innate protective mechanism of fungal clearance and host survival in systemic candidiasis. PMID:26791948

Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function.

PubMed

Przybylowski, P; Koc-Zorawska, E; Malyszko, J S; Kozlowska, S; Mysliwiec, M; Malyszko, J

2011-10-01

Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function. Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits. Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r=0.34; P<.001) and urinary creatinine (r=-0.29; P<.01), and NGAL (r=0.29; P<.01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP. Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function/injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients.

PubMed

Zittema, Debbie; van den Berg, Else; Meijer, Esther; Boertien, Wendy E; Muller Kobold, Anneke C; Franssen, Casper F M; de Jong, Paul E; Bakker, Stephan J L; Navis, Gerjan; Gansevoort, Ron T

2014-09-05

Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney. Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as (125)I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging. Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4-15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8-6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6-6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105 ± 17 to 66 ± 10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=-0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0.001; β=-0.51, P<0.001, respectively). On the basis of the finding in donors that kidney clearance is not a main determinant of plasma copeptin levels, it was hypothesized that, in patients with autosomal dominant polycystic kidney disease, kidney damage and associated impaired urine concentration capacity determine copeptin levels. Copyright © 2014 by the American Society of Nephrology.

Statistical shape modeling based renal volume measurement using tracked ultrasound

NASA Astrophysics Data System (ADS)

Pai Raikar, Vipul; Kwartowitz, David M.

2017-03-01

Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common cause of kidney transplant worldwide accounting for 7-10% of all cases. Although ADPKD usually progresses over many decades, accurate risk prediction is an important task.1 Identifying patients with progressive disease is vital to providing new treatments being developed and enable them to enter clinical trials for new therapy. Among other factors, total kidney volume (TKV) is a major biomarker predicting the progression of ADPKD. Consortium for Radiologic Imaging Studies in Polycystic Kidney Disease (CRISP)2 have shown that TKV is an early, and accurate measure of cystic burden and likely growth rate. It is strongly associated with loss of renal function.3 While ultrasound (US) has proven as an excellent tool for diagnosing the disease; monitoring short-term changes using ultrasound has been shown to not be accurate. This is attributed to high operator variability and reproducibility as compared to tomographic modalities such as CT and MR (Gold standard). Ultrasound has emerged as one of the standout modality for intra-procedural imaging and with methods for spatial localization has afforded us the ability to track 2D ultrasound in physical space which it is being used. In addition to this, the vast amount of recorded tomographic data can be used to generate statistical shape models that allow us to extract clinical value from archived image sets. In this work, we aim at improving the prognostic value of US in managing ADPKD by assessing the accuracy of using statistical shape model augmented US data, to predict TKV, with the end goal of monitoring short-term changes.

Pre-Kidney Transplant Lower Extremity Impairment and Post-Kidney Transplant Mortality.

PubMed

Nastasi, A J; McAdams-DeMarco, M A; Schrack, J; Ying, H; Olorundare, I; Warsame, F; Mountford, A; Haugen, C E; González Fernández, M; Norman, S P; Segev, D L

2018-01-01

Prediction models for post-kidney transplantation mortality have had limited success (C-statistics ≤0.70). Adding objective measures of potentially modifiable factors may improve prediction and, consequently, kidney transplant (KT) survival through intervention. The Short Physical Performance Battery (SPPB) is an easily administered objective test of lower extremity function consisting of three parts (balance, walking speed, chair stands), each with scores of 0-4, for a composite score of 0-12, with higher scores indicating better function. SPPB performance and frailty (Fried frailty phenotype) were assessed at admission for KT in a prospective cohort of 719 KT recipients at Johns Hopkins Hospital (8/2009 to 6/2016) and University of Michigan (2/2013 to 12/2016). The independent associations between SPPB impairment (SPPB composite score ≤10) and composite score with post-KT mortality were tested using adjusted competing risks models treating graft failure as a competing risk. The 5-year posttransplantation mortality for impaired recipients was 20.6% compared to 4.5% for unimpaired recipients (p < 0.001). Impaired recipients had a 2.30-fold (adjusted hazard ratio [aHR] 2.30, 95% confidence interval [CI] 1.12-4.74, p = 0.02) increased risk of postkidney transplantation mortality compared to unimpaired recipients. Each one-point decrease in SPPB score was independently associated with a 1.19-fold (95% CI 1.09-1.30, p < 0.001) higher risk of post-KT mortality. SPPB-derived lower extremity function is a potentially highly useful and modifiable objective measure for pre-KT risk prediction. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Acute Kidney Injury Enhances Outcome Prediction Ability of Sequential Organ Failure Assessment Score in Critically Ill Patients

PubMed Central

Chang, Chih-Hsiang; Fan, Pei-Chun; Chang, Ming-Yang; Tian, Ya-Chung; Hung, Cheng-Chieh; Fang, Ji-Tseng; Yang, Chih-Wei; Chen, Yung-Chang

2014-01-01

Introduction Acute kidney injury (AKI) is a common and serious complication in intensive care unit (ICU) patients and also often part of a multiple organ failure syndrome. The sequential organ failure assessment (SOFA) score is an excellent tool for assessing the extent of organ dysfunction in critically ill patients. This study aimed to evaluate the outcome prediction ability of SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) III score in ICU patients with AKI. Methods A total of 543 critically ill patients were admitted to the medical ICU of a tertiary-care hospital from July 2007 to June 2008. Demographic, clinical and laboratory variables were prospectively recorded for post hoc analysis as predictors of survival on the first day of ICU admission. Results One hundred and eighty-seven (34.4%) patients presented with AKI on the first day of ICU admission based on the risk of renal failure, injury to kidney, failure of kidney function, loss of kidney function, and end-stage renal failure (RIFLE) classification. Major causes of the ICU admissions involved respiratory failure (58%). Overall in-ICU mortality was 37.9% and the hospital mortality was 44.7%. The predictive accuracy for ICU mortality of SOFA (areas under the receiver operating characteristic curves: 0.815±0.032) was as good as APACHE III in the AKI group. However, cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.001) for SOFA score ≤10 vs. ≥11 in these ICU patients with AKI. Conclusions For patients coexisting with AKI admitted to ICU, this work recommends application of SOFA by physicians to assess ICU mortality because of its practicality and low cost. A SOFA score of ≥ “11” on ICU day 1 should be considered an indicator of negative short-term outcome. PMID:25279844

Comparison of Measured GFR, Serum Creatinine, Cystatin C, and Beta-Trace Protein to Predict ESRD in African Americans With Hypertensive CKD

PubMed Central

Bhavsar, Nrupen A.; Appel, Lawrence J.; Kusek, John W.; Contreras, Gabriel; Bakris, George; Coresh, Josef; Astor, Brad C.

2011-01-01

Background Identification of persons with chronic kidney disease (CKD) who are at highest risk to progress to end stage renal disease (ESRD) is necessary to reduce the burden of kidney failure. The relative utility of traditional markers of kidney function, including estimated glomerular filtration rate (GFR) and serum creatinine, and emerging markers of kidney function, including cystatin C and beta-trace protein (BTP), to predict ESRD and mortality has yet to be established. Study Design Randomized clinical trial followed by an observational cohort study. Setting & Participants 865 African American individuals with hypertensive CKD enrolled in a clinical trial of two levels of blood pressure control and three different antihypertensive drugs as initial therapy and subsequently followed by an observational cohort study. Predictors Quintile of measured GFR (mGFR) by iothalamate clearance, serum creatinine, serum creatinine-based estimated GFR (eGFRSCr), cystatin C, and BTP. Outcomes and Measurements Incidence of ESRD and mortality. Results A total of 246 participants reached ESRD over a median follow-up of 102 months. The incidence rate of ESRD was higher with higher quintiles of each marker. The association between higher BTP and ESRD was stronger than those for the other markers, including mGFR. All the markers remained significantly associated with ESRD after adjustment for mGFR and relevant covariates (all p<0.05), with BTP retaining the strongest association (HR for highest versus lowest quintile, 5.7; 95% CI, 2.2-14.9). Associations with the combined endpoint of ESRD or mortality (n=390) were weaker, but remained significant for cystatin C (p=0.05) and BTP (p=0.004). Limitations The ability of these markers to predict ESRD and mortality in other racial and ethnic groups and among individuals with CKD due to other causes is unknown. Conclusions Plasma BTP and cystatin C may be useful adjuncts to serum creatinine and mGFR in evaluating risk for progression of kidney disease. PMID:21944667

Relation between pretransplant serum levels of soluble CD30 and acute rejection during the first 6 months after a kidney transplant.

PubMed

Shooshtarizadeh, Tina; Mohammadali, Ali; Ossareh, Shahrzad; Ataipour, Yousef

2013-06-01

The immunologic status of kidney allograft recipients affects transplant outcome. High levels of pretransplant serum soluble CD30 correlate with an increased risk of acute rejection. Studies show conflicting results. We evaluated the relation between pretransplant serum sCD30 levels with the risk of posttransplant acute kidney rejection in renal transplant recipients. This prospective cohort study was performed between March 2010 and March 2011 on 77 kidney transplant recipients (53 men [68.8%], 24 women [31.2%]; mean age, 41 ± 14 y). Serum samples were collected 24 hours before transplant and analyzed for soluble CD30 levels by enzyme-linked immunosorbent assay. Patients were followed for 6 months after transplant. Acute biopsy-proven rejection episodes were recorded, serum creatinine levels were measured, and glomerular filtration rates were calculated at the first and sixth months after transplant. Preoperative serum soluble CD30 levels were compared in patients with and without rejection. The mean pretransplant serum soluble CD30 level was 92.1 ± 47.3 ng/mL. At 6 months' follow-up, 10 patients experienced acute rejection. Mean pretransplant soluble CD30 levels were 128.5 ± 84 ng/mL versus 86.7 ± 37 ng/mL in patients with and without acute rejection episodes (P = .008). At 100 ng/mL, the sensitivity, specificity, and positive and negative predictive values of pretransplant serum soluble CD30 level to predict acute rejection were 70%, 73.6%, 29.1%, and 94.3%. We showed a significant relation between pretransplant serum soluble CD30 levels and acute allograft rejection. High pretransplant levels of serum soluble CD30 can be a risk factor for kidney transplant rejection, and its high negative predictive value at various cutoffs make it useful to find candidates with a low risk of acute rejection after transplant.

Gap junctions favor normal rat kidney epithelial cell adaptation to chronic hypertonicity.

PubMed

Desforges, Bénédicte; Savarin, Philippe; Bounedjah, Ouissame; Delga, Stéphanie; Hamon, Loïc; Curmi, Patrick A; Pastré, David

2011-09-01

Upon hypertonic stress most often resulting from high salinity, cells need to balance their osmotic pressure by accumulating neutral osmolytes called compatible osmolytes like betaine, myo-inositol, and taurine. However, the massive uptake of compatible osmolytes is a slow process compared with other defense mechanisms related to oxidative or heat stress. This is especially critical for cycling cells as they have to double their volume while keeping a hospitable intracellular environment for the molecular machineries. Here we propose that clustered cells can accelerate the supply of compatible osmolytes to cycling cells via the transit, mediated by gap junctions, of compatible osmolytes from arrested to cycling cells. Both experimental results in epithelial normal rat kidney cells and theoretical estimations show that gap junctions indeed play a key role in cell adaptation to chronic hypertonicity. These results can provide basis for a better understanding of the functions of gap junctions in osmoregulation not only for the kidney but also for many other epithelia. In addition to this, we suggest that cancer cells that do not communicate via gap junctions poorly cope with hypertonic environments thus explaining the rare occurrence of cancer coming from the kidney medulla.

Reduced production of creatinine limits its use as marker of kidney injury in sepsis.

PubMed

Doi, Kent; Yuen, Peter S T; Eisner, Christoph; Hu, Xuzhen; Leelahavanichkul, Asada; Schnermann, Jürgen; Star, Robert A

2009-06-01

Although diagnosis and staging of acute kidney injury uses serum creatinine, acute changes in creatinine lag behind both renal injury and recovery. The risk for mortality increases when acute kidney injury accompanies sepsis; therefore, we sought to explore the limitations of serum creatinine in this setting. In mice, induction of sepsis by cecal ligation and puncture in bilaterally nephrectomized mice increased markers of nonrenal organ injury and serum TNF-alpha. Serum creatinine, however, was significantly lower in septic animals than in animals subjected to bilateral nephrectomy and sham cecal ligation and puncture. Under these conditions treatment with chloroquine decreased nonrenal organ injury markers but paradoxically increased serum creatinine. Sepsis dramatically decreased production of creatinine in nephrectomized mice, without changes in body weight, hematocrit, or extracellular fluid volume. In conclusion, sepsis reduces production of creatinine, which blunts the increase in serum creatinine after sepsis, potentially limiting the early detection of acute kidney injury. This may partially explain why small absolute increases in serum creatinine levels are associated with poor clinical outcomes. These data support the need for new biomarkers that provide better measures of renal injury, especially in patients with sepsis.

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.

Depletion of penicillin G residues in heavy sows after intramuscular injection. Part II: application of kidney inhibition swab tests.

PubMed

Shelver, Weilin L; Lupton, Sara J; Newman, David J; Larsen, Steven; Smith, David J

2014-07-30

Sows (n = 126; 228 ± 30.1 kg) were administered daily IM doses of penicillin G procaine (33 000 IU/kg bw; 5× the label dose) for 3 consecutive days using three different administration patterns. Within treatment, six sows each were slaughtered on withdrawal day 5, 10, 15, 20, 25, 32, and 39. Tissues (injection site, kidney, liver, skeletal muscle) or body fluids (serum and urine) were screened for penicillin G using the KIS test, recently adopted by the USDA Food Safety and Inspection Service. The IM administration patterns had no discernible effect on penicillin G depletion. Residues were depleted more rapidly from liver and skeletal muscle and more slowly from kidney and urine. Kidney was the most sensitive and suitable tissue for detecting penicillin G residues on-site, with two positive results after a 39-day withdrawal period. Urine was the most suitable ante-mortem surrogate to predict the results of kidney tests.

Skin manifestations of chronic kidney disease.

PubMed

Robles-Mendez, J C; Vazquez-Martinez, O; Ocampo-Candiani, J

2015-10-01

Skin manifestations associated with chronic kidney disease are very common. Most of these conditions present in the end stages and may affect the patient's quality of life. Knowledge of these entities can contribute to establishing an accurate diagnosis and prognosis. Severe renal pruritus is associated with increased mortality and a poor prognosis. Nail exploration can provide clues about albumin and urea levels. Nephrogenic systemic fibrosis is a preventable disease associated with gadolinium contrast. Comorbidities, such as diabetes mellitus and secondary hyperparathyroidism, can lead to acquired perforating dermatosis and calciphylaxis, respectively. Effective and innovative treatments are available for all of these conditions. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

[Correlation of fibroblast growth factor 23 with 
adverse prognosis of chronic kidney disease and
therapy strategy].

PubMed

Liu, Haiyang; Liu, Hong

2018-05-28

Fibroblast growth factor 23 (FGF23) is a hormone secreted by the bone. It is not only involved in the pathophysiological process of chronic kidney disease (CKD), but also associated with the poor prognosis. In patients with CKD, serum FGF23 levels are elevated in early phase. The increased FGF23 levels gradually lead to myocardial hypertrophy, inflammatory, vascular calcification, and low level of vitamin D, which contribute to the progress of CKD, cardiovascular complications and even death. Presently, there are several ways to reduce FGF23 levels, including decrease of intake and block of phosphorus absorption, supplement of FGF23 antibody and pseudo calcium or renal transplantation.

Nutritional management and growth in children with chronic kidney disease.

PubMed

Rees, Lesley; Jones, Helen

2013-04-01

Despite continuing improvements in our understanding of the causes of poor growth in chronic kidney disease, many unanswered questions remain: why do some patients maintain a good appetite whereas others have profound anorexia at a similar level of renal function? Why do some, but not all, patients respond to increased nutritional intake? Is feed delivery by gastrostomy superior to oral and nasogastric routes? Do children who are no longer in the 'infancy' stage of growth benefit from enteral feeding? Do patients with protein energy wasting benefit from increased nutritional input? How do we prevent obesity, which is becoming so prevalent in the developed world? This review will address these issues.

A novel method for predicting kidney stone type using ensemble learning.

PubMed

Kazemi, Yassaman; Mirroshandel, Seyed Abolghasem

2018-01-01

The high morbidity rate associated with kidney stone disease, which is a silent killer, is one of the main concerns in healthcare systems all over the world. Advanced data mining techniques such as classification can help in the early prediction of this disease and reduce its incidence and associated costs. The objective of the present study is to derive a model for the early detection of the type of kidney stone and the most influential parameters with the aim of providing a decision-support system. Information was collected from 936 patients with nephrolithiasis at the kidney center of the Razi Hospital in Rasht from 2012 through 2016. The prepared dataset included 42 features. Data pre-processing was the first step toward extracting the relevant features. The collected data was analyzed with Weka software, and various data mining models were used to prepare a predictive model. Various data mining algorithms such as the Bayesian model, different types of Decision Trees, Artificial Neural Networks, and Rule-based classifiers were used in these models. We also proposed four models based on ensemble learning to improve the accuracy of each learning algorithm. In addition, a novel technique for combining individual classifiers in ensemble learning was proposed. In this technique, for each individual classifier, a weight is assigned based on our proposed genetic algorithm based method. The generated knowledge was evaluated using a 10-fold cross-validation technique based on standard measures. However, the assessment of each feature for building a predictive model was another significant challenge. The predictive strength of each feature for creating a reproducible outcome was also investigated. Regarding the applied models, parameters such as sex, acid uric condition, calcium level, hypertension, diabetes, nausea and vomiting, flank pain, and urinary tract infection (UTI) were the most vital parameters for predicting the chance of nephrolithiasis. The final ensemble-based model (with an accuracy of 97.1%) was a robust one and could be safely applied to future studies to predict the chances of developing nephrolithiasis. This model provides a novel way to study stone disease by deciphering the complex interaction among different biological variables, thus helping in an early identification and reduction in diagnosis time. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of cannabinoid signaling in acute and chronic kidney diseases.

PubMed

Barutta, Federica; Bruno, Graziella; Mastrocola, Raffaella; Bellini, Stefania; Gruden, Gabriella

2018-04-26

The endogenous cannabinoids anandamide and 2-arachidonoylglycerol bind to the cannabinoid receptors of type 1 and 2. These receptors are also the binding sites for exogenous, both natural and synthetic, cannabinoids that are used for recreation purposes. Until recently, cannabinoids and cannabinoid receptors have attracted little interest among nephrologists; however, a full endocannabinoid system (ECS) is present in the kidney and it has recently emerged as an important player in the pathogenesis of diabetic nephropathy, drug nephrotoxicity, and progressive chronic kidney disease. This newly established role of the ECS in the kidney might have therapeutic relevance, as pharmacological modulation of the ECS has renoprotective effects in experimental animals, raising hope for future potential applications in humans. In addition, over the last years, there has been a number of reported cases of acute kidney injury (AKI) associated with the use of synthetic cannabinoids that appear to have higher potency and rate of toxicity than natural Cannabis. This poorly recognized cause of renal injury should be considered in the differential diagnosis of AKI, particularly in young people. In this review we provide an overview of preclinical evidence indicating a role of the ECS in renal disease and discuss potential future therapeutic applications. Moreover, we give a critical update of synthetic cannabinoid-induced AKI. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Soft 3D-Printed Phantom of the Human Kidney with Collecting System.

PubMed

Adams, Fabian; Qiu, Tian; Mark, Andrew; Fritz, Benjamin; Kramer, Lena; Schlager, Daniel; Wetterauer, Ulrich; Miernik, Arkadiusz; Fischer, Peer

2017-04-01

Organ models are used for planning and simulation of operations, developing new surgical instruments, and training purposes. There is a substantial demand for in vitro organ phantoms, especially in urological surgery. Animal models and existing simulator systems poorly mimic the detailed morphology and the physical properties of human organs. In this paper, we report a novel fabrication process to make a human kidney phantom with realistic anatomical structures and physical properties. The detailed anatomical structure was directly acquired from high resolution CT data sets of human cadaveric kidneys. The soft phantoms were constructed using a novel technique that combines 3D wax printing and polymer molding. Anatomical details and material properties of the phantoms were validated in detail by CT scan, ultrasound, and endoscopy. CT reconstruction, ultrasound examination, and endoscopy showed that the designed phantom mimics a real kidney's detailed anatomy and correctly corresponds to the targeted human cadaver's upper urinary tract. Soft materials with a tensile modulus of 0.8-1.5 MPa as well as biocompatible hydrogels were used to mimic human kidney tissues. We developed a method of constructing 3D organ models from medical imaging data using a 3D wax printing and molding process. This method is cost-effective means for obtaining a reproducible and robust model suitable for surgical simulation and training purposes.

Role of kidney injury in sepsis.

PubMed

Doi, Kent

2016-01-01

Kidney injury, including acute kidney injury (AKI) and chronic kidney disease (CKD), has become very common in critically ill patients treated in ICUs. Many epidemiological studies have revealed significant associations of AKI and CKD with poor outcomes of high mortality and medical costs. Although many basic studies have clarified the possible mechanisms of sepsis and septic AKI, translation of the obtained findings to clinical settings has not been successful to date. No specific drug against human sepsis or AKI is currently available. Remarkable progress of dialysis techniques such as continuous renal replacement therapy (CRRT) has enabled control of "uremia" in hemodynamically unstable patients; however, dialysis-requiring septic AKI patients are still showing unacceptably high mortality of 60-80 %. Therefore, further investigations must be conducted to improve the outcome of sepsis and septic AKI. A possible target will be remote organ injury caused by AKI. Recent basic studies have identified interleukin-6 and high mobility group box 1 (HMGB1) as important mediators for acute lung injury induced by AKI. Another target is the disease pathway that is amplified by pre-existing CKD. Vascular endothelial growth factor and HMGB1 elevations in sepsis were demonstrated to be amplified by CKD in CKD-sepsis animal models. Understanding the role of kidney injury as an amplifier in sepsis and multiple organ failure might support the identification of new drug targets for sepsis and septic AKI.

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.

Determinants of Acute Kidney Injury Duration After Cardiac Surgery: An Externally Validated Tool

PubMed Central

Brown, Jeremiah R.; Kramer, Robert S.; MacKenzie, Todd A.; Coca, Steven G.; Sint, Kyaw; Parikh, Chirag R.

2013-01-01

Background Acute kidney injury (AKI) duration following cardiac surgery is associated with poor survival in a dose-dependent manner. However, it is not known what peri-operative risk factors contribute to prolonged AKI and delayed recovery. We sought to identify peri-operative risk factors that predict duration of AKI, a complication that effects short and long term survival. Methods We studied 4,987 consecutive cardiac surgery patients from 2002 through 2007. AKI was defined as a ≥0.3 (mg/dL) or ≥50% increase in SCr from baseline. Duration of AKI was defined by the number of days AKI was present. Step-wise multivariable negative binomial regression analysis was conducted using peri-operative risk factors for AKI duration. C-index was estimated by Kendall’s tau. Results AKI developed in 39% of patients with a median duration of AKI at 3 days and ranged from 1 to 108 days. Patients without AKI had duration of zero days. Independent predictors of AKI duration included baseline patient and disease characteristics, operative and post-operative factors. Prediction for mean duration of AKI was developed using coefficients from the regression model and externally validated the model on 1,219 cardiac surgery patients in a separate cardiac surgery cohort (TRIBE-AKI). The C-index was 0.65 (p<0.001) for the derivation cohort and 0.62 (p<0.001) for the validation cohort. Conclusion We identified and externally validated peri-operative predictors of AKI duration. These risk-factors will be useful to evaluate a patient’s risk for the tempo of recovery from AKI after cardiac surgery and subsequent short and long term survival. The level of awareness created by working with these risk factors have implications regarding positive changes in processes of care that have the potential to decrease the incidence and mitigate AKI. PMID:22206952

Preimplantation Kidney Biopsies of Extended Criteria Donors Have a Heavier Inflammatory Burden Than Kidneys From Standard Criteria Donors

PubMed Central

Mazeti-Felicio, Camila M.; Caldas, Heloisa C.; Fernandes-Charpiot, Ida M.M.; Dezotti, Camila Z.; Baptista, Maria A.S.F.; Abbud-Filho, Mario

2017-01-01

Background Donors after brain death develop a systemic proinflammatory state that may predispose the kidneys to injury after transplantation. Because it is not known whether this inflammatory environment similarly affects the kidneys from expanded criteria donor (ECD) and standard criteria donors (SCD), we sought to evaluate differences in the gene expression of inflammatory cytokines in preimplantation biopsies (PIBx) from ECD and SCD kidneys. Methods Cytokines gene expression was measured in 80 PIBx (SCD, 52; ECD, 28) and associated with donor variables. Results Normal histology and chronic histological lesions were not different between both types of kidneys. ECD kidneys showed significant increase in the transcripts of MCP-1, RANTES, TGF-β1, and IL-10 when compared with SCD. Kidneys presenting normal histology had similar inflammatory profile except by a higher expression of RANTES observed in ECD (P = 0.04). Interstitial fibrosis and tubular atrophy (interstitial fibrosis and tubular atrophy ≥ 1) were associated with higher expression of TGF-β1, RANTES, and IL-10 in ECD compared with SCD kidneys. Cold ischemia time of 24 hours or longer was significantly associated with upregulation of FOXP3, MCP-1, RANTES, and IL10, whereas longer duration of donor hospitalization significantly increased gene expression of all markers. High FOXP3 expression was also associated with lower level of serum creatinine at 1 year. Donor age was not associated with any of the transcripts studied. Conclusions PIBx of ECD exhibit a higher gene expression of inflammatory cytokines when compared with SCD kidneys. This molecular profile may be a specific ECD kidney response to brain death and may help to predict the posttransplant outcomes of ECD recipients. PMID:28706983

Dual Kidney Allocation Score: A Novel Algorithm Utilizing Expanded Donor Criteria for the Allocation of Dual Kidneys in Adults.

PubMed

Johnson, Adam P; Price, Thea P; Lieby, Benjamin; Doria, Cataldo

2016-09-08

BACKGROUND Dual kidney transplantation (DKT) of expanded-criteria donors is a cost-intensive procedure that aims to increase the pool of available deceased organ donors and has demonstrated equivalent outcomes to expanded-criteria single kidney transplantation (eSKT). The objective of this study was to develop an allocation score based on predicted graft survival from historical dual and single kidney donors. MATERIAL AND METHODS We analyzed United Network for Organ Sharing (UNOS) data for 1547 DKT and 26 381 eSKT performed between January 1994 and September 2013. We utilized multivariable Cox regression to identify variables independently associated with graft survival in dual and single kidney transplantations. We then derived a weighted multivariable product score from calculated hazard ratios to model the benefit of transplantation as dual kidneys. RESULTS Of 36 donor variables known at the time of listing, 13 were significantly associated with graft survival. The derived dual allocation score demonstrated good internal validity with strong correlation to improved survival in dual kidney transplants. Donors with scores less than 2.1 transplanted as dual kidneys had a worsened median survival of 594 days (24%, p-value 0.031) and donors with scores greater than 3.9 had improved median survival of 1107 days (71%, p-value 0.002). There were 17 733 eSKT (67%) and 1051 DKT (67%) with scores in between these values and no differences in survival (p-values 0.676 and 0.185). CONCLUSIONS We have derived a dual kidney allocation score (DKAS) with good internal validity. Future prospective studies will be required to demonstrate external validity, but this score may help to standardize organ allocation for dual kidney transplantation.

The State of the Human Proteome in 2013 as viewed through PeptideAtlas: Comparing the Kidney, Urine, and Plasma Proteomes for the Biology and Disease-driven Human Proteome Project

PubMed Central

Farrah, Terry; Deutsch, Eric W.; Omenn, Gilbert S.; Sun, Zhi; Watts, Julian D.; Yamamoto, Tadashi; Shteynberg, David; Harris, Micheleen M.; Moritz, Robert L.

2014-01-01

The kidney, urine, and plasma proteomes are intimately related: proteins and metabolic waste products are filtered from the plasma by the kidney and excreted via the urine, while kidney proteins may be secreted into the circulation or released into the urine. Shotgun proteomics datasets derived from human kidney, urine, and plasma samples were collated and processed using a uniform software pipeline, and relative protein abundances were estimated by spectral counting. The resulting PeptideAtlas builds yielded 4005, 2491, and 3553 nonredundant proteins at 1% FDR for the kidney, urine, and plasma proteomes, respectively—for kidney and plasma, the largest high-confidence protein sets to date. The same pipeline applied to all available human data yielded a 2013 Human PeptideAtlas build containing 12,644 nonredundant proteins and at least one peptide for each of ~14,000 Swiss-Prot entries, an increase over 2012 of ~7.5% of the predicted human proteome. We demonstrate that abundances are correlated between plasma and urine, examine the most abundant urine proteins not derived from either plasma or kidney, and consider the biomarker potential of proteins associated with renal decline. This analysis forms part of the Biology and Disease-driven Human Proteome Project (B/D-HPP) and a contribution to the Chromosome-centric Human Proteome Project (C-HPP) special issue. PMID:24261998

Urine biomarkers informative of human kidney allograft rejection and tolerance.

PubMed

Nissaisorakarn, Voravech; Lee, John Richard; Lubetzky, Michelle; Suthanthiran, Manikkam

2018-05-01

We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report. Copyright © 2018. Published by Elsevier Inc.

Multinational Assessment of Accuracy of Equations for Predicting Risk of Kidney Failure: A Meta-analysis.

PubMed

Tangri, Navdeep; Grams, Morgan E; Levey, Andrew S; Coresh, Josef; Appel, Lawrence J; Astor, Brad C; Chodick, Gabriel; Collins, Allan J; Djurdjev, Ognjenka; Elley, C Raina; Evans, Marie; Garg, Amit X; Hallan, Stein I; Inker, Lesley A; Ito, Sadayoshi; Jee, Sun Ha; Kovesdy, Csaba P; Kronenberg, Florian; Heerspink, Hiddo J Lambers; Marks, Angharad; Nadkarni, Girish N; Navaneethan, Sankar D; Nelson, Robert G; Titze, Stephanie; Sarnak, Mark J; Stengel, Benedicte; Woodward, Mark; Iseki, Kunitoshi

2016-01-12

Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations, including such factors as age, sex, estimated glomerular filtration rate, and calcium and phosphate concentrations, were previously developed and validated in 2 Canadian cohorts. Validation in other regions and in CKD populations not under the care of a nephrologist is needed. To evaluate the accuracy of the risk equations across different geographic regions and patient populations through individual participant data meta-analysis. Thirty-one cohorts, including 721,357 participants with CKD stages 3 to 5 in more than 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014. Cohorts participating in the CKD Prognosis Consortium with data on end-stage renal disease. Data were obtained and statistical analyses were performed between July 2012 and June 2015. Using the risk factors from the original risk equations, cohort-specific hazard ratios were estimated and combined using random-effects meta-analysis to form new pooled kidney failure risk equations. Original and pooled kidney failure risk equation performance was compared, and the need for regional calibration factors was assessed. Kidney failure (treatment by dialysis or kidney transplant). During a median follow-up of 4 years of 721,357 participants with CKD, 23,829 cases kidney failure were observed. The original risk equations achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts (overall C statistic, 0.90; 95% CI, 0.89-0.92 at 2 years; C statistic at 5 years, 0.88; 95% CI, 0.86-0.90); discrimination in subgroups by age, race, and diabetes status was similar. There was no improvement with the pooled equations. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original risk equations overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 32.9% at 2 years and 16.5% at 5 years improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively (P = .04 and P = .02). Kidney failure risk equations developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts. However, in some regions the addition of a calibration factor may be necessary.

Application of prescribing recommendations in older people with reduced kidney function: a cross-sectional study in general practice.

PubMed

Wood, Su; Petty, Duncan; Glidewell, Liz; Raynor, Dk Theo

2018-05-01

Kidney function reduces with age, increasing the risk of harm from increased blood levels of many medicines. Although estimated glomerular filtration rate (eGFR) is reported for prescribing decisions in those aged ≥65 years, creatinine clearance (Cockcroft-Gault) gives a more accurate estimate of kidney function. To explore the extent of prescribing outside recommendations for people aged ≥65 years with reduced kidney function in primary care and to assess the impact of using eGFR instead of creatinine clearance to calculate kidney function. A cross-sectional survey of anonymised prescribing data in people aged ≥65 years from all 80 general practices (70 900 patients) in a north of England former primary care trust. The prevalence of prescribing outside recommendations was analysed for eight exemplar drugs. Data were collected for age, sex, actual weight, serum creatinine, and eGFR. Kidney function as creatinine clearance (Cockcroft-Gault) was calculated using actual body weight and estimated ideal body weight. Kidney function was too low for recommended prescribing in 4-40% of people aged ≥65 years, and in 24-80% of people aged ≥85 years despite more than 90% of patients having recent recorded kidney function results. Using eGFR overestimated kidney function for 3-28% of those aged ≥65 years, and for 13-58% of those aged ≥85 years. Increased age predicted higher odds of having a kidney function estimate too low for recommended prescribing of the study drugs. Prescribing recommendations when kidney function is reduced are not applied for many people aged ≥65 years in primary care. Using eGFR considerably overestimates kidney function for prescribing and, therefore, creatinine clearance (Cockcroft-Gault) should be assessed when prescribing for these people. Interventions are needed to aid prescribers when kidney function is reduced. © British Journal of General Practice 2018.

A Dynamic Graph Cuts Method with Integrated Multiple Feature Maps for Segmenting Kidneys in 2D Ultrasound Images.

PubMed

Zheng, Qiang; Warner, Steven; Tasian, Gregory; Fan, Yong

2018-02-12

Automatic segmentation of kidneys in ultrasound (US) images remains a challenging task because of high speckle noise, low contrast, and large appearance variations of kidneys in US images. Because texture features may improve the US image segmentation performance, we propose a novel graph cuts method to segment kidney in US images by integrating image intensity information and texture feature maps. We develop a new graph cuts-based method to segment kidney US images by integrating original image intensity information and texture feature maps extracted using Gabor filters. To handle large appearance variation within kidney images and improve computational efficiency, we build a graph of image pixels close to kidney boundary instead of building a graph of the whole image. To make the kidney segmentation robust to weak boundaries, we adopt localized regional information to measure similarity between image pixels for computing edge weights to build the graph of image pixels. The localized graph is dynamically updated and the graph cuts-based segmentation iteratively progresses until convergence. Our method has been evaluated based on kidney US images of 85 subjects. The imaging data of 20 randomly selected subjects were used as training data to tune parameters of the image segmentation method, and the remaining data were used as testing data for validation. Experiment results demonstrated that the proposed method obtained promising segmentation results for bilateral kidneys (average Dice index = 0.9446, average mean distance = 2.2551, average specificity = 0.9971, average accuracy = 0.9919), better than other methods under comparison (P < .05, paired Wilcoxon rank sum tests). The proposed method achieved promising performance for segmenting kidneys in two-dimensional US images, better than segmentation methods built on any single channel of image information. This method will facilitate extraction of kidney characteristics that may predict important clinical outcomes such as progression of chronic kidney disease. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Fully automatic region of interest selection in glomerular filtration rate estimation from 99mTc-DTPA renogram.

PubMed

Lin, Kun-Ju; Huang, Jia-Yann; Chen, Yung-Sheng

2011-12-01

Glomerular filtration rate (GFR) is a common accepted standard estimation of renal function. Gamma camera-based methods for estimating renal uptake of (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) without blood or urine sampling have been widely used. Of these, the method introduced by Gates has been the most common method. Currently, most of gamma cameras are equipped with a commercial program for GFR determination, a semi-quantitative analysis by manually drawing region of interest (ROI) over each kidney. Then, the GFR value can be computed from the scintigraphic determination of (99m)Tc-DTPA uptake within the kidney automatically. Delineating the kidney area is difficult when applying a fixed threshold value. Moreover, hand-drawn ROIs are tedious, time consuming, and dependent highly on operator skill. Thus, we developed a fully automatic renal ROI estimation system based on the temporal changes in intensity counts, intensity-pair distribution image contrast enhancement method, adaptive thresholding, and morphological operations that can locate the kidney area and obtain the GFR value from a (99m)Tc-DTPA renogram. To evaluate the performance of the proposed approach, 30 clinical dynamic renograms were introduced. The fully automatic approach failed in one patient with very poor renal function. Four patients had a unilateral kidney, and the others had bilateral kidneys. The automatic contours from the remaining 54 kidneys were compared with the contours of manual drawing. The 54 kidneys were included for area error and boundary error analyses. There was high correlation between two physicians' manual contours and the contours obtained by our approach. For area error analysis, the mean true positive area overlap is 91%, the mean false negative is 13.4%, and the mean false positive is 9.3%. The boundary error is 1.6 pixels. The GFR calculated using this automatic computer-aided approach is reproducible and may be applied to help nuclear medicine physicians in clinical practice.

Changes in urine volume and serum albumin in incident hemodialysis patients.

PubMed

Eriguchi, Rieko; Obi, Yoshitsugu; Rhee, Connie M; Chou, Jason A; Tortorici, Amanda R; Mathew, Anna T; Kim, Taehee; Soohoo, Melissa; Streja, Elani; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-10-01

Hypoalbuminemia is a predictor of poor outcomes in dialysis patients. Among hemodialysis patients, there has not been prior study of whether residual kidney function or decline over time impacts serum albumin levels. We hypothesized that a decline in residual kidney function is associated with an increase in serum albumin levels among incident hemodialysis patients. In a large national cohort of 38,504 patients who initiated hemodialysis during 1/2007-12/2011, we examined the association of residual kidney function, ascertained by urine volume and renal urea clearance, with changes in serum albumin over five years across strata of baseline residual kidney function, race, and diabetes using case-mix adjusted linear mixed effects models. Serum albumin levels increased over time. At baseline, patients with greater urine volume had higher serum albumin levels: 3.44 ± 0.48, 3.50 ± 0.46, 3.57 ± 0.44, 3.59 ± 0.45, and 3.65 ± 0.46 g/dL for urine volume groups of <300, 300-<600, 600-<900, 900-<1,200, and ≥1,200 mL/day, respectively (P trend  < 0.001). Over time, urine volume and renal urea clearance declined and serum albumin levels rose, while the baseline differences in serum albumin persisted across groups of urinary volume. In addition, the rate of decline in residual kidney function was not associated with the rate of change in albumin. Hypoalbuminemia in hemodialysis patients is associated with lower residual kidney function. Among incident hemodialysis patients, there is a gradual rise in serum albumin that is independent of the rate of decline in residual kidney function, suggesting that preservation of residual kidney function does not have a deleterious impact on serum albumin levels. © 2016 International Society for Hemodialysis.

(Pro)renin Receptor Is an Amplifier of Wnt/β-Catenin Signaling in Kidney Injury and Fibrosis.

PubMed

Li, Zhen; Zhou, Lili; Wang, Yongping; Miao, Jinhua; Hong, Xue; Hou, Fan Fan; Liu, Youhua

2017-08-01

The (pro)renin receptor (PRR) is a transmembrane protein with multiple functions. However, its regulation and role in the pathogenesis of CKD remain poorly defined. Here, we report that PRR is a downstream target and an essential component of Wnt/ β -catenin signaling. In mouse models, induction of CKD by ischemia-reperfusion injury (IRI), adriamycin, or angiotensin II infusion upregulated PRR expression in kidney tubular epithelium. Immunohistochemical staining of kidney biopsy specimens also revealed induction of renal PRR in human CKD. Overexpression of either Wnt1 or β -catenin induced PRR mRNA and protein expression in vitro Notably, forced expression of PRR potentiated Wnt1-mediated β -catenin activation and augmented the expression of downstream targets such as fibronectin, plasminogen activator inhibitor 1, and α -smooth muscle actin ( α -SMA). Conversely, knockdown of PRR by siRNA abolished β -catenin activation. PRR potentiation of Wnt/ β -catenin signaling did not require renin, but required vacuolar H + ATPase activity. In the mouse model of IRI, transfection with PRR or Wnt1 expression vectors promoted β -catenin activation, aggravated kidney dysfunction, and worsened renal inflammation and fibrotic lesions. Coexpression of PRR and Wnt1 had a synergistic effect. In contrast, knockdown of PRR expression ameliorated kidney injury and fibrosis after IRI. These results indicate that PRR is both a downstream target and a crucial element in Wnt signal transmission. We conclude that PRR can promote kidney injury and fibrosis by amplifying Wnt/ β -catenin signaling. Copyright © 2017 by the American Society of Nephrology.

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

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.

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.

Circulating osteoprotegerin is associated with chronic kidney disease in hypertensive patients.

PubMed

Bernardi, Stella; Toffoli, Barbara; Bossi, Fleur; Candido, Riccardo; Stenner, Elisabetta; Carretta, Renzo; Barbone, Fabio; Fabris, Bruno

2017-07-06

Osteoprotegerin (OPG) is a glycoprotein that plays an important regulatory role in the skeletal, vascular, and immune system. It has been shown that OPG predicts chronic kidney disease (CKD) in diabetic patients. We hypothesized that OPG could be a risk marker of CKD development also in non-diabetic hypertensive patients. A case-control study was carried out to measure circulating OPG levels in 42 hypertensive patients with CKD and in 141 hypertensive patients without CKD. A potential relationship between OPG and the presence of CKD was investigated and a receiver-operating characteristic (ROC) curve was designed thereafter to identify a cut-off value of OPG that best explained the presence of CKD. Secondly, to evaluate whether OPG increase could affect the kidney, 18 C57BL/6J mice were randomized to be treated with saline or recombinant OPG every 3 weeks for 12 weeks. Circulating OPG levels were significantly higher in hypertensive patients with CKD, and there was a significant inverse association between OPG and renal function, that was independent from other variables. ROC analysis showed that OPG levels had a high statistically predictive value on CKD in hypertensive patients, which was greater than that of hypertension. The OPG best cut-off value associated with CKD was 1109.19 ng/L. In the experimental study, OPG delivery significantly increased the gene expression of pro-inflammatory and pro-fibrotic mediators, as well as the glomerular nitrosylation of proteins. This study shows that OPG is associated with CKD in hypertensive patients, where it might have a higher predictive value than that of hypertension for CKD development. Secondly, we found that OPG delivery significantly increased the expression of molecular pathways involved in kidney damage. Further longitudinal studies are needed not only to evaluate whether OPG predicts CKD development but also to clarify whether OPG should be considered a risk factor for CKD.

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

[Urinary L-type fatty acid binding protein (L-FABP) as a new urinary biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan].

PubMed

Kamijo-Ikemori, Atsuko; Ichikawa, Daisuke; Matsui, Katsuomi; Yokoyama, Takeshi; Sugaya, Takeshi; Kimura, Kenjiro

2013-07-01

Liver-type fatty acid binding protein (L-FABP) is a 14kDa protein found in the cytoplasm of human renal proximal tubules. Fatty acids are bound with L-FABP and transported to the mitochondria or peroxisomes, where fatty acids are beta-oxidized, and this may play a role in fatty acid homeostasis. Moreover, L-FABP has high affinity and capacity to bind long-chain fatty acid oxidation products, and may be an effective endogenous antioxidant. Renal L-FABP is rarely expressed in the kidneys of rodents. In order to evaluate the pathological dynamics of renal L-FABP in kidney disease, human L-FABP chromosomal transgenic mice were generated. Various stress, such as massive proteinuria, hyperglycemia, hypertension, and toxins overloaded in the proximal tubules were revealed to up-regulate the gene expression of renal L-FABP and increase the excretion of L-FABP derived from the proximal tubules into urine. In clinical studies of chronic kidney disease (CKD), urinary L-FABP accurately reflected the degree of tubulointerstitial damage and correlated with the rate of CKD progression. Furthermore, a multicenter trial has shown that urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. With respect to diabetic nephropathy and acute kidney disease (AKI), urinary L-FABP is an early diagnostic of kidney disease or a predictive marker for renal prognosis. After many clinical studies, urinary L-FABP was approved as a new tubular biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan.

Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

PubMed

Chonchol, Michel; Gitomer, Berenice; Isakova, Tamara; Cai, Xuan; Salusky, Isidro; Pereira, Renata; Abebe, Kaleab; Torres, Vicente; Steinman, Theodor I; Grantham, Jared J; Chapman, Arlene B; Schrier, Robert W; Wolf, Myles

2017-09-07

Increases in fibroblast growth factor 23 precede kidney function decline in autosomal dominant polycystic kidney disease; however, the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease has not been well characterized. We measured intact fibroblast growth factor 23 levels in baseline serum samples from 1002 participants in the HALT-PKD Study A ( n =540; mean eGFR =91±17 ml/min per 1.73 m 2 ) and B ( n =462; mean eGFR =48±12 ml/min per 1.73 m 2 ). We used linear mixed and Cox proportional hazards models to test associations between fibroblast growth factor 23 and eGFR decline, percentage change in height-adjusted total kidney volume, and composite of time to 50% reduction in eGFR, onset of ESRD, or death. Median (interquartile range) intact fibroblast growth factor 23 was 44 (33-56) pg/ml in HALT-PKD Study A and 69 (50-93) pg/ml in Study B. In adjusted models, annualized eGFR decline was significantly faster in the upper fibroblast growth factor 23 quartile (Study A: quartile 4, -3.62; 95% confidence interval, -4.12 to -3.12 versus quartile 1, -2.51; 95% confidence interval, -2.71 to -2.30 ml/min per 1.73 m 2 ; P for trend <0.001; Study B: quartile 4, -3.74; 95% confidence interval, -4.14 to -3.34 versus quartile 1, -2.78; 95% confidence interval, -2.92 to -2.63 ml/min per 1.73 m 2 ; P for trend <0.001). In Study A, higher fibroblast growth factor 23 quartiles were associated with greater longitudinal percentage increase in height-adjusted total kidney volume in adjusted models (quartile 4, 6.76; 95% confidence interval, 5.57 to 7.96 versus quartile 1, 6.04; 95% confidence interval, 5.55 to 6.54; P for trend =0.03). In Study B, compared with the lowest quartile, the highest fibroblast growth factor 23 quartile was associated with elevated risk for the composite outcome (hazard ratio, 3.11; 95% confidence interval, 1.84 to 5.25). Addition of fibroblast growth factor 23 to a model of annualized decline in eGFR≥3.0 ml/min per 1.73 m 2 did not improve risk prediction. Higher serum fibroblast growth factor 23 concentration was associated with kidney function decline, height-adjusted total kidney volume percentage increase, and death in patients with autosomal dominant polycystic kidney disease. However, fibroblast growth factor 23 did not substantially improve prediction of rapid kidney function decline. Copyright © 2017 by the American Society of Nephrology.

Post-transplant increased levels of serum sCD30 is a marker for prediction of kidney allograft loss in a 5-year prospective study.

PubMed

Delgado, Julio C; Pavlov, Igor Y; Shihab, Fuad S

2009-12-01

Levels of sCD30 represent a biomarker for early outcome in kidney transplantation. The purpose of this study was to determine the role of sCD30 levels for prediction of graft loss in the late post-transplant period. Sera were collected immediately pre-transplant and yearly thereafter for up to 5-year post-transplant in 37 primary renal transplant recipients. Levels of serum sCD30 were tested using a fluorescent microsphere assay. Levels of sCD30 significantly decreased after transplantation and remained normal in 34 patients without graft loss up to 5-year post-transplant. Elevated levels of serum sCD30 preceded the increase of serum creatinine in patients with subsequent graft loss. Elevated levels of serum sCD30 post-transplant might be a marker for predicting subsequent graft loss in the post-transplant period.

Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models

PubMed Central

Li, Shunan; Abedin, Md. Joynal; Noppakun, Kajohnsak; Wang, Lawrence; Kaur, Tarundeep; Najafian, Behzad; Rodrigues, Cecília M. P.

2012-01-01

Background Acute kidney injury (AKI) has grave short- and long-term consequences. Often the onset of AKI is predictable, such as following surgery that compromises blood flow to the kidney. Even in such situations, present therapies cannot prevent AKI. As apoptosis is a major form of cell death following AKI, we determined the efficacy and mechanisms of action of tauroursodeoxycholic acid (TUDCA), a molecule with potent anti-apoptotic and pro-survival properties, in prevention of AKI in rat and cell culture models. TUDCA is particularly attractive from a translational standpoint, as it has a proven safety record in animals and humans. Methodology/Principal Findings We chose an ischemia-reperfusion model in rats to simulate AKI in native kidneys, and a human kidney cell culture model to simulate AKI associated with cryopreservation in transplanted kidneys. TUDCA significantly ameliorated AKI in the test models due to inhibition of the mitochondrial pathway of apoptosis and upregulation of survival pathways. Conclusions This study sets the stage for testing TUDCA in future clinical trials for prevention of AKI, an area that needs urgent attention due to lack of effective therapies. PMID:23152827

Kidney measures beyond traditional risk factors for cardiovascular prediction: A collaborative meta-analysis

PubMed Central

Matsushita, Kunihiro; Coresh, Josef; Sang, Yingying; Chalmers, John; Fox, Caroline; Guallar, Eliseo; Jafar, Tazeen; Jassal, Simerjot K.; Landman, Gijs W.D.; Muntner, Paul; Roderick, Paul; Sairenchi, Toshimi; Schöttker, Ben; Shankar, Anoop; Shlipak, Michael; Tonelli, Marcello; Townend, Jonathan; van Zuilen, Arjan; Yamagishi, Kazumasa; Yamashita, Kentaro; Gansevoort, Ron; Sarnak, Mark; Warnock, David G.; Woodward, Mark; Ärnlöv, Johan

2015-01-01

Background The utility of estimated glomerular filtration rate (eGFR) and albuminuria for cardiovascular prediction is controversial. Methods We meta-analyzed individual-level data from 24 cohorts (with a median follow-up time longer than 4 years, varying from 4.2 to 19.0 years) in the Chronic Kidney Disease Prognosis Consortium (637,315 participants without a history of cardiovascular disease) and assessed C-statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in 5-year timeframe, contrasting prediction models consisting of traditional risk factors with and without creatinine-based eGFR and/or albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria). Findings The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR and more evident for cardiovascular mortality (c-statistic difference 0.0139 [95%CI 0.0105–0.0174] and 0.0065 [0.0042–0.0088], respectively) and heart failure (0.0196 [0.0108–0.0284] and 0.0109 [0.0059–0.0159]) than for coronary disease (0.0048 [0.0029–0.0067] and 0.0036 [0.0019–0.0054]) and stroke (0.0105 [0.0058–0.0151] and 0.0036 [0.0004–0.0069]). Dipstick proteinuria demonstrated smaller improvement than ACR. The discrimination improvement with kidney measures was especially evident in individuals with diabetes or hypertension but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these conditions. In participants with chronic kidney disease (CKD), the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the c-statistic for cardiovascular mortality declined by 0.023 [0.016–0.030] vs. <0.007 when omitting eGFR and ACR vs. any single modifiable traditional predictors, respectively. Interpretation Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when they are already assessed for clinical purpose and/or cardiovascular mortality and heart failure are the outcomes of interest (e.g., the European guidelines on cardiovascular prevention). ACR may have particularly broad implications for cardiovascular prediction. In CKD populations, the simultaneous assessment of eGFR and ACR will facilitate improved cardiovascular risk classification, supporting current CKD guidelines. Funding US National Kidney Foundation and NIDDK PMID:26028594

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.

Comparison of Nutritional Risk Scores for Predicting Mortality in Japanese Chronic Hemodialysis Patients.

PubMed

Takahashi, Hiroshi; Inoue, Keiko; Shimizu, Kazue; Hiraga, Keiko; Takahashi, Erika; Otaki, Kaori; Yoshikawa, Taeko; Furuta, Kumiko; Tokunaga, Chika; Sakakibara, Tomoyo; Ito, Yasuhiko

2017-05-01

Protein energy wasting (PEW) is consistently associated with poor prognosis in hemodialysis (HD) patients. We compared the predictability of PEW as diagnosed by The International Society of Renal Nutrition and Metabolism criteria (PEW ISRNM ) and geriatric nutritional risk index (GNRI) for all-cause mortality in Japanese HD patients. As cut-off values for body mass index (BMI) for PEW have not been established in PEW ISRNM for Asian populations, these were also investigated. The nutritional status from 409 HD patients was evaluated according to ISRNM and GNRI criteria. To compare the predictability of mortality, C-index, net reclassification improvement (NRI) and integrated discrimination improvement were evaluated. During follow-up (median, 52 months; range, 7 months), 70 patients (17.1%) presented PEW according to ISRNM and 131 patients (32.1%) according to GNRI; in addition, 101 patients (24.7%) died. PEW ISRNM and GNRI were identified as independent predictors of death. Addition of PEW ISRNM and GNRI to a predictive model based on established risk factors improved NRI and integrated discrimination improvement. However, no differences were found between models including PEW ISRNM and GNRI. When lowering the criterion level of BMI per 1 kg/m 2 sequentially, PEW ISRNM at BMI <20 kg/m 2 maximized the hazard ratio for mortality. The model including PEW ISRNM at BMI <20 kg/m 2 improved NRI compared with the model including GNRI. PEW ISRNM and GNRI represent independent predictors of mortality, with comparable predictability. The diagnostic criterion of BMI in the ISRNM for Japanese population might be better at <20 kg/m 2 than at <23 kg/m 2 . Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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

Assessing glomerular filtration rate (GFR) in critically ill patients with acute kidney injury - true GFR versus urinary creatinine clearance and estimating equations

PubMed Central

2013-01-01

Introduction Estimation of kidney function in critically ill patients with acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but challenging due to fluctuations in kidney function, creatinine metabolism and fluid balance. Data on the agreement between estimating and gold standard methods to assess glomerular filtration rate (GFR) in early AKI are lacking. We evaluated the agreement of urinary creatinine clearance (CrCl) and three commonly used estimating equations, the Cockcroft Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in comparison to GFR measured by the infusion clearance of chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), in critically ill patients with early AKI after complicated cardiac surgery. Methods Thirty patients with early AKI were studied in the intensive care unit, 2 to 12 days after complicated cardiac surgery. The infusion clearance for 51Cr-EDTA obtained as a measure of GFR (GFR51Cr-EDTA) was calculated from the formula: GFR (mL/min/1.73m2) = (51Cr-EDTA infusion rate × 1.73)/(arterial 51Cr-EDTA × body surface area) and compared with the urinary CrCl and the estimated GFR (eGFR) from the three estimating equations. Urine was collected in two 30-minute periods to measure urine flow and urine creatinine. Urinary CrCl was calculated from the formula: CrCl (mL/min/1.73m2) = (urine volume × urine creatinine × 1.73)/(serum creatinine × 30 min × body surface area). Results The within-group error was lower for GFR51Cr-EDTA than the urinary CrCl method, 7.2% versus 55.0%. The between-method bias was 2.6, 11.6, 11.1 and 7.39 ml/min for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA. The error was 103%, 68.7%, 67.7% and 68.0% for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA. Conclusions The study demonstrated poor precision of the commonly utilized urinary CrCl method for assessment of GFR in critically ill patients with early AKI, suggesting that this should not be used as a reference method when validating new methods for assessing kidney function in this patient population. The commonly used estimating equations perform poorly when estimating GFR, with high biases and unacceptably high errors. PMID:23767877

Serum human epididymis secretory protein 4 as a potential biomarker of renal fibrosis in kidney transplantation recipients.

PubMed

Luo, Jinmei; Wang, Fen; Wan, Jianxin; Ye, Zhuangjian; Huang, Chumei; Cai, Yuesu; Liu, Min; Wu, Ben-Quan; Li, Laisheng

2018-05-05

Renal fibrosis remains an important cause of kidney allograft failure. The objective of this study was to evaluate the performance of serum human epididymis secretory protein 4 (HE4) as a biomarker for renal fibrosis in kidney transplant recipients. A total of 103 kidney transplantation patients were enrolled in this study, and serum HE4 concentrations were detected using the chemiluminescent microparticle immunoassay. Renal biopsy was carried out, and histological findings were assessed by immunohistochemistry. Median serum HE4 concentrations were significantly increased in kidney transplant recipients (186.2 pmol/l, interquartile range [IQR] 125.6-300.2) compared with control subjects (34.3 pmol/l, IQR 30.4-42.3, p < 0.0001). Meanwhile, serum HE4 concentrations were significantly increased along with disease severity (p < 0.0001). In addition, we found serum HE4 concentrations to be strongly correlated with the severity of fibrosis (IF/TA 0, 1, 2, and 3: 114.3, 179.0, 197.8, and 467.8 pmol/l, respectively; p < 0.0001) and serum HE4 concentrations significantly correlated with HE4 tissue expression concentrations in renal biopsy. Serum HE4 was increased in kidney transplant recipients with decreased kidney function and renal fibrosis and was correlated with the severity of the disease, suggesting that HE4 has the potential to be used as a novel clinical biomarker for evaluating kidney function and predicting renal fibrosis in kidney transplant recipients. Copyright © 2018 Elsevier B.V. All rights reserved.

Pretransplant urinary proteome analysis does not predict development of chronic kidney disease after liver transplantation.

PubMed

Milongo, David; Bascands, Jean-Loup; Huart, Antoine; Esposito, Laure; Breuil, Benjamin; Moulos, Panagiotis; Siwy, Justyna; Ramírez-Torres, Adela; Ribes, David; Lavayssière, Laurence; Del Bello, Arnaud; Muscari, Fabrice; Alric, Laurent; Bureau, Christophe; Rostaing, Lionel; Schanstra, Joost P; Kamar, Nassim

2015-07-01

Chronic kidney disease (CKD) is a common complication after liver transplantation. Kidney biopsies cannot be easily performed before liver transplantation to predict patients at high risk for CKD. The aim of our study was to determine whether pre-, peri- and post-transplant factors, as well as peptides present in preliver transplant urine samples were associated with loss in kidney function at 6 months post-transplantation using proteome analysis. Eighty patients who underwent a liver transplantation and that had pretransplant glomerular filtration rate (GFR) value of ≥60 mL/min/1.73 m² (MDRD) were included in the study. GFR decreased significantly after transplantation. At month 6 post-transplantation, 40 patients displayed a CKD, i.e. eGFR of <60 mL/min/1.73 m², while the other 40 patients did not. Although thousands of peptides were identified, none was significantly associated with the development of CKD at 6 months after liver transplantation. Moreover, using a urinary peptidome classifier to detect preexisting CKD, no difference was found in CKD scores between the 2 groups. After analysis of a large number of pre-, peri- and post-transplant parameters, viral hepatitis as a cause for liver transplantation was the sole independent predictive factor for CKD. No difference in peptides with differential urinary abundance between patients who received a graft for virus related liver disease vs. all other causes of liver disease was observed. Urinary peptidome analysis before liver transplantation failed to identify a peptide pattern associated with the development of CKD at 6 months after liver transplantation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Glycosylation Gap in Patients with Diabetes with Chronic Kidney Disease and Healthy Participants: A Comparative Study.

PubMed

Neelofar, Km; Ahmad, Jamal

2017-01-01

The aim of this study it to determine the level of glycosylation gap in patients with type 2 diabetes and its relation with kidney dysfunction. In this study, 150 individuals were enrolled (aged 20-75 year) and divided into three groups. Group 1 included 50 nondiabetic individuals who served as control. Group 2 included 50 patients with type 2 diabetes without chronic kidney disease (CKD), and in Group 3, there were 50 patients with type 2 diabetes with CKD. Glycated hemoglobin (HbA1c) and fructosamine (FA) were measured in all groups to determine the glycosylation gap (GG), predicted HbA1c, and mean blood glucose (MBG). GG is defined as the difference between measured HbA1c and HbA1c predicted from FA based on the population regression of HbA1c on FA. The variables were compared by correlation analysis. Serum creatinine level was significantly high in patients with CKD (1.93 ± 0.99) as compared to patients with diabetes and control (0.891 ± 0.16; 0.912 ± 0.1), respectively. The study demonstrated a significant elevation in serum FA, measured HbA1c and predicted HbA1c, MBG in patients with diabetes with CKD as compared with those of without CKD, and controls. GG was found in healthy control (0.51 ± 0.78), patients with type 2 diabetes without CKD (0.62 ± 0.45), and patients with diabetes with CKD (1.0 ± 0.91), respectively. It is concluded that GG may be a useful clinical research tool for evaluating pathological source of variation in diabetes complications such as kidney disease.

The optimal definition of contrast-induced acute kidney injury for prediction of inpatient mortality in patients undergoing percutaneous coronary interventions.

PubMed

Parsh, Jessica; Seth, Milan; Briguori, Carlo; Grossman, Paul; Solomon, Richard; Gurm, Hitinder S

2016-05-01

It is unknown which definition of contrast-induced acute kidney injury (CI-AKI) in the setting of percutaneous coronary interventions is best associated with inpatient mortality and whether this association is stable across patients with various preprocedural serum creatinine (SCr) values. We applied logistic regression models to multiple CI-AKI definitions used by the Kidney Disease Improving Global Outcomes guidelines and previously published studies to examine the impact of preprocedural SCr on a candidate definition's correlation with the adverse outcome of inpatient mortality. We used likelihood ratio tests to examine candidate definitions and identify those where association with inpatient mortality remained constant regardless of preprocedural SCr. These definitions were assessed for specificity, sensitivity, and positive and negative predictive values to identify an optimal definition. Our study cohort included 119,554 patients who underwent percutaneous coronary intervention in Michigan between 2010 and 2014. Most commonly used definitions were not associated with inpatient mortality in a constant fashion across various preprocedural SCr values. Of the 266 candidate definitions examined, 16 definition's association with inpatient mortality was not significantly altered by preprocedural SCr. Contrast-induced acute kidney injury defined as an absolute increase of SCr ≥0.3 mg/dL and a relative SCr increase ≥50% was selected as the optimal candidate using Perkins and Shisterman decision theoretic optimality criteria and was highly predictive of and specific for inpatient mortality. We identified the optimal definition for CI-AKI to be an absolute increase in SCr ≥0.3 mg/dL and a relative SCr increase ≥50%. Further work is needed to validate this definition in independent studies and to establish its utility for clinical trials and quality improvement efforts. Copyright © 2016 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.

Soluble CD30 and Hepatocyte growth factor as predictive markers of antibody-mediated rejection of the kidney allograft.

PubMed

Pavlova, Yelena; Viklicky, Ondrej; Slatinska, Janka; Bürgelova, Marcela; Süsal, Caner; Skibova, Jelena; Honsová, Eva; Striz, Ilja; Kolesar, Libor; Slavcev, Antonij

2011-07-01

Our retrospective study was aimed to assess the relevance of pre- and post-transplant measurements of serum concentrations of the soluble CD30 molecule (soluble CD30, sCD30) and the cytokine Hepatocyte growth factor (HGF) for prediction of the risk for development of antibody-mediated rejection (AMR) in kidney transplant patients. Evaluation of sCD30, HGF levels and the presence of HLA-specific antibodies in a cohort of 205 patients was performed before, 2weeks and 6months after transplantation. Patients were followed up for kidney graft function and survival for two years. We found a tendency of higher incidence of AMR in retransplanted patients with elevated pre-transplant sCD30 (≥100U/ml) (p=0.051), however no such correlation was observed in first-transplant patients. Kidney recipients with simultaneously high sCD30 and HLA-specific antibodies (sCD30+/Ab+) before transplantation had significantly lower AMR-free survival compared to the other patient groups (p<0.001). HGF concentrations were not associated with the incidence of AMR at any time point of measurement, nevertheless, the combined analysis HGF and sCD30 showed increased incidence of AMR in recipients with elevated pretransplant sCD30 and low HGF levels. the predictive value of pretransplant sCD30 for the development of antibody-mediated rejection after transplantation is significantly potentiated by the co-presence of HLA specific antibodies. The role of HGF as a rejection-protective factor in patients with high pretransplant HGF levels would need further investigation. Copyright © 2011 Elsevier B.V. All rights reserved.

Nonpharmacological Strategies to Prevent Contrast-Induced Acute Kidney Injury

PubMed Central

Eiam-Ong, Somchai

2014-01-01

Contrast-induced AKI (CI-AKI) has been one of the leading causes for hospital-acquired AKI and is associated with independent risk for adverse clinical outcomes including morbidity and mortality. The aim of this review is to provide a brief summary of the studies that focus on nonpharmacological strategies to prevent CI-AKI, including routine identification of at-risk patients, use of appropriate hydration regimens, withdrawal of nephrotoxic drugs, selection of low-osmolar contrast media or isoosmolar contrast media, and using the minimum volume of contrast media as possible. There is no need to schedule dialysis in relation to injection of contrast media or injection of contrast agent in relation to dialysis program. Hemodialysis cannot protect the poorly functioning kidney against CI-AKI. PMID:24795882

Optimization of barrel temperature and kidney bean flour percentage based on various physical properties of extruded snacks.

PubMed

Agathian, G; Semwal, A D; Sharma, G K

2015-07-01

The aim of the experiment was to optimize barrel temperature (122 to 178 ± 0.5 °C) and red kidney bean flour percentage (KBF) (12 to 68 ± 0.5 %) based on physical properties of extrudates like flash off percentage, water absorption index (WAI), water solubility index (WSI), bulk density (BD), radial expansion ratio (RER) and overall acceptability (OAA) using single screw extruder. The study was carried out by central composite rotatable design (CCRD) using Response surface methodology (RSM) and moisture content of feed was kept as constant 16.0 ± 0.5 % throughout experiments. Mathematical models for various responses were found to fit significantly (P < 0.05) for prediction. Optimization of experimental conditions was carried out using numerical optimization technique and the optimum barrel temperature and kidney bean flour percentage were 120 °C (T1) & 142.62 °C (T2 = T3) and 20 % respectively with desirability value of 0.909. Experiments were carried out using predicted values and verified using t-test and coefficient of variation percentage. Extruded snack prepared with rice flour (80 %) and kidney bean flour (20 %) at optimized conditions was accepted by the taste panellists and above 20 % KB incorporation was found to decrease overall acceptability score.

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.

Lifetime risks of kidney donation: a medical decision analysis.

PubMed

Kiberd, Bryce A; Tennankore, Karthik K

2017-09-01

This study estimated the potential loss of life and the lifetime cumulative risk of end-stage renal disease (ESRD) from live kidney donation. Markov medical decision analysis. USA. 40-year-old live kidney donors of both sexes and black/white race. Live donor nephrectomy. Potential remaining life years lost, quality-adjusted life years (QALYs) lost and added lifetime cumulative risk of ESRD from donation. Overall 0.532-0.884 remaining life years were lost from donating a kidney. This was equivalent to 1.20%-2.34% of remaining life years (or 0.76%-1.51% remaining QALYs). The risk was higher in male and black individuals. The study showed that 1%-5% of average-age current live kidney donors might develop ESRD as a result of nephrectomy. The added risk of ESRD resulted in a loss of only 0.126-0.344 remaining life years. Most of the loss of life was predicted to be associated with chronic kidney disease (CKD) not ESRD. Most events occurred 25 or more years after donation. Reducing the increased risk of death associated with CKD had a modest overall effect on the per cent loss of remaining life years (0.72%-1.9%) and QALYs (0.58%-1.33%). Smoking and obesity reduced life expectancy and increased overall lifetime risks of ESRD in non-donors. However the percentage loss of remaining life years from donation was not very different in those with or without these risk factors. Live kidney donation may reduce life expectancy by 0.5-1 year in most donors. The development of ESRD in donors may not be the only measure of risk as most of the predicted loss of life predates ESRD. The study identifies the potential importance of following donors and treating risk factors aggressively to prevent ESRD and to improve donor survival. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

New Factors Predicting Delayed Graft Function: a Multi-Center Cohort Study of Kidney Donation After Brain Death Followed by Circulatory Death.

PubMed

Sun, Qipeng; Huang, Zhengyu; Zhou, Honglan; Lin, Minzhuan; Hua, Xuefeng; Hong, Liangqing; Na, Ning; Cai, Ruiming; Wang, Gang; Sun, Qiquan

2018-05-30

Delayed graft function (DGF) is a common complication following kidney transplantation adversely affecting graft outcomes. Donation after brain death followed by circulatory death (DBCD), a novel donation pattern, is expected to correlate with high incidence of DGF. However, little information is available about factors associated with DGF in DBCD. A total of 383 kidney transplants from DBCD donation in three institutions were enrolled. Associations of DGF with the clinical characteristics of recipients and donors were quantified. In this retrospective multi-center study, the incidence of DGF was 19.3%. Lower incidence of DGF was found in recipients for whom antithymocyte globulin was used for induction (p < 0.05), which was an independent protective factor against DGF (odds ratio [OR] = 0.48; 95% CI 0.27-0.86). Two novel explicative variables were recognized as independent risk factors, including use of vasoactive drugs (OR = 3.15; 95% CI 1.39-7.14) and cardiopulmonary resuscitation (OR = 2.51; 95% CI 1.05-6.00), which contributed significantly to increased risk of DGF (p < 0.05). Prolonged warm ischemia time (> 18 min; OR = 2.42; 95% CI 1.36-4.32), was also predictive of DGF in DBCD. A prediction model was developed and achieved an area under the curve of 0.89 in predicting DGF when combined with reported parameters. The novel factors, confirmed for the first time in our study, will help to improve risk prediction of DGF and to determine optimal interventions to prevent DGF in clinical practice. © 2018 The Author(s). Published by S. Karger AG, Basel.

Physical performance and frailty in chronic kidney disease.

PubMed

Reese, Peter P; Cappola, Anne R; Shults, Justine; Townsend, Raymond R; Gadegbeku, Crystal A; Anderson, Cheryl; Baker, Joshua F; Carlow, Dean; Sulik, Michael J; Lo, Joan C; Go, Alan S; Ky, Bonnie; Mariani, Laura; Feldman, Harold I; Leonard, Mary B

2013-01-01

Poor physical performance and frailty are associated with elevated risks of death and disability. Chronic kidney disease (CKD) is also strongly associated with these outcomes. The risks of poor physical performance and frailty among CKD patients, however, are not well established. We measured the Short Physical Performance Battery (SPPB; a summary test of gait speed, chair raises and balance; range 0-12) and the five elements of frailty among 1,111 Chronic Renal Insufficiency Cohort participants. Adjusting for demographics and multiple comorbidities, we fit a linear regression model for the outcome of SPPB score and an ordinal logistic regression model for frailty status. Median (interquartile range, IQR) age was 65 (57-71) years, median estimated glomerular filtration rate (eGFR) for non-dialysis patients was 49 (36-62) ml/min/1.73 m(2), and median SPPB score was 9 (7-10). Seven percent of participants were frail and 43% were pre-frail. Compared with the SPPB score for eGFR >60 ml/min/1.73 m(2), the SPPB was 0.51 points lower for eGFR 30-59; 0.61 points lower for eGFR 15-29, and 1.75 points lower for eGFR <15 (p < 0.01 for all comparisons). eGFR 30-59 (odds ratio, OR 1.45; p = 0.024), eGFR 15-29 (OR 2.02; p = 0.002) and eGFR <15 (OR 4.83; p < 0.001) were associated with worse frailty status compared with eGFR >60 ml/min/1.73 m(2). CKD severity was associated with poor physical performance and frailty in a graded fashion. Future trials should determine if outcomes for CKD patients with frailty and poor physical performance are improved by targeted interventions. © 2013 S. Karger AG, Basel.

Monomeric neutrophil gelatinase associated lipocalin is associated with tubulointerstitial damage in chronic kidney disease

PubMed Central

Nickolas, Thomas L.; Forster, Catherine; Sise, Meghan E.; Barasch, Nicholas; Valle, David Solá-Del; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

2012-01-01

The rate of progression of chronic kidney disease (CKD) is difficult to predict using single measurements of serum creatinine or proteinuria. On the other hand, documented tubulointerstitial disease presages worsening CKD, but kidney biopsy is not practical for routine use and generally does not sample the tubulointerstitial compartment of the medulla. Perhaps a urine test that correlates with specific histological findings may serve as a surrogate for the kidney biopsy. Here we compared both immunoblot analysis (under non-reducing conditions) and a commercially available monomer immunoassays of Neutrophil Gelatinase Associated Lipocalin (NGAL) with pathological changes found in kidney biopsies, to determine whether specific histological characteristics associated with a specific NGAL species. We found that the urine of patients with advanced CKD contained NGAL monomers as well as higher molecular weight complexes containing NGAL, identified by MALDI-TOF/TOF mass spectroscopy. The NGAL monomer significantly correlated with glomerular filtration rate, interstitial fibrosis and tubular atrophy. Hence, specific assays of the NGAL monomer implicate histology associated with progressive, severe CKD. PMID:22695331

Kidney-on-a-Chip: a New Technology for Predicting Drug Efficacy, Interactions, and Drug-induced Nephrotoxicity.

PubMed

Lee, Jeonghwan; Kim, Sejoong

2018-03-08

The kidneys play a pivotal role in most drug-removal processes and are important when evaluating drug safety. Kidney dysfunction resulting from various drugs is an important issue in clinical practice and during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and animals, and static cell culture experiments cannot fully reflect the actual microphysiological environment in humans. A kidney-on-a-chip is a microfluidic device that allows the culture of living renal cells in 3-dimensional channels and mimics the human microphysiological environment, thus simulating the actual drug filtering, absorption, and secretion process.. In this review, we discuss recent developments in microfluidic culturing technique and describe current and future kidney-on-a-chip applications. We focus on pharmacological interactions and drug-induced nephrotoxicity, and additionally discuss the development of multi-organ chips and their possible applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Transforming Growth Factor β-1 Stimulates Profibrotic Epithelial Signaling to Activate Pericyte-Myofibroblast Transition in Obstructive Kidney Fibrosis

PubMed Central

Wu, Ching-Fang; Chiang, Wen-Chih; Lai, Chun-Fu; Chang, Fan-Chi; Chen, Yi-Ting; Chou, Yu-Hsiang; Wu, Ting-Hui; Linn, Geoffrey R.; Ling, Hong; Wu, Kwan-Dun; Tsai, Tun-Jun; Chen, Yung-Ming; Duffield, Jeremy S.; Lin, Shuei-Liong

2014-01-01

Pericytes have been identified as the major source of precursors of scar-producing myofibroblasts during kidney fibrosis. The underlying mechanisms triggering pericyte-myofibroblast transition are poorly understood. Transforming growth factor β-1 (TGF-β1) is well recognized as a pluripotent cytokine that drives organ fibrosis. We investigated the role of TGF-β1 in inducing profibrotic signaling from epithelial cells to activate pericyte-myofibroblast transition. Increased expression of TGF-β1 was detected predominantly in injured epithelium after unilateral ureteral obstruction, whereas downstream signaling from the TGF-β1 receptor increased in both injured epithelium and pericytes. In mice with ureteral obstruction that were treated with the pan anti–TGF-β antibody (1D11) or TGF-β receptor type I inhibitor (SB431542), kidney pericyte-myofibroblast transition was blunted. The consequence was marked attenuation of fibrosis. In addition, epithelial cell cycle G2/M arrest and production of profibrotic cytokines were both attenuated. Although TGF-β1 alone did not trigger pericyte proliferation in vitro, it robustly induced α smooth muscle actin (α-SMA). In cultured kidney epithelial cells, TGF-β1 stimulated G2/M arrest and production of profibrotic cytokines that had the capacity to stimulate proliferation and transition of pericytes to myofibroblasts. In conclusion, this study identified a novel link between injured epithelium and pericyte-myofibroblast transition through TGF-β1 during kidney fibrosis. PMID:23142380

Economic Consequences Incurred by Living Kidney Donors: A Canadian Multi-Center Prospective Study

PubMed Central

Klarenbach, S; Gill, J S; Knoll, G; Caulfield, T; Boudville, N; Prasad, G V R; Karpinski, M; Storsley, L; Treleaven, D; Arnold, J; Cuerden, M; Jacobs, P; Garg, A X

2014-01-01

Some living kidney donors incur economic consequences as a result of donation; however, these costs are poorly quantified. We developed a framework to comprehensively assess economic consequences from the donor perspective including out-of-pocket cost, lost wages and home productivity loss. We prospectively enrolled 100 living kidney donors from seven Canadian centers between 2004 and 2008 and collected and valued economic consequences ($CAD 2008) at 3 months and 1 year after donation. Almost all (96%) donors experienced economic consequences, with 94% reporting travel costs and 47% reporting lost pay. The average and median costs of lost pay were $2144 (SD 4167) and $0 (25th–75th percentile 0, 2794), respectively. For other expenses (travel, accommodation, medication and medical), mean and median costs were $1780 (SD 2504) and $821 (25th–75th percentile 242, 2271), respectively. From the donor perspective, mean cost was $3268 (SD 4704); one-third of donors incurred cost >$3000, and 15% >$8000. The majority of donors (83%) reported inability to perform usual household activities for an average duration of 33 days; 8% reported out-of-pocket costs for assistance with these activities. The economic impact of living kidney donation for some individuals is large. We advocate for programs to reimburse living donors for their legitimate costs. In a prospective costing study, the authors find that economic consequences incurred by living kidney donors are frequent and nontrivial, and a notable proportion of donors experience significant costs. PMID:24597854

Stumbling toward equity: the role of government in kidney transplantation.

PubMed

Dooley, L G; Gaston, R S

1998-01-01

In Mortal Peril, Professor Epstein is critical of the current, regulated system for organ donation and suggests that a market for organ tissue would better meet the needs of patients. In this response to Professor Epstein, Professor Laura Dooley and Dr. Robert Gaston pair their skills to attack Professor Epstein's analysis. As they have done on several other occasions, Professors Dooley and Gaston argue that the kidney donation and transplantation arena is fraught with racial inequity, and that Professor Epstein's proposal for a market in kidneys will exacerbate this inequity. The authors maintain that to prevent the poor from being excluded from transplants, the government plays a critical (if imperfect) role in the allocation of these scarce resources. Furthermore, government intervention is acceptable to correct past discrimination because there is scientific evidence that the disproportionate incidence of kidney failure in African Americans is related to the evolutionary pressures of slave trading and slavery. Professors Dooley and Gaston also defend their previous efforts to change the government system of allocation and characterize the government's willingness to adopt their recommendations as an appropriate response to scientific research rather than a governmental susceptibility to lobbying from special interest groups. Finally, the authors criticize Professor Epstein's argument that dialysis is a viable alternative to transplantation because there are significant differences in "quality of life, morbidity and survival." Professors Dooley and Gaston conclude that government intervention is necessary for maintaining the equity in kidney transplantation that a market system would not.

Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients: A Guidance Report and Clinical Checklist by the Consensus on Managing Modifiable Risk in Transplantation (COMMIT) Group.

PubMed

Neuberger, James M; Bechstein, Wolf O; Kuypers, Dirk R J; Burra, Patrizia; Citterio, Franco; De Geest, Sabina; Duvoux, Christophe; Jardine, Alan G; Kamar, Nassim; Krämer, Bernhard K; Metselaar, Herold J; Nevens, Frederik; Pirenne, Jacques; Rodríguez-Perálvarez, Manuel L; Samuel, Didier; Schneeberger, Stefan; Serón, Daniel; Trunečka, Pavel; Tisone, Giuseppe; van Gelder, Teun

2017-04-01

Short-term patient and graft outcomes continue to improve after kidney and liver transplantation, with 1-year survival rates over 80%; however, improving longer-term outcomes remains a challenge. Improving the function of grafts and health of recipients would not only enhance quality and length of life, but would also reduce the need for retransplantation, and thus increase the number of organs available for transplant. The clinical transplant community needs to identify and manage those patient modifiable factors, to decrease the risk of graft failure, and improve longer-term outcomes.COMMIT was formed in 2015 and is composed of 20 leading kidney and liver transplant specialists from 9 countries across Europe. The group's remit is to provide expert guidance for the long-term management of kidney and liver transplant patients, with the aim of improving outcomes by minimizing modifiable risks associated with poor graft and patient survival posttransplant.The objective of this supplement is to provide specific, practical recommendations, through the discussion of current evidence and best practice, for the management of modifiable risks in those kidney and liver transplant patients who have survived the first postoperative year. In addition, the provision of a checklist increases the clinical utility and accessibility of these recommendations, by offering a systematic and efficient way to implement screening and monitoring of modifiable risks in the clinical setting.

Assessment of cisplatin-induced kidney injury using an integrated rodent platform

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

Chen, Yafei; Brott, David; Luo, Wenli

Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15 mg/kg). Glomerular filtrationmore » rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72 h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24 h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6 h post-dose, which preceded significant declines of GFR and ERPF (24 h), increased plasma Cr and BUN (72 h), and associated with renal acute tubular necrosis at 72 h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident. - Highlights: ► CDDP causes direct damage to kidneys without affecting EEG or CVS function. ► α-GST and albumin detect DIKI earlier when compared with traditional indices. ► Integrated “cardiovascular-EEG-renal” model to better understand DIKI mechanisms ► Promotes 3R's principles in drug discovery and development.« less

Ontogenetic shifts and spatial associations in organ positions for snakes.

PubMed

Anderson, Gretchen E; Secor, Stephen M

2015-12-01

Snakes possess an elongated body form and serial placement of organs which provides the opportunity to explore historic and adaptive mechanisms of organ position. We examined the influence of body size and sex on the position of, and spatial associations between, the heart, liver, small intestine, and right kidney for ten phylogenetically diverse species of snakes that vary in body shape and habitat. Snake snout-vent length explained much of the variation in the position of these four organs. For all ten species, the position of the heart and liver relative to snout-vent length decreased as a function of size. As body size increased from neonate to adult, these two organs shifted anteriorly an average of 4.7% and 5.7% of snout-vent length, respectively. Similarly, the small intestine and right kidney shifted anteriorly with an increase in snout-vent length for seven and five of the species, respectively. The absolute and relative positioning of these organs did not differ between male and female Burmese pythons (Python molurus). However, for diamondback water snakes (Nerodia rhombifer), the liver and small intestine were more anteriorly positioned in females as compared to males, whereas the right kidney was positioned more anteriorly for males. Correlations of residuals of organ position (deviation from predicted position) demonstrated significant spatial associations between organs for nine of the ten species. For seven species, individuals with hearts more anterior (or posterior) than predicted also tended to possess livers that were similarly anteriorly (or posteriorly) placed. Positive associations between liver and small intestine positions and between small intestine and right kidney positions were observed for six species, while spatial associations between the heart and small intestine, heart and right kidney, and liver and right kidney were observed in three or four species. This study demonstrates that size, sex, and spatial associations may have potential interacting effects when testing evolutionary scenarios for the position of snake organs. Copyright © 2015 Elsevier GmbH. All rights reserved.

Early safety outcome following transcatheter aortic valve implantation: is the amount of contrast media used a matter of concern?

PubMed

Vontobel, Jan; Possner, Mathias; Schütz, Philipp; Müller, Beat; Taramasso, Maurizio; Binder, Roland K; Haueis, Sabine; Attinger-Toller, Adrian; Maisano, Francesco; Nietlispach, Fabian

2015-01-01

The study objective was to evaluate the impact of the amount of contrast medium used for transcatheter aortic valve implantation (TAVI) on short-term outcome. Patients undergoing TAVI are exposed to repeat contrast medium application both for preprocedural screening and during the TAVI procedure itself. Whether the amount of contrast media is associated with worse outcome is unclear. A total of 257 patients were included (median age 82.7 years) and divided into two groups with preserved and reduced kidney function (glomerular filtration rate <60 ml/min/1.73 m2), respectively. Total volume of contrast media administered during and within 5 days prior to TAVI was analysed. A combined early safety endpoint at 30 days was evaluated. The early safety endpoint was reached by 31 patients and acute kidney injury occurred in 22 patients. The median total volume of contrast media administered was 144 ml (interquartile range 81-225 ml). The amount of contrast did not independently predict the early safety endpoint in the overall population (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.56 to 1.53, p = 0.774) and in subgroups with preserved and reduced kidney function. Change in creatinine was an independent strong predictor of the early safety endpoint in the overall population (OR 18.13, 95% CI 4.70 to 69.99, p <0.001), as well as in subgroups with preserved and reduced kidney function. The amount of contrast did not predict a change in creatinine within 72 hours following TAVI (r = 0.02, 95% CI -0.02 to 0.07, p = 0.368). Decreased kidney function after TAVI influences outcome. When rather small amounts of contrast media are used for screening and the TAVI procedure itself, the amount of contrast media seems not to be an independent predictor of outcome, further suggesting that decreased kidney function after TAVI is multifactorial.

Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test.

PubMed

Nguyen, Kevin A; Syed, Jamil S; Espenschied, Carin R; LaDuca, Holly; Bhagat, Ansh M; Suarez-Sarmiento, Alfredo; O'Rourke, Timothy K; Brierley, Karina L; Hofstatter, Erin W; Shuch, Brian

2017-11-15

Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P < .0001). Overall, 6.1%, 75.5%, and 18.4% of individuals had positive, negative, and inconclusive results, respectively. The most commonly altered genes included folliculin (FLCN) and fumarate hydratase (FH), which were altered in 1.8% and 1.3% of patients, respectively. Tuberous Sclerosis Complex 2 (TSC2), mesenchymal epithelial transition factor proto-oncogene (MET), and PMS1 homolog 2 (PMS2) had the highest rates of variants of unknown significance, which were identified in 2.7%, 2.2%, and 1.7% of patients, respectively. Early age of onset was the only factor that was identified as predictive of a positive test on multivariate analysis (odds ratio, 0.975; P = .0052) and may be the only identifying characteristic of low-penetrant syndromes, such as those associated with MITF (melanogenesis-associated transcription factor) mutations, which do not have singular histology or a family history of kidney cancer. Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society. © 2017 American Cancer Society.

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.

Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing.

PubMed

Cohen, Eric P; Hankey, Kim G; Bennett, Alexander W; Farese, Ann M; Parker, George A; MacVittie, Thomas J

2017-12-01

The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

PIRCHE-II Is Related to Graft Failure after Kidney Transplantation

PubMed Central

Geneugelijk, Kirsten; Niemann, Matthias; Drylewicz, Julia; van Zuilen, Arjan D.; Joosten, Irma; Allebes, Wil A.; van der Meer, Arnold; Hilbrands, Luuk B.; Baas, Marije C.; Hack, C. Erik; van Reekum, Franka E.; Verhaar, Marianne C.; Kamburova, Elena G.; Bots, Michiel L.; Seelen, Marc A. J.; Sanders, Jan Stephan; Hepkema, Bouke G.; Lambeck, Annechien J.; Bungener, Laura B.; Roozendaal, Caroline; Tilanus, Marcel G. J.; Vanderlocht, Joris; Voorter, Christien E.; Wieten, Lotte; van Duijnhoven, Elly M.; Gelens, Mariëlle; Christiaans, Maarten H. L.; van Ittersum, Frans J.; Nurmohamed, Azam; Lardy, Junior N. M.; Swelsen, Wendy; van der Pant, Karlijn A.; van der Weerd, Neelke C.; ten Berge, Ineke J. M.; Bemelman, Fréderike J.; Hoitsma, Andries; van der Boog, Paul J. M.; de Fijter, Johan W.; Betjes, Michiel G. H.; Heidt, Sebastiaan; Roelen, Dave L.; Claas, Frans H.; Otten, Henny G.; Spierings, Eric

2018-01-01

Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor–recipient couples that were transplanted between 1995 and 2005. For these donors–recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04–1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10–1.34, p < 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival. PMID:29556227

Impaired renal function is associated with worse self-reported outcomes after kidney transplantation.

PubMed

Neri, Luca; Dukes, Jonathan; Brennan, Daniel C; Salvalaggio, Paulo R; Seelam, Susmitha; Desiraju, Srividya; Schnitzler, Mark

2011-12-01

We sought to determine the association between health-related quality of life (HRQOL) and graft function in renal transplant recipients. We enrolled 577 kidney transplant recipients aged 18-74 years (response rate 87%). Recipients with multiple or multi-organ transplantation, creatine kinase >200 U/L, acute renal failure or cellular rejection (n = 64), and without creatinine assessments in 3 months pre-enrollment (n = 127) were excluded. The questionnaire included Euro QOL 5 Dimensions (EQ-5D), Health Utility Index III (HUI-III), Kidney Disease Quality of Life-36 (KDQOL36) which include a generic section (RAND SF-12). Data on medical conditions, therapy regimens, and biochemistry results were extracted from clinical charts. We used general linear models adjusted for demographic, socioeconomic, and clinical characteristics to assess the association between HRQOL and severity of chronic kidney disease (CKD). Patients with more advanced CKD were more likely to be African-American, covered by public insurance, more likely to have shorter time after transplantation, higher phosphorus and lower hemoglobin, serum albumin, and calcium levels. All HRQOL scales were inversely associated with CKD severity. All associations were robust to adjustment for possible confounders. Several health-related quality of life dimensions may be affected by poor renal function after transplantation.

Heme induces IL-1β secretion through activating NLRP3 in kidney inflammation.

PubMed

Li, Qianwei; Fu, Weihua; Yao, Jiwei; Ji, Zheng; Wang, Yongquan; Zhou, Zhansong; Yan, Junan; Li, Weibing

2014-07-01

To produce proinflammatory master cytokine IL-1β in macrophages, two stimulation pathways are needed including TLRs-NF-κB axis and NLRPs/ASC-caspase-1 axis. Different signals including exogenous and endogenous trigger inflammatory response distinctly. Among them, the role of endogenous stimulators of inflammation is poorly understood. As a component of hemoglobin, free heme is released when hemolysis or extensive cell damage occur which results in inflammatory response. Here, we find that heme induces IL-1β secretion through activating NLRP3 inflammasome in macrophages. Heme activates NLRP3 through P2X receptors, especially the P2X7R and P2X4R. Most importantly, significantly enhancement of heme level and activation of NLRPs/ASC-caspase-1 axis were observed in mice kidney after unilateral ureteral obstruction which could be inhibited by enforced expression of heme oxygenase-1 (HO-1). Our study proves that heme is a potential danger activator of NLRP3 inflammasome that plays an essential role in IL-1β secretion during kidney inflammation and provides new insight into the mechanism of innate immune initiation. Further investigation will be beneficial to develop new molecular target and molecular diagnosis indicator in therapy of kidney inflammation.

Podometrics as a Potential Clinical Tool for Glomerular Disease Management.

PubMed

Kikuchi, Masao; Wickman, Larysa; Hodgin, Jeffrey B; Wiggins, Roger C

2015-05-01

Chronic kidney disease culminating in end-stage kidney disease is a major public health problem costing in excess of $40 billion per year with high morbidity and mortality. Current tools for glomerular disease monitoring lack precision and contribute to poor outcome. The podocyte depletion hypothesis describes the major mechanisms underlying the progression of glomerular diseases, which are responsible for more than 80% of cases of end-stage kidney disease. The question arises of whether this new knowledge can be used to improve outcomes and reduce costs. Podocytes have unique characteristics that make them an attractive monitoring tool. Methodologies for estimating podocyte number, size, density, glomerular volume and other parameters in routine kidney biopsies, and the rate of podocyte detachment from glomeruli into urine (podometrics) now have been developed and validated. They potentially fill important gaps in the glomerular disease monitoring toolbox. The application of these tools to glomerular disease groups shows good correlation with outcome, although data validating their use for individual decision making is not yet available. Given the urgency of the clinical problem, we argue that the time has come to focus on testing these tools for application to individualized clinical decision making toward more effective progression prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Ballew, Shoshana H; Chen, Yan; Daya, Natalie R; Godino, Job G; Windham, B Gwen; McAdams-DeMarco, Mara; Coresh, Josef; Selvin, Elizabeth; Grams, Morgan E

2017-02-01

Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Observational study. 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013). Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFR cr ) and serum cystatin C level (eGFR cys ) and urine albumin-creatinine ratio. Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). 341 (7%) participants were classified as frail, 1,475 (30%) had eGFR cr <60mL/min/1.73m 2 , 2,480 (50%) had eGFR cys <60mL/min/1.73m 2 , and 1,006 (20%) had albuminuria with albumin excretion ≥ 30mg/g. Among frail participants, prevalences of eGFR cr and eGFR cys <60mL/min/1.73m 2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFR cr and a strong association with eGFR cys and albumin-creatinine ratio. Frail individuals with eGFR cr of 60 to <75mL/min/1.73m 2 were frequently reclassified to lower eGFR categories using eGFR cys (49% to 45-<60, 32% to 30-<45, and 3% to <30mL/min/1.73m 2 ). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants). Cross-sectional study design. Frail individuals had a high prevalence of reduced kidney function, with large discrepancies when reduced kidney function was classified by eGFR cys versus eGFR cr . Given the substantial medication burden and uncertainty in chronic kidney disease classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Quality indicators for the detection and management of chronic kidney disease in primary care in Canada derived from a modified Delphi panel approach.

PubMed

Tu, Karen; Bevan, Lindsay; Hunter, Katie; Rogers, Jess; Young, Jacqueline; Nesrallah, Gihad

2017-01-01

The detection and management of chronic kidney disease lies within primary care; however, performance measures applicable in the Canadian context are lacking. We sought to develop a set of primary care quality indicators for chronic kidney disease in the Canadian setting and to assess the current state of the disease's detection and management in primary care. We used a modified Delphi panel approach, involving 20 panel members from across Canada (10 family physicians, 7 nephrologists, 1 patient, 1 primary care nurse and 1 pharmacist). Indicators identified from peer-reviewed and grey literature sources were subjected to 3 rounds of voting to develop a set of quality indicators for the detection and management of chronic kidney disease in the primary care setting. The final indicators were applied to primary care electronic medical records in the Electronic Medical Record Administrative data Linked Database (EMRALD) to assess the current state of primary care detection and management of chronic kidney disease in Ontario. Seventeen indicators made up the final list, with 1 under the category Prevalence, Incidence and Mortality; 4 under Screening, Diagnosis and Risk Factors; 11 under Management; and 1 under Referral to a Specialist. In a sample of 139 993 adult patients not on dialysis, 6848 (4.9%) had stage 3 or higher chronic kidney disease, with the average age of patients being 76.1 years (standard deviation [SD] 11.0); 62.9% of patients were female. Diagnosis and screening for chronic kidney disease were poorly performed. Only 27.1% of patients with stage 3 or higher disease had their diagnosis documented in their cumulative patient profile. Albumin-creatinine ratio testing was only performed for 16.3% of patients with a low estimated glomerular filtration rate (eGFR) and for 28.5% of patients with risk factors for chronic kidney disease. Family physicians performed relatively better with the management of chronic kidney disease, with 90.4% of patients with stage 3 or higher disease having an eGFR performed in the previous 18 months and 83.1% having a blood pressure recorded in the previous 9 months. We propose a set of measurable indicators to evaluate the quality of the management of chronic kidney disease in primary care. These indicators may be used to identify opportunities to improve current practice in Canada.

Attenuation of NADPH oxidase activation and glomerular filtration barrier remodeling with statin treatment.

PubMed

Whaley-Connell, Adam; Habibi, Javad; Nistala, Ravi; Cooper, Shawna A; Karuparthi, Poorna R; Hayden, Melvin R; Rehmer, Nathan; DeMarco, Vincent G; Andresen, Bradley T; Wei, Yongzhong; Ferrario, Carlos; Sowers, James R

2008-02-01

Activation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase by angiotensin II is integral to the formation of oxidative stress in the vasculature and the kidney. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibition is associated with reductions of oxidative stress in the vasculature and kidney and associated decreases in albuminuria. Effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition on oxidative stress in the kidney and filtration barrier integrity are poorly understood. To investigate, we used transgenic TG(mRen2)27 (Ren2) rats, which harbor the mouse renin transgene and renin-angiotensin system activation, and an immortalized murine podocyte cell line. We treated young, male Ren2 and Sprague-Dawley rats with rosuvastatin (20 mg/kg IP) or placebo for 21 days. Compared with controls, we observed increases in systolic blood pressure, albuminuria, renal NADPH oxidase activity, and 3-nitrotryosine staining, with reductions in the rosuvastatin-treated Ren2. Structural changes on light and transmission electron microscopy, consistent with periarteriolar fibrosis and podocyte foot-process effacement, were attenuated with statin treatment. Nephrin expression was diminished in the Ren2 kidney and trended to normalize with statin treatment. Angiotensin II-dependent increases in podocyte NADPH oxidase activity and subunit expression (NOX2, NOX4, Rac, and p22(phox)) and reactive oxygen species generation were decreased after in vitro statin treatment. These data support a role for increased NADPH oxidase activity and subunit expression with resultant reactive oxygen species formation in the kidney and podocyte. Furthermore, statin attenuation of NADPH oxidase activation and reactive oxygen species formation in the kidney/podocyte seems to play roles in the abrogation of oxidative stress-induced filtration barrier injury and consequent albuminuria.

Sildenafil improves renal function in patients with pulmonary arterial hypertension

PubMed Central

Webb, David J; Vachiery, Jean-Luc; Hwang, Lie-Ju; Maurey, Julie O

2015-01-01

Aim Elevated serum creatinine (sCr) and low estimated glomerular filtration rate (eGFR) are associated with poor outcomes in patients with pulmonary arterial hypertension (PAH) whereas sildenafil treatment improves PAH outcomes. This post hoc analysis assessed the effect of sildenafil on kidney function and links with clinical outcomes including 6-min walk distance, functional class, time to clinical worsening and survival. Methods Patients with PAH received placebo or sildenafil 20, 40 or 80 mg three times daily in the SUPER-1 study and open-label sildenafil titrated to 80 mg three times daily (as tolerated) in the extension study. Results Baseline characteristics were similar among groups (n = 277). PAH was mostly idiopathic (63%) and functional class II (39%) or III (58%). From baseline to week 12, kidney function improved (increased eGFR, decreased sCr) with sildenafil and worsened with placebo. In univariate logistic regression, improved kidney function was associated with significantly improved exercise and functional class (odds ratios 1.17 [95% CI 1.01, 1.36] and 1.21 [95% CI 1.03, 1.41], respectively, for sCr and 0.97 [95% CI 0.94, 0.99] and 0.97 [95% CI 0.94, 0.99] for eGFR, all P < 0.05). In patients who maintained or improved kidney function, time to worsening was significantly delayed (P < 0.02 for both kidney parameters). Observed trends towards improved survival were not significant. Patients with eGFR <60 (vs. ≥60) ml min–1 1.73 m–2 appeared to have worse survival. Conclusions Sildenafil treatment was associated with improved kidney function in patients with PAH, which was in turn associated with improved exercise capacity and functional class, a reduced risk of clinical worsening, and a trend towards reduced mortality. PMID:25727860

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

Early activation of deleterious molecular pathways in the kidney in experimental heart failure with atrial remodeling.

PubMed

Ichiki, Tomoko; Huntley, Brenda K; Harty, Gail J; Sangaralingham, S Jeson; Burnett, John C

2017-05-01

Heart failure (HF) is a major health problem with worsening outcomes when renal impairment is present. Therapeutics for early phase HF may be effective for cardiorenal protection, however the detailed characteristics of the kidney in early-stage HF (ES-HF), and therefore treatment for potential renal protection, are poorly defined. We sought to determine the gene and protein expression profiles of specific maladaptive pathways of ES-HF in the kidney and heart. Experimental canine ES-HF, characterized by de-novo HF with atrial remodeling but not ventricular fibrosis, was induced by right ventricular pacing for 10 days. Kidney cortex (KC), medulla (KM), left ventricle (LV), and left atrial (LA) tissues from ES-HF versus normal canines ( n  = 4 of each) were analyzed using RT-PCR microarrays and protein assays to assess genes and proteins related to inflammation, renal injury, apoptosis, and fibrosis. ES-HF was characterized by increased circulating natriuretic peptides and components of the renin-angiotensin-aldosterone system and decreased sodium and water excretion with mild renal injury and up-regulation of CNP and renin genes in the kidney. Compared to normals, widespread genes, especially genes of the inflammatory pathways, were up-regulated in KC similar to increases seen in LA Protein expressions related to inflammatory cytokines were also augmented in the KC Gene and protein changes were less prominent in the LV and KM The ES-HF displayed mild renal injury with widespread gene changes and increased inflammatory cytokines. These changes may provide important clues into the pathophysiology of ES-HF and for therapeutic molecular targets in the kidney of ES-HF. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Relationship between intracranial aneurysms and the severity of autosomal dominant polycystic kidney disease.

PubMed

Yoshida, Hiroki; Higashihara, Eiji; Maruyama, Keisuke; Nutahara, Kikuo; Nitatori, Toshiaki; Miyazaki, Isao; Shiokawa, Yoshiaki

2017-12-01

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disease characterized by the progressive enlargement of innumerable renal cysts. Although the association of intracranial aneurysms (ICANs) with ADPKD is well known, the relationship between the ICAN and the disease severity including total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) is poorly understood. We screened 265 patients with ADPKD (mean age, 48.8 years; range, 14.9-88.3 years) with MR angiography. The patients with a past history related to ICANs were excluded from the study. The incidence and characteristics of ICAN in patients with ADPKD were evaluated. TKV was measured by volumetric analyses of MR imaging. We detected 65 ICANs in 49 patients (37 women and 12 men, mean age, 52.7 years; range, 20.4-86 years). The incidence of ICANs was 18.5% and female patients had was higher incidence (23.1%) than male patients (11.4%) (p = 0.02). An age of those with ICANs was significantly higher than those without (p = 0.006), and the cumulative risk of diagnosis of ICANs increased with age. TKV was significantly larger in those with ICANs than those without (p = 0.001), but eGFR was not different between two groups (p = 0.07). By multivariate analyses, only TKV was significantly related to the development of ICANs (p = 0.02). The incidence of ICANs increased with age, was higher in females, and correlated with kidney enlargement in patients with ADPKD. Necessity of screening ICANs would be particularly high in elderly women with large kidneys.

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.

Rationale, design and objectives of ARegPKD, a European ARPKD registry study.

PubMed

Ebner, Kathrin; Feldkoetter, Markus; Ariceta, Gema; Bergmann, Carsten; Buettner, Reinhard; Doyon, Anke; Duzova, Ali; Goebel, Heike; Haffner, Dieter; Hero, Barbara; Hoppe, Bernd; Illig, Thomas; Jankauskiene, Augustina; Klopp, Norman; König, Jens; Litwin, Mieczyslaw; Mekahli, Djalila; Ranchin, Bruno; Sander, Anja; Testa, Sara; Weber, Lutz Thorsten; Wicher, Dorota; Yuzbasioglu, Ayse; Zerres, Klaus; Dötsch, Jörg; Schaefer, Franz; Liebau, Max Christoph

2015-02-18

Autosomal recessive polycystic kidney disease (ARPKD) is a rare but frequently severe disorder that is typically characterized by cystic kidneys and congenital hepatic fibrosis but displays pronounced phenotypic heterogeneity. ARPKD is among the most important causes for pediatric end stage renal disease and a leading reason for liver-, kidney- or combined liver kidney transplantation in childhood. The underlying pathophysiology, the mechanisms resulting in the observed clinical heterogeneity and the long-term clinical evolution of patients remain poorly understood. Current treatment approaches continue to be largely symptomatic and opinion-based even in most-advanced medical centers. While large clinical trials for the frequent and mostly adult onset autosomal dominant polycystic kidney diseases have recently been conducted, therapeutic initiatives for ARPKD are facing the challenge of small and clinically variable cohorts for which reliable end points are hard to establish. ARegPKD is an international, mostly European, observational study to deeply phenotype ARPKD patients in a pro- and retrospective fashion. This registry study is conducted with the support of the German Society for Pediatric Nephrology (GPN) and the European Study Consortium for Chronic Kidney Disorders Affecting Pediatric Patients (ESCAPE Network). ARegPKD clinically characterizes long-term ARPKD courses by a web-based approach that uses detailed basic data questionnaires in combination with yearly follow-up visits. Clinical data collection is accompanied by associated biobanking and reference histology, thus setting roots for future translational research. The novel registry study ARegPKD aims to characterize miscellaneous subcohorts and to compare the applied treatment options in a large cohort of deeply characterized patients. ARegPKD will thus provide evidence base for clinical treatment decisions and contribute to the pathophysiological understanding of this severe inherited disorder.

Hemoglobin Decline in Children with Chronic Kidney Disease: Baseline Results from the Chronic Kidney Disease in Children Prospective Cohort Study

PubMed Central

Fadrowski, Jeffrey J.; Pierce, Christopher B.; Cole, Stephen R.; Moxey-Mims, Marva; Warady, Bradley A.; Furth, Susan L.

2008-01-01

Background and objectives: The level of glomerular filtration rate at which hemoglobin declines in chronic kidney disease is poorly described in the pediatric population. Design, setting, participants, & measurements: This cross-sectional study of North American children with chronic kidney disease examined the association of glomerular filtration rate, determined by the plasma disappearance of iohexol, and hemoglobin concentration. Results: Of the 340 patients studied, the mean age was 11 ± 4 yr, the mean glomerular filtration rate was 42 ± 14 ml/min per 1.73 m2, and the mean hemoglobin was 12.5 ± 1.5. Below a glomerular filtration rate of 43, the hemoglobin declined by 0.3 g/dl (95% confidence interval −0.2 to −0.5) for every 5-ml/min per 1.73 m2 decrease in glomerular filtration rate. Above a glomerular filtration rate of 43 ml/min per 1.73 m2, the hemoglobin showed a nonsignificant decline of 0.1 g/dl for every 5-ml/min per 1.73 m2 decrease in glomerular filtration rate. Conclusions: In pediatric patients with chronic kidney disease, hemoglobin declines as an iohexol-determined glomerular filtration rate decreases below 43 ml/min per 1.73 m2. Because serum creatinine–based estimated glomerular filtration rates may overestimate measured glomerular filtration rate in this population, clinicians need to be mindful of the potential for hemoglobin decline and anemia even at early stages of chronic kidney disease, as determined by current Schwartz formula estimates. Future longitudinal analyses will further characterize the relationship between glomerular filtration rate and hemoglobin, including elucidation of reasons for the heterogeneity of this association among individuals. PMID:18235140

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

Protein-Based Urine Test Predicts Kidney Transplant Outcomes

MedlinePlus

... Record Research & Training Medical Research Initiatives Science Highlights Science Education Research in NIH Labs & Clinics Training Opportunities Library Resources Research Resources Clinical Research Resources Safety, Regulation ...

Embolization Materials Made of Gelatin: Comparison Between Gelpart and Gelatin Microspheres

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

Ohta, Shinichi, E-mail: junryuhei@belle.shiga-med.ac.jp; Nitta, Norihisa; Sonoda, Akinaga

2010-02-15

Purpose:The object of this study was to assess the level of embolization in the embolized artery and the degradation period of these two embolic agents in the renal arteries using rabbit models.Materials and Methods: The renal artery was embolized using 5 mg of gelatin microspheres (GMSs; diameter, 35-100 {mu}m; group 1) or 1 mg of Gelpart (diameter, 1 mm; group 2). For each group, angiographies were performed on two kidneys immediately after the embolic procedure and on days 3, 7, and 14 after embolization. This was followed by histopathological examinations of the kidneys.Results:Follow-up angiograms on each day revealed the persistencemore » of poorly enhanced wedge-shaped areas in the parenchymal phase in all cases. In group 1, four of six cases showed poorly enhanced small areas in the follow-up angiograms. In group 2, all cases showed poorly enhanced large areas. In the histopathological specimens, it was observed that immediately after embolization, the particles reached the interlobular arteries in group 1 and the interlobar arteries in group 2. In all cases in group 1, the particles were histologically identified even on day 14. In one case in group 2 on day 14, the particles were not identified.Conclusion:In conclusion, although GMSs and Gelpart were similar in the point of gelatin particles, the level of embolization and the degradation period were different between GMSs and Gelpart.« less

The histopathologic reliability of tissue taken from cadavers within the gross anatomy laboratory.

PubMed

Rae, Guenevere; Newman, William P; McGoey, Robin; Donthamsetty, Supriya; Karpinski, Aryn C; Green, Jeffrey

2018-03-01

The purpose of this study was to examine the histopathologic reliability of embalmed cadaveric tissue taken from the gross anatomy laboratory. Tissue samples from hearts, livers, lungs, and kidneys were collected after the medical students' dissection course was completed. All of the cadavers were embalmed in a formalin-based fixative solution. The tissue was processed, embedded in paraffin, sectioned at six micrometers, and stained with H&E. The microscope slides were evaluated by a board certified pathologist to determine whether the cellular components of the tissues were preserved at a high enough quality to allow for histopathologic diagnosis. There was a statistically significant relationship between ratings and organ groups. Across all organs, there was a smaller proportion of "poor" ratings. The lung group had the highest percentage of "poor" ratings (23.1%). The heart group had the least "poor" ratings (0.0%). The largest percentage of "satisfactory" ratings were in the lung group (52.8%), and the heart group contained the highest percentage of "good" ratings (58.5%) The lung group had the lowest percentage of "good" ratings (24.2%). These results indicate that heart tissue is more reliable than lung, kidney, or liver tissue when utilizing tissue from the gross anatomy laboratory for research and/or educational purposes. This information advises educators and researchers about the quality and histopathologic reliability of tissue samples obtained from the gross anatomy laboratory. Anat Sci Educ 11: 207-214. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

Acute Kidney Injury and Subsequent Frailty Status in Survivors of Critical Illness: A Secondary Analysis.

PubMed

Abdel-Kader, Khaled; Girard, Timothy D; Brummel, Nathan E; Saunders, Christina T; Blume, Jeffrey D; Clark, Amanda J; Vincz, Andrew J; Ely, E Wesley; Jackson, James C; Bell, Susan P; Archer, Kristin R; Ikizler, T Alp; Pandharipande, Pratik P; Siew, Edward D

2018-05-01

Acute kidney injury frequently complicates critical illness and is associated with high morbidity and mortality. Frailty is common in critical illness survivors, but little is known about the impact of acute kidney injury. We examined the association of acute kidney injury and frailty within a year of hospital discharge in survivors of critical illness. Secondary analysis of a prospective cohort study. Medical/surgical ICU of a U.S. tertiary care medical center. Three hundred seventeen participants with respiratory failure and/or shock. None. Acute kidney injury was determined using Kidney Disease Improving Global Outcomes stages. Clinical frailty status was determined using the Clinical Frailty Scale at 3 and 12 months following discharge. Covariates included mean ICU Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation II score as well as baseline comorbidity (i.e., Charlson Comorbidity Index), kidney function, and Clinical Frailty Scale score. Of 317 patients, 243 (77%) had acute kidney injury and one in four patients with acute kidney injury was frail at baseline. In adjusted models, acute kidney injury stages 1, 2, and 3 were associated with higher frailty scores at 3 months (odds ratio, 1.92; 95% CI, 1.14-3.24; odds ratio, 2.40; 95% CI, 1.31-4.42; and odds ratio, 4.41; 95% CI, 2.20-8.82, respectively). At 12 months, a similar association of acute kidney injury stages 1, 2, and 3 and higher Clinical Frailty Scale score was noted (odds ratio, 1.87; 95% CI, 1.11-3.14; odds ratio, 1.81; 95% CI, 0.94-3.48; and odds ratio, 2.76; 95% CI, 1.34-5.66, respectively). In supplemental and sensitivity analyses, analogous patterns of association were observed. Acute kidney injury in survivors of critical illness predicted worse frailty status 3 and 12 months postdischarge. These findings have important implications on clinical decision making among acute kidney injury survivors and underscore the need to understand the drivers of frailty to improve patient-centered outcomes.

SGLT2 inhibition in a kidney with reduced nephron number: modeling and analysis of solute transport and metabolism.

PubMed

Layton, Anita T; Vallon, Volker

2018-05-01

Sodium-glucose cotransporter 2 (SGLT2) inhibitors enhance urinary glucose, Na + and fluid excretion, and lower hyperglycemia in diabetes by targeting Na + and glucose reabsorption along the proximal convoluted tubule. A goal of this study was to predict the effects of SGLT2 inhibitors in diabetic and nondiabetic patients with chronic kidney disease. To that end, we employed computational rat kidney models to explore how SGLT2 inhibition affects renal solute transport and metabolism when nephron populations are normal or reduced. Model simulations suggested that in a nondiabetic rat, acute and chronic SGLT2 inhibition induces glucosuria, diuresis, natriuresis, and kaliuresis. Those effects were stronger with chronic SGLT2 inhibition (due to SGLT1 downregulation) and tempered by nephron loss. In a diabetic rat with normal nephron number, acute SGLT2 inhibition similarly elevated urine fluid, Na + , and K + excretion, whereas the urinary excretory effects of chronic SGLT2 inhibition were attenuated in proportion to its plasma glucose level lowering effect. Nephron loss in a diabetic kidney was predicted to lower the glucosuric and blood glucose-reducing effect of chronic SGLT2 inhibition, but due to the high luminal glucose delivery in the remaining hyperfiltering nephrons, nephron loss enhanced proximal tubular paracellular Na + secretion, thereby augmenting the natriuretic, diuretic, and kaliuretic effects. A proposed shift in oxygen-consuming active transport to the outer medulla, which may simulate systemic hypoxia and enhance erythropoiesis, was also preserved with nephron loss. These effects may contribute to the protective effects of SGLT2 inhibitors on blood pressure and heart failure observed in diabetic patients with chronic kidney diseases.

Kidney function estimating equations in patients with chronic kidney disease.

PubMed

Hojs, R; Bevc, S; Ekart, R; Gorenjak, M; Puklavec, L

2011-04-01

The current guidelines emphasise the need to assess kidney function using predictive equations rather than just serum creatinine. The present study compares serum cystatin C-based equations and serum creatinine-based equations in patients with chronic kidney disease (CKD). Seven hundred and sixty-four adult patients with CKD were enrolled. In each patient serum creatinine and serum cystatin C were determined. Their glomerular filtration rate (GFR) was estimated using three serum creatinine-based equations [Cockcroft-Gault (C&G), modification of diet in renal disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)] and two serum cystatin C-based equations [our own cystatin C formula (GFR=90.63 × cystatin C(-1.192) ) and simple cystatin C formula (GFR=100/cystatin C)]. The GFR was measured using (51) CrEDTA clearance. Statistically significant correlation between (51) CrEDTA clearance with serum creatinine, serum cystatin C and all observed formulas was found. The receiver operating characteristic curve analysis (cut-off for GFR 60 ml/min/1.73m(2)) showed that serum cystatin C and both cystatin C formulas had a higher diagnostic accuracy than C&G formula. Bland and Altman analysis for the same cut-off value showed that all formulas except simple cystatin C formula underestimated measured GFR. The accuracy within 30% of estimated (51) CrEDTA clearance values differs according to stages of CKD. Analysis of ability to correctly predict patient's GFR below or above 60 ml/min/1.73m(2) showed statistically significant higher ability for both cystatin C formulas compared to MDRD formula. Our results indicate that serum cystatin C-based equations are reliable markers of GFR comparable with creatinine-based formulas. © 2011 Blackwell Publishing Ltd.

Hyporesponsiveness to Darbepoetin Alfa in Patients With Heart Failure and Anemia in the RED-HF Study (Reduction of Events by Darbepoetin Alfa in Heart Failure): Clinical and Prognostic Associations.

PubMed

van der Meer, Peter; Grote Beverborg, Niels; Pfeffer, Marc A; Olson, Kurt; Anand, Inder S; Westenbrink, B Daan; McMurray, John J V; Swedberg, Karl; Young, James B; Solomon, Scott D; van Veldhuisen, Dirk J

2018-02-01

A poor response to erythropoiesis-stimulating agents such as darbepoetin alfa has been associated with adverse outcomes in patients with diabetes mellitus, chronic kidney disease, and anemia; whether this is also true in heart failure is unclear. We performed a post hoc analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart Failure), in which 1008 patients with systolic heart failure and anemia (hemoglobin level, 9.0-12.0 g/dL) were randomized to darbepoetin alfa. We examined the relationship between the hematopoietic response to darbepoetin alfa and the incidence of all-cause death or first heart failure hospitalization during a follow-up of 28 months. For the purposes of the present study, patients in the lowest quartile of hemoglobin change after 4 weeks were considered nonresponders. The median initial hemoglobin change in nonresponders (n=252) was -0.25 g/dL and +1.00 g/dL in the remainder of patients (n=756). Worse renal function, lower sodium levels, and less use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were independently associated with nonresponse. Although a low endogenous erythropoietin level helped to differentiate responders from nonresponders, its predictive value in a multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate of all-cause death or first heart failure hospitalization (hazard ratio, 1.25; 95% confidence interval, 1.02-1.54) and a higher risk of all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.04-1.63) than responders. A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00358215. © 2018 American Heart Association, Inc.

Final Year Nursing Students in Nigeria; How Knowledgeable and Prepared are They to Offer Medical Care to Patients with Chronic Kidney Disease?

PubMed Central

Okwuonu, Chimezie Godswill; Kanu, Hannah Sylvanus; Odigie, Ojeh-Oziegbe

2017-01-01

Background: Nurses play an important role in the management of chronic kidney disease (CKD) patients at primary, secondary, and tertiary levels of care. In other to perform their functions, it is pertinent that they have a good understanding of kidney functions and CKD. We do not know if the current educational curriculum prepares them adequately for this role. Aim: To assess the knowledge level of kidney functions and diseases among final year nursing students in Abia State Nigeria. Materials and Methods: This was a cross sectional study involving final year diploma and Bachelor of nursing (B. Nursing) students who were randomly chosen. Structured, self-administered questionnaire containing 18 items was the tool for data collection. A score of one was given for each correctly answered question on functions of the kidney, symptoms, signs, causes, and complications of CKD. A score of 50% and above was regarded as good knowledge. Results: Two hundred questionnaires were distributed, but 186 were returned (response rate of 93%). Male:female ratio was 1:14.5. One hundred and seventeen (62.9%) knew the correct definition of CKD, but only 69 (37.1%) knew the normal range of glomerular filtration rate. Eighty-one percent had good knowledge of kidney functions while 39 (21%) had good knowledge of CKD. Overall, 42 (22.6%) had good knowledge of kidney functions and CKD. Students who rotated through the dialysis unit during their clinical posting had higher mean knowledge score than others (P = 0.03). There was no significant difference in the mean knowledge scores of the diploma and B. Nursing students (P = 0.76). Conclusion: The majority of the final year students had poor knowledge of CKD. There is need to expand the current teaching curriculum so as to increase the knowledge of these future nurses on the basic concepts of CKD to improve outcomes of patient management. PMID:28300046

Urine Fibrosis Markers and Risk of Allograft Failure in Kidney Transplant Recipients: A Case-Cohort Ancillary Study of the FAVORIT Trial.

PubMed

Ix, Joachim H; Katz, Ronit; Bansal, Nisha; Foster, Meredith; Weiner, Daniel E; Tracy, Russell; Jotwani, Vasantha; Hughes-Austin, Jan; McKay, Dianne; Gabbai, Francis; Hsu, Chi-Yuan; Bostom, Andrew; Levey, Andrew S; Shlipak, Michael G

2017-03-01

Kidney tubulointerstitial fibrosis marks risk for allograft failure in kidney transplant recipients, but is poorly captured by estimated glomerular filtration rate (eGFR) or urine albumin-creatinine ratio (ACR). Whether urinary markers of tubulointerstitial fibrosis can noninvasively identify risk for allograft failure above and beyond eGFR and ACR is unknown. Case-cohort study. The FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation) Trial was a randomized double-blind trial testing vitamin therapy to lower homocysteine levels in stable kidney transplant recipients. We selected a subset of participants at random (n=491) and all individuals with allograft failure during follow-up (cases; n=257). Using spot urine specimens from the baseline visit, we measured 4 urinary proteins known to correlate with tubulointerstitial fibrosis on biopsy (urine α 1 -microglobulin [A1M], monocyte chemoattractant protein 1 [MCP-1], and procollagen type III and type I amino-terminal amino pro-peptide). Death-censored allograft failure. In models adjusted for demographics, chronic kidney disease risk factors, eGFR, and ACR, higher concentrations of urine A1M (HR per doubling, 1.73; 95% CI, 1.43-2.08) and MCP-1 (HR per doubling, 1.60; 95% CI, 1.32-1.93) were strongly associated with allograft failure. When additionally adjusted for concentrations of other urine fibrosis and several urine injury markers, urine A1M (HR per doubling, 1.76; 95% CI, 1.27-2.44]) and MCP-1 levels (HR per doubling, 1.49; 95% CI, 1.17-1.89) remained associated with allograft failure. Urine procollagen type III and type I levels were not associated with allograft failure. We lack kidney biopsy data, BK titers, and HLA antibody status. Urine measurement of tubulointerstitial fibrosis may provide a noninvasive method to identify kidney transplant recipients at higher risk for future allograft failure, above and beyond eGFR and urine ACR. Published by Elsevier Inc.

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.

Risk Prediction Models for Acute Kidney Injury in Critically Ill Patients: Opus in Progressu.

PubMed

Neyra, Javier A; Leaf, David E

2018-05-31

Acute kidney injury (AKI) is a complex systemic syndrome associated with high morbidity and mortality. Among critically ill patients admitted to intensive care units (ICUs), the incidence of AKI is as high as 50% and is associated with dismal outcomes. Thus, the development and validation of clinical risk prediction tools that accurately identify patients at high risk for AKI in the ICU is of paramount importance. We provide a comprehensive review of 3 clinical risk prediction tools that have been developed for incident AKI occurring in the first few hours or days following admission to the ICU. We found substantial heterogeneity among the clinical variables that were examined and included as significant predictors of AKI in the final models. The area under the receiver operating characteristic curves was ∼0.8 for all 3 models, indicating satisfactory model performance, though positive predictive values ranged from only 23 to 38%. Hence, further research is needed to develop more accurate and reproducible clinical risk prediction tools. Strategies for improved assessment of AKI susceptibility in the ICU include the incorporation of dynamic (time-varying) clinical parameters, as well as biomarker, functional, imaging, and genomic data. © 2018 S. Karger AG, Basel.

Electronic Health Record-Enabled Big-Data Approaches to Nephrotoxin-Associated Acute Kidney Injury Risk Prediction.

PubMed

Sutherland, Scott M

2018-06-09

Nephrotoxin-associated acute kidney injury (NTx-AKI) has become one of the most common causes of AKI among hospitalized adults and children; across acute and intensive care populations, exposure to nephrotoxins accounts for 15-25% of AKI. Although some interventions have shown promise in observational studies, no treatments currently exist for NTx-AKI once it occurs. Thus, nearly all effective strategies are aimed at prevention. The primary obstacle to prevention is risk prediction and the determination of which patients are more likely to develop NTx-AKI when exposed to medications with nephrotoxic potential. Historically, traditional statistical modeling has been applied to previously recognized clinical risk factors to identify predictors of NTx-AKI. However, increased electronic health record adoption and the evolution of "big-data" approaches to predictive analytics may offer a unique opportunity to prevent NTx-AKI events. This article describes prior and current approaches to NTx-AKI prediction and offers three novel use cases for electronic health record-enabled NTx-AKI forecasting and risk profiling. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Metabolic syndrome definitions and components in predicting major adverse cardiovascular events after kidney transplantation.

PubMed

Prasad, G V Ramesh; Huang, Michael; Silver, Samuel A; Al-Lawati, Ali I; Rapi, Lindita; Nash, Michelle M; Zaltzman, Jeffrey S

2015-01-01

Metabolic syndrome (MetS) associates with cardiovascular risk post-kidney transplantation, but its ambiguity impairs understanding of its diagnostic utility relative to components. We compared five MetS definitions and the predictive value of constituent components of significant definitions for major adverse cardiovascular events (MACE) in a cohort of 1182 kidney transplant recipients. MetS definitions were adjusted for noncomponent traditional Framingham risk factors and relevant transplant-related variables. Kaplan-Meier, logistic regression, and Cox proportional hazards analysis were utilized. There were 143 MACE over 7447 patient-years of follow-up. Only the World Health Organization (WHO) 1998 definition predicted MACE (25.3 vs 15.5 events/1000 patient-years, P = 0.019). Time-to-MACE was 5.5 ± 3.5 years with MetS and 6.8 ± 3.9 years without MetS (P < 0.0001). MetS was independent of pertinent MACE risk factors except age and previous cardiac disease. Among MetS components, dysglycemia provided greatest hazard ratio (HR) for MACE (1.814 [95% confidence interval 1.26-2.60]), increased successively by microalbuminuria (HR 1.946 [1.37-2.75]), dyslipidemia (3.284 [1.72-6.26]), hypertension (4.127 [2.16-7.86]), and central obesity (4.282 [2.09-8.76]). MetS did not affect graft survival. In summary, although the WHO 1998 definition provides greatest predictive value for post-transplant MACE, most of this is conferred by dysglycemia and is overshadowed by age and previous cardiac disease. © 2014 Steunstichting ESOT.

Creatinine measurement on dry blood spot sample for chronic kidney disease screening.

PubMed

Silva, Alan Castro Azevedo E; Gómez, Juan Fidel Bencomo; Lugon, Jocemir Ronaldo; Graciano, Miguel Luis

2016-03-01

Chronic kidney disease (CKD) screening is advisable due to its high morbidity and mortality and is usually performed by sampling blood and urine. Here we present an innovative and simpler method, by measuring creatinine on a dry blood spot on filter paper. One-hundred and six individuals at high risk for CKD were enrolled. The creatinine values obtained using both tests and the demographic data of each participant allowed us to determinate the eGFR. The adopted cutoff for CKD was an eGFR < 60 ml/min. Mean age was 57 ± 12 years, 74% were female, 40% white, and 60% non-white. Seventy-six percent were hypertensive, 30% diabetic, 37% had family history of CKD, and 22% of smoking. The BMI was 29.5 ± 6.9 kg/m2, median systolic blood pressure was 125 mmHg (IQR 120-140 mmHg) and median diastolic blood pressure was 80 mmHg (IQR 70-80 mmHg). According to MDRD equation, sensitivity was 96%, specificity 55%, predictive positive value 96%, predictive negative value 55% and accuracy 92%. By the CKD-EPI equation the sensitivity was 94%, specificity 55%, predictive positive value 94%, predictive negative value 55% and accuracy 90%. A Bland and Altman analysis showed a relatively narrow range of creatinine values differences (+ 0.68mg/dl to -0.55mg/dl) inside the ± 1.96 SD, without systematic differences. Measurement of creatinine on dry blood sample is an easily feasible non-invasive diagnostic test with good accuracy that may be useful to screen chronic kidney disease.

Performance of the Cockcroft-Gault and MDRD equations in adult Nigerians with chronic kidney disease.

PubMed

Agaba, Emmanuel I; Wigwe, Chinyere M; Agaba, Patricia A; Tzamaloukas, Antonios H

2009-01-01

Estimation of the glomerular filtration rate (GFR) is required in the assessment of patients with chronic kidney disease (CKD) in order to provide information regarding the functional status of the kidneys. Current guidelines advocate the use of prediction equations, such as the Cockcroft-Gault (CG) formula and the Modification of Diet in Renal Disease (MDRD) study-derived equations, over clearance of endogenous creatinine (Ccr) in achieving this aim. We were interested in knowing the accuracy of these equations in predicting the GFR in adult Nigerians with CKD. We conducted a review of records of patients who were evaluated for CKD at the Nephrology Clinic of the Jos University Teaching Hospital between 2001 and 2003. We compared the CG and MDRD equations against the Ccr in predicting the GFR in 130 patients (88 males and 42 females) with CKD. The means +/- standard deviation (SD) for the measured and predicted GFR by the CG and MDRD equations were similar (17.6 +/- 25.8 ml/min, 19.9 +/- 24.0 ml/min and 21.5 +/- 28.2 ml/min, respectively; analysis of variance [ANOVA], F = 0.68, P = 0.5). The mean difference between CG and Ccr was -2.2 +/- 14.8 ml/min, with discordance at Ccr values >25 ml/min. The mean difference between MDRD and Ccr was -3.9 +/- 18.1 ml/min, with discordance at Ccr values >40 ml/min. The CG and MDRD equations provide reliable alternatives to measured Ccr in the estimation of the GFR in Nigerian patients with CKD.

Moderator's view: Predictive models: a prelude to precision nephrology.

PubMed

Zoccali, Carmine

2017-05-01

Appropriate diagnosis is fundamental in medicine because it sets the basis for the prediction of disease outcome at the single patient level (prognosis) and decisions regarding the most appropriate therapy. However, given the large series of social, clinical and biological factors that determine the likelihood of an individual's future outcome, prognosis only partly depends on diagnosis and aetiology and treatment is not decided solely on the basis of the underlying diagnosis. This issue is crucial in multifactorial diseases like atherosclerosis, where the use of statins has now shifted from 'treating hypercholesterolaemia' to 'treating the risk of adverse cardiovascular events'. Approaches that take due account of prognosis limit the lingering risk of over-diagnosis and maximize the value of prognostic information in the clinical decision process. In the nephrology realm, the application of a well-validated risk equation for kidney failure in Canada led to a 35% reduction in new referrals. Prognostic models based on simple clinical data extractable from clinical files have recently been developed to predict all-cause and cardiovascular mortality in end-stage kidney disease patients. However, research on predictive models in renal diseases remains suboptimal and non-accounting for competing events and measurement errors, and a lack of calibration analyses and external validation are common fallacies in currently available studies. More focus on this blossoming research area is desirable. The nephrology community may now start to apply the best validated risk scores and further test their potential usefulness in chronic kidney disease patients in diverse clinical situations and geographical areas. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Long-term predictive models of risk factors for early chronic kidney disease: a longitudinal study.

PubMed

Wu, Wen-Chih; Hsieh, Po-Chien; Hu, Fu-Kang; Kuan, Jen-Chun; Chu, Chi-Ming; Sun, Chien-An; Yang, Tsan; Su, Sui-Lung; Chou, Yu-Ching

2018-04-13

The high incidence and prevalence of chronic kidney disease (CKD) in Taiwan have produced tremendous burdens on health care resources. The work environment of air force special operations personnel engenders high psychological stress, and the resulting increased blood pressure can lead to glomerular hypertension and accelerated glomerular injury in the long term. The aim of the study was to establish the predictive models to define the predictors of CKD. The results indicated that the prevalence of CKD over 4 consecutive years was 3.8%, 9.4%, 9.0%, and 9.4%. The capability of using occult blood in urine to predict the risk of CKD after 1, 2, and 3 years was statistically significant. The age-adjusted odds ratio (OR) and 95% confidence interval (CI) were 7.94 (95% CI: 2.61-24.14), 12.35 (95% CI: 4.02-37.94) and 4.25 (95% CI: 1.32-13.70), respectively. The predictive power of occult blood in urine for the risk of CKD in each model was statistically significant. Future investigations can explore the feasibility of implementing simple and accurate urine dipsticks for preliminary testing besides annual aircrew physical examinations to facilitate early detection and treatment. This study was a longitudinal study, in which air force special operations personnel who received physical examinations at military hospitals between 2004 and 2010 were selected. CKD was determined based on the definition provided by the US National Kidney Foundation. Overall, 212 participants that could be followed continuously for 4 years were analyzed.

Prospective validation of a novel renal activity index of lupus nephritis.

PubMed

Gulati, G; Bennett, M R; Abulaban, K; Song, H; Zhang, X; Ma, Q; Brodsky, S V; Nadasdy, T; Haffner, C; Wiley, K; Ardoin, S P; Devarajan, P; Ying, J; Rovin, B H; Brunner, H I

2017-08-01

Objectives The renal activity index for lupus (RAIL) score was developed in children with lupus nephritis as a weighted sum of six urine biomarkers (UBMs) (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin and kidney injury molecule 1) measured in a random urine sample. We aimed at prospectively validating the RAIL in adults with lupus nephritis. Methods Urine from 79 adults was collected at the time of kidney biopsy to assay the RAIL UBMs. Using receiver operating characteristic curve analysis, we evaluated the accuracy of the RAIL to discriminate high lupus nephritis activity status (National Institutes of Health activity index (NIH-AI) score >10), from low/moderate lupus nephritis activity status (NIH-AI score ≤10). Results In this mixed racial cohort, high lupus nephritis activity was present in 15 patients (19%), and 71% had proliferative lupus nephritis. Use of the identical RAIL algorithm developed in children resulted in only fair prediction of lupus nephritis activity status of adults (area under the receiver operating characteristic curve (AUC) 0.62). Alternative weightings of the six RAIL UBMs as suggested by logistic regression yielded excellent accuracy to predict lupus nephritis activity status (AUC 0.88). Accuracy of the model did not improve with adjustment of the UBMs for urine creatinine or albumin, and was little influenced by concurrent kidney damage. Conclusions The RAIL UBMs provide excellent prediction of lupus nephritis activity in adults. Age adaption of the RAIL is warranted to optimize its discriminative validity to predict high lupus nephritis activity status non-invasively.

The potential use of biomarkers in predicting contrast-induced acute kidney injury

PubMed Central

Andreucci, Michele; Faga, Teresa; Riccio, Eleonora; Sabbatini, Massimo; Pisani, Antonio; Michael, Ashour

2016-01-01

Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect. PMID:27672338

Acellular Mouse Kidney ECM can be Used as a Three-Dimensional Substrate to Test the Differentiation Potential of Embryonic Stem Cell Derived Renal Progenitors.

PubMed

Sambi, Manpreet; Chow, Theresa; Whiteley, Jennifer; Li, Mira; Chua, Shawn; Raileanu, Vanessa; Rogers, Ian M

2017-08-01

The development of strategies for tissue regeneration and bio-artificial organ development is based on our understanding of embryogenesis. Differentiation protocols attempt to recapitulate the signaling modalities of gastrulation and organogenesis, coupled with cell selection regimens to isolate the cells of choice. This strategy is impeded by the lack of optimal in vitro culture systems since traditional culture systems do not allow for the three-dimensional interaction between cells and the extracellular matrix. While artificial three-dimensional scaffolds are available, using the natural extracellular matrix scaffold is advantageous because it has a distinct architecture that is difficult to replicate. The adult extracellular matrix is predicted to mediate signaling related to tissue repair not embryogenesis but existing similarities between the two argues that the extracellular matrix will influence the differentiation of stem and progenitor cells. Previous studies using undifferentiated embryonic stem cells grown directly on acellular kidney ECM demonstrated that the acellular kidney supported cell growth but limited differentiation occurred. Using mouse kidney extracellular matrix and mouse embryonic stem cells we report that the extracellular matrix can support the development of kidney structures if the stem cells are first differentiated to kidney progenitor cells before being applied to the acellular organ.

Increased primary non-function in transplanted deceased-donor kidneys flushed with histidine-tryptophan-ketoglutarate solution.

PubMed

Stevens, R B; Skorupa, J Y; Rigley, T H; Yannam, G R; Nielsen, K J; Schriner, M E; Skorupa, A J; Murante, A; Holdaway, E; Wrenshall, L E

2009-05-01

Histidine-Tryptophan-Ketoglutarate (HTK) solution is increasingly used to flush and preserve organ donor kidneys, with efficacy claimed equivalent to University of Wisconsin (UW) solution. We observed and reported increased graft pancreatitis in pancreata flushed with HTK solution, which prompted this review of transplanting HTK-flushed kidneys. We analyzed outcomes of deceased-donor kidneys flushed with HTK and UW solutions with a minimum of 12 months follow-up, excluding pediatric and multi-organ recipients. We evaluated patient and graft survival and rejection rates, variables that might constitute hazards to graft survival and renal function. Two-year patient survival, rejection, renal function and graft survival were not different, but early graft loss (<6 months) was worse in HTK-flushed kidneys (p < 0.03). A Cox analysis of donor grade, cold ischemic time, panel reactive antibodies (PRA), donor race, first vs. repeat transplant, rejection and flush solution showed that only HTK use predicted early graft loss (p < 0.04; relative risk = 3.24), almost exclusively attributable to primary non-function (HTK, n = 5 (6.30%); UW, n = 1 (0.65%); p = 0.02). Delayed graft function and early graft loss with HTK occurred only in lesser grade kidneys, suggesting it should be used with caution in marginal donors.

An unusual case of acute kidney injury due to vancomycin lessons learnt from reliance on eGFR.

PubMed

Barraclough, Katherine; Harris, Marianne; Montessori, Val; Levin, Adeera

2007-08-01

We present a case of renal impairment in an emaciated HIV-infected male that initially went unrecognized because of reliance on serum creatinine and estimated glomerular filtration rate (eGFR). Inaccurate vancomycin dosing led to toxic drug levels (66 mg/l), associated with acute and severe worsening of kidney function. This occurred in the context of escalating doses of vancomycin given in the presence of changing kidney function, albeit kidney function that always remained well within the normal range (serum creatinine 29 - 42 mumol/l). In the absence of other plausible explanations, a presumptive diagnosis of vancomycin nephrotoxicity was made. Given the rarity of this diagnosis in the current era, we discuss the pathophysiology of vancomycin nephrotoxicity. We also explore the potential reasons for inaccuracy of GFR prediction equations in the HIV population, and discuss the potential pitfalls associated with application of eGFR or even serum creatinine without appropriate understanding of their limitations. We believe our case highlights a number of important teaching points: Vancomycin nephrotoxitiy is rare but can occur in the setting of kidney dysfunction. Current assessment of kidney function using creatinine and eGFR requires awareness of the clinical caveats in which these measures may be misleading. Acute changes in kidney function, irrespective of the test used, should be contextualized to the individual situation. Persons with HIV and low muscle mass constitute a specific subgroup in whom assessment of kidney function may be problematic using creatinine. We support ongoing efforts to develop or refine equations for specific unique and easily identifiable populations.

Nationwide multicenter kidney biopsy study of Japanese patients with hypertensive nephrosclerosis.

PubMed

Furuichi, Kengo; Shimizu, Miho; Yuzawa, Yukio; Hara, Akinori; Toyama, Tadashi; Kitamura, Hiroshi; Suzuki, Yoshiki; Sato, Hiroshi; Uesugi, Noriko; Ubara, Yoshifumi; Hoshino, Junichi; Hisano, Satoshi; Ueda, Yoshihiko; Nishi, Shinichi; Yokoyama, Hitoshi; Nishino, Tomoya; Kohagura, Kentaro; Ogawa, Daisuke; Mise, Koki; Shibagaki, Yugo; Kimura, Kenjiro; Haneda, Masakazu; Makino, Hirofumi; Matsuo, Seiichi; Wada, Takashi

2018-06-01

Nephrosclerosis is an increasingly reason for dialysis in Japan. However, kidney biopsy specimens for hypertensive nephrosclerosis are very limited; thus, the pathologic evaluation of hypertensive nephrosclerosis currently remains unclear. Clinical and pathologic data of a total of 184 biopsy-confirmed hypertensive nephrosclerosis patients were collected from 13 centers throughout Japan. Seven pathological findings were assessed in this study. The outcomes of interest for this study were dialysis, composite kidney events, cardiovascular events, and all-cause mortality. The Green and Yellow (G&Y), Orange, and Red groups of the chronic kidney diseases (CKD) heat map contained 36, 57, and 91 cases, respectively. The mean observation period was 7.3 ± 5.2 (median, IQR; 6.1, 2.6-9.7) years. Global glomerulosclerosis (GScle), interstitial fibrosis and tubular atrophy (IFTA), arteriolar hyalinosis in Red exhibited higher scores than those in G&Y and Orange. The incidence rates of the composite kidney end points in 100 person-years for the G&Y, Orange, and Red groups were 1.42, 2.16, and 3.98, respectively. In the univariate Cox analysis for the composite kidney end points, GScle, IFTA and interstitial cell infiltration exhibited statistically significant high hazard ratios (1.18, 1.84, 1.69, respectively). However, after adjustment for clinical and medication data, the Red group in the CKD heat map category was risk factor for the composite kidney end points (HR 9.51). In summary, although pathologic findings had minor impacts on the prediction of composite outcomes in this study, the clinical stage of the CKD heat map is a good predictor of composite kidney events.

Comparison of macrophage migration inhibitory factor and neutrophil gelatinase-associated lipocalin-2 to predict acute kidney injury after liver transplantation: An observational pilot study

PubMed Central

Schiefer, Judith; Miller, Edmund J.; Berlakovich, Gabriela A.

2017-01-01

Introduction Several biomarkers have been suggested as early predictors of acute kidney injury (AKI) after orthotopic liver transplantation (OLT). Neutrophil gelatinase-associated lipocalin-2 (NGAL) appears to be a promising predictor of AKI after OLT, but the clinical benefit remains to be proven. Recently, systemic macrophage migration inhibitory factor (MIF) has been proposed as early indicator for requirement of renal replacement therapy after OLT. The aim of this prospective, observational pilot study was to compare the predictive values of serum and urinary MIF for severe AKI after OLT to those of serum and urinary NGAL. Methods Concentrations of MIF and NGAL were measured in serum and urine samples collected from patients undergoing OLT. Acute kidney injury was classified according to the KDIGO criteria, with stages 2 and 3 summarized as severe AKI. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of MIF and NGAL for the development of severe AKI. Results Forty-five patients (mean age 55±8 years) were included. Nineteen patients (38%) developed severe AKI within 48 hours after reperfusion. At the end of OLT, serum MIF was predictive of severe AKI (AUC 0.73; 95% confidence intervals, CI 0.55–0.90; P = 0.03), whereas urinary MIF, serum NGAL, and urinary NGAL were not. On the first postoperative day, serum MIF (AUC 0.78; CI 0.62–0.93; P = 0.006), urinary MIF (AUC 0.71; CI 0.53–0.88; P = 0.03), and urinary NGAL (AUC 0.79; CI 0.64–0.93; P = 0.02) were predictive for severe AKI, while serum NGAL was not. Conclusion In the setting of OLT, MIF and NGAL had similar predictive values for the development of severe AKI. PMID:28813470

Systematic review of prognostic prediction models for acute kidney injury (AKI) in general hospital populations.

PubMed

Hodgson, Luke Eliot; Sarnowski, Alexander; Roderick, Paul J; Dimitrov, Borislav D; Venn, Richard M; Forni, Lui G

2017-09-27

Critically appraise prediction models for hospital-acquired acute kidney injury (HA-AKI) in general populations. Systematic review. Medline, Embase and Web of Science until November 2016. Studies describing development of a multivariable model for predicting HA-AKI in non-specialised adult hospital populations. Published guidance followed for data extraction reporting and appraisal. 14 046 references were screened. Of 53 HA-AKI prediction models, 11 met inclusion criteria (general medicine and/or surgery populations, 474 478 patient episodes) and five externally validated. The most common predictors were age (n=9 models), diabetes (5), admission serum creatinine (SCr) (5), chronic kidney disease (CKD) (4), drugs (diuretics (4) and/or ACE inhibitors/angiotensin-receptor blockers (3)), bicarbonate and heart failure (4 models each). Heterogeneity was identified for outcome definition. Deficiencies in reporting included handling of predictors, missing data and sample size. Admission SCr was frequently taken to represent baseline renal function. Most models were considered at high risk of bias. Area under the receiver operating characteristic curves to predict HA-AKI ranged 0.71-0.80 in derivation (reported in 8/11 studies), 0.66-0.80 for internal validation studies (n=7) and 0.65-0.71 in five external validations. For calibration, the Hosmer-Lemeshow test or a calibration plot was provided in 4/11 derivations, 3/11 internal and 3/5 external validations. A minority of the models allow easy bedside calculation and potential electronic automation. No impact analysis studies were found. AKI prediction models may help address shortcomings in risk assessment; however, in general hospital populations, few have external validation. Similar predictors reflect an elderly demographic with chronic comorbidities. Reporting deficiencies mirrors prediction research more broadly, with handling of SCr (baseline function and use as a predictor) a concern. Future research should focus on validation, exploration of electronic linkage and impact analysis. The latter could combine a prediction model with AKI alerting to address prevention and early recognition of evolving AKI. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Ballew, Shoshana H.; Chen, Yan; Daya, Natalie R.; Godino, Job G.; Windham, B. Gwen; McAdams-DeMarco, Mara; Coresh, Josef; Selvin, Elizabeth; Grams, Morgan E.

2016-01-01

Background Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. Study Design Observational study. Setting & Participants 4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011–2013). Predictor Kidney measures included glomerular filtration rate (GFR) estimated using serum creatinine (eGFRcr) and serum cystatin C (eGFRcys) and urine albumin-creatinine ratio (ACR). Outcomes Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). Results In total, 341 participants (7%) were classified as frail, 1475 (30%) had eGFRcr <60 ml/min/1.73 m2, 2480 (50%) had eGFRcys <60 ml/min/1.73 m2, and 1006 (20%) had albuminuria ≥30 mg/g. Among frail participants, prevalences of eGFRcr and eGFRcys <60 ml/min/1.73 m2 were 45% and 77%, respectively. Adjusted for covariates, frailty showed a moderate association with eGFRcr and a strong association with eGFRcys and ACR. Frail individuals with eGFRcr 60–<75 ml/min/1.73 m2 were frequently reclassified to lower eGFR categories using eGFRcys (49% to 45–<60, 32% to 30–<45, and 3% to <30 ml/min/1.73 m2). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of non-frail), including classes requiring kidney clearance (e.g., digoxin) and associated with falls and subsequent complications (e.g., hypnotic/sedatives, anticoagulants). Limitations Cross-sectional study design. Conclusions Frail individuals had a high prevalence of reduce kidney function, with large discrepancies when reduced kidney function was classified by eGFRcys versus eGFRcr. Given the substantial medication burden and uncertainty in CKD classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population. PMID:27884475

Long-term prognosis after acute kidney injury (AKI): what is the role of baseline kidney function and recovery? A systematic review.

PubMed

Sawhney, Simon; Mitchell, Mhairi; Marks, Angharad; Fluck, Nick; Black, Corrinda

2015-01-06

To summarise the evidence from studies of acute kidney injury (AKI) with regard to the effect of pre-AKI renal function and post-AKI renal function recovery on long-term mortality and renal outcomes, and to assess whether these factors should be taken into account in future prognostic studies. A systematic review of observational studies listed in Medline and EMBASE from 1990 to October 2012. All AKI studies in adults with data on baseline kidney function to identify AKI; with outcomes either stratified by pre-AKI and/or post-AKI kidney function, or described by the timing of the outcomes. Long-term mortality and worsening chronic kidney disease (CKD). Of 7385 citations, few studies met inclusion criteria, reported baseline kidney function and stratified by pre-AKI or post-AKI function. For mortality outcomes, three studies compared patients by pre-AKI renal function and six by post-AKI function. For CKD outcomes, two studies compared patients by pre-AKI function and two by post-AKI function. The presence of CKD pre-AKI (compared with AKI alone) was associated with doubling of mortality and a fourfold to fivefold increase in CKD outcomes. Non-recovery of kidney function was associated with greater mortality and CKD outcomes in some studies, but findings were inconsistent varying with study design. Two studies also reported that risk of poor outcome reduced over time post-AKI. Meta-analysis was precluded by variations in definitions for AKI, CKD and recovery. The long-term prognosis after AKI varies depending on cause and clinical setting, but it may also, in part, be explained by underlying pre-AKI and post-AKI renal function rather than the AKI episode itself. While carefully considered in clinical practice, few studies address these factors and with inconsistent study design. Future AKI studies should report pre-AKI and post-AKI function consistently as additional factors that may modify AKI prognosis. 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.

Contrast-induced acute kidney injury: potential new strategies.

PubMed

Briguori, Carlo; Donnarumma, Elvira; Quintavalle, Cristina; Fiore, Danilo; Condorelli, Gerolama

2015-03-01

Contrast-induced acute kidney injury (CI-AKI) is an impairment of renal function following contrast media administration in the absence of an alternative cause. It represents a powerful predictor of poor early and late outcomes. Here, we review the major strategies to prevent CI-AKI. Hydration represents the gold standard as a prophylactic measure to prevent CI-AKI, acting by increasing urine flow rate and, thereby, by limiting the time of contact between the contrast media and the tubular epithelial cells. An optimal hydration regimen should be defined according to predefined clinical markers, such as urine flow rate, or left ventricular end-diastolic pressure. Recently, high-dose statins pretreatment has been included in the guidelines of CI-AKI prevention. However, uncertainty still exists on the efficacy of several compounds tested in both observational trials and randomized studies to prevent CI-AKI. Compounds evaluated include diuretics (furosemide), antioxidants (i.e. N-acetylcysteine and statins) and vasodilators (i.e. calcium antagonists, dopamine and fenoldopam). Hydration still represents the most reliable strategy to prevent CI-AKI. New prophylactic strategies for acute kidney injury are still under investigation.

Posttransplant hypertension: multipathogenic disease process.

PubMed

Barbari, Antoine

2013-04-01

Arterial hypertension is prevalent among kidney transplant recipients. The multifactorial pathogenesis involves the interaction of the donor and the recipient's genetic backgrounds with several environmental parameters that may precede or follow the transplant procedure (eg, the nature of the renal disease, the duration of the chronic kidney disease phase and maintenance dialytic therapy, the commonly associated cardiovascular disease with atherosclerosis and arteriosclerosis, the renal mass at implantation, the immunosuppressive regimen used, life of the graft, and de novo medical and surgical complications that may occur after a transplant). Among calcineurin inhibitors, tacrolimus seems to have a better cardiovascular profile. Steroid-free protocols and calcineurin inhibitor-free regimens seem to be associated with better blood pressure control. Posttransplant hypertension is a major amplifier of the chronic kidney disease-cardiovascular disease continuum. Despite the adverse effects of hypertension on graft and patient survival, blood pressure control remains poor because of the high cardiovascular risk profile of the donor-recipient pair. Although the optimal blood pressure level remains unknown, it is recommended to maintain the blood pressure at < 130/80 mm Hg and < 125/75 mm Hg in the absence or presence of proteinuria.

The prohibition of kidney sales and organ markets should remain.

PubMed

Danovitch, Gabriel M; Delmonico, Francis L

2008-08-01

There is an ongoing vigorous debate regarding the wisdom of the current prohibition of organ sales in the United States. We argue that this prohibition must remain in place. We discuss the current international realities regarding organ vending in order to show that even a so-called 'regulated' market brings with it danger to the welfare of transplant donors, their recipients, and potential recipients of nonrenal organs. We counter the specific arguments made in favor of organ sales while recommending multiple measures that can serve to remove disincentives to noncommercial organ donation. We encourage the investment in innovative healthy transplant practice for the benefit of all. In 'natural experiments' performed in developing countries the outcome for kidney vendors, in terms of both their medical and psychosocial health, has been shown to be poor. A high incidence of serious infections has been reported in recipients of vended organs. Commercialization of living kidney donation does not serve the interests of the donors, endangers the health of recipients, and undermines the healthy development of the international transplant endeavor.

The role of plasma triglyceride/high-density lipoprotein cholesterol ratio to predict cardiovascular outcomes in chronic kidney disease.

PubMed

Sonmez, Alper; Yilmaz, Mahmut Ilker; Saglam, Mutlu; Unal, Hilmi Umut; Gok, Mahmut; Cetinkaya, Hakki; Karaman, Murat; Haymana, Cem; Eyileten, Tayfun; Oguz, Yusuf; Vural, Abdulgaffar; Rizzo, Manfredi; Toth, Peter P

2015-04-16

Cardiovascular disease (CVD) risk is substantially increased in subjects with chronic kidney disease (CKD). The Triglycerides (TG) to High-Density Lipoprotein Cholesterol (HDL-C) ratio is an indirect measure of insulin resistance and an independent predictor of cardiovascular risk. No study to date has been performed to evaluate whether the TG/HDL-C ratio predicts CVD risk in patients with CKD. A total of 197 patients (age 53±12 years) with CKD Stages 1 to 5, were enrolled in this longitudinal, observational, retrospective study. TG/HDL-C ratio, HOMA-IR indexes, serum asymmetric dimethyl arginine (ADMA), high sensitivity C-reactive protein (CRP), parathyroid hormone (PTH), calcium, phosphorous, estimated glomerular filtration rate (eGFR), and albumin levels were measured. Flow mediated vasodilatation (FMD) of the brachial artery was assessed by using high-resolution ultrasonography. A total of 11 cardiovascular (CV) deaths and 43 nonfatal CV events were registered in a mean follow-up period of 30 (range 9 to 35) months. Subjects with TG/HDL-C ratios above the median values (>3.29) had significantly higher plasma ADMA, PTH, and phosphorous levels (p=0.04, p=0.02, p=0.01 respectively) and lower eGFR and FMD values (p=0.03, p<0.001 respectively). The TG/HDL-C ratio was an independent determinant of FMD (β=-0.25 p=0.02) along with TG, HDL-C, hsCRP, serum albumin, phosphate levels, systolic blood pressure, PTH, eGFR and the presence of diabetes mellitus. The TG/HDL-C ratio was also a significant independent determinant of cardiovascular outcomes [HR: 1.36 (1.11-1.67) (p=0.003)] along with plasma ADMA levels [HR: 1.31 (1.13-1.52) (p<0.001)] and a history of diabetes mellitus [HR: 4.82 (2.80-8.37) (p<0.001)]. This study demonstrates that the elevated TG/HDL-C ratio predicts poor CVD outcome in subjects with CKD. Being a simple, inexpensive, and reproducible marker of CVD risk, the TG/HDL-C ratio may emerge as a novel and reliable indicator among the many well-established markers of CVD risk in CKD. Clinical trial registration number and date: NCT02113462 / 10-04-2014.

Case mix, outcome and activity for patients with severe acute kidney injury during the first 24 hours after admission to an adult, general critical care unit: application of predictive models from a secondary analysis of the ICNARC Case Mix Programme Database

PubMed Central

Kolhe, Nitin V; Stevens, Paul E; Crowe, Alex V; Lipkin, Graham W; Harrison, David A

2008-01-01

Introduction This study pools data from the UK Intensive Care National Audit and Research Center (ICNARC) Case Mix Programme (CMP) to evaluate the case mix, outcome and activity for 17,326 patients with severe acute kidney injury (AKI) occurring during the first 24 hours of admission to intensive care units (ICU). Methods Severe AKI admissions (defined as serum creatinine ≥300 μmol/l and/or urea ≥40 mmol/l during the first 24 hours) were extracted from the ICNARC CMP database of 276,326 admissions to UK ICUs from 1995 to 2004. Subgroups of oliguric and nonoliguric AKI were identified by daily urine output. Data on surgical status, survival and length of stay were also collected. Severity of illness scores and mortality prediction models were compared (UK Acute Physiology and Chronic Health Evaluation [APACHE] II, Stuivenberg Hospital Acute Renal Failure [SHARF] T0, SHARF II0 and the Mehta model). Results Severe AKI occurred in 17,326 out of 276,731 admissions (6.3%). The source of admission was nonsurgical in 83.7%. Sepsis was present in 47.3% and AKI was nonoliguric in 63.9% of cases. Admission to ICU with severe AKI accounted for 9.3% of all ICU bed-days. Oliguric AKI was associated with longer length of stay for survivors and shorter length of stay for nonsurvivors compared with nonoliguric AKI. Oliguric AKI was associated with significantly greater ICU and hospital mortality (55.8% and 77.3%, respectively) compared with nonoliguric AKI (33.4% and 49.3%, respectively). Surgery during the 1 week before admission or during the first week in the CMP unit was associated with decreased odds of mortality. UK APACHE II and the Mehta scores under-predicted the number of deaths, whereas SHARF T0 and SHARF II0 over-predicted the number of deaths. Conclusions Severe AKI accounts for over 9% of all bed-days in adult, general ICUs, representing a considerable drain on resources. Although nonoliguric AKI continues to confer a survival benefit, overall survival from AKI in the ICU and survival to leave hospital remains poor. The use of APACHE II score measured during the first 24 hours of ICU stay performs well as compared with SHARF T0, SHARF II0 and the Mehta score, but it lacks perfect calibration. PMID:19105800

Febuxostat hypersensitivity: another cause of DRESS syndrome in chronic kidney disease?

PubMed

Paschou, E; Gavriilaki, E; Papaioannou, G; Tsompanakou, A; Kalaitzoglou, A; Sabanis, N

2016-11-01

Febuxostat is a xanthine oxidase inhibitor that during the last years has successfully replaced allopurinol treatment in patients with chronic kidney disease (CKD) and hyperuricemia. Several adverse events have been observed during therapy with febuxostat. DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome induced by febuxostat has been poorly described, mainly in patient with CKD who previously developed allopurinol hypersensitivity syndrome. DRESS syndrome is characterized by manifold cutaneous reactions and systemic disorders with potential devastating consequences. The underlying pathogenetic mechanisms remain unidentified, though immune responses are often complicated. P-i concept can partially explain the phenomenon. The role of renal insufficiency appears to be crucial and further investigation is required. The present article describes the case of a CKD patient that developed febuxostat-related DRESS syndrome.

Obesity and heart failure as a mediator of the cerebrorenal interaction.

PubMed

Jindal, Ankur; Whaley-Connell, Adam; Sowers, James R

2013-01-01

The obesity epidemic is contributing substantially to the burden of cardiovascular disease including heart disease and congestive heart failure, in the United States and the rest of the world. Overnutrition as a driver of obesity, promotes alterations in fatty acid, lipid, and glucose metabolism that influence myocardial function and progression of heart failure from diastolic to systolic failure. The association of progressive heart failure and progressive chronic kidney disease is well documented and often referred to as the cardiorenal syndrome, as well as a prognosticator for cerebrovascular disease (e.g. stroke). Whether the relationship between obesity, heart disease/failure and risk for chronic kidney disease and stroke is direct or a confluence of risk factors is poorly understood. Copyright © 2013 S. Karger AG, Basel.

Development and validation of an electronic phenotyping algorithm for chronic kidney disease

PubMed Central

Nadkarni, Girish N; Gottesman, Omri; Linneman, James G; Chase, Herbert; Berg, Richard L; Farouk, Samira; Nadukuru, Rajiv; Lotay, Vaneet; Ellis, Steve; Hripcsak, George; Peissig, Peggy; Weng, Chunhua; Bottinger, Erwin P

2014-01-01

Twenty-six million Americans are estimated to have chronic kidney disease (CKD) with increased risk for cardiovascular disease and end stage renal disease. CKD is frequently undiagnosed and patients are unaware, hampering intervention. A tool for accurate and timely identification of CKD from electronic medical records (EMR) could improve healthcare quality and identify patients for research. As members of eMERGE (electronic medical records and genomics) Network, we developed an automated phenotyping algorithm that can be deployed to identify rapidly diabetic and/or hypertensive CKD cases and controls in health systems with EMRs It uses diagnostic codes, laboratory results, medication and blood pressure records, and textual information culled from notes. Validation statistics demonstrated positive predictive values of 96% and negative predictive values of 93.3. Similar results were obtained on implementation by two independent eMERGE member institutions. The algorithm dramatically outperformed identification by ICD-9-CM codes with 63% positive and 54% negative predictive values, respectively. PMID:25954398

A Reduced Set of Features for Chronic Kidney Disease Prediction

PubMed Central

Misir, Rajesh; Mitra, Malay; Samanta, Ranjit Kumar

2017-01-01

Chronic kidney disease (CKD) is one of the life-threatening diseases. Early detection and proper management are solicited for augmenting survivability. As per the UCI data set, there are 24 attributes for predicting CKD or non-CKD. At least there are 16 attributes need pathological investigations involving more resources, money, time, and uncertainties. The objective of this work is to explore whether we can predict CKD or non-CKD with reasonable accuracy using less number of features. An intelligent system development approach has been used in this study. We attempted one important feature selection technique to discover reduced features that explain the data set much better. Two intelligent binary classification techniques have been adopted for the validity of the reduced feature set. Performances were evaluated in terms of four important classification evaluation parameters. As suggested from our results, we may more concentrate on those reduced features for identifying CKD and thereby reduces uncertainty, saves time, and reduces costs. PMID:28706750

Intermediate-Term Outcomes With Expanded Criteria Deceased Donors in Kidney Transplantation

PubMed Central

Stratta, Robert J.; Rohr, Michael S.; Sundberg, Aimee K.; Farney, Alan C.; Hartmann, Erica L.; Moore, Phillip S.; Rogers, Jeffrey; Iskandar, Samy S.; Gautreaux, Michael D.; Kiger, David F.; Doares, William; Anderson, Teresa K.; Hairston, Gloria; Adams, Patricia L.

2006-01-01

Objective: To compare intermediate-term outcomes in adult recipients of expanded criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney transplants at a single center using a standardized approach. Summary Background Data: Expanded criteria donors (ECDs) are a source of kidneys that increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns regarding diminished survival and predicted poorer intermediate-term outcomes. Methods: Over a 47-month period, we performed 244 deceased donor kidney transplants into adult recipients, including 143 from SCDs and 101 from ECDs. Management algorithms were implemented to preserve nephron function, and recipient selection for an ECD kidney transplant was based on low immunologic risk. All patients received depleting antibody induction in combination with tacrolimus and mycophenolate mofetil. A total of 188 patients (77%) had at least a 1-year follow-up. Results: ECDs were older, had a higher BMI, had an increased incidence of cerebrovascular brain death and preexisting donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P < 0.01) compared with SCDs. Cold ischemic times were similar between groups, but more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates were similar between groups with a mean follow-up of 24 months. The rates of delayed graft function (DGF), acute rejection, readmissions, operative complications, major infections, and resource utilization were comparable between groups. Renal function followed longitudinally was consistently better in SCD patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection, and graft loss (P < 0.05), but the effects were less pronounced in the ECD group. Conclusions: By appropriate donor and recipient profiling and the use of management algorithms to project and protect renal function, excellent intermediate-term outcomes can be achieved with ECD kidney transplants that are comparable to SCD kidney transplants. PMID:16632993

Renal Histopathologic Findings Associated With Severity of Clinical Acute Kidney Injury.

PubMed

Kudose, Satoru; Hoshi, Masato; Jain, Sanjay; Gaut, Joseph P

2018-05-01

Acute kidney injury (AKI) is a significant cause of morbidity and mortality. Acute tubular injury is considered to be the early pathologic manifestation of AKI, however, the underlying pathology is complex, lacks standards for interpretation, and its relationship with AKI often is unclear or inconsistent. To clarify clinicopathologic correlations in AKI, we evaluated 32 histologic findings in 100 kidney biopsies from patients with AKI as a training set to correlate pathologic findings with clinical AKI grades. Kidney Injury Molecule-1 quantitative immunohistochemistry was performed to confirm tubular injury. A separate cohort of 50 biopsies were evaluated blinded to clinical information to validate the findings. Pathologic tubular injury correlated best with Kidney Disease Improving Global Outcomes criteria. Tubular epithelial simplification, tubular epithelial mitosis, and cell sloughing correlated well with clinically severe AKI and were used to construct a tubular injury classification scheme with sensitivity of 0.93 (0.85, 1), specificity of 0.95 (0.83, 1), and area under the receiver-operating characteristic curve of 0.98 (0.98, 1) for grades 2 to 3 AKI. Predictive ability of the model did not improve when Kidney Injury Molecule-1 immunostaining results were added. The results show a strong correlation between pathologic tubular injury and modern clinical definitions of AKI. The proposed classification scheme may aid in development of more precise and clinically meaningful interpretations of pathologic tubular injury in native kidney biopsies and provides simple pathologic criteria without special studies that can easily be adopted globally.

Biomarkers and a tailored approach for immune monitoring in kidney transplantation

PubMed Central

Salcido-Ochoa, Francisco; Allen, John Carson

2017-01-01

A literature review on immune monitoring in kidney transplantation produced dozens of research articles and a multitude of promising biomarkers, all in the quest for the much sought after - but perennially elusive - “holy grail” of kidney biomarkers able to unequivocally predict acute transplant rejection vs non-rejection. Detection methodologies and study designs were many and varied. Hence the motivation for this editorial, which espouses the notion that in today’s kidney transplantation milieu, the judicious use of disease classifiers tailored to specific patient immune risks may be more achievable and productive in the long run and confer a greater advantage for patient treatment than the pursuit of a single “omniscient” biomarker. In addition, we desire to direct attention toward greater scrutiny of biomarker publications and decisions to implement biomarkers in practice, standardization of methods in the development of biomarkers and consideration for adoption of “biomarker-driven” biopsies. We propose “biomarker-driven” biopsies as an adjunctive to and/or alternative to random surveillance (protocol) biopsies or belated indication biopsies. The discovery of a single kidney transplantation biomarker would represent a major breakthrough in kidney transplantation practice, but until that occurs - if ever it does occur, other approaches offer substantial potential for unlocking prognostic, diagnostic and therapeutic options. We conclude our editorial with suggestions and recommendations for productively incorporating current biomarkers into diagnostic algorithms and for testing future biomarkers of acute rejection in kidney transplantation. PMID:29312857

Associations between Deceased-Donor Urine Injury Biomarkers and Kidney Transplant Outcomes

PubMed Central

Reese, Peter P.; Hall, Isaac E.; Weng, Francis L.; Schröppel, Bernd; Doshi, Mona D.; Hasz, Rick D.; Thiessen-Philbrook, Heather; Ficek, Joseph; Rao, Veena; Murray, Patrick; Lin, Haiqun

2016-01-01

Assessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase–associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean±SD 6-month eGFR was 55.7±23.5 ml/min per 1.73 m2. In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant. PMID:26374609

Prevalence and Determinants of Physical Activity and Fluid Intake in Kidney Transplant Recipients

PubMed Central

Gordon, Elisa J.; Prohaska, Thomas R.; Gallant, Mary P.; Sehgal, Ashwini R.; Strogatz, David; Conti, David; Siminoff, Laura A.

2009-01-01

Background and Significance Self-care for kidney transplantation is recommended to maintain kidney function. Little is known about levels of self-care practices, and demographic, psychosocial, and health-related correlates. Aim We investigated patients’ self-reported exercise and fluid intake, demographic and psychosocial factors associated with these self-care practices, and health-related quality of life. Methods Eighty-eight of 158 kidney recipients from two academic medical centers completed a semi-structured interview and surveys 2 months post-transplant. Results Most patients were sedentary (76%) with a quarter exercising either regularly (11%) or not at current recommendations (13%). One third (35%) reported drinking the recommended three liters of fluid daily. Multivariate analyses indicated that private insurance, high self-efficacy, and better physical functioning were significantly associated with engaging in physical activity (p<0.05); while male gender, private insurance, high self-efficacy, and not attributing oneself responsible for transplant success were significant predictors of adherence to fluid intake (p<0.05). Despite the significance of these predictors, models for physical activity and fluid intake explained 10–15% of the overall variance in these behaviors. Multivariate analyses indicated that younger age, high value of exercise, and higher social functioning significantly (p<0.05) predicted high self-efficacy for physical activity, while being married significantly (p<0.05) predicted high self-efficacy for fluid intake. Conclusion Identifying patients at risk of inadequate self-care practice is essential for educating patients about the importance of self-care. PMID:19925468

Prevalence and determinants of physical activity and fluid intake in kidney transplant recipients.

PubMed

Gordon, Elisa J; Prohaska, Thomas R; Gallant, Mary P; Sehgal, Ashwini R; Strogatz, David; Conti, David; Siminoff, Laura A

2010-01-01

Self-care for kidney transplantation is recommended to maintain kidney function. Little is known about levels of self-care practices and demographic, psychosocial, and health-related correlates. To investigate patients' self-reported exercise and fluid intake, demographic and psychosocial factors associated with these self-care practices, and health-related quality of life. Eighty-eight of 158 kidney recipients from two academic medical centers completed a semi-structured interview and surveys 2 months post-transplant. Most patients were sedentary (76%) with a quarter exercising either regularly (11%) or not at current recommendations (13%). One-third (35%) reported drinking the recommended 3 L of fluid daily. Multivariate analyses indicated that private insurance, high self-efficacy, and better physical functioning were significantly associated with engaging in physical activity (p < 0.05); while male gender, private insurance, high self-efficacy, and not attributing oneself responsible for transplant success were significant predictors of adherence to fluid intake (p < 0.05). Despite the significance of these predictors, models for physical activity and fluid intake explained 10-15% of the overall variance in these behaviors. Multivariate analyses indicated that younger age, high value of exercise, and higher social functioning significantly (p < 0.05) predicted high self-efficacy for physical activity, while being married significantly (p < 0.05) predicted high self-efficacy for fluid intake. Identifying patients at risk of inadequate self-care practice is essential for educating patients about the importance of self-care.

Comparison of immunohistochemistry and polymerase chain reaction for detection of West Nile virus in naturally infected dead birds.

PubMed

Sandhu, Tejbir; Sidhu, Dalbinder; Dhillon, Major; Fang, Ying

2010-10-04

Credible vector-borne disease surveillance programs, especially in developing countries with limited resources, must include diagnostic tests that are efficient, inexpensive and simple and safe to administer while maintaining high levels of sensitivity and specificity. Since immunohistochemistry (IHC) includes most of these features, its sensitivity, specificity, predictive positive value (PPV) and predictive negative value (PNV) for West Nile virus (WNv) screening were compared to those of the gold standard, RT-PCR testing of kidney tissue in dead birds. IHC and RT-PCR were performed for WNv antigen on 41 dead birds (belonging to five orders) collected from the northwest region of the Riverside County of California. Fixed tissue sections were screened by IHC using polyclonal antibodies, and frozen kidney tissues were tested with RT-PCR. Kidney screening with IHC showed sensitivity, specificity, PPV and NPV of 95.45%, 73.68%, 80.77% and 93.33%, respectively. Based on WNv screening of kidney tissue, IHC and RT-PCR were in agreement with 95.45% (21/22) for positive dead birds and were in 100% (22/22) agreement when multi-organ screening by IHC was performed. The present study showed that IHC is as equally effective as RT-PCR in screening for WNv in dead birds. Therefore, IHC can effectively serve as a competent screening technique for those disease surveillance agencies that lack expensive RT-PCR technology while promoting safer biohazardous conditions, except at the initial stage of tissue collection.

Effect of an Educational Program on Adherence to Therapeutic Regimen among Chronic Kidney Disease Stage5 (CKD5) Patients under Maintenance Hemodialysis

ERIC Educational Resources Information Center

Deif, Hala I. Abo; Elsawi, Khiria; Selim, Mohga; NasrAllah, Mohamed M.

2015-01-01

The burden of chronic disease on health care services worldwide is growing and the increased development of educational interventions which help patients to better manage their conditions is evident internationally. It has been recognized that poor adherence can be a serious risk to the health and wellbeing of patients. Adherence to fluid…

Management of Neurogenic Bladder.

PubMed

Sripathi, Venkataramani; Mitra, Aparajita

2017-07-01

This article provides a comprehensive summary of the clinical approach, investigative modalities and management of a child with neurogenic bladder disease due to myelodysplasia. It is aimed at pediatric physicians and surgeons working in developing nations. The methodologies suggested are simple and can be practised even in resource poor regions. The goal of management is avoidance of Chronic kidney disease and for this, meticulous bladder management is the key.

A strain-hardening bi-power law for the nonlinear behaviour of biological soft tissues.

PubMed

Nicolle, S; Vezin, P; Palierne, J-F

2010-03-22

Biological soft tissues exhibit a strongly nonlinear viscoelastic behaviour. Among parenchymous tissues, kidney and liver remain less studied than brain, and a first goal of this study is to report additional material properties of kidney and liver tissues in oscillatory shear and constant shear rate tests. Results show that the liver tissue is more compliant but more strain hardening than kidney. A wealth of multi-parameter mathematical models has been proposed for describing the mechanical behaviour of soft tissues. A second purpose of this work is to develop a new constitutive law capable of predicting our experimental data in the both linear and nonlinear viscoelastic regime with as few parameters as possible. We propose a nonlinear strain-hardening fractional derivative model in which six parameters allow fitting the viscoelastic behaviour of kidney and liver tissues for strains ranging from 0.01 to 1 and strain rates from 0.0151 s(-1) to 0.7s(-1). Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Dietary habits, poverty, and chronic kidney disease in an urban population.

PubMed

Crews, Deidra C; Kuczmarski, Marie Fanelli; Miller, Edgar R; Zonderman, Alan B; Evans, Michele K; Powe, Neil R

2015-03-01

Poverty is associated with chronic kidney disease (CKD) in the United States and worldwide. Poor dietary habits may contribute to this disparity. Cross-sectional study. A total of 2,058 community-dwelling adults aged 30 to 64 years residing in Baltimore City, Maryland. Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet. DASH scoring based on 9 target nutrients (total fat, saturated fat, protein, fiber, cholesterol, calcium, magnesium, sodium, and potassium); adherence defined as score ≥4.5 of maximum possible score of 9. Poverty (self-reported household income <125% of 2004 Department of Health and Human Services guideline) and nonpoverty (≥125% of guideline). CKD defined as estimated glomerular filtration rate <60 mL/minute/1.73 m(2) (CKD epidemiology collaboration equation). Multivariable logistic regression was used to calculate adjusted odds ratios (AORs) for relation of DASH score tertile and CKD, stratified by poverty status. Among 2,058 participants (mean age 48 years; 57% black; 44% male; 42% with poverty), median DASH score was low, 1.5 (interquartile range, 1-2.5). Only 5.4% were adherent. Poverty, male sex, black race, and smoking were more prevalent among the lower DASH score tertiles, whereas higher education and regular health care were more prevalent among the highest DASH score tertile (P < .05 for all). Fiber, calcium, magnesium, and potassium intake were lower, and cholesterol higher, among the poverty compared with nonpoverty group (P < .05 for all), with no difference in sodium intake. A total of 5.6% of the poverty and 3.8% of the nonpoverty group had CKD (P = .05). The lowest DASH tertile (compared with the highest) was associated with more CKD among the poverty (AOR 3.15, 95% confidence interval 1.51-6.56), but not among the nonpoverty group (AOR 0.73, 95% confidence interval 0.37-1.43; P interaction = .001). Poor dietary habits are strongly associated with CKD among the urban poor and may represent a target for interventions aimed at reducing disparities in CKD. Copyright © 2015 National Kidney Foundation, Inc. All rights reserved.

Implications of the angiotensin converting enzyme gene insertion/deletion polymorphism in health and disease: a snapshot review

PubMed Central

Gard, Paul R

2010-01-01

This review considers the 250+ papers concerning the association of the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (rs1799752) and various disease conditions published in 2009. The deletion allele occurs in approximately 55% of the population and is associated with increased activity of the ACE enzyme. It might be predicted that the D allele, therefore, might be associated with pathologies involving increased activity of the renin-angiotensin system. The D allele was seen to be associated with an increased risk of hypertension, pre-eclampsia, heart failure, cerebral infarct, diabetic nephropathy, encephalopathy, asthma, severe hypoglycaemia in diabetes, gastric cancer (in Caucasians) and poor prognosis following kidney transplant. On the positive side, the D allele appears to offer protection against schizophrenia and chronic periodontitis and confers greater up-per-body strength in old age. The I allele, meanwhile, offers improved endurance/athletic performance and aerobic capacity as determined by lung function tests, although it does increase the risk of oral squamous cell carcinoma and obstructive sleep apnoea in hypertensives. PMID:21537387

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

The impact of living-unrelated transplant on establishing deceased-donor liver program in Syria.

PubMed

Saeed, Bassam

2014-10-01

Liver transplant is the criterion standard for patients with end-stage liver disease. Yet there is no liver transplant in Syria. Traveling abroad for a liver transplant is a luxury few Syrians can afford. There is currently an on-going debate whether to start a liver transplant program using living or deceased donors. In 2003, a new law was enacted, authorizing the use of organs from volunteer strangers and deceased donors. Despite the positive aspects of this law (allowing unrelated donors to increase the number of transplants in the country); the negative aspects also were obvious. The poor used the law to sell their organs to the rich, and this model is in violation of the Istanbul Declaration. To better document transplant communities' perceptions on organ donation, an e-mail survey was sent to a nationally representative sample of physicians (n = 115) that showed that 58% of respondents did not support the start of liver transplant from live donors, as they fear a considerable risk for the donor and the recipient. Seventy-one percent of respondents believe that unrelated kidney donation has contributed to tarnishing the reputation of transplant, and 56% believe that a deceased-donor program can run in parallel with unrelated organ donations. The interest in deceased-donor program has been affected negatively by the systematic approach of using poor persons as the source of the organ. This lack of interest has affected starting a liver program that relies on deceased donors; especially the need for kidneys is more than livers. Health authorities in Syria were inclined to initiate a liver transplant program from live donors, despite the risks of serious morbidities and mortality. In conclusion then, paid kidney donation in actual effect is actually a hindrance to establishing a deceased-donor liver program.

ET-1 deletion from endothelial cells protects the kidney during the extension phase of ischemia/reperfusion injury

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

Arfian, Nur; Emoto, Noriaki, E-mail: emoto@med.kobe-u.ac.jp; Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe

Highlights: Black-Right-Pointing-Pointer Ischemia/reperfusion injury (IRI) induced increased endothelin-1 (ET-1) expression. Black-Right-Pointing-Pointer IRI was accompanied by tubular injury and remodeling of renal arteries. Black-Right-Pointing-Pointer IRI increased oxidative stress and inflammation. Black-Right-Pointing-Pointer Genetic suppression of ET-1 in endothelial cells attenuates IRI in the kidney. Black-Right-Pointing-Pointer The mechanisms include the inhibition of oxidative stress and inflammation. -- Abstract: Background: The prognosis of patients after acute kidney injury (AKI) is poor and treatment is limited. AKI is mainly caused by renal ischemia/reperfusion injury (IRI). During the extension phase of IRI, endothelial damage may participate in ischemia and inflammation. Endothelin-1 (ET-1) which is mostly secretedmore » by endothelial cells is an important actor of IRI, particularly through its strong vasoconstrictive properties. We aimed to analyze the specific role of ET-1 from the endothelial cells in AKI. Methods: We used mice lacking ET-1 in the vascular endothelial cells (VEETKO). We induced IRI in VEETKO mice and wild type controls by clamping both kidneys for 30 min. Sham operated mice were used as controls. Mice were sacrificed one day after IRI in order to investigate the extension phase of IRI. Kidney function was assessed based on serum creatinine concentration. Levels of expression of ET-1, its receptor ET{sub A}, protein kinase C, eNOS, E-Cadherin and inflammation markers were evaluated by real time PCR or western blot. Tubular injury was scored on periodic acid Schiff stained kidney preparations. Lumen and wall area of small intrarenal arteries were measured on kidney slices stained for alpha smooth muscle cell actin. Oxidative stress, macrophage infiltration and cell proliferation was evaluated on slices stained for 8-hydroxy-2 Prime -deoxyguanosine, F4/80 and PCNA, respectively. Results: IRI induced kidney failure and increased ET-1 and ET{sub A} receptor expression. This was accompanied by tubular injury, wall thickening and reduction of lumen area/wall area ratio of small renal arteries, increased oxidative stress and inflammation. These parameters were attenuated in VEETKO mice. Conclusion: Our results suggest that suppression of ET-1 from the endothelial cells attenuates IRI kidney injury. Blocking ET-1 effects may represent a therapeutic strategy in the management of AKI.« less

Clinical Features of Kidney Transplant Recipients Admitted to the Intensive Care Unit.

PubMed

Freitas, Flávio Geraldo Rezende; Lombardi, Fábio; Pacheco, Eduardo Souza; Sandes-Freitas, Tainá Veras de; Viana, Laila Almeida; Junior, Hélio Tedesco-Silva; Medina-Pestana, José Osmar; Bafi, Antônio Tonete; Machado, Flavia Ribeiro

2018-03-01

There is a paucity of data regarding the complications in kidney transplant patients who may require intensive care unit (ICU) management, despite being the most common solid organ transplant worldwide. To identify the main reasons for ICU admission and to determine the factors associated with hospital mortality in kidney transplant recipients. This single-center retrospective cohort study was conducted between September 2013 and June 2014, including all consecutive kidney transplant patients requiring ICU admission. We collected data on patient demographics, transplant characteristics, clinical data, and prognostic scores. The independent determinants of hospital mortality were identified by multiple logistic regression analysis. We also assessed the performance of Simplified Acute Physiology Score 3 (SAPS 3) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. We analyzed data from 413 patients, the majority of whom were admitted late after renal transplantation (1169 days; 63-3003 days). The main reason for admission was sepsis (33.2%), followed by cardiovascular disease (16%). Age (odds ratio [OR] 1.05, confidence interval [CI], 1.01-1.09), SAPS 3 score (OR 1.04, CI, 1.01-1.08), the need for mechanical ventilation (OR 26.47, CI, 10.30-68.08), and vasopressor use (OR 3.34, CI, 1.37-8.13) were independently associated with hospital mortality. The performance of SAPS 3 and APACHE II scores was poor in this population and overestimated the mortality rates. Sepsis was the main reason for ICU admission in kidney transplant recipients, followed by cardiovascular disease. Age and disease severity were associated with hospital mortality.

Immunosuppression With CD40 Costimulatory Blockade Plus Rapamycin for Simultaneous Islet-Kidney Transplantation in Nonhuman Primates.

PubMed

Oura, T; Hotta, K; Lei, J; Markmann, J; Rosales, I; Dehnadi, A; Kawai, K; Ndishabandi, D; Smith, R-N; Cosimi, A B; Kawai, T

2017-03-01

The lack of a reliable immunosuppressive regimen that effectively suppresses both renal and islet allograft rejection without islet toxicity hampers a wider clinical application of simultaneous islet-kidney transplantation (SIK). Seven MHC-mismatched SIKs were performed in diabetic cynomolgus monkeys. Two recipients received rabbit antithymocyte globulin (ATG) induction followed by daily tacrolimus and rapamycin (ATG/Tac/Rapa), and five recipients were treated with anti-CD40 monoclonal antibody (mAb) and rapamycin (aCD40/Rapa). Anti-inflammatory therapy, including anti-interleukin-6 receptor mAb and anti-tumor necrosis factor-α mAb, was given in both groups. The ATG/Tac/Rapa recipients failed to achieve long-term islet allograft survival (19 and 26 days) due to poor islet engraftment and cytomegalovirus pneumonia. In contrast, the aCD40/Rapa regimen provided long-term islet and kidney allograft survival (90, 94, >120, >120, and >120 days), with only one recipient developing evidence of allograft rejection. The aCD40/Rapa regimen was also tested in four kidney-alone transplant recipients. All four recipients achieved long-term renal allograft survival (100% at day 120), which was superior to renal allograft survival (62.9% at day 120) with triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and steroids). The combination of anti-CD40 mAb and rapamycin is an effective and nontoxic immunosuppressive regimen that uses only clinically available agents for kidney and islet recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Distinguishing internal property from external property in kidney transplantation.

PubMed

Prasad, G V Ramesh

2016-08-01

What determines the ownership of human body parts? In this paper, I argue that this question can be informed by an exploration of the cognitive distinction between property external to the human body such as houses, cars or land, and internal property such as organs that are located within anatomical body confines. Each type of property has distinct brain representations and possibly different effects on the sense of self. This distinction may help explain the divergence in post-donation outcomes seen in different kidney donor populations. Poor outcomes in some types of kidney donors may be due not only to a failure in their proper selection by standard medical testing or post-donation care but may also be a manifestation of differing effects on sense of self resulting from transfer of their internal property. Because a kidney is internal property, a hypothesis worth exploring is that those who experience good outcomes post-donation experience dopaminergic activation and a feeling of reward, while those experiencing bad outcomes are instead overcoming cortisol or adrenergic-based stress or fear responses without a corresponding feeling of reward, disrupting of their sense of self. Discussions about the rules for internal property transfer must be based not only on values and laws designed to govern external property but also on cognitive science-based facts, values and judgments that discussions of external property do not presently accommodate. Any future system of rules for governing organ distribution requires a framework different from that of external property to prevent harm to living kidney donors. © 2016 John Wiley & Sons, Ltd.

Expression of TNF-alpha, TGF-beta, IP-10 and IL-10 mRNA in kidneys of hamsters infected with pathogenic Leptospira.

PubMed

Lowanitchapat, Alisa; Payungporn, Sunchai; Sereemaspun, Amornpun; Ekpo, Pattama; Phulsuksombati, Duangporn; Poovorawan, Yong; Chirathaworn, Chintana

2010-09-01

Leptospirosis is a worldwide zoonosis caused by pathogenic Leptospira. Although several components of this organism have been identified, the molecular mechanisms underlying pathogenesis of this infectious disease are still poorly understood. Besides, direct injury by microbial factors, cytokines produced in response to infection have been proposed to be involved in pathogenesis of leptospirosis. In this study, cytokine gene expression in kidneys was investigated. Hamsters were injected with pathogenic Leptospira interrogans serovar Pyrogenes and were sacrificed on days 3, 5 and 7 after infection. RNA was extracted from kidney tissues. Real-time PCR was performed to demonstrate expression of TNF-alpha, TGF-beta, IP-10 and IL-10 mRNA in kidneys. TNF-alpha, TGF-beta and IP-10 expression could be demonstrated since day 3 post-infection whereas IL-10 expression was detected later on day 5. Leptospira infection resulted in not only expression of a proinflammatory cytokine, TNF-alpha, but also a T cell chemokine, IP-10. Detection of IP-10 suggested the involvement of T cell recruitment in the immune response or pathology in infected kidneys. Expressions of anti-inflammatory cytokines, TGF-beta and IL-10 were also observed. However, the level of TGF-beta expression was prominent since day 3 post-infection whereas IL-10 expression was clearly observed on day 5. Further experiments will provide additional information whether there is a correlation between the expression of these cytokines and pathologies found in an affected organ. Copyright 2009 Elsevier Ltd. All rights reserved.

Sociodemographic factors contribute to the depressive affect among African Americans with chronic kidney disease.

PubMed

Fischer, Michael J; Kimmel, Paul L; Greene, Tom; Gassman, Jennifer J; Wang, Xuelei; Brooks, Deborah H; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A; Bruce, Marino A; Kusek, John W; Norris, Keith C; Lash, James P

2010-06-01

Depression is common in end-stage renal disease and is associated with poor quality of life and higher mortality; however, little is known about depressive affect in earlier stages of chronic kidney disease. To measure this in a risk group burdened with hypertension and kidney disease, we conducted a cross-sectional analysis of individuals at enrollment in the African American Study of Kidney Disease and Hypertension Cohort Study. Depressive affect was assessed by the Beck Depression Inventory II and quality of life by the Medical Outcomes Study-Short Form and the Satisfaction with Life Scale. Beck Depression scores over 14 were deemed consistent with an increased depressive affect and linear regression analysis was used to identify factors associated with these scores. Among 628 subjects, 166 had scores over 14 but only 34 were prescribed antidepressants. The mean Beck Depression score of 11.0 varied with the estimated glomerular filtration rate (eGFR) from 10.7 (eGFR 50-60) to 16.0 (eGFR stage 5); however, there was no significant independent association between these. Unemployment, low income, and lower quality and satisfaction with life scale scores were independently and significantly associated with a higher Beck Depression score. Thus, our study shows that an increased depressive affect is highly prevalent in African Americans with chronic kidney disease, is infrequently treated with antidepressants, and is associated with poorer quality of life. Sociodemographic factors have especially strong associations with this increased depressive affect. Because this study was conducted in an African-American cohort, its findings may not be generalized to other ethnic groups.