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Sample records for renal function biomarkers

  1. Biomarkers of renal injury and function: diagnostic, prognostic and therapeutic implications in heart failure.

    PubMed

    van Veldhuisen, Dirk J; Ruilope, Luis M; Maisel, Alan S; Damman, Kevin

    2016-09-01

    Heart failure guidelines suggest evaluating renal function as a routine work-up in every patient with heart failure. Specifically, it is advised to calculate glomerular filtration rate and determine blood urea nitrogen. The reason for this is that renal impairment and worsening renal function (WRF) are common in heart failure, and strongly associate with poor outcome. Renal function, however, consists of more than glomerular filtration alone, and includes tubulointerstitial damage and albuminuria. For each of these renal entities, different biomarkers exist that have been investigated in heart failure. Hypothetically, and in parallel to data in nephrology, these markers may aid in the diagnosis of renal dysfunction, or for risk stratification, or could help in therapeutic decision-making. However, as reviewed in the present manuscript, while these markers may carry prognostic information (although not always additive to established markers of renal function), their role in predicting WRF is limited at best. More importantly, none of these markers have been evaluated as a therapeutic target nor have their serial values been used to guide therapy. The evidence is most compelling for the oldest-serum creatinine (in combination with glomerular filtration rate)-but even for this biomarker, evidence to guide therapy to improve outcome is circumstantial at best. Although many new renal biomarkers have emerged at the horizon, they have only limited usefulness in clinical practice until thoroughly and prospectively studied. For now, routine measurement of (novel) renal biomarkers can help to determine cardiovascular risk, but there is no role for these biomarkers to change therapy to improve clinical outcome in heart failure.

  2. The Combined Influence of Psychological Factors on Biomarkers of Renal Functioning in African Americans

    PubMed Central

    Gholson, Georica K.; Mwendwa, Denée T.; Wright, Regina Sims; Callender, Clive O.; Campbell, Alfonso L.

    2015-01-01

    Objective African Americans are disproportionately affected by chronic kidney disease (CKD). Recent research has documented that psychological factors have a significant influence on the progression and treatment of CKD. However, extant evidence exists that has examined the link between psychological factors and renal function in African Americans. The purpose of the study was to determine if psychological factors were associated with several biomarkers of renal functioning in this group. Participants 129 African American participants, with a mean age of 44.4 years (SD512.25). Design and Setting Data were analyzed from a cross-sectional study entitled Stress and Psychoneuroimmunological Factors in Renal Health and Disease. Main Predictor Measures Participants completed the Beck Depression Inventory-II, Cook Medley Scale, and Perceived Stress Scale-10. Main Outcome Measures Systolic blood pressure, as well as blood and urine samples, were collected and served as biomarkers of renal functioning. Results Our findings indicated that psychological factors were not associated with renal functioning. Age, sex, and systolic blood pressure emerged as significant predictors of renal functioning. Conclusions Depressive symptomatology, perceived stress, and hostility did not influence renal functioning in this sample. This unexpected finding may be attributed to the fact that this sample population was not elevated on depressive symptoms, perceived stress, or hostility. Elevated levels of these psychological factors, as well as other psychological factors associatd with the CKD, may be more influential on renal functioning in African Americans. PMID:26118136

  3. The Combined Influence of Psychological Factors on Biomarkers of Renal Functioning in African Americans.

    PubMed

    Gholson, Georica K; Mwendwa, Denée T; Wright, Regina Sims; Callender, Clive O; Campbell, Alfonso L

    2015-01-01

    African Americans are disproportionately affected by chronic kidney disease (CKD). Recent research has documented that psychological-factors have a significant influence on the progression and treatment of CKD. However, extant evidence exists that has examined the link between psychological factors and renal function in African Americans. The purpose of the study was to determine if psychological factors were associated with several biomarkers of renal functioning in this group. 129 African American participants, with a mean age of 44.4 years (SD = 12.25). Data were analyzed from a cross-sectional study entitled Stress and Psychoneuroimmunological Factors in Renal Health and Disease. MAIN PREDICTOR MEASURES: Participants completed the Beck Depression Inventory-II, Cook Medley Scale, and Perceived Stress Scale-10. Systolic blood pressure, as well as blood and urine samples, were collected and served as biomarkers of renal functioning. Our findings indicated that psychological factors were not associated with renal functioning. Age, sex, and systolic blood pressure emerged as significant predictors of renal functioning. Depressive symptomatology, perceived stress, and hostility did not influence renal functioning in this sample. This unexpected finding may be attributed to the fact that this sample population was not elevated on depressive symptoms, perceived stress, or hostility. Elevated levels of these psychological factors, as well as other psychological factors associated with the CKD, may be more influential on renal functioning in African Americans.

  4. The association between renal function biomarkers and subclinical cardiovascular measures in African Caribbean families.

    PubMed

    Li, Hu; Kuipers, Allison; Kammerer, Candace M; Bunker, Clareanne H; Kuller, Lewis H; Miljkovic, Iva; Patrick, Alan L; Wheeler, Victor W; Zmuda, Joseph M

    2013-01-01

    Risk of cardiovascular disease (CVD) and mortality are increased in people with subclinical CVD. The impact of ethnicity and race on subclinical CVD is substantial. Previous studies assessed the heritability of several renal function biomarkers and their relationship with subclinical CVD among populations of European ancestries, but, to our knowledge, no such data are available in African ancestry populations. Our aim was to investigate the relationships between renal function biomarkers and subclinical CVD among Afro-Caribbeans residing on the island of Tobago. 402 participants, aged 18 to 103 years, from seven large, multi-generation pedigrees (average family size: 50; range: 19 to 96; -3500 relative pairs) were included in this study. Subclinical cardiovascular disease (SCVD) was assessed by brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT). Serum cystatin C, creatinine, and eGFR based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation were used to assess kidney function. The variance component approach, implemented in Sequential Oligogenic Linkage Analysis Routines (SOLAR), was used to assess heritability of these traits, and association with SCVD. Heritability of renal function biomarkers ranged from .19-.32 (all P < .001), and was highest for cystatin C (h2 = .32, P < .0001). Serum cystatin C was independently associated with arterial stiffness (P = .04). This association was not found with other renal function biomarkers. No significant association between renal function and IMT was found. Our data suggest that cystatin C is significantly heritable and associated with arterial stiffness among Afro-Caribbeans.

  5. Effects of creatine supplementation on biomarkers of hepatic and renal function in young trained rats.

    PubMed

    Souza, William Marciel; Heck, Thiago Gomes; Wronski, Evanio Castor; Ulbrich, Anderson Zampier; Boff, Everton

    2013-11-01

    Creatine supplementation has been widely used by athletes and young physical exercise practioneers in order of increasing muscle mass and enhancing athletic performance, but their use/overuse may represent a health risk on hepatic and renal impaired function. In this study, we evaluated the effects of 40 days of oral creatine supplementation on hepatic and renal function biomarkers in a young animal model. Wistar rats (5 weeks old) were divided in five groups (n = 7): control (CONTR), oral creatine supplementation (CREAT), moderate exercise training (EXERC), moderate exercise training plus oral creatine supplementation (EXERC + CREAT) and pathological group (positive control for liver and kidney injury) by the administration of rifampicin (RIFAMPICIN). Exercise groups were submitted to 60 min/day of swimming exercise session with a 4% of body weight workload for six weeks. The EXERC + CREAT showed the higher body weight at the end of the training protocol. The CREAT and EXERC + CREAT group showed an increase in hepatic (Aspartate transaminase and gamma-glutamyl transpeptidase) and renal (urea and creatinine) biomarkers levels (p < 0.05). Our study showed that the oral creatine supplementation promoted hepatic and renal function challenge in young rats submitted to moderate exercise training.

  6. Associations of lead biomarkers with renal function in Korean lead workers

    PubMed Central

    Weaver, V; Lee, B; Ahn, K; Lee, G; Todd, A; Stewart, W; Wen, J; Simon, D; Parsons, P; Schwartz, B

    2003-01-01

    Aims: To compare associations of lead biomarkers with renal function in current and former lead workers. Methods: Cross sectional analysis of first year results from a longitudinal study of 803 lead workers and 135 controls in South Korea. Clinical renal function was assessed by blood urea nitrogen (BUN), serum creatinine, and measured and calculated creatinine clearance. Urinary N-acetyl-ß-D-glucosaminidase (NAG) and retinol-binding protein were also measured. Results: Mean (SD) tibia lead, blood lead, and DMSA chelatable lead levels in lead workers were 37.2 (40.4) µg/g bone mineral, 32.0 (15.0) µg/dl, and 767.8 (862.1) µg/g creatinine, respectively. Higher lead measures were associated with worse renal function in 16/42 models. When influential outliers were removed, higher lead measures remained associated with worse renal function in nine models. An additional five associations were in the opposite direction. Effect modification by age was observed. In 3/16 models, associations between higher lead measures and worse clinical renal function in participants in the oldest age tertile were significantly different from associations in those in the youngest age tertile which were in the opposite direction. Mean urinary cadmium (CdU) was 1.1 µg/g creatinine (n = 191). Higher CdU levels were associated with higher NAG. Conclusions: These data suggest that lead has an adverse effect on renal function in the moderate dose range, particularly in older workers. Associations between higher lead measures and lower BUN and serum creatinine and higher creatinine clearances may represent lead induced hyperfiltration. Environmental cadmium may also have an adverse renal impact, at least on NAG. PMID:12883015

  7. Urinary Extracellular Vesicles: Potential Biomarkers of Renal Function in Diabetic Patients

    PubMed Central

    Platt, Mark; Kasprzyk, Joanna; Kuśnierz-Cabala, Beata; Gala-Błądzińska, Agnieszka; Woźnicka, Olga; Jany, Benedykt R.; Krok, Franciszek; Piekoszewski, Wojciech; Kuźniewski, Marek

    2016-01-01

    The aim of this study was to check the relationship between the density of urinary EVs, their size distribution, and the progress of early renal damage in type 2 diabetic patients (DMt2). Patients were enrolled to this study, and glycated hemoglobin (HbA1c) below 7% was a threshold for properly controlled diabetic patients (CD) and poorly controlled diabetic patients (UD). Patients were further divided into two groups: diabetic patients without renal failure (NRF) and with renal failure (RF) according to the Glomerular Filtration Rate. Density and diameter of EVs were determined by Tunable Resistive Pulse Sensing. Additionally, EVs were visualized by means of Transmission and Environmental Scanning Electron Microscopy. Nano-liquid chromatography coupled offline with mass spectrometry (MALDI-TOF-MS/MS) was applied for proteomic analysis. RF had reduced density of EVs compared to NRF. The size distribution study showed that CD had larger EVs (mode) than UD (115 versus 109 nm; p < 0.05); nevertheless the mean EVs diameter was smaller in controls than in the CD group (123 versus 134 nm; p < 0.05). It was demonstrated that EVs are abundant in urine. Albumin, uromodulin, and number of unique proteins related to cell stress and secretion were detected in the EVs fraction. Density and size of urinary EVs reflect deteriorated renal function and can be considered as potential renal damage biomarkers. PMID:28105442

  8. Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial

    PubMed Central

    Nadkarni, Girish N.; Rao, Veena; Ismail-Beigi, Faramarz; Fonseca, Vivian A.; Shah, Sudhir V.; Simonson, Michael S.; Cantley, Lloyd; Devarajan, Prasad; Parikh, Chirag R.

    2016-01-01

    Background and objectives Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome. Design, setting, participants, & measurements We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μg/mg, and baseline eGFR within 10 ml/min per 1.73 m2), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression. Results Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio. Conclusions Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2

  9. Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial.

    PubMed

    Nadkarni, Girish N; Rao, Veena; Ismail-Beigi, Faramarz; Fonseca, Vivian A; Shah, Sudhir V; Simonson, Michael S; Cantley, Lloyd; Devarajan, Prasad; Parikh, Chirag R; Coca, Steven G

    2016-08-08

    Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome. We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μg/mg, and baseline eGFR within 10 ml/min per 1.73 m(2)), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression. Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio. Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function. Copyright © 2016 by the American Society of

  10. Utility of Urinary Biomarkers in Predicting Loss of Residual Renal Function: The balANZ Trial

    PubMed Central

    Cho, Yeoungjee; Johnson, David W.; Vesey, David A.; Hawley, Carmel M.; Clarke, Margaret; Topley, Nicholas

    2015-01-01

    ♦ Background: The ability of urinary biomarkers to predict residual renal function (RRF) decline in peritoneal dialysis (PD) patients has not been defined. The present study aimed to explore the utility of established biomarkers from kidney injury models for predicting loss of RRF in incident PD patients, and to evaluate the impact on RRF of using neutral-pH PD solution low in glucose degradation products. ♦ Methods: The study included 50 randomly selected participants from the balANZ trial who had completed 24 months of follow-up. A change in glomerular filtration rate (GFR) was used as the primary clinical outcome measure. In a mixed-effects general linear model, baseline measurements of 18 novel urinary biomarkers and albumin were used to predict GFR change. The model was further used to evaluate the impact of biocompatible PD solution on RRF, adjusted for each biomarker. ♦ Results: Baseline albuminuria was not a useful predictor of change in RRF in PD patients (p = 0.84). Only clusterin was a significant predictor of GFR decline in the whole population (p = 0.04, adjusted for baseline GFR and albuminuria). However, the relationship was no longer apparent when albuminuria was removed from the model (p = 0.31). When the effect of the administered PD solutions was examined using a model adjusted for PD solution type, baseline albuminuria, and GFR, higher baseline urinary concentrations of trefoil factor 3 (TFF3, p = 0.02), kidney injury molecule 1 (KIM-1, p = 0.04), and interferon γ-induced protein 10 (IP-10, p = 0.03) were associated with more rapid decline of RRF in patients receiving conventional PD solution compared with biocompatible PD solution. ♦ Conclusions: Higher urinary levels of kidney injury biomarkers (TFF3, KIM-1, IP-10) at baseline predicted significantly slower RRF decline in patients receiving biocompatible PD solutions. Findings from the present investigation should help to guide future studies to validate the utility of urinary

  11. The ribosomal protein S6 in renal cell carcinoma: functional relevance and potential as biomarker

    PubMed Central

    Knoll, Maximilian; Macher-Goeppinger, Stephan; Kopitz, Jürgen; Duensing, Stefan; Pahernik, Sascha; Hohenfellner, Markus; Schirmacher, Peter; Roth, Wilfried

    2016-01-01

    Inhibitors of the mTOR pathway, such as everolimus, are promising compounds to treat patients with renal cell carcinomas (RCCs). However, the precise mechanisms of action are far from clear, and biomarkers predicting the response to mTOR inhibitors are still missing. Here, we provide evidence that in RCCs the rpS6 protein is the major mediator of anti-tumoral effects exerted by everolimus. Inhibition of mTOR signaling results in substantially decreased clonogenicity and proliferation of RCC cells, but did not significantly induce apoptosis. Everolimus effectively blocked protein biosynthesis both in vitro and in a novel ex vivo tissue slice model using fresh vital human RCC tissue. Compared to other components of the mTOR pathway, phosphorylation of rpS6 was most effectively downregulated by everolimus. Importantly, siRNA-mediated downregulation of rpS6, but not of 4ebp1 or p27, abolished the inhibitory effects of everolimus on proliferation and protein synthesis. Moreover, we analyzed the tissue expression of phosphorylated rpS6 (p-rpS6) and non-phosphorylated rpS6 in a large collection of patients with RCCs (n=598 and n=548, respectively). Expression of both proteins qualified as independent negative prognostic markers with a substantially shorter survival of patients with RCCs exhibiting high levels of rpS6 and p-rpS6. Taken together, our functional studies identified rpS6 as a main mediator of the anti-tumoral activity of Everolimus. Therefore, further (pre-)clinical evaluations of rpS6 as a predictive marker for everolimus-based treatment for RCC patients are warranted. Finally, the combined detection of phosphorylated and non-phosphorylated rpS6 could represent a robust prognostic marker to identify patients with high risk RCCs. PMID:26506236

  12. Biomarkers of renal cell carcinoma.

    PubMed

    Ngo, Tin C; Wood, Christopher G; Karam, Jose A

    2014-04-01

    The incidence of renal cell carcinoma (RCC) has increased steadily in past few decades and is partially attributable to the increased utilization of cross-sectional imaging. Many of these carcinomas are small incidental discoveries, although a subset leads to locally advanced or distant disease. Although its molecular pathophysiology is not completely understood, knowledge of hereditary RCCs has shed light on some of the pathways involved. More recently, the rapid advances in genomics, proteomics, and metabolomics have allowed for a deeper and more nuanced understanding of the genetic aberrations that lead up to and result from the transformation of a renal tubular epithelial cell into a carcinoma. These discoveries have allowed for the development of novel therapeutics that target these pathways. They have also led to the development of diagnostic, prognostic, and predictive biomarkers that could radically change the way RCC is diagnosed and treated. Although some of the current investigations are nascent and it remains to be seen which biomarkers will become clinically available, many candidate biomarkers show promise and require external validation. Ultimately, biomarkers may allow for cost-effective screening of high-risk patients, the identification of aggressive cancers among small renal masses, the identification of high-risk patients, the detection of recurrences postoperatively with minimal imaging, and the ability to choose appropriate targeted therapies for patients with metastatic disease.

  13. Hepcidin as a Biomarker of Impaired Renal Function in Rat Models for Chronic Allograft Nephropathy.

    PubMed

    Xue, Dong; Zhou, Cuixing; Shi, Yunbo; Lu, Hao; He, Xiaozhou

    2016-02-23

    BACKGROUND To explore the use of hepcidin as a marker of impaired renal function in a rat model for chronic allograft nephropathy (CAN). MATERIAL AND METHODS Twenty-four models were developed and 20 models were included in this study, using Fisher (F344) rats (donors) and Lewis rats (recipients). Renal function tests were performed preoperatively and postoperatively. Hepcidin, interleukin-6 (IL-6), and erythropoietin levels in serum and urine were measured by enzyme-linked immunosorbent assay (ELISA). To observe pathological changes in the kidneys, 10 rats each were sacrificed at 2 months and 4 months after surgery. RESULTS After transplantation, the serum hepcidin and IL-6 levels increased, while urine hepcidin levels decreased. Erythropoietin levels showed a similar trend; all P<0.05. Serum creatinine (SCr) and blood urea nitrogen significantly increased post-operatively, with SCr positively correlating with serum hepcidin. Serum hepcidin positively correlated with IL-6 and negatively correlated with EPO. Histopathological results were consistent with CAN, after transplantation. CONCLUSIONS Hepcidin may be considered as a potential marker of impaired renal function.

  14. Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

    PubMed Central

    Nkuipou-Kenfack, Esther; Duranton, Flore; Gayrard, Nathalie; Argilés, Àngel; Lundin, Ulrika; Weinberger, Klaus M.; Dakna, Mohammed; Delles, Christian; Mullen, William; Husi, Holger; Klein, Julie; Koeck, Thomas; Zürbig, Petra; Mischak, Harald

    2014-01-01

    Chronic kidney disease (CKD) is part of a number of systemic and renal diseases and may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis and management of CKD. We hypothesised that combining metabolomic and proteomic approaches could generate a more systemic and complete view of the disease mechanisms. To test this approach, we examined samples from a cohort of 49 patients representing different stages of CKD. Urine samples were analysed for proteomic changes using capillary electrophoresis-mass spectrometry and urine and plasma samples for metabolomic changes using different mass spectrometry-based techniques. The training set included 20 CKD patients selected according to their estimated glomerular filtration rate (eGFR) at mild (59.9±16.5 mL/min/1.73 m2; n = 10) or advanced (8.9±4.5 mL/min/1.73 m2; n = 10) CKD and the remaining 29 patients left for the test set. We identified a panel of 76 statistically significant metabolites and peptides that correlated with CKD in the training set. We combined these biomarkers in different classifiers and then performed correlation analyses with eGFR at baseline and follow-up after 2.8±0.8 years in the test set. A solely plasma metabolite biomarker-based classifier significantly correlated with the loss of kidney function in the test set at baseline and follow-up (ρ = −0.8031; p<0.0001 and ρ = −0.6009; p = 0.0019, respectively). Similarly, a urinary metabolite biomarker-based classifier did reveal significant association to kidney function (ρ = −0.6557; p = 0.0001 and ρ = −0.6574; p = 0.0005). A classifier utilising 46 identified urinary peptide biomarkers performed statistically equivalent to the urinary and plasma metabolite classifier (ρ = −0.7752; p<0.0001 and ρ = −0.8400; p<0.0001). The combination of both urinary proteomic and urinary and plasma metabolic biomarkers did not improve the correlation with eGFR. In

  15. Influence of renal impairment on myocardial function in outpatients with systolic heart failure: an echocardiographic and cardiac biomarker study.

    PubMed

    Bosselmann, Helle; Tonder, Niels; Sölétormos, György; Rossing, Kasper; Iversen, Kasper; Goetze, Jens P; Gustafsson, Finn; Schou, Morten

    2014-12-20

    Renal dysfunction (RD) is associated with poor outcome in systolic heart failure (HF). Left ventricular ejection fraction (LVEF) is not depressed to a greater extent in patients with RD compared to patients with normal renal function, but it is relatively unknown whether other measures of myocardial function are impaired by RD. The objective of the present study is to evaluate whether RD in systolic HF is associated with excessive impairment of myocardial function, evaluated by strain analysis and cardiac biomarkers. Patients with LVEF <0.45% were enrolled from an outpatient HF clinic. The patients underwent advanced echocardiography. Glomerular filtration rate was estimated by the CKD-EPI equation (eGFR) and patients grouped by eGFR: eGFR group-I, ≥ 90 ml/min/1.73 m(2); eGFR group-II, 60-89 ml/min/1.73 m(2); and eGFR group-III, ≤ 59 ml/min/1.73 m(2). Multivariate regression models were developed to evaluate the associations between eGFR groups, echocardiographic measures and cardiac biomarkers. A total of 149 patients participated in the study. Median age was 69 years, 26% were female; LVEF was 33%. Patients with a low eGFR were older (P < 0.001), but there were no differences in frequency of atrial fibrillation, hypertension, diabetes and ischemic heart disease between eGFR groups (P > 0.05 for all). RD was associated with impaired global longitudinal strain (P = 0.018), increased E/e' (P = 0.032), larger left atria (P = 0.038) and increased levels of proANP (P < 0.001), NT-proBNP (P < 0.001) and troponin I (P = 0.019) after adjustment for traditional confounders. Echocardiographic measures and biomarkers reflecting different aspects of myocardial function are impaired in systolic HF patients with RD and the increased mortality risk in these patients may partly be explained by a depressed cardiac function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Associations between biomarkers of renal function with cerebral microbleeds in hypertensive patients.

    PubMed

    Zhang, Jin-biao; Liu, Li-feng; Li, Zhen-guang; Sun, Hai-rong; Jü, Xiao-hua

    2015-06-01

    Cerebral microbleeds (CMBs) have been observed in the elderly and have been regarded as a manifestation of small vessel disease (SVD). Cerebral and glomerular SVD may have a common source of pathogenesis because these organs are closely connected through anatomic and hemodynamic similarities. The purpose of this study was to clarify the associations between kidney biomarker levels and CMBs in hypertensive patients. The presence and number of CMBs were assessed on susceptibility-weighted imaging. We calculated the urinary albumin/creatinine ratio (UACR) from morning spot urine and the estimated glomerular filtration rate (eGFR) in serum samples. Serum cystatin C (CysC) was measured with an automated particle-enhanced turbidimetric immunoassay. UACR and CysC levels were higher in the patients with CMBs than those without, and the eGFR was lower in the patients with CMBs than those without. A logistic regression analysis indicates that eGFR and UACR were independently associated with the prevalence of deep or infratentorial CMBs. The odds ratio (OR) (95% confidence interval (CI)) of eGFR and UACR was 1.95 (1.37-3.27) and 2.25 (1.66-4.46), respectively. CysC was independently associated with CMBs in both deep or infratentorial and lobar locations. The ORs (95% CI) were 2.59 (1.57-6.22) and 1.57 (1.15-4.85), respectively. Furthermore, CysC exhibited fair diagnostic value for CMBs, with an area under the curve of 0.80. Kidney biomarker levels are associated with the presence of CMB in hypertensive patients without a history of transient ischemic attack (TIA) or stroke, independent of conventional risk factors, and CysC was a better marker for CMBs than eGFR and UACR. © Crown copyright 2014.

  17. Novel Renal Biomarkers to Assess Cardiorenal Syndrome

    PubMed Central

    Brisco, Meredith A.; Testani, Jeffrey M.

    2014-01-01

    Renal dysfunction (RD) in heart failure portends adverse outcomes and often limits aggressive medical and decongestive therapies. Despite the high prevalence in this population, not all forms of RD are prognostically or mechanistically equivalent: RD can result from irreversible nephron loss secondary to diabetic or hypertensive kidney disease or it can develop secondary to the HF itself, i.e. the cardiorenal syndrome. Furthermore, filtration is only one aspect of renal performance such that significant renal impairment secondary to cardiorenal syndrome can exist despite a normal glomerular filtration rate. Renal biomarkers have the potential to inform some of the intricacies involved in accurately assessing cardiorenal interactions. This article discusses novel biomarkers for cardiorenal syndrome and their utility in prognosis, diagnosis, and targeted treatment of heart failure-induced RD. PMID:25239434

  18. Renal tumors: diagnostic and prognostic biomarkers.

    PubMed

    Tan, Puay Hoon; Cheng, Liang; Rioux-Leclercq, Nathalie; Merino, Maria J; Netto, George; Reuter, Victor E; Shen, Steven S; Grignon, David J; Montironi, Rodolfo; Egevad, Lars; Srigley, John R; Delahunt, Brett; Moch, Holger

    2013-10-01

    The International Society of Urological Pathology convened a consensus conference on renal cancer, preceded by an online survey, to address issues relating to the diagnosis and reporting of renal neoplasia. In this report, the role of biomarkers in the diagnosis and assessment of prognosis of renal tumors is addressed. In particular we focused upon the use of immunohistochemical markers and the approach to specific differential diagnostic scenarios. We enquired whether cytogenetic and molecular tools were applied in practice and asked for views on the perceived prognostic role of biomarkers. Both the survey and conference voting results demonstrated a high degree of consensus in participants' responses regarding prognostic/predictive markers and molecular techniques, whereas it was apparent that biomarkers for these purposes remained outside the diagnostic realm pending clinical validation. Although no individual antibody or panel of antibodies reached consensus for classifying renal tumors, or for confirming renal metastatic disease, it was noted from the online survey that 87% of respondents used immunohistochemistry to subtype renal tumors sometimes or occasionally, and a majority (87%) used immunohistochemical markers (Pax 2 or Pax 8, renal cell carcinoma [RCC] marker, panel of pan-CK, CK7, vimentin, and CD10) in confirming the diagnosis of metastatic RCC. There was consensus that immunohistochemistry should be used for histologic subtyping and applied before reaching a diagnosis of unclassified RCC. At the conference, there was consensus that TFE3 and TFEB analysis ought to be requested when RCC was diagnosed in a young patient or when histologic appearances were suggestive of the translocation subtype; whereas Pax 2 and/or Pax 8 were considered to be the most useful markers in the diagnosis of a renal primary.

  19. Functions of the Renal Nerves.

    ERIC Educational Resources Information Center

    Koepke, John P.; DiBona, Gerald F.

    1985-01-01

    Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…

  20. Functions of the Renal Nerves.

    ERIC Educational Resources Information Center

    Koepke, John P.; DiBona, Gerald F.

    1985-01-01

    Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…

  1. MicroRNA biomarkers in clinical renal disease: from diabetic nephropathy renal transplantation and beyond.

    PubMed

    Nassirpour, Rounak; Raj, Dominic; Townsend, Raymond; Argyropoulos, Christos

    2016-12-01

    Chronic Kidney Disease (CKD) is a common health problem affecting 1 in 12 Americans. It is associated with elevated risks of mortality, cardiovascular disease, and high costs for the treatment of renal failure with dialysis or transplantation. Advances in CKD care are impeded by the lack of biomarkers for early diagnosis, assessment of the extent of tissue injury, estimation of disease progression, and evaluation of response to therapy. Such biomarkers should improve the performance of existing measures of renal functional impairment (estimated glomerular filtration rate, eGFR) or kidney damage (proteinuria). MicroRNAs (miRNAs) a class of small, non-coding RNAs that act as post-transcriptional repressors are gaining momentum as biomarkers in a number of disease areas. In this review, we examine the potential utility of miRNAs as promising biomarkers for renal disease. We explore the performance of miRNAs as biomarkers in two clinically important forms of CKD, diabetes and the nephropathy developing in kidney transplant recipients. Finally, we highlight the pitfalls and opportunities of miRNAs and provide a broad perspective for the future clinical development of miRNAs as biomarkers in CKD beyond the current gold standards of eGFR and albuminuria.

  2. Evaluation of White Sesame Seed Oil on Glucose Control and Biomarkers of Hepatic, Cardiac, and Renal Functions in Male Sprague-Dawley Rats with Chemically Induced Diabetes.

    PubMed

    Aslam, Farhan; Iqbal, Sanaullah; Nasir, Muhammad; Anjum, Aftab Ahmad; Swan, Pamela; Sweazea, Karen

    2017-05-01

    White sesame seed oil (WSSO) has been used in cooking and food preparations for centuries. It has many purported health benefits and may be a promising nutraceutical. The primary purpose of this study was to examine the effects of WSSO on fasting blood glucose (GLU) and insulin (INS) in male Sprague-Dawley rats with chemically induced diabetes. A secondary aim was to explore other hematological biomarkers of hepatic, cardiac, and renal function. Sixty-three male Sprague-Dawley rats were randomized into standard diet groups, normal control (NCON) (n = 21) and diabetic control (DCON) (n = 21), and a diabetic sesame oil (DSO) (n = 21) group, which were fed a diet containing 12% WSSO. Blood samples were analyzed at 0, 30, and 60 days. Differences between groups and across days were assessed with two-way repeated measures analysis of variance. At baseline, GLU and INS were similar in both diabetic groups, mean 248.4 ± 2.8 mg/dL and mean 23.4 ± 0.4 μU/mL, respectively. At 60 days, GLU was significantly (P < .05) higher in DCON (298.0 ± 2.3 mg/dL) compared with DSO (202.1 ± 1.0 mg/dL). INS showed similar favorable trends after WSSO supplementation. Consumption of WSSO significantly improved glucose control and other biomarkers of hepatic stress, as well as cardiac and renal health. WSSO may be a viable functional food to help reduce the detrimental effects of diabetes.

  3. GlycA, a Pro-Inflammatory Glycoprotein Biomarker, and Incident Cardiovascular Disease: Relationship with C-Reactive Protein and Renal Function.

    PubMed

    Gruppen, Eke G; Riphagen, Ineke J; Connelly, Margery A; Otvos, James D; Bakker, Stephan J L; Dullaart, Robin P F

    2015-01-01

    GlycA is a novel nuclear magnetic resonance spectroscopy-measured biomarker of systemic inflammation. We determined whether GlycA is associated with incident cardiovascular disease (CVD) in men and women, examined whether this association with CVD is modified by renal function, and compared this association with high sensitivity C-reactive protein (hsCRP). A prospective cohort study was performed among 4,759 subjects (PREVEND study) without a history of CVD and cancer. Incident CVD was defined as the combined endpoint of cardiovascular morbidity and mortality. Cox regression analyses were used to examine associations of baseline GlycA and hsCRP with CVD. 298 first CVD events occurred during a median follow-up of 8.5 years. After adjustment for clinical and lipid measures the hazard ratio (HR) for CVD risk in the highest GlycA quartile was 1.58 (95% CI, 1.05-2.37, P for trend = 0.004). This association was similar after further adjustment for renal function (estimated glomerular filtration rate and urinary albumin excretion). After additional adjustment for hsCRP, GlycA was still associated with incident CVD (HR: 1.16 per SD change (95% CI, 1.01-1.33), P = 0.04). Similar results were obtained for hsCRP (HR per SD change after adjustment for GlycA: 1.17 (95% CI 1.17 (95% CI, 1.01-3.60), P = 0.04). CVD risk was highest in subjects with simultaneously higher GlycA and hsCRP (fully adjusted HR: 1.79 (95% CI, 1.31-2.46), P<0.001). GlycA is associated with CVD risk in men and women, independent of renal function. The association of GlycA with incident CVD is as strong as that of hsCRP.

  4. Prognostic clinical and molecular biomarkers of renal disease in type 2 diabetes.

    PubMed

    Pena, Michelle J; de Zeeuw, Dick; Mischak, Harald; Jankowski, Joachim; Oberbauer, Rainer; Woloszczuk, Wolfgang; Benner, Jacqueline; Dallmann, Guido; Mayer, Bernd; Mayer, Gert; Rossing, Peter; Lambers Heerspink, Hiddo J

    2015-08-01

    Diabetic kidney disease occurs in ∼ 25-40% of patients with type 2 diabetes. Given the high risk of progressive renal function loss and end-stage renal disease, early identification of patients with a renal risk is important. Novel biomarkers may aid in improving renal risk stratification. In this review, we first focus on the classical panel of albuminuria and estimated glomerular filtration rate as the primary clinical predictors of renal disease and then move our attention to novel biomarkers, primarily concentrating on assay-based multiple/panel biomarkers, proteomics biomarkers and metabolomics biomarkers. We focus on multiple biomarker panels since the molecular processes of renal disease progression in type 2 diabetes are heterogeneous, rendering it unlikely that a single biomarker significantly adds to clinical risk prediction. A limited number of prospective studies of multiple biomarkers address the predictive performance of novel biomarker panels in addition to the classical panel in type 2 diabetes. However, the prospective studies conducted so far have small sample sizes, are insufficiently powered and lack external validation. Adequately sized validation studies of multiple biomarker panels are thus required. There is also a paucity of studies that assess the effect of treatments on novel biomarker panels and determine whether initial treatment-induced changes in novel biomarkers predict changes in long-term renal outcomes. Such studies can not only improve our healthcare but also our understanding of the mechanisms of actions of existing and novel drugs and may yield biomarkers that can be used to monitor drug response. We conclude that this will be an area to focus research on in the future. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  5. Magnetic Resonance Imaging as a Biomarker for Renal Cell Carcinoma

    PubMed Central

    Wu, Yan; Kwon, Young Suk; Labib, Mina; Foran, David J.; Singer, Eric A.

    2015-01-01

    As the most common neoplasm arising from the kidney, renal cell carcinoma (RCC) continues to have a significant impact on global health. Conventional cross-sectional imaging has always served an important role in the staging of RCC. However, with recent advances in imaging techniques and postprocessing analysis, magnetic resonance imaging (MRI) now has the capability to function as a diagnostic, therapeutic, and prognostic biomarker for RCC. For this narrative literature review, a PubMed search was conducted to collect the most relevant and impactful studies from our perspectives as urologic oncologists, radiologists, and computational imaging specialists. We seek to cover advanced MR imaging and image analysis techniques that may improve the management of patients with small renal mass or metastatic renal cell carcinoma. PMID:26609190

  6. Soluble biglycan as a biomarker of inflammatory renal diseases

    PubMed Central

    Hsieh, Louise Tzung-Harn; Nastase, Madalina-Viviana; Zeng-Brouwers, Jinyang; Iozzo, Renato V.; Schaefer, Liliana

    2014-01-01

    Chronic renal inflammation is often associated with a progressive accumulation of various extracellular matrix constituents, including several members of the small leucine-rich proteoglycan (SLRP) gene family. It is becoming increasingly evident that the matrix-unbound SLRPs strongly regulate the progression of inflammation and fibrosis. Soluble SLRPs are generated either via partial proteolytic processing of collagenous matrices or by de novo synthesis evoked by stress or injury. Liberated SLRPs can then bind to and activate Toll-like receptors, thus modulating downstream inflammatory signaling. Preclinical animal models and human studies have recently identified soluble biglycan as a key initiator and regulator of various inflammatory renal diseases. Biglycan, generated by activated macrophages, can enter the circulation and its elevated levels in plasma and renal parenchyma correlate with unfavorable renal function and outcome. In this review, we will focus on the critical role of soluble biglycan in inflammatory signaling in various renal disorders. Moreover, we will provide new data implicating proinflammatory effects of soluble decorin in unilateral ureteral obstruction. Finally, we will critically evaluate the potential application of soluble biglycan vis-à-vis other SLRPs (decorin, lumican and fibromodulin) as a promising target and novel biomarker of inflammatory renal diseases. PMID:25091702

  7. Discovering Biomarkers within the Genomic Landscape of Renal Cell Carcinoma

    PubMed Central

    A, Sankin

    2016-01-01

    Recent advances in molecular sequencing technology have led to the discovery of numerous biomarkers in renal cell carcinoma (RCC). These biomarkers have the potential to predict clinical outcomes and aid in clinical management decisions. The following commentary is a review of the preliminary data on some of the most promising genetic biomarker candidates. PMID:27104219

  8. Discovering Biomarkers within the Genomic Landscape of Renal Cell Carcinoma.

    PubMed

    A, Sankin

    2016-02-01

    Recent advances in molecular sequencing technology have led to the discovery of numerous biomarkers in renal cell carcinoma (RCC). These biomarkers have the potential to predict clinical outcomes and aid in clinical management decisions. The following commentary is a review of the preliminary data on some of the most promising genetic biomarker candidates.

  9. GlycA, a Pro-Inflammatory Glycoprotein Biomarker, and Incident Cardiovascular Disease: Relationship with C-Reactive Protein and Renal Function

    PubMed Central

    Gruppen, Eke G.; Riphagen, Ineke J.; Connelly, Margery A.; Otvos, James D.; Bakker, Stephan J. L.; Dullaart, Robin P. F.

    2015-01-01

    Objective GlycA is a novel nuclear magnetic resonance spectroscopy-measured biomarker of systemic inflammation. We determined whether GlycA is associated with incident cardiovascular disease (CVD) in men and women, examined whether this association with CVD is modified by renal function, and compared this association with high sensitivity C-reactive protein (hsCRP). Research design and methods A prospective cohort study was performed among 4,759 subjects (PREVEND study) without a history of CVD and cancer. Incident CVD was defined as the combined endpoint of cardiovascular morbidity and mortality. Cox regression analyses were used to examine associations of baseline GlycA and hsCRP with CVD. Results 298 first CVD events occurred during a median follow-up of 8.5 years. After adjustment for clinical and lipid measures the hazard ratio (HR) for CVD risk in the highest GlycA quartile was 1.58 (95% CI, 1.05–2.37, P for trend = 0.004). This association was similar after further adjustment for renal function (estimated glomerular filtration rate and urinary albumin excretion). After additional adjustment for hsCRP, GlycA was still associated with incident CVD (HR: 1.16 per SD change (95% CI, 1.01–1.33), P = 0.04). Similar results were obtained for hsCRP (HR per SD change after adjustment for GlycA: 1.17 (95% CI 1.17 (95% CI, 1.01–3.60), P = 0.04). CVD risk was highest in subjects with simultaneously higher GlycA and hsCRP (fully adjusted HR: 1.79 (95% CI, 1.31–2.46), P<0.001). Conclusion GlycA is associated with CVD risk in men and women, independent of renal function. The association of GlycA with incident CVD is as strong as that of hsCRP. PMID:26398105

  10. Effect of food azo dyes tartrazine and carmoisine on biochemical parameters related to renal, hepatic function and oxidative stress biomarkers in young male rats.

    PubMed

    Amin, K A; Abdel Hameid, H; Abd Elsttar, A H

    2010-10-01

    Tartrazine and carmoisine are an organic azo dyes widely used in food products, drugs and cosmetics. The present study conducted to evaluate the toxic effect of these coloring food additives; on renal, hepatic function, lipid profile, blood glucose, body-weight gain and biomarkers of oxidative stress in tissue. Tartrazine and carmoisine were administered orally in two doses, one low and the other high dose for 30 days followed by serum and tissue sample collection for determination of ALT, AST, ALP, urea, creatinine, total protein, albumin, lipid profile, fasting blood glucose in serum and estimation of GSH, catalase, SOD and MDA in liver tissue in male albino rat. Our data showed a significant increase in ALT, AST, ALP, urea, creatinine total protein and albumin in serum of rats dosed with tartrazine and carmoisine compared to control rats and these significant change were more apparent in high doses than low, GSH, SOD and Catalase were decreased and MDA increased in tissue homogenate in rats consumed high tartrazine and both doses of carmoisine. We concluded that tartrazine and carmoisine affect adversely and alter biochemical markers in vital organs e.g. liver and kidney not only at higher doses but also at low doses.

  11. LITHIUM AND RENAL FUNCTIONS

    PubMed Central

    Sethi, N.; Trivedi, J.K.; Sethi, B.B.

    1987-01-01

    SUMMARY Thirty patients of affective disorder who were on lithium for a year and thirty patients on antidepressant were studied in detail for renal functions. Our observation is that lithium therapy does not lead to any deterioration in kidney functions. The results are discussed. PMID:21927211

  12. The impact of oat (Avena sativa) consumption on biomarkers of renal function in patients with chronic kidney disease: A parallel randomized clinical trial.

    PubMed

    Rouhani, Mohammad Hossein; Mortazavi Najafabadi, Mojgan; Surkan, Pamela J; Esmaillzadeh, Ahmad; Feizi, Awat; Azadbakht, Leila

    2016-12-02

    Animal studies report that oat (Avena sativa L) intake has favorable effects on kidney function. However, the effects of oat consumption have not been assessed in humans. The aim of this study was to examine the impact of oat intake on biomarkers of renal function in patients with chronic kidney disease (CKD). Fifty-two patients with CKD were randomly assigned to a control group (recommended to reduce intake of dietary protein, phosphorus, sodium and potassium) or an oat consumption group (given nutritional recommendations for controls +50 g/day oats). Blood urea nitrogen (BUN), serum creatinine (SCr), urine creatinine, serum albumin, serum potassium, parathyroid hormone (PTH), serum klotho and urine protein concentration were measured at baseline and after an eight-week intervention. Creatinine clearance was calculated using urine creatinine concentration. Within group analysis showed a significant increase in BUN (P = 0.02) and serum potassium (P = 0.01) and a marginally significant increment in SCr (P = 0.08) among controls. However, changes in the oat group were not significant. In a multivariate adjusted model, we observed a significant difference in change of serum potassium (-0.03 mEq/L for oat group and 0.13 mEq/L for control group; P = 0.01) and a marginally significant difference in change of serum albumin (0.01 g/dl for oat group and -0.08 for control group; P = 0.08) between the two groups. There was no change in PTH concentration. Intake of oats may have a beneficial effect on serum albumin and serum potassium in patients with CKD. Present study registered under IRCT.ir identifier no. IRCT2015050414551N2. Copyright © 2016. Published by Elsevier Ltd.

  13. Renal function assessment in heart failure.

    PubMed

    Pérez Calvo, J I; Josa Laorden, C; Giménez López, I

    Renal function is one of the most consistent prognostic determinants in heart failure. The prognostic information it provides is independent of the ejection fraction and functional status. This article reviews the various renal function assessment measures, with special emphasis on the fact that the patient's clinical situation and response to the heart failure treatment should be considered for the correct interpretation of the results. Finally, we review the literature on the performance of tubular damage biomarkers. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  14. New Biomarkers of Acute Kidney Injury and the Cardio-renal Syndrome

    PubMed Central

    2011-01-01

    Changes in renal function are one of the most common manifestations of severe illness. There is a clinical need to intervene early with proven treatments in patients with potentially deleterious changes in renal function. Unfortunately progress has been hindered by poor definitions of renal dysfunction and a lack of early biomarkers of renal injury. In recent years, the definitional problem has been addressed with the establishment of a new well-defined diagnostic entity, acute kidney injury (AKI), which encompasses the wide spectrum of kidney dysfunction, together with clearer definition and sub-classification of the cardio-renal syndromes. From the laboratory have emerged new biomarkers which allow early detection of AKI, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C. This review describes the new concepts of AKI and the cardio-renal syndromes as well as novel biomarkers which allow early detection of AKI. Panels of AKI biomarker tests are likely to revolutionise the diagnosis and management of critically ill patients in the coming years. Earlier diagnosis and intervention should significantly reduce the morbidity and mortality associated with acute kidney damage. PMID:21474979

  15. The ischemic/nephrotoxic acute kidney injury and the use of renal biomarkers in clinical practice.

    PubMed

    Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Perticone, Maria; Michael, Ashour

    2017-04-01

    The term Acute Renal Failure (ARF) has been replaced by the term Acute Kidney Injury (AKI). AKI indicates an abrupt (within 24-48h) decrease in Glomerular Filtraton Rate, due to renal damage, that causes fluid and metabolic waste retention and alteration of electrolyte and acid-base balance. The renal biomarkers of AKI are substances or processes that are indicators of normal or impaired function of the kidney. The most used renal biomarker is still serum creatinine that is inadequate for several reasons, one of which is its inability to differentiate between hemodynamic changes of renal function ("prerenal azotemia") from intrinsic renal failure or obstructive nephropathy. Cystatin C is no better in this respect. After the description of the pathophysiology of "prerenal azotemia" and of Acute Kidney Injury (AKI) due to ischemia or nephrotoxicity, the renal biomarkers are listed and described: urinary NAG, urinary and serum KIM-1, serum and urinary NGAL, urinary IL-18, urinary L-FABP, serum Midkine, urinary IGFBP7 and TIMP2, urinary α-GST and π-GST, urinary ɣGT and AP, urinary β2M, urinary RBP, serum and urinary miRNA. All have been shown to appear much earlier than the rise of serum Creatinine. Some of them have been demonstrated to predict the clinical outcomes of AKI, such as the need for initiation of dialysis and mortality.

  16. Plasma kininogen and kininogen fragments are biomarkers of progressive renal decline in type-1 diabetes

    PubMed Central

    Merchant, Michael L.; Niewczas, Monika; Ficociello, Linda H.; Lukenbill, Janice; Wilkey, Daniel W.; Li, Ming; Khundmiri, Syed J.; Warram, James H.; Krolewski, Andrzej S.; Klein, Jon B.

    2013-01-01

    The ability of microalbuminuria to predict early progressive renal function decline in type-1 diabetic patients has been questioned. To resolve this, we determined the plasma proteome differences between microalbuminuric patients with type-1 diabetes and stable renal function (controls) and patients at risk for early progressive renal function decline (cases) and asked whether these differences have value as surrogate biomarkers. Mass spectrometry was used to analyze small (less than 3 kDa) plasma peptides isolated from well-matched case and control plasma obtained at the beginning of an 8-12 year follow-up period. Spearman analysis of plasma peptide abundance and the rate of renal function decline during follow-up identified seven masses with a significant negative correlation with early progressive renal function decline. Tandem mass spectrometry identified three fragments of high molecular weight kininogen. Increased plasma high molecular weight kininogen in the cases was confirmed by immunoblot. One peptide, des-Arg9-BK(1-8), induced Erk1/2 phosphorylation when added apically to two proximal tubular cell lines grown on permeable inserts. Thus, we have identified plasma protein fragments, some of which have biological activity with moderate to strong correlation, with early progressive renal function decline in microalbuminuric patients with type-1 diabetes. Other peptides are candidates for validation as candidate biomarkers of diabetes-associated renal dysfunction. PMID:23466993

  17. [Definition and biomarkers of acute renal damage: new perspectives].

    PubMed

    Seijas, M; Baccino, C; Nin, N; Lorente, J A

    2014-01-01

    The RIFLE and AKIN criteria have definitely help out to draw attention to the relationship between a deterioration of renal function that produces a small increase in serum creatinine and a worse outcome. However, the specific clinical utility of using these criteria remains to be well-defined. It is believed that the main use of these criteria is for the design of epidemiological studies and clinical trials to define inclusion criteria and objectives of an intervention. AKI adopting term, re-summoning former ARF terminology, it is appropriate to describe the clinical condition characterized by damage to kidney, in the same way as the term is used to describe acute lung damage where the lung injury situation still has not increased to a situation of organ failure (dysfunction). The serum and urine biomarkers (creatinine, urea, and diuresis) currently in use are not sensitive or specific for detecting kidney damage, limiting treatment options and potentially compromising the outcome. New biomarkers are being studied in order to diagnose an earlier and more specific AKI, with the potential to change the definition criteria of AKI with different stages, currently based in diuresis and serum creatinine. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  18. Extracellular Vesicles in Renal Diseases: More than Novel Biomarkers?

    PubMed Central

    Le, Thu H.

    2016-01-01

    Extracellular vesicles from the urine and circulation have gained significant interest as potential diagnostic biomarkers in renal diseases. Urinary extracellular vesicles contain proteins from all sections of the nephron, whereas most studied circulating extracellular vesicles are derived from platelets, immune cells, and the endothelium. In addition to their diagnostic role as markers of kidney and vascular damage, extracellular vesicles may have functional significance in renal health and disease by facilitating communication between cells and protecting against kidney injury and bacterial infection in the urinary tract. However, the current understanding of extracellular vesicles has derived mostly from studies with very small numbers of patients or in vitro data. Moreover, accurate assessment of these vesicles remains a challenge, in part because of a lack of consensus in the methodologies to measure extracellular vesicles and the inability of most techniques to capture the entire size range of these vesicles. However, newer techniques and standardized protocols to improve the detection of extracellular vesicles are in development. A clearer understanding of the composition and biology of extracellular vesicles will provide insights into their pathophysiologic, diagnostic, and therapeutic roles. PMID:26251351

  19. Extracellular Vesicles in Renal Diseases: More than Novel Biomarkers?

    PubMed

    Erdbrügger, Uta; Le, Thu H

    2016-01-01

    Extracellular vesicles from the urine and circulation have gained significant interest as potential diagnostic biomarkers in renal diseases. Urinary extracellular vesicles contain proteins from all sections of the nephron, whereas most studied circulating extracellular vesicles are derived from platelets, immune cells, and the endothelium. In addition to their diagnostic role as markers of kidney and vascular damage, extracellular vesicles may have functional significance in renal health and disease by facilitating communication between cells and protecting against kidney injury and bacterial infection in the urinary tract. However, the current understanding of extracellular vesicles has derived mostly from studies with very small numbers of patients or in vitro data. Moreover, accurate assessment of these vesicles remains a challenge, in part because of a lack of consensus in the methodologies to measure extracellular vesicles and the inability of most techniques to capture the entire size range of these vesicles. However, newer techniques and standardized protocols to improve the detection of extracellular vesicles are in development. A clearer understanding of the composition and biology of extracellular vesicles will provide insights into their pathophysiologic, diagnostic, and therapeutic roles. Copyright © 2016 by the American Society of Nephrology.

  20. Urinary C-type natriuretic peptide: an emerging biomarker for heart failure and renal remodeling.

    PubMed

    Zakeri, Rosita; Burnett, John C; Sangaralingham, S Jeson

    2015-03-30

    The public health and economic burden of heart failure (HF) is staggering and the need for relevant pathophysiologic and clinical biomarkers to advance the field and improve HF therapy remains high. Renal dysfunction is common among HF patients and is associated with increased HF hospitalization and mortality. It is widely recognized that mechanisms contributing to HF pathogenesis include a complex bidirectional interaction between the kidney and heart, encompassed by the term cardiorenal syndrome (CRS). Among a new wave of urinary biomarkers germane to CRS, C-type natriuretic peptide (CNP) has emerged as an innovative biomarker of renal structural and functional impairment in HF and chronic renal disease states. CNP is a hormone, synthesized in the kidney, and is an important regulator of cell proliferation and organ fibrosis. Hypoxia, cytokines and fibrotic growth factors, which are inherent to both cardiac and renal remodeling processes, are among the recognized stimuli for CNP production and release. In this review we aim to highlight current knowledge regarding the biology and pathophysiological correlates of urinary CNP, and its potential clinical utility as a diagnostic and prognostic biomarker in HF and renal disease states. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Characterization of renal biomarkers for use in clinical trials: biomarker evaluation in healthy volunteers

    PubMed Central

    Brott, David A; Adler, Scott H; Arani, Ramin; Lovick, Susan C; Pinches, Mark; Furlong, Stephen T

    2014-01-01

    Background Several preclinical urinary biomarkers have been qualified and accepted by the health authorities (US Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency) for detecting drug-induced kidney injury during preclinical toxicologic testing. Validated human assays for many of these biomarkers have become commercially available, and this study was designed to characterize some of the novel clinical renal biomarkers. The objective of this study was to evaluate clinical renal biomarkers in a typical Phase I healthy volunteer population to determine confidence intervals (pilot reference intervals), intersubject and intrasubject variability, effects of food intake, effect of sex, and vendor assay comparisons. Methods Spot urine samples from 20 male and 19 female healthy volunteers collected on multiple days were analyzed using single analyte and multiplex assays. The following analytes were measured: α-1-microglobulin, β-2-microglobulin, calbindin, clusterin, connective tissue growth factor, creatinine, cystatin C, glutathione S-transferase-α, kidney injury marker-1, microalbumin, N-acetyl-β-(D) glucosaminidase, neutrophil gelatinase-associated lipocalin, osteopontin, Tamm-Horsfall urinary glycoprotein, tissue inhibitor of metalloproteinase 1, trefoil factor 3, and vascular endothelial growth factor. Results Confidence intervals were determined from the single analyte and multiplex assays. Intersubject and intrasubject variability ranged from 38% to 299% and from 29% to 82% for biomarker concentration, and from 24% to 331% and from 10% to 67% for biomarker concentration normalized to creatinine, respectively. There was no major effect of food intake or sex. Single analyte and multiplex assays correlated with r2≥0.700 for five of six biomarkers when evaluating biomarker concentration, but for only two biomarkers when evaluating concentration normalized to creatinine. Conclusion Confidence intervals as well as

  2. Radionuclide evaluation of renal function.

    PubMed

    Bueschen, A J; Witten, D M

    1979-06-01

    The renal scintillation camera study and the excretory urogram should be considered to be complementary studies. The renal scintillation camera study provides an accurate evaluation of changes in total, differential, and segmental renal function but affords only a gross assessment of anatomic changes. The excretory urogram provides superior information about renal anatomic changes but only inferior information about functional changes of the kidney. The advantages of a renal scintillation camera study with regard to the patient are that it is done in a state of normal hydration, it requires no bowel preparation, it is not associated with allergic reactions, it provides a low radiation exposure, and it is a noninvasive procedure for differential renal function which requires no ureteral catheters.

  3. Neural control of renal function.

    PubMed

    Johns, Edward J; Kopp, Ulla C; DiBona, Gerald F

    2011-04-01

    The kidney is innervated with efferent sympathetic nerve fibers that directly contact the vasculature, the renal tubules, and the juxtaglomerular granular cells. Via specific adrenoceptors, increased efferent renal sympathetic nerve activity decreases renal blood flow and glomerular filtration rate, increases renal tubular sodium and water reabsorption, and increases renin release. Decreased efferent renal sympathetic nerve activity produces opposite functional responses. This integrated system contributes importantly to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease. The kidney contains afferent sensory nerve fibers that are located primarily in the renal pelvic wall where they sense stretch. Stretch activation of these afferent sensory nerve fibers elicits an inhibitory renorenal reflex response wherein the contralateral kidney exhibits a compensatory natriuresis and diuresis due to diminished efferent renal sympathetic nerve activity. The renorenal reflex coordinates the excretory function of the two kidneys so as to facilitate homeostatic regulation of sodium and water balance. There is a negative feedback loop in which efferent renal sympathetic nerve activity facilitates increases in afferent renal nerve activity that in turn inhibit efferent renal sympathetic nerve activity so as to avoid excess renal sodium retention. In states of renal disease or injury, there is activation of afferent sensory nerve fibers that are excitatory, leading to increased peripheral sympathetic nerve activity, vasoconstriction, and increased arterial pressure. Proof of principle studies in essential hypertensive patients demonstrate that renal denervation produces sustained decreases in arterial pressure. © 2011 American Physiological Society. Compr Physiol 1:699-729, 2011.

  4. Biomarkers of Renal Tumor Burden and Progression in TSC

    DTIC Science & Technology

    2013-09-01

    AD_________________ Award Number: W81XWH-10- 1 -0433 TITLE: Biomarkers of Renal Tumor Burden and...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching...ADDRESS. 1 . REPORT DATE September 2013 2. REPORT TYPE Final 3. DATES COVERED 1 September 2010 - 31 August 2013 4. TITLE AND SUBTITLE 5a

  5. Urinary mitochondrial DNA is a biomarker of mitochondrial disruption and renal dysfunction in acute kidney injury

    PubMed Central

    Whitaker, Ryan M.; Stallons, L. Jay; Kneff, Joshua E.; Alge, Joseph L.; Harmon, Jennifer L.; Rahn, Jennifer J.; Arthur, John M.; Beeson, Craig C.; Chan, Sherine L.; Schnellmann, Rick G.

    2015-01-01

    Recent studies show the importance of mitochondrial dysfunction in the initiation and progression of acute kidney injury (AKI). However, no biomarkers exist linking renal injury to mitochondrial function and integrity. To this end, we evaluated urinary mitochondrial DNA (UmtDNA) as a biomarker of renal injury and function in humans with AKI following cardiac surgery. mtDNA was isolated from the urine of patients following cardiac surgery and quantified by qPCR. Patients were stratified into no AKI, stable AKI and progressive AKI groups based on Acute Kidney Injury Network (AKIN) staging. UmtDNA was elevated in progressive AKI patients, and was associated with progression of patients with AKI at collection to higher AKIN stages. To evaluate the relationship of UmtDNA to measures of renal mitochondrial integrity in AKI, mice were subjected to sham surgery or varying degrees of ischemia followed by 24 hours of reperfusion. UmtDNA increased in mice after 10-15 minutes of ischemia and positively correlated with ischemia time. Furthermore, UmtDNA was predictive of AKI in the mouse model. Finally, UmtDNA levels were negatively correlated with renal cortical mtDNA and mitochondrial gene expression. These translational studies demonstrate that UmtDNA is associated with recovery from AKI following cardiac surgery by serving as an indicator of mitochondrial integrity. Thus, UmtDNA may serve as valuable biomarker for the development of mitochondrial targeted therapies in AKI. PMID:26287315

  6. 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

  7. Fetal programming of renal function.

    PubMed

    Dötsch, Jörg; Plank, Christian; Amann, Kerstin

    2012-04-01

    Results from large epidemiological studies suggest a clear relation between low birth weight and adverse renal outcome evident as early as during childhood. Such adverse outcomes may include glomerular disease, hypertension, and renal failure and contribute to a phenomenon called fetal programming. Other factors potentially leading to an adverse renal outcome following fetal programming are maternal diabetes mellitus, smoking, salt overload, and use of glucocorticoids during pregnancy. However, clinical data on the latter are scarce. Here, we discuss potential underlying mechanisms of fetal programming, including reduced nephron number via diminished nephrogenesis and other renal (e.g., via the intrarenal renin-angiotensin-aldosterone system) and non-renal (e.g., changes in endothelial function) alterations. It appears likely that the outcomes of fetal programming may be influenced or modified postnatally, for example, by the amount of nutrients given at critical times.

  8. Melamine Impairs Renal and Vascular Function in Rats

    PubMed Central

    Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Wang, Yi-Xiang; Cheang, Wai San; Liu, Jian; Lu, Ye; Huang, Huihui; Xia, Yin; Chen, Zhen Yu; Mok, Chuen-Shing; Lau, Chau-Ming; Huang, Yu

    2016-01-01

    Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products. PMID:27324576

  9. Melamine Impairs Renal and Vascular Function in Rats.

    PubMed

    Tian, Xiao Yu; Wong, Wing Tak; Lau, Chi Wai; Wang, Yi-Xiang; Cheang, Wai San; Liu, Jian; Lu, Ye; Huang, Huihui; Xia, Yin; Chen, Zhen Yu; Mok, Chuen-Shing; Lau, Chau-Ming; Huang, Yu

    2016-06-21

    Melamine incident, linked to nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products, was unprecedentedly grave in China in 2008 as little was known about the mechanistic process leading to renal dysfunction in affected children. This study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring. A combination of approaches employed includes functional studies in rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and detection of plasma and renal melamine. We provide mechanistic evidence showing for the first time that melamine reduces renal blood flow and impairs renal and vascular function associated with overexpression of inflammatory markers, transforming growth factor-β1, bone morphogenic protein 4 and cyclooxygenase-2 in kidney and renal vasculature. Melamine also induces renal inflammation and fibrosis. More importantly, melamine causes nephropathies in offsprings from pregnant rat exposed to melamine during pregnancy, as well as in neonatal rat exposed to melamine afterbirth, thus supporting the clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products.

  10. Serum and urine biomarkers for human renal cell carcinoma.

    PubMed

    Pastore, A L; Palleschi, G; Silvestri, L; Moschese, D; Ricci, S; Petrozza, V; Carbone, A; Di Carlo, A

    2015-01-01

    Renal cell carcinoma (RCC) diagnosis is mostly achieved incidentally by imaging provided for unrelated clinical reasons. The surgical management of localized tumors has reported excellent results. The therapy of advanced RCC has evolved considerably over recent years with the widespread use of the so-called "targeted therapies." The identification of molecular markers in body fluids (e.g., sera and urine), which can be used for screening, diagnosis, follow-up, and monitoring of drug-based therapy in RCC patients, is one of the most ambitious challenges in oncologic research. Although there are some promising reports about potential biomarkers in sera, there is limited available data regarding urine markers for RCC. The following review reports some of the most promising biomarkers identified in the biological fluids of RCC patients.

  11. Renal tubular function in hyperparathyroidism.

    PubMed Central

    van 't Hoff, W.; Bicknell, E. J.

    1989-01-01

    Renal tubular function was assessed in a group of patients with mild hyperparathyroidism before and after a mean period of 2.7 years conservative management. It was also assessed, before and after a mean of 3.3 years following surgery in a group of patients with initially higher plasma calcium concentration. Mean maximum urine osmolality was within the accepted range as was the maximum urine plasma hydrogen ion gradient in both groups at the time of diagnosis. No significant change in renal tubular function was observed in either group over the periods of this study. Although deterioration after a long period cannot be excluded, we do not consider that regular assessment of renal tubular function is necessary in the conservative management of primary hyperparathyroidism. PMID:2616415

  12. Association between cardiac, renal, and hepatic biomarkers and outcomes in patients with acute heart failure.

    PubMed

    Chan, Wing W; Waltman Johnson, Katherine; Friedman, Howard S; Navaratnam, Prakash

    2016-08-01

    Myocardial injury, worsening renal function, and hepatic impairment are independent risk factors for poor patient acute heart failure (AHF) outcomes. Biomarkers of organ damage may be useful in identifying patients at risk for poor outcomes. The objective of this analysis was to assess the relationship between abnormal AHF biomarkers and outcomes in AHF patients. AHF admissions (N = 104,794) data from the Cerner Health Facts® inpatient database were analyzed retrospectively. Multivariate predictive models determined the impact of biomarkers on mortality, readmission, length of stay (LOS), and cost from index admission through 180 days post discharge. Thirty and 60 day time windows are reported but 180 day results were consistent with 60 day outcomes. Biomarkers evaluated were aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), high sensitivity cardiac troponin, bilirubin, alanine transaminase (ALT), sodium, high sensitivity C-reactive protein (hs-CRP), uric acid, B-type natriuretic peptide (BNP), NT-ProBNP, blood urea nitrogen (BUN), serum creatinine (SCr), and hemoglobin. All biomarkers evaluated except hs-CRP, uric acid, and NT-ProBNP were significant (p < 0.0001) predictors of mortality at all timepoints; non-significance for these 3 biomarkers is likely due to low patient counts (1%-2%). Odds ratios for significant biomarkers of mortality ranged from 1.168-2.076 at index admission, 1.205-1.946 at 30 days post-discharge, and 1.233-1.991 at 60 days post-discharge. AST, eGFR, troponin, ALT, BNP, BUN, SCr, and hemoglobin were significant (p < 0.0001) predictors of readmission risk at all timepoints. AST, eGFR, troponin, bilirubin, BUN, SCr, and hemoglobin were significant (p < 0.0001) predictors of cumulative LOS at all timepoints. AST, eGFR, troponin, ALT, sodium, BUN, and hemoglogin were significant (p < 0.0001) cost predictors at 30 and 60 days post-discharge. Renal function measures were associated with outcomes in

  13. Ambient Melamine Exposure and Urinary Biomarkers of Early Renal Injury

    PubMed Central

    Wu, Chia-Fang; Peng, Chiung-Yu; Liu, Chia-Chu; Lin, Wen-Yi; Pan, Chih-Hong; Cheng, Ching-Mei; Hsieh, Hui-Min; Hsieh, Tusty-Jiuan; Chen, Bai-Hsiun

    2015-01-01

    Information about environmental exposure to melamine and renal injury in adults is lacking. We investigated this relationship in 44 workers at two melamine tableware manufacturing factories in Taiwan (16 manufacturers, eight grinders, ten packers, and ten administrators) and 105 nonexposed workers (controls) at one shipbuilding company who were enrolled in August–December of 2012. For melamine workers, personal and area air samples were obtained at the worksite over 1 workweek (Monday–Friday). In the same week, pre- and post-shift one-spot urine samples were collected each workday and one first-spot urine sample was collected on each weekend morning and the following Monday morning. For each control, a one-spot urine sample was collected on Friday morning. A blood sample was also obtained from each participant at this time. Melamine levels were measured in air, urine, and serum, and early renal injury biomarkers were measured in urine. Urinary melamine concentrations in manufacturers increased sharply between pre- and post-shift measurements on Monday, remained significantly elevated throughout the workweek, and decreased over the weekend; changes in urinary melamine concentrations were substantially lower for other melamine workers. Manufacturers were exposed to the highest concentrations of ambient melamine and had significantly higher urinary and serum melamine concentrations than did the controls (P<0.001). Urinary melamine levels were positively associated with urinary N-acetyl β-d-glucosaminidase (NAG) levels but not microalbumin levels, and the detectable β2-microglobulin rate increased in the manufacturers group. In conclusion, ambient melamine exposure may increase the levels of urinary biomarkers of renal tubular injury in this occupational setting. PMID:26045090

  14. Ambient Melamine Exposure and Urinary Biomarkers of Early Renal Injury.

    PubMed

    Wu, Chia-Fang; Peng, Chiung-Yu; Liu, Chia-Chu; Lin, Wen-Yi; Pan, Chih-Hong; Cheng, Ching-Mei; Hsieh, Hui-Min; Hsieh, Tusty-Jiuan; Chen, Bai-Hsiun; Wu, Ming-Tsang

    2015-11-01

    Information about environmental exposure to melamine and renal injury in adults is lacking. We investigated this relationship in 44 workers at two melamine tableware manufacturing factories in Taiwan (16 manufacturers, eight grinders, ten packers, and ten administrators) and 105 nonexposed workers (controls) at one shipbuilding company who were enrolled in August-December of 2012. For melamine workers, personal and area air samples were obtained at the worksite over 1 workweek (Monday-Friday). In the same week, pre- and post-shift one-spot urine samples were collected each workday and one first-spot urine sample was collected on each weekend morning and the following Monday morning. For each control, a one-spot urine sample was collected on Friday morning. A blood sample was also obtained from each participant at this time. Melamine levels were measured in air, urine, and serum, and early renal injury biomarkers were measured in urine. Urinary melamine concentrations in manufacturers increased sharply between pre- and post-shift measurements on Monday, remained significantly elevated throughout the workweek, and decreased over the weekend; changes in urinary melamine concentrations were substantially lower for other melamine workers. Manufacturers were exposed to the highest concentrations of ambient melamine and had significantly higher urinary and serum melamine concentrations than did the controls (P<0.001). Urinary melamine levels were positively associated with urinary N-acetyl β-d-glucosaminidase (NAG) levels but not microalbumin levels, and the detectable β2-microglobulin rate increased in the manufacturers group. In conclusion, ambient melamine exposure may increase the levels of urinary biomarkers of renal tubular injury in this occupational setting. Copyright © 2015 by the American Society of Nephrology.

  15. Fibrate therapy and renal function.

    PubMed

    Sica, Domenic A

    2009-09-01

    Fibrates are a class of lipid-lowering medications primarily used as second-line agents behind statins. The adverse-effect profile of fibrates has been marked by a puzzling yet reversible rise in serum creatinine values with their use. It is not known whether this finding represents a true change in renal function. One proposed explanation for this phenomenon is that fibrates increase the production of creatinine, in which case a rise in serum creatinine values would not represent a true deterioration in renal function. An alternative theory is that fibrates reduce the production of vasodilatory prostaglandins, which would lead to a true change in renal function in patients who experience a rise in serum creatinine values. Routine serum creatinine monitoring is advisable in fibrate-treated patients, particularly in those with preexisting renal disease. A 30% increase in serum creatinine values in the absence of other causes of serum creatinine change warrants discontinuation of fibrate therapy. Serum creatinine values can take several weeks to return to their baseline values following discontinuation of a fibrate.

  16. Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice

    PubMed Central

    Schüler, Emil; Larsson, Maria; Parris, Toshima Z.; Johansson, Martin E.; Helou, Khalil; Forssell-Aronsson, Eva

    2015-01-01

    The kidneys are one of the main dose-limiting organs in peptide receptor radionuclide therapy and due to large inter-individual variations in renal toxicity, biomarkers are urgently needed in order to optimize therapy and reduce renal tissue damage. The aim of this study was to investigate the transcriptional, functional, and morphological effects on renal tissue after 177Lu-octreotate administration in normal mice, and to identify biomarkers for radiation induced renal toxicity. Methods C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys). At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a) global transcriptional variations in kidney tissues, (b) morphological changes in the kidneys, (c) changes in white and red blood cell count as well as blood levels of urea, and (d) changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy. Results In general, the highest number of differentially regulated transcripts was observed at 12 months after administration. The Cdkn1a, C3, Dbp, Lcn2, and Per2 genes displayed a distinct dose-dependent regulation, with increased expression level with increasing absorbed dose. Ifng, Tnf, and Il1B were identified as primary up-stream regulators of the recurrently regulated transcripts. Furthermore, previously proposed biomarkers for kidney injury and radiation damage were also observed. The functional investigation revealed reduced excretion of 99mTc-DTPA after 150 MBq, an increased uptake of 99mTc-DMSA at all dose levels compared with the controls, and markedly increased urea level in blood after 150 MBq at 12 months. Conclusion Distinct dose-response relationships were found for several of the regulated transcripts. The Cdkn1a, Dbp, Lcn2, and Per2 genes are proposed as biomarkers for 177Lu-octreotate exposure of kidney. Correlations to functional and morphological effects further confirm

  17. [Scintigraphic assessment of function in renal dystopia].

    PubMed

    Pilgrim, S

    1998-06-01

    In patients with renal dystopia radionuclide urography in commonly used technique may yield inaccurate results concerning split renal function. In a case of unilateral pelvic kidney a simple strategy to avoid this methodical error is demonstrated.

  18. Detection and evaluation of renal biomarkers in a swine model of acute myocardial infarction and reperfusion.

    PubMed

    Duan, Su-Yan; Xing, Chang-Ying; Zhang, Bo; Chen, Yan

    2015-01-01

    The prevalence of type 1 cardiorenal syndrome (CRS) is increasing and strongly associated with long-term mortality. However, lack of reliable animal models and well-defined measures of renoprotection, made early diagnosis and therapy difficult. We previously successfully established the swine acute myocardial infarction (AMI) model of ischemia-reperfusion by blocking left anterior descending branch (LAD). Reperfusion was performed after 90-minute occlusion of the LAD. AMI was confirmed by ECG and left ventricular angiography (LVG). Then those 52 survived AMI reperfusion swine, including ventricular fibrillation-cardiac arrest after restoration of blood flow, were randomly divided into four groups (four/group) according to different interventions: resuscitation in room temperature, resuscitation with 500 ml saline in room temperature, resuscitation with 4°C 500 ml saline and normal control (with no intervention of resuscitation). Each group was further observed in four groups according to different time of resuscitation after ventricular arrhythmias: 1, 3, 5, 10-minute reperfusion after ventricular arrhythmias. Plasma and random urine were collected to evaluate renal function and test renal biomarkers of acute kidney injury (AKI). Our swine AMI model of ischemia-reperfusion provoked subclinical AKI with the elevation of the tubular damage biomarker, NGAL, IL-18 and L-FABP. Renal damage rapidly observed after hemodynamic instability, rather than observation after several hours as previously reported. The increasing rate of biological markers declined after interventions, however, its impact on the long-term prognosis remains to be further studied. These data show that elevation of tubular damage biomarkers without glomerular function loss may indicate appropriate timing for effective renoprotections like hypothermia resuscitation in type 1 CRS.

  19. [Nucleotide receptors and renal function].

    PubMed

    Jankowski, Maciej

    2014-01-01

    Kidney plays a key role in homeostasis of human body. It has heterogenic structure and is characterized by complicated vascular beds and numbers of sympathetic nerves endings. Nucleotides receptors are involved in the regulation of blood flow, a fundamental process for renal function. Plasma is filtrated in renal glomerulus and activity of nucleotides receptors located on cells of glomerular filter modifies the physi- cochemical properties of filter and affects the filtration process. Electrolytes, water and low molecular weight molecules are reabsorbed from tubular fluid or secreted into fluid in proximal and distal tubules. Glomerular filtration rate and activity of tubular processes are regulated via nucleotides receptors by glomerulotubularbalance and tubuloglomerular feedback. Nucleotides receptors are involved in systemic regulation of blood pressure and carbohydrate metabolism.

  20. Renal functional outcomes after surgery for renal cortical tumors

    PubMed Central

    Finkelstein, Julia B.; DeCastro, G. Joel; McKiernan, James M.

    2015-01-01

    Historically, radical nephrectomy represented the gold standard for the treatment of small (≤ 4cm) as well as larger renal masses. Recently, for small renal masses, the risk of ensuing chronic kidney disease and end stage renal disease has largely favored nephron-sparing surgical techniques, mainly partial nephrectomy. In this review, we surveyed the literature on renal functional outcomes after partial nephrectomy for renal tumors. The largest randomized control trial comparing radical and partial nephrectomy failed to show a survival benefit for partial nephrectomy. With regards to overall survival, surgically induced chronic kidney disease (GFR < 60 ml/min/ 1.73m2) caused by nephrectomy might not be as deleterious as medically induced chronic kidney disease. In evaluating patients who underwent donor nephrectomy, transplant literature further validates that surgically induced reductions in GFR may not affect patient survival, unlike medically induced GFR declines. Yet, because patients who present with a renal mass tend to be elderly with multiple comorbidities, many develop a mixed picture of medically, and surgically-induced renal disease after extirpative renal surgery. In this population, we believe that nephron sparing surgery optimizes oncological control while protecting renal function.

  1. Preoperative nuclear renal scan underestimates renal function after radical nephrectomy.

    PubMed

    Bachrach, Laurie; Negron, Edris; Liu, Joceline S; Su, Yu-Kai; Paparello, James J; Eggener, Scott; Kundu, Shilajit D

    2014-12-01

    To compare expected and actual renal function after nephrectomy. Nuclear renal scan estimates differential kidney function and is commonly used to calculate expected postoperative renal function after radical nephrectomy. However, the observed postoperative renal function is often different from the expected. A retrospective review was performed on 136 patients who underwent radical nephrectomy or nephroureterectomy and had a preoperative renal scan with calculated differential function. Glomerular filtration rate (GFR) values, preoperative and postoperative, were calculated with the Modification of Diet in Renal Disease (MDRD) equation. The expected postoperative GFR based on renal scan was compared with the actual postoperative GFR. The average age of patients undergoing surgery was 58.6 years, and the indication for surgery was for benign causes in 59 (44%) patients and cancer in 76 (56%) patients. The average preoperative creatinine and estimated GFR were 1.0 mg/dL and 69.9 mL/min/1.73 m(2). At a median follow-up of 3.3 months, the actual postoperative GFR exceeded the expected GFR by an average of 12.1% (interquartile range, 2.6%-25.2%). When stratified by preoperative GFR >90, 60-90, and <60 mL/min/1.73 m(2), respectively, the observed GFR exceeded the expected GFR by 4.3%, 12.6%, and 14.9%, respectively (P = .16). This trend was maintained when GFR was plotted over time. After nephrectomy, the remaining kidney exceeded the expected postoperative GFR by 12% in this cohort of patients with preoperative renal scans. Patients with existing renal insufficiency had the greatest compensatory response, and this was durable over time. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Urinary Biomarkers for Screening for Renal Scarring in Children with Febrile Urinary Tract Infection: Pilot Study.

    PubMed

    Kitao, Tetsuya; Kimata, Takahisa; Yamanouchi, Sohsaku; Kato, Shogo; Tsuji, Shoji; Kaneko, Kazunari

    2015-09-01

    Recurrent febrile urinary tract infections during infancy cause renal scarring, which is characterized by progressive focal interstitial fibrosis and may lead to renal failure. Renal scarring can be diagnosed through scintigraphy, although it seems impractical to perform renal scintigraphy for all infants with febrile urinary tract infections. Therefore, it is important to search for a biomarker to identify the presence of renal scarring. We hypothesized that urinary biomarkers of nephropathy may increase in infants with renal scarring following febrile urinary tract infections. A total of 49 infants who underwent renal scintigraphy for febrile urinary tract infections were enrolled in the study. Several measurements were performed using urine samples, including total proteins, beta2-microglobulins, N-acetyl-β-D-glucosaminidase, neutrophil gelatinase associated lipocalin, liver-type fatty acid binding protein and angiotensinogen. Values were corrected by creatinine and compared between patients with and without renal scarring. Among urinary biomarkers only angiotensinogen in patients with scarring (median 14.6 μg/gm creatinine) demonstrated significantly higher levels than in patients without scarring (3.6 μg/gm creatinine, p <0.001). Urinary angiotensinogen may be useful for diagnosing the presence of renal scarring. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. Hemostatic Parameters according to Renal Function and Time after Transplantation in Brazilian Renal Transplanted Patients

    PubMed Central

    Mota, Ana Paula Lucas; Alpoim, Patrícia Nessralla; de Figueiredo, Roberta Carvalho; Simões e Silva, Ana Cristina; Braga Gomes, Karina; Dusse, Luci Maria SantAna

    2015-01-01

    Kidney transplantation is the key for patients with end-stage renal disease, improving quality of life and longer survival. However, kidney transplant triggers an intense inflammatory response and alters the hemostatic system, but the pathophysiological mechanisms of these changes are not completely understood. The aim of this cross-sectional cohort study was to investigate hemostatic biomarkers in Brazilian renal transplanted patients according to renal function and time after transplantation. A total of 159 renal transplanted patients were enrolled and D-Dimer (D-Di), Thrombomodulin (TM), von Willebrand Factor (VWF), and ADAMTS13 plasma levels were assessed by ELISA. An increase of D-Di was observed in patients with higher levels of creatinine. ADAMTS13 levels were associated with creatinine plasma levels and D-Di levels with Glomerular Filtration Rate. These results suggested that D-Di and ADAMTS13 can be promising markers to estimate renal function. ADAMTS13 should be investigated throughout the posttransplant time to clarify the participation of this enzyme in glomerular filtration and acceptance or rejection of the graft in Brazilian transplanted patients. PMID:26229221

  4. Renal

    MedlinePlus

    ... term "renal" refers to the kidney. For example, renal failure means kidney failure. Related topics: Kidney disease Kidney disease - diet Kidney failure Kidney function tests Renal scan Kidney transplant

  5. Diagnostic biomarkers for renal cell carcinoma: selection using novel bioinformatics systems for microarray data analysis

    PubMed Central

    Osunkoya, Adeboye O; Yin-Goen, Qiqin; Phan, John H; Moffitt, Richard A; Stokes, Todd H; Wang, May D; Young, Andrew N

    2009-01-01

    Summary The differential diagnosis of clear cell, papillary and chromophobe renal cell carcinoma is clinically important, because these tumor subtypes are associated with different pathobiology and clinical behavior. For cases in which histopathology is equivocal, immunohistochemistry and quantitative RT-PCR can assist in the differential diagnosis by measuring expression of subtype-specific biomarkers. Several renal tumor biomarkers have been discovered in expression microarray studies. However, due to heterogeneity of gene and protein expression, additional biomarkers are needed for reliable diagnostic classification. We developed novel bioinformatics systems to identify candidate renal tumor biomarkers from the microarray profiles of 45 clear cell, 16 papillary and 10 chromophobe renal cell carcinoma; the microarray data was derived from two independent published studies. The ArrayWiki biocomputing system merged the microarray datasets into a single file, so gene expression could be analyzed from a larger number of tumors. The caCORRECT system removed non-random sources of error from the microarray data, and the omniBioMarker system analyzed data with several gene-ranking algorithms, in order to identify algorithms effective at recognizing previously described renal tumor biomarkers. We predicted these algorithms would also be effective at identifying unknown biomarkers that could be verified by independent methods. We selected six novel candidate biomakers from the omniBioMarker analysis, and verified their differential expression in formalin-fixed paraffin-embedded tissues by quantitative RT-PCR and immunohistochemistry. The candidate biomarkers were carbonic anhydrase IX, ceruloplasmin, schwannomin-interacting protein 1, E74-like factor 3, cytochrome c oxidase subunit 5a and acetyl-CoA acetyltransferase 1. Quantitative RT-PCR was performed on 17 clear cell, 13 papillary and 7 chromophobe renal cell carcinoma. Carbonic anhydrase IX and ceruloplasmin were

  6. Impaired renal function and development in Belgrade rats

    PubMed Central

    Veuthey, Tania; Hoffmann, Dana; Vaidya, Vishal S.

    2013-01-01

    Belgrade rats carry a disabling mutation in the iron transporter divalent metal transporter 1 (DMT1). Although DMT1 plays a major role in intestinal iron absorption, the transporter is also highly expressed in the kidney, where its function remains unknown. The goal of this study was to characterize renal physiology of Belgrade rats. Male Belgrade rats died prematurely with ∼50% survival at 20 wk of age. Necropsy results indicated marked glomerular nephritis and chronic end-stage renal disease. By 15 wk of age, Belgrade rats displayed altered renal morphology associated with sclerosis and fibrosis. Creatinine clearance was significantly lower compared with heterozygote littermates. Urinary biomarkers of kidney injury, including albumin, fibrinogen, and kidney injury molecule-1, were significantly elevated. Pilot morphological studies suggest that nephrogenesis is delayed in Belgrade rat pups due to their low iron status and fetal growth restriction. Such defects in renal development most likely underlie the compromised renal metabolism observed in adult b/b rats. Belgrade rat kidney nonheme iron levels were not different from controls but urinary iron and transferrin levels were higher. These results further implicate an important role for the transporter in kidney function not only in iron reabsorption but also in glomerular filtration of the serum protein. PMID:24226520

  7. Renal Function and Hematology in Rats with Congenital Renal Hypoplasia.

    PubMed

    Yasuda, Hidenori; Amakasu, Kohei; Tochigi, Yuki; Katayama, Kentaro; Suzuki, Hiroetsu

    2016-02-01

    Renal hypoplasia due to a congenitally reduced number of nephrons progresses to chronic kidney disease and may cause renal anemia, given that the kidneys are a major source of erythropoietin in adults. Hypoplastic kidney (HPK) rats have only about 20% of the normal number of nephrons and develop CKD. This study assessed the renal function and hematologic changes in HPK rats from 70 to 210 d of age. HPK rats demonstrated deterioration of renal excretory function, slightly macrocytic erythropenia at all days examined, age-related increases in splenic hemosiderosis accompanied by a tendency toward increased hemolysis, normal plasma erythropoietin levels associated with increased hepatic and decreased renal erythropoietin production, and maintenance of the response for erythropoietin production to hypoxic conditions, with increased interstitial fibrosis at 140 d of age. These results indicate that increases in splenic hemosiderosis and the membrane fragility of RBC might be associated with erythropenia and that hepatic production of erythropoietin might contribute to maintaining the blood Hgb concentration in HPK rats.

  8. Renal cell carcinoma in functional renal graft: Toward ablative treatments.

    PubMed

    Tillou, Xavier; Guleryuz, Kerem; Collon, Sylvie; Doerfler, Arnaud

    2016-01-01

    The occurrence of a kidney transplant tumor is a rare but serious issue with a double risk: the return to dialysis and the development of metastatic cancer. Publications on this topic are mainly case reports. The purpose of this review was to report an exhaustive literature review of functional graft renal cell carcinomas to highlight the impact of tumors on the renal graft outcomes. 201 de novo renal carcinomas in functional renal grafts from 69 publications were included. Incidence was estimated at 0.18%. Graft tumors were mostly asymptomatic (85.9%). Whatever the discovery circumstances of graft tumors, they were mostly documented by graft ultrasounds supplemented by CT-scanning or MR imaging. Nephron sparing surgery (95 patients) was the first treatment performed followed by radiofrequency ablation (38 patients) and cryotherapy (10 patients). The most common tumor graft histology was clear cell carcinoma (46.4%), followed by papillary carcinoma (43.7%). Specific mortality was 2.9% with 6 deaths. Renal graft cell carcinoma is a rare pathology with a low specific death. When possible, conservative treatment should be the first choice. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Renal relevant radiology: renal functional magnetic resonance imaging.

    PubMed

    Ebrahimi, Behzad; Textor, Stephen C; Lerman, Lilach O

    2014-02-01

    Because of its noninvasive nature and provision of quantitative measures of a wide variety of physiologic parameters, functional magnetic resonance imaging (MRI) shows great potential for research and clinical applications. Over the past decade, application of functional MRI extended beyond detection of cerebral activity, and techniques for abdominal functional MRI evolved. Assessment of renal perfusion, glomerular filtration, interstitial diffusion, and parenchymal oxygenation turned this modality into an essential research and potentially diagnostic tool. Variations in many renal physiologic markers can be detected using functional MRI before morphologic changes become evident in anatomic magnetic resonance images. Moreover, the framework of functional MRI opened a window of opportunity to develop novel pathophysiologic markers. This article reviews applications of some well validated functional MRI techniques, including perfusion, diffusion-weighted imaging, and blood oxygen level-dependent MRI, as well as some emerging new techniques such as magnetic resonance elastography, which might evolve into clinically useful tools.

  10. [Kidney function and renal cancer surgery].

    PubMed

    Izzedine, Hassan; Méjean, Arnaud; Escudier, Bernard

    2014-02-01

    Although radical nephrectomy is still practiced in many patients with large renal tumors, oncology and nephrology arguments for kidney-sparing approach for small renal masses has taken over this first. Indeed, partial nephrectomy provides equivalent oncologic results while preserving renal function and thereby limit morbidity and cardiovascular mortality related to chronic kidney disease. In addition, patients who develop kidney cancer often have medical comorbidities that may affect renal function, such as diabetes and hypertension. Histological examination of renal tissue adjacent to the tumor showed significant pathological changes in the majority of patients. For elderly patients or patients with comorbidities, active surveillance allows kidney-sparing approach with extremely low rates of progression and metastasis of cancer disease. Despite these significant advances in understanding for the treatment of small renal masses, partial nephrectomy remains underused. Better management must take into account the preservation of renal function in order to increase overall survival. A strategy for the systematic evaluation of renal function in patients with CR, with multidisciplinary staff (nephrologist urologist and oncologist), is therefore highly desirable.

  11. Effects of Sugammadex and Neostigmine on Renal Biomarkers

    PubMed Central

    Isik, Yasemin; Palabiyik, Onur; Cegin, Bilal Muhammed; Goktas, Ugur; Kati, Ismail

    2016-01-01

    Background Neostigmine, the currently commonly used agent for reversal of neuromuscular blockade. Sugammadex is a novel and unique compound designed as an antagonist of steroidal neuromuscular blockers. In this study, we evaluated the effects of sugammadex or neostigmine on kidney functions in patients scheduled for elective surgery. Material/Methods Patients scheduled for a surgical procedure under desflurane/opioid anesthesia received an intubating dose rocuronium. Patients were divided into 2 groups receiving either sugammadex or neostigmine atropine to reverse neuromuscular blockade. Cystatin C, creatinine, urea, blood urea nitrogen, sodium, potassium, and calcium levels in the blood and α1microglobulin, β2microglobulin, and microalbumin levels in the urine were measured. Results There was no significant difference between the groups with regard to the demographic data. In the Neostigmine Group, although β2microglobulin and microalbumin were similar, a significant increase was found in the postoperative α1microglobulin and cystatin C values. In the Sugammadex Group, although β2-microglobulin and cystatin C were similar, a significant increase was found in the postoperative α1-microglobulin and microalbumin values. The only significant difference was cystatin C value variation in the Neostigmine Group compared to the Sugammadex Group. Conclusions We believe that the use of more specific and sensitive new-generation markers like cystatin C to evaluate kidney function will provide a better understanding and interpretation of our results. Sugammadex has more tolerable effects on kidney function in patients than does neostigmine. However, when compared to preoperative values, there is a negative alteration of postoperative values. Neostigmine and sugammadex do not cause renal failure but they may affect kidney function. PMID:26963316

  12. Effects of Sugammadex and Neostigmine on Renal Biomarkers.

    PubMed

    Isik, Yasemin; Palabiyik, Onur; Cegin, Bilal Muhammed; Goktas, Ugur; Kati, Ismail

    2016-03-10

    Neostigmine, the currently commonly used agent for reversal of neuromuscular blockade. Sugammadex is a novel and unique compound designed as an antagonist of steroidal neuromuscular blockers. In this study, we evaluated the effects of sugammadex or neostigmine on kidney functions in patients scheduled for elective surgery. Patients scheduled for a surgical procedure under desflurane/opioid anesthesia received an intubating dose rocuronium. Patients were divided into 2 groups receiving either sugammadex or neostigmine atropine to reverse neuromuscular blockade. Cystatin C, creatinine, urea, blood urea nitrogen, sodium, potassium, and calcium levels in the blood and α1microglobulin, β2microglobulin, and microalbumin levels in the urine were measured. There was no significant difference between the groups with regard to the demographic data. In the Neostigmine Group, although β2microglobulin and microalbumin were similar, a significant increase was found in the postoperative α1microglobulin and cystatin C values. In the Sugammadex Group, although β2-microglobulin and cystatin C were similar, a significant increase was found in the postoperative α1-microglobulin and microalbumin values. The only significant difference was cystatin C value variation in the Neostigmine Group compared to the Sugammadex Group. We believe that the use of more specific and sensitive new-generation markers like cystatin C to evaluate kidney function will provide a better understanding and interpretation of our results. Sugammadex has more tolerable effects on kidney function in patients than does neostigmine. However, when compared to preoperative values, there is a negative alteration of postoperative values. Neostigmine and sugammadex do not cause renal failure but they may affect kidney function.

  13. Serum Endocan Levels Associated with Hypertension and Loss of Renal Function in Pediatric Patients after Two Years from Renal Transplant

    PubMed Central

    de Souza, Livia Victorino; Oliveira, Vanessa; Laurindo, Aline Oliveira; Huarachı, DelmaRegına Gomes; Nogueira, Paulo Cesar Koch; Feltran, Luciana de Santis; Medina-Pestana, José Osmar

    2016-01-01

    Endocan is an important biomarker of inflammation and endothelial dysfunction that increases in association with several chronic diseases. Few published data have described the role of endocan in pediatric renal transplant (RT) patients. We evaluated the endocan concentrations in 62 children who underwent renal transplantation and assessed their relationships with the patients' blood pressure and loss of renal function. The endocan levels were significantly elevated in the pediatric RT patients who had hypertension and a loss of renal function. We determined positive correlations between the endocan concentrations and the hemodynamic variables (systolic blood pressure: r = 0.416; P = 0.001; pulse pressure: r = 0.412; P = 0.003). The endocan levels were inversely correlated with the estimated glomerular filtration rate (r = −0.388; P = 0.003). An endocan cutoff concentration of 7.0 ng/mL identified pediatric RT patients who had hypertension and a loss of renal function with 100% sensitivity and 75% specificity. In conclusion, the endocan concentrations were significantly elevated in pediatric RT patients who had both hypertension and a loss of renal function. The correlations between the endocan levels and the hemodynamic variables and the markers of renal function strengthen the hypothesis that it is an important marker of cardiorenal risk. PMID:28083150

  14. Renal Cancer Biomarkers | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's Laboratory of Proteomics and Analytical Technologies is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diagnostic, therapeutic and prognostic cancer biomarkers from clinical specimens.

  15. Neurocognitive functions in pediatric renal transplant patients.

    PubMed

    Gulleroglu, K; Baskin, E; Bayrakci, U S; Aydogan, M; Alehan, F; Kantar, A; Karakayali, F; Moray, G; Haberal, M

    2013-01-01

    Neurocognitive dysfunction is one of the major complications of chronic renal failure (CRF). Uremic state during CRF encompasses a wide spectrum of neurobehavioral and neurological disturbances. Recent studies showed that the pathophysiology of neurocognitive dysfunction in CRF is related to plasma levels of uremic solutes. Successful renal transplantation improves renal, metabolic, and endocrine functions and the quality of life. The aim of our study was to determine the state of neurocognitive function in pediatric renal transplant recipients. We prospectively performed a neurological examination and neuropsychological test battery (Bender-Gestalt Test, Cancellation Test, and Visual and Auditory Number Assay Test) in 20 pediatric renal transplant recipients between 6 and 16 years of age. Twenty healthy children and 20 children with CRF were included in the study as the control groups. Mean age of the renal transplant recipients was 13.50 ± 3.40 years old. Mean evaluation time after transplantation was 2.0 ± 0.5 years. Bender-Gestalt Test result was abnormal in 40% of patients. The results of the Cancellation Test and the Visual and Auditory Number Assay Test showed significant decline in pediatric renal transplant patients when compared with the control. We found that neurocognitive dysfunction was frequent in pediatric renal transplantation patients. Awareness of this potential problem may be helpful for early recognition and treatment. Our findings suggest that periodic neurocognitive assessments may be indicated in transplant recipients.

  16. Renal functional reserve and renal recovery after acute kidney injury.

    PubMed

    Sharma, Aashish; Mucino, Marìa Jimena; Ronco, Claudio

    2014-01-01

    Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use.

  17. Circadian regulation of renal function.

    PubMed

    Firsov, Dmitri; Bonny, Olivier

    2010-10-01

    Urinary excretion of water and all major electrolytes exhibit robust circadian oscillations. The 24-h periodicity has been well documented for several important determinants of urine formation, including renal blood flow, glomerular filtration, tubular reabsorption, and tubular secretion. Disturbance of the renal circadian rhythms is increasingly recognized as a risk factor for hypertension, polyuria, and other diseases and may contribute to renal fibrosis. The origin of these rhythms has been attributed to the reactive response of the kidney to circadian changes in volume and/or in the composition of extracellular fluids that are entrained by rest/activity and feeding/fasting cycles. However, numerous studies have shown that most of the renal excretory rhythms persist for long periods of time, even in the absence of periodic environmental cues. These observations led to the hypothesis of the existence of a self-sustained mechanism, enabling the kidney to anticipate various predictable circadian challenges to homeostasis. The molecular basis of this mechanism remained unknown until the recent discovery of the mammalian circadian clock made of a system of autoregulatory transcriptional/translational feedback loops, which have been found in all tissues studied, including the kidney. Here, we present a review of the growing evidence showing the involvement of the molecular clock in the generation of renal excretory rhythms.

  18. Renal Heme Oxygenase-1 Induction with Hemin Augments Renal Hemodynamics, Renal Autoregulation, and Excretory Function

    PubMed Central

    Botros, Fady T.; Dobrowolski, Leszek; Navar, L. Gabriel

    2012-01-01

    Heme oxygenases (HO-1; HO-2) catalyze conversion of heme to free iron, carbon monoxide, and biliverdin/bilirubin. To determine the effects of renal HO-1 induction on blood pressure and renal function, normal control rats (n = 7) and hemin-treated rats (n = 6) were studied. Renal clearance studies were performed on anesthetized rats to assess renal function; renal blood flow (RBF) was measured using a transonic flow probe placed around the left renal artery. Hemin treatment significantly induced renal HO-1. Mean arterial pressure and heart rate were not different (115 ± 5 mmHg versus 112 ± 4 mmHg and 331 ± 16 versus 346 ± 10 bpm). However, RBF was significantly higher (9.1 ± 0.8 versus 7.0 ± 0.5 mL/min/g, P < 0.05), and renal vascular resistance was significantly lower (13.0 ± 0.9 versus 16.6 ± 1.4 [mmHg/(mL/min/g)], P < 0.05). Likewise, glomerular filtration rate was significantly elevated (1.4 ± 0.2 versus 1.0 ± 0.1 mL/min/g, P < 0.05), and urine flow and sodium excretion were also higher (18.9 ± 3.9 versus 8.2 ± 1.0 μL/min/g, P < 0.05 and 1.9 ± 0.6 versus 0.2 ± 0.1 μmol/min/g, P < 0.05, resp.). The plateau of the autoregulation relationship was elevated, and renal vascular responses to acute angiotensin II infusion were attenuated in hemin-treated rats reflecting the vasodilatory effect of HO-1 induction. We conclude that renal HO-1 induction augments renal function which may contribute to the antihypertensive effects of HO-1 induction observed in hypertension models. PMID:22518281

  19. Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium.

    PubMed

    Dieterle, Frank; Sistare, Frank; Goodsaid, Federico; Papaluca, Marisa; Ozer, Josef S; Webb, Craig P; Baer, William; Senagore, Anthony; Schipper, Matthew J; Vonderscher, Jacky; Sultana, Stefan; Gerhold, David L; Phillips, Jonathan A; Maurer, Gérard; Carl, Kevin; Laurie, David; Harpur, Ernie; Sonee, Manisha; Ennulat, Daniela; Holder, Dan; Andrews-Cleavenger, Dina; Gu, Yi-Zhong; Thompson, Karol L; Goering, Peter L; Vidal, Jean-Marc; Abadie, Eric; Maciulaitis, Romaldas; Jacobson-Kram, David; Defelice, Albert F; Hausner, Elizabeth A; Blank, Melanie; Thompson, Aliza; Harlow, Patricia; Throckmorton, Douglas; Xiao, Shen; Xu, Nancy; Taylor, William; Vamvakas, Spiros; Flamion, Bruno; Lima, Beatriz Silva; Kasper, Peter; Pasanen, Markku; Prasad, Krishna; Troth, Sean; Bounous, Denise; Robinson-Gravatt, Denise; Betton, Graham; Davis, Myrtle A; Akunda, Jackie; McDuffie, James Eric; Suter, Laura; Obert, Leslie; Guffroy, Magalie; Pinches, Mark; Jayadev, Supriya; Blomme, Eric A; Beushausen, Sven A; Barlow, Valérie G; Collins, Nathaniel; Waring, Jeff; Honor, David; Snook, Sandra; Lee, Jinhe; Rossi, Phil; Walker, Elizabeth; Mattes, William

    2010-05-01

    The first formal qualification of safety biomarkers for regulatory decision making marks a milestone in the application of biomarkers to drug development. Following submission of drug toxicity studies and analyses of biomarker performance to the Food and Drug Administration (FDA) and European Medicines Agency (EMEA) by the Predictive Safety Testing Consortium's (PSTC) Nephrotoxicity Working Group, seven renal safety biomarkers have been qualified for limited use in nonclinical and clinical drug development to help guide safety assessments. This was a pilot process, and the experience gained will both facilitate better understanding of how the qualification process will probably evolve and clarify the minimal requirements necessary to evaluate the performance of biomarkers of organ injury within specific contexts.

  20. Evaluation of snake envenomation-induced renal dysfunction in dogs using early urinary biomarkers of nephrotoxicity.

    PubMed

    Hrovat, A; Schoeman, J P; de Laat, B; Meyer, E; Smets, P; Goddard, A; Nagel, S; Daminet, S

    2013-10-01

    Renal dysfunction in dogs envenomed by poisonous snakes is currently detected using traditional serum and urinary biomarkers such as creatinine and proteinuria. However, these markers lack sensitivity at the early stages of renal dysfunction and their diagnostic accuracy is affected by pre-analytical factors commonly occurring in these dogs, such as haemolysis and haemoglobinuria. Early detection of renal dysfunction would allow for the identification of dogs requiring intensive treatment and monitoring and may help inform prognosis. The aim of this study was to evaluate the performance of several novel urinary biomarkers of glomerular dysfunction, namely, urinary albumin (uAlb), immunoglobulin G (uIgG) and C-reactive protein (uCRP) and of proximal tubular dysfunction (urinary retinol binding protein (uRBP)) compared to traditional end points in dogs with renal damage caused by snake envenomation. Biomarker results were compared between 19 dogs bitten by snakes producing either neurotoxins or cytotoxins and 10 clinically healthy controls. uAlb, uIgG, and uRBP were significantly increased in snake-envenomed dogs at presentation compared to controls, whereas only uIgG and uCRP were significantly elevated 24h post-envenomation. The urinary protein:creatinine ratio was also increased in envenomed dogs compared to controls, but because of the presence of haematuria and haemoglobinuria, differentiation between pre-renal and renal proteinuria was not possible. The results showed that these novel urinary biomarkers may assist in better detecting renal dysfunction in dogs envenomed by poisonous snakes at the acute disease stage compared to traditional laboratory endpoints.

  1. Renal function in diabetic nephropathy

    PubMed Central

    Dabla, Pradeep Kumar

    2010-01-01

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Thus, chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy. Cystatin-C (Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research. Various studies have shown the importance of measurement of albuminuria, eGFR, serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease. PMID:21537427

  2. Use of urinary renal biomarkers to evaluate the nephrotoxic effects of melamine or cyanuric acid in non-pregnant and pregnant rats.

    PubMed

    Bandele, O J; Stine, C B; Ferguson, M; Black, T; Olejnik, N; Keltner, Z; Evans, E R; Crosby, T C; Reimschuessel, R; Sprando, R L

    2014-12-01

    Although traditional assessments of renal damage detect loss of kidney function, urinary renal biomarkers are proposed to indicate early changes in renal integrity. The recent adulteration of infant formula and other milk-based foods with melamine revealed a link between melamine ingestion and nephropathy. Thus, the effects of melamine and related analogs (e.g., cyanuric acid) should be assessed in other potentially sensitive groups. We evaluated whether urinary Kim-1, clusterin, and osteopontin could detect the effects of high doses of melamine or cyanuric acid in pregnant and non-pregnant female rats gavaged with 1000 mg/kg bw/day for 10 days. We demonstrate that these biomarkers can differentiate the severity of effects induced by melamine or cyanuric acid. All melamine-treated animals experienced adverse effects; however, pregnant rats were most sensitive as indicated by increased SCr, BUN, and kidney weights, decreased body weight, and presence of renal crystals. These effects coincided with elevated urinary biomarker levels as early as day 2 of exposure. One cyanuric acid-treated rat displayed effects similar to melamine, including increased urinary biomarker levels. This work illustrates that these biomarkers can detect early effects of melamine or cyanuric acid crystal-induced nephropathy and further supports the use of urinary protein immunoassays as a powerful, non-invasive method to assess nephrotoxicity.

  3. Tissue and Metabolomic Biomarkers of Recurrent Renal Cell Carcinoma

    DTIC Science & Technology

    2013-04-01

    project. The cumulative data is currently being analyzed with the clinical data in the partnering PIs facility. 15. SUBJECT TERMS Kidney cancer ...American Association of Cancer Research Annual Meeting, Washington, DC, April 2013. Conclusions: We have developed a combined proteomics, metabolomics ...1 AD_________________ Award Number: W81XWH-10-1-0173 TITLE: Tissue and Metabolomic Biomarkers of

  4. 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.

  5. Homocysteine as a predictive biomarker in early diagnosis of renal failure susceptibility and prognostic diagnosis for end stages renal disease.

    PubMed

    Amin, Hatem K; El-Sayed, Mohamed-I Kotb; Leheta, Ola F

    2016-09-01

    Glomerular filtration rate and/or creatinine are not accurate methods for renal failure prediction. This study tested homocysteine (Hcy) as a predictive and prognostic marker for end stage renal disease (ESRD). In total, 176 subjects were recruited and divided into: healthy normal group (108 subjects); mild-to-moderate impaired renal function group (21 patients); severe impaired renal function group (7 patients); and chronic renal failure group (40 patients) who were on regular hemodialysis. Blood samples were collected, and serum was separated for analysis of total Hcy, creatinine, high sensitive C-reactive protein (CRP), serum albumin, and calcium. Data showed that Hcy level was significantly increased from normal-to-mild impairment then significantly decreases from mild impairment until the patient reaches severe impairment while showing significant elevation in the last stage of chronic renal disease. Creatinine level was increased in all stages of kidney impairment in comparison with control. CRP level was showing significant elevation in the last stage. A significant decrease in both albumin and calcium was occurred in all stages of renal impairment. We conclude Hcy in combination with CRP, creatinine, albumin, and calcium can be used as a prognostic marker for ESRD and an early diagnostic marker for the risk of renal failure.

  6. The utility of tetraspanin CD9 as a biomarker for metastatic clear cell renal cell carcinoma.

    PubMed

    Garner, Jo M; Herr, Michael J; Hodges, Kurt B; Jennings, Lisa K

    2016-02-26

    The use of tetraspanin CD9 as a biomarker for renal cell carcinomas (RCC) has been explored with minor conclusions. Identification of a biomarker that not only distinguishes between the different types of renal cell carcinomas, but also predicts the metastatic potential of these tumors would significantly advance diagnosis and prognosis of kidney cancers. We utilized established cell lines to better understand the contribution of CD9 to the metastatic potential of clear cell renal cell carcinomas, and then applied our findings to the TCGA database and immunohistochemical analysis of human samples based on tumor grading to determine the utility of CD9 as a biomarker for RCC. Clear cell renal cell carcinoma (ccRCC) cell expression of tetraspanin CD9 was compared to normal kidney cells and found to be elevated. Upon knockdown of CD9, ccRCC cells obtained a more metastatic phenotype. We found E-cadherin expression to be repressed and the endothelial to mesenchymal transition markers Snail, Twist1, and Zeb1 to be elevated upon CD9 knockdown. Upon observing these gene expression changes in the TCGA database and in 10 cases, we found that CD9 and E-cadherin expression was lowered in higher grade ccRCC tumors. There was a significant correlation between CD9 and either E-cadherin, Snail, or Zeb1 in these tumors. Collectively, using tetraspanin CD9 in tandem with E-cadherin as a biomarker in renal cell carcinoma will help to not only distinguish between types, but also predict the metastatic potential of RCC. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes.

    PubMed

    Betz, Boris B; Jenks, Sara J; Cronshaw, Andrew D; Lamont, Douglas J; Cairns, Carolynn; Manning, Jonathan R; Goddard, Jane; Webb, David J; Mullins, John J; Hughes, Jeremy; McLachlan, Stela; Strachan, Mark W J; Price, Jackie F; Conway, Bryan R

    2016-05-01

    Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m(2) (odds ratio 0.48; 95% confidence interval, 0.26-0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations.

  8. Effect of mercury (Hg) dental amalgam fillings on renal and oxidative stress biomarkers in children.

    PubMed

    Al-Saleh, Iman; Al-Sedairi, Al anoud; Elkhatib, Rola

    2012-08-01

    We examined the effect of mercury (Hg) associated with dental amalgam fillings on biomarkers of renal and oxidative stress in children between the ages of 5-15.5 years. Urine samples were analyzed for N-acetyl-β-D-glucosaminidase (NAG), α(1)-microglobulin (α(1)-MG), β(2)-microglobulin (β(2)-MG), retinol binding protein (RBP), albumin (ALB), 8-hydroxy-2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). The level of urinary Hg (UHg-C) was calculated as μg/g creatinine. Multiple regression analyses revealed that the excretion of urinary NAG was significantly associated with the presence of dental amalgam fillings (β=0.149, P=0.03) and the levels of UHg-C (β=0.531, P=0), with an interaction between the two (P=0). The increase in urinary NAG in relation to UHg-C levels had a dose-effect pattern. The lowest observed effect was seen at UHg-C levels above 1.452 μg/g creatinine, which is lower than previously reported. In contrast, α(1)-MG was negatively associated with the presence of dental amalgam fillings (β=-0.270, P=0), but positively with UHg-C levels (β=0.393, P=0). There were 7 children without, and one child with, dental amalgam fillings with urinary α(1)-MG levels above the reference limit of >7 mg/g creatinine. Even though α(1)-MG seems to be a reliable biomarker for early changes in renal functions, it might exert its effect only at a higher level of exposure. An inverse relationship was also observed between urinary 8-OHdG levels and the presence of dental amalgam fillings. This might suggest that the dental amalgam does not increase DNA damage but reduces the capacity to repair DNA, leading to lower urinary excretion of 8-OHdG. On the other hand, we found that Hg affected the excretion of urinary 8-OHdG in a dose-related pattern that was mostly associated with long-term exposure to low Hg levels. Urinary NAG levels were positively associated with urinary MDA levels (β=0.516, P=0) but not with 8-OHdG (β=0.134, P=0.078) after adjustment for

  9. Renal function in cyanotic congenital heart disease.

    PubMed

    Burlet, A; Drukker, A; Guignard, J P

    1999-01-01

    We performed renal function tests in 18 young patients, 1.8-14.6 years of age, with cyanotic congenital heart disease (CCHD). Glomerular filtration rate was normal (116 +/- 4.5 ml/min/1.73 m2), and renal plasma flow was decreased (410 +/- 25 ml/min/1.73 m2) with a rise in the filtration fraction (29 +/- 1.1%). The suggested pathophysiologic explanation of these findings is that the blood hyperviscosity seen in patients with CCHD causes an overall increase in renal vascular resistance with a rise in intraglomerular blood pressure. Despite a sluggish flow of blood in the glomerular capillary bed, the effective filtration pressure was adjusted to conserve the glomerular filtration rate. In addition to these renal hemodynamic parameters, we also studied renal acidification and tubular sodium and water handling during a forced water diuresis. Our data indicate that children with CCHD have a mild to moderate normal ion gap metabolic acidosis due to a low proximal tubular threshold for bicarbonate. Proximal tubular sodium and water reabsorption under these conditions were somewhat increased, though not significantly, probably due to intrarenal hydrostatic forces, in particular the rise in the oncotic pressure in the postglomerular capillaries in patients with high hematocrit values. The distal tubular functions such as sodium handling and acidification were not affected.

  10. Optical Detection of Hepatic and Renal Function.

    NASA Astrophysics Data System (ADS)

    Dorshow, Richard B.; Bugaj, Joseph E.; Burleigh, B. Daniel; Johnson, Michael A.; Jones, William B.; Duncan, James R.

    1997-03-01

    The feasibility of a new methodology for organ function determination, based on optical detection, is investigated. Differentiation between normal and abnormal organ function is demonstrated in an animal model for both the liver and the kidney. Two commercial dyes were employed in this initial study. Characteristic blood clearance curves associated with normal hepatic function and normal renal function are obtained. Upon ablation of a portion of the liver, the clearance curve ascribed to hepatic function is greatly extended as expected. Upon ligation of both kidneys, the clearance curve ascribed to renal function remains elevated and constant, indicating little if any clearance. The clearance curves are fit to standard physiological compartment models to yield quantitative information on decay times.

  11. Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion.

    PubMed

    Mohamed, Fahim; Buckley, Nicholas A; Jayamanne, Shaluka; Pickering, John W; Peake, Philip; Palangasinghe, Chathura; Wijerathna, Thilini; Ratnayake, Indira; Shihana, Fathima; Endre, Zoltan H

    2015-09-02

    Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine samples from patients from 5 Sri Lankan hospitals. Functional AKI was diagnosed using serum creatinine (sCr) or serum cystatin C (sCysC). The 95th centile in healthy subjects defined the urinary biomarker cutoffs for diagnosing structural AKI. 50 poisoned patients provided 2 or more specimens, 76% developed functional AKI [AKIN stage 1 (n=12), 2 (n=7) or 3 (n=19)]; 19/26 patients with AKIN stage 2/3 also had functional AKI by sCysC criteria (≥50% increase). Urinary cystatin C (uCysC), clusterin (uClu) and NGAL (uNGAL) increased within 24h of ingestion compared with NoAKI patients and healthy controls. Each biomarker demonstrated moderate diagnostic utility [AUC-ROC: uCysC 0.79, uNGAL 0.79, uClu 0.68] for diagnosis of functional AKI at 16h. Death occurred only in subjects with functional AKI. Structural biomarker-based definitions detected more AKI than did sCr or sCysC, but did not independently predict death. Renal injury biomarkers did not add clinical value to patients who died rapidly due to multi-organ failure. Use of injury biomarkers within 16-24h may guide early intervention for reno-protection in less severe paraquat poisoning.

  12. Characterization of kidney damage using several renal biomarkers in dogs with naturally occurring heatstroke.

    PubMed

    Segev, G; Daminet, S; Meyer, E; De Loor, J; Cohen, A; Aroch, I; Bruchim, Y

    2015-11-01

    Heatstroke is often associated with acute kidney injury (AKI). The objectives of this study were to characterize the kidney damage occurring in canine heatstroke using routine and novel biomarkers and to assess their diagnostic and prognostic performance. Thirty dogs with naturally occurring heatstroke were enrolled prospectively. Blood and urine specimens were collected at presentation, at 4 h post-presentation and every 12 h until discharge or death. The glomerular filtration rate (GFR) and electrolyte fractional excretion (FE) at 4 h post-presentation were also calculated, based on urinary clearances. AKI was further characterized by evaluating urine neutrophil gelatinase-associated lipocalin/creatinine ratio (UNGAL), urine retinol-binding protein/creatinine ratio (URBP), urine C-reactive protein/creatinine ratio (UCRP) and urine protein to creatinine ratio (UPC). These biomarkers were compared to those for 13 healthy dogs. Thirteen dogs (43%) died and 17 (57%) survived. Median serum creatinine concentration at presentation was 1.69 mg/dL (range, 0.5-4.7 mg/dL), while concurrent GFR was markedly decreased (median 0.60 mL/min/kg; range, 0.00-3.10 mL/min/kg). Median Na fractional excretion was 0.08 (range, 0.01-0.41) and was an accurate predictor of AKI (area under curve 0.89; 95% confidence intervals 0.76-1.00). Median UPC at presentation was 4.8 (range, 0.4-46.0). Median UCRP, URBP and UNGAL were increased in all dogs with heatstroke, and were mean 232, 133, and 1213-fold higher than healthy control dogs, respectively. In conclusion, although AKI occurs invariably in dogs with heatstroke, it is often subclinical at presentation. Damage occurs in both the renal tubules and the glomeruli. Novel kidney function tests for the characterization of renal injury and its severity are superior to conventional markers and could be used to facilitate early diagnosis of AKI.

  13. Urinary Aminopeptidase Activities as Early and Predictive Biomarkers of Renal Dysfunction in Cisplatin-Treated Rats

    PubMed Central

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

    2012-01-01

    This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p<0.011; r2>0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice. PMID:22792302

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

    PubMed

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

    2012-01-01

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

  15. Biomarkers for evaluating racial disparities in clinical outcome in patients with renal cell carcinoma.

    PubMed

    Harris, Wayne B

    2015-11-01

    The bulk of the literature on kidney cancer in African Americans comes from population-based studies of incidence and survival over varying periods of time using databases from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI). The purpose of this review is to summarize the literature on racial disparities in clinical outcome in patients with renal cell carcinoma (RCC) with the objective of identifying any biomarkers that might point to a biological explanation for these differences. Special attention is given to biomarkers of systemic inflammation and their potential utility for kinetic risk assessment. In addition, arguments are presented as to why the study of ethnic and racial disparities is a promising strategy for accelerating the pace of biomarker development for all patients with RCC.

  16. Renal cell carcinoma: a critical analysis of metabolomic biomarkers emerging from current model systems.

    PubMed

    Rodrigues, Daniela; Monteiro, Márcia; Jerónimo, Carmen; Henrique, Rui; Belo, Luís; Bastos, Maria de Lourdes; Guedes de Pinho, Paula; Carvalho, Márcia

    2017-02-01

    Metabolomics, an emerging field of "omics" sciences, has caught wide scientific attention in the area of biomarker research for cancers in which early diagnostic biomarkers have the potential to greatly improve patient outcome, such as renal cell carcinoma (RCC). Metabolomic approaches have been successfully applied to various human RCC model systems, mostly ex vivo neoplastic renal tissues and biofluids (urine and serum) from patients with RCC. Importantly, in contrast to other cancers, only a few studies have addressed the RCC metabolome using cancer cell culture-based in vitro models. Herein, we first carried out a comprehensive review of current metabolomic data in RCC, with emphasis on metabolite disturbances and dysregulated metabolic pathways identified in each of these experimental models. We then critically analyzed the consistency of evidence in this field and whether metabolites found altered in tumor cell and tissue microenvironment are reflected in biofluids, which constitute the rationale underlying the translation of discovered metabolic biomarkers into noninvasive diagnostic tools. Finally, dominant metabolic pathways and promising metabolites as biomarkers for diagnosis and prognosis of RCC are outlined.

  17. Evaluation of oxidative stress biomarkers in patients with chronic renal failure: a case control study

    PubMed Central

    2010-01-01

    Background Oxidative stress is related to several diseases, including chronic renal insufficiency. The disequilibrium in the oxidant-antioxidant balance is the result of several metabolic changes. The majority of studies to-date have evaluated the grade of oxidative stress with a single biomarker, or a very limited number of them. Findings The present study used several important biomarkers to establish a score relating to oxidative stress status (glutathione S-transferase, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced and oxidized glutathione, thiobarbituric acid reactive substances and hemolysis test). The score of oxidative stress (SOS) was then applied to a group of patients with renal insufficiency not on hemodialysis, and compared to healthy control individuals. The score for patients with chronic renal insufficiency was significantly different from that of the healthy control group (0.62 ± 1.41 vs. -0.05 ± 0.94; p < 0.001). The comparison between patients with chronic renal insufficiency and control individuals showed significant differences with respect to changes in the enzymatic antioxidant systems (glutathione S-transferase, glutathione reductase), non-enzymatic antioxidant system (oxidized glutathione) and oxidizability (hemolysis test) indicating significant oxidative stress associated with chronic renal insufficiency. Conclusions Patients with chronic renal insufficiency not on hemodialysis are susceptible to oxidative stress. The mechanisms that underlie this status are the consequence of changes in glutathione and related enzymes. The SOS scoring system is a useful biochemical parameter to evaluate the influence of oxidative stress on the clinical status of these patients. PMID:20181004

  18. Urinary l-type fatty acid-binding protein is a predictor of early renal function after partial nephrectomy.

    PubMed

    Yanishi, Masaaki; Kinoshita, Hidefumi; Mishima, Takao; Taniguchi, Hisanori; Yoshida, Kenji; Komai, Yoshihiro; Yasuda, Kaneki; Watanabe, Masato; Sugi, Motohiko; Matsuda, Tadashi

    2017-11-01

    Urinary biomarkers of renal injury urinary may identify loss of renal function following nephron-sparing surgery (NSS). This study was designed to evaluate whether urinary l-type fatty acid-binding protein (l-FABP) is an early biomarker of loss of renal function after NSS. Specifically, the kinetics of urinary l-FABP level after NSS and its correlation with factors related to ischemic renal injury were analyzed. This study prospectively evaluated 18 patients who underwent NSS between July and December 2014, including 12 who underwent laparoscopic and six who underwent robot-assisted partial nephrectomy. Urinary l-FABP concentrations were measured preoperatively and 1, 2, 3, 6, 12, 24, 48, and 72 h after renal artery declamping. Loss of renal function loss was calculated by comparing the effective renal plasma flow, as determined by (99m)Tc-mercaptoacetyltriglycine (MAG3) clearance, on the operated and normal sides. The decrease in estimated glomerular filtration rate from before surgery to six months after surgery was also measured. Urinary l-FABP concentration peaked within 2 h of declamping, which may quantify nephron damage caused by ischemia. The decrease in MAG3 reduction ratio correlated with both the ischemia time and peak urinary l-FABP concentration. Peak urinary l-FABP concentration showed a significant correlation with MAG3 reduction ratio. l-FABP is a suitable urinary biomarker for predicting the extent of ischemic renal injury.

  19. Environment biomarkers: Fiction, fantasy, or functional?

    SciTech Connect

    McCarty, L.S.; Munkittrick, K.R.

    1995-12-31

    The first biomarkers used in ecotoxicology were biochemical in nature. Subsequently, this approach was extended to other levels of biological organization. Although popular biomarkers can be problematic. They can be viewed as a ``short-cut`` methodology which must ultimately be based on a clear understanding of an established biological indicator. Thus, a biomarker should be a quantitative or semi-quantitative surrogate measurement for either cause or effect (i.e., dose or response). If the biomarker-biological indicator relationship is established a biomarker can be a useful, practical, scientifically valid tool. Unfortunately, validation is not common and some current biochemical biomarker approaches are critically examined in this regard under the categories of exposure (dose), effect (response), and causality. Observations include: (1) Most popular biochemical biomarkers provide only qualitative estimates of exposure which are of underwhelming value as some exposure can essentially be assumed at many sites of concern. (2) At the same site different biomarkers can suggest exactly opposite trends and conclusions. (3) Correlation between a biomarker and an effect does NOT prove causality. Biomarkers, biochemical or otherwise, represent a ``short-cut`` that should be used only after both a general validation of the concept and a site specific confirmation of applicability.

  20. Posterior urethral valves: relationship between vesicoureteral reflux and renal function.

    PubMed

    Cozzi, Denis A; Morgante, Debora; Frediani, Simone; Iaconelli, Romina; Ceccanti, Silvia; Mele, Ermelinda; Cozzi, Francesco

    2011-05-01

    To investigate the relationship between renal function and vesicoureteral reflux before and after valve ablation in patients with posterior urethral valves. In these patients, back pressure may not be the only cause of renal damage. We conducted a retrospective review of 37 patients with valves consecutively treated between 1970 and 2002. Data were available for 31 patients, 19 of whom presented reflux at presentation. Grade of reflux was ascertained by voiding cystourethrography. Overall renal function was measured by serum creatinine, and split renal function was estimated by dimercaptosuccinic acid scan available for all patients but two. Before relief of obstruction, there was no correlation between split renal function and grade of reflux into 25 kidneys of the 17 patients (r = -.13; 95% CI, -.50 to .27; P = .51). High-grade reflux (grade IV-V) affected 6 of the 11 renal units, with split renal function >40% vs 11 of the 14 units with split renal function <40% (P = .38). After successful valve ablation, reflux resolved in all the 11 units with split renal function >40% vs 4 of the 14 units with split renal function <40% (P = .0005). The good renal function of more than half of the renal units with high-grade reflux at presentation, and the persistence of reflux mainly in nonfunctioning or poorly functioning kidneys after valve ablation, support the concept that in some patients with valves, reflux and renal damage are associated anomalies. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Precision Oncology: Identifying Predictive Biomarkers for the Treatment of Metastatic Renal Cell Carcinoma

    PubMed Central

    Modi, Parth K.; Farber, Nicholas J.; Singer, Eric A.

    2016-01-01

    The recent FDA approval of multiple new pharmaceutical agents for metastatic renal cell carcinoma (RCC) has left physicians with several options for first- and second- line therapy. With limited head-to-head comparisons, however, there is a paucity of evidence to recommend the use of one agent over another. To address this knowledge gap, Voss et al. identified serum biomarkers from specimens collected during the RECORD-3 trial, a comparative study of first-line sunitinib versus first-line everolimus. Of the biomarkers identified, the 5 most strongly associated with first-line everolimus progression-free survival (PFS1L) were combined to form a composite biomarker score (CBS). The CBS was significantly associated with everolimus PFS1L in multivariate regression analysis. This study is an example of the additional value offered by a randomized trial with prospective biospecimen collection and a significant step towards identifying predictive biomarkers for the treatment of metastatic RCC. As further comparative trials are performed, it will be essential that biomarkers are appropriately identified and validated in order to further the goal of precision oncology. PMID:27540511

  2. Biomarkers of Aging: From Function to Molecular Biology.

    PubMed

    Wagner, Karl-Heinz; Cameron-Smith, David; Wessner, Barbara; Franzke, Bernhard

    2016-06-02

    Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

  3. Biomarkers of Aging: From Function to Molecular Biology

    PubMed Central

    Wagner, Karl-Heinz; Cameron-Smith, David; Wessner, Barbara; Franzke, Bernhard

    2016-01-01

    Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products. PMID:27271660

  4. Kidney function outcomes following thermal ablation of small renal masses

    PubMed Central

    Raman, Jay D; Jafri, Syed M; Qi, David

    2016-01-01

    The diagnosis of small renal masses (SRMs) continues to increase likely attributable to widespread use of axial cross-sectional imaging. Many of these SRMs present in elderly patients with abnormal baseline renal function. Such patients are at risk for further decline following therapeutic intervention. Renal thermal ablation presents one approach for management of SRMs whereby tumors are treated in situ without need for global renal ischemia. These treatment characteristics contribute to favorable renal function outcomes following kidney tumor ablation particularly in patients with an anatomic or functional solitary renal unit. PMID:27152264

  5. Proteome analysis of acute kidney injury - Discovery of new predominantly renal candidates for biomarker of kidney disease.

    PubMed

    Malagrino, Pamella Araujo; Venturini, Gabriela; Yogi, Patrícia Schneider; Dariolli, Rafael; Padilha, Kallyandra; Kiers, Bianca; Gois, Tamiris Carneiro; Cardozo, Karina Helena Morais; Carvalho, Valdemir Melechco; Salgueiro, Jéssica Silva; Girardi, Adriana Castello Costa; Titan, Silvia Maria de Oliveira; Krieger, José Eduardo; Pereira, Alexandre Costa

    2017-01-16

    The main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are organ and process specific. Here, we have used different tissues from a controlled porcine renal ischemia/reperfusion (I/R) model to identify new, predominantly renal biomarker candidates for kidney disease. Urine and serum samples were analyzed in pre-ischemia, ischemia (60min) and 4, 11 and 16h post-reperfusion, and renal cortex samples after 24h of reperfusion. Peptides were analyzed on the Q-Exactive™. In renal cortex proteome, we observed an increase in the synthesis of proteins in the ischemic kidney compared to the contralateral, highlighted by transcription factors and epithelial adherens junction proteins. Intersecting the set of proteins up- or down-regulated in the ischemic tissue with both serum and urine proteomes, we identified 6 proteins in the serum that may provide a set of targets for kidney injury. Additionally, we identified 49, being 4 predominantly renal, proteins in urine. As prove of concept, we validated one of the identified biomarkers, dipeptidyl peptidase IV, in a set of patients with diabetic nephropathy. In conclusion, we identified 55 systemic proteins, some of them predominantly renal, candidates for biomarkers of renal disease.

  6. Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication

    PubMed Central

    Pires-Luís, Ana Sílvia; Vieira-Coimbra, Márcia; Vieira, Filipa Quintela; Costa-Pinheiro, Pedro; Silva-Santos, Rui; Dias, Paula C; Antunes, Luís; Lobo, Francisco; Oliveira, Jorge; Gonçalves, Céline S; Costa, Bruno M; Henrique, Rui; Jerónimo, Carmen

    2015-01-01

    Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of 3 genes—SMYD2, SETD3, and NO66—was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity [area under curve (AUC) = 0.959], and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC = 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness. PMID:26488939

  7. Urinary exosomal transcription factors, a new class of biomarkers for renal disease

    PubMed Central

    Zhou, Hua; Cheruvanky, Anita; Hu, Xuzhen; Matsumoto, Takayuki; Hiramatsu, Noriyuki; Cho, Monique E.; Berger, Alexandra; Leelahavanichkul, Asada; Doi, Kent; Chawla, Lakhmir S.; Illei, Gabor G.; Kopp, Jeffrey B.; Balow, James E.; Austin, Howard A.; Yuen, Peter S.T.; Star, Robert A.

    2008-01-01

    Urinary exosomes are excreted from all nephron segments and are a rich source of kidney injury biomarkers. Because exosomes contain intracellular proteins, we asked if transcription factors (TF) can be measured in urinary exosomes. We collected urine from two acute kidney injury (AKI) models (cisplatin or ischemia/reperfusion) and two podocyte injury models (puromycin-treated rats and podocin/Vpr transgenic mice). Human urine was obtained from patients with AKI, focal segmental glomerulosclerosis (FSGS), and matched controls. After isolating urine exosomes by differential centrifugation, activating transcription factor 3 (ATF3) and Wilms Tumor 1 (WT-1) were detected by western blot. ATF3 was continuously detected in urine exosomes 2–24 hr after ischemia/reperfusion and in a biphasic pattern after cisplatin. In both models, urinary ATF3 was detected earlier than serum creatinine. Urinary ATF3 was detected in AKI patients but not in normal subjects or patients with chronic kidney disease (CKD). Urinary WT-1 was detected in animal models before significant glomerular sclerosis. Urinary WT-1 was detected in 9/10 FSGS patients, but not in 8 controls. Transcription factors can be detected in urine exosomes, but not in whole urine. Urinary ATF3 may be a novel renal tubular cell injury biomarker for detecting early AKI, whereas urinary WT-1 may detect early podocyte injury. Urinary exosomal TFs represent a new class of biomarkers for acute and chronic renal diseases and may offer insight into cellular regulatory pathways. PMID:18509321

  8. Urinary neutrophil gelatinase-associated lipocalin is a potential biomarker for renal damage in patients with systemic lupus erythematosus.

    PubMed

    Yang, Chun-Chen; Hsieh, Song-Chou; Li, Ko-Jen; Wu, Cheng-Han; Lu, Ming-Chi; Tsai, Chang-Youh; Yu, Chia-Li

    2012-01-01

    Neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a novel biomarker in acute and chronic kidney disease. We hypothesized that 24-hour urinary NGAL excretion may be a predictor for renal damage in patients with systemic lupus erythematosus (SLE). Thirty-four SLE patients with renal involvement (SLE-renal group), 8 SLE patients without renal involvement (SLE-nonrenal group), 14 patients with non-SLE autoimmune diseases (disease control or DC group), and 12 healthy volunteers (normal control or NC group) were compared for 24-hour urinary excretion of NGAL and different cytokines. We found that the 24-hour urinary NGAL excretion in the SLE-renal group was higher than that in the SLE-non-renal, DC, and NC groups. However, the excretion of interleukin-10, transforming growth factor-β1, and tumor necrosis factor-α was not different between the SLE-renal and SLE-non-renal groups. Furthermore, NGAL excretion in the SLE-renal group was correlated with serum creatinine levels and creatinine clearance, but not with the SLE Disease Activity Index score. Multivariate logistic regression analysis and receiver operating characteristic curve analysis revealed that 24-hour urinary NGAL excretion is a potential biomarker for renal damage in SLE patients, with higher sensitivity and specificity than anti-dsDNA antibody titers.

  9. LncRNAs act as prognostic and diagnostic biomarkers in renal cell carcinoma: a systematic review and meta-analysis

    PubMed Central

    Gu, Liangyou; Li, Xintao; Gao, Yu; Lyu, Xiangjun; Chen, Luyao; Luo, Guoxiong; Wang, Lei; Xie, Yongpeng; Duan, Junyao; Peng, Cheng; Ma, Xin

    2016-01-01

    We conducted a systematic review and meta-analysis to investigate the clinical values, including clinicopathology, prognosis, and diagnosis of different long non-coding RNAs (lncRNAs) in renal cell carcinoma (RCC). A total of 14 eligible studies, including 10 on clinicopathological features, 11 on prognosis, and 3 on diagnosis were identified. Results revealed that metastasis-associated lung adenocarcinoma transcript 1(MALAT1) expression was associated with tumor stage (odds ratio [OR], 3.46; 95% confidence interval [CI], 1.63-7.36; p=0.001). The high expression of MALAT1 could be considered a biomarker of the early detection of lymph node metastasis and predictor of poor survival in RCC patients, who likely manifested short overall survival (OS; hazard ratio [HR], 2.97; 95% CI, 1.68-5.28; p<0.001). For diagnostic value, the pooled result showed that lncRNA maintained a sensitivity of 0.89 and specificity of 0.91 in RCC diagnosis, The area under the curve of 0.94 (95% CI, 0.92-0.96) for lncRNA in RCC diagnosis also indicated a significant advantage over other biomarkers. Our systematic review and meta-analysis demonstrated that lncRNAs could be considered biomarkers to detect lymph node metastasis and distant metastasis in early stages. LncRNAs could function as potential prognostic markers in RCC. LncRNAs could also display high accuracy for RCC diagnosis. PMID:27527868

  10. Role of renal nerves on renal functional change after back heating in the rat.

    PubMed

    Chen, C F; Chien, C T; Wu, M S; Fu, T C

    1994-06-20

    This study was designed to investigate the possible role of renal nerves in the regulation of renal function after the application of heat (BH), by means of an electric heating pad (42 +/- 1 degree C) to the skin of the back overlying the kidneys. Both renal efferent (RENA) and renal afferent nervous activity (RANA) were recorded in 7 anesthetized female Wistar rats. It was found that RENA reduced to less than 80% of the control level during 30 min of back heating, accompanied by an increase in excretion of urine, sodium and potassium, and enhanced the glomerular filtration rate. BH in 9 chronic bilateral renal denervated rats (RD) showed the same renal responses as in the renal nerve intact rats (RI) after back heating. It is concluded that renal nerves played only a partially role in the renal diuretic action of back heating.

  11. Visual determination of differential renal function

    SciTech Connect

    Kipper, M.S.; Witztum, K.F.; Taylor, A. Jr.

    1986-05-01

    Forty patients (43 studies) referred for determination of differential renal function were imaged 24 hours after intravenous administration of Tc-99m-2, 3 DMSA. Visual assessment of relative renal uptake was estimated independently by three observers at three different hospitals from analog images on standard x-ray film. The results were compared with the relative DMSA uptake obtained by summing counts in computer-assisted regions of interest placed over each kidney. There was excellent correlation between the visual estimates of each observer and the computer-generated values (r = 0.98, 0.96, and 0.98, respectively). If a computer is not available, good visual estimates of differential uptake still may be obtained when static imaging agents such as DMSA are administered.

  12. Why and how to measure renal function in patients with liver disease.

    PubMed

    Piano, Salvatore; Romano, Antonietta; Di Pascoli, Marco; Angeli, Paolo

    2017-01-01

    Patients with advanced liver disease frequently have impaired renal function. Both acute kidney injury (AKI) and chronic kidney disease (CKD) are quite common in patients with cirrhosis and both are associated with a worse prognosis in these patients. A careful assessment of renal function is highly important in these patients to help physicians determine their diagnosis, prognosis and therapeutic management and to define transplantation strategies (liver transplantation alone vs simultaneous liver and kidney transplantation). Although they are still widely used in clinical practice, conventional biomarkers of renal function such as serum creatinine have several limitations in these patients. Recent progress has been made in the evaluation of renal function and new diagnostic criteria for AKI have been proposed. However, certain issues such as the noninvasive assessment of the glomerular filtration rate and/or improvement in the differential diagnosis between hepatorenal syndrome and acute tubular necrosis must still be addressed. The purposes of this paper are: (i) to highlight the importance of the evaluation of renal function in patients with cirrhosis; (ii) to review the state of the art in the assessment of renal function in these patients as well as advances that we expect will be made to improve the accuracy of available tools. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Changes in differential renal function after pyeloplasty in children.

    PubMed

    Harraz, Ahmed M; Helmy, Tamer; Taha, Diaa-Eldin; Shalaby, Ibrahim; Sarhan, Osama; Dawaba, Moahmed; Hafez, Ashraf T

    2013-10-01

    Previous series showed controversial differential renal function outcomes after pyeloplasty in children. However, they were limited by study power, methodology and lack of comparable end points. We determined the status of differential renal function after pyeloplasty in children in what is to our knowledge the largest series to date. After excluding patients with renal anomalies, solitary kidney or bilateral pyeloplasty from analysis, we retrospectively identified 196 younger than 18 years who were treated with pyeloplasty between May 2002 and January 2010 and had preoperative and postoperative renal scintigraphy available. Primary outcome measures were greater than 5% improvement in baseline differential renal function and baseline weighted differential renal function at last followup. Clinical variables predicting outcome measures were determined using univariable and multivariable analyses. During a median followup of 12 months, mean ± SD differential renal function improved from 35.8% ± 10% to 38.7% ± 11% (p <0.001). In the poor and intermediate groups baseline differential renal function improved, while in the good group function was static postoperatively (p <0.001). The linear regression model showed that only baseline differential renal function explained the variance in baseline weighted differential renal function (β = -0.393, p <0.001). In the Cox proportional hazards model baseline differential renal function (less than 35% HR 3.196, p <0.001 and 35% to 40% HR 2.733, p = 0.002) and cortical thickness (HR 2.114, p = 0.029) were the only predictors of a greater than 5% improvement in postoperative differential renal function. Renal function improves after pyeloplasty in children. Baseline differential renal function and cortical thickness predict improvement after surgery. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  14. Biomarkers in chronic kidney disease, from kidney function to kidney damage

    PubMed Central

    Lopez-Giacoman, Salvador; Madero, Magdalena

    2015-01-01

    Chronic kidney disease (CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate (GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine (SCr) and cystatin C (CysC). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associations with disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 mL/min per 1.73 m2. Equations combining CysC and SCr perform better than the equations using either CysC or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, CysC and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD. PMID:25664247

  15. Biomarkers and Personalized Therapy in Lower Functional Gastrointestinal Disorders

    PubMed Central

    Camilleri, Michael

    2015-01-01

    SUMMARY Background Treatment of IBS and lower functional gastrointestinal disorders is still based predominantly on symptoms; biomarkers that reflect the mechanism or pathophysiology have been identified. Given the diverse mechanisms that result in the same clinical phenotype of IBS, it is hypothesized that identification of biomarkers may lead to individualization of medical therapy. Aim To review the biomarkers that have been appraised in IBS. Methods A single author reviewed the published literature on biomarkers appraised in IBS. Results The current literature suggests that these biomarkers are insufficiently sensitive or specific to differentiate IBS from health or from other diseases causing similar symptoms, such as celiac disease or inflammatory bowel disease. Most of the proposed biomarkers are not actionable, that is, they do not lead to an efficacious therapy based on the biological inference of the biomarker itself. However, among proposed biomarkers in IBS, some are actionable, as they specifically reflect a quantitative difference in a mediator of dysfunction or result in a quantifiable disturbance of function that can be specifically treated. Such biomarkers may potentially identify relevant subgroups that respond to specific therapy. The most promising actionable biomarkers are measurement of colonic transit (leading to treatments that reverse the abnormal transit) and measurements of bile acid diarrhea to identify responders to bile acid sequestrants. Conclusions Therefore, although biomarkers are not ready for prime time as diagnostic tests in IBS, some biomarkers could identify subgroups of patients with IBS for inclusion in clinical trials that target specific dysfunctions. Such an approach may enhance treatment efficacy, and may ultimately help reduce costs in drug development and in the management of patients in clinical practice. PMID:26264216

  16. Anatrophic nephrolithotomy: preservation of renal function demonstrated by differential quantitative radionuclide renal scans

    SciTech Connect

    Belis, J.A.; Morabito, R.A.; Kandzari, S.J.; Lai, J.C.; Gabriele, O.F.

    1981-06-01

    Differential quantitative radionuclide renal scans have been used to confirm that early removal of staghorn calculi by anatrophic nephrolithotomy preserves renal parenchyma without significant renal damage by the surgical procedure. The /sup 99m/technetium diethylenetriaminepentaacetic acid scan was useful in predicting recovery of function in the involved kidney, while the /sup 131/iodine orthoiodohippurate scan provided a quantitative evaluation of the effect of the surgical procedure on individual kidney function. All of 13 consecutive patients evaluated by /sup 131/iodine orthoiodohippurate renal scans had stable or improved effective renal plasma flow to the involved kidney and an unchanged or improved total excretory index 6 months after nephrolithotomy.

  17. Anatrophic nephrolithotomy: preservation of renal function demonstrated by differential quantitative radionuclide renal scans.

    PubMed

    Belis, J A; Morabito, R A; Kandzari, S J; Lai, J C; Gabriele, O F

    1981-06-01

    Differential quantitative radionuclide renal scans have been used to confirm that early removal of staghorn calculi by anatrophic nephrolithotomy preserves renal parenchyma without significant renal damage by the surgical procedure. The 99mtechnetium diethylenetriaminepentaacetic acid scan was useful in predicting recovery of function in the involved kidney, while the 131iodine orthoiodohippurate scan provided a quantitative evaluation of the effect of the surgical procedure on individual kidney function. All of 13 consecutive patients evaluated by 131iodine orthoiodohippurate renal scans had stable or improved effective renal plasma flow to the involved kidney and an unchanged or improved total excretory index 6 months after nephrolithotomy.

  18. [Renal function study assessed by 99mTc-DMSA renal scintigraphy before and after PNL].

    PubMed

    Sakurai, M; Hioki, T; Okuno, T; Sugimura, Y; Yamakawa, K; Yanagawa, M; Tajima, K; Tochigi, H; Kawamura, J

    1990-01-01

    99mTc-DMSA renal scintigraphy was carried out in 54 patients with unilateral renal stones before and after PNL. Four to 8 weeks after PNL the DMSA renal uptake significantly decreased to 17.2 +/- 6.0% from 18.2 +/- 6.7% before PNL. DMSA renal uptake did not change in the contralateral side. Since in some patients changes in the DMSA renal uptake of 5-7% were observed after PNL not only in the PNL side but also in the contralateral side, the renal function was assessed by the formula: DMSA renal uptake in the PNL side/DMSA renal uptake in the contralateral side, and the change of this ratio was evaluated in 44 patients, in whom the renal DMSA uptake in the PNL side was less than two times that in the contralateral side. The DMSA renal uptake ratio decreased to 95.6 +/- 8.7% from the base line 4-8 weeks after PNL. This change was statistically significant. Some functional risks such as massive bleeding with PNL, the fever after PNL and the number of nephrostomy tract did not affect the decrease in the renal function. In 29 patients in whom renal function was reevaluated one year after PNL, the DMSA renal uptake ratio significantly decreased to 94.2 +/- 9.6% from the base line 4-8 weeks after PNL. But the ratio significantly improved to 99.6 +/- 11.6% about one year after PNL. In two patients with a cold area on the renal image, the renal function of the operated side still remained at about 80% levels from the base line even one year after PNL.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Protective effect of Garcinia against renal oxidative stress and biomarkers induced by high fat and sucrose diet

    PubMed Central

    2011-01-01

    Background Obesity became major health problem in the world, the objective of this work was to examine the effect of high sucrose and high fat diet to induce obesity on antioxidant defense system, biochemical changes in blood and tissue of control, non treated and treated groups by administration of Garcinia cambogia, and explore the mechanisms that link obesity with altered renal function Methods Rats were fed a standard control diet for 12 week (wk) or a diet containing 65% high sucrose (HSD) or 35% fat (HFD) for 8 wk and then HFD group divided into two groups for the following 4 wks. One group was given Garcinia+HFD, the second only high fat, Also the HSD divided into two groups, 1st HSD+Garcinia and 2nd HSD. Blood and renal, mesenteric, Perirenal and epididymal adipose tissues were collected for biochemical assays. Results HFD and HSD groups of rats showed a significant increase in feed intake, Body weight (BW) and body mass index (BMI). Also there were significant increases in weights of mesenteric, Perirenal and epididymal adipose tissues in HFD and HSD groups. HFD and HSD affect the kidney by increasing serum urea and creatinine levels and decreased level of nitric oxide (NO) and increased blood glucose, low density lipoproteins (LDL), triacylglycerol (TG), total cholesterol (TC) and malondialdehyde (MDA). Glucose 6-phosphate dehydrogenase (G6PD) activities were significantly decreased in HFD while there were significant increases in HSD and HSD+G groups p ≤ 0.05 compared with control. Moreover, renal catalase activities and MDA levels were significantly increased while NO level was lowered. These changes improved by Garcinia that decreased the oxidative stress biomarkers and increased NO level. There were significant positive correlations among BMI, kidney functions (Creatinine and urea), TG and Oxidative markers (renal MDA and catalase). Conclusions Rats fed a diet with HFD or HSD showed, hypertriglyceridemia, increased LDL production, increased

  20. Optimising assessment of kidney function when managing localised renal masses.

    PubMed

    Ellis, Robert J; Joshi, Andre; Ng, Keng L; Francis, Ross S; Gobe, Glenda C; Wood, Simon T

    2017-08-07

    Increased early and incidental detection, improved surgical techniques and technological advancement mean that the management of renal mass lesions is constantly evolving. The treatment of choice for renal mass lesions has historically been radical nephrectomy. Partial nephrectomy is now recommended for localised renal masses, owing to favourable renal functional outcomes. Ablative renal surgery confers a significant risk of chronic kidney disease. There are few studies assessing long term outcomes of nephrectomy on renal outcomes, and virtually no studies assessing long term outcomes for less invasive therapies such as ablation. Unless a renal mass is clearly benign on imaging, management decisions will be made with an assumption of malignancy. The content of this review applies to both benign and malignant renal mass lesions. We advocate for improved strategies for kidney function assessment and risk stratification, early targeted referral, and regular screening for chronic kidney disease for all patients after surgery.

  1. Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease

    PubMed Central

    Miranda, Kevin C.; Bond, Daniel T.; McKee, Mary; Skog, Johan; Păunescu, Teodor G.; Da Silva, Nicolas; Brown, Dennis; Russo, Leileata M.

    2015-01-01

    Urinary exosomes or microvesicles are being studied intensively to identify potential new biomarkers for renal disease. We sought to identify whether these microvesicles contain nucleic acids. We isolated microvesicles from human urine in the same density range as that previously described for urinary exosomes and found them to have an RNA integrity profile similar to that of kidney tissue, including 18S and 28S rRNA. This profile was better preserved in urinary microvesicles compared with whole cells isolated from urine, suggesting that microvesicles may protect RNA during urine passage. We were able to detect mRNA in the human urinary microvesicles encoding proteins from all regions of the nephron and the collecting duct. Further, to provide a proof of principle, we found that microvesicles isolated from the urine of the V-ATPase B1 subunit knockout mice lacked mRNA of this subunit while containing a normal amount of the B2 subunit and aquaporin 2. The microvesicles were found to be contaminated with extraneous DNA potentially on their surface; therefore, we developed a rapid and reliable means to isolate nucleic acids from within urine microvesicles devoid of this extraneous contamination. Our study provides an experimental strategy for the routine isolation and use of urinary microvesicles as a novel and non-invasive source of nucleic acids to further renal disease biomarker discovery. PMID:20428099

  2. Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease.

    PubMed

    Miranda, Kevin C; Bond, Daniel T; McKee, Mary; Skog, Johan; Păunescu, Teodor G; Da Silva, Nicolas; Brown, Dennis; Russo, Leileata M

    2010-07-01

    Urinary exosomes or microvesicles are being studied intensively to identify potential new biomarkers for renal disease. We sought to identify whether these microvesicles contain nucleic acids. We isolated microvesicles from human urine in the same density range as that previously described for urinary exosomes and found them to have an RNA integrity profile similar to that of kidney tissue, including 18S and 28S rRNA. This profile was better preserved in urinary microvesicles compared with whole cells isolated from urine, suggesting that microvesicles may protect RNA during urine passage. We were able to detect mRNA in the human urinary microvesicles encoding proteins from all regions of the nephron and the collecting duct. Further, to provide a proof of principle, we found that microvesicles isolated from the urine of the V-ATPase B1 subunit knockout mice lacked mRNA of this subunit while containing a normal amount of the B2 subunit and aquaporin 2. The microvesicles were found to be contaminated with extraneous DNA potentially on their surface; therefore, we developed a rapid and reliable means to isolate nucleic acids from within urine microvesicles devoid of this extraneous contamination. Our study provides an experimental strategy for the routine isolation and use of urinary microvesicles as a novel and non-invasive source of nucleic acids to further renal disease biomarker discovery.

  3. Adverse effects of low occupational cadmium exposure on renal and oxidative stress biomarkers in solderers.

    PubMed

    Hambach, Ramona; Lison, Dominique; D'Haese, Patrick; Weyler, Joost; François, Guido; De Schryver, Antoon; Manuel-Y-Keenoy, Begoña; Van Soom, Ulrik; Caeyers, Tine; van Sprundel, Marc

    2013-02-01

    Recent studies suggest adverse health effects after low exposure to cadmium (Cd). Brazing with Cd-containing solder exposes workers to Cd. The purpose of this study was to assess: (1) indicators of Cd exposure in blood (Cd-B)/ urine (Cd-U); (2) the association between Cd-B, Cd-U and renal and oxidative stress biomarkers. In this cross-sectional study Cd-B, Cd-U, renal (ie, N-acetyl-β-D-glucosaminidase/urinary intestinal alkaline phosphatase (IAP)/microalbumin/beta-2-microglobulin/retinol binding protein and oxidative stress markers (ie, derivatives of reactive oxygen metabolites/glutathione peroxidase/superoxide dismutase (SOD)/ advanced oxidation protein products/8-hydroxy-2'-deoxyguanosin/8-isoprostanes) were determined in 36 solderers. Multiple linear regression analysis adjusting for age and pack-years of smoking show that IAP is statistically significantly associated with Cd-B (B=0.24; SE=0.11) and Cd-U (B=0.15; SE=0.07). Also SOD is statistically significantly associated with Cd-B (B=62.96; SE=29.62). The association between SOD and Cd-U is of borderline statistical significance (B=37.69; SE=19.59). While there is still some debate as whether the Cd-induced tubular effects are reversible or not, IAP and SOD appear as sensitive and potentially useful early biomarkers for the health surveillance of workers exposed to low levels of Cd.

  4. The renal quantitative scintillation camera study for determination of renal function

    SciTech Connect

    Thompson, I.M. Jr.; Boineau, F.G.; Evans, B.B.; Schlegel, J.U.

    1983-03-01

    The renal quantitative scintillation camera study assesses glomerular filtration rate and effective renal plasma flow based upon renal uptake of 99mtechnetium-iron ascorbate and 131iodine-hippuran, respectively. The method was compared to inulin, para-aminohippuric acid and creatinine clearance studies in 7 normal subjects and 9 patients with various degrees of reduced renal function. The reproducibility of the technique was determined in 15 randomly selected pediatric patients. The values of glomerular filtration rate and effective renal plasma flow were not significantly different from those of inulin and para-aminohippuric acid studies. The reproducibility of the technique was comparable to that of inulin and para-aminohippuric acid studies. Patient acceptance of the technique is excellent and the cost is minimal. Renal morphology and excretory dynamics also are demonstrated. The technique is advocated as a clinical measure of renal function.

  5. Klotho deficiency is an early biomarker of renal ischemia–reperfusion injury and its replacement is protective

    PubMed Central

    Hu, Ming-Chang; Shi, Mingjun; Zhang, Jianning; Quiñones, Henry; Kuro-o, Makoto; Moe, Orson W.

    2011-01-01

    Klotho is an antiaging substance with pleiotropic actions including regulation of mineral metabolism. It is highly expressed in the kidney and is present in the circulation and urine but its role in acute kidney injury (AKI) is unknown. We found that ischemia–reperfusion injury (IRI) in rodents reduced Klotho in the kidneys, urine, and blood, all of which were restored upon recovery. Reduction in kidney and plasma Klotho levels were earlier than that of neutrophil gelatinase-associated lipocalin (NGAL), a known biomarker of kidney injury. Patients with AKI were found to have drastic reductions in urinary Klotho. To examine whether Klotho has a pathogenic role, we induced IRI in mice with different endogenous Klotho levels ranging from heterozygous Klotho haploinsufficient, to wild-type (WT), to transgenic mice overexpressing Klotho. Klotho levels in AKI were lower in haploinsufficient and higher in transgenic compared with WT mice. The haploinsufficient mice had more extensive functional and histological alterations compared with WT mice, whereas these changes were milder in overexpressing transgenic mice, implying that Klotho is renoprotective. Rats with AKI given recombinant Klotho had higher Klotho protein, less kidney damage, and lower NGAL than rats with AKI given vehicle. Hence, AKI is a state of acute reversible Klotho deficiency, low Klotho exacerbates kidney injury and its restoration attenuates renal damage and promotes recovery from AKI. Thus, endogenous Klotho not only serves as an early biomarker for AKI but also functions as a renoprotective factor with therapeutic potential. PMID:20861825

  6. [Renal function in patients after purulent pyelonephritis].

    PubMed

    Loran, O B; Siniakova, L A; Bernikov, E V

    2008-01-01

    The kidneys of the patients with purulent pyelonephritis (PP) undergo anatomic and functional alterations. The latter may be irreversible in some cases. The severity of the above alterations depends on PP form, choice and time of treatment. Our study included 84 patients who had PP at the age of 15 to 70 years. Primary PP was detected in 47 (56%) patients, secondary--in 37 (44%) patients. Open surgery was performed in 18 patients (group 1), transcutaneous drainage was used in 38 patients (group 2), conservative treatment was conducted in 28 patients (group 3). Comparison of dynamic nephroscintigraphic findings showed that recovery of renal function in groups 2 and 3 lasted 6-12 months versus 60-84 months in group 1. The degree of the renal function recovery depends on the PP form, age of the patient, duration of the disease, virulence of the causing agent, comorbid pathology, immune status, method of treatment. This was confirmed by the data of complex radionuclide examination. Long term complications, for instance, progress of arterial hypertension (41% cases) and chronic pyelonephritis (44% cases) were observed more frequently and earlier in patients after open operations.

  7. Human renal allograft blood flow and early renal function.

    PubMed Central

    Anderson, C B; Etheredge, E E

    1977-01-01

    Renal allograft blood flow (RBF) was measured at operation by electromagnetic flow meter and probes in 45 patients (34 cadaver donors and 11 living related donors). Mean RBF in 26 patients without acute tubular necrosis (ATN), was 412 +/- 80 ml/min and in 19 patients with ATN, 270 +/- 100 ml/min (p less than .001). Only two of 24 transplants (8%) with RBF greater than 350 ml/min had ATN; whereas, 17 of 21 transplants (81 per cent) with RBF less than 350 ml/min had ATN (p less than .001). In cadaver donor transplants, RBF did not correlate with duration of ATN, warm ischemia time, total ischemia time, pulsatile perfusion time or renal vascular resistance during perfusion. Measurement of renal allograft blood flow can predict presence or absence of postoperative ATN in 87% of patients. PMID:335986

  8. Tissue Biomarkers in Predicting Response to Sunitinib Treatment of Metastatic Renal Cell Carcinoma.

    PubMed

    Trávníček, Ivan; Branžovský, Jindřich; Kalusová, Kristýna; Hes, Ondřej; Holubec, Luboš; Pele, Kevin Bauleth; Ürge, Tomáš; Hora, Milan

    2015-10-01

    To identify tissue biomarkers that are predictive of the therapeutic effect of sunitinib in treatment of metastatic clear cell renal cell carcinoma (mCRCC). Our study included 39 patients with mCRCC treated with sunitinib. Patients were stratified into two groups based on their response to sunitinib treatment: non-responders (progression), and responders (stable disease, regression). The effect of treatment was measured by comparing imaging studies before the initiation treatment with those performed at between 3rd and 7th months of treatment, depending on the patient. Histological samples of tumor tissue and healthy renal parenchyma, acquired during surgery of the primary tumor, were examined with immunohistochemistry to detect tissue targets involved in the signaling pathways of tumor growth and neoangiogenesis. We selected mammalian target of rapamycine, p53, vascular endothelial growth factor, hypoxia-inducible factor 1 and 2 and carbonic anhydrase IX. We compared the average levels of biomarker expression in both, tumor tissue, as well as in healthy renal parenchyma. Results were evaluated using the Student's t-test. For responders, statistically significant differences in marker expression in tumor tissue versus healthy parenchyma were found for mTOR (4%/16.7%; p=0.01031), p53 (4%/12.7%; p=0.042019), VEGF (62.7%/45%; p=0.019836) and CAIX (45%/15.33%; p=0.001624). A further significant difference was found in the frequency of high expression (more than 60%) between tumor tissue and healthy parenchyma in VEGF (65%/35%; p=0.026487) and CAIX (42%/8%; p=0.003328). CAIX was expressed at high levels in the tumor tissue in both evaluated groups. A significantly higher expression of VEGF in CRCC in comparison to healthy parenchyma can predict a better response to sunitinib. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Urinary volatile organic compounds as potential biomarkers for renal cell carcinoma

    PubMed Central

    WANG, DONGCHUN; WANG, CHANGSONG; PI, XIN; GUO, LEI; WANG, YUE; LI, MINGJUAN; FENG, YUE; LIN, ZIWEI; HOU, WEI; LI, ENYOU

    2016-01-01

    Currently, there is no adequate, sensitive, reproducible, specific and noninvasive biomarker that can reliably be used to detect renal cell carcinoma (RCC). Previous studies have elucidated the urinary non-volatile metabolic profile of RCC. However, whether urinary volatile organic compound (VOC) profiles are able to identify RCC remains to be elucidated. In the present study, urine was collected from 22 patients with RCC and 25 healthy subjects. Principal component analysis and orthogonal partial least square discriminant analysis were used to compare the data of patients and healthy subjects, and preoperative and postoperative patients undergoing radical nephrectomy. In total, 11 VOC biomarkers were elevated in the RCC patients compared to the healthy subjects, which were phenol; decanal; 1,6-dioxacyclododecane-7,12-dione; 1-bromo-1-(3-methyl-1-pentenylidene)-2,2,3,3-tetramethyl-cyclopropane; nonanal; 3-ethyl-3-methylheptane; isolongifolene-5-ol; 2,5-cyclohexadiene-1,4-dione, 2,6-bis(1,1-dimethylethyl); tetradecane; aniline; and 2,6,10,14-tetramethyl-pentadecane. Three biomarkers were decreased in RCC patients: styrene, 4-heptanone and dimethylsilanediol. In preoperative patients, 2-ethyl-1-hexanol and cyclohexanone were elevated, while 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne were decreased when compared to postoperative patients. Compared with the healthy subjects, RCC has a unique VOC profile, suggesting that VOC profiles may be a useful diagnostic assay for RCC. PMID:27347408

  10. Circulating Fibroblast Growth Factor 21 (Fgf21) as Diagnostic and Prognostic Biomarker in Renal Cancer

    PubMed Central

    Knott, ME; Minatta, JN; Roulet, L; Gueglio, G; Pasik, L; Ranuncolo, SM; Nuñez, M; Puricelli, L; De Lorenzo, MS

    2016-01-01

    Background The finding of new biomarkers is needed to have a better sub-classification of primary renal tumors (RCC) as well as more reliable predictors of outcome and therapy response. In this study, we evaluated the role of circulating FGF21, an endocrine factor, as a diagnostic and prognostic biomarker for ccRCC. Materials and Methods Serum samples from healthy controls (HC), clear cell and chromophobe RCC cancer patients were obtained from the serum biobank “Biobanco Público de Muestras Séricas Oncológicas” (BPMSO) of the “Instituto de Oncología “Ángel H. Roffo”. Serum FGF21 and leptin were measured by ELISA while other metabolic markers were measured following routinely clinical procedures. Results One of our major findings was that FGF21 levels were significantly increased in ccRCC patients compared with HC. Moreover, we showed an association between the increased serum FGF21 levels and the shorter disease free survival in a cohort of 98 ccRCC patients, after adjustment for other predictors of outcome. Conclusion Our results suggest that higher FGF21 serum level is an independent prognostic biomarker, associated with worse free-disease survival. PMID:27358750

  11. A re-appraisal of volume status and renal function impairment in chronic heart failure: combined effects of pre-renal failure and venous congestion on renal function.

    PubMed

    Sinkeler, Steef J; Damman, Kevin; van Veldhuisen, Dirk J; Hillege, Hans; Navis, Gerjan

    2012-03-01

    The association between cardiac failure and renal function impairment has gained wide recognition over the last decade. Both structural damage in the form of systemic atherosclerosis and (patho) physiological hemodynamic changes may explain this association. As regards hemodynamic factors, renal impairment in chronic heart failure is traditionally assumed to be mainly due to a decrease in cardiac output and a subsequent decrease in renal perfusion. This will lead to a decrease in glomerular filtration rate and a compensatory increase in tubular sodium retention. The latter is a physiological renal response aimed at retaining fluids in order to increase cardiac filling pressure and thus renal perfusion. In heart failure, however, larger increases in cardiac filling pressure are needed to restore renal perfusion and thus more volume retention. In this concept, in chronic heart failure, an equilibrium exists where a certain degree of congestion is the price to be paid to maintain adequate renal perfusion and function. Recently, this hypothesis was challenged by new studies, wherein it was found that the association between right-sided cardiac filling pressures and renal function is bimodal, with worse renal function at the highest filling pressures, reflecting a severely congested state. Renal hemodynamic studies suggest that congestion negatively affects renal function in particular in patients in whom renal perfusion is also compromised. Thus, an interplay between cardiac forward failure and backward failure is involved in the renal function impairment in the congestive state, presumably along with other factors. Only few data are available on the impact of intervention in volume status on the cardio-renal interaction. Sparse data in cardiac patients as well as evidence from cohorts with primary renal disease suggest that specific targeting of volume overload may be beneficial for long-term outcome, in spite of a certain further decrease in renal function, at least

  12. [Influences of renal stone surgeries on renal function--evaluation of renal function with 99mTc-DMSA renal scintigraphy].

    PubMed

    Katayama, Y

    1991-10-01

    From 1984 to 1990, 99mTc-DMSA renal scintigraphy was performed before and after nephrolithotomy (15 cases), pyelolithotomy (15 cases), percutaneous nephrolithotripsy (PNL: 15 cases) and extracorporeal shock wave lithotripsy (ESWL: 16 cases, 17 kidneys) in order to evaluate of influences of renal stone surgeries on split renal function. DMSA renal uptake change ratio of treated kidneys of nephrolithotomy (-24.94 +/- 5.60%) was significantly lower than that of PNL (-0.06 +/- 3.92%), pyelolithotomy (-4.08 +/- 4.79%) (p less than 0.01) and ESWL (-7.72 +/- 3.87%) (p less than 0.05). The average change ratios of contralateral kidneys were as follows: PNL 4.80 +/- 4.21% nephrolithotomy 4.67 +/- 4.73%, pyelolithotomy -1.46 +/- 5.39% and ESWL -2.02 +/- 4.44%. One to 3 weeks after PNL, the cold area on the renal image was found in 10 (66.7%) of 15 cases. In cases of ESWL, DMSA renal uptake decreased even 4-10 weeks (mean 7 weeks) after treatment. In conclusion, possivility of deterioration of renal function after ESWL was suggested.

  13. The Renal Functional Defect of Postobstructive Nephropathy

    PubMed Central

    Jaenike, John R.

    1972-01-01

    This study was designed to examine the pathogenesis of the excretory defect produced by bilateral ureteral obstruction in the rat. After release of obstruction of 24 hr duration glomerular filtration rate was reduced to 20% of normal. Free flow proximal tubular pressure was normal, excluding residual obstruction as a cause of depressed filtration, and indicating that an intrarenal hemodynamic abnormality was primarily responsible for the excretory defect. Total renal blood flow and cortical distribution of flow were normal. Clearance and micropuncture studies indicated the presence of marked heterogeneity of nephron function with residual excretory function residing primarily in vasodilated nephrons in which decreased postglomerular arteriolar resistance effected a reduction in glomerular filtration pressure. Heterogeneity of nephron function was evidenced by a wide scatter of values for single nephron filtration rate and from direct intratubular injection of dye which revealed that at least 28% of surface nephrons were either nonfiltering or had filtration rates too low to measure. The observed decrease in Hippuran extraction and increased ratio of Hippuran to inulin clearance ratio is characteristic of the vasodilated kidney. Further evidence of the vasodilated nature of residual functioning nephrons was demonstrated by the failure of intrarenal papaverine infusion to increase filtration rate in this lesion. The hemodynamic defect produced by bilateral obstruction is contrasted with that seen after release of unilateral ureteral ligation in which depression of filtration rate appears to result primarily from preglomerular vasoconstriction. This difference raises the possibility that a vasodilating substance accumulates during total suppression of renal excretory function. Diuresis and natriuresis were constant features of the postobstructive lesion. The present data support previously published studies which localize the defect in sodium transport to the distal

  14. Osteoporosis biomarkers act as predictors for diagnosis of chronic renal insufficiency in elder patients.

    PubMed

    Li, Zhong-Xin; Xu, Chen; Li, Yan-Chun; Sun, Qian-Mei

    2015-01-01

    Chronic renal insufficiency and osteoporosis have become very common among old people in China. Hyperparathyroidism caused by renal insufficiency would result in turbulence of bone metabolism and unbalance between serum calcium and phosphorus. The aim of this study is to investigate the BMD, PTH, CT and 25(OH)-Vit's significance for screening and diagnosing chronic renal insufficiency. In this study, seventy cases with chronic renal insufficiency from Jun. 2010 to Oct. 2013 were selected as the observation group. Meanwhile, another 70 volunteers with normal renal functions were set as the control group. The level of BMD, PTH, CT and 25(OH)-Vit were detected by using ELISA assay. DPX bone density meters (UNIGAMMA X-RAY PLUS) were used for the detection of BMD. The results indicated that BMD levels of the proximal femur (include Troch, Shaft, Total, Neck, Ward) and lumbar vertebra in the observation group were significantly lower while the PTH and CT were significantly higher compared with the control group (P<0.05). A positive correlation was identified between the serum creatinine (Scr) concentrations and CT, PTH, while the correlation with 25(OH)-Vit was considered to be negative. In conclusion, the BMD, PTH, CT, and 25 (OH)-Vit would provide reference in diagnosing and treatment for chronic renal insufficiency. These indexes would be important clinical significance for screening and early diagnose of osteoporosis in these patients.

  15. The rebirth of interest in renal tubular function.

    PubMed

    Lowenstein, Jerome; Grantham, Jared J

    2016-06-01

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

  16. Effect of tolazoline on renal function in newborn puppies.

    PubMed

    John, E G; Bhat, R; Assadi, F K; Vidyasagar, D; Fornell, L

    1986-01-01

    Tolazoline is used in pulmonary hypertension and hypoperfusion syndrome during the neonatal period. Some of the side effects of tolazoline are hypotension, bleeding disorders and renal dysfunction. The present study was designed to investigate the effect of hypoxia and tolazoline on renal function in newborn puppies. The data in normal animals administered tolazoline alone did not reveal any statistically significant changes in blood pressure or in renal function. In the hypoxia group changes in renal function were noticed in spite of normal blood pressure. When tolazoline was administered to the hypoxic animals, a marked decrease in blood pressure resulted. Indeed, changes in renal function were more profound in the hypoxic animals receiving tolazoline than in hypoxic animals not receiving tolazoline, even though some of the renal functional values did not reach statistical significance.

  17. Impaired renal function impacts negatively on vascular stiffness in patients with coronary artery disease

    PubMed Central

    2013-01-01

    Background Chronic kidney disease (CKD) and coronary artery disease (CAD) are independently associated with increased vascular stiffness. We examined whether renal function contributes to vascular stiffness independently of CAD status. Methods We studied 160 patients with CAD and 169 subjects without CAD. The 4-variable MDRD formula was used to estimate glomerular filtration rate (eGFR); impaired renal function was defined as eGFR <60 mL/min. Carotid-femoral pulse wave velocity (PWV) was measured with the SphygmoCor® device. Circulating biomarkers were assessed in plasma using xMAP® multiplexing technology. Results Patients with CAD and impaired renal function had greater PWV compared to those with CAD and normal renal function (10.2 [9.1;11.2] vs 7.3 [6.9;7.7] m/s; P < 0.001). In all patients, PWV was a function of eGFR (β = −0.293; P < 0.001) even after adjustment for age, sex, systolic blood pressure, body mass index and presence or absence of CAD. Patients with CAD and impaired renal function had higher levels of adhesion and inflammatory molecules including E-selectin and osteopontin (all P < 0.05) compared to those with CAD alone, but had similar levels of markers of oxidative stress. Conclusions Renal function is a determinant of vascular stiffness even in patients with severe atherosclerotic disease. This was paralleled by differences in markers of cell adhesion and inflammation. Increased vascular stiffness may therefore be linked to inflammatory remodeling of the vasculature in people with impaired renal function, irrespective of concomitant atherosclerotic disease. PMID:23937620

  18. Functional, Structural, and Neurotoxicity Biomarkers in Integrative Assessment of Concussions

    PubMed Central

    Dambinova, Svetlana A.; Maroon, Joseph C.; Sufrinko, Alicia M.; Mullins, John David; Alexandrova, Eugenia V.; Potapov, Alexander A.

    2016-01-01

    Concussion is a complex, heterogeneous process affecting the brain. Accurate assessment and diagnosis and appropriate management of concussion are essential to ensure that athletes do not prematurely return to play or others to work or active military duty, risking re-injury. To date, clinical diagnosis relies primarily on evaluating subjects for functional impairment using instruments that include neurocognitive testing, subjective symptom report, and neurobehavioral assessments, such as balance and vestibular-ocular reflex testing. Structural biomarkers, defined as advanced neuroimaging techniques and biomarkers assessing neurotoxicity and immunoexcitotoxicity, may complement the use of functional biomarkers. We hypothesize that neurotoxicity AMPA, NMDA, and kainite receptor biomarkers might be utilized as a part of comprehensive approach to concussion evaluations, with the goal of increasing diagnostic accuracy and facilitating treatment planning and prognostic assessment. PMID:27761129

  19. Renal function status in patients with primary osteoporosis (type 2).

    PubMed

    Nava-Bringas, Tania Inés; Chávez-Arias, Daniel David; del Pilar Diez-García, María; Miranda-Duarte, Antonio

    2009-01-01

    Several studies correlate renal function with lower bone mineral density (BMD); however, the relationship between early stages of renal dysfunction and BMD has not been clearly defined. Our objective was to determine renal function in patients with primary osteoporosis (type 2) and its relationship with BMD. Patients with primary osteoporosis diagnosed using DEXA were evaluated in this cross-sectional analysis. Renal function was estimated according to the modification of diet in renal disease (MDRD) equation and classified according to the National Kidney Foundation for chronic kidney disease (CKD). The relationship between renal function and BMD was analyzed. Included in the study were 120 women with a mean age 67.9 + or - 6.56 years. There was a positive relationship between spine BMD and moderate affection of renal function (F = 4.860, p = 0.009). No relationship was found between hip BMD or fracture with renal function (p = 0.223). Although women with poor renal function have significantly lower spine BMD, no relationship between early stages of CKD and low BMD has been demonstrated.

  20. Redox Control of Renal Function and Hypertension

    PubMed Central

    Whaley-Connell, Adam; Sowers, James R.

    2008-01-01

    Abstract Loss of redox homeostasis and formation of excessive free radicals play an important role in the pathogenesis of kidney disease and hypertension. Free radicals such as reactive oxygen species (ROS) are necessary in physiologic processes. However, loss of redox homeostasis contributes to proinflammatory and profibrotic pathways in the kidney, which in turn lead to reduced vascular compliance and proteinuria. The kidney is susceptible to the influence of various extracellular and intracellular cues, including the renin–angiotensin–aldosterone system (RAAS), hyperglycemia, lipid peroxidation, inflammatory cytokines, and growth factors. Redox control of kidney function is a dynamic process with reversible pro– and anti-free radical processes. The imbalance of redox homeostasis within the kidney is integral in hypertension and the progression of kidney disease. An emerging paradigm exists for renal redox contribution to hypertension. Antioxid. Redox Signal. 11, 2047–2089. PMID:18821850

  1. Drug-induced impairment of renal function

    PubMed Central

    Pazhayattil, George Sunny; Shirali, Anushree C

    2014-01-01

    Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. However, all agents also carry adverse drug effect profiles. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that impacts negatively on patient morbidity and mortality. Recognizing adverse effects is important for administering appropriate drug doses, instituting preventive strategies, and withdrawing the offending agent due to toxicity. In the present article, we will review those drugs that are associated with impaired renal function. By focusing on pharmaceutical agents that are currently in clinical practice, we will provide an overview of nephrotoxic drugs that a treating physician is most likely to encounter. In doing so, we will summarize risk factors for nephrotoxicity, describe clinical manifestations, and address preventive and treatment strategies. PMID:25540591

  2. A combined-biomarker approach to clinical phenotyping renal dysfunction in heart failure

    PubMed Central

    Testani, Jeffrey M.; Damman, Kevin; Brisco, Meredith A.; Chen, Susan; Laur, Olga; Kula, Alexander J.; Tang, W. H. Wilson; Parikh, Chirag

    2014-01-01

    Background Differentiating heart failure (HF) induced renal dysfunction (RD) from intrinsic kidney disease is challenging. It has been demonstrated that biomarkers such as B-type natriuretic peptide (BNP) or the blood urea nitrogen to creatinine ratio (BUN/Creat) can identify high vs. low risk RD. Our objective was to determine if combination these biomarkers could further improve risk stratification and clinical phenotyping of patients with RD and HF. Methods and Results 908 patients with a discharge diagnosis of HF were included. Median values were used to define elevated BNP (>1296 pg/ml) and BUN/Creat (>17). In the group without RD, survival was similar regardless of BNP and BUN/Creat (n=430, adjusted p=0.52). Similarly, in patients with both a low BNP and BUN/Creat, RD was not associated with mortality (n=250, adjusted HR=1.0, 95% CI 0.6-1.6, p=0.99). However, in patients with both an elevated BNP and BUN/Creat those with RD had a cardio-renal profile characterized by venous congestion, diuretic resistance, hypotension, hyponatremia, longer length of stay, greater inotrope use, and substantially worse survival compared to patients without RD (n=249, adjusted HR=1.8, 95% CI 1.2-2.7, p=0.008, p interaction=0.005). Conclusions In the setting of decompensated HF, the combined use of BNP and BUN/Creat stratifies patients with RD into groups with significantly different clinical phenotypes and prognosis. PMID:25152498

  3. Studies on renal function in patients with cystinuria.

    PubMed

    Lindell, A; Denneberg, T; Granerus, G

    1997-01-01

    Total and separate renal functions were evaluated in 40 patients with cystinuria. The average duration of the renal stone disease was 26 years (range 1-53). The patients had been subjected to a stone-preventing regimen composed of increased fluid intake, urinary alkalinization and treatment with a sulphydryl compound, tiopronin or D-penicillamine, for an average of 11.7 years (range 1-24). Urinary cystine concentration was determined regularly to monitor the treatment. All patients were examined with gamma camera renography and an assessment of glomerular filtration rate (GFR), and early and late renographic results could be compared in 30 patients. The early renographic evaluation showed that 43% of binephric patients (13/30) had an abnormal relative renal function (RRF) before the start of the stone-preventing treatment. At the late evaluation, 50% of binephric patients (17/34) had an abnormal RRF, while 30% of all patients (12/40) had a GFR below the age-related normal range. Thirty percent of 74 evaluated kidneys (22/74) had a separate GFR below an estimated age-related normal range. At the late evaluation only 30% of the patients had functionally unaffected kidneys with both normal GFR and bilateral normal renography. There was, however, no case with terminal renal failure. The separate GFR of kidneys with a history of staghorn stones was significantly lower than for kidneys without that special type of stones, but otherwise there was no relationship between renal functional impairment and other estimates of the activity of the renal stone disease. In conclusion, impairment of renal function is common in patients with stone-forming cystinuria. Stone-preventive treatment appears to be effective in preserving renal function. The high frequency of renal functional impairment justifies close surveillance of this group of patients. By renographic examination, unilateral changes in renal function can be detected at an early stage and patients at risk for further

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

    PubMed Central

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

    2016-01-01

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

  5. Pre- and postoperative evaluation of renal function in patients with staghorn calculi utilizing quantitative renal scanning.

    PubMed

    Stage, K H; Lewis, S

    1981-01-01

    Differential quantitative renal scans using 99-technetium diethylene triaminepentaacetic acid (DTPA) or 131I Hippuran were obtained properatively on 12 patients with unilateral or bilateral staghorn calculi. Of the 14 renal units studied, 12 kidneys underwent anatrophic nephrolithotomy, pyelolithotomy, or a combination of both techniques; 2 patients underwent nephrectomy based on poor function of the affected side preoperatively. Postoperative follow-up scans were obtained on the 12 kidneys undergoing stone cleanout. Seven of 12 kidneys (58 per cent) studied pre- and postoperatively showed moderate to significant improvement in per cent contribution to total renal function. Seven of 10 kidneys (70 per cent) studied pre- and postoperatively showed improvement in glomerular filtration rate or effective renal plasma flow. The scans revelaed no dramatic difference in postoperative functional loss between pyelolithotomy and anatrophic nephrolithotomy. The computerizewd quantitative renal scan helps in selection of surgical technique and objective postoperative assessment of surgical results.

  6. Biomarkers of renal toxicity caused by exposure to arsenic in drinking water.

    PubMed

    Feng, Hongqi; Gao, Yanhui; Zhao, Lijun; Wei, Yudan; Li, Yuanyuan; Wei, Wei; Wu, Yu; Sun, Dianjun

    2013-05-01

    This study is intended to explore effective and sensitive biomarkers for kidney damage after low level arsenic (As) exposure and to provide scientific evidence on cut-off values of arsenic concentrations in drinking water. The levels of α1-MG detected in urine samples were found to have statistically significant differences between high As group (As>0.05 mg/L) and a combination of low and medium As exposure groups (As<0.05 mg/L, p=0.018), as well as between the patient and high As groups (As in two group were both higher than 0.05 mg/L, p<0.001). After the logistic regression analysis the AUC values of α1-MG between two comparisons were 0.613 and 0.701, and p value was less than 0.05. The present data demonstrate the potential value of α1-MG excretion as a biomarker of renal toxicity, which could contribute to the enforcement of the maximum limit of 0.05 mg/L arsenic in drinking water for non-central water supply in rural areas. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. The non-functioning kidney in renal tuberculosis.

    PubMed

    Tabakov, I; Totsev, N; Chervenakov, A

    1976-01-01

    The authors have found a non-functioning kidney in 117 patients, constituting more than 24 per cent of 487 patients with bacteriologically and/or histologically confirmed renal tuberculosis, treated and followed up in the last ten years. In 2/3 of the patients with non-functioning kidney and renal tuberculosis, the conditions of non-functioning had been already present from the very beginning, at the time when renal tuberculosis was established. In the remaining 1/3 of the patients, one of the kidneys had ceased to function in the course of treatment. The authors found that the main causes for the failure of the kidney function in renal tuberculosis are strictures of the draining urinary pathways. Emphasis is laid upon the necessity of a careful observation of the patients with renal tuberculosis in the course of drug treatment in view of a timely detection and treatment ofthe strictures in the draining urinary pathways.

  8. Renal Function Recovery with Total Artificial Heart Support.

    PubMed

    Quader, Mohammed A; Goodreau, Adam M; Shah, Keyur B; Katlaps, Gundars; Cooke, Richard; Smallfield, Melissa C; Tchoukina, Inna F; Wolfe, Luke G; Kasirajan, Vigneshwar

    2016-01-01

    Heart failure patients requiring total artificial heart (TAH) support often have concomitant renal insufficiency (RI). We sought to quantify renal function recovery in patients supported with TAH at our institution. Renal function data at 30, 90, and 180 days after TAH implantation were analyzed for patients with RI, defined as hemodialysis supported or an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m. Between January 2008 and December 2013, 20 of the 46 (43.5%) TAH recipients (age 51 ± 9 years, 85% men) had RI, mean preoperative eGFR of 48 ± 7 ml/min/1.73 m. Renal function recovery was noted at each follow-up interval: increment in eGFR (ml/min/1.73 m) at 30, 90, and 180 days was 21 ± 35 (p = 0.1), 16.5 ± 18 (p = 0.05), and 10 ± 9 (p = 0.1), respectively. Six patients (30%) required preoperative dialysis. Of these, four recovered renal function, one remained on dialysis, and one died. Six patients (30%) required new-onset dialysis. Of these, three recovered renal function and three died. Overall, 75% (15 of 20) of patients' renal function improved with TAH support. Total artificial heart support improved renal function in 75% of patients with pre-existing significant RI, including those who required preoperative dialysis.

  9. Quantitation of renal function using radioisotopic techniques.

    PubMed

    O'Malley, J P; Ziessman, H A

    1993-03-01

    Radioisotopic methods are practical for clinical use because they do not require continuous intravenous infusion or urine collection. This obviously is of great advantage in infants and small children, in whom accurate urine collection is difficult, but the techniques apply to adults as well. The ability to determine individual kidney function is a major benefit. Accuracies of the radioisotopic techniques vary but generally are within clinically acceptable ranges. The need for accuracy and reproducibility can be balanced with the desire for speed and convenience when choosing among the different techniques. Methods that use plasma sampling provide greater accuracy and are recommended in cases of severe dysfunction, whereas methods such as Gates' camera method, which eliminates plasma samples, can be completed in minutes. Radioisotopic techniques are most useful in the ranges of mild to moderately decreased function, in which serum creatinine concentration is nondiagnostic, and although they are much less accurate at markedly low renal function levels, so is 24-hour creatinine clearance. In conclusion, radiopharmaceutical agents offer a wide array of possible techniques for simple, accurate, and noninvasive measurement of global as well as individual GFR and ERPF.

  10. [Imaging evaluation of renal function: principles and limitations].

    PubMed

    Vivier, P-H; Dolores, M; Le Cloirec, J; Beurdeley, M; Liard, A; Elbaz, F; Roset, J-B; Dacher, J-N

    2011-04-01

    The kidney performs multiple functions. Glomerular filtration is the most studied of these functions. In clinical practice, the surgical indication for patients with unilateral uropathy is frequently based on the split renal function as demonstrated by scintigraphy. MRI is not yet validated as a technique but nonetheless offers an interesting non-radiating alternative to achieve both morphological and functional renal evaluation. Recent pulse sequences such as diffusion, arterial spin labeling, and blood oxygenation dependent imaging may also provide additional information. CT and US remain of limited value for the evaluation of renal function.

  11. Early postnatal hyperalimentation impairs renal function via SOCS-3 mediated renal postreceptor leptin resistance.

    PubMed

    Alcazar, Miguel Angel Alejandre; Boehler, Eva; Rother, Eva; Amann, Kerstin; Vohlen, Christina; von Hörsten, Stephan; Plank, Christian; Dötsch, Jörg

    2012-03-01

    Early postnatal hyperalimentation has long-term implications for obesity and developing renal disease. Suppressor of cytokine signaling (SOCS) 3 inhibits phosphorylation of signal transducer and activator of transcription (STAT) 3 and ERK1/2 and thereby plays a pivotal role in mediating leptin resistance. In addition, SOCS-3 is induced by both leptin and inflammatory cytokines. However, little is known about the intrinsic-renal leptin synthesis and function. Therefore, this study aimed to elucidate the implications of early postnatal hyperalimentation on renal function and on the intrinsic-renal leptin signaling. Early postnatal hyperalimentation in Wistar rats during lactation was induced by litter size reduction at birth (LSR) either to LSR10 or LSR6, compared with home cage control male rats. Assessment of renal function at postnatal day 70 revealed decreased glomerular filtration rate and proteinuria after LSR6. In line with this impairment of renal function, renal inflammation and expression as well as deposition of extracellular matrix molecules, such as collagen I, were increased. Furthermore, renal expression of leptin and IL-6 was up-regulated subsequent to LSR6. Interestingly, the phosphorylation of Stat3 and ERK1/2 in the kidney, however, was decreased after LSR6, indicating postreceptor leptin resistance. In accordance, neuropeptide Y (NPY) gene expression was down-regulated; moreover, SOCS-3 protein expression, a mediator of postreceptor leptin resistance, was strongly elevated and colocalized with NPY. Thus, our findings not only demonstrate impaired renal function and profibrotic processes but also provide compelling evidence of a SOCS-3-mediated intrinsic renal leptin resistance and concomitant up-regulated NPY expression as an underlying mechanism.

  12. Effects of exercise on renal function in patients with moderate impairment of renal function compared to normal men.

    PubMed

    Taverner, D; Craig, K; Mackay, I; Watson, M L

    1991-01-01

    The renal excretory and haemodynamic responses to sustained moderate exertion were investigated in normotensive humans with impaired renal function and normal volunteers. The heart rate increase with exercise was similar in each group. Subjects with impaired renal function showed a significant fall in glomerular filtration rate on exertion, while normals did not. In the presence of renal disease, urine osmolality did not rise with exertion, although it rose markedly in the normal group. Free water clearance became negative after exercise in the normal group only. The diseased kidney is unable to maintain glomerular filtration rate or conserve water under the stress of exertion as well as the normal kidney.

  13. Effects of radiofrequency ablation on individual renal function: assessment by technetium-99m mercaptoacetyltriglycine renal scintigraphy.

    PubMed

    Mukai, Takashi; Sato, Shuhei; Iguchi, Toshihiro; Mimura, Hidefumi; Yasui, Kotaro; Gobara, Hideo; Saika, Takashi; Nasu, Yasutomo; Kumon, Hiromi; Kanazawa, Susumu

    2006-04-01

    We quantitatively evaluated total and individual renal function by technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) renal scintigraphy before and after radiofrequency ablation (RFA) of renal tumors. Eleven patients who underwent Tc-99m MAG3 renal scintigraphy 1 week before and after RFA were evaluated (7 men and 4 women; age range: 23-83 years; mean age: 60.6 years). Five patients had solitary kidneys, and five had normally or minimally functioning contralateral kidneys. One patient had a renal cell carcinoma in the contralateral kidney. One patient with a solitary kidney underwent RFA a second time for a residual tumor. In patients with a solitary kidney, MAG3 clearance decreased after 5 of 6 RFAs, and in patients with a normally functioning contralateral kidney, MAG3 clearance decreased after 4 of 5 RFAs, but no significant differences were observed between before and after treatments. In addition to the total MAG3 clearance, the split MAG3 clearance was evaluated in patients with a normally functioning contralateral kidney. MAG3 clearance decreased in 4 of 5 treated kidneys, while it adversely increased in the contralateral kidneys after 4 of 5 RFAs. No significant differences, however, were observed between before and after treatments. The results of our study revealed no significant differences in sCr, BUN, CCr, or MAG3 clearance between pre- and post-RFA values. These results support data regarding the functional impact and safety of renal RFA in published reports. We evaluated total and individual renal function quantitatively using Tc-99m MAG3 renal scintigraphy before and after treatment. This scintigraphy was very useful in assessing the effects of RFA on renal function.

  14. Urinary cystatin C as a renal biomarker and its immunohistochemical localization in anti-GBM glomerulonephritis rats.

    PubMed

    Togashi, Yuko; Imura, Naoko; Miyamoto, Yohei

    2013-11-01

    The usefulness of urinary cystatin C for the early detection of renal damage in anti-glomerular basement membrane (GBM) glomerulonephritis rats was investigated and compared to other biomarkers (β2-microglobulin, calbindin, clusterin, epidermal growth factor (EGF), alpha-glutathione S-transferase (GST-α), mu-glutathione S-transferase (GST-μ), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, tissue inhibitor of metalloprotease-1 (TIMP-1), and vascular endothelial growth factor (VEGF)). Urinary levels of cystatin C increased in anti-GBM glomerulonephritis rats, whereas the conventional markers, plasma creatinine and UN did not, demonstrating its usefulness for the early detection of renal damage associated with anti-GBM glomerulonephritis. As well as cystatin C, urinary β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL also had the potential to detect renal damage associated with anti-GBM glomerulonephritis. Furthermore, the immunohistochemical localization of cystatin C in the kidney was examined. Cystatin C expression was mainly observed in the proximal renal tubules in anti-GBM glomerulonephritis rats, and its expression barely changed with the progression of glomerulonephritis. Cystatin C expression was also observed in the tubular lumen of the cortex and medulla when glomerulonephritis was marked, which was considered to be characteristic of renal damage. In conclusion, urinary cystatin C, β2-microglobulin, clusterin, GST-α, GST-μ, KIM-1, and NGAL could be useful biomarkers of renal damage in anti-GBM glomerulonephritis rats. Immunohistochemical cystatin C expression in the proximal renal tubules was barely changed by the progression of glomerulonephritis, but it was newly observed in the tubular lumen when renal damage was apparent. Crown Copyright © 2013. Published by Elsevier GmbH. All rights reserved.

  15. Anaesthesia for the patient with impaired renal function.

    PubMed

    Maddern, P J

    1983-11-01

    Patients with renal disease are at risk of further deterioration of renal function and acute tubular necrosis when subjected to anaesthesia and surgery. Optimal fluid loading and careful selection of anaesthetic techniques and agents, appropriate monitoring and the use of mannitol and dopamine assist in the maintenance of renal blood flow and help preserve renal function in these patients. In association with renal failure, physiological changes in other systems result in reduced oxygen supply to the tissues, metabolic disturbances, impairment of the coagulation and immune defence mechanisms and an increased risk of cardiac and cerebrovascular catastrophe. Although many anaesthetic techniques including regional analgesia may be used successfully in these patients caution with most drugs, especially pethidine, phenoperidine, suxamethonium and all non-depolarising neuromuscular relaxants is recommended. Of the volatile anaesthetics currently available, halothane is the agent of choice. Oxygen therapy and close monitoring of cardiorespiratory function are necessary postoperatively.

  16. [Pharmacokinetic study of pyrazinamide and pyrazinoic acid in subjects with normal renal function and patients with renal failure].

    PubMed

    Vayre, P; Chambraud, E; Fredj, G; Thuillier, A

    1989-01-01

    The main pharmacokinetic parameters of pyrazinamide and pyrazinoïc acid (its major metabolite) were determined after oral administration of 1,500 mg/d in 10 patients with normal renal function and of 1,000 mg/d in 10 patients with impaired renal function (renal insufficiency). This study shows that, with these dosage regimens, almost all the pharmacokinetic parameters are identical for pyrazinamide and pyrazinoic acid in patients with normal renal function and patients with impaired renal function. Comparison of results between patients allows us to propose a dosage regimen of 1,000 mg/d as maintenance in patients with renal insufficiency.

  17. Influence of dietary protein on renal function in dogs.

    PubMed

    Bovée, K C

    1991-11-01

    Two previously published studies in dogs with reduced renal function are reviewed. In the first study, renal function and biochemical responses to dietary changes were studied in four dogs with stable chronic renal failure. The objective was to determine if dogs with moderate stable failure adjust to diets with varied protein and electrolyte content. These dogs were found to have the capacity to adapt to a wide range of dietary protein and electrolyte intake. The only exception was found in dogs fed a reduced-protein diet, which failed to appropriately adjust renal tubular excretion of sodium and phosphate. The only advantage of reduced dietary protein in this study was a reduction in blood urea nitrogen (BUN). Disadvantages of reduced-protein diets were reduced glomerular filtration rate (GFR) and renal plasma flow. In the second study, the hypothesis that large amounts of dietary protein sustain renal hyperfunction and produce progressive glomerulosclerosis in dogs as previously reported in rats was tested. Results failed to find a pattern of deterioration of renal function over 4 y. Light microscopic changes and electron microscopy also failed to find glomerular injury similar to that reported in rodents. These results do not support the hypothesis that feeding a high protein diet had a significant adverse effect on renal function or morphology.

  18. [Renal function after surgical treatment of stag-horned nephrolithiasis].

    PubMed

    Akulin, S M; Ianenko, E K; Demin, A I; Nikitinskaia, L P

    2010-01-01

    Renal function in patients with stag-horn nephrolithiasis was assessed after two surgical treatments--percutaneous nephrolitholapaxy (PCN L) and pyelonephrolithotomy. The function of the operated and contralateral kidneys was studied early and late after operation by parameters of blood biochemistry, Doppler investigation of renal parenchyma, dynamic nephroscintigraphy. Stabilization or improvement of blood biochemical indices was observed in 58 (70%) patients. A secretory renal function late after surgery (from 6 months to 2 years) evidenced for improvement or stabilization of renal function (according to radionuclide test) in 71 (85.5%) patients. Integral parameters of renal blood flow were physiological or improved versus preoperative ones. PCNL was made in patients with deficient secretion less than 70%, 35 (87.5%) patients were diagnosed to have stabilization or functional improvement. After open intervention functional improvement took place in 11 (25.6%) patients, stabilization of renal function occurred in 25 (58.1%) patients. Tubular secretion deterioration was seen much more frequently in patients after open intervention. PCNL is less invasive surgical intervention than pyelonephrolithotomy as this technique produces milder surgical trauma and does not result in intraoperative renal ischemia. PCNL is the most effective surgical modality in stag-horn concrements of the kidneys and significantly expands potential of low-invasive treatment of such patients.

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

    PubMed

    Alberti, C

    2012-02-01

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

  20. Deterioration in Renal Function Is Associated With Increased Arterial Stiffness

    PubMed Central

    2014-01-01

    BACKGROUND Higher levels of baseline pulse wave velocity (PWV) have been associated with longitudinal decline in renal function in patients with kidney disease. We examined longitudinal decline in renal function in relation to levels of PWV. We hypothesized that longitudinal decline in renal function in a community-based, nonclinic sample would be associated with higher levels of PWV. METHODS We conducted a 4–5 year longitudinal study with 482 community-living individuals free from acute stroke, dementia, and end-stage renal disease (mean age = 60.9 years; 59% women; 93.2% white; 10% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) = 79.2ml/min/1.73 m2). Multiple linear regression analyses were used to examine the association between changes in renal function (eGFR and serum creatinine) from baseline to follow-up and PWV levels at follow-up, the outcome measure. Regression coefficients were adjusted for age, sex, education, race/ethnicity, weight, activity level, mean arterial pressure, treatment of hypertension, and cardiovascular risk factors. RESULTS With adjustment for covariables, decline in renal function was associated with higher levels of PWV over a mean follow-up of 4.68 years. CONCLUSIONS Decline in renal functioning from baseline levels measured 4–5 years before measurement of PWV is related to higher levels of PWV in a community sample. PMID:24080989

  1. Tubular reabsorption in normal renal function.

    PubMed

    O'Connor, W J

    1984-01-01

    The purpose here is to examine in relation to normal renal function three factors which might affect tubular reabsorption: (1) The reabsorption of SO4, PO4, K, Cl, HCO3 and water are all linked to the reabsorption of Na. This would amount to the reabsorption by the tubules of a net reabsorbate of a composition similar to Locke's fluid. Fixed linkage of the reabsorption of a substance to the reabsorption of Na would be a very effective way of maintaining its plasma concentration within a narrow range. The substance would be retained unless its plasma concentration exceeds a threshold value and then small increase in plasma concentration determines its excretion. (2) The rate of reabsorption of Na and substances linked to it is increased when the volume of the intraluminal fluid is increased. This would explain why there is only a small increase in the excretion of Na and other electrolytes when glomerular filtration rate is increased after a meal of meat. (3) Plasma protein concentration affects tubular reabsorption. This would explain why fall in plasma protein is a main agent determining Na excretion in normal animals. Trying to see 'how far the observed facts can be brought into accord with a theory' reveals the difficulty of applying critical tests. On the one hand, the theories are not stated quantitatively in reference to the small changes of normal life; rather the evidence is from experiments with large changes. On the other hand, the small changes within the range of normal function, while themselves statistically significant, are too small for effective investigation of circumstances which may modify them. In the examples discussed here, we cannot say more than that the theories could explain the facts and their participation cannot be excluded.

  2. Renal Artery Stenting in Patients with a Solitary Functioning Kidney

    SciTech Connect

    Cioni, Roberto; Vignali, Claudio; Petruzzi, Pasquale; Neri, Emanuele; Caramella, Davide; Vagli, Paola; Bargellini, Irene; Napoli, Vinicio; Pinto, Stefania; Bartolozzi, Carlo

    2001-12-15

    Purpose: To retrospectively evaluate the results of renal artery stenting in patients with renovascular disease and a solitary functioning kidney.Methods: Palmazstents were placed in 16 patients with a solitary functioning kidney,renal artery stenosis, hypertension and renal failure. Stenoses were evaluated with color Doppler ultrasound, MR angiography and digital subtraction angiography (DSA). Indications for stenting were: recoil after percutaneous transluminal renal angioplasty (PTRA) (63%),arterial dissection after PTRA (13%) and primary stenting (25%).Immediate results were evaluated by DSA. On follow-up (6-36 months),patients underwent periodical evaluation of clinical conditions (blood pressure and serum creatinine level) and stent patency, by means of color Doppler ultrasound.Results: Stent placement was successful in all patients (100%). Cumulative primary patency rate was: 100% at 1 day, 93.75% at 6 months, 81.25% at 12 months and 75% at 24 months. A significant reduction in diastolic blood pressure occurred (mean {+-} SD 104 {+-} 6 vs 92 {+-} 3;p < 0.05); renal function improved or stabilized in over 80% of patients. However, there was no significant difference in the creatinine values before and after treatment (mean {+-} SD 200 {+-} 142 mmol/l vs 197 {+-} 182 mmol/l; p> 0.05).Conclusion: Renal artery stenting, both after PTRA and as primary stenting, represents a safe procedure, able to preserve renal function in patients with a solitary functioning kidney.

  3. Exploring Vascular Function Biomarkers: Implications for Rehabilitation

    PubMed Central

    Phillips, Shane A.; Andaku, Daniela Kuguimoto; Mendes, Renata Gonçalves; Caruso, Flávia Rossi; Cabiddu, Ramona; Jaenisch, Rodrigo Boemo; Arena, Ross; Borghi-Silva, Audrey

    2017-01-01

    The endothelium plays an important role in maintaining vascular homeostasis and regulating blood vessel function. Endothelial function is considered an independent predictor for risk of future cardiovascular events in cardiovascular and non-cardiovascular patients, as well as a predictor for postoperative complications in cardiovascular surgery patients. Brachial artery flow-mediated dilation by high-resolution ultrasound is widely used to evaluate endothelium-dependent vasodilation, which is mainly mediated by nitric oxide release. Physical exercise exerts beneficial effects on endothelial function and can be used in both primary and secondary prevention of cardiac and peripheral artery diseases, even in the postoperative period of cardiovascular surgery. PMID:28492794

  4. [Impact of lung cancer treatments on renal function].

    PubMed

    Toffart, A-C; Belaiche, S; Moro-Sibilot, D; Couraud, S; Sakhri, L

    2014-12-01

    Renal failure in patients with lung cancer may be multifactorial: related to the patients and their comorbidities, direct tumor compression or the toxicity of cancer treatments and other associated medications. This literature review is intended to describe the state of knowledge regarding the nephrotoxicity of treatments used in thoracic oncology. The majority of chemotherapy treatments are potentially nephrotoxic. Cisplatin and pemetrexed exhibit mainly renal tubular toxicity, while vascular renal impairment is found with gemcitabine and bevacizumab. Cisplatin results in acute renal failure in 30% of patients. Renal protective strategies (compliance with recommendations, limitation of nephrotoxic treatments, hydration, magnesium supplementation) must be employed systematically. Targeted therapies do not require any adjustment of the dosage in case of moderate or severe renal insufficiency but adapting the doses of biphosphonates to renal function is necessary. This review highlights the need for monitoring of renal function in patients with lung cancer during treatment with chemotherapy or biphosphonates. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  5. Functional magnetic resonance: biomarkers of response in breast cancer

    PubMed Central

    2011-01-01

    Functional magnetic resonance (MR) encompasses a spectrum of techniques that depict physiological and molecular processes before morphological changes are visible on conventional imaging. As understanding of the pathophysiological and biomolecular processes involved in breast malignancies evolves, newer functional MR techniques can be employed that define early predictive and surrogate biomarkers for monitoring response to chemotherapy. Neoadjuvant chemotherapy is increasingly used in women with primary breast malignancies to down-stage the tumour and enable successful breast conservation surgery. It also plays a role in the treatment of undetected micrometastases. Cardinal physiological features of tumours that occur as a result of interactions between cancer cells, stromal cells and secreted factors and cytokines and how they change with treatment provide the opportunity to detect changes in the tumour microenvironment prior to any morphological change. Through sequential imaging, tumour response can be assessed and non-responders can be identified early to enable alternative therapies to be considered. This review summarises the functional magnetic resonance biomarkers of response in patients with breast cancer that are currently available and under development. We describe the current state of each biomarker and explore their potential clinical uses and limitations in assessing treatment response. With the aid of selected interesting cases, biomarkers related to dynamic contrast-enhanced MRI, diffusion-weighted MRI, T2*/BOLD and MR spectroscopy are described and illustrated. The potential of newer approaches, such as MR elastography, are also reviewed. PMID:21392409

  6. Acid-base balance of cats with chronic renal failure: effect of deterioration in renal function.

    PubMed

    Elliott, J; Syme, H M; Markwell, P J

    2003-06-01

    In a previous cross-sectional study of feline chronic renal failure (CRF), metabolic acidosis was identified in 52.6 per cent of animals with severe renal failure (plasma creatinine concentration >400 micromol/litre). The aim of this longitudinal study was to determine whether metabolic acidosis preceded or accompanied a deterioration in renal function in cats with CRF. Data were analysed from 55 cats with CRF that had been followed longitudinally for at least four months. Twenty-one cases showed deterioration in renal function over the period of the study, as evidenced by significant rises in their plasma creatinine concentrations and decreases in bodyweight. In five of the 21 cases, acidaemia accompanied the deterioration in renal function. Only one of these cats had evidence of metabolic acidosis before renal function deterioration. One other case developed metabolic acidosis without a rise in plasma creatinine concentration. These data suggest that biochemical evidence of metabolic acidosis does not generally occur until late in the course of feline CRF.

  7. Heritability of Renal Function and Inflammatory Markers in Adult Male Twins

    PubMed Central

    Raggi, Paolo; Su, Shaoyong; Karohl, Cristina; Veledar, Emir; Rojas-Campos, Enrique; Vaccarino, Viola

    2010-01-01

    Background Loss of renal function is accompanied by a progressive increase in markers of inflammation; it is unknown whether they share common genetic pathways. Study Design We evaluated the shared heritability of estimated glomerular filtration rate (eGFR) and markers of inflammation and endothelial activation in 524 twin males from the Vietnam Era Twin Registry; 9 twins were excluded due to incomplete or incorrect data. Models were adjusted for age, race, body mass index, smoking, hypertension, diabetes mellitus, prior coronary artery disease and intercurrent medications. Results The mean eGFR was 89 ± 13 ml/min/1.73 m2 (range 35–146); eGFR, intracellular adhesion molecule (ICAM) and TNF-α receptor (TNF-αR) were moderately heritable (all ∼50%), while IL-6 receptor (IL-6R) and P-selectin were highly heritable (68 and 76%, respectively). IL-6R and TNF-αR showed a significant inverse association with eGFR (p = 0.04 and p < 0.0001) while the association with ICAM and P-selectin was direct (p = 0.001 and p = 0.06). Bivariate structural equation models showed that the association between eGFR and biomarkers was due to unique environmental factors and there were no shared genetic pathways. Conclusion We found no shared genetic pathways between renal function and inflammation. Thus, increased inflammation represents a response to declining renal function rather than being a mechanism contributing to renal deterioration. PMID:20720405

  8. A comparison of three methods of assessing renal function.

    PubMed

    Macleod, M A; Houston, A S

    1981-01-01

    In a study of 100 patients referred for assessment of renal function a comparison is made between gamma camera computer assisted displays of 99mTc-DTPA(Sn) nephrograms, intra-venous urography (I.V.U.) and triple probe 131I-Hippuran renography. The computer processed data displays renal morphology and activity/time curves which are deconvolved enabling quantitative assessment of glomerular function to be made. Pattern recognition techniques for feature extraction are employed to facilitate classification of the curves. It is concluded that the computer processed data gives better results both in the recognition of morphological defects and in the indication and measurement of renal damage.

  9. Renal function, protein binding and pharmacological response to diazoxide.

    PubMed Central

    Pearson, R M; Breckenridge, A M

    1976-01-01

    1 The effect of rapid (10s) injections of diazoxide was studied in ten hypertensive patients with varying degrees of impairment of renal function. 2 There was a significant correlation between the patient's plasma urea concentration and reduction in mean arterial blood pressure. Diazoxide was also shown to be less highly protein bound in patients with renal failure. 3 It is suggested that the explanation for the increased hypotensive effect of diazoxide observed in patients with reduced renal function is related to higher unbound drug concentrations. PMID:973937

  10. An investigation of renal function in chronic bronchitis.

    PubMed Central

    Daggett, P.

    1977-01-01

    An investigation has been made into various parameters of renal function in patients with chronic bronchitis and in a group of hypoxic controls. Abnormalities of glomerular filtration rate and of water handling have been demostrated in chronic bronchitic patients but not in hypoxic controls. The abnormalities are related to the arterial Pco2. A hypothesis is presented as to the role of CO2 in causing abnormalities of renal function in chronic bronchitis. PMID:17853

  11. Apelin and copeptin: two opposite biomarkers associated with kidney function decline and cyst growth in autosomal dominant polycystic kidney disease.

    PubMed

    Lacquaniti, Antonio; Chirico, Valeria; Lupica, Rosaria; Buemi, Antoine; Loddo, Saverio; Caccamo, Chiara; Salis, Paola; Bertani, Tullio; Buemi, Michele

    2013-11-01

    Vasopressin (AVP) plays a detrimental role in autosomal dominant polycystic kidney disease (ADPKD). Copeptin represents a measurable substitute for circulating AVP whereas apelin counteracts AVP signaling. The aim of this study was to investigate the predictive value of apelin and copeptin for the progression of ADPKD disease. 52 ADPKD patients were enrolled and followed until the end of the observation period or the primary study endpoint was reached, defined by the combined outcome of decrease of glomerular filtration rate associated with a total renal volume increase. Receiver operating characteristics (ROC) analysis was employed for identifying the progression of renal disease and Kaplan-Meier curves assessed the renal survival. Adjusted risk estimates for progression endpoint and incident renal replacement therapy (RRT) were calculated using Cox proportional hazard regression analysis. ADPKD patients were characterized by lower apelin levels and higher copeptin levels when compared with healthy subjects. These biomarkers were strictly correlated with osmolality and markers of renal function. At ROC analysis, apelin and copeptin showed a very good diagnostic profile in identifying ADPKD progression. After the follow up of 24 months, 33 patients reached the endpoint. Cox proportional hazard regression analysis showed that apelin predicted renal disease progression and incident RRT independently of other potential confounders. Apelin is associated with kidney function decline in ADPKD, suggesting that it may be a new marker to predict kidney outcome.

  12. Gene expression-based biomarkers for discriminating early and late stage of clear cell renal cancer

    PubMed Central

    Bhalla, Sherry; Chaudhary, Kumardeep; Kumar, Ritesh; Sehgal, Manika; Kaur, Harpreet; Sharma, Suresh; Raghava, Gajendra P. S.

    2017-01-01

    In this study, an attempt has been made to identify expression-based gene biomarkers that can discriminate early and late stage of clear cell renal cell carcinoma (ccRCC) patients. We have analyzed the gene expression of 523 samples to identify genes that are differentially expressed in the early and late stage of ccRCC. First, a threshold-based method has been developed, which attained a maximum accuracy of 71.12% with ROC 0.67 using single gene NR3C2. To improve the performance of threshold-based method, we combined two or more genes and achieved maximum accuracy of 70.19% with ROC of 0.74 using eight genes on the validation dataset. These eight genes include four underexpressed (NR3C2, ENAM, DNASE1L3, FRMPD2) and four overexpressed (PLEKHA9, MAP6D1, SMPD4, C11orf73) genes in the late stage of ccRCC. Second, models were developed using state-of-art techniques and achieved maximum accuracy of 72.64% and 0.81 ROC using 64 genes on validation dataset. Similar accuracy was obtained on 38 genes selected from subset of genes, involved in cancer hallmark biological processes. Our analysis further implied a need to develop gender-specific models for stage classification. A web server, CancerCSP, has been developed to predict stage of ccRCC using gene expression data derived from RNAseq experiments. PMID:28349958

  13. FOXC2 and CLIP4 : a potential biomarker for synchronous metastasis of ≤7-cm clear cell renal cell carcinomas.

    PubMed

    Ahn, Jinwoo; Han, Kyung Seok; Heo, Jun Hyeok; Bang, Duhee; Kang, You Hyun; Jin, Hyun A; Hong, Sung Joon; Lee, Ji Hyun; Ham, Won Sik

    2016-08-09

    Renal cell carcinomas (RCC) smaller than 7-cm are heterogeneous and exhibit metastatic potential in approximately 15% of cases. Although large-scale characterization of mutations in clear cell RCC (ccRCC), the most common RCC subtype, has been established, the genetic alterations related to ≤7-cm ccRCCs undergoing synchronous metastasis are poorly understood. To discover biomarkers that can be used to estimate the risk of synchronous metastasis in these ccRCC patients, we performed whole exome sequencing on the formalin-fixed paraffin-embedded (FFPE) samples of 10 ccRCC patients with ≤7-cm tumors and synchronous metastasis and expanded our study using The Cancer Genome Atlas (TCGA) ccRCC dataset (n = 201). Recurrent mutations were selected according to functional prediction and statistical significance. Mutations in three candidate genes, RELN (1 out of 10), FOXC2 (1 out of 10), and CLIP4 (2 out of 10) were found in expanded analysis using a TCGA cohort. Furthermore, siRNA-mediated target gene knockdown (FOXC2 and CLIP4) and overexpression (RELN) assays showed that FOXC2 and CLIP4 significantly increased cell migration and viability in ccRCCs. Our study demonstrated that FOXC2 and CLIP4 activity correlates to the presence of ≤7-cm ccRCCs with synchronous metastasis and may be potential molecular predictors of synchronous metastasis of ≤7-cm ccRCCs.

  14. Multi-parametric profiling of renal cell, colorectal, and ovarian cancer identifies tumour-type-specific stroma phenotypes and a novel vascular biomarker.

    PubMed

    Corvigno, Sara; Frödin, Magnus; Wisman, G Bea A; Nijman, Hans W; Van der Zee, Ate Gj; Jirström, Karin; Nodin, Björn; Hrynchyk, Ina; Edler, David; Ragnhammar, Peter; Johansson, Martin; Dahlstrand, Hanna; Mezheyeuski, Artur; Östman, Arne

    2017-07-01

    A novel set of integrated procedures for quantification of fibroblast-rich stroma and vascular characteristics has recently been presented allowing discovery of novel perivascular and stromal biomarkers in colorectal, renal cell, and ovarian cancer. In the present study, data obtained through these procedures from clinically well-annotated collections of these three tumour types have been used to address two novel questions. First, data have been used to investigate if the three tumour types demonstrate significant differences regarding features such as vessel diameter, vessel density, and perivascular marker expression. Second, analyses of the cohorts have been used to explore the prognostic significance of a novel vascular metric, 'vessel distance inter-quartile range (IQR)' that describes intra-case heterogeneity regarding vessel distribution. The comparisons between the three tumour types demonstrated a set of significant differences. Vessel density of renal cell cancer was statistically significantly higher than in colorectal and ovarian cancer. Vessel diameter was statistically significantly higher in ovarian cancer. Concerning perivascular status, colorectal cancer displayed significantly higher levels of perivascular PDGFR-β expression than the other two tumour types. Intra-case heterogeneity of perivascular PDGFR-β expression was also higher in colorectal cancer. Notably, these fibroblast-dominated stroma phenotypes matched previously described experimental tumour stroma characteristics, which have been linked to differential sensitivity to anti-VEGF drugs. High 'vessel distance IQR' was significantly associated with poor survival in both renal cell cancer and colorectal cancer. In renal cell cancer, this characteristic also acted as an independent prognostic marker according to multivariate analyses including standard clinico-pathological characteristics. Explorative subset analyses indicated particularly strong prognostic significance of 'vessel

  15. MicroRNAs in clear cell renal cell carcinoma: biological functions and applications

    PubMed Central

    2015-01-01

    MicroRNAs (miRs) are small noncoding RNAs that govern many biological processes. They frequently acquire a gain or a loss of function in cancer and hence play a causative role in the development and progression of neoplasms. They could be used as biomarkers to improve our knowledge on diagnosis, prognosis and drug resistance, and to attempt therapeutic approaches in several types of cancer including clear cell renal cell carcinoma (ccRCC). ccRCC is the most predominant subtype of RCC that accounts for about 90% of all renal cancers. Since ccRCC is generally asymptomatic until very late, it is difficult to diagnose early. Moreover, in the absence of preventive treatments for metastatic ccRCC after surgical resection of the primary cancer, predictive prognostic biomarkers are needed in order to achieve appropriate therapies. Herein the role of miRs in the biology of ccRCC and the potential applications of these molecules are discussed. Moreover, future applications in the diagnostic and prognostic field, as well as their impact on drug response and therapeutic targets are also explored. Their use in clinical practice as molecular biomarkers alone, or in combination with other biological markers could accelerate progress, help design personalized therapies, limit side effects, and improve quality of life of ccRCC patients.

  16. Effects of Renal Denervation on Renal Artery Function in Humans: Preliminary Study

    PubMed Central

    Doltra, Adelina; Hartmann, Arthur; Stawowy, Philipp; Goubergrits, Leonid; Kuehne, Titus; Wellnhofer, Ernst; Gebker, Rolf; Schneeweis, Christopher; Schnackenburg, Bernhard; Esler, Murray; Fleck, Eckart; Kelle, Sebastian

    2016-01-01

    Aim To study the effects of RD on renal artery wall function non-invasively using magnetic resonance. Methods and Results 32 patients undergoing RD were included. A 3.0 Tesla magnetic resonance of the renal arteries was performed before RD and after 6-month. We quantified the vessel sharpness of both renal arteries using a quantitative analysis tool (Soap-Bubble®). In 17 patients we assessed the maximal and minimal cross-sectional area of both arteries, peak velocity, mean flow, and renal artery distensibility. In a subset of patients wall shear stress was assessed with computational flow dynamics. Neither renal artery sharpness nor renal artery distensibility differed significantly. A significant increase in minimal and maximal areas (by 25.3%, p = 0.008, and 24.6%, p = 0.007, respectively), peak velocity (by 16.9%, p = 0.021), and mean flow (by 22.4%, p = 0.007) was observed after RD. Wall shear stress significantly decreased (by 25%, p = 0.029). These effects were observed in blood pressure responders and non-responders. Conclusions RD is not associated with adverse effects at renal artery level, and leads to an increase in cross-sectional areas, velocity and flow and a decrease in wall shear stress. PMID:27003912

  17. Renal infarct volume and renal function decline in acute and chronic phases.

    PubMed

    Kagaya, Saeko; Yoshie, Ojima; Fukami, Hirotaka; Sato, Hiroyuki; Saito, Ayako; Takeuchi, Yoichi; Matsuda, Ken; Nagasawa, Tasuku

    2017-03-10

    Acute renal infarction (ARI) is a rare disease. ARI causes decline in renal function in both the acute and chronic phases. However, the correlation between the volume of the infarction and degree of renal function decline has not been fully investigated. Therefore, we aimed to examine the relationship between the volume of the infarction and degree of renal function decline. We performed a single-center, retrospective, observational study investigating clinical parameters and the volume of the infarction. The volume of the infarction was measured using reconstructed computed tomography data. A total of 39 patients (mean age, 72.6 ± 13.2 years; men, 59%) were enrolled. The median infarction volume was 45 mL (interquartile range, 14-91 mL). The volume of the infarction was significantly associated with the peak lactate dehydrogenase (LDH) level (median, 728 IU/L; interquartile range, 491-1227 U/L) (r = 0.58, p < 0.01) and the degree of renal function decline in both acute and chronic phases (r = -0.44, -0.38, respectively, p < 0.05). The peak LDH level was significantly correlated with the degree of renal function decline in the acute phase but not in the chronic phase (r = -0.35, -0.21; p < 0.05, N.S., respectively). The volume of the infarction may be a factor in the degree of renal function decline in ARI. Therefore, assessment of infarct volume in ARI is important.

  18. Obesity-Associated Biomarkers and Executive Function in Children

    PubMed Central

    Miller, Alison L.; Jong, Hannah; Lumeng, Julie C.

    2015-01-01

    There is a growing focus on links between obesity and cognitive decline in adulthood, including Alzheimer’s disease. It is also increasingly recognized that obesity in youth is associated with poorer cognitive function, specifically executive functioning skills such as inhibitory control and working memory, which are critical for academic achievement. Emerging literature provides evidence for possible biological mechanisms driven by obesity; obesity-associated biomarkers such as adipokines, obesity-associated inflammatory cytokines, and obesity-associated gut hormones have been associated with learning, memory, and general cognitive function. To date, examination of obesity-associated biology with brain function has primarily occurred in animal models. The few studies examining such biologically-mediated pathways in adult humans have corroborated the animal data, but this body of work has gone relatively unrecognized by the pediatric literature. Despite the fact that differences in these biomarkers have been found in association with obesity in children, the possibility that obesity-related biology could affect brain development in children has not been actively considered. We review obesity-associated biomarkers that have shown associations with neurocognitive skills, specifically executive functioning skills which have far-reaching implications for child development. Understanding such gut-brain associations early in the lifespan may yield unique intervention implications. PMID:25310758

  19. The importance of residual renal function in peritoneal dialysis.

    PubMed

    Sikorska, Dorota; Pawlaczyk, Krzysztof; Olewicz-Gawlik, Anna; Czepulis, Natasza; Posnik, Bartlomiej; Baum, Ewa; Wanic-Kossowska, Maria; Lindholm, Bengt; Oko, Andrzej

    2016-12-01

    Peritoneal dialysis (PD) patients with preserved residual diuresis have a lower risk of death and complications. Here we analyzed associations between residual diuresis and presence of fluid overload and biomarkers of cardiac strain and nutrition in PD patients. Among 44 PD patients placed into three subgroups, depending on volume of residual diuresis (group A ≤ 500; group B 600-1900; and group C ≥ 2000 mL/day), we examined: overhydration (OH) assessed by bioimpedance analysis (BIA; yielding OH index OHBIA) and by clinical criteria (edema and hypertension); nutritional status (by subjective global assessment, SGA); metabolic status (electrolytes, serum lipid profile, CRP, and albumin); biomarkers of fluid overload and cardiac strain (N-terminal probrain natriuretic peptide, NT-proBNP, and troponin T, TnT); and, echocardiography and chest X-ray. With increasing residual diuresis in group A, B and C, fewer patients had signs of overhydration defined as OHBIA > 1.1 L (75.0, 42.9 and 33.3 %) or peripheral edema (25.0, 21.4 and 0 %) and NT-proBNP (15199 ± 16150 vs. 5930 ± 9256 vs. 2600 ± 3907 pg/mL; p < 0.05) and TnT (0.15 ± 0.17 vs. 0.07 ± 0.09 vs. 0.04 ± 0.03 ng/mL; p < 0.05) were significantly lower. Significant differences were found also in ejection fraction, SGA, and total cholesterol, albumin and hemoglobin levels whereas blood pressures and serum CRP did not differ significantly. Signs of OH and cardiac strain are common in PD patients, even in those with diuresis of 1000-2000 mL/day and with no clinical signs or symptoms, suggesting that even moderate decrease in residual renal function in PD patients associate with OH and other complications.

  20. Impact of Stone Removal on Renal Function: A Review

    PubMed Central

    Wood, Kyle; Keys, Tristan; Mufarrij, Patrick; Assimos, Dean G

    2011-01-01

    Stone removal can improve renal function by eradicating obstruction and, in certain cases, an underlying infection. Stone-removing procedures, however, may negatively impact functional integrity. Many things may impact the latter, including the procedures used, the methods of assessing function, the time when these assessments are made, the occurrence of complications, the baseline condition of the kidney, and patient-related factors. In the majority of cases, little significant functional impairment occurs. However, there are gaps in our knowledge of this subject, including the cumulative effects of multiple procedures violating the renal parenchyma and long-term functional outcomes. PMID:21935339

  1. Renal Function and Transplantation in Liver Disease.

    PubMed

    Parajuli, Sandesh; Foley, David; Djamali, Arjang; Mandelbrot, Didier

    2015-09-01

    Kidney injury is associated with increased morbidity and mortality in liver transplant recipients. Since the introduction of the model for end-stage liver disease for the allocation of organs for liver transplantation in 2002, the heavy weighting of serum creatinine in the model for end-stage liver disease score has significantly increased the incidence of renal dysfunction seen among patients undergoing liver transplantation. As a result, the frequency of simultaneous liver-kidney (SLK) transplantation compared to liver transplantation alone (LTA) has also increased. The decision to perform SLK rather than LTA is an important one because the benefits to the liver transplant recipient receiving a kidney transplant must be balanced with the benefits of using that organ for a patient with end-stage renal disease. However, predicting whether or not a patient with liver failure has reversible kidney disease, and therefore does not also need a kidney transplant, is difficult. The severity and duration of pretransplant renal dysfunction, hepatitis c, diabetes, and other risk factors for kidney disease are associated with an increased risk of posttransplant end-stage renal disease. However, there are currently no clinical findings that accurately predict renal recovery post liver transplant. As a result, the rate of SLK versus LTA differs significantly between transplant centers. To increase consistency across centers, multiple guidelines have been proposed to guide the decision between SLK and LTA, but their poor predictive value has limited their uniform adoption. Nevertheless, adoption of uniform rules for the allocation of kidneys would reduce the variability between centers in rates of SLK transplant.

  2. Impaired renal functional reserve and albuminuria in essential hypertension

    PubMed Central

    Losito, Attilio; Fortunati, Federico; Zampi, Ivano; Del Favero, Albano

    1988-01-01

    The stimulatory effects of an infusion of amino acids on glomerular filtration rate has previously been used to measure renal functional reserve and detect glomerular hyperfiltration. Thirty four patients with mild to moderate essential hypertension and seemingly normal renal function and 22 healthy controls were given infusions of amino acids to investigate whether renal functional reserve is reduced in essential hypertension and to detect patients at risk of renal damage. Although basal creatinine clearance increased after the infusion of amino acids in the controls (mean 27·9 ml/min; 95% confidence interval 18·2 to 37·6), the overall change was lower in the patients (mean 13·4 ml/min; 8·3 to 18·5), 11 of the 34 showing no increase at all. In these 11 non-responders the mean systolic blood pressure was higher than that in the 23 others (178·5 mm Hg v 157 mm Hg, respectively). Mean urinary albumin excretion was abnormal in the patients (93·3 mg/24 h; 44·2 to 142·4); eight of the 11 non-responders had an albumin excretion above the normal range (>20 mg/24 h). In the 11 patients without renal functional reserve a positive correlation was found between basal creatinine clearance and albumin excretion (r=0·695). As consumed renal reserve and albuminuria are markers of glomerular hyperfiltration studying renal function before and after infusion of amino acids can detect hypertensive patients at risk of progressive renal damage. PMID:3135009

  3. Effect of first myocardial ischemic event on renal function.

    PubMed

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

    2007-07-01

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

  4. MicroRNAs in the pathogenesis of renal cell carcinoma and their diagnostic and prognostic utility as cancer biomarkers.

    PubMed

    Fedorko, Michal; Pacik, Dalibor; Wasserbauer, Roman; Juracek, Jaroslav; Varga, Gabriel; Ghazal, Motasem; Nussir, Mohamed I

    2016-02-28

    To provide information about the role of microRNAs in the pathogenesis of renal cell carcinoma (RCC) and their diagnostic and prognostic utility as cancer biomarkers. A literature search was performed in the PubMed and Web of Science databases using the keywords "renal cancer/renal cell carcinoma/kidney cancer" and "miR*/miRNA*/microRNA*". Articles dealing with the role of miRNAs in the pathogenesis of RCC, diagnostic miRNAs and prognostic miRNAs were separated. MiRNAs act both as oncogenes and tumor suppressors. They regulate apoptosis, cell growth, migration, invasion, proliferation, colony formation and angiogenesis through target proteins involved in several signaling pathways, and they are involved in key pathogenetic mechanisms such as hypoxia (HIF/VHL dependent) and epithelial-to-mesenchymal transition. Differentially expressed miRNAs can discriminate either tumor tissue from healthy renal tissue or different RCC subtypes. Circulating miRNAs are promissing as diagnostic biomarkers of RCC. Information about urinary miRNAs associated with RCC is sparse. Detection of a relapse is another implication of diagnostic miRNAs. The expression profiles of several miRNAs correlate with the prognosis of RCC patients. Comparison between primary tumor tissue and metastasis may help identify high-risk primary tumors. Finally, response to target therapy can be estimated thanks to differences in miRNA expression in tissue and serum of therapy-resistant versus therapy-sensitive patients. Our understanding of the role of microRNAs in RCC pathogenesis has been increasing dramatically. Identification and validation of their gene targets may have direct impact on developing microRNA-based anticancer therapy. Several microRNAs can serve as diagnostic and prognostic biomarkers.

  5. Evaluation of Renal Histopathological Changes, as a Predictor of Recoverability of Renal Function Following Pyeloplasty for Ureteropelvic Junction Obstruction

    PubMed Central

    Kumar, Kaushal; Ahmad, Ahsan; Kumar, Shailendra; Choudhry, Vijyanand; Tiwari, Rajesh Kumar; Singh, Mahendra; Muzaffar, Mohammad Ali

    2015-01-01

    Background: Pyeloplasty is a widely accepted treatment for ureteropelvic junction obstruction (UPJO). However, the renal function recoverability after pyeloplasty is still a matter of debate. Different parameters have been used to predict renal functional recoverability after corrective surgery, with conflicting results. Objectives: In this study, renal biopsy was carried on a series of cases of UPJO, during pyeloplasty, to study the extent of histological alterations in renal parenchyma, as a result of obstruction, and its predictive value in renal function recoverability after pyeloplasty. Patients and Methods: We retrospectively analyzed the renal biopsy obtained during pyeloplasty in 53 adult patients. Histopathological changes were graded on a scale of 1 to 3, according to their severity, and compared with the differential renal function (DRF) revealed on the preoperative and postoperative follow up diethylene triamine pentaacetic acid (DTPA) renal scan. A Fischer’s t test was used to evaluate statistical differences between values. Results: This study showed a linear relationship between the severity of histological changes and renal function recovery, after pyeloplasty. Out of 24 obstructed renal units (ORU), with minimal histopathological changes (grade I), 21 ORU (87.5%), with > 35% DRF preoperatively, showed significant improvement in renal function after 12 months of pyeloplasty (P < 0.05). On the other hand, all kidneys (n = 29) with moderate to severe obstructive changes (grade II and III) had minimal improvement in DRF, after pyeloplasty, which was clinically insignificant (P > 0.05). Renal function deterioration after pyeloplasty was not observed in any of the cases. Conclusions: The severity of pathological changes in renal parenchyma, due to UPJO, is a good predictor of renal function recoverability, after pyeloplasty. The ORUs, with DRF > 35%, usually have normal (grade I) renal biopsy and might be expected to present better functional

  6. Selective renal vasodilation and active renal artery perfusion improve renal function in dogs with acute heart failure.

    PubMed

    Suehiro, K; Shimizu, J; Yi, G H; Gu, A; Wang, J; Keren, G; Burkhoff, D

    2001-09-01

    Renal failure is common in heart failure due to renovascular constriction and hypotension. We tested whether selective pharmacological renal artery vasodilation and active renal artery perfusion (ARP) could improve renal function without adverse effects on systemic blood pressure in a canine model of acute heart failure (AHF). AHF was induced by coronary microembolization in 16 adult mongrel dogs. In five dogs, selective intrarenal (IR) papaverine (1, 2, and 4 mg/min) was administered into the left renal artery. In six dogs, ARP was performed in the left renal artery to normalize mean renal arterial pressure followed by administration of IR papaverine (2 mg/min). In five dogs, ARP plus intravenous furosemide was tested. Urine output (UO) and cortical renal blood flow decreased during AHF and were restored by 2 mg/min IR papaverine (UO: baseline 4.2 +/- 0.6, AHF 1.6 +/- 1.3, IR papaverine 5.8 +/- 1.1 ml/15 min; cortical blood flow: baseline 4.3 +/- 0.2, AHF 2.4 +/- 0.6, IR papaverine 4.2 +/- 1.2 ml/min/g) with no significant change in aortic pressure. ARP also increased urine output and cortical renal blood flow (UO: baseline 5.0 +/- 1.1, AHF 0.5 +/- 0.4, ARP 3.8 +/- 3.1 ml/15 min; cortical blood flow: baseline 4.0 +/- 0.5, AHF 2.0 +/- 0.8, ARP 3.52 +/- 1.1 ml/min/g). A combination of these methods in AHF further increased urine output to twice the normal baseline (10.5 +/- 7.5 ml/15 min). Addition of furosemide synergistically increased UO above that achieved with ARP alone (5.5 +/- 2.6 versus 40.3 +/- 24.7 ml/15 min, p = 0.03). In conclusion, ARP and selective renal vasodilation may effectively promote salt and water excretion in the setting of heart failure, particularly when systemic blood pressure is low.

  7. Circulating Biomarkers of One-Carbon Metabolism in Relation to Renal Cell Carcinoma Incidence and Survival

    PubMed Central

    Johansson, Mattias; Fanidi, Anouar; Muller, David C.; Bassett, Julie K.; Midttun, Øivind; Vollset, Stein Emil; Travis, Ruth C.; Palli, Domenico; Mattiello, Amalia; Sieri, Sabina; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Ljungberg, Börje; Hallmans, Göran; Weiderpass, Elisabete; Skeie, Guri; González, Carlos A.; Dorronsoro, Miren; Peeters, Petra H.; Bueno-de-Mesquita, H. B(as).; Ros, Martine M.; Boutron Ruault, Marie-Christine; Fagherazzi, Guy; Clavel, Françoise; Sánchez, María-José; Gurrea, Aurelio Barricarte; Navarro, Carmen; Quiros, J. Ramon; Overvad, Kim; Tjønneland, Anne; Aleksandrova, Krassimira; Vineis, Paolo; Gunter, Marc J.; Kaaks, Rudolf; Giles, Graham; Relton, Caroline; Riboli, Elio; Boeing, Heiner; Ueland, Per Magne; Severi, Gianluca; Brennan, Paul

    2014-01-01

    Background The etiology of renal cell carcinoma (RCC) is only partially understood, but a metabolic component appears likely. We investigated biomarkers of one-carbon metabolism and RCC onset and survival. Methods The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 385747 participants with blood samples between 1992 and 2000, and this analysis included 556 RCC case-control pairs. A subsequent replication study included 144 case-control pairs nested within the Melbourne Collaborative Cohort Study (MCCS). Plasma concentrations of vitamin B2, vitamin B6, folate, vitamin B12, methionine and homocysteine were measured in prediagnostic samples and evaluated with respect to RCC risk using conditional and unconditional logistic regression models, and to all-cause mortality in RCC cases using Cox regression models. All statistical tests were two-sided. Results EPIC participants with higher plasma concentrations of vitamin B6 had lower risk of RCC, the odds ratio comparing the 4th and 1st quartiles (OR4vs1) being 0.40 95% confidence interval [CI] = 0.28 to 0.57, P trend < .001. We found similar results after adjusting for potential confounders (adjusted P trend < .001). In survival analysis, the hazard ratio for all-cause mortality in RCC cases when comparing the 4th and 1st quartiles (HR4vs1) of vitamin B6 was 0.57 (95% CI = 0.37 to 0.87, P trend < .001). Subsequent replication of these associations within the MCCS yielded very similar results for both RCC risk (OR4vs1 = 0.47, 95% CI = 0.23 to 0.99, P trend = .07) and all-cause mortality (HR4vs1 = 0.56, 95% CI = 0.27 to 1.17, P trend = .02). No association was evident for the other measured biomarkers. Conclusion Study participants with higher circulating concentrations of vitamin B6 had lower risk of RCC and improved survival following diagnosis in two independent cohorts. PMID:25376861

  8. A simple and accurate grading system for orthoiodohippurate renal scans in the assessment of post-transplant renal function

    SciTech Connect

    Zaki, S.K.; Bretan, P.N.; Go, R.T.; Rehm, P.K.; Streem, S.B.; Novick, A.C. )

    1990-06-01

    Orthoiodohippurate renal scanning has proved to be a reliable, noninvasive method for the evaluation and followup of renal allograft function. However, a standardized system for grading renal function with this test is not available. We propose a simple grading system to distinguish the different functional phases of hippurate scanning in renal transplant recipients. This grading system was studied in 138 patients who were evaluated 1 week after renal transplantation. There was a significant correlation between the isotope renographic functional grade and clinical correlates of allograft function such as the serum creatinine level (p = 0.0001), blood urea nitrogen level (p = 0.0001), urine output (p = 0.005) and need for hemodialysis (p = 0.007). We recommend this grading system as a simple and accurate method to interpret orthoiodohippurate renal scans in the evaluation and followup of renal allograft recipients.

  9. Growth and endocrine function after renal transplantation.

    PubMed Central

    Rees, L; Greene, S A; Adlard, P; Jones, J; Haycock, G B; Rigden, S P; Preece, M; Chantler, C

    1988-01-01

    Longitudinal height data and physical development were assessed in 45 boys and 34 girls after renal transplantation. All children received alternate day steroids and either azathioprine or cyclosporin A for immunosuppression. There was a significant increase in growth velocity after transplantation in prepubertal children. Growth velocity declined at the expected age of the normal pubertal growth spurt, however, with delay in the appearance of secondary sexual characteristics. Overnight hormone profiles in 17 adolescent subjects with short stature or maturational delay, or both, showed blunting of growth hormone and gonadotrophin pulsatility. It is likely that long term steroid treatment after renal transplantation induces the clinical and endocrine picture of delayed puberty. Failure of growth to accelerate at this time is a cause of short stature, which may have an effect on adult height. PMID:3060022

  10. [The relevance of a decline in renal function for risk of renal failure, cardiovascular events and all-cause mortality].

    PubMed

    Bots, Michiel L; Blankestijn, Peter J

    2015-01-01

    It is well established that the presence of impaired renal function is associated with an increased risk of end-stage renal disease, cardiovascular events and all-cause mortality. Irrespective of the starting level of renal function, a decline in renal function over two years is a relevant and strong risk factor for end-stage renal disease, cardiovascular death and all-cause mortality. Even a decline of 20 to 30 per cent is associated with to a considerable increased risk and requires further attention.

  11. Renal Function Outcomes for Multifocal Renal Neoplasms Managed by Radiofrequency Ablation

    SciTech Connect

    Gupta, Pushpender Allen, Brian C. Chen, Michael Y. Childs, David D. Kota, Gopi Zagoria, Ronald J.

    2013-10-15

    Purpose: To evaluate renal function changes related to radiofrequency ablation (RFA) for the treatment of multifocal renal neoplasms. Methods: This is an institutional review board-approved, Health Insurance Portability and Accountability Act compliant retrospective study of all patients treated with computed tomography guided RFA for multifocal renal neoplasms at one institution. Fifty-seven subjects, mean age 70 (range 37-88) years, underwent RFA of 169 renal neoplasms (average size 2.0 cm). Subjects had between 2 and 8 (mean 2.96) neoplasms ablated. Estimated glomerular filtration rate (eGFR) was measured before and after RFA. Complications related to RFA were recorded. Results: eGFR decreased on average of 4.4 % per tumor treated and 6.7 % per ablation session (average 1.76 tumors treated per session). For subjects with the largest neoplasm measuring >3 cm, eGFR decreased an average of 14.5 % during the course of their treatment. If the largest neoplasm measured 2-3 cm, eGFR decreased an average of 7.7 %, and if the largest neoplasm measured <2 cm, eGFR decreased an average of 3.8 %. Subjects with reduced baseline renal function were more likely to have a greater decline in eGFR after RFA. There was a minor complication rate of 6.3 % (6 of 96 sessions), none of which required treatment, and a major complication rate of 4.2 % (4 of 96 sessions). Conclusion: RFA for the treatment of multifocal renal neoplasms results in mild decline of renal function.

  12. Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

    PubMed

    Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

    2011-01-01

    The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

  13. A prospective study of one-carbon metabolism biomarkers and risk of renal cell carcinoma

    PubMed Central

    Gibson, Todd M.; Weinstein, Stephanie J.; Mayne, Susan T.; Pfeiffer, Ruth M.; Selhub, Jacob; Taylor, Philip R.; Virtamo, Jarmo; Albanes, Demetrius; Stolzenberg-Solomon, Rachael

    2010-01-01

    Objective Previous studies have found associations between one-carbon metabolism factors and risk of several cancers, but little is known regarding renal cell carcinoma (RCC). We conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a prospective study of Finnish male smokers aged 50-69 at baseline. Methods Prediagnostic folate, vitamin B6, vitamin B12, cysteine, riboflavin and homocysteine concentrations were measured in fasting serum from 224 incident RCC cases and 224 controls (matched on age and date of serum collection). Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders. Results Serum folate tended to be inversely associated with RCC; compared to the first quartile, the odds ratios (95% CI) for subsequent quartiles were 0.62 (0.35-1.08), 0.52 (0.29-0.93), and 0.67 (0.37-1.20) (P-trend = 0.19). When modeled as a threshold effect, subjects in the lowest serum folate quartile (≤ 6.64 nmol/L), which corresponds to deficient folate status, had a significant increased RCC risk (OR = 1.68, 95% CI 1.06-2.65) compared to those with higher serum folate. The other one-carbon metabolism biomarkers were not associated with RCC. Conclusions This study in male smokers suggests that deficient folate status may increase risk of RCC, but confirmation is needed in other epidemiologic studies that include women and non-smokers. PMID:20383577

  14. Prognostic value of tissue-based biomarker signature in clear cell renal cell carcinoma.

    PubMed

    Haddad, Ahmed Q; Luo, Jun-Hang; Krabbe, Laura-Maria; Darwish, Oussama; Gayed, Bishoy; Youssef, Ramy; Kapur, Payal; Rakheja, Dinesh; Lotan, Yair; Sagalowsky, Arthur; Margulis, Vitaly

    2017-05-01

    To improve risk stratification for recurrence prognostication in patients with localised clear cell renal cell carcinoma (ccRCC). In all, 367 patients with non-metastatic ccRCC were included. The cohort was divided into a training and validation set. Using tissue microarrays, immunostaining was performed for 24 biomarkers representative of key pathways in ccRCC. Using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, we identified several markers that were used to construct a risk classifier for risk of disease recurrence. The median (interquartile range) follow-up was 63.5 (24.0-85.3) months. Five out of 24 markers were selected by LASSO Cox regression for the risk classifier: N-cadherin, E-cadherin, Ki67, cyclin D1 and phosphorylated eukaryotic initiation factor 4E binding protein-1 (p-4EBP1). Patients were classified as either low, intermediate or high risk of disease recurrence by tertiles of risk score. The 5-year recurrence-free survival (RFS) was 93.8%, 87.7% and 70% for patients with low-, intermediate- and high-risk scores, respectively (P < 0.001). Patients with a high marker score had worse RFS on multivariate analysis adjusted for age, gender, race and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score (hazard ratio 3.66, 95% confidence interval 1.58-8.49, P = 0.003 for high vs low marker score in the overall cohort). The five-marker classifier increased the concordance index of the clinical model in both the training and validation sets. We developed a five-marker-based prognostic tool that can effectively classify patients with ccRCC according to risk of disease recurrence after surgery. This tool, if prospectively validated, could provide individualised risk estimation for patients with ccRCC. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  15. The long non-coding RNA lnc-ZNF180-2 is a prognostic biomarker in patients with clear cell renal cell carcinoma

    PubMed Central

    Ellinger, Jörg; Alam, Jahedul; Rothenburg, Jannik; Deng, Mario; Schmidt, Doris; Syring, Isabella; Miersch, Herdis; Perner, Sven; Müller, Stefan C

    2015-01-01

    Clear cell renal cell carcinoma (ccRCC) is among the most common human malignancies. Long non-coding RNAs (lncRNA) regulate various cellular functions and have been implicated in ccRCC pathogenesis. In order to decipher the molecular biology of this tumor and to identify potential prognostic biomarkers and therapeutic targets, we re-evaluated published lncRNA expression profiling data. An expression profile of 49 lncRNAs allowed discrimination of localized and advanced ccRCC. The expression profile of six lncRNAs transcripts (lnc-ACO1625, lnc-CYP4A22-2/3, lnc-PEAK1.1-1, lnc-PCYOX1L, lnc-VCAN-1, lnc-ZNF180-2) with potential prognostic interest were validated in a cohort of 50 normal renal, 57 localized ccRCC and 45 advanced ccRCC tissues. lnc-ZNF180-2 levels were similar in localized ccRCC and normal renal tissue, but we observed a significant increase of lnc-ZNF180-2 expression in advanced ccRCC tissue. Furthermore, lnc-ZNF180-2 expression levels were an independent predictor of progression-free survival, cancer-specific survival and overall survival in ccRCC patients. We also observed that lnc-CYP4A22-2/3 expression levels allowed discrimination of ccRCC and normal renal tissue. In conclusion, lncRNAs are involved in renal carcinogenesis, and quantification of lnc-ZNF180-2 may be useful for the prediction of ccRCC patients outcome following nephrectomy. PMID:26609485

  16. Study on Assessment of Renal Function in Chronic Liver Disease

    PubMed Central

    Das, Nupur; Paria, Baishakhi; Sarkar, Sujoy

    2015-01-01

    Introduction: Renal dysfunction is common in chronic liver disease. The cause of this renal dysfunction is either multi-organ involvement in acute conditions or secondary to advanced liver disease. Objectives: The study was undertaken to assess the renal function in chronic liver diseases and find out the association of alteration of renal function with gradation of liver disease. (assessed by child-pugh criteria) and to find out the association of alteration of renal function among the cases of chronic liver disease of different aetiology. Materials and Methods: This cross-sectional, observational study was undertaken in Department of General Medicine, Calcutta National Medical College & Hospital, Kolkata during March 2012 to July 2013 with 50 admitted patients of chronic liver disease after considering the exclusion criteria. The patients were interviewed with a pre-designed and pre-tested schedule, examined clinically, followed by some laboratory investigations relevant to diagnose the aetiology of chronic liver disease, and to assess the severity of liver and renal dysfunction. Data was analysed by standard statistical method. Results: Eighty six percent of the patients were male and the mean age of study population was 43.58 y, 68% patients suffered from alcoholic liver disease, followed by 14% patients had chronic Hepatitis-B, 10% patients developed acute kidney injury, 20% had hepato renal syndrome and 14% had IgA deposition. The distribution of serum urea and creatinine across the categories of Child Pugh classification tested by Mann-Whitney test and the distribution was statistically significant. Conclusion: The present study has found significant association between severity of liver dysfunction and certain parameters of renal dysfunction. PMID:25954647

  17. Micro RNA-320 as a novel potential biomarker in renal ischemia reperfusion.

    PubMed

    Güçlü, Aydın; Koçak, Cengiz; Koçak, Fatma Emel; Akçılar, Raziye; Dodurga, Yavuz; Akçılar, Aydın; Seçme, Mücahit

    2016-10-01

    MicroRNAs (miR) are important diagnostic and treatment targets due to their different tissue expressions and their central position in the regulation of gene expressions. miR studies might pioneer emerging of new diagnostic tools and treatment goals in kidney diseases. Captopril (CAP) and telmisartan (TEL) were shown to be effective in ischemia reperfusion (IR) injury. There is not any study about the effect of TEL and CAP over miR-21-320-146a. Our aim was to study the effects of CAP and TEL over miR on renal IR model. We used 12-16 weeks-old Wistar-Albino rats that weigh 300-350 g. Rats (n, 6) were randomized into four groups (Control, IR, IR + CAP, IR + TEL). Urea, creatinine, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), super oxide dismutase (SOD), and miRs were analyzed. Urea, creatinine, TOS, OSI levels of IR + CAP, and IR + TEL groups were lower comparing to IR group. TAS and SOD levels were higher in IR group than IR + TEL group. miR-21-320-146a showed increase in renal IR injury. miR-320, 146a showed significant decrease in IR + CAP and IR + TEL groups comparing to IR group. We showed histopathological recovery and decreased apoptosis in IR + CAP and IR + T groups than IR group. We, for the first time in the literature, showed that miR-320 is increased in IR injury. miR-320 might be a novel diagnosis and treatment target in renal ischemic reperfusion injury. Also, for the first time, we showed that CAP and TEL cause functional and histopathological recovery and lower miR-146a and miR-320.

  18. Quantified kidney echogenicity in mice with renal ischemia reperfusion injury: evaluation as a noninvasive biomarker of acute kidney injury.

    PubMed

    Murata, Shinya; Sugiyama, Noriyuki; Maemura, Kentaro; Otsuki, Yoshinori

    2017-09-01

    The purpose is to evaluate quantified kidney echogenicity as a biomarker for the early diagnosis of acute kidney injury (AKI) and predicting progression to chronic kidney disease (CKD) in a mouse model of ischemia-reperfusion injury (IRI). Two separate protocols of murine models of IRI were used: (1) 10, 30, and 40 min of bilateral ischemia duration and (2) 45 and 60 min of unilateral ischemia duration. Renal echogenicity was measured with ultrasound and compared with serum creatinine or urine neutrophil gelatinase-associated lipocalin (NGAL) at various timepoints after IRI. In mice subjected to 10, 30, and 40 min of bilateral ischemia, renal echogenicity increased about 2 h after IRI for all ischemia times, earlier than serum creatinine or urine NGAL. In those subjected to 45 and 60 min of unilateral ischemia, 60 min of unilateral ischemia, which represents atrophic changes 28 days after IRI, resulted in a sustained high level of echogenicity and was significantly different 24 h after IRI, while 45 min of unilateral ischemia resulted in trivial levels of histological damage 28 days after IRI. Renal echogenicity might have the potential to be a biomarker for the early diagnosis of AKI and the prognosis of CKD.

  19. Beneficial effects of soy protein consumption for renal function.

    PubMed

    Anderson, James W

    2008-01-01

    Alterations in dietary protein intake have an important role in prevention and management of several forms of kidney disease. Using soy protein instead of animal protein reduces development of kidney disease in animals. Reducing protein intake preserves kidney function in persons with early diabetic kidney disease. Our clinical observations led us to the soy-protein hypothesis that "substitution of soy protein for animal protein results in less hyperfiltration and glomerular hypertension with resulting protection from diabetic nephropathy." These components of soy protein may lead to the benefits: specific peptides, amino acids, and isoflavones. Substituting soy protein for animal protein usually decreases hyperfiltration in diabetic subjects and may reduce urine albumin excretion. Limited data are available on effects of soy peptides, isoflavones, and other soy components on renal function on renal function in diabetes. Further studies are required to discern the specific benefits of soy protein and its components on renal function in diabetic subjects.

  20. Ciprofloxacin pharmacokinetics in patients with normal and impaired renal function.

    PubMed Central

    Gasser, T C; Ebert, S C; Graversen, P H; Madsen, P O

    1987-01-01

    The pharmacokinetics of ciprofloxacin following single oral doses of 500 and 750 mg in 32 patients with various degrees of renal function impairment were investigated in an open, randomized crossover fashion. Ciprofloxacin was administered after overnight fasting; the washout time between the two doses was 1 week. Serum and urine samples were collected serially between 0 and 24 h and subjected to bioassay and high-performance liquid chromatography. Pharmacokinetic parameters were analyzed, assuming an open two-compartment model with first-order input and elimination. A distinct difference was observed in pharmacokinetic parameters between patients with impaired renal function (creatinine clearance, less than 50 ml/min per 1.73 m2) and those with normal renal function (creatinine clearance, greater than or equal to 50 ml/min per 1.73 m2). For the former group, the area under the curve of serum concentration versus time was doubled, the renal clearance of ciprofloxacin was cut to one-fourth, the total and nonrenal ciprofloxacin clearance was reduced by 50%, and the elimination half-life was prolonged by a factor of approximately 1.7. The correlation between renal drug clearance and creatinine clearance was highly significant (r = 0.890; P less than 0.001). On the basis of these findings, it appears that a 50% dose reduction of ciprofloxacin in patients with impaired renal function (creatinine clearance, less than 50 ml/min per 1.73 m2) may be indicated to achieve concentrations in serum similar to those observed in normal individuals. As the concentration of ciprofloxacin in urine after 24 h remained above the MIC for most urinary pathogens, this drug appears to be of potential benefit for the treatment of urinary tract infections in patients with impaired renal function. PMID:3300537

  1. The relationship between renal volume and renal function in autosomal dominant polycystic kidney disease.

    PubMed

    Tokiwa, Shino; Muto, Satoru; China, Toshiyuki; Horie, Shigeo

    2011-08-01

    In patients with autosomal dominant polycystic kidney disease (ADPKD), renal cysts grow exponentially. Since remaining renal parenchyma has a capacity to compensate for the loss of glomerular filtration, the glomerular filtration rate (GFR) may be sustained until the disease progresses. The purpose of this study was to determine if renal volumetric indices and clinical parameters are associated with renal function in Japanese patients with ADPKD. In 73 ADPKD patients (28 men, 45 women), the associations of mean systolic blood pressure, mean diastolic blood pressure, estimated GFR (eGFR), the amount of proteinuria and albuminuria, body mass index (BMI), brachial-ankle pulse wave velocity (baPWV), ankle-brachial index, and total kidney volume (TKV) were retrospectively analyzed. Multivariate linear regression analysis showed that eGFR was significantly and independently inversely correlated with patients' age and BMI. The median change in eGFR per year (ΔeGFR/y) was -2.8 ml/min/1.73 m(2)/year. Multiple linear regression analysis showed that ΔeGFR/y was significantly and independently inversely correlated with the change in TKV per year (ΔTKV/y). Multiple linear regression analysis showed that ΔTKV/y was significantly related to initial TKV and the change in albuminuria per year. This study demonstrated a significant relationship between the change in renal function and the change in renal volume in Japanese ADPKD patients without renal insufficiency. It is possible that the volume measurements can be used as useful markers for disease progression in Japanese ADPKD patients.

  2. Differential renal function in unilateral renal injury: possible effects of radiopharmaceutical choice. [Rats

    SciTech Connect

    Taylor, A. Jr.; Lallone, R.

    1985-01-01

    An abnormal filtration fraction or a significant divergence between a kidney's ability to extract Tc-99m dimercaptosuccinic acid (DMSA) and other function parameters, such as the glomerular filtration rate (GFR) or the effective renal plasma flow (ERPF, could lead to different estimates of relative or absolute renal function, depending on the radiopharmaceutical administered. To evaluate this possible divergence, the authors measured the relative GFR (I-125 iothalamate), ERPF (I-131 hippurate), and Tc-99m DMSA accumulation in adult male Sprague-Dawley rats with unilateral ureteral obstruction or unilateral ischemia at various times after renal injury. The relative ERPF of the obstructed kidney was significantly greater than the relative GFR at all time periods studied; significant but less dramatic differences were noted comparing DMSA with GFR in obstruction and DMSA and ERPF with GRF in ischemia.

  3. Validation of a Functional Pyelocalyceal Renal Model for the Evaluation of Renal Calculi Passage While Riding a Roller Coaster.

    PubMed

    Mitchell, Marc A; Wartinger, David D

    2016-10-01

    The identification and evaluation of activities capable of dislodging calyceal renal calculi require a patient surrogate or validated functional pyelocalyceal renal model. To evaluate roller coaster facilitation of calyceal renal calculi passage using a functional pyelocalyceal renal model. A previously described adult ureteroscopy and renoscopy simulator (Ideal Anatomic) was modified and remolded to function as a patient surrogate. Three renal calculi of different sizes from the patient who provided the original computed tomographic urograph on which the simulator was based were used. The renal calculi were suspended in urine in the model and taken for 20 rides on the Big Thunder Mountain Railroad roller coaster at Walt Disney World in Orlando, Florida. The roller coaster rides were analyzed using variables of renal calculi volume, calyceal location, model position on the roller coaster, and renal calculi passage. Sixty renal calculi rides were analyzed. Independent of renal calculi volume and calyceal location, front seating on the roller coaster resulted in a passage rate of 4 of 24. Independent of renal calculi volume and calyceal location, rear seating on the roller coaster resulted in a passage rate of 23 of 36. Independent of renal calculi volume in rear seating, calyceal location differed in passage rates, with an upper calyceal calculi passage rate of 100%; a middle calyceal passage rate of 55.6%; and a lower calyceal passage rate of 40.0%. The functional pyelocalyceal renal model serves as a functional patient surrogate to evaluate activities that facilitate calyceal renal calculi passage. The rear seating position on the roller coaster led to the most renal calculi passages.

  4. sup 99m Tc renal tubular function agents: Current status

    SciTech Connect

    Eshima, D.; Fritzberg, A.R.; Taylor, A. Jr. )

    1990-01-01

    Orthoiodohippuric (OIH) acid labeled with 131I is a widely used renal radiopharmaceutical agent and has been the standard radiopharmaceutical agent for the measurement of effective renal plasma flow (EPRF). Limitations to the routine clinical use of 131I OIH are related to the suboptimal imaging properties of the 131I radionuclide and its relatively high radiation dose. 123I has been substituted for 131I; however, its high cost and short shelf-life have limited its widespread use. Recent work has centered on the development of a new 99mTc renal tubular function agent, which would use the optimal radionuclidic properties and availability of 99mTc and combine the clinical information provided by OIH. The search for a suitable 99mTc renal tubular function agent has focused on the diamide dithiolate (N2S2), the paraaminohippuric iminodiacetic acid (PAHIDA), and the triamide mercaptide (N3S) donor ligand systems. To date, the most promising 99mTc tubular function agent is the N3S complex: 99mTc mercaptoacetyltriglycine (99mTc MAG3). Studies in animal models in diuresis, dehydration, acid or base imbalance, ischemia, and renal artery stenosis demonstrate that 99mTc MAG3 behaves similarly to 131I OIH. A simple kit formulation is available that yields the 99mTc MAG3 complex in high radiochemical purity. Studies in normal subjects and patients indicate that 99mTc MAG3 is an excellent 99mTc renal tubular agent, but its plasma clearance is only 50% to 60% that of OIH. In an effort to develop an improved 99mTc renal tubular function agent, changes have been made in the core N3S donor ligand system, but to date no agent has been synthesized that is clinically superior to 99mTc MAG3. 61 references.

  5. Biomarkers of monitoring and functional reserve of physiological systems over time in HIV: expert opinions for effective secondary prevention.

    PubMed

    Andreoni, Massimo; Mussi, Chiara; Bellagamba, Rita; Di Campli, Francesco; Montinaro, Vincenzo; Babiloni, Claudio

    2017-10-10

    HIV-positive individuals are more vulnerable to poor health than HIV-negative individuals. This vulnerability is characterized by a higher risk of several common, age-related health problems, even after adjustment for established risk factors. This expert opinion report aims at identifying the optimal biomarkers for monitoring the structural integrity and function of physiological systems at risk across aging in HIV-seropositive subjects. These biomarkers, readily available locally and relatively cost-effective for clinicians in primary and secondary care, should allow early detection of the first preclinical structural and functional changes in renal, brain, cardiovascular, and skeleton systems or apparatus in HIV subjects across aging (Table 8). A particular interest of this report is the definition of the concept of biomarker of the "organ functional reserve". This definition emphasizes the fact that some biomarkers for monitoring the molecular, structural and functional integrity of a given organ reflect a level of impairment that is basically irremediable despite effective pharmacological or nonpharmacological intervention.

  6. [Methods for the estimation of the renal function].

    PubMed

    Fontseré Baldellou, Néstor; Bonal I Bastons, Jordi; Romero González, Ramón

    2007-10-13

    The chronic kidney disease represents one of the pathologies with greater incidence and prevalence in the present sanitary systems. The ambulatory application of different methods that allow a suitable detection, monitoring and stratification of the renal functionalism is of crucial importance. On the basis of the vagueness obtained by means of the application of the serum creatinine, a set of predictive equations for the estimation of the glomerular filtration rate have been developed. Nevertheless, it is essential for the physician to know its limitations, in situations of normal renal function and hyperfiltration, certain associate pathologies and extreme situations of nutritional status and age. In these cases, the application of the isotopic techniques for the calculation of the renal function is more recommendable.

  7. Serum IL-18 as biomarker in predicting long-term renal outcome among pediatric-onset systemic lupus erythematosus patients

    PubMed Central

    Wu, Chao-Yi; Yang, Huang-Yu; Yao, Tsung-Chieh; Liu, Su-Hsun; Huang, Jing-Long

    2016-01-01

    Abstract An urge of biomarker identification is needed to better monitor lupus nephritis (LN) disease activity, guide clinical treatment, and predict patient's long-term outcome. With the proinflammatory effect and its association with inflammasomes, the significance of interleukin-18 (IL-18) among pediatric-onset systemic lupus erythematous (pSLE) patient, especially, its importance in predicting long-term renal outcome was investigated. In a pSLE cohort of 96 patients with an average follow-up period of 10.39 ± 3.31 years, clinical data and laboratory workups including serum IL-18 were collected at time of disease onset and 6 months after treatment despite their initial renal status. Through Cox regression analysis, the parameters at baseline and at 6 months posttreatment were carefully analyzed. Average age of all cases was 12.74 ± 3.01 years old and 65 of them underwent renal biopsy at the time of diagnosis. Nine subjects (9.38%) progressed to end-stage renal disease (ESRD) and 2 cases (2.08%) died during follow-up. Through multivariate analysis, serum IL-18 level 6 months posttreatment was found to be the most unfavorable factor associating poor clinical outcome despite patient's initial renal status. In addition, the presentation of serum IL-18 in its correlation with SLE global disease activity as well as the presence and severity of LN were all significant (P < 0.001, P = 0.03, and P = 0.02, respectively). The histological classification of LN, however, was not associated with the level of IL-18 among the pSLE patients (P = 0.64). The role of serum IL-18 as biomarker representing global disease activity and status of renal flares among pSLE population was shown for the first time. Additionally, we have identified IL-18 at 6 months posttreatment a novel marker for long-term renal outcome prediction. PMID:27749566

  8. Renal Function Recovery after Nephrectomy or Nephron-Sparing Surgery in Children with Unilateral Renal Tumor.

    PubMed

    Cozzi, Denis A; Ceccanti, Silvia; Cozzi, Francesco

    2017-02-01

    Introduction Children with unilateral renal tumor (URT) and preoperative renal dysfunction (PRD) may benefit from nephron-sparing surgery (NSS). To test this hypothesis, we studied the outcome of baseline renal function after nephrectomy or NSS among children with URT. Materials and Methods Retrospective records review of children with URT who underwent nephrectomy (25 children) or NSS (11 children) at our institution. We analyzed the estimated glomerular filtration rate (eGFR) changes over time among patients, stratified by both preoperative renal function (with or without PRD) and surgical extent (NSS vs. nephrectomy). The primary end point was evaluation of compensatory recovery of preoperative eGFR after surgery. Only children older than 2 years at surgery were included in the study. Renal dysfunction was defined as an eGFR < 90 mL/min/1.73 m(2). Results After nephrectomy or NSS, patients with PRD presented, on average during adolescence, a significant increase in eGFR, whereas patients without PRD presented, on average during adolescence, a stable eGFR. However, after nephrectomy, 5 of 17 (29%) and 7 of 8 (87%) adolescent patients with baseline eGFR ≤ or > 100 mL/min/1.73 m(2), respectively, achieved or maintained two-kidney eGFR values (T-KEV) (p = 0.01). After NSS, four adolescent patients with PRD and seven without PRD achieved or maintained T-KEV. Conclusion The majority of children with URT and low baseline eGFR present with an impaired renal function recovery after nephrectomy and may benefit from NSS. Collaborative studies are needed to support present findings. Georg Thieme Verlag KG Stuttgart · New York.

  9. Biomarker and competing endogenous RNA potential of tumor-specific long noncoding RNA in chromophobe renal cell carcinoma

    PubMed Central

    He, Hai-Tao; Xu, Mu; Kuang, Ye; Han, Xiao-Yun; Wang, Ming-Qi; Yang, Qing

    2016-01-01

    Background Accumulating evidence suggests long noncoding RNAs (lncRNAs) play important roles in the initiation and progression of cancers. However, their functions in chromophobe renal cell carcinoma (chRCC) are not fully understood. Methods We analyzed the expression profiles of lncRNA, microRNA, and protein-coding RNA, along with the clinical information of 59 primary chRCC patients collected from The Cancer Genome Atlas database to identify lncRNA biomarkers for prognosis. We also constructed an lncRNA–microRNA–mRNA coexpression network (competitive endogenous RNAs network) by bioinformational approach. Results One hundred and forty-two lncRNAs were found to be differentially expressed between the cancer and normal tissues (fold change ≥1.5, P<0.001). Among them, 12 lncRNAs were also differentially expressed with the corresponding clinical characteristics (fold change ≥1.5, P<0.01). Besides, 7 lncRNAs (COL18A1-AS, BRE-AS1, SNHG7, TMEM51-AS1, C21orf62-AS1, LINC00336, and LINC00882) were identified to be significantly correlated with overall survival (log-rank P<0.05). A competitive endogenous RNA network in chRCC containing 16 lncRNAs, 18 miRNAs, and 168 protein-coding RNAs was constructed. Conclusion Our results identified specific lncRNAs associated with chRCC progression and prognosis, and presented competing endogenous RNA potential of lncRNAs in the tumor. PMID:27799788

  10. Residual Renal Function in Children Treated with Chronic Peritoneal Dialysis

    PubMed Central

    Roszkowska-Blaim, Maria

    2013-01-01

    Residual renal function (RRF) in patients with end-stage renal disease (ESRD) receiving renal replacement therapy is defined as the ability of native kidneys to eliminate water and uremic toxins. Preserved RRF improves survival and quality of life in adult ESRD patients treated with peritoneal dialysis. In children, RRF was shown not only to help preserve adequacy of renal replacement therapy but also to accelerate growth rate, improve nutrition and blood pressure control, reduce the risk of adverse myocardial changes, facilitate treatment of anemia and calcium-phosphorus balance abnormalities, and result in reduced serum and dialysate fluid levels of advanced glycation end-products. Factors contributing to RRF loss in children treated with peritoneal dialysis include the underlying renal disease such as hemolytic-uremic syndrome and hereditary nephropathy, small urine volume, severe proteinuria at the initiation of renal replacement therapy, and hypertension. Several approaches can be suggested to decrease the rate of RRF loss in pediatric patients treated with chronic peritoneal dialysis: potentially nephrotoxic drugs (e.g., aminoglycosides), episodes of hypotension, and uncontrolled hypertension should be avoided, urinary tract infections should be treated promptly, and loop diuretics may be used to increase salt and water excretion. PMID:24376376

  11. Occupational exposure to lead: effects on renal function

    SciTech Connect

    Hong, C.D.; Hanenson, I.B.; Lerner, S.; Hammond, P.B.; Pesce, A.J.; Pollak, V.E.

    1980-10-01

    Although nephrotoxicity is common following exposure to lead, the dose-response relationship in adults with occupational exposure is not well understood because information is lacking on early nephrotoxic effects. By the time serum urea nitrogen and creatinine levels are elevated, renal damage may be advanced and not fully reversible. Detailed investigations of renal glomerular and tubular function were performed in six adults with occupational exposure to lead. In all patients, the serum creatinine and urea nitrogen concentrations were within the normal range. GFR was decreased in all but two. Glucose reabsorptive capacity (TmG) was decreased in all, and this decrease was disproportionately greater than expected from the reduced GFR in all but one. Normal values for renal plasma flow (RFP) were observed in four of the six, and for rho-aminohippurate (PAH) secretory capacity (TmPAh) in all but one. Bicarbonate reabsorptive capacity (TmHCO3) and urinary excretion of beta2-microglobulin were normal in all. Routine clinical laboratory tests are insensitive for the detection of early renal effects of heavy metal exposure. Measurements of renal tubular reabsorptive capacity for glucose appears to be a sensitive method for the early detection of renal effect of lead.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  14. Role of the renal sympathetic nervous system in mediating renal ischaemic injury-induced reductions in renal haemodynamic and excretory functions.

    PubMed

    Salman, Ibrahim M; Ameer, Omar Z; Sattar, Munavvar A; Abdullah, Nor A; Yam, Mun F; Najim, Hafsa S; Khan, Abdul Hye; Johns, Edward J

    2010-04-01

    We investigated the role of renal sympathetic innervation in the deterioration of renal haemodynamic and excretory functions during the early post-ischaemic phase of renal ischaemia/reperfusion injury. Anaesthetised male Sprague-Dawley rats were subjected to unilateral renal ischaemia by clamping the left renal artery for 30 min followed by reperfusion. Following acute renal denervation clearance experiments were performed. In a different set of experiments, the renal nerves were electrically stimulated at increasing frequencies and responses in renal blood flow and renal vascular resistance were recorded. Denervated post-ischaemic acute renal failure (ARF) rats showed higher urine flow rate, absolute and fractional sodium excretions, urinary sodium to urinary potassium, glomerular filtration rate and basal renal blood flow but lower basal renal vascular resistance (all p < 0.05 vs innervated ARF rats). Potassium excretion was significantly lower in denervated group as per fractional (p < 0.05 vs innervated ARF rats) but not absolute potassium excretion (p > 0.05 vs innervated ARF rats). The rise in mean arterial pressure and renal vasoconstrictor response to renal nerve stimulation were blunted in denervated ischaemic ARF rats (all p < 0.05 vs innervated ARF rats). Renal histopathology in denervated ARF rats manifested a significantly lower medullary congestion, inflammation and tubular injury compared to innervated counterparts (p < 0.05 vs innervated ARF rats). The findings strongly suggest the involvement of renal sympathetic tone in the post-ischaemic events of ischaemic ARF, as the removal of its action to a degree ameliorated the post-ischaemic renal dysfunctions.

  15. Diabetes mellitus with normal renal function is associated with anaemia.

    PubMed

    Grossman, Chagai; Dovrish, Zamir; Koren-Morag, Nira; Bornstein, Gil; Leibowitz, Avshalom

    2014-05-01

    Anaemia is a common complication of diabetes mellitus (DM), usually related to renal failure. There is scarce information as to the levels of haemoglobin (Hb) and the rate of anaemia in diabetic patients with normal renal function. We, therefore, evaluated haemoglobin levels and the rate of anaemia in diabetic subjects with normal renal functions [estimated glomerular filtration rate (eGFR) > 60 mL/min]. The charts of 9250 subjects who attended the Institute of Periodic Medical Examinations at the Chaim Sheba Medical Center for a routine yearly check-up were reviewed. Four hundred and forty-five subjects with type 2 DM and normal renal function were indentified and compared with those without DM who were routinely examined at the same time. Subjects' electronic records were used to build a biochemical and clinical database. Mean haemoglobin levels were lower in subjects with DM than in those without (14.2 vs. 14.7 g/dL, respectively; p < 0.001). Anaemia was observed in 48 (10.8%) subjects in the diabetic group and in only 12 (2.7%) in the nondiabetic group (p < 0.001). Multivariate analysis revealed that age, gender, history of gastrointestinal disease, use of beta blockers, renal function and DM were independent determinants of haemoglobin levels. After adjustment for age, gender, history of gastrointestinal tract diseases and renal function, DM remained a significant determinant of anaemia with an odds ratio of 2.15 (confidence interval: 1.07-4.31). Anaemia is more common in diabetic patients even when eGFR > 60 mL/min. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Vesicoureteral Reflux Detected with 99mTc-DTPA Renal Scintigraphy during Evaluation of Renal Function

    PubMed Central

    Manevska, Nevena; Stojanoski, Sinisa; Majstorov, Venjamin; Pop-Gjorcheva, Daniela; Zdraveska, Nikolina; Kuzmanovska, Dafina

    2016-01-01

    BACKGROUND: Radionuclide techniques, as direct radionuclide cystography and 99mTc-DMSA scintigraphy, have been used in evaluation of vesicoureteral reflux (VUR) and reflux nephropathy (RN) in children. Dynamic 99mTc-DTPA scintigraphy is reserved for evaluation of differential renal function and obstruction in children, where hydronephrosis is detected by ultrasonography (US) pre- or postnatally. CASE REPORT: Six year old boy was prenatally diagnosed with bilateral hydronephrosis. Postnatal, severe bilateral VUR was detected by voiding urethrocytography. US and 99mTc-DTPA scintigraphy performed in the first month of life showed small left kidney that participated with 2% in the global renal function. Bilateral cutaneous ureterostomy has been performed in order to obtain good renal drainage and promote optimal renal growth. Twelve months later, classic antireflux procedure was done. Control 99mTc-DTPA scintigraphy, 5 ys after antireflux surgery, revealed persisting radioactivity during the diuretic phase, in the left kidney that indicated antireflux procedure failure with VUR reappearance. CONCLUSION: 99mTc-DTPA scintigraphy is the first method of choice for long-term monitoring of individual kidney function in children with VUR and other congenital urinary tract anomalies. Additionally, it can be used as indirect radionuclide cystography when rising of radioactivity in the kidney region, during the diuretic phase can indicate presence of VUR. PMID:27275347

  17. Restoration of renal function by a novel prostaglandin EP4 receptor-derived peptide in models of acute renal failure.

    PubMed

    Leduc, Martin; Hou, Xin; Hamel, David; Sanchez, Melanie; Quiniou, Christiane; Honoré, Jean-Claude; Roy, Olivier; Madaan, Ankush; Lubell, William; Varma, Daya R; Mancini, Joseph; Duhamel, François; Peri, Krishna G; Pichette, Vincent; Heveker, Nikolaus; Chemtob, Sylvain

    2013-01-01

    Acute renal failure (ARF) is a serious medical complication characterized by an abrupt and sustained decline in renal function. Despite significant advances in supportive care, there is currently no effective treatment to restore renal function. PGE(2) is a lipid hormone mediator abundantly produced in the kidney, where it acts locally to regulate renal function; several studies suggest that modulating EP(4) receptor activity could improve renal function following kidney injury. An optimized peptidomimetic ligand of EP(4) receptor, THG213.29, was tested for its efficacy to improve renal function (glomerular filtration rate, renal plasma flow, and urine output) and histological changes in a model of ARF induced by either cisplatin or renal artery occlusion in Sprague-Dawley rats. THG213.29 modulated PGE(2)-binding dissociation kinetics, indicative of an allosteric binding mode. Consistently, THG213.29 antagonized EP(4)-mediated relaxation of piglet saphenous vein rings, partially inhibited EP(4)-mediated cAMP production, but did not affect Gα(i) activation or β-arrestin recruitment. In vivo, THG213.29 significantly improved renal function and histological changes in cisplatin- and renal artery occlusion-induced ARF models. THG213.29 increased mRNA expression of heme-oxygenase 1, Bcl2, and FGF-2 in renal cortex; correspondingly, in EP(4)-transfected HEK293 cells, THG213.29 augmented FGF-2 and abrogated EP(4)-dependent overexpression of inflammatory IL-6 and of apoptotic death domain-associated protein and BCL2-associated agonist of cell death. Our results demonstrate that THG213.29 represents a novel class of diuretic agent with noncompetitive allosteric modulator effects on EP(4) receptor, resulting in improved renal function and integrity following acute renal failure.

  18. The correct renal function evaluation in patients with thyroid dysfunction.

    PubMed

    Simeoni, Mariadelina; Cerantonio, Annamaria; Pastore, Ida; Liguori, Rossella; Greco, Marta; Foti, Daniela; Gulletta, Elio; Brunetti, Antonio; Fuiano, Giorgio

    2016-05-01

    Thyroid dysfunction induces several renal derangements involving all nephron portions. Furthermore, dysthyroidism is a recognized risk factor associated with the development of chronic kidney disease. Current data, in fact, demonstrate that either subclinical or overt thyroid disease is associated with significant changes in creatinine, estimated glomerular filtration rate, measured glomerular filtration rate and Cystatin C. Herein, we systematically reviewed several relevant studies aiming at the identification of the most sensitive and specific parameter for the correct renal function evaluation in patients with thyroid dysfunction, that are usually treated as outpatients. Our systematic review indicates that estimated glomerular filtration rate, preferably with CKD-EPI equation, appears to be the most reliable and wieldy renal function parameter. Instead, Cystatin C should be better used in the grading of thyroid dysfunction severity.

  19. Imaging regional renal function parameters using radionuclide tracers

    NASA Astrophysics Data System (ADS)

    Qiao, Yi

    A compartmental model is given for evaluating kidney function accurately and noninvasively. This model is cast into a parallel multi-compartment structure and each pixel region (picture element) of kidneys is considered as a single kidney compartment. The loss of radionuclide tracers from the blood to the kidney and from the kidney to the bladder are modelled in great detail. Both the uptake function and the excretion function of the kidneys can be evaluated pixel by pixel, and regional diagnostic information on renal function is obtained. Gamma Camera image data are required by this model and a screening test based renal function measurement is provided. The regional blood background is subtracted from the kidney region of interest (ROI) and the kidney regional rate constants are estimated analytically using the Kuhn-Pucker multiplier method in convex programming by considering the input/output behavior of the kidney compartments. The detailed physiological model of the peripheral compartments of the system, which is not available for most radionuclide tracers, is not required in the determination of the kidney regional rate constants and the regional blood background factors within the kidney ROI. Moreover, the statistical significance of measurements is considered to assure the improved statistical properties of the estimated kidney rate constants. The relations between various renal function parameters and the kidney rate constants are established. Multiple renal function measurements can be found from the renal compartmental model. The blood radioactivity curve and the regional (or total) radiorenogram determining the regional (or total) summed behavior of the kidneys are obtained analytically with the consideration of the statistical significance of measurements using convex programming methods for a single peripheral compartment system. In addition, a new technique for the determination of 'initial conditions' in both the blood compartment and the kidney

  20. Trace cancer biomarker quantification using polystyrene-functionalized gold nanorods

    PubMed Central

    Wu, Jian; Li, Wei; Hajisalem, Ghazal; Lukach, Ariella; Kumacheva, Eugenia; Hof, Fraser; Gordon, Reuven

    2014-01-01

    We demonstrate the application of polystyrene-functionalized gold nanorods (AuNRs) as a platform for surface enhanced Raman scattering (SERS) quantification of the exogenous cancer biomarker Acetyl Amantadine (AcAm). We utilize the hydrophobicity of the polystyrene attached to the AuNR surface to capture the hydrophobic AcAm from solution, followed by drying and detection using SERS. We achieve a detection limit of 16 ng/mL using this platform. This result shows clinical potential for low-cost early cancer detection. PMID:25574423

  1. Karyopherins: potential biological elements involved in the delayed graft function in renal transplant recipients

    PubMed Central

    2014-01-01

    Background Immediately after renal transplantation, patients experience rapid and significant improvement of their clinical conditions and undergo considerable systemic and cellular modifications. However, some patients present a slow recovery of the renal function commonly defined as delayed graft function (DGF). Although clinically well characterized, the molecular mechanisms underlying this condition are not totally defined, thus, we are currently missing specific clinical markers to predict and to make early diagnosis of this event. Methods We investigated, using a pathway analysis approach, the transcriptomic profile of peripheral blood mononuclear cells (PBMC) from renal transplant recipients with DGF and with early graft function (EGF), before (T0) and 24 hours (T24) after transplantation. Results Bioinformatics/statistical analysis showed that 15 pathways (8 up-regulated and 7 down-regulated) and 11 pathways (5 up-regulated and 6 down-regulated) were able to identify DGF patients at T0 and T24, respectively. Interestingly, the most up-regulated pathway at both time points was NLS-bearing substrate import into nucleus, which includes genes encoding for several subtypes of karyopherins, a group of proteins involved in nucleocytoplasmic transport. Signal transducers and activators of transcription (STAT) utilize karyopherins-alpha (KPNA) for their passage from cytoplasm into the nucleus. In vitro functional analysis demonstrated that in PBMCs of DGF patients, there was a significant KPNA-mediated nuclear translocation of the phosphorylated form of STAT3 (pSTAT3) after short-time stimulation (2 and 5 minutes) with interleukin-6. Conclusions Our study suggests the involvement, immediately before transplantation, of karyopherin-mediated nuclear transport in the onset and development of DGF. Additionally, it reveals that karyopherins could be good candidates as potential DGF predictive clinical biomarkers and targets for pharmacological interventions in renal

  2. Comparison of renal function after donor and radical nephrectomy.

    PubMed

    Gazel, Eymen; Biçer, Sait; Ölçücüoğlu, Erkan; Yığman, Metin; Taştemur, Sedat; Çamtosun, Ahmet; Ceylan, Cavit; Ateş, Can

    2015-04-01

    Glomerular filtration rate (GFR) is directly proportionate to nephron reserves. In this respect, it is known that the patients who underwent radical nephrectomy due to renal tumor are under high risk of chronic kidney disease (CKD) in the long term. In this study, it was aimed to compare post-operative renal functions of patients who underwent radical nephrectomy due to renal malignancy and who underwent donor nephrectomy as renal donors, to observe whether renal failure process develops or not, and to determine the factors that affect post-operative renal functions. 70 patients who underwent donor nephrectomy as renal donors and 130 patients who underwent radical nephrectomy due to renal tumor were studied. When we divided the groups as those with a GFR of below 60 mL/min/1.73 m(2) and those with a GFR of above 60 mL/min/1.73 m(2), we observed that GFR values of patients who underwent radical nephrectomy had a significantly stronger tendency to stay below 60 mL/min/1.73 m(2) compared to patients who underwent donor nephrectomy (p < 0.001). When we divided the groups as those with a GFR of below 30 mL/min/1.73 m(2) and those with a GFR of above 30 mL/min/1.73 m(2), we observed that there were no patients in donor nephrectomy group whose GFR values dropped below 30 mL/min/1.73 m(2) and there was not a statistically significant difference between the groups (p = 0.099). If possible, nephron sparing methods should be preferred for patients to undergo nephrectomy because of the tumor without ignoring oncologic results and it should be remembered that patient's age and pre-operative renal functions may affect post-operative results in donor selection.

  3. Comparative Analysis of Novel Noninvasive Renal Biomarkers and Metabonomic Changes in a Rat Model of Gentamicin Nephrotoxicity

    PubMed Central

    Sieber, Max; Hoffmann, Dana; Adler, Melanie; Vaidya, Vishal S.; Clement, Matthew; Bonventre, Joseph V.; Zidek, Nadine; Rached, Eva; Amberg, Alexander; Callanan, John J.; Dekant, Wolfgang; Mally, Angela

    2009-01-01

    Although early detection of toxicant induced kidney injury during drug development and chemical safety testing is still limited by the lack of sensitive and reliable biomarkers of nephrotoxicity, omics technologies have brought enormous opportunities for improved detection of toxicity and biomarker discovery. Thus, transcription profiling has led to the identification of several candidate kidney biomarkers such as kidney injury molecule (Kim-1), clusterin, lipocalin-2, and tissue inhibitor of metalloproteinase 1 (Timp-1), and metabonomic analysis of urine is increasingly used to indicate biochemical perturbations due to renal toxicity. This study was designed to assess the value of a combined 1H-NMR and gas chromatography–mass spectrometry (GC-MS) metabonomics approach and a set of novel urinary protein markers for early detection of nephrotoxicity following treatment of male Wistar rats with gentamicin (60 and 120 mg/kg bw, sc) for 7 days. Time- and dose-dependent separation of gentamicin-treated animals from controls was observed by principal component analysis of 1H-NMR and GC-MS data. The major metabolic alterations responsible for group separation were linked to the gut microflora, thus related to the pharmacology of the drug, and increased glucose in urine of gentamicin-treated animals, consistent with damage to the S1 and S2 proximal tubules, the primary sites for glucose reabsorption. Altered excretion of urinary protein biomarkers Kim-1 and lipocalin-2, but not Timp-1 and clusterin, was detected before marked changes in clinical chemistry parameters were evident. The early increase in urine, which correlated with enhanced gene and protein expression at the site of injury, provides further support for lipocalin-2 and Kim-1 as sensitive, noninvasive biomarkers of nephrotoxicity. PMID:19349640

  4. Bone disease in patients with long-term renal transplantation and normal renal function.

    PubMed

    Carlini, R G; Rojas, E; Weisinger, J R; Lopez, M; Martinis, R; Arminio, A; Bellorin-Font, E

    2000-07-01

    Renal osteodystrophy may persist during the early years after renal transplantation. However, information on bone status after a successful long-term renal transplantation is limited. We examined biochemical parameters, bone mineral density (BMD), and bone histomorphometry in 25 asymptomatic men with normal renal function after 7.5 +/- 5.7 years of a renal transplantation. Serum calcium, phosphorus, alkaline phosphatase, and 1,25(OH)(2)D(3) levels and urinary calcium level and cyclic andenosine monophosphate excretion were within normal range in all patients. Serum intact parathyroid hormone (PTH) level was elevated in 11 subjects (133.6 +/- 78 pg/mL) and normal in the other 14 subjects (47.9 +/- 13.6 pg/mL). Mean BMD at the lumbar spine and femoral neck was low in the entire group. However, it progressively increased as time after transplantation increased, approaching normal values after 10 years. Bone histomorphometric analysis showed bone resorption, osteoid volume, and osteoid surface greater than normal range in the majority of patients. Bone formation rate and mineralization surface were low, and mineralization time was delayed in most patients. These lesions were more severe in patients after 3 to 4 years of transplantation but improved with time and approached normal values after a period of 10 years. PTH values did not correlate with bone histological characteristics or BMD. These results show that the bone alterations observed after long-term renal transplantation consist of a mixed bone disease in which features of high bone turnover coexist with altered bone formation and delayed mineralization. These findings may result from the combined effect of preexisting bone disease and immunosuppressive therapy.

  5. Strategies for preserving residual renal function in peritoneal dialysis patients

    PubMed Central

    Nongnuch, Arkom; Assanatham, Montira; Panorchan, Kwanpeemai; Davenport, Andrew

    2015-01-01

    Although there have been many advancements in the treatment of patients with chronic kidney disease (CKD) over the last 50 years, in terms of reducing cardiovascular risk, mortality remains unacceptably high, particularly for those patients who progress to stage 5 CKD and initiate dialysis (CKD5d). As mortality risk increases exponentially with progressive CKD stage, the question arises as to whether preservation of residual renal function once dialysis has been initiated can reduce mortality risk. Observational studies to date have reported an association between even small amounts of residual renal function and improved patient survival and quality of life. Dialysis therapies predominantly provide clearance for small water-soluble solutes, volume and acid-base control, but cannot reproduce the metabolic functions of the kidney. As such, protein-bound solutes, advanced glycosylation end-products, middle molecules and other azotaemic toxins accumulate over time in the anuric CKD5d patient. Apart from avoiding potential nephrotoxic insults, observational and interventional trials have suggested that a number of interventions and treatments may potentially reduce the progression of earlier stages of CKD, including targeted blood pressure control, reducing proteinuria and dietary intervention using combinations of protein restriction with keto acid supplementation. However, many interventions which have been proven to be effective in the general population have not been equally effective in the CKD5d patient, and so the question arises as to whether these treatment options are equally applicable to CKD5d patients. As strategies to help preserve residual renal function in CKD5d patients are not well established, we have reviewed the evidence for preserving or losing residual renal function in peritoneal dialysis patients, as urine collections are routinely collected, whereas few centres regularly collect urine from haemodialysis patients, and haemodialysis dialysis

  6. Effects of chronic and acute protein administration on renal function in patients with chronic renal insufficiency.

    PubMed

    Bilo, H J; Schaap, G H; Blaak, E; Gans, R O; Oe, P L; Donker, A J

    1989-01-01

    In 6 volunteers with normal renal function, we investigated the effects of various kinds of protein (soy, lactoprotein and beef) and various amounts of an intravenously administered amino acid solution on glomerular filtration (GFR) and effective renal plasma flow (ERPF). As for the protein-induced changes in renal function, rises in GFR and ERPF were lowest with soy protein, and highest with beef (baseline GFR, 110 +/- 5; soy, 122 +/- 5; beef, 131 +/- 5 ml/min/1.73 m2; mean +/- SEM). High doses of intravenous amino acids induced a rise in GFR comparable to that after beef (132 +/- 5 ml/min/1.73 m2). In a combined test a liquid mixed meal together with intravenously administered amino acids induced a comparable increase of the GFR (baseline 114 +/- 5 versus 129 +/- 5 ml/min/1.73 m2). When investigating 9 patients with chronic renal insufficiency after 4 weeks of low protein intake (LP) and after 4 weeks of high protein intake (HP), GFR and ERPF rose significantly under baseline conditions (GFR-LP41 +/- 9 versus GFR-HP 45 +/- 9 ml/min/1.73 m2, p less than 0.02; ERPF-LP 169 +/- 39 versus ERPF-HP 180 +/- 40 ml/min/1.73 m2, p less than 0.02; paired Wilcoxon). At the end of both dietary periods a comparable rise in renal function could be induced through acute stimulation (GFR-LP 20 +/- 5, GFR-HP 16 +/- 4; ERPF-LP 23 +/- 7, ERPF-HP 22 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Renal function damage in 131 cases of urogenital tuberculosis.

    PubMed

    Wisnia, L G; Kukolj, S; Lopez de Santa Maria, J; Camuzzi, F

    1978-05-01

    The functional sequelae of 131 patients with urogenital tuberculosis were examined. At the time of diagnosis, more than half of the patients already suffered from global renal failure which was moderate in 42.7 per cent and severe in 15.5 per cent. We believe that the primary functional damage occurs at the medullary level with tubular and interstitial involvement. Indeed, the red phenol test for postglomerular blood flow was altered in a higher proportion than was the creatinine clearance (67.9 per cent). The maximum concentrating ability was altered even more frequently (84 per cent). When we compared various glomerular filtration levels with the grade of alteration of the maximum ability concentration test, we also saw clearly that the alteration of the tubular interstitial medullar function dominated the alteration of the glomerular global function. This proves at a functional level the predominantly medullary localization of the lesion in renal tuberculosis.

  8. Renal tumour anatomical characteristics and functional outcome after partial nephrectomy.

    PubMed

    Nisen, Harry; Heimonen, Petri; Kenttä, Lauri; Visapää, Harri; Nisen, Jessica; Taari, Kimmo

    2015-06-01

    Anatomical features of renal tumours may be useful in predicting glomerular filtration rate (GFR) after partial nephrectomy. In this study, anatomical classification systems (ACSs) were compared to predict changes in renal function after surgery. A group of 294 patients with T1 renal tumours receiving partial nephrectomy between January 2006 and June 2013 were identified from the institutional kidney tumour database. Preoperative images from computed tomography or magnetic resonance imaging were reviewed to assess diameter, PADUA (preoperative aspects and dimensions used for an anatomical) classification score, RENAL (radius, exophytic/endophytic properties of the tumour, nearness of tumour deepest portion to the collecting system or sinus, anterior/posterior descriptor and location relative to polar lines) nephrometry score, centrality index (C index) and renal tumour invasion index (RTII). GFR was estimated using the Modification of Diet in Renal Disease equation preoperatively and 3 months after operation. Linear and logistic regression were applied as statistical methods. Mean tumour diameter was 3.0 ± 2.2 cm (range 1.0-7.0 cm). GFR was 85 ± 22 ml/min/1.73 m² before the operation and 77 ± 21 ml/min/1.73 m² (-8% change) 3 months after the operation. In univariate linear regression, the percentage change in GFR was weakly but statistically significantly associated with surgical approach (p = 0.04), indication for nephron sparing (p = 0.02), preoperative GFR (p < 0.001), PADUA (p = 0.02), RENAL (p = 0.01) and RTII (p = 0.003). In multivariate logistic regression analysis among patients with tumours 3 cm or larger, PADUA (odds ratio 1.55, p = 0.021) and RTII (odds ratio 3.87, p = 0.037) predicted at least a 20% reduction in GFR. Renal tumour ACSs may be clinically useful in predicting changes in renal function after partial nephrectomy in patients with larger tumours. The performance of RTII is equal to that of other ACSs in predicting changes in GFR.

  9. Treatment of severe hypothyroidism in a patient with progressive renal failure leads to significant improvement of renal function.

    PubMed

    van Welsem, M E; Lobatto, S

    2007-06-01

    The case of a 41-year-old patient with end-stage renal failure and diabetes mellitus Type 1 who was being prepared for renal replacement therapy is described. After severe hypothyroidism was diagnosed, thyroid hormone substitution therapy was started. Subsequently, a substantial decline in serum creatinine was observed. Creatinine clearance rose from 19 to 40 ml/min and renal replacement therapy was no longer imminent. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown amelioration of end-stage renal failure as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. Diagnosing signs of hypothyroidism and therapy with thyroid hormone in progressive renal failure could be very important in delaying the need for renal replacement therapy.

  10. The Effects of Heart Failure on Renal Function

    PubMed Central

    Udani, Suneel M; Koyner, Jay L

    2010-01-01

    Summary Heart-kidney interactions have been increasingly recognized by clinicians and researchers involved in the study and treatment of heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Recent work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of the concomitant cardiac and renal dysfunction remains unclear; however, increasing evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. PMID:20621250

  11. Expression and Function of Interleukin-1β-Induced Neutrophil Gelatinase-Associated Lipocalin in Renal Tubular Cells

    PubMed Central

    Mamiya, Ryo; Tsuchiya, Hisashi; Kitanaka, Taku; Namba, Shinichi; Kitanaka, Nanako; Okabayashi, Ken; Narita, Takanori; Sugiya, Hiroshi

    2016-01-01

    Acute kidney injury (AKI) is characterized by a sudden loss of renal function. Early recognition of AKI, especially in critically ill patients, is essential for adequate therapy. Currently, neutrophil gelatinase-associated lipocalin (NGAL) is considered to be an effective biomarker of AKI; however, the regulation of its expression and function in renal tubular cells remains unclear. In this study, we investigated the regulation of the expression and function of NGAL in IL-1β-treated Madin–Darby canine kidney (MDCK) cells as a model of renal tubular cells. IL-1β induced a disturbance in the localization of E-cadherin and zonaoccludin-1 (ZO-1). The transepithelial electrical resistance (TER) also decreased 5 days after IL-1β treatment. IL-1β induced NGAL mRNA expression and protein secretion in a time- and dose-dependent manner, which occurred faster than the decrease in TER. In the presence of ERK1/2 and p38 inhibitors, IL-1β-induced NGAL mRNA expression and protein secretion were significantly attenuated. In the presence of recombinant NGAL, IL-1β-induced disturbance in the localization of E-cadherin and ZO-1 was attenuated, and the decrease in TER was partially maintained. These results suggest that NGAL can be used as a biomarker for AKI and that it functions as a protector from AKI. PMID:27851800

  12. Anxiety, Family Functioning and Neuroendocrine Biomarkers in Obese Children.

    PubMed

    Pinto, Inês; Wilkinson, Simon; Virella, Daniel; Alves, Marta; Calhau, Conceição; Coelho, Rui

    2017-04-28

    This observational study explores potential links between obese children's cortisol, and parental mental state, family functioning, and the children's symptoms of anxiety and depression. A non-random sample of 104 obese children (55 boys), mean age 10.9 years (standard deviation 1.76), was recruited from a childhood obesity clinic. Obesity was defined as body mass index above the 95th age- and gender-specific percentiles. Neuroendocrine biomarkers were measured. Symptoms of anxiety and depression were assessed with self and parent-reported questionnaires (Anxiety, Depression and Stress Scales; Child Behaviour Checklist). Family functioning was assessed with parent-reported questionnaires (Family Adaptation and Cohesion Scales-III). A significant, negative correlation (rs = -0.779; p = 0.003) between girls' cortisol and their parents' anxiety symptoms was found, limited to high functioning families. Boys scored significantly higher than girls on parent-reported internalizing symptoms but not on self-report. No association was found between cortisol in children and parental depressive symptoms. Whether the association between cortisol levels in obese children and parental mental health is effectively restricted to girls from high functioning families or is due to study limitations, requires further research. The lack of associations between cortisol in children and parental depressive symptoms, suggests a specific association between cortisol and parental anxiety symptoms. These results highlight the importance of taking into account family functioning, parental mental state and gender, when investigating neuroendocrine biomarkers in obese children associated with symptoms of anxiety and depression.

  13. Biomarker and Drug Target Discovery Using Proteomics in a New Rat Model of Sepsis-Induced Acute Renal Failure

    PubMed Central

    Holly, Mikaela K.; Dear, James W.; Hu, Xuzhen; Schechter, Alan N.; Gladwin, Mark T.; Hewitt, Stephen M.; Yuen, Peter S.T.; Star, Robert A.

    2008-01-01

    Background Sepsis is one of the common causes of acute renal failure (ARF). The objective of this study was to identify new biomarkers and therapeutic targets. We present a new rat model of sepsis-induced ARF based on cecal ligation and puncture (CLP). We used this model to find urinary proteins which may be potential biomarkers and/or drug targets. Methods Aged rats were treated with fluids and antibiotics after CLP. Urinary proteins from septic rats without ARF and urinary proteins from septic rats with ARF were compared by difference in-gel electrophoresis (DIGE). Results CLP surgery elevated IL-6 and IL-10 serum cytokines and blood nitrite compared with sham-operated rats. However there was a range of serum creatinine values at 24 hrs (0.4–2.3 mg/dL) and only 24% developed ARF. Histology confirmed renal injury in these rats. 49% of rats did not develop ARF. Rats without ARF also had less liver injury. The mortality rate at 24 hrs was 27% but was increased by housing the post-surgery rats in metabolic cages. Creatinine clearance and urine output 2–8 hours after CLP was significantly reduced in rats which died within 24 hours. Using DIGE we identified changes in a number of urinary proteins including albumin, brush-border enzymes (eg., meprin-1-alpha) and serine protease inhibitors. The meprin-1-alpha inhibitor actinonin prevented ARF in aged mice. Conclusion In summary we describe a new rat model of sepsis-induced ARF which has a heterogeneous response similar to humans. This model allowed us to use DIGE to find changes in urinary proteins and this approach identified a potential biomarker and drug target – meprin-1-alpha. PMID:16760904

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

    PubMed

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

    2011-01-01

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

  15. Time-dependent effects of prognostic biomarkers of systemic inflammation in patients with metastatic renal cell carcinoma.

    PubMed

    Harris, Wayne B; Zhang, Chao; Liu, Yuan; Robertson, Dale K; Akbashev, Mikhail Y; Lingerfelt, Brian M; Kucuk, Omer; Carthon, Bradley C; Gillespie, Theresa W; Osunkoya, Adeboye O; Master, Viraj A

    2017-06-01

    The goal of this study was to examine time-dependent effects of prognostic biomarkers of systemic inflammation in patients with metastatic renal cell carcinoma. Retrospective chart reviews were conducted at the Winship Cancer Institute of Emory University and the Atlanta Veterans Administration Medical Center with authorization from the Emory University Institutional Review Board and the Veterans Administration Research and Development Committee. Inclusion criteria included age ⩾18 years, treatment with targeted therapy for clear cell or non-clear cell metastatic renal cell carcinoma and concomitant assessment of C-reactive protein and albumin levels on ⩾3 occasions that were ⩾10 days apart. Discovery, expansion, and external validation cohorts were identified. Established prognostic variables were evaluated by univariate and multivariate analyses. Intensity of systemic inflammation was assessed at all time points with C-reactive protein and albumin as prognostic covariates for overall survival in an extended Cox regression model. Intensity of systemic inflammation was assessed on 3186 occasions in 181 patients. Risk status changed in 131 patients (72%). The hazard ratio for overall survival was 21.41 (95% confidence interval = 8.26-55.50) with a type 3 p value of <0.001 for the reference cohort and 9.68 (2.07-45.31) with a type-3 p value of 0.006 for the external validation cohort when time points associated with severe systemic inflammation were compared to all other time points. The bias-corrected c-statistic was 0.839 (0.773-0.905) and 0.818 (0.691-0.946), respectively. Terminal disease progression with severe systemic inflammation was detected in 87% of the 90 patients who died. In conclusion, time-dependent effects are a prominent feature of intensity of systemic inflammation, a powerful prognostic biomarker for metastatic renal cell carcinoma.

  16. iTRAQ-Based Quantitative Proteomic Analysis Identified HSC71 as a Novel Serum Biomarker for Renal Cell Carcinoma

    PubMed Central

    Zhang, Yushi; Cai, Yi; Yu, Hongyan; Li, Hanzhong

    2015-01-01

    Renal cell carcinoma (RCC) is one of the most lethal urologic cancers and about 80% of RCC are of the clear-cell type (ccRCC). However, there are no serum biomarkers for the accurate diagnosis of RCC. In this study, we performed a quantitative proteomic analysis on serum samples from ccRCC patients and control group by using isobaric tag for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to access differentially expressed proteins. Overall, 16 proteins were significantly upregulated (ratio > 1.5) and 14 proteins were significantly downregulated (ratio < 0.67) in early-stage ccRCC compared to control group. HSC71 was selected and subsequently validated by Western blot in six independent sets of patients. ELISA subsequently confirmed HSC71 as a potential serum biomarker for distinguishing RCC from benign urologic disease with an operating characteristic curve (ROC) area under the curve (AUC) of 0.86 (95% confidence interval (CI), 0.76~0.96), achieving sensitivity of 87% (95% CI 69%~96%) at a specificity of 80% (95% CI 61~92%) with a threshold of 15 ng/mL. iTRAQ-based quantitative proteomic analysis led to identification of serum HSC71 as a novel serum biomarker of RCC, particularly useful in early diagnosis of ccRCC. PMID:26425554

  17. Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment.

    PubMed

    Saag, Kenneth G; Whelton, Andrew; Becker, Michael A; MacDonald, Patricia; Hunt, Barbara; Gunawardhana, Lhanoo

    2016-08-01

    Renal impairment is a risk factor for gout and a barrier to optimal gout management. We undertook this exploratory study to obtain data that have been heretofore limited regarding the safety and efficacy of febuxostat in patients with moderate-to-severe renal impairment (estimated glomerular filtration rate [GFR] 15-50 ml/minute/1.73 m(2) ). Ninety-six gout patients with moderate-to-severe renal impairment were enrolled in a 12-month multicenter, randomized, double-blind, placebo-controlled study. Patients were randomly assigned at a 1:1:1 ratio to receive 30 mg febuxostat twice daily, 40/80 mg febuxostat once daily, or placebo. The primary efficacy end point was the change in serum creatinine (Cr) level from baseline to month 12. Secondary end points included the change in estimated GFR from baseline to month 12 and the proportion of patients with a serum uric acid (UA) level of <6.0 mg/dl at month 12. At month 12, there were no significant differences in the change in serum Cr level from baseline, or in the change in estimated GFR from baseline, in either febuxostat group compared to the placebo group. The proportion of patients with a serum UA level of <6.0 mg/dl at month 12 was significantly greater in both febuxostat groups compared to the placebo group (both P < 0.001). At least 1 treatment-emergent adverse event (TEAE) occurred in 78.1% of patients receiving 30 mg febuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat once daily, and 78.1% of patients receiving placebo. TEAEs most frequently involved the categories of renal failure and impairment and renal function analyses. Febuxostat proved to be efficacious in serum UA reduction and was well tolerated in gout patients with moderate-to-severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function. © 2016, American College of Rheumatology.

  18. Effect of 2'-phosphophloretin on renal function in chronic renal failure rats.

    PubMed

    Peerce, B E; Weaver, L; Clarke, R D

    2004-07-01

    Hyperhosphatemia and secondary hyperparathyroidism are common and severe complications of chronic renal failure. Therapies to reduce serum phosphate have been shown to reduce serum parathyroid hormone (PTH) and slow the progression of renal failure. The effect of the inhibitor of intestinal phosphate absorption, 2'-phosphophloretin (2'-PP), on serum and urine chemistry, renal histology, and cardiac structure in the uremic rat model of renal failure, 5/6 nephrectomy (5/6 NX), was examined. The effect of 2'-PP on serum phosphate, serum PTH, serum total Ca(2+), and ionized Ca(2+), Ca(2+) x P(i) product, urine protein, urine osmolality, and creatinine clearance in 5/6 NX rats was examined. Uremic rats in chronic renal failure were gavaged daily with 25 microM 2'-PP. Over the course of a 5-wk experiment, serum chemistry in untreated uremic rats, 2'-PP-treated uremic rats, and age-matched control rats with normal renal function was determined twice a week. Urine creatinine, urine osmolality, urine phosphate, and urine protein were determined once a week from 24-h collections. 2'-PP reduced serum phosphate 40 +/- 3% compared with a 17% increase in untreated uremic control rats. 2'-PP did not alter total serum Ca(2+). During 5-wk experiments, serum PTH increased 65 +/- 25% in untreated uremic rats and decreased 70 +/- 7% in uremic rats treated with 25 microM 2'-PP. Creatinine clearance decreased 20% in untreated uremic rats compared with a 100% increase in 2'-PP-treated uremic rats. Urine protein decreased and urine osmolality increased in uremic rats treated with 2'-PP. The mechanism of the effect of 2'-PP on serum phosphate was inhibition of intestinal phosphate absorption. 2-PP inhibited intestinal phosphate absorption 50% without altering dietary protein absorption or intestinal Ca(2+) absorption. Over the course of the 5-wk treatment with 2'-PP, uremic animals treated with 2'-PP had a 2-4% weight gain/wk, similar to the weight gain seen in age-matched control rats

  19. Live Donor Renal Anatomic Asymmetry and Post-Transplant Renal Function

    PubMed Central

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

    2014-01-01

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

  20. Estimation of renal function in lung cancer patients.

    PubMed

    Trobec, Katja; Knez, Lea; Meško Brguljan, Pika; Cufer, Tanja; Lainščak, Mitja

    2012-06-01

    In lung cancer patients treated with chemotherapy, renal function is an important parameter to be monitored. Since measurement of renal function with either isotope or creatinine clearance is time consuming and expensive, we evaluated which of the following equations: Cockcroft-Gault (CG), Wright, modification of diet in renal disease equation (MDRD), MDRD adjusted for body surface area (BSA) and chronic kidney disease epidemiology collaboration (CKD-EPI) best resembles endogenous creatinine clearance (ECC) and could therefore replace its measurement in clinical practice. 218 lung cancer patients, who had their 24-h creatinine secretion in urine measured prior to the start of any chemotherapy, were included. Estimation of renal function was calculated and compared to ECC. There were no major differences in the performance of the tested equations. Mean percentage error of more than 20% and general underestimation was common to all equations. Wright equation performed best although it describes only 43% of ECC variability. Mean measured ECC was 94 mL/min (95% confidence interval [CI]: 90-98 mL/min) and 90 mL/min for Wright equation (95% CI: 87-93 mL/min) (Supp. Fig. 3). MDRD and CKD-EPI equation performed poorest since they do not include any body size descriptor. Large deviations of differences were observed, with a median standard deviation of more than 20% and deviations from ECC exceeding 100%. Wright equation performed best, whereas, despite their leading role in the detection of renal diseases, the MDRD and CKD-EPI equation performed poorest since they do not include any body size descriptor. In the range of ECC<50 mL/(min×1.73 m(2)), the CG equation most often detected a contraindication for cisplatin use. Differences between ECC and calculated values correlated with patients' weight, BSA and body mass index when these were not included in the equation itself. In evaluating the renal function of lung cancer patients, equations adjusted for body size

  1. Hypothyroidism and renal function in patients with systolic heart failure.

    PubMed

    Merla, Ramanna; Martinez, Juan D; Martinez, Milagros A; Khalife, Wissam; Bionat, Susan; Bionat, Joanne; Barbagelata, Alejandro

    2010-01-01

    The extent to which hypothyroidism affects renal function in patients with heart failure remains incompletely explored, despite the known adverse prognostic implications of renal dysfunction in these patients.In a pilot retrospective study, we evaluated 75 patients (age, >or=18 yr) with left ventricular ejection fractions <0.40. Forty-five patients had normal thyroid function (thyroid-stimulating hormone [TSH], 0.35-5.5 micro IU/mL) and 30 had hypothyroidism. The group with hypothyroidism was subdivided into 17 patients who had controlled hypothyroidism (TSH, 0.35-5.5 micro IU/mL) and 13 who had uncontrolled hypothyroidism (TSH, >5.5 micro IU/mL). Renal function, measured in terms of glomerular filtration rate, was analyzed once in each patient, and the populations were statistically compared, with P <0.05 conferring statistical significance.Baseline characteristics in all groups were similar. Mean glomerular filtration rate was better in patients with normal thyroid function than those with hypothyroidism (75.45 +/- 31.48 vs 63.95 +/- 21.43 mL/min/1.73 m2; P=0.032). There was no significant difference between patients with controlled hypothyroidism (66.89 +/- 24.18 mL/min/1.73 m2) and those with normal thyroid function (P=0.131). In patients with uncontrolled hypothyroidism, mean glomerular filtration rate (60.2 +/- 17.4 mL/min/1.73 m2) was significantly worse than in patients with normal thyroid function (P=0.015).We found that heart-failure patients with insufficiently treated hypothyroidism have worse renal function than do patients whose thyroid function is normal or whose hypothyroidism is effectively treated. Larger studies will be needed in order to evaluate this conclusion further. We recommend that hypothyroidism in heart-failure patients be strictly controlled, lest it affect prognosis adversely.

  2. Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney Disease.

    PubMed

    Coca, Steven G; Nadkarni, Girish N; Huang, Yuan; Moledina, Dennis G; Rao, Veena; Zhang, Jane; Ferket, Bart; Crowley, Susan T; Fried, Linda F; Parikh, Chirag R

    2017-09-01

    Biomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such biomarkers, we performed a nested case-control study (n=190 cases of incident DKD and 190 matched controls) and a prospective cohort study (n=1156) using banked baseline plasma samples from participants of randomized, controlled trials of early (ACCORD) and advanced (VA NEPHRON-D) DKD. We assessed the association and discrimination obtained with baseline levels of plasma TNF receptor-1 (TNFR-1), TNFR-2, and kidney injury molecule-1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D). At baseline, median concentrations of TNFR-1, TNFR-2, and KIM-1 were roughly two-fold higher in the advanced DKD population (NEPHRON-D) than in the early DKD population (ACCORD). In both cohorts, patients who reached the renal outcome had higher baseline levels than those who did not reach the outcome. Associations between doubling in TNFR-1, TNFR-2, and KIM-1 levels and risk of the renal outcomes were significant for both cohorts. Inclusion of these biomarkers in clinical models increased the area under the curve (SEM) for predicting the renal outcome from 0.68 (0.02) to 0.75 (0.02) in NEPHRON-D. Systematic review of the literature illustrated high consistency in the association between these biomarkers of inflammation and renal outcomes in DKD. In conclusion, TNFR-1, TNFR-2, and KIM-1 independently associated with higher risk of eGFR decline in persons with early or advanced DKD. Moreover, addition of these biomarkers to clinical prognostic models significantly improved discrimination for the renal outcome. Copyright © 2017 by the American Society of Nephrology.

  3. Targeting Sirtuin-1 prolongs murine renal allograft survival and function.

    PubMed

    Levine, Matthew H; Wang, Zhonglin; Xiao, Haiyan; Jiao, Jing; Wang, Liqing; Bhatti, Tricia R; Hancock, Wayne W; Beier, Ulf H

    2016-05-01

    Current immunosuppressive medications used after transplantation have significant toxicities. Foxp3(+) T-regulatory cells can prevent allograft rejection without compromising protective host immunity. Interestingly, inhibiting the class III histone/protein deacetylase Sirtuin-1 can augment Foxp3(+) T-regulatory suppressive function through increasing Foxp3 acetylation. Here we determined whether Sirtuin-1 targeting can stabilize biological allograft function. BALB/c kidney allografts were transplanted into C57BL/6 recipients with a CD4-conditional deletion of Sirtuin-1 (Sirt1(fl/fl)CD4(cre)) or mice treated with a Sirtuin-1-specific inhibitor (EX-527), and the native kidneys removed. Blood chemistries and hematocrit were followed weekly. Sirt1(fl/fl)CD4(cre) recipients showed markedly longer survival and improved kidney function. Sirt1(fl/fl)CD4(cre) recipients exhibited donor-specific tolerance, accepted BALB/c, but rejected third-party C3H cardiac allografts. C57BL/6 recipients of BALB/c renal allografts that were treated with EX-527 showed improved survival and renal function at 1, but not 10 mg/kg/day. Pharmacologic inhibition of Sirtuin-1 also improved renal allograft survival and function with dosing effects having relevance to outcome. Thus, inhibiting Sirtuin-1 can be a useful asset in controlling T-cell-mediated rejection. However, effects on non-T cells that could adversely affect allograft survival and function merit consideration.

  4. Resting-State Functional Connectivity-Based Biomarkers and Functional MRI-Based Neurofeedback for Psychiatric Disorders: A Challenge for Developing Theranostic Biomarkers.

    PubMed

    Yamada, Takashi; Hashimoto, Ryu-Ichiro; Yahata, Noriaki; Ichikawa, Naho; Yoshihara, Yujiro; Okamoto, Yasumasa; Kato, Nobumasa; Takahashi, Hidehiko; Kawato, Mitsuo

    2017-10-01

    Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., "theranostic biomarker") is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce a recent approach for creating a theranostic biomarker, which consists mainly of 2 parts: (1) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (2) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  5. Importance of renal depth correction for quantitation of differential renal function

    SciTech Connect

    Choi, H.; Kirchner, P.T.

    1985-05-01

    To assess the frequency and magnitude of errors caused by asymmetries in renal depth, when estimates of differential function are based only posterior projections (as in DTPA studies). The authors compared ratios of right-to-left (R/L) DMSA localization derived from posterior camera images with R/L ratios based on geometric mean of posterior and anterior counts of each kidney. The factor (X) required to convert the ratio of R/L posterior counts to the more accurate R/L geometric counts (Rp/Lp.X = Rg/Lg) was determined in 55 randomly selected patients referred for DMSA studies. Frequency distributions for X and l/X reveal that the use of posterior counts alone is likely to produce differential flow/function estimates with errors greater than 30% in 5% of patients, greater than 20% in 16 of patients. Lack of depth correction also widens the normal range derived from normal controls, thus reducing sensitivity and specificity of quantitative renal studies by two different mechanisms. The authors recommend routine application of depth correction by conjugate counting or ultrasound techniques for all quantitations of renal function.

  6. Alterations in VHL as potential biomarkers in renal-cell carcinoma.

    PubMed

    Gossage, Lucy; Eisen, Tim

    2010-05-01

    Germ line mutations in the VHL tumor-suppressor gene cause von Hippel-Lindau (VHL) disease, a hereditary neoplastic disease associated with clear-cell renal-cell carcinomas (ccRCCs), central nervous system hemangioblastomas and pheochromocytomas. Disruption of VHL, by somatic mutation, hypermethylation of its promoter or chromosomal loss, is also seen in the majority of cases of sporadic ccRCC. The protein product of VHL, pVHL, has multiple functions, the best-documented of which relates to its ability to target hypoxia-inducible factors (HIFs) for polyubiquitination and proteasomal degradation through its role in substrate recognition as part of a ubiquitin ligase complex. Consequently, pVHL-defective ccRCCs overexpress mRNAs that are under the transcriptional control of HIF. Drugs that modulate the downstream targets of the pVHL/HIF pathway, including sunitinib, sorafenib, temsirolimus and bevacizumab, have proven benefit in treating ccRCC. In VHL disease, clear evidence supports strong genotype-phenotype correlations, but the situation in sporadic ccRCC is less clear. Data indicate that VHL alterations have a potential role as prognostic and predictive markers in ccRCC. Future clinical trials should prospectively define the VHL alteration status of study participants so that the true utility of such markers can be determined.

  7. Renal function alterations during skeletal muscle disuse in simulated microgravity

    NASA Technical Reports Server (NTRS)

    Tucker, Bryan J.

    1992-01-01

    This project was to examine the alterations in renal functions during skeletal muscle disuse in simulated microgravity. Although this area could cover a wide range of investigative efforts, the limited funding resulted in the selection of two projects. These projects would result in data contributing to an area of research deemed high priority by NASA and would address issues of the alterations in renal response to vasoactive stimuli during conditions of skeletal muscle disuse as well as investigate the contribution of skeletal muscle disuse, conditions normally found in long term human exposure to microgravity, to the balance of fluid and macromolecules within the vasculature versus the interstitium. These two projects selected are as follows: investigate the role of angiotensin 2 on renal function during periods of simulated microgravity and skeletal muscle disuse to determine if the renal response is altered to changes in circulating concentrations of angiotensin 2 compared to appropriate controls; and determine if the shift of fluid balance from vasculature to the interstitium, the two components of extracellular fluid volume, that occur during prolonged exposure to microgravity and skeletal muscle disuse is a result, in part, to alterations in the fluid and macromolecular balance in the peripheral capillary beds, of which the skeletal muscle contains the majority of recruitment capillaries. A recruitment capillary bed would be most sensitive to alterations in Starling forces and fluid and macromolecular permeability.

  8. Impairment of cardiac function and energetics in experimental renal failure.

    PubMed Central

    Raine, A E; Seymour, A M; Roberts, A F; Radda, G K; Ledingham, J G

    1993-01-01

    Cardiac function and energetics in experimental renal failure in the rat (5/6 nephrectomy) have been investigated by means of an isolated perfused working heart preparation and an isometric Langendorff preparation using 31P nuclear magnetic resonance (31P NMR). 4 wk after nephrectomy cardiac output of isolated hearts perfused with Krebs-Henseleit buffer was significantly lower (P < 0.0001) at all levels of preload and afterload in the renal failure groups than in the pair-fed sham operated control group. In control hearts, cardiac output increased with increases in perfusate calcium from 0.73 to 5.61 mmol/liter whereas uremic hearts failed in high calcium perfusate. Collection of 31P NMR spectra from hearts of renal failure and control animals during 30 min normoxic Langendorff perfusion showed that basal phosphocreatine was reduced by 32% to 4.7 mumol/g wet wt (P < 0.01) and the phosphocreatine to ATP ratio was reduced by 32% (P < 0.01) in uremic hearts. During low flow ischemia, there was a substantial decrease in phosphocreatine in the uremic hearts and an accompanying marked increase in release of inosine into the coronary effluent (14.9 vs 6.1 microM, P < 0.01). We conclude that cardiac function is impaired in experimental renal failure, in association with abnormal cardiac energetics and increased susceptibility to ischemic damage. Disordered myocardial calcium utilization may contribute to these derangements. PMID:8254048

  9. Effects of dietary sodium chloride intake on renal function and blood pressure in cats with normal and reduced renal function.

    PubMed

    Buranakarl, Chollada; Mathur, Sheerin; Brown, Scott A

    2004-05-01

    To determine effects of variations in dietary intake of sodium chloride (NaCl) on systemic arterial blood pressure (ABP) in cats with normal and reduced renal function. 21 adult cats (7 with intact kidneys [control cats; group C], 7 with unilateral renal infarction with contralateral nephrectomy [remnant-kidney model; group RK], and 7 with unilateral renal infarction and contralateral renal wrapping and concurrent oral administration of amlodipine [remnant-wrap model; group WA]). All cats were sequentially fed 3 diets that differed only in NaCl content (50, 100, or 200 mg of Na/kg); each diet was fed for 7 days. The ABP was recorded continuously by radiotelemetry, and renal function (glomerular filtration rate [GFR]) was determined on the sixth day of each feeding period. Dietary supplementation with NaCl did not affect ABP, but it increased GFR in groups C and WA. The renin-angiotensin-aldosterone axis was activated in groups RK and WA at the lowest NaCl intake, but supplementation with NaCl suppressed this activation in group WA. The lowest NaCl intake was associated with hypokalemia and a high fractional excretion of potassium that decreased in response to supplementation with NaCl. Arterial baroreceptor resetting was evident after chronic hypertension but was not modified by dietary supplementation with NaCl. Low NaCl intake was associated with inappropriate kaliuresis, reduced GFR, and activation of the renin-angiotensin-aldosterone axis without evidence of a beneficial effect on ABP. Therefore, this common dietary maneuver could contribute to hypokalemic nephropathy and progressive renal injury in cats.

  10. OLDER PEOPLE WITH CHRONIC KIDNEY DISEASE: DEFINITION, AND INFLUENCE OF BIOMARKERS AND MEDICATIONS UPON CARDIOVASCULAR AND RENAL OUTCOMES.

    PubMed

    Raman, Maharajan; Green, Darren; Middleton, Rachel J; Kalra, Philip A

    2016-09-01

    Chronic kidney disease (CKD) is a global problem. With an ageing population the burden on the health services has increased due to the growing number of older people with CKD. This group of individuals is far different to the younger CKD population and their risk of cardiovascular death is far greater than the risk of progressing to end stage kidney disease (ESKD). In this review we explore the role of certain biomarkers and medications in predicting the risk of progression to ESKD and death in old people with CKD. An electronic literature search of EMBASE and MEDLINE databases was performed using Healthcare Databases Advanced Search (HDAS) in December 2014. Albuminuria is a key biomarker in predicting the risk of death and progression to ESKD. Cystatin C appears to be superior in predicting the risk of cardiovascular and non-cardiovascular death compared to GFR or creatinine. Several inflammatory biomarkers can be used to predict the risk of death and progression to CKD but measuring and monitoring them in routine clinical practice will be expensive and impractical. The effects of long-term RAAS inhibition in older people are not well established. Older people especially those with CKD receive suboptimal secondary preventive measures. Due to multiple comorbidities older people with CKD are usually receiving a number of medications. This can potentially lead to significant adverse drug events (ADE) due to drug interactions. Novel non-traditional risk factors like albuminuria, Cystatin C and inflammatory biomarkers play an important role in predicting their risk of death and progression to ESKD. The efficacy and safety of medications in older people with CKD is not well established and requires more extensive, focused study. © 2016 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  11. Dengue in renal transplant recipients: Clinical course and impact on renal function

    PubMed Central

    Fernandes, Paula Frassinetti Castelo Branco Camurça; Siqueira, Reed André; Girão, Evelyne Santana; Siqueira, Rainne André; Mota, Márcia Uchoa; Marques, Leyla Castelo Branco Fernandes; Andrade, Silvana Cristina Albuquerque; Barroso, Wilson Mendes; Silva, Sônia Leite; Rodrigues dos Santos, Bruno Gomes; de Oliveira, Claúdia Maria Costa

    2017-01-01

    AIM To present clinical characteristics from renal transplant recipients with dengue fever and its impact on graft function. METHODS We retrospectively evaluated 11 renal transplant recipients (RTR) with dengue infection confirmed by laboratory test, between January 2007 and July 2012, transplanted in the Renal Transplant Center of Walter Cantídio University Hospital from Federal University of Ceará. RESULTS Positive dengue serology (IgM) was found in all patients. The mean time between transplant and dengue infection was 43 mo. Fever was presented in all patients. Nine patients presented with classical dengue and two (18%) with dengue hemorrhagic fever. All cases had satisfactory evolution with complete recovery of the symptoms. The time for symptom resolution varied from 2 to 20 d, with an average of 9 d. An increase of creatinine after the infection was observed in three (27.2%) patients with no clinically impact on the kidney graft function. CONCLUSION RTR with dengue infection seems to have a clinical presentation and evolution similar to those seen in the general population, with no long-term damage to patient and to the graft. PMID:28280696

  12. Kidney biomarkers in cirrhosis.

    PubMed

    Francoz, Claire; Nadim, Mitra K; Durand, François

    2016-10-01

    Impaired renal function due to acute kidney injury (AKI) and/or chronic kidney diseases (CKD) is frequent in cirrhosis. Recurrent episodes of AKI may occur in end-stage cirrhosis. Differential diagnosis between functional (prerenal and hepatorenal syndrome) and acute tubular necrosis (ATN) is crucial. The concept that AKI and CKD represent a continuum rather than distinct entities, is now emerging. Not all patients with AKI have a potential for full recovery. Precise evaluation of kidney function and identification of kidney changes in patients with cirrhosis is central in predicting reversibility. This review examines current biomarkers for assessing renal function and identifying the cause and mechanisms of impaired renal function. When CKD is suspected, clearance of exogenous markers is the reference to assess glomerular filtration rate, as creatinine is inaccurate and cystatin C needs further evaluation. Recent biomarkers may help differentiate ATN from hepatorenal syndrome. Neutrophil gelatinase-associated lipocalin has been the most extensively studied biomarker yet, however, there are no clear-cut values that differentiate each of these conditions. Studies comparing ATN and hepatorenal syndrome in cirrhosis, do not include a gold standard. Combinations of innovative biomarkers are attractive to identify patients justifying simultaneous liver and kidney transplantation. Accurate biomarkers of underlying CKD are lacking and kidney biopsy is often contraindicated in this population. Urinary microRNAs are attractive although not definitely validated. Efforts should be made to develop biomarkers of kidney fibrosis, a common and irreversible feature of CKD, whatever the cause. Biomarkers of maladaptative repair leading to irreversible changes and CKD after AKI are also promising.

  13. Radionuclide determination of individual kidney function in the treatment of chronic renal obstruction

    SciTech Connect

    Belis, J.A.; Belis, T.E.; Lai, J.C.; Goodwin, C.A.; Gabriele, O.F.

    1982-04-01

    Differential radionuclide renal scans can be useful in the management of patients with chronic partial obstruction of 1 kidney. The /sup 99m/Tc diethylenetriaminepentaacetic acid perfusion scan can be used to assess glomerular blood flow. The /sup 131/I orthoiodohippurate renal scan provides qualitative functional information from scintigrams and quantitative evaluation of effective renal plasma flow to each kidney, as well as a total excretory index. Sequential /sup 99m/Tc diethylenetriaminepentaacetic acid and /sup 131/I orthoiodohippurate renal scans were used to assess individual renal function before and after surgical correction of unilateral chronic renal obstruction in 31 patients. The preservation of cortical perfusion on /supb 99m/Tc diethylenetriaminepentaacetic acid scans indicated that potential existed for partial recovery of renal function. Effective renal plasma flow and excretory index determined in conjunction with the /sup 131/I orthoiodohippurate scans provided a quantitative assessment of preoperative renal function, an evaluation of the effect of surgery and a sensitive method for long-term evaluation of differential renal function. Correction of ureteropelvic junction obstruction usually resulted in improvement in unilateral renal function. Neither nephrolithotomy nor extended pyelolithotomy diminished renal function in the kidney subjected to an operation and often improved it. Patients with long-standing distal ureteral obstruction had the least improvement in renal function postoperatively.

  14. Radionuclide determination of individual kidney function in the treatment of chronic renal obstruction.

    PubMed

    Belis, J A; Belis, T E; Lai, J C; Goodwin, C A; Gabriele, O F

    1982-04-01

    Differential radionuclide renal scans can be useful in the management of patients with chronic partial obstruction of 1 kidney. The 99mtechnetium diethylenetriaminepentaacetic acid perfusion scan can be used to assess glomerular blood flow. The 131iodine orthoiodohippurate renal scan provides qualitative functional information from scintigrams and quantitative evaluation of effective renal plasma flow to each kidney, as well as a total excretory index. Sequential 99mtechnetium diethylenetriaminepentaacetic acid and 131iodine orthoiodohippurate renal scans were used to assess individual renal function before and after surgical correction of unilateral chronic renal obstruction in 31 patients. The preservation of cortical perfusion on 99mtechnetium diethylenetriaminepentaacetic acid scans indicated that potential existed for partial recovery of renal function. Effective renal plasma flow and excretory index determined in conjunction with the 131iodine orthoiodohippurate scans provided a quantitative assessment of preoperative renal function, an evaluation of the effect of surgery and a sensitive method for long-term evaluation of differential renal function. Correction of ureteropelvic junction obstruction usually resulted in improvement in unilateral renal function. Neither nephrolithotomy nor extended pyelolithotomy diminished renal function in the kidney subjected to an operation and often improved it. Patients with long-standing distal ureteral obstruction had the least improvement in renal function postoperatively.

  15. Decline in renal function after partial nephrectomy: etiology and prevention.

    PubMed

    Mir, Maria C; Ercole, Cesar; Takagi, Toshio; Zhang, Zhiling; Velet, Lily; Remer, Erick M; Demirjian, Sevag; Campbell, Steven C

    2015-06-01

    Partial nephrectomy is the reference standard for the management of small renal tumors and is commonly used for localized kidney cancer. A primary goal of partial nephrectomy is to preserve as much renal function as possible. New baseline glomerular filtration rate after partial nephrectomy can have prognostic significance with respect to long-term outcomes. Recent studies provide an increased understanding of the factors that determine functional outcomes after partial nephrectomy as well as preventive measures to minimize functional decline. We review these advances, highlight ongoing controversies and stimulate further research. A comprehensive literature review consistent with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria was performed from January 2006 to April 2014 using PubMed®, Cochrane and Ovid Medline. Key words included partial nephrectomy, renal function, warm ischemia, hypothermia, nephron mass, parenchymal volume, surgical approaches to partial nephrectomy, preoperative and intraoperative imaging, enucleation, hemostatic agents and energy based resection. Relevant reviews were also examined as well as their cited references. An additional Google Scholar search was conducted to broaden the scope of the review. Only English language articles were included in the analysis. The primary outcomes of interest were the new baseline level of function after early postoperative recovery, percent decline in function, potential etiologies and preventive measures. Decline in function after partial nephrectomy averages approximately 20% in the operated kidney, and can be due to incomplete recovery from the ischemic insult or loss of nephron mass related to parenchymal excision or collateral damage during reconstruction. Compensatory hypertrophy in the contralateral kidney after partial nephrectomy in adults is marginal and decline in global renal function for patients with 2 kidneys averages about 10%, although there is

  16. Renal function is independently associated with circulating betatrophin

    PubMed Central

    Maurer, Lukas; Schwarz, Franziska; Fischer-Rosinsky, Antje; Schlueter, Nina; Brachs, Sebastian; Möhlig, Matthias; Pfeiffer, Andreas; Mai, Knut; Bobbert, Thomas

    2017-01-01

    Objective Betatrophin has been identified as a marker linking liver with beta cell function and lipid metabolism in murine models. Until now, the regulation of circulating betatrophin in humans is not entirely clear. We here analyzed the relation of betatrophin levels to phenotypes of the metabolic syndrome and speculated that renal function might influence circulating betatrophin levels and explain age-dependent changes of betatrophin. Subjects We analyzed blood samples from 535 individuals participating in the Metabolic Syndrome Berlin Potsdam study. Results In a crude analysis we found a positive correlation between betatrophin levels and HbA1c (r = 0.24; p < 0.001), fasting glucose (r = 0.20; p < 0.001) and triglycerides (r = 0.12; p = 0.007). Furthermore betatrophin was positively correlated with age (r = 0.47; p <0.001), systolic blood pressure (r = 0.17; p < 0.001), intima media thickness (r = 0.26; p < 0.001) and negatively correlated with CKD-EPI eGFR (r = -0.33; p < 0.001) as an estimate of renal function. Notably, eGFR remained highly associated with betatrophin after adjustment for age, waist circumference, gender, HbA1c and lipid parameters in a multivariate linear regression model (β = -0.197, p< 0.001). Conclusions Our data suggest that circulating levels of betatrophin depend on age, gender, waist circumference, total/HDL cholesterol ratio and renal function. Especially the association to eGFR highlights the importance for future studies to address renal function as possible influence on betatrophin regulation and consider eGFR as potential confounder when analyzing the role of betatrophin in humans. PMID:28257453

  17. Renal function is independently associated with circulating betatrophin.

    PubMed

    Maurer, Lukas; Schwarz, Franziska; Fischer-Rosinsky, Antje; Schlueter, Nina; Brachs, Sebastian; Möhlig, Matthias; Pfeiffer, Andreas; Mai, Knut; Spranger, Joachim; Bobbert, Thomas

    2017-01-01

    Betatrophin has been identified as a marker linking liver with beta cell function and lipid metabolism in murine models. Until now, the regulation of circulating betatrophin in humans is not entirely clear. We here analyzed the relation of betatrophin levels to phenotypes of the metabolic syndrome and speculated that renal function might influence circulating betatrophin levels and explain age-dependent changes of betatrophin. We analyzed blood samples from 535 individuals participating in the Metabolic Syndrome Berlin Potsdam study. In a crude analysis we found a positive correlation between betatrophin levels and HbA1c (r = 0.24; p < 0.001), fasting glucose (r = 0.20; p < 0.001) and triglycerides (r = 0.12; p = 0.007). Furthermore betatrophin was positively correlated with age (r = 0.47; p <0.001), systolic blood pressure (r = 0.17; p < 0.001), intima media thickness (r = 0.26; p < 0.001) and negatively correlated with CKD-EPI eGFR (r = -0.33; p < 0.001) as an estimate of renal function. Notably, eGFR remained highly associated with betatrophin after adjustment for age, waist circumference, gender, HbA1c and lipid parameters in a multivariate linear regression model (β = -0.197, p< 0.001). Our data suggest that circulating levels of betatrophin depend on age, gender, waist circumference, total/HDL cholesterol ratio and renal function. Especially the association to eGFR highlights the importance for future studies to address renal function as possible influence on betatrophin regulation and consider eGFR as potential confounder when analyzing the role of betatrophin in humans.

  18. The effects of environmental chemicals on renal function

    PubMed Central

    Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

    2015-01-01

    The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease. PMID:26100504

  19. The effects of environmental chemicals on renal function.

    PubMed

    Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

    2015-10-01

    The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease.

  20. Markers of Renal Function and Injury

    SciTech Connect

    Ragan, Harvey A.; Weller, Richard E.

    1999-04-15

    Designed to aid the laboratory animal veterinarian, researcher, or toxicologist in the proper evaluation of organ function, this updated and revised edition provides the only comprehensive reference of the clinical chemistry of laboratory animals. With contributions from recognized experts in the field, new chapters are included that focus on the pig and the ferret, while many chapters have been rewritten. Expanded coverage was given to urine chemistry, hormones, including melatonin, and the control mechanisms of analytes. Reference values are given in both conventional and S.I. units.

  1. Measurement of renal function in patients with chronic kidney disease.

    PubMed

    Sandilands, Euan A; Dhaun, Neeraj; Dear, James W; Webb, David J

    2013-10-01

    Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease.

  2. Measurement of renal function in patients with chronic kidney disease

    PubMed Central

    Sandilands, Euan A; Dhaun, Neeraj; Dear, James W; Webb, David J

    2013-01-01

    Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease. PMID:23802624

  3. Tracing the evolutionary origins of insect renal function.

    PubMed

    Halberg, Kenneth A; Terhzaz, Selim; Cabrero, Pablo; Davies, Shireen A; Dow, Julian A T

    2015-04-21

    Knowledge on neuropeptide receptor systems is integral to understanding animal physiology. Yet, obtaining general insight into neuropeptide signalling in a clade as biodiverse as the insects is problematic. Here we apply fluorescent analogues of three key insect neuropeptides to map renal tissue architecture across systematically chosen representatives of the major insect Orders, to provide an unprecedented overview of insect renal function and control. In endopterygote insects, such as Drosophila, two distinct transporting cell types receive separate neuropeptide signals, whereas in the ancestral exopterygotes, a single, general cell type mediates all signals. Intriguingly, the largest insect Order Coleoptera (beetles) has evolved a unique approach, in which only a small fraction of cells are targets for neuropeptide action. In addition to demonstrating a universal utility of this technology, our results reveal not only a generality of signalling by the evolutionarily ancient neuropeptide families but also a clear functional separation of the types of cells that mediate the signal.

  4. Tracing the evolutionary origins of insect renal function

    PubMed Central

    Halberg, Kenneth A.; Terhzaz, Selim; Cabrero, Pablo; Davies, Shireen A.; Dow, Julian A. T.

    2015-01-01

    Knowledge on neuropeptide receptor systems is integral to understanding animal physiology. Yet, obtaining general insight into neuropeptide signalling in a clade as biodiverse as the insects is problematic. Here we apply fluorescent analogues of three key insect neuropeptides to map renal tissue architecture across systematically chosen representatives of the major insect Orders, to provide an unprecedented overview of insect renal function and control. In endopterygote insects, such as Drosophila, two distinct transporting cell types receive separate neuropeptide signals, whereas in the ancestral exopterygotes, a single, general cell type mediates all signals. Intriguingly, the largest insect Order Coleoptera (beetles) has evolved a unique approach, in which only a small fraction of cells are targets for neuropeptide action. In addition to demonstrating a universal utility of this technology, our results reveal not only a generality of signalling by the evolutionarily ancient neuropeptide families but also a clear functional separation of the types of cells that mediate the signal. PMID:25896425

  5. Renal function monitoring in patients receiving lithium carbonate.

    PubMed

    Gelenberg, A J; Wojcik, J D; Coggins, C H; Rosenbaum, J F; LaBrie, R A

    1981-11-01

    As a screening test for renal function, urine concentration was measured following a 12-hour overnight fast in 54 outpatients taking lithium carbonate and 19 patients receiving antidepressant drugs. A significantly greater percentage of lithium patients failed to achieve a maximum urine concentration of 600 mOsm/kg (63% versus 33% in the antidepressant group, p less than .001). This level, a compromise between the sensitivity and specificity of the test, is viewed as a cutoff point for further testing. It is concluded that urine concentration testing is a feasible first-line screen for renal function among lithium-treated patients. Other preliminary studies include routine urinalysis, serum creatinine determination, and estimated creatinine clearance. Second-line testing includes a repeated dehydration test and administration of DDAVP.

  6. The cancer-retina antigen recoverin as a potential biomarker for renal tumors.

    PubMed

    Golovastova, Marina O; Tsoy, Larisa V; Bocharnikova, Anna V; Korolev, Dmitry O; Gancharova, Olga S; Alekseeva, Ekaterina A; Kuznetsova, Ekaterina B; Savvateeva, Lyudmila V; Skorikova, Elena E; Strelnikov, Vladimir V; Varshavsky, Vladimir A; Vinarov, Andrey Z; Nikolenko, Vladimir N; Glybochko, Peter V; Zernii, Evgeni Yu; Zamyatnin, Andrey A; Bazhin, Alexandr V; Philippov, Pavel P

    2016-07-01

    The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.

  7. Renal function in familial longevity: the Leiden Longevity Study.

    PubMed

    de Goeij, Moniek C M; Halbesma, Nynke; Dekker, Friedo W; Wijsman, Carolien A; van Heemst, Diana; Maier, Andrea B; Mooijaart, Simon P; Slagboom, P Eline; Westendorp, Rudi G J; de Craen, Anton J M

    2014-03-01

    Studying renal function in subjects with a familial propensity for longevity may provide insight in (un)known mechanisms that determine the age-related decline in renal function of normal subjects. In the Leiden Longevity Study, middle-aged offspring of non-agenarian siblings and their partners as environmentally matched controls were included. Information was collected on lifestyle, medical history, medication use, and a non-fasting blood sample was drawn. Renal function (estimated glomerular filtration rate, eGFR) was assessed with the Chronic Kidney Disease epidemiology collaboration (CKD-EPI) formula. Linear mixed models were used to account for familial dependencies within the offspring and all analyses were stratified by sex. eGFR was similar between female offspring and female controls (0.44ml/min/1.73m(2) (SE 0.72) difference, p=0.54, age-adjusted). Male offspring had a higher eGFR compared to male controls (1.78ml/min/1.73m(2) (SE 0.78) difference, p=0.022, age-adjusted), and further adjustments for various characteristics did not materially change this difference. Among men with a history of hypertension, or myocardial infarction and/or stroke, offspring had a higher eGFR compared to controls (4.74ml/min/1.73m(2) (SE 1.53) difference, p=0.002, age-adjusted, and 6.21ml/min/1.73m(2) (SE 2.85) difference, p=0.033, age-adjusted, respectively). Middle-aged men, but not women, with a propensity for longevity have better renal function compared to environmentally matched controls, especially among those with a history of cardiovascular disease.

  8. Function-informed transcriptome analysis of Drosophila renal tubule

    PubMed Central

    Wang, Jing; Kean, Laura; Yang, Jingli; Allan, Adrian K; Davies, Shireen A; Herzyk, Pawel; Dow, Julian AT

    2004-01-01

    Background Comprehensive, tissue-specific, microarray analysis is a potent tool for the identification of tightly defined expression patterns that might be missed in whole-organism scans. We applied such an analysis to Drosophila melanogaster Malpighian (renal) tubule, a defined differentiated tissue. Results The transcriptome of the D. melanogaster Malpighian tubule is highly reproducible and significantly different from that obtained from whole-organism arrays. More than 200 genes are more than 10-fold enriched and over 1,000 are significantly enriched. Of the top 200 genes, only 18 have previously been named, and only 45% have even estimates of function. In addition, 30 transcription factors, not previously implicated in tubule development, are shown to be enriched in adult tubule, and their expression patterns respect precisely the domains and cell types previously identified by enhancer trapping. Of Drosophila genes with close human disease homologs, 50 are enriched threefold or more, and eight enriched 10-fold or more, in tubule. Intriguingly, several of these diseases have human renal phenotypes, implying close conservation of renal function across 400 million years of divergent evolution. Conclusions From those genes that are identifiable, a radically new view of the function of the tubule, emphasizing solute transport rather than fluid secretion, can be obtained. The results illustrate the phenotype gap: historically, the effort expended on a model organism has tended to concentrate on a relatively small set of processes, rather than on the spread of genes in the genome. PMID:15345053

  9. Renal impairment and worsening of renal function in acute heart failure: can new therapies help? The potential role of serelaxin.

    PubMed

    Schmieder, Roland E; Mitrovic, Veselin; Hengstenberg, Christian

    2015-08-01

    Renal dysfunction is a frequent finding in patients with acute heart failure (AHF) and an important prognostic factor for adverse outcomes. Worsening of renal function occurs in 30-50% of patients hospitalised for AHF, and is associated with increased mortality, prolonged hospital stay and increased risk of readmission. Likely mechanisms involved in the decrease in renal function include impaired haemodynamics and activation of neurohormonal factors, such as the renin-angiotensin-aldosterone system, the sympathetic nervous system and the arginine-vasopressin system. Additionally, many drugs currently used to treat AHF have a detrimental effect on renal function. Therefore, pharmacotherapy for AHF should carefully take into account any potential complications related to renal function. Serelaxin, currently in clinical development for the treatment of AHF is a recombinant form of human relaxin-2, identical in structure to the naturally occurring human relaxin-2 peptide hormone that mediates cardiac and renal adaptations during pregnancy. Data from both pre-clinical and clinical studies indicate a potentially beneficial effect of serelaxin on kidney function. In this review, we discuss the mechanisms and impact of impairment of renal function in AHF, and the potential benefits of new therapies, such as serelaxin, in this context.

  10. Indapamide is superior to thiazide in the preservation of renal function in patients with renal insufficiency and systemic hypertension.

    PubMed

    Madkour, H; Gadallah, M; Riveline, B; Plante, G E; Massry, S G

    1996-02-22

    The long-term effects of indapamide or hydrochlorothiazide on blood presssure and renal function were examined in patents with impaired renal function and moderate hypertension. Both drugs controlled hypertension and blood pressure remained normal during the 2 years of the study. Despite this comparable control of hypertension, indapamide therapy was associated with a 28.5 +/- 4.4% increase in creatinine clearance, whereas treatment with hydrochlorothiazide was associated with a 17.4 +/- 3.0% decrease in creatinine clearance. The results of the study indicate that indapamide is superior to hydrochlorothiazide in the treatment of patients with impaired renal function and moderate hypertension.

  11. Factors Predicting Renal Function Outcome after Augmentation Cystoplasty

    PubMed Central

    Seyam, Raouf; Firdous, Sadia

    2017-01-01

    We determined the cause of renal deterioration after augmentation cystoplasty (AC). Twenty-nine adult patients with refractory bladder dysfunction and who underwent ileocystoplasty from 2004 to 2015 were studied. Patients with a decline in glomerular filtration rate (GFR) after augmentation were reviewed. The primary outcome was to determine the factors that might lead to deterioration of estimated GFR. Median follow-up was 7.0 ± 2.6 years. Significant bladder capacity, end filling pressure, and bladder compliance were achieved from median 114 ± 53.6 to 342.1 ± 68.3 ml (p = .0001), 68.5 ± 19.9 to 28.2 ± 6.9 cm H2O (p = .0001), and 3.0 ± 2.1 to 12.8 ± 3.9 (p = .0001), respectively. Renal function remained stable and improved in 22 (76%) patients from median eGFR 135 ± 81.98 to 142.82 ± 94.4 ml/min/1.73 m2 (p = .160). Significant deterioration was found in 7 (24%) patients from median eGFR 68.25 ± 42 to 36.57 ± 35.33 (p = .001). The causes of renal deterioration were noncompliance to self-catheterization (2 patients), posterior urethral valve/dysplastic kidneys (2 patients), and reflux/infection (2 patients). On multivariate analysis, recurrent pyelonephritis (OR 3.87, p = 0.0155) and noncompliance (OR 30.78, p = 0.0156) were significant. We concluded that AC is not the cause of progression to end-stage renal disease in patients with renal insufficiency. PMID:28367330

  12. The level of ethylene biomarker in the renal failure of elderly patients analyzed by photoacoustic spectroscopy

    NASA Astrophysics Data System (ADS)

    Popa, C.; Patachia, M.; Banita, S.; Matei, C.; Bratu, A. M.; Dumitras, D. C.

    2013-12-01

    In recent years there has been a large increase in the areas related to developments in the prevention of diseases, especially in explaining the role of oxidative stress. Lipid peroxidation and oxidative stress contributes to morbidity in hemodialysis (HD) patients. It is therefore relevant to analyze the impact of oxidative stress and its related species (ethylene) immediately after dialysis treatment in order to prevent trauma in the renal failure of elderly patients. In this paper we describe recent progress in laser photoacoustic spectroscopy detection of ethylene in renal failure patients. We have found that HD treatment increases ethylene concentration in the exhaled breath of elderly patients and may intensify oxidative stress.

  13. Calculation of renal differential function following renal transplant: retrospective validation of a simplified method.

    PubMed

    Mansouri, Ali M; Vejdani, Kaveh; Bastani, Bahar; Nguyen, Nghi C

    2012-10-01

    The estimation of differential function (DF) in post-renal transplant patients (PRTPs) is challenging because of the different distances of the native kidneys (NKs) and transplant kidney (TK) to the gamma camera and because current commercial software allows evaluation of only 2 kidneys instead of 3. We retrospectively validated a simplified method (SM) to process renal scans and hypothesized that it is comparable with the reference method (RM). Twelve 99mTc MAG3 renal scintigraphies of 10 PRTPs were performed on a dual-head gamma camera. The RM was a 2-step process, with the left and right NKs being compared with the TK separately. The SM was a 1-step process combining both NKs together. The DF estimates were consistent with geometric means in both methods. Statistical evaluation included linear correlation and Bland-Altman analysis. The RM and SM showed DF of 78% ± 25% versus 79% ± 27% for the TK and 22% ± 25% versus 21% ± 27% for the NKs (P = 0.3). There was excellent correlation between SM and RM measurements (r = 0.99, P < 0.001). Bland-Altman plot demonstrated a mean difference of 1.2 ± 3.8 at a 95% confidence interval (95% CI) of agreement of -6.2 to + 8.5 for the TK and -1.2 ± 3.8 at a 95% CI of agreement of -8.5 to + 6.2 for the NKs. Only 1 (8%) of 12 scans showed a difference slightly beyond the 95% CI, indicating a good agreement between SM and RM. The SM offers a simple way to evaluate renal DF in PRTP and shows comparable results with the RM. It may have great potential in clinical practice; however, larger studies are needed to verify and further extend the results of this study.

  14. 75 FR 13562 - Revised Draft Guidance for Industry on Pharmacokinetics in Patients With Impaired Renal Function...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-22

    ... Patients With Impaired Renal Function--Study Design, Data Analysis, and Impact on Dosing and Labeling... ``Pharmacokinetics in Patients With Impaired Renal Function--Study Design, Data Analysis, and Impact on Dosing and... influence of renal impairment on the pharmacokinetics of an investigational drug. It...

  15. Prokaryotic cDNA Subtraction: A Method to Rapidly Identify Functional Gene Biomarkers

    DTIC Science & Technology

    2008-10-01

    FINAL REPORT Prokaryotic cDNA Subtraction: A Method to Rapidly Identify Functional Gene Biomarkers SERDP Project ER-1563 OCTOBER 2008... Method to Rapidly Identify Functional Gene Biomarkers 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...Studying Biological Treatment with MBT ...................................................................5 2.2 Methods for Obtaining Gene Sequences

  16. Acute presentations of renal artery stenosis in three patients with a solitary functioning kidney.

    PubMed

    Pun, E; Dowling, R J; Mitchell, P J

    2004-12-01

    Renal artery stenosis can present uncommonly in the acute state as flash pulmonary oedema and hypertensive encephalopathy. We present three such cases in patients with a solitary functioning kidney, with successful management via renal artery angioplasty and stent insertion.

  17. Prognostic value of preoperative inflammatory response biomarkers in patients with sarcomatoid renal cell carcinoma and the establishment of a nomogram

    PubMed Central

    Gu, Liangyou; Ma, Xin; Li, Hongzhao; Chen, Luyao; Xie, Yongpeng; Zhao, Chaofei; Luo, Guoxiong; Zhang, Xu

    2016-01-01

    To examine the prognostic role of inflammatory response biomarkers in sarcomatoid renal cell carcinoma (sRCC). From January 2004 to May 2015, 103 patients with sRCC were enrolled in this study. Preoperative neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) were analyzed. Besides well-established clinicopathological prognostic factors, we evaluated the prognostic value of this four markers using Kaplan-Meier method and Cox regression models. Additionally, a nomogram was established to predict the prognosis of sRCC patients. Elevated NLR, dNLR and PLR were significantly associated with worse overall survival (OS), nevertheless, elevated LMR showed an adverse effect on reduced OS. Multivariate analysis revealed that NLR (HR = 4.07, 95% CI = 1.50–11.00, P = 0.006) retained as independent factor. Incorporation of the NLR into a prognostic model including T stage, M stage, tumor necrosis and percentage of sarcomatoid generated a nomogram, which accurately predicted OS for sRCC patients. Preoperative NLR may serve as a potential prognostic biomarker in patients with sRCC and may help with clinical decisions about treatment intervention in clinical practice. The proposed nomogram can be used for the prediction of OS in patients with sRCC. PMID:27035802

  18. Analysis and validation of tissue biomarkers for renal cell carcinoma using automated high-throughput evaluation of protein expression☆

    PubMed Central

    Abel, E. Jason; Bauman, Tyler M.; Weiker, Madelyn; Shi, Fangfang; Downs, Tracy M.; Jarrard, David F.; Huang, Wei

    2014-01-01

    Summary The objective of this study was to compare the predictive ability of potential tissue biomarkers to known prognostic factors that predict renal cell carcinoma (RCC) recurrence using an automated system of immunohistochemical analysis. After institutional review board approval, a tissue microarray was constructed using tissue from patients who had partial or radical nephrectomy for RCC. Patients with metastatic disease were excluded. Immunohistochemical staining of the tissue microarray for Ki-67, C-reactive protein, carbonic anhydrase 9, and hypoxia-inducible factors 1α and 2α was analyzed using automated image analysis. Univariable and multivariable analyses were performed to evaluate the association of putative biomarkers and known prognostic factors. Of 216 patients who met the entrance criteria, 34 (16%) patients developed metastatic recurrence within a median follow-up interval of 60.9 (interquartile range, 13.9–87.1) months. RCC morphotypes analyzed in this study include clear cell (n = 156), papillary (n = 38), chromophobe (n = 16), and collecting duct/unclassified (n = 6). Univariate analysis identified that only increased Ki-67 was predictive of RCC recurrence among the proteins evaluated, in addition to other known clinicopathological prognostic factors. After multivariate analysis, Ki-67 was identified as an independently predictive risk factor for RCC recurrence (hazard ratio [HR], 3.73 [confidence interval {CI}, 1.60–8.68]). Other independent predictors of RCC recurrence included tumor diameter (HR, 1.20 [CI, 1.02–1.41]) and perinephric fat invasion (HR, 4.49 [CI, 1.11–18.20]). We conclude that Ki-67 positivity is independently predictive of RCC recurrence after surgery in nonmetastatic patients. Automated analysis of tissue protein expression can facilitate a more objective and expedient investigation of tissue biomarkers for RCC. PMID:24746216

  19. Renal dysfunction in cirrhosis

    PubMed Central

    Urrunaga, Nathalie H.; Mindikoglu, Ayse L.; Rockey, Don C.

    2015-01-01

    Purpose of review Renal dysfunction causes significant morbidity in cirrhotic patients. Diagnosis is challenging because it is based on serum creatinine, which is used to calculate estimated glomerular filtration rate, which itself is not an ideal measure of renal function in patients with cirrhosis. Finding the exact cause of renal injury in patients with cirrhosis remains problematic due to the limitations of the current diagnostic tests. The purpose of this review is to highlight studies used to diagnose renal dysfunction in patients with renal dysfunction and review current treatments. Recent findings New diagnostic criteria and classification of renal dysfunction, especially for acute kidney injury (AKI), have been proposed in hopes of optimizing treatment and improving outcomes. New biomarkers that help to differentiate structural from functional AKI in cirrhotic patients have been developed, but require further investigation. Vasoconstrictors are the most commonly recommended treatment of hepatorenal syndrome (HRS). Given the high mortality in patients with type 1 HRS, all patients with HRS should be evaluated for liver transplantation. When renal dysfunction is considered irreversible, combined liver–kidney transplantation is advised. Summary Development of new biomarkers to differentiate the different types of AKI in cirrhosis holds promise. Early intervention in cirrhotic patients with renal dysfunction offers the best hope of improving outcomes. PMID:25763790

  20. Investigation of the relationship between low environmental exposure to metals and bone mineral density, bone resorption and renal function.

    PubMed

    Callan, A C; Devine, A; Qi, L; Ng, J C; Hinwood, A L

    2015-07-01

    Environmental exposure to metals has been linked to adverse health outcomes. Exposure to cadmium has been associated with decreased bone density, an increased risk of osteoporotic fracture and possible renal dysfunction. Older women are a group at risk of renal and bone density impacts and exposure to metals may be an important risk factor for these health outcomes. This study was a cross sectional study of 77 women aged 50 years and above examining the relationship between metals exposure and renal and bone health. Urinary and blood metals concentrations, plasma creatinine, iron, ferritin and transferrin were measured in these subjects. Bone biomarkers assessed included the pyridinium crosslinks, pyridinoline and deoxypyridinoline measured by ELISA. Renal function was assessed using eGFR and KIM-1. Whole body, hip and lumbar spine bone mineral density was assessed using DEXA. Blood and urinary metals concentrations were generally low in the subjects, with a median urinary cadmium concentration of 0.26 μg/g creatinine (range <0.065-1.03 μg/g). Urinary cadmium was found to be a significant predictor of bone mineral density at whole body, lumber spine, total hip and femoral neck, with increasing urinary Cd concentrations associated with decreased bone density. Urinary cadmium and aluminium concentrations were positively correlated with bone resorption whilst blood zinc and mercury concentrations were negatively correlated. Urinary aluminium was positively correlated with KIM-1 concentrations, a marker of early kidney damage, however blood zinc concentrations were significantly negatively correlated with this biomarker. This study provides additional support for low cadmium exposure being of concern for the health of older women. Further investigation into the role of exposure to other metals on bone and renal health is warranted.

  1. Safe conversion from cyclosporine to azathioprine with improved renal function in pediatric renal transplantation.

    PubMed

    Kaiser, B A; Lawless, S T; Palmer, J M; Dunn, S P; Polinsky, M S; Baluarte, H J

    1989-10-01

    Although cyclosporine has improved allograft survival in renal transplant patients, problems with drug toxicity remain, raising the question whether cyclosporine should be stopped at some point post-transplant. However, the relative safety of converting from cyclosporine to another immunosuppressive agent, or simply stopping cyclosporine remains an issue of debate and has not been evaluated in children. We have developed a protocol to convert children, who are 6 months post-transplant and have stable kidney function, from cyclosporine and prednisone to azathioprine and prednisone. Eleven children have undergone conversion because of suspected/potential nephrotoxicity or because of other difficulties with cyclosporine (expense, hirsutism). These children were compared with a control group of 12 children who met all criteria for conversion at 6 months but remained on cyclosporine. Allograft survival was similar in both groups but the children converted from cyclosporine experienced an improvement in renal function as measured by calculated creatinine clearance. There were no episodes of rejection for a period of 4 months post-conversion and all rejection episodes that developed subsequently occurred during or after the change from daily to alternate-day prednisone. We believe that conversion from cyclosporine to azathioprine can be accomplished safely in children with stable allograft function but long-term risks and benefits need further evaluation.

  2. Renal remodeling after abdominal radiation therapy: parenchymal and functional changes.

    PubMed

    Tran, Linda K; Maturen, Katherine E; Feng, Mary U; Wizauer, Eric J; Watcharotone, Kuanwong; Parker, Robert A; Ellis, James H

    2014-08-01

    The purpose of this study was to quantify changes in renal length, volume, and function over time after upper abdominal radiation therapy. Imaging and clinical data were retrospectively reviewed for 27 adults with abdominal radiation therapy between 2001 and 2012. All had two kidneys, radiation exposure to one kidney, and survival of at least 1 year after therapy. Mean prescribed dose was 52 ± 9 Gy to extrarenal targets. Length and volume of exposed and unexposed kidneys were measured on CT scans before treatment (baseline) and at intervals 0-3, 3-6, 6-12, 12-24, 24-36, and more than 36 months after completion of radiotherapy. Serum creatinine was correlated at each interval. Mixed-models ANOVA was used to test renal length and volume, serum creatinine, and time against multiple models to assess for temporal effects; specific time intervals were compared in pairwise manner. Mean follow-up duration was 35 months (range, 5-94 months). Exposed kidney length and volume progressively decreased from baseline throughout follow-up, with mean loss of 23% (p < 0.001) and 47% (p < 0.001), respectively. Slight increase in unexposed kidney length was not significant. Mean serum creatinine increased from 0.86 ± 0.18 mg/dL at baseline to 1.12 ± 0.27 mg/dL at 12-24 months (p < 0.001), then stabilized. Kidneys exposed to radiation during therapy of adjacent malignancies exhibited continuous progressive atrophy for the entire follow-up period, nearly 8 years. Volume changes were twice as great as length changes. Renal function also declined. To accurately interpret follow-up studies in cancer survivors, radiologists should be aware of the potential for progressive renal atrophy, even many years after radiation therapy.

  3. Temafloxacin pharmacokinetics in subjects with normal and impaired renal function.

    PubMed Central

    Granneman, G R; Braeckman, R; Kraut, J; Shupien, S; Craft, J C

    1991-01-01

    The pharmacokinetics of temafloxacin were investigated following oral administration of single 400-mg doses to 6 normal subjects and 18 subjects with various degrees of impaired renal function. Renal impairment did not significantly affect the peak concentration, time to peak concentration, or the nonrenal clearance of temafloxacin. Both renal clearance (CLR) and total apparent clearance (CLT/F, where F represents the fraction of dose absorbed) of temafloxacin were highly correlated with creatinine clearance (CLCR). The regression equations were as follows: CLR = 0.85.CLCR, with R2 = 0.907, and CLT/F = 56.0 + 0.92.CLCR, with R2 = 0.656. The half-life (mean +/- standard deviation) increased from 10.6 +/- 2.4 h in the normal volunteers to 24.6 +/- 7.3 h in the subjects with a CLCR of less than 10 ml/min; the respective CLT/F decreased from 169 +/- 58 to 70 +/- 27 ml/min. Compared with the CLT/F in the subjects with normal renal function, CLT/F was reduced 60% in subjects with a CLCR of less than 40 ml/min, indicating that the dosage should be reduced by at least one-half for patients with comparable impairment. For the subjects on chronic hemodialysis, most of the variability in the nonrenal clearance and the terminal-phase rate constant of temafloxacin was associated with the quantity of calcium carbonate and related medication taken for the treatment of hyperphosphatemia. Supplemental dosage is not required for patients undergoing hemodialysis, since the distribution of temafloxacin in tissue is extensive and the recoveries from 4-h dialysis sessions accounted for less than 10% of the drug present at the start of the dialysis. PMID:1666497

  4. [Capacities of examination of renal function at excretory urography].

    PubMed

    Bosin, V Iu; Zyrianov, V Iu

    2004-01-01

    The study was undertaken to enhance the diagnostic capacities of excretory urography in evaluating renal function, by determining the renal clearance of a contrast medium. The main task of the study was to develop bloodless and rather reliable ways of estimating the volume of the body's distributed contrast medium and its urinary concentration in the patient at urography. Excretory urography was performed in 248 patients aged 12 to 75 years. The specific gravity of excreted urine was determined with a standard laboratory urometer to 0.001 g/cm3. Absoption spectrophotometry was used to determine the serum concentration of contrast medium in 67 patients. The values of concentrations were plotted in the semilogarithmic ordinate system, followed by extrapolation of the initial segment of the plot to the so-called zero point determining the value of the concentration of contrast medium at the moment of its complete distribution in the intercellular space. The derived value was compared with the medium's dose coming into the body, which made it possible to determine the degree of dilution of the substance, i.e. the volume of its distribution in the organism. There was a linear relationship between the concentrations of renally eliminated contrast medium and the specific gravity of excreted urine. The numerical value of the constant reflecting this relationship is equal to 6. There was evidence for that such studies could be made by routine urometry. A high correlation was found between the body mass and the volume of distribution of contrast medium in the intercellular space. The discovery of the above regularities permitted the procedure for measuring the values of two most important physiological renal process (glomerular filtration and trabecular water reabsorption) to be simplified and widely available. The paper outlines the great promises for using excretory urography as a scanning functional test during a primary study and a follow-up of the patient's status.

  5. Urinary exosome-derived microRNAs reflecting the changes of renal function and histopathology in dogs

    PubMed Central

    Ichii, Osamu; Ohta, Hiroshi; Horino, Taro; Nakamura, Teppei; Hosotani, Marina; Mizoguchi, Tatsuya; Morishita, Keitaro; Nakamura, Kensuke; Hoshino, Yuki; Takagi, Satoshi; Sasaki, Noboru; Takiguchi, Mitsuyoshi; Sato, Ryo; Oyamada, Kazuhisa; Kon, Yasuhiro

    2017-01-01

    MicroRNAs act as post-transcriptional regulators, and urinary exosome (UExo)-derived microRNAs may be used as biomarkers. Herein, we screened for UExo-derived microRNAs reflecting kidney disease (KD) status in dogs. Examined dogs were divided into healthy kidney control (HC) and KD groups according to renal dysfunction. We confirmed the appearance of UExo having irregular globe-shapes in a dog by immunoblot detection of the exosome markers, TSG101 and CD9. Based on our previous data using KD model mice and the data obtained herein by next generation sequencing of UExo-derived microRNAs in dogs, miR-26a, miR-146a, miR-486, miR-21a, and miR-10a/b were selected as candidate microRNAs. In particular, UExo-derived miR-26a and miR-10a/b were significantly decreased in KD dogs, and miR-26a levels negatively correlated with deteriorated renal function compared to the other miRNAs. UExo-derived miR-21a levels corrected or not to that of internal control microRNAs in UExo, miR-26a and miR-191, significantly increased with renal dysfunction. In kidney tissues, the decrease of miR-26a and miR-10a/b in the glomerulus and miR-10b in the tubulointerstitium negatively correlated with deteriorated renal function and histopathology. Increased miR-21a in the tubulointerstitium rather than in the glomerulus correlated with deteriorated renal histopathology. In conclusion, microRNAs reflecting the changes in renal function and histopathology in dogs were identified in this study. PMID:28074869

  6. Impact of cystatin C and RIFLE on renal function assessment after cardiac surgery.

    PubMed

    Magro, Marcia Cristina da Silva; Vattimo, Maria de Fatima Fernandes

    2013-10-01

    The lack of a consensus classification system and of a specific, sensitive, and early-stage biomarker for kidney injury frequently results in late diagnosis of acute kidney injury (AKI). The aim of the present study was to characterize the discriminatory power of cystatin C and the RIFLE and Acute Kidney Injury Network (AKIN) criteria for the assessment of renal dysfunction after cardiac surgery. A longitudinal, quantitative study was conducted in intensive care units of the Heart Institute (São Paulo, Brazil) in which 121 patients were followed for the first 72 hr after cardiac surgery. Most of the patients were male (61.2%), and the mean age was 50 years. The most frequent surgeries were valve replacement (48.8%) and myocardial revascularization (43.8%). AKI was defined as an increase of at least 50%, 0.3 mg/dl or 0.5 mg/dl in baseline serum creatinine. The percentage of participants meeting each of these criteria was 13.2%, 28.1%, and 11.6%, respectively. A progressive increase in cystatin C levels was associated with a worsening of renal function, as classified by RIFLE and AKIN (p < .05). Analysis of the receiver operating characteristic (ROC) curves showed the RIFLE and AKIN classification to have good discriminatory power for the assessment of renal function, with the performance of cystatin C being poorer (area under the curve: 0.804 and 0.794 vs. 0.719). However, combining cystatin C and RIFLE resulted in greater discriminatory power for detecting kidney injury in postoperative patients than any marker in isolation.

  7. Nutritional Interventions that Slow the Age-Associated Decline in Renal Function in a Canine Geriatric Model for Elderly Humans.

    PubMed

    Hall, J A; Yerramilli, M; Obare, E; Yerramilli, M; Panickar, K S; Bobe, G; Jewell, D E

    2016-01-01

    To determine the effects of feeding traditional and renal protective foods (RPF) supplemented with functional food bioactives on glomerular filtration rate (GFR), lean body percent (LB%), and selected circulating biomarker and metabolite concentrations in a geriatric dog model. Randomized block design and cross-sectional study. Hill's Pet Nutrition, Inc. dog colony. Eighty-one geriatric dogs (mean age, 10.4; range, 7.9-14.2 years) and 30 mature-adult dogs (mean age, 5.0; range, 3.3-6.9 years). Geriatric dogs were fed one of three foods (n = 27 per group) for 6 months: a traditional RPF (control) that was energy dense and mildly protein-restricted, or control food supplemented with increasing amounts of functional food bioactives: fish oil, lipoic acid, fruits and vegetables, and higher quality protein sources [functional foods one (FF1) and two (FF2)]. Geriatric dogs were compared before and after the feeding trial with mature adult dogs. Renal function was assessed by GFR, LB% was determined by dual energy x-ray absorptiometry, and circulating biomarkers and metabolites were measured in blood. Before the feeding trial, GFR (+28.2%), LB% (+18.6%), and serum total protein (+10.0%) were higher in mature versus healthy geriatric dogs (all P<0.001). Geriatric dogs consuming all three foods increased (P<0.001) GFR over time; group averages ranged from 13.0-16.9%. Dogs fed the highest supplemented level of bioactives (FF2) had lower (P<0.001) symmetric dimethylarginine (SDMA) concentrations (-14.3%). Feeding functional foods did not alter body weight, but increased (P<0.001) serum protein concentration (+6.7%). Supplementation with functional food bioactives can temporarily reverse the age-associated decline in renal function and serum total protein.

  8. Challenges for environmental epidemiology research: are biomarker concentrations altered by kidney function or urine concentration adjustment?

    PubMed

    Weaver, Virginia M; Kotchmar, Dennis J; Fadrowski, Jeffrey J; Silbergeld, Ellen K

    2016-01-01

    Biomonitoring has become a standard approach for exposure assessment in occupational and environmental epidemiology. The use of biological effect markers to identify early adverse changes in target organs has also become widely adopted. However, the potential for kidney function to affect biomarker levels in the body and the optimal approach to adjustment of biomarker concentrations in spot urine samples for hydration status are two important but underappreciated challenges associated with biomarker use. Several unexpected findings, such as positive associations between urine nephrotoxicant levels and estimated glomerular filtration rate (eGFR), have been reported recently in research using biomarkers. These and other findings, discussed herein, suggest an impact of kidney glomerular filtration or tubule processing on biomarker levels. This is more commonly raised in the context of decreased kidney filtration, traditionally referred to as reverse causality; however, recent data suggest that populations with normal kidney filtration may be affected as well. Misclassification bias would result if biomarkers reflect kidney function as well as either exposures or early biological effect outcomes. Furthermore, urine biomarker associations with eGFR that differ markedly by approach used to adjust for urine concentration have been reported. Associations between urine measures commonly used for this adjustment, such as urine creatinine, and specific research outcomes could alter observed biomarker associations with outcomes. Research recommendations to address the potential impact of kidney function and hydration status adjustment on biomarkers are provided, including a range of approaches to study design, exposure and outcome assessment, and adjustment for urine concentration.

  9. Reference intervals for urinary renal injury biomarkers KIM-1 and NGAL in healthy children

    PubMed Central

    McWilliam, Stephen J; Antoine, Daniel J; Sabbisetti, Venkata; Pearce, Robin E; Jorgensen, Andrea L; Lin, Yvonne; Leeder, J Steven; Bonventre, Joseph V; Smyth, Rosalind L; Pirmohamed, Munir

    2014-01-01

    Aim The aim of this study was to establish reference intervals in healthy children for two novel urinary biomarkers of acute kidney injury, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Materials & Methods Urinary biomarkers were determined in samples from children in the UK (n = 120) and the USA (n = 171) using both Meso Scale Discovery (MSD) and Luminex-based analytical approaches. Results 95% reference intervals for each biomarker in each cohort are presented and stratified by sex or ethnicity where necessary, and age-related variability is explored using quantile regression. We identified consistently higher NGAL concentrations in females than males (p < 0.0001), and lower KIM-1 concentrations in African–Americans than Caucasians (p = 0.02). KIM-1 demonstrated diurnal variation, with higher concentrations in the morning (p < 0.001). Conclusion This is the first report of reference intervals for KIM-1 and NGAL using two analytical methods in a healthy pediatric population in both UK and US-based populations. PMID:24661102

  10. Improvement of Renal Functions After Embolization of Renal AVF in a Patient Who had been on Dialysis for 5 Years

    SciTech Connect

    Ulusoy, Suekrue Oezkan, Guelsuem; Dinc, Hasan; Kaynar, Kuebra; Oeztuerk, Mehmet Halil; Guel, Semih; Kaplan, Safiye Tuba

    2011-02-15

    Recently, ultrasound-guided percutaneous renal biopsy has been used in the diagnosis of renal diseases. Development of an arteriovenous fistula (AVF), which is one of the post-biopsy complications, is not frequently encountered. AVFs are usually asymptomatic; however, they may lead to serious outcomes. We report a 21-year-old patient, who had been on dialysis for 5 years. Due to high blood pressure (230/160 mmHg) and a thrill in the lumbar area detected on physical examination, Doppler examination was performed and a renal AVF was detected. Because the patient had a history of renal biopsy 5 years previously, the fistula was thought to be secondary to the biopsy. After embolization of the AVF, renal functions improved enough to terminate dialysis treatment.

  11. Simple tests of renal function using creatinine, phenolsulphonphthalein, and pitressin

    PubMed Central

    Healy, J. K.; Edwards, K. D. G.; Whyte, H. M.

    1964-01-01

    The reciprocals of the blood urea nitrogen and plasma creatinine levels, the maximum specific gravity of the urine after vasopressin, and three modified forms of the phenolsulphonphthalein (P.S.P.) excretion test were found to be directly related to the glomerular filtration rate (G.F.R.) in hospital patients. From 34 to 75 patients were studied for each test, and in 21 patients all tests were performed concurrently. The plasma creatinine level and the 15-minute urinary excretion of P.S.P. were found to be the most useful simple tests of renal function and gave sufficiently accurate estimates of total function (G.F.R.) to justify their more extensive use. The G.F.R. (ml./min./1·73 sq. m. of body surface area) could be calculated from each test, using the following equations:— [Formula: see text] G.F.R. = 3·15 × P.S.P.% + 19, where P.S.P.% is the 15-minute urinary excretion of P.S.P., expressed as a percentage of the administered dose. Satisfactory estimates of G.F.R. were also given by the simplified relationships [Formula: see text]. In the presence of impaired renal function more accurate estimates of G.F.R. were obtained from the plasma creatinine and P.S.P. excretion tests (S.D. of estimate 8 and 13 ml./min. respectively). It was thought that these tests could well replace the commonly used blood urea nitrogen estimation as simple tests of renal function. PMID:14207792

  12. Serum levels of WNT1-inducible signaling pathway protein-1 (WISP-1): a noninvasive biomarker of renal fibrosis in subjects with chronic kidney disease

    PubMed Central

    Zhong, Xiang; Tu, Yue Ju; Li, Yi; Zhang, Ping; Wang, Wei; Chen, Sha Sha; Li, Li; Chung, Arthur CK; Lan, Hui Yao; Chen, Hai Yong; Li, Gui Sen; Wang, Li

    2017-01-01

    WNT1-inducible signaling pathway protein-1 (WISP-1) is an extracellular matrix-related protein that plays multiple roles in cellular physiology and pathology. Accumulating evidence shows that WISP-1 is involved in the process underlying fibrotic diseases. However, the correlation between WISP-1 and renal fibrosis is unknown. In this study, we hypothesized that WISP-1 levels might be correlated with renal fibrosis and could be used as a noninvasive biomarker to screen for renal fibrosis in patients with chronic kidney disease (CKD). We first measured the WISP-1 expression levels using a transforming growth factor-β (TGF-β)-induced renal fibrosis tubular epithelial cell (TEC) model and a mouse model of obstructive nephropathy. We then evaluated the correlation between serum WISP-1 levels and fibrosis scores in biopsy-proven renal fibrosis of patients with CKD. Based on the findings from both in vivo and in vitro studies, the levels of WISP-1 and fibrotic parameters (collagen I, fibronectin and α-smooth muscle actin) were significantly increased in the fibrotic models. Consistently, patients with focal proliferative IgA nephropathy, focal segmental glomerular sclerosis and diabetic nephropathy displayed markedly elevated serum WISP-1 levels and fibrosis scores of renal biopsies compared with normal subjects and patients with minimal change disease (P<0.05). Importantly, the serum WISP-1 levels were positively correlated with fibrosis scores in the renal biopsies of these patients (r=0.475, P=0.0001). Thus, serum WISP-1 levels may be used as a potential noninvasive biomarker of renal fibrosis in patients with CKD. PMID:28670380

  13. Serum levels of WNT1-inducible signaling pathway protein-1 (WISP-1): a noninvasive biomarker of renal fibrosis in subjects with chronic kidney disease.

    PubMed

    Zhong, Xiang; Tu, Yue Ju; Li, Yi; Zhang, Ping; Wang, Wei; Chen, Sha Sha; Li, Li; Chung, Arthur Ck; Lan, Hui Yao; Chen, Hai Yong; Li, Gui Sen; Wang, Li

    2017-01-01

    WNT1-inducible signaling pathway protein-1 (WISP-1) is an extracellular matrix-related protein that plays multiple roles in cellular physiology and pathology. Accumulating evidence shows that WISP-1 is involved in the process underlying fibrotic diseases. However, the correlation between WISP-1 and renal fibrosis is unknown. In this study, we hypothesized that WISP-1 levels might be correlated with renal fibrosis and could be used as a noninvasive biomarker to screen for renal fibrosis in patients with chronic kidney disease (CKD). We first measured the WISP-1 expression levels using a transforming growth factor-β (TGF-β)-induced renal fibrosis tubular epithelial cell (TEC) model and a mouse model of obstructive nephropathy. We then evaluated the correlation between serum WISP-1 levels and fibrosis scores in biopsy-proven renal fibrosis of patients with CKD. Based on the findings from both in vivo and in vitro studies, the levels of WISP-1 and fibrotic parameters (collagen I, fibronectin and α-smooth muscle actin) were significantly increased in the fibrotic models. Consistently, patients with focal proliferative IgA nephropathy, focal segmental glomerular sclerosis and diabetic nephropathy displayed markedly elevated serum WISP-1 levels and fibrosis scores of renal biopsies compared with normal subjects and patients with minimal change disease (P<0.05). Importantly, the serum WISP-1 levels were positively correlated with fibrosis scores in the renal biopsies of these patients (r=0.475, P=0.0001). Thus, serum WISP-1 levels may be used as a potential noninvasive biomarker of renal fibrosis in patients with CKD.

  14. Non-Chimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers

    PubMed Central

    Leventhal, J.R.; Mathew, J.M.; Salomon, D.R.; Kurian, S.M.; Friedewald, J.J.; Gallon, L.; Konieczna, I.; Tambur, A.R.; charette, j.; Levitsky, J.; Jie, C.; Kanwar, Y. S.; Abecassis, M. M.; Miller, J.

    2015-01-01

    We previously described early results of a non-chimeric operational tolerance protocol in HLA identical living donor renal transplants and now update these results. Recipients given alemtuzumab, tacrolimus/MPA with early sirolimus conversion were multiply infused with donor hematopoietic CD34+ stem cells. Immunosuppression was withdrawn by 24 months. Twelve months later operational tolerance was confirmed by rejection-free transplant biopsies. Five of the first 8 enrollees were initially tolerant one year off immunosuppression. Biopsies of 3 others after total withdrawal showed Banff 1A acute cellular rejection without renal dysfunction. With longer follow-up including 5 year post-transplant biopsies 4 of the 5 tolerant recipients remain without rejection while one developed Banff 1A without renal dysfunction. We now add 7 new subjects (2 operationally tolerant), and demonstrate time-dependent increases of circulating CD4+CD25+++CD127−FOXP3+ Tregs vs. losses of Tregs in non-tolerant subjects (p< 0.001). Gene expression signatures, developed using global RNA expression profiling of sequential whole blood and protocol biopsy samples, were highly associative with operational tolerance as early as 1 year post-transplant. The blood signature was validated by an external ITN data set. Our approach to non-chimeric operational HLA identical tolerance reveals association with Treg immunophenotypes and serial gene expression profiles. PMID:26227106

  15. Proteinuria and baseline renal function predict mortality and renal outcomes after sirolimus therapy in liver transplantation recipients.

    PubMed

    Li, Lung-Chih; Hsu, Chien-Ning; Lin, Chih-Che; Cheng, Yu-Fan; Hu, Tsung-Hui; Chen, Ding-Wei; Lee, Chih-Hsiung; Nakano, Toshiaki; Chen, Chao-Long

    2017-04-20

    Chronic kidney disease is a significant complication after liver transplantation (LT), but the role of pre-existing renal insufficiency and proteinuria remains unclear among LT recipients receiving sirolimus. We assessed the effects of proteinuria and baseline renal function on long-term renal and survival outcomes among 576 LT recipients who received SRL in a medical center between 2005 and 2014. Renal outcomes were the incidences of >50% reduction in their baseline estimated glomerular filtration rate and end stage kidney disease requiring renal replacement therapy. Proteinuria was identified using morning dipstick results (≥30 mg/dL) at baseline and within the first year after the initiation of SRL therapy. A Kaplan-Meier analysis was performed to estimate time to event. Factors associated with the outcomes were determined using the Cox proportional hazards model with a significance level set at P <0.05. During the study period, renal function deteriorated in 135 (25.3%) patients and 68 (11.8%) patients died. Persistent and new onset proteinuria contributed to a high rate of mortality and the deterioration of renal function (both log-rank tests, P <0.0001). After adjustments, new onset proteinuria within the first year after the initiation of SRL therapy increased the risk of deteriorating renal function, regardless of baseline estimated glomerular filtration rate. Moreover, pre-existing (hazard ratio = 1.91; P <0.001) and new onset diabetes (hazard ratio = 2.34; P <0.0001) were significantly associated with new onset proteinuria among SRL users. These findings support the effective monitoring and early management of the predictable risks for proteinuria among new SRL users in order to delay the progression of renal disease.

  16. Cardio-renal interaction: impact of renal function and anemia on the outcome of chronic heart failure.

    PubMed

    Kimura, Hisashi; Hiramitsu, Shinya; Miyagishima, Kenji; Mori, Kazumasa; Yoda, Ryuji; Kato, Shigeru; Kato, Yasuchika; Morimoto, Shin-ichiro; Hishida, Hitoshi; Ozaki, Yukio

    2010-07-01

    The purpose of this study is to investigate the effects of renal function and anemia on the outcome of chronic heart failure (CHF). We targeted 711 consecutive patients who were hospitalized at the Division of Cardiology of Fujita Health University Hospital during a 5-year period. The subjects were divided into four groups according to their estimated glomerular filtration rate (e-GFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula. Intergroup comparisons were conducted for underlying heart diseases, clinical findings at the time of hospitalization, treatment, and outcome. Moreover, the patients were divided into two groups according to their serum hemoglobin concentration at the time of hospitalization, using 12.0 g/dl as the dividing point, to study the effects of anemia on the outcome. In the group with decreased renal function, the average age was higher, and ischemic heart disease and associated conditions such as hypertension and diabetes mellitus were observed in most of the patients. In addition, the rate of anemia development and the plasma B-type natriuretic peptide concentration were also high. The greater the deterioration in renal function, the poorer the outcome became (P < 0.0001). Chronic heart failure complicated by anemia showed an especially poor outcome (P < 0.0001). As this study showed that renal function and anemia significantly affected the outcome of CHF, it is clear that the preservation of renal function and the management of anemia are important in addition to the conventional treatments for CHF.

  17. Modified renal function in pregnancy: impact on emtricitabine pharmacokinetics

    PubMed Central

    Valade, Elodie; Tréluyer, Jean-Marc; Dabis, François; Arrivé, Elise; Pannier, Emmanuelle; Benaboud, Sihem; Fauchet, Floris; Bouazza, Naïm; Foissac, Frantz; Urien, Saïk; Hirt, Déborah

    2014-01-01

    Aims The aims were to describe emtricitabine (FTC) pharmacokinetics in a large population of pregnant women during the different trimesters of pregnancy, and to explain FTC pharmacokinetic variability during pregnancy. Methods FTC plasma concentrations were measured in 103 non-pregnant and 83 pregnant women, including women in the different trimesters of pregnancy and on the day of delivery. A total of 457 plasma concentrations were available for analysis. A population pharmacokinetic model was developed with Monolix 4.1.3. Results FTC pharmacokinetics was best described by a two compartment model. The effect of creatinine clearance on apparent elimination clearance (CL/F) was significant. CL/F in pregnant women was significantly higher compared with non-pregnant women (geometric mean 24.1 vs 20.5 l h−1, P < 0.001), reflecting a modified renal function. FTC daily exposures (AUC) during pregnancy were lower than AUC in non-pregnant women, regardless of the trimester of pregnancy. FTC AUC geometric means were 8.38 mg l−1 h in the second trimester of pregnancy, 8.16 mg l−1 h in the third trimester of pregnancy, 8.30 mg l−1 h on the day of delivery and 9.77 mg l−1 h in non-pregnant women. FTC concentrations 24 h after administration were lower in pregnant women compared with non-pregnant women (0.054 vs. 0.079 mg l−1, P < 0.001) but still above the inhibitory concentration 50%. Conclusions FTC CL/F was increased by 18% during pregnancy, reflecting a modified renal function with 50% increase in estimated glomerular filtration rate. However, the impact of this modified renal function on FTC pharmacokinetics was not sufficiently large to consider dose adjustments during pregnancy. PMID:24995851

  18. Renal Function Following Nephron Sparing Procedures: Simply a Matter of Volume?

    PubMed

    Biles, Michael J; DeCastro, G Joel; Woldu, Solomon L

    2016-01-01

    Partial nephrectomy (PN) is the current standard of care for the management of small renal masses (SRM), providing comparable oncologic control with improved renal functional outcomes. Additionally, new technologies such as thermal ablation provide attractive alternatives to traditional extirpative surgery. The obvious benefit of these nephron sparing procedures (NSPs) is to the preservation of renal parenchymal volume (RPV), but the factors that influence postoperative renal function are complex and inter-related, and include non-modifiable factors such as baseline renal function and tumor size, complexity, and location as well as potentially modifiable factors such as ischemia time, ischemia type, and RPV preservation. Our review presents the most recent evidence analyzing the relationship between the modifiable factors in PN and renal outcomes, with a focus on RPV preservation. Furthermore, novel surgical techniques, imaging modalities, and NSPs are discussed, evaluating their efficacy in maximizing functional nephron mass and improving long-term renal outcomes.

  19. WE-D-204-07: Development of An ImageJ Plugin for Renal Function Quantification: RenalQuant

    SciTech Connect

    Marques da Silva, A; Narciso, L

    2015-06-15

    Purpose: Commercial workstations usually have their own software to calculate dynamic renal functions. However, usually they have low flexibility and subjectivity on delimiting kidney and background areas. The aim of this paper is to present a public domain software, called RenalQuant, capable to semi-automatically draw regions of interest on dynamic renal scintigraphies, extracting data and generating renal function quantification parameters. Methods: The software was developed in Java and written as an ImageJ-based plugin. The preprocessing and segmentation steps include the user’s selection of one time frame with higher activity in kidney’s region, compared with background, and low activity in the liver. Next, the chosen time frame is smoothed using a Gaussian low pass spatial filter (σ = 3) for noise reduction and better delimitation of kidneys. The maximum entropy thresholding method is used for segmentation. A background area is automatically placed below each kidney, and the user confirms if these regions are correctly segmented and positioned. Quantitative data are extracted and each renogram and relative renal function (RRF) value is calculated and displayed. Results: RenalQuant plugin was validated using retrospective 20 patients’ 99mTc-DTPA exams, and compared with results produced by commercial workstation software, referred as reference. The renograms intraclass correlation coefficients (ICC) were calculated and false-negative and false-positive RRF values were analyzed. The results showed that ICC values between RenalQuant plugin and reference software for both kidneys’ renograms were higher than 0.75, showing excellent reliability. Conclusion: Our results indicated RenalQuant plugin can be trustingly used to generate renograms, using DICOM dynamic renal scintigraphy exams as input. It is user friendly and user’s interaction occurs at a minimum level. Further studies have to investigate how to increase RRF accuracy and explore how to solve

  20. Chemical and Physical Sensors in the Regulation of Renal Function

    PubMed Central

    Pluznick, Jennifer L.

    2015-01-01

    In order to assess the status of the volume and composition of the body fluid compartment, the kidney monitors a wide variety of chemical and physical parameters. It has recently become clear that the kidney’s sensory capacity extends well beyond its ability to sense ion concentrations in the forming urine. The kidney also keeps track of organic metabolites derived from a surprising variety of sources and uses a complex interplay of physical and chemical sensing mechanisms to measure the rate of fluid flow in the nephron. Recent research has provided new insights into the nature of these sensory mechanisms and their relevance to renal function. PMID:25280495

  1. Evaluation of renal function in a specific population of living kidney donors.

    PubMed

    de Souza Rodrigues, Thalyta; Amorim de Albuquerque, Ana Letícia; de Oliveira Cosme, Fillipe Agra; de Oliveira, José Ayrton Macedo Guimarães; Magalhães, Indalécio; Teles, Flávio; Pedrosa, André Falcão

    2017-06-01

    The increase in candidates for kidney transplant has led to growth in the number of living donor transplants. Therefore, studies that adequately evaluate the possible long-term consequences of elective transplant nephrectomy are needed. To evaluate the possible long-term adverse effects of transplant nephrectomy on the renal function of living kidney donors. A cross-sectional study. Thirty-three living kidney donors registered in the transplant programme of a centre in Alagoas, Brazil. Demographic characteristics, anthropometric measures, clinical data and biomarkers (creatinine, eGFR, microalbuminuria, cholesterol and triglycerides) were measured. Creatinine clearance was calculated using the Cockcroft-Gault and Modification of Diet in Renal Disease formulae. Of the 33 individuals, 63.63% were female, and the median age was 45 years. Additionally, 24.24% of these individuals had altered blood pressure, 39.39% had altered abdominal circumference (AC) and 36.36% were obese, with a body mass index ≥30. Furthermore, 33.33% of these individuals had elevated triglyceride levels. The average eGFR was 97.33 (33.03-175.9) ml/min/1.73 m(2) (CG) and 84.14 (29.4-131) ml/min/1.73 m(2) (MDRD). The microalbuminuria level was altered in 12.12% patients. Kidney donation is unquestionably a safe procedure. However, a better understanding of the long-term consequences of living donor kidney transplantation is still needed. This knowledge may have important implications for the follow-up of these patients. Our study has demonstrated a non-negligible presence of an early marker of glomerular injury and a decrease in the GFR of some patients, thereby reinforcing the proposal for long-term follow-up of living kidney donors. © 2017 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  2. Stable cystatin C serum levels confirm normal renal function in patients with dronedarone-associated increase in serum creatinine.

    PubMed

    Duncker, David; Oswald, Hanno; Gardiwal, Ajmal; Lüsebrink, Ulrich; König, Thorben; Schreyer, Hendrik; Klein, Gunnar

    2013-03-01

    Dronedarone is a new antiarrhythmic drug for patients with nonpermanent atrial fibrillation (AF). A relatively consistent finding in all trials studying dronedarone was a moderate but significant elevation of serum creatinine. Since dronedarone competes for the same organic cation transporter in the distal renal tubule with creatinine, serum creatinine and its derived estimated glomerular filtration rate might not reflect true renal function in patients on dronedarone. We therefore investigated alternative markers for renal function in these patients. We prospectively included 20 patients with nonpermanent AF in whom dronedarone 400 mg twice daily was started. Patients had normal renal function and serum creatinine; serum cystatin C and creatinine clearance were measured before treatment and 10 and 90 days after treatment started. Mean serum creatinine level for all 20 patients at baseline (day 0) was 84.55 ± 12.14 and 87.8 ± 17.59 µmol/L on day 10. This slight increase in all patients was not significant. Patients were now divided into the predefined groups of "increased creatinine" (increase in serum creatinine level > 1 standard deviation) and "not increased creatinine." Patients with increased creatinine levels (n = 5) showed a significant elevation of serum creatinine levels from day 0 to day 10 (82.4 ± 9.18 to 104.4 ± 12.74 µmol/L; P = .003), whereas change in serum creatinine levels in the not increased creatinine group (n = 15) was not significant. Serum cystatin C levels remained stable in both of these groups (increased creatinine group: 0.76 ± 0.08 to 0.78 ± 0.08 mg/L; P = .65; not increased creatinine group: 0.77 ± 0.108 to 0.77 ± 0.107 mg/L; P = .906). In conclusion, cystatin C represents an easily available and reliable biomarker for estimation of true renal function in patients on dronedarone treatment.

  3. New optical probes for the continuous monitoring of renal function

    NASA Astrophysics Data System (ADS)

    Dorshow, Richard B.; Asmelash, Bethel; Chinen, Lori K.; Debreczeny, Martin P.; Fitch, Richard M.; Freskos, John N.; Galen, Karen P.; Gaston, Kimberly R.; Marzan, Timothy A.; Poreddy, Amruta R.; Rajagopalan, Raghavan; Shieh, Jeng-Jong; Neumann, William L.

    2008-02-01

    The ability to continuously monitor renal function via the glomerular filtration rate (GFR) in the clinic is currently an unmet medical need. To address this need we have developed a new series of hydrophilic fluorescent probes designed to clear via glomerular filtration for use as real time optical monitoring agents at the bedside. The ideal molecule should be freely filtered via the glomerular filtration barrier and be neither reabsorbed nor secreted by the renal tubule. In addition, we have hypothesized that a low volume of distribution into the interstitial space could also be advantageous. Our primary molecular design strategy employs a very small pyrazine-based fluorophore as the core unit. Modular chemistry for functionalizing these systems for optimal pharmacokinetics (PK) and photophysical properties have been developed. Structure-activity relationship (SAR) and pharmacokinetic (PK) studies involving hydrophilic pyrazine analogues incorporating polyethylene glycol (PEG), carbohydrate, amino acid and peptide functionality have been a focus of this work. Secondary design strategies for minimizing distribution into the interstitium while maintaining glomerular filtration include enhancing molecular volume through PEG substitution. In vivo optical monitoring experiments with advanced candidates have been correlated with plasma PK for measurement of clearance and hence GFR.

  4. Impact of Ramadan fasting on renal allograft function.

    PubMed

    Einollahi, B; Lessan-Pezeshki, M; Simforoosh, N; Nafar, M; Pour-Reza-Gholi, F; Firouzan, A; Khatami, M R; Nourbala, M H; Pourfarzini, V

    2005-09-01

    Fasting during the holy month of Ramadan is a religious duty for all healthy adult Muslims. They are only allowed to eat and drink between sunset and dawn. This study was designed to find the effect of Ramadan fasting on allograft function. We prospectively studied 19 kidney transplant recipients who voluntarily chose to fast during Ramadan versus 20 matched recipients, who had not fasted for 3 consecutive years. Data were recorded before, during, and after the fasting month. The mean posttransplant periods in the fasting and control groups were 52.6 +/- 30.3 and 56.6 +/- 30.0 months, respectively. A statistical analysis showed no significant changes in serum creatinine concentrations before and after Ramadan 1.07 +/- 0.24 versus 1.08 +/- 0.22 mg/dL (P > .05) and 1.00 +/- 0.24 versus 1.03 +/- 0.28 mg/dL (P > .05) in fasting and control groups, respectively. The results did not show any adverse effects of fasting in recipients with stable renal function. In conclusion, our study suggests that fasting during the month of Ramadan is safe and has no significant harmful effects on kidney transplant recipients with normal renal function.

  5. Succinate Dehydrogenase B (SDHB): A New Prognostic Biomarker in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Cornejo, Kristine M.; Lu, Min; Yang, Ping; Wu, Shulin; Cai, Chao; Zhong, Wei-de; Olumi, Aria; Young, Robert H.; Wu, Chin-Lee

    2015-01-01

    Succinate dehydrogenase B (SDHB) is a mitochondrial enzyme complex subunit. Loss of SDHB protein expression has been found to correlate with SDHx gene mutations. Little is known about its expression in subtypes of renal cell carcinoma (RCC), and whether it’s a prognostic indicator. Four-hundred-fifty renal epithelial neoplasms were analyzed for SDHB, comprising of clear cell RCC (CCRCC) (n=240), papillary RCC (PRCC) (n=84), chromophobe RCC (ChRCC) (n=49), renal oncocytoma (RO) (n=47), clear cell papillary RCC (CCPRCC) (n=19) and von Hippel Lindau (VHL)- associated CCPRCC-like tumors (n=11). SDHB expression was graded based upon staining intensity using a 4-tiered system (0–3+), in which 3+ was strongest and complete absence was 0. Neoplasms were further categorized based upon staining extent into SDHB-weak (1–2+) and strong (3+). SDHB was strongly preserved in 131/240 (55%) CCRCCs, 84/84 (100%) PRCCs, 49/49 (100%) ChRCCs, 1/19 (5%) CCPRCC, 5/11 (45%) VHL-associated CCPRCC-like tumors and 47/47 (100%) ROs. The remaining 109 CCRCCs (45%), 18 CCPRCCs and 6 VHL-associated CCPRCC-like tumors had weak but preserved SDHB. SDHB expression in CCRCCs with high International Society of Urological Pathology (ISUP) nucleolar grade (G3-G4) correlated significantly with survival (log rank P=0.0004). SDHB is variably expressed in RCCs with clear cell morphology and strongly preserved in most other neoplasms. Therefore, weak staining, particularly in clear neoplasms, should not be misinterpreted as negative. Finally, SDHB expression in CCRCCs with high nucleolar grade (G3-G4) is significantly associated with survival, indicating it may be both a diagnostic and prognostic marker in RCC. PMID:25827535

  6. The importance of bone biomarkers in the diagnosis of renal osteodystrophy.

    PubMed

    Pena, Y T; Soyibo, A K; McGrowder, D; Clarke, T R; Barton, E N

    2010-06-01

    To evaluate the association of serum biochemical markers in patients with chronic kidney disease (CKD) in Jamaica for early detection of renal osteodystrophy (ROD). The study contained two groups: CKD group (221) which consisted of adult patients, from dialysis units and renal clinics, with stage III to V CKD. The control group (237) had adult individuals, from the medical outpatient clinics, with mild and controlled chronic diseases and absence of renal failure. The patients in the study were between 18-80 years of age and gave informed consent to participate in the study. The differences in distribution of demographic, clinical and pathologic variables between the two groups were evaluated. Pearson's chi-squared test and Spearman' rho correlation coefficient test was used, with p < 0.01 considered statistically significant. Data analysis was conducted using the statistical package for the social sciences (SPSS) version 17.0. Among the 221 CKD patients in the study, 174 (78.7%) had ROD based on serum intact parathyroid hormone (iPTH) levels. The majority of patients in the control group did not have bone disease ie 95-96%. The majority of CKD patients (70.0%) had high-turnover (HTO) bone disease compared to 29.3% of patients with low-turnover (LTO) bone disease. Dialysis patients who had HTO bone disease compared with those with LTO had significantly higher levels of iPTH and total serum alkaline phosphatase (ALP). A similar relationship was observed among CKD patients not on dialysis. There was a significant individual variation in bone turnover biochemical markers. A total of 237 patients were recruited in the control group. Based on the levels of iPTH and tALP six of them were found to have bone disease. The majority of these patients with bone disease were diabetic (83.3%) while the other patient had cancer (16.7%). The six patients in the control group with bone disease were within the age cohort of 64-80 years, most of whom were 78 years old. A combination

  7. Plasma Polyunsaturated Fatty Acids and the Decline of Renal Function

    PubMed Central

    Lauretani, Fulvio; Semba, Richard D.; Bandinelli, Stefania; Miller, Edgar R.; Ruggiero, Carmelinda; Cherubini, Antonio; Guralnik, Jack M.; Ferrucci, Luigi

    2009-01-01

    Background Recent studies suggest an association between polyunsaturated fatty acids (PUFAs) and the development of chronic kidney disease. The aim of this study was to examine the relationship between PUFAs and renal function in older adults. Methods We performed a cross-sectional and prospective analysis of 931 adults, ≥65 years old, enrolled in the InCHIANTI study, a population-based cohort in Tuscany, Italy. Plasma PUFAs were measured at enrollment, and creatinine clearance was estimated by the Cockcroft-Gault equation at baseline and after 3-year follow-up. Results At enrollment, participants with higher creatinine clearance had higher concentrations of HDL cholesterol, total plasma PUFAs, plasma n-3 fatty acid (FA), and plasma n-6 FA and lower triglycerides. From enrollment to the 3-year follow-up visit, creatinine clearance declined by 7.8 (12.2) mL/min (P <0.0001). Baseline total plasma PUFAs, n-3 FA, n-6 FA, and linoleic, linolenic, and arachidonic acids were strong independent predictors of less steep decline in creatinine clearance from baseline to follow-up (P <0.0001, after adjusting for baseline creatinine clearance). After adjusting for baseline creatinine, baseline total plasma PUFAs, n-3 FA, and linoleic, linolenic, and arachidonic acids were negatively associated with creatinine at 3-year follow-up. Participants with higher plasma PUFAs at enrollment had a lower risk of developing renal insufficiency, defined by a creatinine clearance <60 mL/min, during 3-year follow-up. Conclusion High PUFA concentrations, both n-3 FA and n-6 FA, may attenuate the age-associated decline in renal function among older community-dwelling women and men. PMID:18202159

  8. Effect of Cydonia oblonga Mill. leaf extracts or captopril on blood pressure and related biomarkers in renal hypertensive rats.

    PubMed

    Zhou, Wen-ting; Abdurahman, Adil; Abdusalam, Elzira; Yiming, Wuliya; Abliz, Parida; Aji, Qimangul; Issak, Mehray; Iskandar, Guldiyar; Moore, Nicholas; Umar, Anwar

    2014-05-14

    Cydonia oblonga Mill. (COM) is used in traditional Uyghur medicine to treat or prevent cardiovascular disease. In a previous study COM leaf extracts were found to be active in renal hypertensive rats (RHR). The present study tests the dose-dependence of the effect of ethanol leaf extracts on hypertension and on biomarkers associated with blood pressure control, such as angiotensin-II (AII), plasma renin activity (PRA), apelin-12 (A), endothelin (ET) and nitric oxide (NO), compared to captopril. Two-kidney one-clip (2K1C) Goldblatt model rats were divided randomly into six groups: sham, model, captopril 25 mg/kg, COM leaf extract 80, 160 and 320 mg/kg (n=10 each). Drugs were administered orally daily for eight weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before treatment and every 2 weeks. Blood and kidney samples were collected after the last treatment to measure AII, PRA, A, ET and NO. RHR had increased blood pressure, AII, A, PRA, ET and decreased NO. Treatment with captopril reduced blood pressure, AII, A, PRA, and ET, though not quite to normal values. COM leaf extracts significantly and dose-dependently reduced blood pressure, AII, A, RA and ET, whereas NO was increased. The highest dose of COM had the same effects as captopril. The effects of COM extracts on blood pressure and biomarkers were dose-dependent and at the highest dose similar to those of captopril. This suggests an action of COM on the renin-angiotensin system, which could explain its antihypertensive effect. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Renal ultrastructure, renal function, and parameters of lead toxicity in workers with different periods of lead exposure

    PubMed Central

    CramÉr, Kim; Goyer, Robert A.; Jagenburg, Rudolf; Wilson, Marion H.

    1974-01-01

    Cramér, K., Goyer, R. A., Jagenburg, R., and Wilson, Marion H. (1974).British Journal of Industrial Medicine,31, 113-127. Renal ultrastructure, renal function, and parameters of lead toxicity in workers with different periods of lead exposure. Renal biopsies were obtained from five men with heavy occupational exposure to lead and compared with studies of their renal function and parameters of lead toxicity. Two men had lead exposure of less than one year while three men had been exposed for from four to more than 30 years. In addition, renal function studies were performed in two men from whom renal biopsies could not be obtained. Their lead exposures were five and 12 years, respectively. Significantly lower plasma levels, when compared with non-exposed controls, were found for proline, valine, tyrosine, and phenylalanine although no excessive aminoaciduria was found. Renal function tests were normal in all except for a reduced glomerular filtration rate (GFR) in one worker. Plasma ALA was measured by a new and highly specific method and ALA clearance was found to follow GFR closely. Those workers with prolonged lead exposure showed a lower urinary lead excreation. Typical lead-induced intranuclear inclusion bodies were found only in those with short exposure. The ultrastructural changes were localized to the proximal tubules, while the glomeruli were only nonspecifically affected. Mitochondrial changes were found in all men. Reasons for the decrease in inclusion body formation in chronic lead nephropathy are uncertain but may be due to an increased rate of renal cell turnover or a consequence of chelation therapy. Images PMID:4830763

  10. Clinical, functional, behavioural and epigenomic biomarkers of obesity.

    PubMed

    Lafortuna, Claudio L; Tovar, Armando R; Rastelli, Fabio; Tabozzi, Sarah A; Caramenti, Martina; Orozco-Ruiz, Ximena; Aguilar-Lopez, Miriam; Guevara-Cruz, Martha; Avila-Nava, Azalia; Torres, Nimbe; Bertoli, Gloria

    2017-06-01

    Overweight and obesity are highly prevalent conditions worldwide, linked to an increased risk for death, disability and disease due to metabolic and biochemical abnormalities affecting the biological human system throughout different domains. Biomarkers, defined as indicators of biological processes in health and disease, relevant for body mass excess management have been identified according to different criteria, including anthropometric and molecular indexes, as well as physiological and behavioural aspects. Analysing these different biomarkers, we identified their potential role in diagnosis, prognosis and treatment. Epigenetic biomarkers, cellular mediators of inflammation and factors related to microbiota-host interactions may be considered to have a theranostic value. Though, the molecular processes responsible for the biological phenomenology detected by the other analysed markers, is not clear yet. Nevertheless, these biomarkers possess valuable diagnostic and prognostic power. A new frontier for theranostic biomarkers can be foreseen in the exploitation of parameters defining behaviours and lifestyles linked to the risk of obesity, capable to describe the effects of interventions for obesity prevention and treatment which include also behaviour change strategies.

  11. Potential biomarkers of human salivary function: a modified proteomic approach

    PubMed Central

    Rudney, J.D.; Staikov, R.K.; Johnson, J.D.

    2009-01-01

    Summary Objective In previous studies, we defined groups of subjects with opposite salivary function. Group membership was associated with clinically-relevant outcomes. High aggregation-adherence (HAA) groups showed lower levels of caries, supragingival plaque, total streptococci, and Tannerella forsythensis than low high aggregation-adherence (LAA) groups. In this study, we used a proteomic approach to search for biomarkers which could be useful as risk indicators for those outcomes. Design Clarified resting whole saliva from each of 41 HAA and LAA subjects was separated by preparative isoelectric focusing. Fractions showing the most distinctive protein profiles were pooled into four sets (pI 3–3.5, pI 4–4.7, pI 5.7–7.7, pI 10–11.5). Each pool then was compared by SDS-PAGE. Image analysis software was used to quantify matched bands. Partial least squares analysis (PLS) was used to determine which of the 65 bands from all four pools were the best predictors of group membership, caries, total plaque, total streptococci, and T. forsythensis counts. Those bands were identified by mass spectroscopy (MSMS). Results Two bands consistently were strong predictors in separate PLS analyses of each outcome variable. In follow-up univariate analyses, those bands showed the strongest significant differences between the HAA and LAA groups. They also showed significant inverse correlations with caries and all the microbiological variables. MSMS identified those bands as statherin, and a truncated cystatin S missing the first eight N-terminal amino acids. Conclusions Levels of statherin and truncated cystatin S may be potential risk indicators for the development of caries and other oral diseases. PMID:18804197

  12. Alkaline Phosphatase: A Biomarker of Cardiac Function in Pediatric Patients.

    PubMed

    Makil, Elizabeth S; Tang, Xinyu; Frazier, Elizabeth A; Collins, R Thomas

    2017-02-09

    Myocardial dysfunction and heart failure are common in pediatric patients with congenital and acquired heart disease. Alkaline phosphatase (AP) has been suggested as a biomarker for myocardial dysfunction after Fontan operation. We hypothesized that pediatric patients with myocardial dysfunction requiring orthotopic heart transplant (OHT) have diminished AP compared to normal. A retrospective review was performed in all patients who underwent OHT at Arkansas Children's Hospital between January 2007 and October 2012. Anatomic diagnoses, therapeutic interventions, and ventricular ejection fraction (EF) were recorded. Z scores for AP levels in the study group were determined by comparing the observed AP levels to age- and gender-matched normative values. T tests were performed to compare the mean AP Z score prior to and after OHT. p values <0.05 were considered statistically significant. During the study period, 124 OHTs were performed. Complete study data were available and analyzed from 71/124 patients (mean age at OHT 3.9 years; 51% female). The mean AP Z score was significantly lower in the study group prior to OHT compared to normal (p < 0.0001). The initiation of ACE inhibitor therapy prior to OHT was associated with a significant increase in AP and the ventricular EF (p < 0.001 for both). Treatment with milrinone was associated with an increase in EF. AP is significantly lower in pediatric patients with myocardial dysfunction prior to OHT compared to normal. AP increases significantly after the initiation of therapies to improve myocardial function. Diminished AP is an indicator of myocardial dysfunction in pediatric patients.

  13. Alteration of renal function of rats following spaceflight.

    PubMed

    Wade, C E; Morey-Holton, E

    1998-10-01

    Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

  14. Alteration of renal function of rats following spaceflight

    NASA Technical Reports Server (NTRS)

    Wade, C. E.; Morey-Holton, E.

    1998-01-01

    Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

  15. Quantitation of renal function with technetium-99m MAG3

    SciTech Connect

    Russell, C.D.; Thorstad, B.L.; Yester, M.V.; Stutzman, M.; Dubovsky, E.V.

    1988-12-01

    The technetium-labeled hippuran analog (/sup 99m/Tc)MAG3 was compared with ( T I)hippuran in 50 patients using a quantitative renal function protocol that includes: (a) estimation of effective renal plasma flow by a single-injection, single-sample plasma clearance method, (b) determination of relative function of right and left kidney from the initial count rate over each kidney, and (c) comparison of recovered urine activity with plasma disappearance. This protocol is suitable for routine clinical use, and, in fact, has been used heavily at our clinic for a number of years. By slight modification of the formulas, the results obtained with (/sup 99m/Tc)MAG3 agreed well with those using ( T I)hippuran. We conclude that (/sup 99m/Tc)MAG3 can be substituted for ( T I)hippuran in the quantitative protocol, with the better image quality and lower radiation dose (in abnormals) of a technetium-labeled agent.

  16. Benefits of preserving residual renal function in peritoneal dialysis.

    PubMed

    Marrón, B; Remón, C; Pérez-Fontán, M; Quirós, P; Ortíz, A

    2008-04-01

    Residual renal function (RRF) is of paramount importance in patients with end-stage renal disease, with benefits that go beyond contributing to achievement of adequacy targets. Several studies have found that RRF rather than overall adequacy (as estimated from total small solute removal rates) is an essential marker of patient and, to a lesser extent, technique survival during chronic peritoneal dialysis (PD) therapy. In addition, RRF is associated with a reduction in blood pressure and left ventricular hypertrophy, increased sodium removal and improved fluid status, lower serum beta(2)-microglobulin, phosphate and uric acid levels, higher serum hemoglobin and bicarbonate levels, better nutritional status, a more favorable lipid profile, decreased circulating inflammatory markers, and lower risk for peritonitis in PD. As compared with conventional hemodialysis, PD is associated with a slower decrease in RRF. This highlights the usefulness of strategies oriented to preserve both RRF and the long-term viability of the peritoneal membrane. Several factors contributing to the loss of RRF have been identified and should be avoided. Renoprotective drugs and new glucose-sparing, more biocompatible PD regimes may prove useful tools to preserve RRF and peritoneal membrane function in the near future.

  17. Alteration of renal function of rats following spaceflight

    NASA Technical Reports Server (NTRS)

    Wade, C. E.; Morey-Holton, E.

    1998-01-01

    Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

  18. Genetic Association for Renal Traits among Participants of African Ancestry Reveals New Loci for Renal Function

    PubMed Central

    Tin, Adrienne; Kottgen, Anna; Franceschini, Nora; Peralta, Carmen A.; de Boer, Ian H.; Lu, Xiaoning; Atkinson, Elizabeth; Ding, Jingzhong; Nalls, Michael; Shriner, Daniel; Coresh, Josef; Kutlar, Abdullah; Bibbins-Domingo, Kirsten; Siscovick, David; Akylbekova, Ermeg; Wyatt, Sharon; Astor, Brad; Mychaleckjy, Josef; Li, Man; Reilly, Muredach P.; Townsend, Raymond R.; Adeyemo, Adebowale; Zonderman, Alan B.; de Andrade, Mariza; Turner, Stephen T.; Mosley, Thomas H.; Harris, Tamara B.; Rotimi, Charles N.; Liu, Yongmei; Kardia, Sharon L. R.; Evans, Michele K.; Shlipak, Michael G.; Kramer, Holly; Flessner, Michael F.; Dreisbach, Albert W.; Goessling, Wolfram; Cupples, L. Adrienne; Kao, W. Linda; Fox, Caroline S.

    2011-01-01

    Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m2), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10−7) and FNDC1 (p-value = 3.0×10−7) for UACR, and KCNQ1 with eGFR (p = 3.6×10−6). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish. PMID:21931561

  19. Atherosclerotic renal artery stenosis in the post-CORAL era part 1: the renal penumbra concept and next-generation functional diagnostic imaging.

    PubMed

    Sag, Alan Alper; Inal, Ibrahim; Okcuoglu, John; Rossignol, Patrick; Ortiz, Alberto; Afsar, Baris; Sos, Thomas A; Kanbay, Mehmet

    2016-04-01

    After three neutral trials in which renal artery stenting failed to improve renal function or reduce cardiovascular and renal events, the controversy surrounding diagnosis and treatment of atherosclerotic renal artery stenosis and renovascular hypertension has led to paradigm shifts in the diagnostic algorithm. Noninvasive determination of earlier events (cortex hypoxia and renal artery hemodynamic changes) will supersede late sequelae (calcific stenosis, renal cortical thinning). Therefore, this review proposes the concept of renal penumbra in defining at-risk ischemic renal parenchyma. The complex field of functional renal magnetic resonance imaging will be reviewed succinctly in a clinician-directed fashion. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  20. Nephrotic range proteinuria as a strong risk factor for rapid renal function decline during pre-dialysis phase in type 2 diabetic patients with severely impaired renal function.

    PubMed

    Kitai, Yuichiro; Doi, Yohei; Osaki, Keisuke; Sugioka, Sayaka; Koshikawa, Masao; Sugawara, Akira

    2015-12-01

    Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function. 125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein-creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation. In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51-1.46) ml/min/1.73 m(2) per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24-1.25] versus 1.07 [0.64-1.54] ml/min/1.73 m(2) per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium-phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08-14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m(2) per month. Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

  1. Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease.

    PubMed

    Missailidis, Catharina; Hällqvist, Jenny; Qureshi, Abdel Rashid; Barany, Peter; Heimbürger, Olof; Lindholm, Bengt; Stenvinkel, Peter; Bergman, Peter

    2016-01-01

    The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population. To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality. Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3-5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed. GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3-5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32-14.2; p = 0.016). Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3-5 patients.

  2. Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease

    PubMed Central

    Missailidis, Catharina; Hällqvist, Jenny; Qureshi, Abdel Rashid; Barany, Peter; Heimbürger, Olof; Lindholm, Bengt

    2016-01-01

    Background The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population. Objective To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality. Methods Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3–5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed. Results GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3–5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32–14.2; p = 0.016). Conclusion Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3–5 patients. PMID:26751065

  3. Effects of exposure to low levels of environmental cadmium on renal biomarkers.

    PubMed Central

    Noonan, Curtis W; Sarasua, Sara M; Campagna, Dave; Kathman, Steven J; Lybarger, Jeffrey A; Mueller, Patricia W

    2002-01-01

    We conducted a study among residents of a small community contaminated with heavy metals from a defunct zinc smelter and residents from a comparison community to determine whether biologic measures of cadmium exposure were associated with biomarkers of early kidney damage. Creatinine-adjusted urinary cadmium levels did not differ between the smelter and comparison communities; thus we combined individuals from both communities (n = 361) for further analyses. The overall mean urinary cadmium level was low, 0.26 microg/g creatinine, similar to reference values observed in the U.S. general population. For children ages 6-17 years, urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and albumin were positively associated with urinary cadmium, but these associations did not remain statistically significant after adjusting for urinary creatinine and other potential confounders. For adults ages 18 or older, urinary concentration of NAG, AAP, and albumin were positively associated with urinary cadmium. The associations with NAG and AAP but not with albumin remained statistically significant after adjusting for creatinine and other potential confounders. We found a positive dose-effect relationship between levels of creatinine-adjusted urinary cadmium and NAG and AAP activity, and statistically significant differences in mean activity for these two enzymes between the highest (> or =1.0 microg cadmium/g creatinine) and the lowest (< or =0.25 microg cadmium/g creatinine) exposure groups. The findings of this study indicate that biologic measures of cadmium exposure at levels below 2.0 microg/g creatinine may produce measurable changes in kidney biomarkers. PMID:11836143

  4. Biomarker discovery: success as a function of risk mitigation.

    PubMed

    Weiser, Stefan

    2016-01-01

    Protein biomarker discovery is a fascinating enterprise; however, success in terms of products for in vitro diagnostic use is sparse. New developments in mass spectrometry-based quantitative proteomics as discovery technology have opened up new avenues for this endeavor. In addition to choice of technology, sample properties, study design and validation strategy are potent pillars required for project success. The challenge for successful biomarker discovery can be described by a series of risks that need to be mitigated. This article intends to describe the major risks along with possible solutions.

  5. Renal tubular function in children with beta-thalassemia minor.

    PubMed

    Kalman, Süleyman; Atay, A Avni; Sakallioglu, Onur; Ozgürtaş, Taner; Gök, Faysal; Kurt, Ismail; Kürekçi, A Emin; Ozcan, Okan; Gökçay, Erdal

    2005-10-01

    beta-thalassemia minor is a common heterozygous haemoglobinopathy that is characterized by both microcytosis and hypochromia. It requires no treatment. It has been postulated that low-grade haemolysis, tubular iron deposition and toxins derived from erythrocytes might cause renal tubular damage in adult patients with beta-thalassemia minor. Our aim was to investigate the renal tubular functions in children with beta-thalassemia minor and to determine its possible harmful effects. The study was conducted on 32 children (14 female and 18 male) at the age of 5.8 +/- 3.1 years (range 2-14 years) with beta-thalassemia minor. The patients were classified as anaemic (haemoglobin (Hb) 11 g/dL) (Group 2, n = 18). A control group was formed with 18 healthy children whose ages and sexes match those in other groups (Group 3, n = 18). Fractional excretion of sodium (FE(Na), %), fractional excretion of magnesium (FE(Mg), %), fractional excretion of uric acid (FE(UA), %) and tubular phosphorus reabsorption (TPR,%) were calculated with standard formulas. Urinary calcium excretion (mg/kg per 24 h), zinc (Zn) (microg/dL), glucosuria (mg/dL), beta-2 microglobulin (mg/dL) and N-acetyl-beta-D-glycosaminidase (NAG, U/mmol creatinine) levels were measured through biochemical methods. There was no statistically significant difference among the three groups in terms of the results of FE(Na) (%), FE(Mg) (%), FE(UA) (%), TPR (%), calciuria (mg/kg per 24 h), NAG, urine Zn, proteinuria, glucosuria or urine beta- 2 microglobulin levels (P > 0.05). On the contrary of children with beta-thalassemia major, renal tubular dysfunction has not been determined in children with beta-thalassemia minor in the present study.

  6. Xeropreservation of Functionalized Lipid Biomarkers in Hyperarid Soils in the Atacama Desert, Chile

    NASA Astrophysics Data System (ADS)

    Wilhelm, M. B.; Davila, A. F.; Eigenbrode, J. L.; Parenteau, M. N.; Jahnke, L. L.; Liu, X.; Summons, R. E.; Stamos, B. N.; Wray, J. J.; O'Reilly, S. S.; Williams, A. J.

    2016-05-01

    The preservation of lipid biomarkers was investigated in hyperarid soils with depth in the Atacama Desert. Clays sealed from rainwater for 2 Ma contained functionalized lipids, indicating that minimal degradation has occurred since their deposition.

  7. Renal effects of nabumetone, a COX-2 antagonist: impairment of function in isolated perfused rat kidneys contrasts with preserved renal function in vivo.

    PubMed

    Reichman, J; Cohen, S; Goldfarb, M; Shina, A; Rosen, S; Brezis, M; Karmeli, F; Heyman, S N

    2001-01-01

    The constitutive cyclooxygenase (COX)-1 enzyme has been considered the physiologically important isoform for prostaglandin synthesis in the normal kidney. It has, therefore, been suggested that selective inhibitors of the 'inducible' isoform (COX-2) may be free from renal adverse effects. We studied the renal effects of the predominantly COX-2 antagonist nabumetone in isolated perfused kidneys. As compared with controls, kidneys removed after in vivo administration of oral nabumetone (15 mg/kg) disclosed altered renal function with reduced glomerular filtration rate, filtration fraction, and urine volume and enhanced hypoxic outer medullary tubular damage. By contrast, renal function and morphology were not affected in vivo by nabumetone or its active metabolite 6-methoxy-2-naphthylacetic acid. The latter agent (10-20 mg/kg i.v.) did not significantly alter renal microcirculation, as opposed to a selective substantial reduction in medullary blood flow noted with the nonselective COX inhibitor indomethacin (5 mg/kg i.v.). In a rat model of acute renal failure, induced by concomitant administration of radiocontrast, nitric oxide synthase, and COX inhibitors, the decline in kidney function and the extent of hypoxic medullary damage with oral nabumetone (80 mg/kg) were comparable to a control group, and significantly less than those induced by indomethacin. In rats subjected to daily oral nabumetone for 3 consecutive weeks, renal function and morphology were preserved as well. Both nabumetone and 6-methoxy-2-naphthylacetic acid reduced renal parenchymal prostaglandin E2 to the same extent as indomethacin. It is concluded that while nabumetone adversely affects renal function and may intensify hypoxic medullary damage ex vivo, rat kidneys are not affected by this agent in vivo, both in acute and chronic studies. COX selectivity may not explain the renal safety of nabumetone.

  8. Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat: Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers

    PubMed Central

    Sereno, José; Nunes, Sara; Rodrigues-Santos, Paulo; Rocha-Pereira, Petronila; Fernandes, João; Teixeira, Frederico; Reis, Flávio

    2014-01-01

    Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (n = 6) were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks). Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-β, NF-κ β, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-β and IL-7, TBARs clearance, and kidney TGF-β and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL. PMID:24971338

  9. Extracellular vesicles: structure, function, and potential clinical uses in renal diseases

    PubMed Central

    Borges, F.T.; Reis, L.A.; Schor, N.

    2013-01-01

    Interest in the role of extracellular vesicles in various diseases including cancer has been increasing. Extracellular vesicles include microvesicles, exosomes, apoptotic bodies, and argosomes, and are classified by size, content, synthesis, and function. Currently, the best characterized are exosomes and microvesicles. Exosomes are small vesicles (40-100 nm) involved in intercellular communication regardless of the distance between them. They are found in various biological fluids such as plasma, serum, and breast milk, and are formed from multivesicular bodies through the inward budding of the endosome membrane. Microvesicles are 100-1000 nm vesicles released from the cell by the outward budding of the plasma membrane. The therapeutic potential of extracellular vesicles is very broad, with applications including a route of drug delivery and as biomarkers for diagnosis. Extracellular vesicles extracted from stem cells may be used for treatment of many diseases including kidney diseases. This review highlights mechanisms of synthesis and function, and the potential uses of well-characterized extracellular vesicles, mainly exosomes, with a special focus on renal functions and diseases. PMID:24141609

  10. Renal function and long-term decline in cognitive function: the Baltimore Longitudinal Study of Aging.

    PubMed

    Seliger, Stephen L; Wendell, Carrington R; Waldstein, Shari R; Ferrucci, Luigi; Zonderman, Alan B

    2015-01-01

    Renal disease has been associated with greater risk of dementia and greater cognitive impairment. However, the relationship of lower renal function with long-term decline in specific domains of cognitive function remains unclear among community-dwelling, non-demented individuals. Stroke- and dementia-free participants (n = 2,116) were enrolled in the Baltimore Longitudinal Study of Aging, a community-based, prospective, longitudinal study. Renal function was estimated by the inverse of serum creatinine adjusted for age, sex and race and (in sensitivity analyses) estimated glomerular filtration rate (eGFR) using the MDRD formula. Outcome measures were changes in scores on 6 cognitive tests encompassing a range of cognitive functions, measured at 2-year intervals. Mixed-effects regression models examined the longitudinal relations of renal function with cognitive functions after adjusting for demographics, comorbidity and other potential confounders. Mean age at initial testing was 53.9 years (SD 17.1), and 94 participants (4.4%) had an eGFR <60 ml/min/1.73 m(2) and 18.5% had at least one comorbidity. With increasing age, longitudinal increases in creatinine concentrations were associated with more rapid decline in performance on several cognitive measures, including the learning slope of the California Verbal Learning Test, a test of verbal learning (p < 0.01), and the Benton Visual Retention Test, a test of visual memory (p < 0.01). Associations were similar for changes in eGFRMDRD, which was also associated with the rate of decline in verbal memory. In a community-based adult population, declines in renal function independently associated with greater long-term declines in visual memory and verbal memory and learning. © 2015 National Institutes of Health (NIH). Published by S. Karger AG, Basel.

  11. The association of simple renal cysts with abdominal aortic aneurysms and their impact on renal function after endovascular aneurysm repair.

    PubMed

    Spanos, Konstantinos; Rountas, Christos; Saleptsis, Vasileios; Athanasoulas, Athanasios; Fezoulidis, Ioannis; Giannoukas, Athanasios D

    2016-04-01

    We validated the association of simple renal cysts with abdominal aortic aneurysm and other cardiovascular factors and assessed simple renal cysts' impact on renal function before and after endovascular abdominal aortic aneurysm repair. A retrospective analysis of prospectively collected data was conducted. Computed tomography angiograms of 100 consecutive male patients with abdominal aortic aneurysm who underwent endovascular abdominal aortic aneurysm repair (Group 1) were reviewed and compared with 100 computed tomography angiogram of aged-matched male patients without abdominal aortic aneurysm (Group 2). Patients' demographic data, risk factors, abdominal aortic aneurysm diameter, the presence of simple renal cyst and laboratory tests were recorded. No difference was observed between the two groups in respect to other cardiovascular risk factors except hyperlipidemia with higher prevalence in Group 1 (p < 0.05). Presence of simple renal cysts was independently associated with age (p < 0.05) and abdominal aortic aneurysm (p = 0.0157). There was no correlation between simple renal cysts and abdominal aortic aneurysm size or pre-operative creatinine and urea levels. No difference was observed in post-operative creatinine and urea levels either immediately after endovascular abdominal aortic aneurysm repair or in 12-month follow-up. In male patients, the presence of simple renal cysts is associated with abdominal aortic aneurysm and is increasing with age. However, their presence is neither associated with impaired renal function pre-endovascular abdominal aortic aneurysm repair and post-endovascular abdominal aortic aneurysm repair nor after 12-month follow-up.

  12. Regulation of Vascular and Renal Function by Metabolite Receptors*

    PubMed Central

    Peti-Peterdi, János; Kishore, Bellamkonda K.; Pluznick, Jennifer L.

    2016-01-01

    To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis—from salt and water balance to metabolism—by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families—(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and (c) short-chain fatty acid receptors—we emphasize the unique and important roles that these receptors play in renal and vascular physiology and pathophysiology. PMID:26667077

  13. Cystatin C and renal function in pediatric kidney transplant recipients.

    PubMed

    Franco, M C P; Nagasako, S S; Machado, P G; Nogueira, P C K; Pestana, J O M; Sesso, R

    2009-12-01

    In clinical practice, the glomerular filtration rate (GFR) is often determined with serum creatinine. However, studies have shown cystatin C to be a better parameter for the diagnosis of impaired renal function. We compared GFR estimated by plasma cystatin C with GFR estimated by serum creatinine in a sample of 50 pediatric renal transplant recipients and 24 healthy children. The correlation between GFR estimated by serum creatinine and by cystatin C was significant (r = 0.75; P < 0.001, Person's correlation); however, in pediatric kidney transplant recipients, the GFR was 6.7 mL/min lower when determined using cystatin C rather than serum creatinine. Moreover, using GFR estimated by cystatin C we found that 42% of the pediatric kidney transplant recipients had an estimated GFR <60 mL.min-1.1.73 (m(2))-1, whereas when GFR was estimated by the serum creatinine formula only 16% of the children had values below this cutoff point indicative of chronic kidney disease (P < 0.001). We conclude that, in pediatric kidney transplant recipients, estimation of GFR yields lower values when cystatin C is used rather than serum creatinine.

  14. Renal function in sheep during infusion of alkali metal ions into the renal artery.

    PubMed Central

    Beal, A M; Harrison, F A

    1975-01-01

    1. The effect on renal function of 1 M solutions of LiCl, NaCl, KCl, RbCl and CsCl and 3 M-NaCl infused close-arterially to the kidney for 10 min at 0-7ml./min has been studied in nine experiments on four unilaterally nephrectomized sheep. The levels of flow, electrolyte concentration and electrolyte excretion in the urine were measured before, during and for 50 min after the infusions. 2. The infusion of 1-M-NaCl produced little change in urine flow and composition whereas 3 M-NaCl resulted in relatively small increases in urine flow and sodium excretion. 3. The infusion of lithium, potassium, rubidium and caesium resulted in marked increases in urine flow, urinary sodium concentration and excretion, urinary potassium excretion and osmolal clearance while the urinary potassium concentration decreased. 4. Changes in urine flow and urinary pH during the infusions of all the alkali ions except sodium were consistent with increased urinary bicarbonate excretion. 5. The osmolal clearance was increased by the infusion of lithium, potassium, rubidium and caesium, but equivalent increases in the rate of solutefree water reabsorption did not occur. 6. The infusion of caesium resulted in a depression of the glomerular filtration rate (G.F.R.) which was not observed when the other alkali ions were infused. 7. The effects of lithium, potassium and rubidium on urine flow and composition were rapid in onset and the residual effects on these ions, on cessation of infusion, were relatively short. The effects on caesium were slow in onset and prolonged in duration. 8. It was concluded that lithium, potassium, rubidium, and caesium altered urine flow and electrolyte excretion by acting upon common mechanisms which were predominantly intra-renal and located in the proximal segment of the nephron. PMID:236381

  15. Preserving Renal Function through Partial Nephrectomy Depends on Tumor Complexity in T1b Renal Tumors

    PubMed Central

    2017-01-01

    This study aimed to determine patients with T1b renal cell carcinoma (RCC) who could benefit from partial nephrectomy (PN) and method to identify them preoperatively using nephrometry score (NS). From a total of 483 radical nephrectomy (RN)-treated patients and 40 PN-treated patients who received treatment for T1b RCC between 1995 and 2010, 120 patients identified through 1:2 propensity-score matching were included for analysis. Probability of chronic kidney disease (CKD) until postoperative 5-years was calculated and regressed with respect to the surgical method and NS. Median follow-up was 106 months. CKD-probability at 5-years was 40.7% and 13.5% after radical and PN, respectively (P = 0.005). While PN was associated with lower risk of CKD regardless of age, comorbidity, preoperative estimated renal function, the effect was observed only among patients with NS ≤ 8 (P < 0.001) but not in patients with NS ≥ 9 (P = 0.746). Percent operated-kidney volume reduction and ischemia time were similar between the patients with NS ≥ 9 and ≤ 8. In the stratified Cox regression accounting for the interaction observed between the surgical method and the NS, PN reduced CKD-risk only in patients with NS ≤ 8 (hazard ratio [HR], 0.054; P = 0.005) but not in ≥ 9 (HR, 0.996; P = 0.994). In T1b RCC with NS ≥ 9, the risk of postoperative CKD was not reduced following PN compared to RN. Considering the potential complications of PN, minimally invasive RN could be considered with priority in this subgroup of patients. PMID:28145654

  16. Effects of flurbiprofen on renal function in patients with moderate renal insufficiency.

    PubMed Central

    Murray, M D; Greene, P K; Brater, D C; Manatunga, A K; Hall, S D

    1992-01-01

    1. Renal function was assessed in eight patients with chronic renal insufficiency following the administration of flurbiprofen 50 mg as a single dose and after chronic administration of 50 mg four times daily for 8 and 27 days. Diet and fluid intake were controlled. 2. Inulin and creatinine clearances and urinary excretion of sodium were measured at baseline and every 20 min for at least 3 h after dosing. The time of the mean peak concentration of (S)-flurbiprofen was used to guide the analysis of the clearances. Creatinine clearance, urinary excretion of sodium, and serum sodium and potassium were also assessed for 24 h after the dose and on a daily basis. Body weight and blood pressure were measured on a daily basis. 3. Decrements in inulin and creatinine clearances were small and reversible within 3 h of an oral dose of flurbiprofen. Comparison of baseline clearances for the three study periods (first dose and at 8 and 27 days of chronic dosing) revealed a lack of chronic effect on glomerular filtration rate. 4. In contrast, flurbiprofen caused a substantial (73 to 86%) and progressive decrease in the urinary excretion of sodium that reached a nadir within 4-5 h after drug administration. However, comparison of baseline values did not differ, indicating that balance conditions had been re-established. 5. Results of 24 h assessments were in agreement with the clearance study results. Reduced urinary excretion of sodium appeared to be limited to the first few days of flurbiprofen administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1576067

  17. Black tea improves endothelial function in renal transplant recipients.

    PubMed

    Ardalan, M R; Tarzamni, M K; Shoja, M M; Tubbs, R S; Rahimi-Ardabili, B; Ghabili, K; Khosroshahi, H T

    2007-05-01

    Endothelial damage and dysfunction are commonplace in renal transplant recipients. Impaired endothelial function is an important contributor to cardiovascular diseases. We hypothesized that short-term black tea consumption may improve endothelium-dependent arterial dilation in kidney recipients. Fifteen recipients were studied on an outpatient basis in a single, university-affiliated clinic. Inclusion criteria were stable and good allograft function. The main exclusion criteria were uncontrolled hypertension, smoking, alcohol consumption, coffee drinking, diabetes mellitus, and coronary artery disease, or a history of upper limb vascular manipulations. After overnight fasting, the brachial artery diameter (BAD) was measured at the end of diastole using an ultrasound machine before (basal BAD) and 1 minute after temporary ( approximately 3 minutes) external occlusion (posthyperemia BAD). Flow-mediated vasodilation (FMV) and percent of FMV (FMV%) were calculated by appropriate formula. FMV and FMV% were determined at baseline and 2 hours after consuming 0.5 L freshly brewed black tea. For control, the study was repeated for each patient the next day and FMV and FMV% were determined before and 2 hours after consuming 0.5 L of water. The men age of patients was 37.2 +/- 9.7 years (range, 25 to 50) with a male:female ratio of 3:2. Patients were 26.8 +/- 10.6 months postrenal transplantation. Black tea consumption significantly increased posthyperemia BAD, FMV, and FMV% (P<.05). However, water consumption did not alter the basal or posthyperemia BAD, FMV, or FMV% (P>.05). Based on our study, short-term consumption of black tea may improve endothelial function and endothelium-dependent arterial vasodilation in renal transplant recipients.

  18. Predictive biomarker candidates to delineate efficacy of antiangiogenic treatment in renal cell carcinoma.

    PubMed

    Romero-Laorden, N; Doger, B; Hernandez, M; Hernandez, C; Rodriguez-Moreno, J F; Garcia-Donas, J

    2016-01-01

    Antiangiogenic therapy is currently considered as the cornerstone of treatment in metastatic kidney cancer. A monoclonal antibody against the vascular endothelial growth factor (VEGF) and several tyrosine kinase inhibitors targeting the VEGF receptors demonstrated, 7 years ago, to deeply impact the outcome of this tumor and became a model of integration of molecular knowledge into clinical practice. Unfortunately, no further improvement in survival has been made and 20-25 % of cases remain primary refractory to these drugs, with an overall dismal prognosis. Since biomarker predictors of activity are lacking, their development could highly help in the process of making clinical decisions when choosing the best option for every patient or prompting the inclusion in clinical trials. This unmet medical need could become even more relevant if new immunotherapy confirms its initial promising results in this pathology. In this article, we provide an insight of current state of the art regarding the prediction of antiangiogenic efficacy in kidney cancer and propose new strategies for the implementation of such markers in clinical practice.

  19. Urinary Netrin-1: A New Biomarker for the Early Diagnosis of Renal Damage in Obese Children

    PubMed Central

    Övünç Hacıhamdioğlu, Duygu; Hacıhamdioğlu, Bülent; Altun, Demet; Müftüoğlu, Tuba; Karademir, Ferhan; Süleymanoğlu, Selami

    2016-01-01

    Objective: Urinary netrin-1 is a new marker to demonstrate early tubular damage. The aim of this study was to determine whether urinary netrin-1 is increased in obese children. Methods: A total of 68 normoalbuminuric and normotensive obese patients and 65 controls were included in the study. Urine samples were collected for assessment of urinary phosphorus, sodium, potassium, creatinine, albumin, and netrin-1. Blood samples were collected for measurements of fasting glucose, insulin, lipid, phosphorus, sodium, potassium, and creatinine levels. Homeostatic model assessment insulin resistance index was calculated. Results: Gender and age were similar between obese and control groups (12.01±3.03 vs. 11.7±3.2 years, p=0.568 and 33 vs. 35 girls, p=0.543, respectively). Obese patients had significantly higher netrin-1 excretion than the controls (841.68±673.17 vs. 228.94±137.25 pg/mg creatinine, p=0.000). Urinary netrin-1 level was significantly higher in obese subjects with insulin resistance compared to those without insulin resistance (1142±1181 vs. 604.9±589.91 pg/mg creatinine, p=0.001). Conclusion: In normotensive and normoalbuminuric obese children, urinary netrin-1 level can increase before onset of albuminuria. Urinary netrin-1 excretion appears to be affected predominantly by insulin resistance and hyperinsulinemia. Urinary netrin-1 may be a new biomarker for determining early tubular injury in obese children. PMID:27087488

  20. Functional renal failure (FRF) in cirrhosis of the liver and liver carcinoma

    PubMed Central

    Vesin, P.; Traverso, H.

    1975-01-01

    The term ‘functional renal failure’ has been used to describe the renal failure developing in advanced cirrhosis in which tubular function and structure remain intact. It may develop spontaneously, in which case prognosis is poor, but may be secondary to gastro-intestinal haemorrhage or excessive use of diuretics, in which case correction of the precipitating factor leads to improvement in renal function. It is suggested that the renal failure is due to a reduction in effective circulating plasma volume. PMID:1234327

  1. Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers.

    PubMed

    Weaver, Virginia M; Lee, Byung-Kook; Todd, Andrew C; Ahn, Kyu-Dong; Shi, Weiping; Jaar, Bernard G; Kelsey, Karl T; Lustberg, Mark E; Silbergeld, Ellen K; Parsons, Patrick J; Wen, Jiayu; Schwartz, Brian S

    2006-09-01

    Genetic polymorphisms that affect lead toxicokinetics or toxicodynamics may be important modifiers of risk for adverse outcomes in lead-exposed populations. We recently reported associations between higher patella lead, which is hypothesized to represent a lead pool that is both bioavailable and cumulative, and adverse renal outcomes in current and former Korean lead workers. In the present study, we assessed effect modification by polymorphisms in the genes encoding for delta-aminolevulinic acid dehydratase (ALAD), the vitamin D receptor (VDR), and endothelial nitric oxide synthase on those associations. Similar analyses were conducted with three other lead biomarkers. Renal function was assessed via blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, urinary N-acetyl-beta-D-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) microg/dl, 75.1 (101.1)and 33.6 (43.4) microg Pb/g bone mineral, and 0.63 (0.75) microg Pb/mg creatinine, respectively, in 647 lead workers. Little evidence of effect modification by genotype on associations between patella lead and renal outcomes was observed. The VDR polymorphism did modify associations between the other lead biomarkers and the serum creatinine and calculated creatinine clearance. Higher lead dose was associated with worse renal function in participants with the variant B allele. Models in two groups, dichotomized by median age, showed that this effect was present in the younger half of the population. Limited evidence of effect modification by ALAD genotype was observed; higher blood lead levels were associated with higher calculated creatinine clearance among participants with the ALAD(1-2) genotype. In conclusion, VDR and/or ALAD genotypes modified associations between all the lead biomarkers, except patella lead, and the renal outcomes.

  2. Biomarkers Predicting Survival of Sepsis Patients Treated with Continuous Renal Replacement Therapy

    PubMed Central

    Lee, Jeong Ho; Kim, Ha Yeon; Bae, Eun Hui; Kim, Soo Wan

    2017-01-01

    The present study investigated the prognostic factors predicting survival of patients with sepsis and acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). This retrospective observational study included 165 sepsis patients treated with CRRT. The patients were divided into two groups; the survivor group (n=73, 44.2%) vs. the nonsurvivor group (n=92, 55.8%). AKI was defined by the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guidelines. We analyzed medical histories, clinical characteristics and laboratory findings of the enrolled patients when they started CRRT. In addition, we performed binary logistic regression and cox regression analysis. In the survivor group, urine output during the first day was significantly higher compared with the nonsurvivor group (55.7±66.3 vs. 26.6±46.4, p=0.001). Patients with urine output <30 mL/hour during the 1st day showed worse outcomes than ≥30 mL/hour in the logistic regression (hazard ratio 2.464, 95% confidence interval 1.152-5.271, p=0.020) and the cox regression analysis (hazard ratio 1.935, 95% confidence interval 1.147-3.263, p=0.013). In conclusion, urine output may predict survival of septic AKI patients undergoing CRRT. In these patients, urine output <30 mL/hour during the first day was the strongest risk factor for in-hospital mortality. PMID:28184340

  3. Noninvasive fluorescence detection of hepatic and renal function

    NASA Astrophysics Data System (ADS)

    Dorshow, Richard B.; Bugaj, Joseph E.; Burleigh, B. D.; Duncan, James R.; Johnson, Michael A.; Jones, William B.

    1998-07-01

    A noninvasive in vivo fluorescence detection scheme was employed to continuously monitor exogenous dye clearance from the vasculature. Differentiation between normal and impaired physiological function in a rat model was demonstrated for both liver and kidney. A fiber optic transmitted light from source to ear; a second fiber optic positioned near the ear transmitted the fluorescent light to a detector system. Two model dye systems were employed in this initial study. Indocyanine green, known to be exclusively cleared from the blood stream by the liver, was excited in vivo with laser light at 780 nm. The fluorescence signal was detected at 830 nm. A characteristic clearance curve of normal hepatic function was obtained. After a partial hepatectomy of the liver, the clearance curve was extended in time, as would be expected from reduced hepatic function. In addition, fluorescein labeled poly-D-lysine, a small polymer predominantly cleared from the blood stream by the kidney, was excited in vivo with laser light at 488 nm. The fluorescence signal was detected at 518 nm. A characteristic clearance curve of normal renal function was obtained. After a bilateral ligation of the kidneys, the clearance curve remained elevated and constant, indicating little if any clearance. Thus, the feasibility of a new noninvasive method for physiological function assessment was established.

  4. Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney.

    PubMed

    Graceli, J B; Cicilini, M A; Bissoli, N S; Abreu, G R; Moysés, M R

    2013-06-01

    The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg · kg(-1) · day(-1), sc) and progesterone (OVP, 1.7 mg · kg(-1) · day(-1), sc). We assessed Na+ and Cl- fractional excretion (FENa+ and FECl- , respectively) and renal and plasma catecholamine release concentrations. FENa+ , FECl- , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+ , FECl- , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6 ± 36.1 ng/g) and denervated rat groups (D: 102.1 ± 15.7; ODE: 108.7 ± 23.2; ODP: 101.1 ± 22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9 ± 25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.

  5. Hepatic, renal and inflammatory biomarkers are positively associated with blood pressure changes in healthy pregnant women: a prospective cohort.

    PubMed

    Kac, Gilberto; Mendes, Roberta H; Farias, Dayana R; Eshriqui, Ilana; Rebelo, Fernanda; Benaim, Camila; Vilela, Ana Amélia F; Lima, Natália S; Peres, Wilza A F; Salles, Gil F

    2015-05-01

    This article evaluates the association of hepatic, renal, and inflammatory biomarkers with changes in systolic (SBP) and diastolic (DBP) blood pressure (BP) during healthy pregnancies.A prospective cohort study with 225 healthy pregnant women was conducted in Rio de Janeiro, Brazil. SBP and DBP were evaluated throughout pregnancy (5th-13th, 20th-26th, and 30th-36th gestational weeks) and were the outcomes. The following biomarkers were measured at the first trimester and analyzed according to tertiles of the sample distribution and were considered the main independent predictors: alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA), creatinine (Cr), and C-reactive protein (CRP) concentrations. The statistical analysis included 3 stages of modeling with the longitudinal linear mixed-effects procedures: Model 1 was adjusted for gestational age and quadratic gestational age; Model 2 included interactions between the biomarkers and gestational age; and Model 3 was adjusted for self-reported skin color, education, parity, early-pregnancy body mass index (BMI) (under/normal <25; overweight/obese ≥25 kg/m), smoking habit, and leisure-time physical activity. Additional models were performed for CRP and UA with the inclusion of interaction terms between the biomarkers and BMI.Women classified in the third tertile of the ALP (≥61.1 U/L; βSBP = 3.474; 95% confidence interval [CI]: 0.955-5.992; βDBP = 3.291; 95% CI: 1.098-5.485), ALT (≥14.3 U/L; βSBP = 2.232; 95% CI: 0.221-4.242; βDBP = 2.355; 95% CI: 0.721-3.989), and Cr values (≥48.6 μmol/L; βDBP = 1.927; 95% CI: 0.347-3.508) presented higher BP levels during pregnancy compared to those in the first and second tertiles. Women in the highest tertile of the ALP concentration distribution presented a lower rate of change in SBP and DBP during pregnancy (interaction term with gestational age βSBP = -0.004; 95% CI: -0.007 to -0

  6. Hypophosphatemic rickets due to perturbations in renal tubular function.

    PubMed

    Penido, Maria Goretti M G; Alon, Uri S

    2014-03-01

    The common denominator for all types of rickets is hypophosphatemia, leading to inadequate supply of the mineral to the growing bone. Hypophosphatemia can result from insufficient uptake of the mineral from the gut or its disproportionate losses in the kidney, the latter being caused by either tubular abnormalities per se or the effect on the tubule of circulating factors like fibroblast growth factor-23 and parathyroid hormone (PTH). High serum levels of the latter result in most cases from abnormalities in vitamin D metabolism which lead to decreased calcium absorption in the gut and hypocalcemia, triggering PTH secretion. Rickets is a disorder of the growth plate and hence pediatric by definition. However, it is important to recognize that the effect of hypophosphatemia on other parts of the skeleton results in osteomalacia in both children and adults. This review addresses the etiology, pathophysiologic mechanisms, clinical manifestations and treatment of entities associated with hypophosphatemic rickets due to perturbations in renal tubular function.

  7. Sevelamer hydrochloride, a phosphate binder, protects against deterioration of renal function in rats with progressive chronic renal insufficiency.

    PubMed

    Nagano, Nobuo; Miyata, Sonoe; Obana, Sachiko; Kobayashi, Nami; Fukushima, Naoshi; Burke, Steven K; Wada, Michihito

    2003-10-01

    Dietary phosphate restriction prevents renal function deterioration in animal models. This study examined whether sevelamer hydrochloride (Renagel(R); 'sevelamer' hereafter), a non-calcaemic phosphate binder could slow deterioration of renal function in rats with progressive renal insufficiency. Wistar Kyoto male rats were singly injected with normal rabbit serum or rabbit anti-rat glomerular basement membrane serum. Three days later, rats were fed a powder diet containing 0, 1 or 3% sevelamer for 58 days. Time course changes of serum levels of blood urea nitrogen (BUN), creatinine, calcium, phosphorus and parathyroid hormone (PTH) were measured throughout, and creatinine clearance (CCr), kidney calcium content and renal histology examined at the end of the study. Sevelamer partially inhibited elevation of BUN and serum creatinine, and completely inhibited increases in serum phosphorus, PTH and calcium xphosphorus product. Sevelamer significantly prevented the decrease in CCr and kidney calcium content elevation. Kidney calcium content and BUN and serum creatinine were strongly positively correlated, and kidney calcium content and CCr strongly negatively correlated. Kidney calcium content correlated well with serum phosphorus, serum calcium x phosphorus product and PTH, but not serum calcium. Sevelamer treatment partly prevented histological deterioration of both glomerular and tubulointerstitial lesions of the kidney. The results suggest that sevelamer protects against renal function deterioration by maintaining kidney calcium at a low level as a result of reducing serum phosphorus and PTH.

  8. Changes in Renal Function and Blood Pressure in Patients with Stone Disease

    NASA Astrophysics Data System (ADS)

    Worcester, Elaine M.

    2007-04-01

    Stone disease is a rare cause of renal failure, but a history of kidney stones is associated with an increased risk for chronic kidney disease, particularly in overweight patients. Loss of renal function seems especially notable for patients with stones associated with cystinuria, hyperoxaluria, and renal tubular acidosis, in whom the renal pathology shows deposits of mineral obstructing inner medullary collecting ducts, often diffusely. However, even idiopathic calcium oxalate stone formers have a mild but significant decrease in renal function, compared to age, sex and weight-matched normals, and appear to lose renal function with age at a slightly faster rate than non-stone formers. There is also an increased incidence of hypertension among stone formers, although women are more likely to be affected than men.

  9. Renal function in children with congenital neurogenic bladder

    PubMed Central

    Olandoski, Karen Previdi; Koch, Vera; Trigo‐Rocha, Flavio Eduardo

    2011-01-01

    AIMS: Preservation of renal function in children with congenital neurogenic bladder is an important goal of treatment for the disease. This study analyzed the evolution of renal function in patients with congenital neurogenic bladder. METHODS: We reviewed the records of 58 pediatric patients with respect to the following attributes: gender, age, etiology of neurogenic bladder, reason for referral, medical/surgical management, episodes of treated urinary tract infections, urodynamics, DMSA scintigraphy, weight, height, blood pressure, glomerular filtration rate, microalbuminuria and metabolic acidosis. Statistical analysis was performed, adopting the 5% significance level. RESULTS: The mean age at presentation was 4.2 ± 3.5 years. Myelomeningocele was the most frequent etiology (71.4%). Recurrent urinary tract infection was the reason for referral in 82.8% of the patients. Recurrent urinary tract infections were diagnosed in 84.5% of the patients initially; 83.7% of those patients experienced improvement during follow‐up. The initial mean glomerular filtration rate was 146.7 ± 70.1 mL/1.73 m2/min, and the final mean was 193.6 ± 93.6 mL/1.73 m2/min, p  =  0.0004. Microalbuminuria was diagnosed in 54.1% of the patients initially and in 69% in the final evaluation. Metabolic acidosis was present in 19% of the patients initially and in 32.8% in the final assessment. CONCLUSIONS: Patient referral to a pediatric nephrologist was late. A reduction in the number of urinary tract infections was observed with adequate treatment, but microalbuminuria and metabolic acidosis occurred frequently despite adequate management. PMID:21484032

  10. Plasma vitamins, amino acids, and renal function in postexercise hyperhomocysteinemia.

    PubMed

    Venta, Rafael; Cruz, Elena; Valcárcel, Gracia; Terrados, Nicolás

    2009-08-01

    Several studies have assessed the effect of the physical activity on plasma homocysteine (Hcy) concentrations, although the findings have been contradictory, and the exact mechanism by which plasma Hcy concentrations varied after an acute intense exercise remains unknown. We studied the effect of different acute aerobic intense exercises on plasma, reduced, and total Hcy (rHcy, tHcy) and cysteine (rCys, tCys) and on its metabolically related vitamins and amino acids. Parallel effects on renal function were assessed by plasma creatinine. Fifteen cyclists and 14 kayakers were examined before and 30 +/- 5 min after a specific test to exhaustion during a low-intensity training period. After a bout of specific exercise, the concentrations of aminothiols were increased regardless of the group considered. Plasma concentrations were higher than baseline values in tHcy (17.7 +/- 1.5%; P < 0.001), rHcy (10.6 +/- 1.6%; P < 0.001), tCys (9.9 +/- 1.6%; P < 0.001), and rCys (7.6 +/- 2.2%; P < 0.01). Both groups showed significant elevations of pyridoxal-5'-phosphate (PLP; P < 0.01), vitamin B12 (P < 0.001), and creatinine concentrations (P < 0.001) after acute exercises, but no changes were seen in folate. Changes in plasma aminothiols after exercise did not reach significant correlation with changes in free amino acids or baseline vitamins, but significant and positive correlations were observed with changes in plasma PLP, vitamin B12, and creatinine concentrations, when the pooled data were considered. Our results show that higher plasma concentrations of tHcy after an acute intense exercise are associated to higher concentrations of rHcy, and this effect is independent of the type of exercise, vitamin status, or amino acid metabolic stress but could be related to potential changes in the renal function.

  11. Renal function and anaemia in acute myocardial infarction.

    PubMed

    Pinto de Carvalho, Leonardo; McCullough, Peter A; Gao, Fei; Sim, Ling Ling; Tan, Huay Cheem; Foo, David; Ooi, Yau Wei; Richards, A Mark; Chan, Mark Y; Yeo, Tiong-Cheng

    2013-09-30

    Impaired renal function and anaemia are common among patients with acute myocardial infarction (AMI). While both conditions are known independent risk factors for increased mortality, their interaction as risk factors for increased mortality in AMI is unclear. We studied 5395 subjects hospitalized for AMI between January 2000 and December 2005. An estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) was defined as impaired GFR and GFR ≥ 60 mL/min/1.73 m(2) was defined as preserved GFR. Anaemia was defined as <13 g/dL (males) and <12 g/dL (females). The odds ratio (OR) for one-year mortality and its 95% confidence interval (CI) were calculated by logistic regression. We identified 758 (14%) patients with impaired GFR and anaemia, 1105 (20.5%) patients with impaired GFR without anaemia, 465 (8.6%) patients with preserved GFR and anaemia, and 3012 (55.8%) patients with preserved GFR without anaemia; one-year mortality rates were 56.5%, 41.8%, 31.8% and 10.3% respectively in these 4 groups. Among patients with impaired GFR, anaemia was associated with an adjusted OR of 1.47 (95% CI=1.17-1.85) for one-year mortality, while among patients with preserved GFR, anaemia was associated with a higher adjusted OR of 2.07 (95% CI=1.54-2.76) for one-year mortality, interaction P<0.001. The combination of impaired GFR and anaemia confers greater than five-fold increased risk of mortality after AMI. The differential effect of anaemia among patients with impaired and preserved GFR on mortality suggests that in patients with preserved GFR anaemia confers a greater relative hazard than in patients with impaired renal function. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. The Impact of Diabetes Mellitus on Vascular Biomarkers in Patients with End-Stage Renal Disease

    PubMed Central

    Moon, Jeonggeun; Lee, Chan Joo; Lee, Sang-Hak; Kang, Seok-Min; Choi, Donghoon

    2017-01-01

    Purpose Diabetes mellitus (DM) is the most common cause of end-stage renal disease (ESRD) and an important risk factor for cardiovascular (CV) disease. We investigated the impact of DM on subclinical CV damage by comprehensive screening protocol in ESRD patients. Materials and Methods Echocardiography, coronary computed tomography angiogram, 24-h ambulatory blood pressure monitoring, and central blood pressure with pulse wave velocity (PWV) were performed in 91 ESRD patients from the Cardiovascular and Metabolic disease Etiology Research Center-HIgh risk cohort. Results The DM group (n=38) had higher systolic blood pressure than the non-DM group (n=53), however, other clinical CV risk factors were not different between two groups. Central aortic systolic pressure (148.7±29.8 mm Hg vs. 133.7±27.0 mm Hg, p= 0.014), PWV (12.1±2.7 m/s vs. 9.4±2.1 m/s, p<0.001), and early mitral inflow to early mitral annulus velocity (16.7±6.4 vs. 13.7±5.9, p=0.026) were higher in the DM group. Although the prevalence of coronary artery disease (CAD) was not different between the DM and the non-DM group (95% vs. 84.4%, p=0.471), the severity of CAD was higher in the DM group (p=0.01). In multivariate regression analysis, DM was an independent determinant for central systolic pressure (p=0.011), PWV (p<0.001) and the prevalence of CAD (p=0.046). Conclusion Diabetic ESRD patients have higher central systolic pressure and more advanced arteriosclerosis than the non-DM control group. These findings suggest that screening for subclinical CV damage may be helpful for diabetic ESRD patients. PMID:27873498

  13. Correlation between loss of renal function and loss of renal volume after partial nephrectomy for tumor in a solitary kidney.

    PubMed

    Sharma, Nidhi; O'Hara, Jerome; Novick, Andrew C; Lieber, Michael; Remer, Erick M; Herts, Brian R

    2008-04-01

    We assessed the correlation between reduced renal function and parenchymal volume following partial nephrectomy. In 21 of 42 patients with tumors in a solitary kidney who were enrolled in a study measuring function before and after surgery underwent computerized tomography, and measurement of the glomerular filtration rate and estimated glomerular filtration rate (the latter at baseline and 2 to 6 months) before and after surgery. A segmentation algorithm was used to measure renal parenchymal volume. The percent of renal parenchymal volume loss was correlated with the percent loss in glomerular filtration rate using the Pearson correlation coefficient. Mean +/- SD net preoperative volume was 284 +/- 67 cc (range 179 to 413) and mean net postoperative volume was 240 +/- 61 cc (range 119 to 346) with an absolute functional volume loss of between 5 and 160 cc. The average percent of parenchymal volume loss was 15% (range -2% to 47%). The mean loss of the measured glomerular filtration rate 3 days postoperatively was 33.9% (range -70.7% to 74.4%) and the estimated glomerular filtration rate 2 to 6 months postoperatively was 19.7 % (-6.0% to 45.5%). There was a low degree of correlation between the percent volume loss and the percent measured glomerular filtration rate loss at 3 days (r = 0.28, p = 0.22). However, there was a moderate degree of correlation between the percent volume loss and the percent estimated glomerular filtration rate loss at 2 to 6 months (r = 0.48, p = 0.03). In patients with partial nephrectomy the renal parenchymal volume loss correlates best with the renal function loss several months after surgery. Estimates of volume loss may be useful for predicting postoperative renal function when planning partial nephrectomy in patients with a solitary kidney.

  14. Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers

    PubMed Central

    Gillen, Michael; Valdez, Shakti; Zhou, Dongmei; Kerr, Bradley; Lee, Caroline A; Shen, Zancong

    2016-01-01

    Introduction Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Methods Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60–89 mL/min; N=8), moderate (eCrCl 30–59 mL/min; N=16), or severe (eCrCl <30 mL/min; N=6) renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24) or 400 mg (N=18). Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data. Results Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration–time curve by 34%, 54%–65%, and 102%, respectively. Lesinurad plasma Cmax was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects. Conclusion Lesinurad exposure increased with decreasing renal function; however, the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment. PMID:27843295

  15. Rapid estimation of split renal function in kidney donors using software developed for computed tomographic renal volumetry.

    PubMed

    Kato, Fumi; Kamishima, Tamotsu; Morita, Ken; Muto, Natalia S; Okamoto, Syozou; Omatsu, Tokuhiko; Oyama, Noriko; Terae, Satoshi; Kanegae, Kakuko; Nonomura, Katsuya; Shirato, Hiroki

    2011-07-01

    To evaluate the speed and precision of split renal volume (SRV) measurement, which is the ratio of unilateral renal volume to bilateral renal volume, using a newly developed software for computed tomographic (CT) volumetry and to investigate the usefulness of SRV for the estimation of split renal function (SRF) in kidney donors. Both dynamic CT and renal scintigraphy in 28 adult potential living renal donors were the subjects of this study. We calculated SRV using the newly developed volumetric software built into a PACS viewer (n-SRV), and compared it with SRV calculated using a conventional workstation, ZIOSOFT (z-SRV). The correlation with split renal function (SRF) using (99m)Tc-DMSA scintigraphy was also investigated. The time required for volumetry of bilateral kidneys with the newly developed software (16.7±3.9s) was significantly shorter than that of the workstation (102.6±38.9s, p<0.0001). The results of n-SRV (49.7±4.0%) were highly consistent with those of z-SRV (49.9±3.6%), with a mean discrepancy of 0.12±0.84%. The SRF also agreed well with the n-SRV, with a mean discrepancy of 0.25±1.65%. The dominant side determined by SRF and n-SRV showed agreement in 26 of 28 cases (92.9%). The newly developed software for CT volumetry was more rapid than the conventional workstation volumetry and just as accurate, and was suggested to be useful for the estimation of SRF and thus the dominant side in kidney donors. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  16. Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase

    PubMed Central

    Guerrero-Orriach, José Luis; Ariza-Villanueva, Daniel; Florez-Vela, Ana; Garrido-Sánchez, Lourdes; Moreno-Cortés, María Isabel; Galán-Ortega, Manuel; Ramírez-Fernández, Alicia; Alcaide Torres, Juan; Fernandez, Concepción Santiago; Navarro Arce, Isabel; Melero-Tejedor, José María; Rubio-Navarro, Manuel; Cruz-Mañas, José

    2016-01-01

    Purpose To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. Methods This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. Results After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. Conclusion Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery. PMID:27143905

  17. A Urinary Fragment of Mucin-1 Subunit α Is a Novel Biomarker Associated With Renal Dysfunction in the General Population.

    PubMed

    Zhang, Zhen-Yu; Ravassa, Susana; Pejchinovski, Martin; Yang, Wen-Yi; Zürbig, Petra; López, Begoña; Wei, Fang-Fei; Thijs, Lutgarde; Jacobs, Lotte; González, Arantxa; Voigt, Jens-Uwe; Verhamme, Peter; Kuznetsova, Tatiana; Díez, Javier; Mischak, Harald; Staessen, Jan A

    2017-09-01

    Sequencing peptides included in the urinary proteome identifies the parent proteins and may reveal mechanisms underlying the pathophysiology of chronic kidney disease. In 805 randomly recruited Flemish individuals (50.8% women; mean age, 51.1 years), we determined the estimated glomerular filtration rate (eGFR) from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. We categorized eGFR according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guideline. We analyzed 74 sequenced urinary peptides with a detectable signal in more than 95% of participants. Follow-up measurements of eGFR were available in 597 participants. In multivariable analyses, baseline eGFR decreased (P ≤ 0.022) with urinary fragments of mucin-1 (standardized association size expressed in ml/min/1.73 m(2), -4.48), collagen III (-2.84), and fibrinogen (-1.70) and was bi-directionally associated (P ≤ 0.0006) with 2 urinary collagen I fragments (+2.28 and -3.20). The eGFR changes over 5 years (follow-up minus baseline) resulted in consistent estimates (P ≤ 0.025) for mucin-1 (-1.85), collagen (-1.37 to 1.43) and fibrinogen (-1.45) fragments. Relative risk of having or progressing to eGFR <60 ml/min/1.73 m(2) was associated with mucin-1. Partial least-squares analysis confirmed mucin-1 as the strongest urinary marker associated with decreased eGFR, with a score of 2.47 compared with 1.80 for a collagen I fragment as the next contender. Mucin-1 predicted eGFR decline to <60 ml/min/1.73 m(2) over and above microalbuminuria (P = 0.011) and retained borderline significance (P = 0.05) when baseline eGFR was accounted for. In the general population, mucin-1 subunit α, an extracellular protein that is shed from renal tubular epithelium, is a novel biomarker associated with renal dysfunction.

  18. Pharmacokinetics of sulphadiazine, sulphamethoxazole and trimethoprim in patients with varying renal function.

    PubMed

    Bergan, T; Brodwall, E K; Vik-Mo, H; Anstad, U

    1979-01-01

    The pharmacokinetics of tablets containing combinations of sulphadiazine (SDZ) and trimethoprim (TMP) (cotrimazine) and tablets with sulphamethoxazole (SMZ) and TMP (co-trimoxazole) were compared in patients with different renal functions. In normal renal function, SMZ is more similar to TMP than in renal impairment. In renal impairment although the serum half-life (t1/2) of both active and total SDZ remains similar to that of TMP, the t1/2 of total SMZ becomes several times higher than the t1/2 of TMP. The unchanged SMZ maintains approximately the same elimination velocity in reduced as in normal renal function. Consequently, for co-trimoxazole there is a buildup of SMZ metabolites which can only contribute to toxicity for co-trimoxazole, whereas the co-trimazine components have t1/2 values of the same order, also in renal dysfunction. The distribution volumes of SDZ, SMZ or TMP are the same regardless of renal function. However, the distribution volume of SDZ is closer to that of TMP, i.e. higher than the SMZ values. More active SDZ is excreted in the urine than SMZ both in normal and in reduced renal function. Thus co-trimazine, in addition to having some advantages in the normal individual, is in many respects distinctly more suitable in patients with renal functional impairment. On the basis of the patients with renal functional impairment. On the basis of the pharmacokinetic properties, dosage schedules are suggested that will give approximately the same plasma levels regardless of renal function.

  19. Normal ranges and variability of novel urinary renal biomarkers in Sprague-Dawley Rats: comparison of constitutive values between males and females and across assay platforms.

    PubMed

    Gautier, Jean-Charles; Gury, Thierry; Guffroy, Magali; Khan-Malek, Richard; Hoffman, David; Pettit, Syril; Harpur, Ernie

    2014-10-01

    Differences were examined between male and female Sprague-Dawley rats in basal levels of a wide range of urinary biomarkers, including 7 recently qualified biomarkers. The data were generated from urine samples collected on 3 occasions from untreated rats included in a study of the effect of gentamicin nephrotoxicity on urinary renal biomarkers, reported in a companion article in this journal (Gautier et al. 2014). The performance of multiple assays (9 singleplex assays and 2 multiplex platforms from Rules Based Medicine [RBM] and Meso Scale Discovery [MSD]) was evaluated, and normal ranges and variability estimates were derived. While variability was generally greater on the RBM platform than other assays, the more striking difference in the results from different assays was in magnitude. Where differences were observed between assays for an individual biomarker, they were seen in both sexes and consistent across samples collected at different time points. Differences of up to 15-fold were observed for some biomarker values between assays indicating that results generated using different assays should not be compared. For 8 biomarkers, there was compelling evidence for a sex difference. Baseline values in males were significantly higher than in females for total protein, β2-microglobulin, clusterin, cystatin-C, glutathione-S-transferase (GST-α), tissue inhibitor of metalloproteinases (TIMP-1), and vascular endothelial growth factor (VEGF); female values were significantly higher than that of males for albumin. The largest sex differences (male greater than female by 2- to 11-fold) were seen with β2-microglobulin, GST-α, and TIMP-1. These data add substantially to the limited body of knowledge in this area and provide a useful framework for evaluation of the potential relevance of sex differences in the diagnostic performance of these biomarkers. © 2014 by The Author(s).

  20. Use of functional mass in renal scintigraphy to detect segmental arterial lesions

    SciTech Connect

    Stibolt, T.B. Jr.; Bacher, J.D.; Dunnick, N.R.; Lock, A.; Jones, A.E.; Bailey, J.J.

    1982-04-01

    Renography using a gamma camera, a minicomputer, (/sup 123/I)orthoiodohippurate ((/sup 123/I)OIH), and a canine model was employed to evaluate computer-generated maps of regional renal function. Renograms were obtained before and after ligations of the right renal arterial branch in four dogs, with subsequent angiographic and histologic confirmation of the lesions. Postoperative time-activity curves were normal. Washout and persistence index in three of four right kidneys showed regional abnormality. Functional renal mapping may provide a clinical technique for evaluating human renal vascular hypertension.

  1. Compensatory renal growth and function in postnephrectomized patients with Wilms tumor

    SciTech Connect

    Walker, R.D.; Reid, C.F.; Richard, G.A.; Talbert, J.L.; Rogers, B.M.

    1982-02-01

    The objective of this study was to determine whether or not renal growth and function were adversely affected in the remaining kidneys of patients who had undergone nephrectomy for Wilms tumor. These patients received chemotherapy and some radiotherapy (tumoricidal agents which might affect the remaining kidney). Renal growth was compared between the treatment groups and normal renal growth. Hypertrophy did occur and did not appear to be affected by subsequent treatment. Renal function was minimally altered in all treatment groups irrespective of the type of treatment.

  2. Supplementation with chromium picolinate recovers renal Cr concentration and improves carbohydrate metabolism and renal function in type 2 diabetic mice.

    PubMed

    Mita, Yukiko; Ishihara, Kengo; Fukuchi, Yoshiko; Fukuya, Yoko; Yasumoto, Kyoden

    2005-01-01

    To study the preventive effect of supplemented chromium picolinate (CrPic) on the development of diabetic nephropathy in mice, we analyzed the effects of CrPic supplementation on renal function and concentrations of serum glucose and tissue chromium (Cr). In experiment 1, male KK-Ay obese diabetic mice were fed either a control diet (control) or a diet supplemented with 2 mg/kg diet (Cr2) or 10 mg/kg diet (Cr10) of Cr for 12 wk. Cr10 significantly ameliorated hyperglycemia after a glucose load, creatinine clearance rates, and urinary microalbumin levels (p<0.05). In experiment 2, the Cr10 diet was fed to male KK-Ay obese diabetic mice and C57BL nondiabetic mice for 4 wk. The CrPic diet reduced urinary albumin excretion in the diabetic mice (p<0.05). Inductively coupled plasma-mass spectrometry analysis revealed that the renal Cr content and the recovery of renal Cr concentration after Cr supplementation were significantly lower in the diabetic mice than in the nondiabetic mice (p<0.01). These observations suggest that Cr supplementation of type 2 diabetic mice reduces the symptoms of hyperglycemia and improves the renal function by recovering renal Cr concentration.

  3. Discoidin domain receptor 1 (DDR1), a promising biomarker, induces epithelial to mesenchymal transition in renal cancer cells.

    PubMed

    Song, Jingyuan; Chen, Xiao; Bai, Jin; Liu, Qinghua; Li, Hui; Xie, Jianwan; Jing, Hui; Zheng, Junnian

    2016-08-01

    Discoidin domain receptor I (DDR1) is confirmed as a receptor tyrosine kinase (RTK), which plays a consequential role in a variety of cancers. Nevertheless, the influence of DDR1 expression and development in renal clear cell carcinoma (RCCC) are still not well corroborated. In our research, we firstly discovered that the expression level of DDR1 was remarkable related to TNM stage (p = 0.032), depth of tumor invasion (p = 0.047), and lymph node metastasis (p = 0.034) in 119 RCCC tissue samples using tissue microarray. The function of DDR1 was then evaluated in vitro using collagen I and DDR1 small interfering RNA (siRNA) to regulate the expression of DDR1 in OS-RC-2 and ACHN renal cancer cells (RCC). DDR1 expression correlated with increased RCC cell migration, invasion, and angiogenesis. Further study revealed that high expression of DDR1 can result in epithelial to mesenchymal transition (EMT) activation. Western blot assay showed that the N-cadherin protein and vimentin were induced while E-cadherin was reduced after DDR1 over expression. Our results suggest that DDR1 is both a prognostic marker for RCCC and a potential functional target for therapy.

  4. Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI

    DTIC Science & Technology

    2016-09-01

    Award Number: W81XWH-14-1-0317 TITLE: Genetic and Diagnostic Biomarker Development in ASD Toddlers Using 
 Resting State Functional MRI...include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Genetic and Diagnostic Biomarker Development in ASD Toddlers Using... genetics and exposure to teratogens (Dufour-Rainfray et al., 2011). Although beyond the scope of this Annual Summary Report, our current findings are

  5. Renal function changes after elective cardiac surgery with cardiopulmonary bypass.

    PubMed

    de Moraes Lobo, E M; Burdmann, E A; Abdulkader, R C

    2000-01-01

    Cardiac surgery can either induce acute renal failure or improve GFR by improving the cardiac performance. In order to study renal function changes after elective cardiac surgery (CS) with cardiopulmonary bypass (CPBP), 21 patients undergoing valvular CS (VCS) or coronary artery bypass (CAB) were prospectively evaluated in three time periods: before, 24 hours after surgery and 48 hours after surgery. Patients were divided in 2 groups according to the GFR percent change in comparison to the baseline value found 24 hours after CS (deltaGFR24): Group 1, deltaGFR24 decrease higher than 20% (n = 11) and Group 2, deltaGFR24 decrease < or = 20% or deltaGFR24 increase (n = 10). In Group 1, 73% of the patients underwent VCS (p = 0.05 vs. Group 2) and all of them had previous VCS in sharp contrast with Group 2, where none of the patients had previous CS (p = 0.006). Patients in Group I required more volume replacement than Group 2 during the first 24 hours after CS: 2,699+/-704 mL versus 217+/-603 mL respectively, p = 0.019. Despite similar baseline GFR, Group 1 presented lower GFR 24 hours after CS when compared to Group 2 (39+/-5 versus 75+/-8 mL/(min x 1.73m2), p = 0.001) and a significantly different deltaGFR 48 hours after CS as compared to Group 2 (-21+/-11 versus +88+/-36%, p<0.01). Baseline sodium fractional excretion (FENa) in Group 1 was lower than in Group 2 (0.27+/-0.04 versus 0.70+/-0.12%, p = 0.01). No changes were observed after CS in urinary osmolality (Uosm) and urinary pH (UpH) in both groups. The deltaGFR24 showed positive correlation with baseline FENa (r = 0.44 p = 0.04) and negative correlation with volume balance during the first 24h after CS (r = -0.63, p = 0.007). More patients in Group 1 required nitroprusside than in Group 2 (66% vs. 14%, p = 0.04). Anesthesia time was shorter in Group 1 as compared to Group 2: 323+/-21 vs. 395+/-26 min, p = 0.04. No significant hemolysis occurred during CS in either group. There were no differences in age, gender

  6. Functional Imaging Biomarkers: Potential to Guide an Individualised Approach to Radiotherapy.

    PubMed

    Prestwich, R J D; Vaidyanathan, S; Scarsbrook, A F

    2015-10-01

    The identification of robust prognostic and predictive biomarkers would transform the ability to implement an individualised approach to radiotherapy. In this regard, there has been a surge of interest in the use of functional imaging to assess key underlying biological processes within tumours and their response to therapy. Importantly, functional imaging biomarkers hold the potential to evaluate tumour heterogeneity/biology both spatially and temporally. An ever-increasing range of functional imaging techniques is now available primarily involving positron emission tomography and magnetic resonance imaging. Small-scale studies across multiple tumour types have consistently been able to correlate changes in functional imaging parameters during radiotherapy with disease outcomes. Considerable challenges remain before the implementation of functional imaging biomarkers into routine clinical practice, including the inherent temporal variability of biological processes within tumours, reproducibility of imaging, determination of optimal imaging technique/combinations, timing during treatment and design of appropriate validation studies.

  7. Renal function and histology after acute hemorrhage in rats under dexmedetomidine action.

    PubMed

    Marangoni, Marco Aurelio; Hausch, Alex; Vianna, Pedro Thadeu Galvão; Braz, José Reinaldo Cerqueira; Viero, Rosa Marlene; Castiglia, Yara Marcondes Machado

    2007-01-01

    About 50 % of indications for dialysis in acute renal failure are related to problems originated during the perioperative period. Intraoperative hemodynamic changes lead to renal vasoconstriction and hypoperfusion. Previous studies have not defined the dexmedetomidine renal role in hemorrhage situations. This study evaluated the effect of dexmedetomidine on renal function and histology after acute hemorrhage in rats. Covered study with 20 Wistars rats, anesthetized with sodium pentobarbital, 50 mg.kg(-1), intraperitoneal, randomized into 2 groups submitted to 30% volemia bleeding: DG - iv dexmedetomidine, 3 microg.kg(-1) (10 min) and continuous infusion - 3 microg.kg(-1).h(-1); CG - pentobarbital. For renal clearance estimative, sodium p-aminohippurate and iothalamate were administered. Studied attributes: heart rate, mean arterial pressure, rectal temperature, hematocrit, iothalamate and p-aminohippurate clearance, filtration fraction, renal blood flow, renal vascular resistance, and histological evaluations of the kidneys. DG showed smaller values of heart rate, mean arterial pressure, and renal vascular resistance, but iothalamate clearance and filtration fraction values were higher. There was similarity in p-aminohippurate clearance and renal blood flow. Both groups had histological changes ischemia-like, but dexmedetomidine determined higher tubular dilatation scores. In rats, after acute hemorrhage, dexmedetomidine determined better renal function, but higher tubular dilation scores.

  8. The pharmacokinetics of remoxipride and metabolites in patients with various degrees of renal function.

    PubMed Central

    Movin-Osswald, G; Boelaert, J; Hammarlund-Udenaes, M; Nilsson, L B

    1993-01-01

    1. The pharmacokinetics of remoxipride, a new neuroleptic, were investigated in an open study with three parallel groups. Twenty-one patients with severely impaired (ClCr < 25 ml min-1), moderately impaired (ClCr 25-50 ml min-1) and normal (ClCr > 65 ml min-1) renal function were evaluated. A single oral dose of remoxipride hydrochloride 100 mg was administered, and blood and urine were collected over 48 h. Concentrations of remoxipride and metabolites were measured by h.p.l.c. 2. In patients with severely decreased renal function, the AUC and Cmax of remoxipride were increased significantly, and t1/2 was prolonged, as compared with the control patients. The renal clearance and urinary recovery of the unchanged drug were significantly diminished. 3. The unbound fraction of remoxipride in plasma was decreased in patients with renal failure, in association with a disease-related increase in alpha 1-acid glycoprotein. In spite of a 25% recovery of unchanged drug in the urine in patients with normal renal function, the AUC of unbound drug was twice as high in patients with severely impaired renal function. 4. A strong correlation between creatinine clearance and renal drug clearance was observed indicating a direct relationship between kidney function and the renal clearance of remoxipride. 5. Remoxipride was the predominant compound in plasma as well as in urine in patients with severely decreased as well as normal renal function. In patients with severely decrease renal function, remoxipride and all five pharmacologically inactive metabolites showed increased peak plasma concentrations, delayed tmax, increased AUC, prolonged half-lives and decreased renal clearance. PMID:8329289

  9. Circulating biomarkers in renal cell carcinoma: the link between microRNAs and extracellular vesicles, where are we now?

    PubMed Central

    Teixeira, Ana L; Dias, Francisca; Gomes, Mónica; Fernandes, Mara

    2014-01-01

    Renal cell carcinoma (RCC) is a lethal urological cancer, with incidence and mortality rates increasing by 2-3% per decade. The lack of standard screening tests contributes to the fact that one-third of patients are diagnosed with locally invasive or metastatic disease. Moreover, 20-40% of RCC patients submitted to surgical nephrectomy will develop metastasis. MicroRNAs (miRNAs) are small non-coding RNAs responsible for gene regulation at a post-transcriptional level. It is accepted that they are deregulated in cancer and can influence tumor development. Thus, miRNAs are promising RCC biomarkers, since they can be detected using non-invasive methods. They are highly stable and easier to quantify in circulating biofluids. The elevated miRNA stability in circulating samples may be the consequence of their capacity to circulate inside of extracellular microvesicles (EMVs), for example, the exosomes. The EMVs are bilayered membrane vesicles secreted by all cell types. They can be released in the interstitial space or into circulating biofluids, which allows the travelling, binding and entrance of these vesicles in receptor cells. This type of cell communication can shuttle bioactive molecules between cells, allowing the horizontal transference of genetic material. In this review, we focus on circulating miRNAs (miR-210, miR-1233, miR-221, miR-15a, miR-451, miR-508, miR-378) in the biofluids of RCC patients and attempt to establish the diagnostic and prognostic accuracy, their synergic effects, and the pathways involved in RCC biology. PMID:28326253

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

    PubMed

    Hsiao, Shih-Hung; Chiou, Kuan-Rau

    2017-05-01

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

  11. Associations of Proanthocyanidin Intake with Renal Function and Clinical Outcomes in Elderly Women

    PubMed Central

    Ivey, Kerry L.; Lewis, Joshua R.; Lim, Wai H.; Lim, Ee M.; Hodgson, Jonathan M.; Prince, Richard L.

    2013-01-01

    Background Progression to chronic renal failure involves accelerated atherosclerosis and vascular calcification. Oxidative stress and endothelial dysfunction play a role in renal failure pathophysiology. In addition to improving vascular health and function, proanthocyanidins have been shown to exert renoprotective effects in animal models. Thus we hypothesize that proanthocyanidins may contribute to the maintenance of healthy renal function. Objective Determine the association of habitual proanthocyanidin intake with renal function and the risk of clinical renal outcomes in a population of elderly women. Design 948 women aged over 75 y, free of prevalent renal disease at baseline, were randomly selected from ambulant Caucasian women. Proanthocyanidin consumption was determined using a validated food frequency questionnaire and the United States Department of Agriculture proanthocyanidin food content database. Fasting serum cystatin C and creatinine were assessed at baseline. Renal failure hospitalisations and deaths were assessed over 5 years of follow-up through the Western Australia Data Linkage System. Results Compared to participants with low consumption, participants in the highest tertile of proanthocyanidin intake had a 9% lower cystatin C concentration (P<0.001). High proanthocyanidin consumers were at 50% lower risk of moderate chronic kidney insufficiency, and 65% lower risk of experiencing a 5-year renal disease event (P<0.05). These relationships remained significant following adjustment for renal disease risk factors and diet-related potential confounders. Conclusion Increased consumption of proanthocyanidins was associated with better renal function and substantially reduced renal associated events, which has been supported by mechanistic and animal model data. Proanthocyanidin intake should be further examined as a dietary contributor to better renal health. PMID:23940710

  12. FUT11 as a potential biomarker of clear cell renal cell carcinoma progression based on meta-analysis of gene expression data.

    PubMed

    Zodro, Elżbieta; Jaroszewski, Marcin; Ida, Agnieszka; Wrzesiński, Tomasz; Kwias, Zbigniew; Bluyssen, Hans; Wesoly, Joanna

    2014-03-01

    In this paper, we provide a comprehensive summary of available clear cell renal cell carcinoma (ccRCC) microarray data in the form of meta-analysis of genes differentially regulated in tumors as compared to healthy tissue, using effect size to measure the strength of a relationship between the disease and gene expression. We identified 725 differentially regulated genes, with a number of interesting targets, such as TMEM213, SMIM5, or ATPases: ATP6V0A4 and ATP6V1G3, of which limited or no information is available in terms of their function in ccRCC pathology. Downregulated genes tended to represent pathways related to tissue remodeling, blood clotting, vasodilation, and energy metabolism, while upregulated genes were classified into pathways generally deregulated in cancers: immune system response, inflammatory response, angiogenesis, and apoptosis. One hundred fifteen deregulated genes were included in network analysis, with EGLN3, AP-2, NR3C1, HIF1A, and EPAS1 (gene encoding HIF2-α) as points of functional convergence, but, interestingly, 610 genes failed to join previously identified molecular networks. Furthermore, we validated the expression of 14 top deregulated genes in independent sample set of 32 ccRCC tumors by qPCR and tested if it could serve as a marker of disease progression. We found a correlation of high fucosyltransferase 11 (FUT11) expression with non-symptomatic course of the disease, which suggests that FUT11's expression might be potentially used as a biomarker of disease progression.

  13. Comparison of renal function and other health outcomes in vegetarians versus omnivores in Taiwan.

    PubMed

    Lin, Chih-Kuang; Lin, Deng-Juin; Yen, Chi-Hwa; Chen, Shiuan-Chih; Chen, Chun-Chieh; Wang, Tsun-Yen; Chou, Ming-Chih; Chang, Horng-Rong; Lee, Meng-Chih

    2010-10-01

    Renal disease is one of the top 10 leading causes of death, and the incidence of end-stage renal disease in Taiwan is the highest in the world. Many dietitians consider the diet of plant origin consumed by vegans to be 'lighter' and 'more healthful' than the diet of both plant and animal origin consumed by omnivores. Dietary protein has significant effects on renal functions. The study explored the effects of both the diets on renal functions. The study subjects included 102 Buddhist nun vegetarians and an equal number of matched control group (omnivores). A cross-sectional study was performed to investigate the effects of the diet of plant origin and the diet of both plant and animal origin on renal functions. There was no difference in the renal functions between the two groups. However, systolic blood pressure, blood urea nitrogen, serum sodium, glucose, cholesterol levels, and urinary specific gravity were lower in the vegetarian group. Although these results were compatible with general concepts regarding diet of plant origin, after adjusting for age, the duration of intake of this diet had no effect on the renal functions. Based on the findings, it is concluded that the renal functions, in terms of the estimated glomerular filtration rate, were not different between the vegetarians and the omnivores.

  14. Comparison of Renal Function and Other Health Outcomes in Vegetarians versus Omnivores in Taiwan

    PubMed Central

    Lin, Chih-Kuang; Lin, Deng-Juin; Yen, Chi-Hwa; Chen, Shiuan-Chih; Chen, Chun-Chieh; Wang, Tsun-Yen; Chou, Ming-Chih

    2010-01-01

    Renal disease is one of the top 10 leading causes of death, and the incidence of end-stage renal disease in Taiwan is the highest in the world. Many dietitians consider the diet of plant origin consumed by vegans to be ‘lighter’ and ‘more healthful’ than the diet of both plant and animal origin consumed by omnivores. Dietary protein has significant effects on renal functions. The study explored the effects of both the diets on renal functions. The study subjects included 102 Buddhist nun vegetarians and an equal number of matched control group (omnivores). A cross-sectional study was performed to investigate the effects of the diet of plant origin and the diet of both plant and animal origin on renal functions. There was no difference in the renal functions between the two groups. However, systolic blood pressure, blood urea nitrogen, serum sodium, glucose, cholesterol levels, and urinary specific gravity were lower in the vegetarian group. Although these results were compatible with general concepts regarding diet of plant origin, after adjusting for age, the duration of intake of this diet had no effect on the renal functions. Based on the findings, it is concluded that the renal functions, in terms of the estimated glomerular filtration rate, were not different between the vegetarians and the omnivores. PMID:20941898

  15. Functional consequences of prenatal methylmercury exposure: effects on renal and hepatic responses to trophic stimuli and on renal excretory mechanisms

    SciTech Connect

    Slotkin, T.A.; Kavlock, R.J.; Cowdery, T.; Orband, L.; Bartolome, M.

    1986-01-01

    The effects of prenatal exposure to methylmercury on the functional development of renal and hepatic response systems was examined in the developing rat. Methylmercury produced an elevation of basal activity of renal ornithine decarboxylase (ODC, an enzyme involved in regulation of cellular maturation) and an eventual relative hypertrophy; liver ODC was reduced and hypertrophy was not evident. In contrast, the reactivity of liver ODC to trophic stimulants (vasopressin, isoproterenol) was markedly enhanced by prenatal methylmercury exposure, whereas renal ODC responses were much less affected (vasopressin) or actually reduced (isoproterenol). Targeted actions of methylmercury on renal excretory function were also prominent, with increased fractional excretions urea and electrolytes and an eventual reduction in glomerular filtration as assessed by creatinine clearance. These studies show that doses of methylmercury ordinarily associated with selective actions on development of neurobehavioral patterns also influence the functional ontogeny of other organ systems; furthermore, the fact that the target tissues are different for prenatal vs postnatal methylmercury exposure, indicates that the functional teratology of methylmercury exhibits critical periods of sensitivity.

  16. Modified Differential Renal Function Measurement Revised by Renal Cross Sectional Area in Children with Ureteropelvic Junction Obstruction

    PubMed Central

    Nam, Jong Kil; Chung, Moon Kee

    2010-01-01

    Purpose Diuretic 99mTc-diethylenetriaminepentaacetic acid (Tc-DTPA) renal scans may show false-negative or false-positive results in children with ureteropelvic junction obstruction (UPJO). We evaluated whether modified differential renal function (DRF) revised by the renal cross-sectional area on imaging study may be a more valuable predictor than conventional DRF on a renal scan for deciding on a proper interventional time. Materials and Methods Between September 2001 and January 2008, we reviewed the diuretic renal scan results of 29 pediatric patients who underwent pyeloplasty due to unilateral UPJO. Diuretic renal scans using the standard 99mTc-DTPA protocol and imaging studies for renal unit measurement area were done. Conventional DRF measurement and modified calculation of DRF per unit area were done. Conventional DRF was classified into group I (below 40%) and group II (above 40%). Results The mean age of all patients was 42.6±52.6 months (range, 3-198 months). The mean cross-sectional areas of the UPJO kidney and of the normal contralateral kidney were 62.1±29.2 cm2 and 41.3±22.5 cm2, respectively (p<0.01). The conventional and modified DRF of the UPJO kidney were 45.2±9.2% and 35.2±9.5%, respectively (p<0.01). Thirteen children (62%) in group II (n=21) were classified in group I by the modified DRF measurement. Conclusions The modified DRF measurement calculated according to cross-sectional area showed fewer false-negative results and may be a valuable method for deciding on pyeloplasty under equivocal circumstances. PMID:20428431

  17. Serum cystatin C-A useful endogenous marker of renal function in intensive care unit patients at risk for or with acute renal failure?

    PubMed

    Royakkers, Annick A N M; van Suijlen, Jeroen D E; Hofstra, Lieuwe S; Kuiper, Michael A; Bouman, Catherine S C; Spronk, Peter E; Schultz, Marcus J

    2007-01-01

    Critically ill patients are at high risk for developing acute renal failure (ARF). The prevention of ARF is of outmost importance in order to improve the increased morbidity and mortality associated with ARF. Unfortunately, there is lack of adequate endogenous markers that can identify renal dysfunction early - this hampers timely application of measures to prevent further renal damage. The use of exogenous markers of renal function is not only time-consuming but also expensive, and therefore can not be used on a regular basis in the intensive care unit. Both the presently used endogenous and exogenous markers are not reliable during continuous renal replacement therapy (CRRT) because these markers are removed by the therapy itself impeding early detection of recovering of renal function. Cystatin C has been proposed as an alternative endogenous marker of renal function for more than 15 years. In this manuscript we review the literature on the role of cystatin C as marker for renal function, focusing on the critically ill patient. Serum cystatin C concentrations have been found to relate to renal impairment and suggest that cystatin C is more sensitive to detect mild decreases in GFR. Cystatin C could be an important tool both to recognize early renal dysfunction and to identify renal recovery while on CRRT in the critically ill patient, however, we are in need of more studies.

  18. Epidemiologic study of renal function in copper smelter workers.

    PubMed Central

    Lilis, R; Valciukas, J A; Weber, J P; Malkin, J; Selikoff, I J

    1984-01-01

    A medical cross-sectional examination of a copper smelter work force was undertaken after environmental contamination with lead, cadmium and arsenic had been documented. A total of 920 subjects was examined, including active smelter employees, retired workers and copper mine employees who had never worked in the smelter. Slight to moderate absorption of lead and cadmium was definitely present in the active copper smelter employees, who had significantly higher levels of Pb-B, ZPP and Cd-B than retired employees and miners. Cd-U levels were higher in retired workers, who were also older and had, as a group, longer duration of exposure in the smelter. Cd-U did not exceed 10 micrograms/g creatinine, the level considered critical for nephrotoxicity, in any of the subjects. Median Cd-B level for active workers was 2.75 micrograms/L. Lead absorption was characterized by a relatively small proportion (16.7%) of active employees with Pb-B levels 40 micrograms/dL or higher. We were particularly interested in exploring the possibility that simultaneous exposure to lead and cadmium, although at levels not associated with nephrotoxicity for each metal separately, could result in renal function impairment. Distribution patterns of BUN and serum creatinine levels were unremarkable. Urinary beta 2-microglobulin levels were less than 200 micrograms/g creatinine in 95% of copper smelter employees. There were no significant correlations between urinary beta 2-microglobulin levels and Cd-U, Cd-B, Pb-B and ZPP or between urinary beta 2-microglobulin excretion and serum creatinine or BUN levels. Urinary beta 2-microglobulin levels were significantly correlated with age in the copper smelter workers, but not in the miners. Nevertheless, in the absence of any significant correlations between urinary beta 2-microglobulin and Cd-U, Cd-B, a causal relationship with cadmium absorption cannot be affirmed. That kidney function could be impaired by long-term exposure in the smelter was only

  19. Pre-terminal renal insufficiency in a patient with enteric hyperoxaluria: effect of medical management on renal function.

    PubMed

    Pipeleers, L; Wissing, K M; Pirson, Y; Cosyns, J P; Geers, C; Tielemans, C

    2012-01-01

    Enteric hyperoxaluria causes tubular deposition calcium oxalate crystals and severe chronic interstitial nephritis. We describe a patient with pre-terminal renal failure due to oxalate nephropathy after ileal resection. Increased oral hydration, low oxalate diet, and oral calcium carbonate and potassium citrate supplements resulted in a significant improvement of renal function. During the three-year follow-up, urinary oxalate concentration was repeatedly reduced below the crystallization threshold and serum creatinine decreased from 4.5 to 1.7 mg/dL. This case illustrates the benefit of combining and optimizing dietary and medical management in enteric hyperoxaluria, even in patients with advanced chronic kidney disease.

  20. Cardiorenal biomarkers in acute heart failure

    PubMed Central

    Choudhary, Rajiv; Gopal, Dipika; Kipper, Ben A.; De La Parra Landa, Alejandro; Lee, Hermineh Aramin Elizabeth; Shah, Saloni; Maisel, Alan S.

    2012-01-01

    Managing patients with heart failure (HF) is a challenging task within itself, but the presence of associated worsening renal function can greatly increase mortality and morbidity. Early diagnosis and treatment is the key to prevent re-hospitalizations and reduce healthcare costs. Biomarkers have long been established as highly sensitive and specific tools in diagnosing and prognosticating patients with HF. Reflecting distinct pathophysiological events and ongoing cellular insult, biomarkers have been proven superior to conventional laboratory tests. Availability of better assays and rapid analysis has allowed the use of biomarkers as point-of-care tests in the emergency department and at the patient's bed-side. Acute HF patients often go on to develop worsening renal function, termed as acute cardiorenal syndrome. The growing breadth of studies has shown the implications of combining multiple biomarkers to better chart outcomes and produce desirable results in such patients. PMID:23097660

  1. Epidemiologic study of renal function in copper smelter workers

    SciTech Connect

    Lilis, R.; Valciukas, J.A.; Weber, J.P.; Malkin, J.; Selikoff, I.J.

    1984-03-01

    A medical cross-sectional examination of a copper smelter work force was undertaken after environmental contamination with lead, cadmium and arsenic had been documented. A total of 920 subjects was examined, including active smelter employees, retired workers and copper mine employees who had never worked in the smelter. Slight to moderate absorption of lead and cadmium was definitely present in the active copper smelter employees, who had significantly higher levels of Pb-B, ZPP and Cd-B than retired employees and miners. Cd-U levels were higher in retired workers, who were also older and had, as a group, longer duration of exposure in the smelter. Cd-U did not exceed 10 ..mu..g/g creatinine, the level considered critical for nephrotoxicity, in any of the subjects. Median Cd-B level for active workers was 2.75 ..mu..g/L. Lead absorption was characterized by a relatively small proportion (16.7%) of active employees with Pb-B levels 40 ..mu..g/dL or higher. That kidney function could be impaired by long-term exposure in the smelter was only indirectly suggested. Effects on renal function at the low levels of cadmium and lead absorption that were observed in this smelter population are minimal. 21 references, 8 figures, 21 tables.

  2. Renal Function and Hemodynamic Study in Obese Zucker Rats

    PubMed Central

    Park, Sung Kwang; Kang, Sung Kyew

    1995-01-01

    Objectives To investigate the renal function and hemodynamic changes in obesity and hyperinsulinemia which are characteristics of type II diabetes. Methods Studies were carried out in two groups of female Zucker rats. Group 1 rats were obese Zucker rats with hereditary insulin resistance. Group 2 rats were lean Zucker rats and served as controls. In comparison with lean Zucker rats, obese Zucker rats exhibited hyperinsulinemia but normoglycemia. Micropuncture studies and morphologic studies were performed in these rats. Results Functional studies showed that obese Zucker rats exhibited increases in kidney weight and GFR(obese Zucker, 1.23±.07)ml/min; lean Zucker, 0.93±.03ml/min). Micropuncture studies revealed that the increase in GFR in obese Zucker rats was attributable to the increases in the single nephron plasma flow rate and glomerular transcapillary hydraulic pressure. The glomerular ultrafiltration coefficient was the same in both groups. Morphologic studies revealed that the increase in GFR in obese Zucker rats was associated with an increase in glomerular volume. Conclusions These results suggest that obesity and hyperinsulinemia, which are the characteristics of type II diabetes, can be associated with glomerular hyperfiltration and glomerular capillary hypertension. PMID:7626557

  3. Common biomarkers of oxidative stress do not reflect cardiovascular dys/function in rats.

    PubMed

    Mladenka, Premysl; Zatloukalova, Libuse; Filipsky, Tomas; Vavrova, Jaroslava; Holeckova, Magdalena; Palicka, Vladimir; Hrdina, Radomir

    2013-06-01

    Predicting cardiovascular events remains challenging despite the range of known biomarkers. To establish relationships between various biochemical and functional parameters of the cardiovascular system. The relationship between cardiovascular dys/function and various biomarkers was examined in 145 experimental rats half of which received isoprenaline 100 mg/kg s.c. to induce cardiac impairment. Serum concentration of cardiac troponin T (cTnT), a known marker of cardiac derangement, correlated strongly with degree of myocardial injury (e.g. calcium overload, stroke volume) but correlations between cTnT and oxidative stress parameters were weak (for glutathione and vitamin C) or not found (for serum vitamin E and plasma thiobarbituric acid reactive substances levels). Relationships between cTnT and other parameters were exponential with the exception of myocardial calcium, where a power function was found. Commonly used biomarkers of oxidative stress cannot reliably predict cardiovascular dys/function in experimental rats.

  4. High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

    PubMed

    Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

    2015-01-01

    The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

  5. Worsening renal function in heart failure: the need for a consensus definition.

    PubMed

    Sheerin, Noella J; Newton, Phillip J; Macdonald, Peter S; Leung, Dominic Y C; Sibbritt, David; Spicer, Stephen Timothy; Johnson, Kay; Krum, Henry; Davidson, Patricia M

    2014-07-01

    Acute decompensated heart failure is a common cause of hospitalisation. This is a period of vulnerability both in altered pathophysiology and also the potential for iatrogenesis due to therapeutic interventions. Renal dysfunction is often associated with heart failure and portends adverse outcomes. Identifying heart failure patients at risk of renal dysfunction is important in preventing progression to chronic kidney disease or worsening renal function, informing adjustment to medication management and potentially preventing adverse events. However, there is no working or consensus definition in international heart failure management guidelines for worsening renal function. In addition, there appears to be no concordance or adaptation of chronic kidney disease guidelines by heart failure guideline development groups for the monitoring of chronic kidney disease in heart failure. Our aim is to encourage the debate for an agreed definition given the prognostic impact of worsening renal function in heart failure. We present the case for the uptake of the Acute Kidney Injury Network criteria for acute kidney injury with some minor alterations. This has the potential to inform study design and meta-analysis thereby building the knowledgebase for guideline development. Definition consensus supports data element, clinical registry and electronic algorithm innovation as instruments for quality improvement and clinical research for better patient outcomes. In addition, we recommend all community managed heart failure patients have their baseline renal function classified and routinely monitored in accordance with established renal guidelines to help identify those at increased risk for worsening renal function or progression to chronic kidney disease.

  6. Long-term renal function in heart transplant children on cyclosporine treatment.

    PubMed

    Dello Strologo, Luca; Parisi, Francesco; Legato, Antonia; Pontesilli, Claudia; Pastore, Anna; Ravà, Lucilla; Tozzi, Alberto E; Rizzoni, Gianfranco

    2006-04-01

    Renal function deterioration is a reason of concern in heart transplantation. Our aim was to evaluate long-term renal function in heart transplant children on cyclosporine (CsA) treatment and to investigate the effect of several variables possibly involved in renal function deterioration. Creatinine clearances were retrospectively reviewed in 50 children (median follow 99.7 months after heart transplant). Gender, age, and body weight at transplant, rejection episodes, CsA cumulative dose, and trough levels were analyzed. After an initial increase of the glomerular filtration rate (GFR), renal function worsened in most patients; 28% of the children developed renal insufficiency (defined as GFR <80 ml/min per 1.73 m2), which was already evident in the first 3 years. Neither CsA dose, trough levels, nor other patient characteristics were found to be associated with renal function deterioration. In this study renal failure occurred in one-third of the patients. The lack of association of CsA with renal insufficiency may be explained by several reasons, including the limitations of the retrospective design of the study. However, it is possible that the nephrotoxic effect of CsA is more likely to occur in a set of predisposed patients. These must be soon identified to evaluate early a calcineurin inhibitor-sparing strategy.

  7. [Factors related to renal dysfunction after liver transplantation in patients with normal preoperative function].

    PubMed

    Koo, M; Sabaté, A; Ramos, E; Dalmau, A; León, E; Fabregat, J; Rafecas, A

    2006-11-01

    To determine perioperative factors related to postoperative renal dysfunction in patients receiving liver transplants who had normal renal function before surgery. We analyzed the cases of 189 consecutive patients. Patients with hepatorenal syndrome and previously diagnosed renal insufficiency were excluded, as were patients undergoing a second transplant operation. Postoperative renal dysfunction was diagnosed when creatinine levels exceeded 1.5 mg x dL(-1) in the first postoperative week. Multivariate analysis of preoperative variables (patient characteristics; Child-Pugh score; status with the United Network for Organ Sharing; and sodium, coagulation, hemoglobin, and creatinine levels); intraoperative variables (blood product units required, duration of surgery, reperfusion syndrome, surgical technique, and crystalloids required); and postoperative variables (hemodialysis or filtration, reoperation, mortality, creatinine levels at 6 and 12 months). One hundred fifty patients with normal kidney function were included. Postoperative renal dysfunction developed in 45 (30%). Differences between patients with and without postoperative renal dysfunction were found for weight; sex; Child-Pugh score; blood transfusion requirements (mean [SD] of 2.36 [2.4] units of packed red cells in the group of patients with renal dysfunction vs 1.3 [1.8] in the patients with normal function); and reperfusion syndrome (26 [66.7%] patients with renal dysfunction and 35 [21.5%] without). The last 2 variables continued to be significantly correlated with renal dysfunction in the multivariate analysis with a relative risk of 1.25, (95% confidence interval [CI], 1.01-1.55) for units of blood transfusion and 2.41 (95% CI, 1.04-5.57) for reperfusion syndrome. Renal replacement therapy was used in 4 patients (2.7%). Mortality rates were similar. At 6 and 12 months, 26 (17.3%) and 18 (12%) patients had renal dysfunction. Acute renal dysfunction is a frequent complication following a liver

  8. Prognosis of renal transplant function by renography with radioactive hippuran

    SciTech Connect

    Riccabona, G.; Fill, H.; Hilty, E.; Leidlmair, K.

    1986-01-01

    The relation of the functional prognosis of a kidney graft to the results of renography with radioactive hippuran (OIH-RG) was assessed in 96 patients after renal allograft transplantation in 1982. By October 1, 1984 26 of these kidneys had lost their function. The curves obtained from the gamma-camera OIH-RG are classified into six different curve patterns (curve types 1 to 6) as published earlier. For the evaluation of the long-term prognosis, the survival times of the kidneys were related to the curve types. The distribution of the curve types obtained in patients with a kidney survival longer than 144 weeks differs significantly from the curve type distribution when the kidney survival is shorter than 144 weeks. The individual survival times in the collective 26 lost kidneys show a relation to the different curve types. All kidneys with curve type 4 in the last examination before hospital discharge are lost within the first 20 weeks while curve types 1 and 2 promise a functional survival up to 144 weeks. Serum creatinine time courses and their relation to the OIH-RG curve patterns are analyzed by analyses of variance and covariance with repeated measurement. These statistical analyses reveal significant differences between the creatinine courses in the single curve types and, in addition, a significant interaction of the curve types with the creatinine courses. In curve type 1, a rapid normalization of an elevated creatinine level can be predicted, while in curve type 4 no improvement of the creatinine level and thus of kidney function can be expected at least within the five days following discharge.

  9. Recovery of renal function after glucocorticoid therapy for IgG4-related kidney disease with renal dysfunction.

    PubMed

    Saeki, Takako; Kawano, Mitsuhiro; Mizushima, Ichiro; Yamamoto, Motohisa; Wada, Yoko; Ubara, Yoshifumi; Nakashima, Hitoshi; Ito, Tomoyuki; Yamazaki, Hajime; Narita, Ichiei; Saito, Takao

    2016-02-01

    Although renal dysfunction in IgG4-related kidney disease (IgG4-RKD) shows rapid resolution with glucocorticoid therapy, little is known about the appropriate initial glucocorticoid dose for induction therapy or long-term renal outcome. We retrospectively examined the differences in recovery of renal function according to the dose of glucocorticoid used for induction therapy and the long-term renal outcome in 43 patients with definite IgG4-RKD (mostly IgG4-tubulointerstitial nephritis), in whom the estimated glomerular filtration rate (eGFR) before glucocorticoid therapy was <60 ml/min. Most patients were treated with glucocorticoid alone and had been maintained on glucocorticoid. The initial dose of prednisolone employed was ≤0.6 mg/kg/day (mean 0.47) in 27 patients (group L), and >0.6 mg/kg/day (mean 0.81) in 16 patients (group H). In both groups, the pretreatment eGFR was significantly improved at 1 month after the start of glucocorticoid therapy and the degree of improvement showed no significant inter-group difference. Relapse of IgG4-RKD occurred in 16.7% of the group L patients and 13.3% of the group H patients (p = 0.78). Among 29 patients who were followed up for over 36 months (mean 74 months) and had been maintained on glucocorticoid, none showed progression to end-stage renal disease and there was no significant difference between eGFR at 1 month after treatment and eGFR at the last review. In glucocorticoid monotherapy for IgG4-RKD, a moderate dose is sufficient for induction, and recovery of renal function can be maintained for a long period on low-dose maintenance, although relapse can occur even in patients receiving maintenance therapy.

  10. [Effect of percutaneous nephrostolithotomy combined with flexible ureteroscopy on renal function in elderly patients with renal calculi].

    PubMed

    Zhao, Zhongwei; Zhang, Xiaobo; Chen, Xiong; Dai, Yuanqing; Li, Dongjie; Bai, Yao; Xiao, Xi

    2015-03-01

    To detect the levels of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (Cys-C ) in blood and the level of kidney injury molecule 1 (KIM-1) in urine in elderly patients with renal calculi at diff erent times, and to explore the eff ect of percutaneous nephrostolithotomy (PCNL) combined with flexible ureteroscopy (FU) on early postoperative renal function. A total of 46 patients with renal calculi were selected, and their blood or urine specimens were collected respectively at preoperative and postoperative 2, 12, 24, 48, and 72 h. The concentrations of NGAL, Cys-C, KIM-1 were detected. The levels of NGAL and Cys-C began to increase respectively at postoperative 2 and 12 h, and reached peak at postoperative 12 to 24 h. There was significant difference in the levels of NGAL and Cys-C between the postoperative 12 and 2 h or between postoperative 48 and 24 h (all P<0.05). The levels of NGAL and Cys-C began to decline and eventually returned to preoperative levels respectively at postoperative 48 and postoperative 72 h. The KIM-1 began to increase at postoperative 2 h and peaked at postoperative 24 h, which was significant difference between the postoperative 24 and 12 h or postoperative 48 and 24 h (both P<0.05). The level of KIM-1 began to decline and eventually returned to preoperative levels at postoperative 48 h. After the combined treatment of percutaneous nephrostolithotomy with flexible ureteroscopy, the concentrations of NGAL, Cys-C and KIM-1 are significantly increased, suggesting injuries on renal function. The time of renal tubular injury and recovery is earlier than that of renal glomerulus.

  11. Effect of chronic accumulation of aluminum on renal function, cortical renal oxidative stress and cortical renal organic anion transport in rats.

    PubMed

    Mahieu, Stella T; Gionotti, Marisa; Millen, Néstor; Elías, María Mónica

    2003-11-01

    The aim of the present work was to study the nephrotoxicity of aluminum lactate administered for 3 months (0.57 mg/100 g bodyweight aluminum, i.p., three times per week) to male Wistar rats. Renal function was studied after 6 weeks of treatment (urine was obtained from rats in metabolic cages) and at the end of the treatment using clearance techniques. Another group of rats was used as kidneys donors at the end of treatment. The renal cortex was separated and homogenized to determine glutathione (GSH) level, glutathione S-transferase (GST) activity and lipid peroxidation (LPO) level. Renal cortex slices were also used to study the p-aminohippuric acid (PAH) accumulation during steady-state conditions and the kinetics of uptake process. Clearance results, at the end of the treatment, indicated that renal functions in treated-rats were not different from those measured in control rats, although the renal concentration parameters differ when they were measured in treated rats after 24 h of food and water deprivation. Balances of water and sodium were also modified at both 1.5 and 3 months of treatment. The activity of alkaline phosphatase (AP) relative to inulin excreted in urine was significantly impaired: controls 2.2+/-0.6 IUI/mg, Al-treated 5.1+/-0.5 IU/mg, P<0.05. These data indicated that proximal tubular cells were loosing apical brush border membranes. Data obtained in cortex homogenates indicated that both GSH and GST activity were significantly decreased, and a significant increase of LPO was noted simultaneously in Al-treated rats. Renal accumulation of PAH, estimated as slice-to-medium ratio, decreased significantly in the Al-treated rats: control rats 3.06+/-0.02 ( n=12), Al-treated rats 2.26+/-0.04 ( n=12), P<0.0001. The maximal rate of uptake was also diminished in treated rats, while the apparent affinity remained unchanged. All these results indicate that aluminum accumulation in renal tissue affects cellular metabolism, promotes oxidative stress and

  12. How does your kidney smell? Emerging roles for olfactory receptors in renal function.

    PubMed

    Shepard, Blythe D; Pluznick, Jennifer L

    2016-05-01

    Olfactory receptors (ORs) are chemosensors that are responsible for one's sense of smell. In addition to this specialized role in the nose, recent evidence suggests that ORs are also found in a variety of additional tissues including the kidney. As this list of renal ORs continues to expand, it is becoming clear that they play important roles in renal and whole-body physiology, including a novel role in blood pressure regulation. In this review, we highlight important considerations that are crucial when studying ORs and present the current literature on renal ORs and their emerging relevance in maintaining renal function.

  13. How does your kidney smell? Emerging roles for olfactory receptors in renal function

    PubMed Central

    Shepard, Blythe D.; Pluznick, Jennifer L.

    2015-01-01

    Olfactory receptors (ORs) are chemosensors that are responsible for one’s sense of smell. In addition to this specialized role in the nose, recent evidence suggests that ORs are also found in a variety of additional tissues including the kidney. As this list of renal ORs continues to expand, it is becoming clear that these ORs play important roles in renal and whole-body physiology, including a novel role in blood pressure regulation. In this review, we highlight important considerations that are crucial when studying ORs, and present the current literature on renal ORs and their emerging relevance in maintaining renal function. PMID:26264790

  14. Predicting angiography-induced acute renal function impairment: clinical risk model

    SciTech Connect

    Cochran, S.T.; Wong, W.S.; Roe, D.J.

    1983-11-01

    Two hundred sixty-six patients were evaluated for development of acute renal function impairment after renal angiography. Forty-five (16.9%) had a significant increase in serum level of creatinine (sCr), six developed oliguria or anuria, and one required permanent dialysis. Age, proteinuria, abnormal baseline sCr, use of Renografin 76, and preexisting renal disease were the five independent risk factors in the series. An odds-ratio analysis establishes the relative risk (i.e., likelihood) of developing acute renal insufficientcy after renal angiography on the basis of the number of risk factors present. An increasing relation was demonstrated; the more factors present, the more likely it becomes that a patient will develop acute renal insufficiency.

  15. Neutrophil Gelatinase Associated Lipocalin (NGAL) – a biomarker of renal dysfunction in patients with liver cirrhosis: Do we have enough proof?

    PubMed Central

    Firu, SG; Streba, CT; Firu, D; Tache, DE; Rogoveanu, I

    2015-01-01

    Rationale. Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker. Objective. To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis. Methods and results. We have searched through current literature and analyzed all significant full text articles on this topic. Discussions. NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed. Abbreviations: ADQI = Acute Dialysis Quality Initiative, AKI = acute kidney injury, AKIN = Acute Kidney Injury Network, ATN = acute tubular necrosis, CKD = chronic kidney disease, Cys C = cystatin C, GFR = glomerular filtration rate, HRS = hepatorenal syndrome, IAC = International Ascites Club, IL-18 = interleukin-18, KIM-1 = kidney injury molecule-1, L-FABP = liver-type fatty acid-binding protein, LT = liver transplantation, MDRD6 = Modification of Diet in Renal Disease 6, NAG = N-acetyl-β-D-glucosaminidase, NGAL = Neutrophil Gelatinase-Associated Lipocalin, pi-GST = pi-glutathione S-transferase, PRA = prerenal azotemia, RBP = retinol binding protein, RRT = renal replacement therapies, SCr = serum creatinine, SLKT = simultaneous liver and kidney transplant, UO = urine output, γ-GT = γ-glutamyl transpeptidase PMID:26361506

  16. ROLE OF ATP IN REGULATING RENAL MICROVASCULAR FUNCTION AND IN HYPERTENSION

    PubMed Central

    Guan, Zhengrong; Inscho, Edward W.

    2011-01-01

    Adenosine triphosphate (ATP) is an essential energy substrate for cellular metabolism but it can also influence many biological processes when released into the extracellular milieu. Research has established that extracellular ATP acts as an autocrine/paracrine factor that regulates many physiological functions. Alternatively, excessive extracellular ATP levels contribute to pathophysiological processes such as inflammation, cell proliferation and apoptosis, and atherosclerosis. Renal P2 receptors are widely distributed throughout glomeruli, vasculature and tubular segments, and participate in controlling renal vascular resistance, mediating renal autoregulation, and regulating tubular transport function. This review will focus on the role of ATP-P2 receptor signaling in regulating renal microvascular function and autoregulation, recent advances on the role of ATP-P2 signaling in hypertension-associated renal vascular injury, and emerging new directions. PMID:21768526

  17. [Assessment of renal function in elderly after eighty years: Cockroft and Gault or Modification of diet in renal disease equation?].

    PubMed

    Andro, M; Estivin, S; Comps, E; Gentric, A

    2011-11-01

    Assessment of renal function is essential in the management of hospitalised patients, particularly in geriatric practice. Impairment of renal function is common in the elderly, aged of 80 years and over, and should be taken into account before prescribing drugs eliminated through the kidneys or performing investigations requiring iodine injection. Renal failure is also a predictor of mortality. In clinical practice, creatinine-based equations are recommended to assess kidney function. The most widely used equations are the Cockroft and Gault (CG) and the simplified Modification of diet in renal disease (MDRD) formulas. The former estimates the clearance of creatinine in millilitres per minute, the latter estimates the glomerular filtration rate in millilitres per minute per 1.73 m(2). In 2002, the French high authority for health recommended the use of the CG formula, but no recommendation was given for the elderly. In the literature, no study has compared CG and MDRD formulas with a reference method in this very old population. In the octogenarians, two studies have compared these formulas with the creatinine clearance calculated on the basis of a 24-hour urine collection and four studies have compared the formulas head to head. All these studies showed that the results obtained with the MDRD formula are higher from 10 to 30 mL/min/1.73 m(2) than the results obtained with the CG formula. Studies simulating drug prescription showed that the use of the MDRD formula would lead to a risk of drug over dosage in 20 to 36% of the elderly. Also, two studies have suggested that only creatinine clearance measured by the CG formula is a predictor of mortality in the very old population. In conclusion, in the octogenarian, none of these two formulas is ideal. However, based on the results of studies targeted to this elderly population, the best solution seems to be the use of the CG formula expecting new methods of evaluation of renal function.

  18. Identification of Endogenous Biomarkers to Predict the Propensity of Drug Candidates to Cause Hepatic or Renal Transporter-Mediated Drug-Drug Interactions.

    PubMed

    Chu, Xiaoyan; Chan, Grace Hoyee; Evers, Raymond

    2017-09-01

    Drug transporters expressed in liver and kidney play a critical role in the elimination of a wide range of drugs and xenobiotics and inhibition of these transporters may therefore cause clinically significant drug-drug interactions (DDIs). Currently, in vitro transporter inhibition data are used to assess the risk that a drug candidate may act as an inhibitor of a transporter in patients at clinically relevant exposures. However, this approach is hampered by low confidence in in vitro to in vivo extrapolations, and large inter-system and inter-laboratory variability in in vitro data. Several endogenous compounds have been identified as substrates of drug transporters. Determining the impact of perpetrator drugs on the plasma or urinary exposure of these potential endogenous biomarkers in humans is being explored as an alternative approach to assess the DDI liability of drug candidates, especially in early drug development. In this review, we provide an overview of recently identified biomarkers used to study the inhibition of hepatic and renal transporters; summarize the methods and strategies employed to identify biomarkers; and discuss the utility, limitation, and future direction of biomarker approaches to predict transporter-mediated DDIs. Copyright © 2017. Published by Elsevier Inc.

  19. Human embryonic stem cells differentiate into functional renal proximal tubular-like cells.

    PubMed

    Narayanan, Karthikeyan; Schumacher, Karl M; Tasnim, Farah; Kandasamy, Karthikeyan; Schumacher, Annegret; Ni, Ming; Gao, Shujun; Gopalan, Began; Zink, Daniele; Ying, Jackie Y

    2013-04-01

    Renal cells are used in basic research, disease models, tissue engineering, drug screening, and in vitro toxicology. In order to provide a reliable source of human renal cells, we developed a protocol for the differentiation of human embryonic stem cells into renal epithelial cells. The differentiated stem cells expressed markers characteristic of renal proximal tubular cells and their precursors, whereas markers of other renal cell types were not expressed or expressed at low levels. Marker expression patterns of these differentiated stem cells and in vitro cultivated primary human renal proximal tubular cells were comparable. The differentiated stem cells showed morphological and functional characteristics of renal proximal tubular cells, and generated tubular structures in vitro and in vivo. In addition, the differentiated stem cells contributed in organ cultures for the formation of simple epithelia in the kidney cortex. Bioreactor experiments showed that these cells retained their functional characteristics under conditions as applied in bioartificial kidneys. Thus, our results show that human embryonic stem cells can differentiate into renal proximal tubular-like cells. Our approach would provide a source for human renal proximal tubular cells that are not affected by problems associated with immortalized cell lines or primary cells.

  20. SDF-1 provides morphological and functional protection against renal ischaemia/reperfusion injury.

    PubMed

    Stokman, Geurt; Stroo, Ingrid; Claessen, Nike; Teske, Gwendoline J D; Florquin, Sandrine; Leemans, Jaklien C

    2010-12-01

    The chemokine stromal cell-derived factor-1 (SDF-1) is thought to be involved in mediating tissue repair by promoting migration of bone marrow stem or progenitor cells to the site of injury. Increased levels of renal SDF-1 are found after kidney injury. However, recently, we showed that SDF-1 does not play an important role in the migration of haematopoietic stem cells to the post-ischaemic kidney. The function of increased post-ischaemic renal SDF-1 expression in modulating renal ischaemia/reperfusion injury remains, therefore, unknown. We studied the role of SDF-1 in renal ischaemia/reperfusion injury by locally decreasing SDF-1 expression and subsequent SDF-1 signalling in the corticomedullary region of the kidney using antisense oligonucleotide treatment in mice. Renal SDF-1 protein increased significantly in the early phase of ischaemia/reperfusion injury. Antisense treatment resulted in a reduction of corticomedullary SDF-1 expression which was accompanied by severely increased tubular injury and decreased renal function. We did not observe any difference in mobilization or retention of CXCR4-positive haematopoietic stem or progenitor cells after induction of renal ischaemia. Rather, antisense-treated animals showed markedly increased apoptosis of the tubular epithelium accompanied by an increased renal inflammatory response. Conclusions. These data indicate a new role for SDF-1 in renal pathogenesis by mediating tubular epithelial protection against ischaemic injury and suggest that SDF-1 by itself is not crucial for the influx of haematopoietic stem or progenitor cells towards the ischaemic injured kidney.

  1. Deficient dopamine D2 receptor function causes renal inflammation independently of high blood pressure.

    PubMed

    Zhang, Yanrong; Cuevas, Santiago; Asico, Laureano D; Escano, Crisanto; Yang, Yu; Pascua, Annabelle M; Wang, Xiaoyan; Jones, John E; Grandy, David; Eisner, Gilbert; Jose, Pedro A; Armando, Ines

    2012-01-01

    Renal dopamine receptors participate in the regulation of blood pressure. Genetic factors, including polymorphisms of the dopamine D(2) receptor gene (DRD2) are associated with essential hypertension, but the mechanisms of their contribution are incompletely understood. Mice lacking Drd2 (D(2)-/-) have elevated blood pressure, increased renal expression of inflammatory factors, and renal injury. We tested the hypothesis that decreased dopamine D(2) receptor (D(2)R) function increases vulnerability to renal inflammation independently of blood pressure, is an immediate cause of renal injury, and contributes to the subsequent development of hypertension. In D(2)-/- mice, treatment with apocynin normalized blood pressure and decreased oxidative stress, but did not affect the expression of inflammatory factors. In mouse RPTCs Drd2 silencing increased the expression of TNFα and MCP-1, while treatment with a D(2)R agonist abolished the angiotensin II-induced increase in TNF-α and MCP-1. In uni-nephrectomized wild-type mice, selective Drd2 silencing by subcapsular infusion of Drd2 siRNA into the remaining kidney produced the same increase in renal cytokines/chemokines that occurs after Drd2 deletion, increased the expression of markers of renal injury, and increased blood pressure. Moreover, in mice with two intact kidneys, short-term Drd2 silencing in one kidney, leaving the other kidney undisturbed, induced inflammatory factors and markers of renal injury in the treated kidney without increasing blood pressure. Our results demonstrate that the impact of decreased D(2)R function on renal inflammation is a primary effect, not necessarily associated with enhanced oxidant activity, or blood pressure; renal damage is the cause, not the result, of hypertension. Deficient renal D(2)R function may be of clinical relevance since common polymorphisms of the human DRD2 gene result in decreased D(2)R expression and function.

  2. Effects of chronic sympatho-inhibition on renal excretory function in renovascular hypertension.

    PubMed

    Burke, Sandra L; Evans, Roger G; Head, Geoffrey A

    2011-05-01

    Treatment of renovascular hypertension with drugs that directly target the renin-angiotensin system may compromise glomerular filtration and renal excretory function, leading to renal failure. Centrally acting sympathoinhibitory agents also inhibit the renin-angiotensin system, so we determined whether this treatment modality alters renal excretory function in rabbits with renovascular hypertension. Rabbits were equipped with bilateral renal artery flow probes and a renal nerve electrode. Hypertension was induced with a renal artery clip (2K1C) or rabbits were sham-clipped. After 2 weeks, a subcutaneous minipump was implanted to deliver rilmenidine (2.5 mg/kg per day) or vehicle for 3 weeks. Haemodynamic variables and renal function were studied under control conditions and during intravenous infusion of isotonic saline (154 mmol/l NaCl) at increasing rates of 4, 12 and 36 ml/kg per hour. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were greater in 2K1C rabbits than sham-clipped rabbits, but total urine flow, sodium excretion and glomerular filtration rate were similar in the two groups. In 2K1C rabbits, rilmenidine reduced MAP to close to control levels and reduced RSNA (40%), but did not significantly alter basal renal blood flow, glomerular filtration rate, urine flow or sodium excretion. The natriuretic response to isotonic saline load in 2K1C rabbits was not significantly altered by rilmenidine. These observations show that chronic treatment of rabbits with renal artery stenosis with a centrally acting sympathoinhibitory agent, despite normalizing MAP, does not compromise renal excretory function. Thus, this treatment modality may be particularly useful in renovascular hypertension. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

  3. Renal function evaluation in an adult female with cat-eye syndrome.

    PubMed

    Bellinghieri, G; Triolo, O; Stella, N C; Gemelli, M; Musolino, R; Monardo, P; Savica, V

    1994-01-01

    Cat-eye syndrome is a rare congenital anomaly involving the kidney. It is rarely reported in literature, while renal function has never been studied up to now. Shown here are the morphofunctional renal alterations observed in a female patient affected by cat-eye syndrome.

  4. Quantitative imaging of basic functions in renal (patho)physiology.

    PubMed

    Kang, Jung Julie; Toma, Ildiko; Sipos, Arnold; McCulloch, Fiona; Peti-Peterdi, Janos

    2006-08-01

    Multiphoton fluorescence microscopy offers the advantages of deep optical sectioning of living tissue with minimal phototoxicity and high optical resolution. More importantly, dynamic processes and multiple functions of an intact organ can be visualized in real time using noninvasive methods, and quantified. These studies aimed to extend existing methods of multiphoton fluorescence imaging to directly observe and quantify basic physiological parameters of the kidney including glomerular filtration rate (GFR) and permeability, blood flow, urinary concentration/dilution, renin content and release, as well as more integrated and complex functions like the tubuloglomerular feedback (TGF)-mediated oscillations in glomerular filtration and tubular flow. Streptozotocin-induced diabetes significantly increased single-nephron GFR (SNGFR) from 32.4 +/- 0.4 to 59.5 +/- 2.5 nl/min and glomerular permeability to a 70-kDa fluorophore approximately eightfold. The loop diuretic furosemide 2-fold diluted and increased approximately 10-fold the volume of distal tubular fluid, while also causing the release of 20% of juxtaglomerular renin content. Significantly higher speeds of individual red blood cells were measured in intraglomerular capillaries (16.7 +/- 0.4 mm/s) compared with peritubular vessels (4.7 +/- 0.2 mm/s). Regular periods of glomerular contraction-relaxation were observed, resulting in oscillations of filtration and tubular flow rate. Oscillations in proximal and distal tubular flow showed similar cycle times ( approximately 45 s) to glomerular filtration, with a delay of approximately 5-10 and 25-30 s, respectively. These innovative technologies provide the most complex, immediate, and dynamic portrayal of renal function, clearly depicting the components and mechanisms involved in normal physiology and pathophysiology.

  5. Cardiovascular disease biomarkers on cognitive function in older adults: Joint effects of cardiovascular disease biomarkers and cognitive function on mortality risk.

    PubMed

    Loprinzi, Paul D; Crush, Elizabeth; Joyner, Chelsea

    2017-01-01

    Previous research demonstrates an inverse association between age and cardiovascular disease (CVD) biomarkers with cognitive function; however, little is known about the combined associations of CVD risk factors and cognitive function with all-cause mortality in an older adult population, which was the purpose of this study. Data from the 1999-2002 NHANES were used (N=2,097; 60+yrs), with mortality follow-up through 2011. Evaluated individual biomarkers included mean arterial pressure (MAP), high-sensitivity C-reactive protein (CRP), HDL-C, total cholesterol (TC), A1C, and measured body mass index (BMI). Cognitive function was assessed using the Digit Symbol Substitution Test (DSST). Further, 4 groups were created based on CVD risk and cognitive function. Group 1: high cognitive function and low CVD risk; Group 2: high cognitive function and high CVD risk; Group 3: low cognitive function and low CVD risk; Group 4: low cognitive function and high CVD risk. An inverse relationship was observed where those with more CVD risk factors had a lower (worse) cognitive function score. Compared to those in Group 1, only those in Group 3 and 4 had an increase mortality risk.

  6. Successful renal transplantation from a brain-dead deceased donor with head injury, disseminated intravascular coagulation and deranged renal functions.

    PubMed

    Ghuge, P P; Kute, V B; Vanikar, A V; Gumber, M R; Gera, D N; Patel, H V; Shah, P R; Modi, P R; Shah, V R; Trivedi, H L

    2013-11-01

    Deceased donors (DDs) with the brain death due to head injury are the major source of organs for transplantation. The incidence of post-head injury disseminated intravascular coagulation (DIC) ranges from 24% to 50%. Many centers do not accept organs from donors with DIC due to increased risk of primary graft non-function and/or high chances of morbidity/mortality. We performed two successful renal transplants from a DD with head injury with DIC and deranged renal function. One of the recipients developed transient thrombocytopenia, but there was no evidence of DIC or delayed graft functions in either of the recipients. Over a follow-up of 1 month, both are doing well with stable graft function and hematological profile. Thus, a carefully selected DD with severe DIC even with deranged renal function is not a contraindication for organ donation if other risk factors for primary non-function are excluded. This approach will also help in overcoming organ shortage.

  7. Urinary Retinol-Binding Protein: Relationship to Renal Function and Cardiovascular Risk Factors in Chronic Kidney Disease

    PubMed Central

    Domingos, Maria Alice Muniz; Moreira, Silvia Regina; Gomez, Luz; Goulart, Alessandra; Lotufo, Paulo Andrade; Benseñor, Isabela; Titan, Silvia

    2016-01-01

    The role of urinary retinol-binding protein (RBP) as a biomarker of CKD in proximal tubular diseases, glomerulopathies and in transplantation is well established. However, whether urinary RBP is also a biomarker of renal damage and CKD progression in general CKD is not known. In this study, we evaluated the association of urinary RBP with renal function and cardiovascular risk factors in the baseline data of the Progredir Study, a CKD cohort in Sao Paulo, Brazil, comprising 454 participants with stages 3 and 4 CKD. In univariate analysis, urinary RBP was inversely related to estimated glomerular filtration rate (CKD-EPI eGFR) and several cardiovascular risk factors. After adjustments, however, only CKD-EPI eGFR, albuminuria, systolic blood pressure, anemia, acidosis, and left atrium diameter remained significantly related to urinary RBP. The inverse relationship of eGFR to urinary RBP (β-0.02 ± 95CI -0.02; -0.01, p<0.0001 for adjusted model) remained in all strata of albuminuria, even after adjustments: in normoalbuminuria (β-0.008 ± 95CI (-0.02; -0.001, p = 0.03), in microalbuminuria (β-0.02 ± 95CI (-0.03; -0.02, p<0,0001) and in macroalbuminuria (β-0.02 ± 95CI (-0.03; -0.01, p<0,0001). Lastly, urinary RBP was able to significantly increase the accuracy of a logistic regression model (adjusted for sex, age, SBP, diabetes and albuminuria) in diagnosing eGFR<35 ml/min/1.73m2 (AUC 0,77, 95%CI 0,72–0,81 versus AUC 0,71, 95%CI 0,65–0,75, respectively; p = 0,05). Our results suggest that urinary RBP is significantly associated to renal function in CKD in general, a finding that expands the interest in this biomarker beyond the context of proximal tubulopathies, glomerulopathies or transplantation. Urinary RBP should be further explored as a predictive marker of CKD progression. PMID:27655369

  8. Regulation of Vascular and Renal Function by Metabolite Receptors.

    PubMed

    Peti-Peterdi, János; Kishore, Bellamkonda K; Pluznick, Jennifer L

    2016-01-01

    To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis-from salt and water balance to metabolism-by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families-(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and

  9. [Dosing adjustment and renal function: Which equation(s)?].

    PubMed

    Delanaye, Pierre; Flamant, Martin; Cavalier, Étienne; Guerber, Fabrice; Vallotton, Thomas; Moranne, Olivier; Pottel, Hans; Boffa, Jean-Jacques; Mariat, Christophe

    2016-02-01

    While the CKD-EPI (for Chronic Kidney Disease Epidemiology) equation is now implemented worldwide, utilization of the Cockcroft formula is still advocated by some physicians for drug dosage adjustment. Justifications for this recommendation are that the Cockcroft formula was preferentially used to determine dose adjustments according to renal function during the development of many drugs, better predicts drugs-related adverse events and decreases the risk of drug overexposure in the elderly. In this opinion paper, we discuss the weaknesses of the rationale supporting the Cockcroft formula and endorse the French HAS (Haute Autorité de santé) recommendation regarding the preferential use of the CKD-EPI equation. When glomerular filtration rate (GFR) is estimated in order to adjust drug dosage, the CKD-EPI value should be re-expressed for the individual body surface area (BSA). Given the difficulty to accurately estimate GFR in the elderly and in individuals with extra-normal BSA, we recommend to prescribe in priority monitorable drugs in those populations or to determine their "true" GFR using a direct measurement method.

  10. Long-term Effects of Remote Ischemic Preconditioning on Kidney Function in High-risk Cardiac Surgery Patients: Follow-up Results from the RenalRIP Trial.

    PubMed

    Zarbock, Alexander; Kellum, John A; Van Aken, Hugo; Schmidt, Christoph; Küllmar, Mira; Rosenberger, Peter; Martens, Sven; Görlich, Dennis; Meersch, Melanie

    2017-05-01

    In a multicenter, randomized trial, the authors enrolled patients at high-risk for acute kidney injury as identified by a Cleveland Clinic Foundation score of 6 or more. The authors enrolled 240 patients at four hospitals and randomized them to remote ischemic preconditioning or control. The authors found that remote ischemic preconditioning reduced acute kidney injury in high-risk patients undergoing cardiac surgery. The authors now report on the effects of remote ischemic preconditioning on 90-day outcomes. In this follow-up study of the RenalRIP trial, the authors examined the effect of remote ischemic preconditioning on the composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction at 90 days. Secondary outcomes were persistent renal dysfunction and dialysis dependence in patients with acute kidney injury. Remote ischemic preconditioning significantly reduced the occurrence of major adverse kidney events at 90 days (17 of 120 [14.2%]) versus control (30 of 120 [25.0%]; absolute risk reduction, 10.8%; 95% CI, 0.9 to 20.8%; P = 0.034). In those patients who developed acute kidney injury after cardiac surgery, 2 of 38 subjects in the remote ischemic preconditioning group (5.3%) and 13 of 56 subjects in the control group (23.2%) failed to recover renal function at 90 days (absolute risk reduction, 17.9%; 95% CI, 4.8 to 31.1%; P = 0.020). Acute kidney injury biomarkers were also increased in patients reaching the major adverse kidney event endpoint compared to patients who did not. Remote ischemic preconditioning significantly reduced the 3-month incidence of a composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction in high-risk patients undergoing cardiac surgery. Furthermore, remote ischemic preconditioning enhanced renal recovery in patients with acute kidney injury.

  11. Radiolabeled technetium chelates for use in renal function determinations

    DOEpatents

    Fritzberg, Alan; Kasina, Sudhaker; Johnson, Dennis L.

    1994-01-01

    The present invention is directed to novel radiopharmaceutical imaging agents incorporating Tc-99m as a radiolabel. In particular, the novel imaging agents disclosed herein have relatively high renal extraction efficiencies, and hence are useful for conducting renal function imaging procedures. The novel Tc-99m compounds of a present invention have the following general formula: ##STR1## wherein X is S or N; and wherein Y is --H or wherein Y is ##STR2## and where R.sub.1 is --H, --CH.sub.3, or --CH.sub.2 CH.sub.3 ; R.sub.2 is --H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.3, --CH.sub.2 CH.sub.3, CH.sub.2 C.sub.6 H.sub.5, or --CH.sub.2 OH; and Z is --H, --CO.sub.2 H, --CONH.sub.2, --SO.sub.3 H, --SO.sub.2 NH.sub.2, or --CONHCH.sub.2 CO.sub.2 H; and the Tc is Tc-99m; and water-soluble salts thereof. Of the foregoing, the presently preferred Tc-99m compound of the present invention is Tc-99m-mercaptoacetylglycylglycylglycine (Tc-99m-MAGGG). The present invention is also directed to novel chelating agents that may be reacted with Tc-99m to form the foregoing compounds. Such novel chelating agents have the following general formula. ##STR3## where X and Y have the same definitions as above, and wherein Y' is --H.sub.2 when X is N, or wherein Y' is --H, or a suitable protective group such as --COCH.sub.3, --COC.sub.6 H.sub.5, --CH.sub.2 NHCOCH.sub.3, --COCF.sub.3, or --COCH.sub.2 OH when X is S. The present invention also provides methods for preparing and using the novel Tc-99m compounds.

  12. Radiolabeled technetium chelates for use in renal function determinations

    DOEpatents

    Fritzberg, Alan; Kasina, Sudhakar; Johnson, Dennis L.

    1990-01-01

    The present invention is directed to novel radiopharmaceutical imaging agents incorporating Tc-99m as a radiolabel. In particular, the novel imaging agents disclosed herein have relatively high renal extraction efficiencies, and hence are useful for conducting renal function imaging procedures. The novel Tc-99m compounds of a present invention have the following general formula: ##STR1## wherein X is S or N; and wherein Y is--H or wherein Y is ##STR2## and where R.sub.1 is --H, --CH.sub.3, or --CH.sub.2 CH.sub.3 ; R.sub.2 is --H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CONH.sub.2, --CH.sub.2 CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.3, --CH.sub.2 CH.sub.3, CH.sub.2 C.sub.6 H.sub.5, or --CH.sub.2 OH; and Z is --H, --CO.sub.2 H, --CONH.sub.2, --SO.sub.3 H, --SO.sub.2 NH.sub.2, or --CONHCH.sub.2 CO.sub.2 H; and the Tc is Tc-99m; and water-soluble salts thereof. Of the foregoing, the presently preferred Tc-99m compound of the present invention is Tc-99m-mercaptoacetylglycylglycylglycine (Tc-99m-MAGGG). The present invention is also directed to novel chelating agents that may be reacted with Tc-99m to form the foregoing compounds. Such novel chelating agents have the following general formula. ##STR3## where X and Y have the same definitions as above, and wherein Y' is --H.sub.2 when X is N, or wherein Y' is --H, or a suitable protective group such as --COCH.sub.3, --COC.sub.6 H.sub.5, --CH.sub.2 NHCOCH.sub.3, --COCF.sub.3, or --COCH.sub.2 OH when X is S. The present invention also provides methods for preparing and using the novel Tc-99m compounds.

  13. Cystatin C estimated glomerular filtration rate to assess renal function in early stages of autosomal dominant polycystic kidney disease

    PubMed Central

    Sans, Laia; Radosevic, Aleksandar; Quintian, Claudia; Montañés, Rosario; Gràcia, Silvia; Vilaplana, Carles; Mojal, Sergi; Ballarin, José A.

    2017-01-01

    Background/Aims Height-adjusted total kidney volume (htTKV) is the best marker of disease progression in early autosomal dominant polycystic kidney disease (ADPKD) when renal function still remains normal. The usefulness of cystatin-C as a biomarker to assess renal function according to renal volume has not been studied in ADPKD patients. Methods Observational and cross-sectional study of 62 ADPKD patients. htTKV, creatinine and cystatin-C estimated glomerular filtration rate (eGFR) were determined. Correlations between htTKV and eGFR were studied. A control group was used to determine the association between renal function differences and htTKV. Results htTKV significantly correlated with cystatin-C-eGFR (r = -0.384, p = 0.002) but not with creatinine-eGFR (r = -0.225, p = 0.078). With htTKV stratified into tertiles, a significant difference of cystatin-C-eGFR but not in creatinine-eGFR was detected in the third tertile when compared with the first tertile group (110.0±22.2 vs 121.3±7.2; p = 0.023 and 101.8±17.2 vs 106.9±15.1; p = 0.327 respectively). When cystatin-C-eGFR of the controls was used as the reference, htTKV above 605 ml/m identified with a 75% sensitivity and 84.9% specificity those patients with a significant worse kidney function. However, this cut-off value could not be identified using creatinine-eGFR. Conclusions Cystatin-C-eGFR but not creatinine-eGFR correlated with htTKV in ADPKD patients in early stages of the disease. Differences in cystatin-C-eGFR but not in creatinine-eGFR have been identified through htTKV tertiles. A htTKV above 605 ml/m is associated with a worse renal function only if cystatin-C-eGFR is used. Cystatin-C-eGFR should be studied in prospective studies of early stages of ADPKD to determine its usefulness as an early marker of disease progression. PMID:28346513

  14. Cystatin C estimated glomerular filtration rate to assess renal function in early stages of autosomal dominant polycystic kidney disease.

    PubMed

    Sans, Laia; Radosevic, Aleksandar; Quintian, Claudia; Montañés, Rosario; Gràcia, Silvia; Vilaplana, Carles; Mojal, Sergi; Ballarin, José A; Fernández-Llama, Patricia; Torra, Roser; Pascual, Julio

    2017-01-01

    Height-adjusted total kidney volume (htTKV) is the best marker of disease progression in early autosomal dominant polycystic kidney disease (ADPKD) when renal function still remains normal. The usefulness of cystatin-C as a biomarker to assess renal function according to renal volume has not been studied in ADPKD patients. Observational and cross-sectional study of 62 ADPKD patients. htTKV, creatinine and cystatin-C estimated glomerular filtration rate (eGFR) were determined. Correlations between htTKV and eGFR were studied. A control group was used to determine the association between renal function differences and htTKV. htTKV significantly correlated with cystatin-C-eGFR (r = -0.384, p = 0.002) but not with creatinine-eGFR (r = -0.225, p = 0.078). With htTKV stratified into tertiles, a significant difference of cystatin-C-eGFR but not in creatinine-eGFR was detected in the third tertile when compared with the first tertile group (110.0±22.2 vs 121.3±7.2; p = 0.023 and 101.8±17.2 vs 106.9±15.1; p = 0.327 respectively). When cystatin-C-eGFR of the controls was used as the reference, htTKV above 605 ml/m identified with a 75% sensitivity and 84.9% specificity those patients with a significant worse kidney function. However, this cut-off value could not be identified using creatinine-eGFR. Cystatin-C-eGFR but not creatinine-eGFR correlated with htTKV in ADPKD patients in early stages of the disease. Differences in cystatin-C-eGFR but not in creatinine-eGFR have been identified through htTKV tertiles. A htTKV above 605 ml/m is associated with a worse renal function only if cystatin-C-eGFR is used. Cystatin-C-eGFR should be studied in prospective studies of early stages of ADPKD to determine its usefulness as an early marker of disease progression.

  15. Relationship between renal function and renal volume in autosomal dominant polycystic kidney disease: cross-sectional study.

    PubMed

    Torres-Sánchez, M J; Ávila-Barranco, E; Esteban de la Rosa, R J; Fernández-Castillo, R; Esteban, M A; Carrero, J J; García-Valverde, M; Bravo-Soto, J A

    2016-03-01

    To determine in patients with autosomal dominant polycystic kidney disease the relationship between total renal volume (the sum of both kidneys, TRV) as measured by magnetic resonance and renal function; and its behaviour according to sex and the presence of arterial hypertension, hypercholesterolaemia and hyperglycemia. Cross-sectional study including patients with autosomal dominant polycystic kidney disease who underwent periodic reviews at Nephrology external consultations at Hospital de las Nieves de Granada, and who underwent an magnetic resonance to estimate renal volume between January 2008 and March 2011. We evaluated 67 patients (59.7% women, average age of 48±14.4 years) and found a significant positive association between TRV and serum creatinine or urea, which was reversed compared with estimated glomerular filtration by MDRD-4 and Cockcroft-Gault. Women showed an average serum creatinine level and a significantly lower TRV level compared with males. Subgroups affected by arterial hypertension and hyperuricemia presented average values for serum creatinine and urea, higher for TRV and lower for estimated glomerular filtration. The hypercholesterolaemia subgroup showed higher average values for urea and lower for estimated glomerular filtration, without detecting significant differences compared with TRV. The volume of polycystic kidneys measured by magnetic resonance is associated with renal function, and can be useful as a complementary study to monitor disease progression. The presence of arterial hypertension, hyperuricemia or hypercholesterolaemia is associated with a poorer renal function. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  16. Renal function after reduction in cadmium exposure: an 8-year follow-up of residents in cadmium-polluted areas.

    PubMed

    Liang, Yihuai; Lei, Lijian; Nilsson, Johan; Li, Huiqi; Nordberg, Monica; Bernard, Alfred; Nordberg, Gunnar F; Bergdahl, Ingvar A; Jin, Taiyi

    2012-02-01

    Long-term exposure to cadmium (Cd) causes renal dysfunction, but the change in renal function with exposure is unknown. We assessed the evolution of Cd-induced renal effects after a reduction in dietary exposure to Cd in rice. Four hundred twelve residents in previously Cd-polluted and nonpolluted areas were examined twice, in 1998 and in 2006. Changes in blood Cd, urinary Cd, and kidney function [N-acetyl-β-d-glucosaminidase (NAG), β2-microglobulin, and albumin in urine] were measured. In the most polluted area, mean blood Cd was 8.9 μg/L and 3.3 μg/L in 1998 and in 2006, respectively, and urinary Cd was 11.6 and 9.0 μg/g creatinine. Urinary albumin in 1998 increased with urinary Cd, but no such exposure-response relation appeared for 2006 albumin versus urinary Cd 1998, indicating recovery. Other biomarkers of kidney function were also elevated in 1998. Partial recovery was observed for NAG among women and was suggested for β2-microglobulin among young individuals. The probability of having β2-microglobulin levels above the 95th percentile in 2006 was high in those with elevated β2-microglobulin in 1998 [odds ratio (OR) = 24.8; 95% confidence interval (CI): 11.2, 55.3] compared with albumin (OR = 3.0; 95% CI: 1.2, 7.5) and NAG (OR = 2.6; 95% CI: 1.6, 4.4). Results suggest that a Cd-mediated increase in urinary albumin excretion is reversible upon substantial reduction of exposure. For markers of tubular effects, we observed a tendency toward improvement but not complete recovery. Data from repeated observations suggest that β2-microglobulin may be more informative than NAG as an indicator for an individual's future tubular function.

  17. Effect of Organophosphate Compounds on Renal Function and Transport.

    DTIC Science & Technology

    1983-09-15

    analysis by serial section electron microscopy. J . Ultrastruct. Res., 43 (1973) 107-132. 5. L. Barajas , AJ. Silverman and J . Muller, Ultrastructure...localization of acetylcholinesterase in the renal nerves. J . Ultrastruct. Res., 49 (1974) 297-311. 6. L. Barajas and P. Wang, Demonstration of...acetylcholinesterase in the adrenergic nerves of the renal glomerular arterioles. J . Ultrastruct. Res., 53 (1975) 244-253. 7. L. Barajas , P. Wang and S. DeSantis

  18. Renal function parameters during early and late recovery periods following an all-out 21-km run in trained adolescent runners.

    PubMed

    Tian, Ye; Tong, Tom K; Lippi, Giuseppe; Huang, Chuanye; Shi, Qingde; Nie, Jinlei

    2011-06-01

    This study investigated the changes in biomarkers of renal function and the corresponding estimated glomerular filtration rate (eGFR) in 10 male adolescent (16.2±0.6 years) trained runners during early and late recovery periods after an all-out 21-km run. Venous blood samples were taken immediately before, and at 2-h, 4-h, and 24-h following the 21-km run. Samples were analyzed for hemoglobin (Hb) and hematocrit (Hct), and serum urea (U), creatinine (Cr), creatine kinase (CK) and lactate dehydrogenase (LDH). U/Cr ratio, eGFR, and plasma volume change (%ΔPV) were calculated based on the associated measured variables. At 2-h and 4-h, there were increases (26%-146%) in U, Cr, U/Cr, CK, and LDH, and decreases (8%-13%) in Hb and Hct, as compared with the corresponding pre-exercise values. The calculated %ΔPV increased by 17% while the eGFR decreased 20% from the corresponding pre-exercise value, respectively. At 24-h, the changes of the blood variables and renal function parameters observed at early recovery period were sustained. Taken together, the findings of this study suggest that mild decline in renal function occurred during the early recovery period following the 21-km run. The decline in renal function did not return to normal during the later recovery period.

  19. Cystatin-C, Renal Function and Incidence of Hip Fracture in Postmenopausal Women

    PubMed Central

    LaCroix, Andrea Z.; Lee, Jennifer S.; Wu, LieLing; Cauley, Jane A.; Shlipak, Michael G.; Ott, Susan M.; Robbins, John; Curb, J. David; Leboff, Meryl; Bauer, Douglas C.; Jackson, Rebecca D.; Kooperberg, Charles L.; Cummings, Steven R.

    2010-01-01

    OBJECTIVES To evaluate the association of chronic kidney disease with incident hip fracture using serum cystatin-C as a biomarker of renal function calculated without reference to muscle mass. DESIGN Case-control study nested within a prospective study. SETTING The Women’s Health Initiative Observational Study conducted at 40 US clinical centers. PARTICIPANTS From 93,676 women ages 50–79 years followed for an average of 7 years, 397 incident hip fracture cases and 397 matched controls were studied. MEASUREMENTS Cystatin-C levels were measured on baseline serum using a particle-enhanced immunonepholometric assay. Estimated glomerular filtration rates (eGFRcys-c) were calculated with a validated equation and categorized into three groups: 1) eGFRcys-c >90 mL/min/1.73 m2; 2) eGFRcys-c 60–90 mL/min/1.73 m2; or 3) eGFRcys-c <60 mL/min/1.73 m2 indicating chronic kidney disease Stages 3–4. RESULTS The odds ratio (OR) for hip fracture was 2.50 (95% confidence interval (CI) 1.32–4.72) for eGFRcys-c <60 ml/min/1.73 m2 compared to Stages 0–1 after adjustment for body mass, parental hip fracture, smoking, alcohol consumption and physical function. No association was observed for eGFRcys-c 60–90 mL/min/1.73 m2 (OR=1.04; CI 0.66–1.64). These associations were unaffected by additional adjustment for poor health status, hemoglobin, serum 25hydroxyvitamin D, or bone metabolism markers. Adjustment for plasma homocysteine reduced the OR for eGFRcys-c <60 mL/min/1.73 m2 to 1.83 (CI 0.93–3.61). CONCLUSION Women with cystatin-C eGFR levels <60 have a substantially increased risk of hip fracture. This association may be partially mediated, or accompanied by, effects of renal function on homocysteine levels. PMID:18662213

  20. MicroRNAs in diabetic nephropathy: functions, biomarkers, and therapeutic targets

    PubMed Central

    Kato, Mitsuo; Natarajan, Rama

    2015-01-01

    MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene expression by posttranscriptional and epigenetic mechanisms and affect many cellular processes and disease states. Over 2,000 human mature miRNAs have been identified, and at least 60% of all human protein-coding genes are known to be regulated by miRNAs. MicroRNA biogenesis involves classical transcription regulation and processing by key ribonucleases, as well as other protein factors and epigenetic mechanisms. Diabetic nephropathy (DN), a severe microvascular complication frequently associated with diabetes mellitus, is a major cause of renal failure. Although several mechanisms of regulation of key renal genes implicated in DN pathogenesis have been identified, a greater understanding is needed to develop better treatment modalities. Recent studies show that miRNAs can be induced in renal cells in vivo and in vitro under diabetic conditions and promote the accumulation of extracellular matrix proteins related to fibrosis and glomerular dysfunction. In this review, we highlight the significance of the expression of miRNAs in various stages of DN and emerging approaches to exploit them as biomarkers for early detection or novel therapeutic targets to prevent progression of DN. PMID:25877817

  1. Acute effects of percutaneous tract dilation on renal function and structure.

    PubMed

    Handa, Rajash K; Matlaga, Brian R; Connors, Bret A; Ying, Jun; Paterson, Ryan F; Kuo, Ramsay L; Kim, Samuel C; Lingeman, James E; Evan, Andrew P; Willis, Lynn R

    2006-12-01

    Percutaneous nephrolithotomy (PCNL) is performed on a routine basis for the rapid and efficient removal of large caliceal stones. After percutaneous puncture, rigid dilators or an inflatable balloon are used to dilate the nephrostomy tract to allow access to the collecting system for stone removal. Little is known of the acute impact of tract dilation procedures on renal function. We compared renal hemodynamic and excretory function in female pigs immediately before and up to 5 hours after percutaneous nephrostomy (PCN) using sequential Amplatz dilators (N = 8) or Nephromax balloon inflation (N = 7) and control pigs with no PCN access (N = 8). We also examined renal function in patients undergoing PCNL. The two PCN procedures produced a renal lesion of comparable size and morphology, as well as similar changes in renal function. Glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary sodium excretion (U(Na)V) were significantly reduced in Amplatz- and Nephromax-treated kidneys throughout the 5-hour observation period, by about 50%, 60%, and 80%, respectively. In control pigs, GFR and RPF remained stable and U(Na)V declined progressively to about 50% of baseline over the course of the experiment. The contralateral kidney showed changes in renal function similar to those in the PCN-treated or control kidney in all three groups. A retrospective analysis of 196 adults with normal renal function who underwent unilateral PCNL using the Nephromax balloon dilator revealed a significant increase in serum creatinine of 0.14 mg/dL at 1 day. Both animal and human studies show that PCN is associated with an acute decline in renal function.

  2. Formoterol restores mitochondrial and renal function after ischemia-reperfusion injury.

    PubMed

    Jesinkey, Sean R; Funk, Jason A; Stallons, L Jay; Wills, Lauren P; Megyesi, Judit K; Beeson, Craig C; Schnellmann, Rick G

    2014-06-01

    Mitochondrial biogenesis may be an adaptive response necessary for meeting the increased metabolic and energy demands during organ recovery after acute injury, and renal mitochondrial dysfunction has been implicated in the pathogenesis of AKI. We proposed that stimulation of mitochondrial biogenesis 24 hours after ischemia/reperfusion (I/R)-induced AKI, when renal dysfunction is maximal, would accelerate recovery of mitochondrial and renal function in mice. We recently showed that formoterol, a potent, highly specific, and long-acting β2-adrenergic agonist, induces renal mitochondrial biogenesis in naive mice. Animals were subjected to sham or I/R-induced AKI, followed by once-daily intraperitoneal injection with vehicle or formoterol beginning 24 hours after surgery and continuing through 144 hours after surgery. Treatment with formoterol restored renal function, rescued renal tubules from injury, and diminished necrosis after I/R-induced AKI. Concomitantly, formoterol stimulated mitochondrial biogenesis and restored the expression and function of mitochondrial proteins. Taken together, these results provide proof of principle that a novel drug therapy to treat AKI, and potentially other acute organ failures, works by restoring mitochondrial function and accelerating the recovery of renal function after injury has occurred.

  3. Baroreflex function is reduced in Alzheimer's disease: a candidate biomarker?

    PubMed

    Meel-van den Abeelen, Aisha S S; Lagro, Joep; Gommer, Erik D; Reulen, Jos P H; Claassen, Jurgen A H R

    2013-04-01

    The baroreflex (BR) reflects autonomic blood pressure control. Alzheimer's disease (AD) affects the autonomic system. Detailed properties of BR in AD are unknown. We hypothesized that BR is reduced in AD, and is influenced by autonomic effects of cholinesterase inhibitors (ChEI). BR was determined in 18 AD patients, 11 patients with mild cognitive impairment (MCI) and 19 healthy control subjects. In AD, BR was measured again after ChEI treatment. Receiver operating characteristic analysis was used to define a BR cutoff value, which was then tested in an independent validation sample of 16 AD, 18 MCI, and 18 control subjects. BR was lower in AD compared with MCI (p < 0.05) and in MCI compared with healthy control subjects (p < 0.01). Receiver operating characteristic analysis between AD and healthy control subjects yielded a sensitivity of 89% and a specificity of 94%. ChEI treatment increased BR with 66% (p < 0.01). BR was reduced in AD and increased after treatment with ChEI. BR might be a good biomarker to further explore the link between cardiovascular disease and AD.

  4. Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

    PubMed Central

    von Roemeling, Christina A.; Marlow, Laura A.; Radisky, Derek C.; Rohl, Austin; Larsen, Hege E.; Wei, Johnny; Sasinowska, Heather; Zhu, Heng; Drake, Richard; Sasinowski, Maciek; Tun, Han W.; Copland, John A.

    2014-01-01

    Currently there is a lack of targeted therapies that lead to long-term attenuation or regression of disease in patients with advanced clear cell renal cell carcinoma (ccRCC). Our group has implemented a high-throughput genetic analysis coupled with a high-throughput proliferative screen in order to investigate the genetic contributions of a large cohort of overexpressed genes at the functional level in an effort to better understand factors involved in tumor initiation and progression. Patient gene array analysis identified transcripts that are consistently elevated in patient ccRCC as compared to matched normal renal tissues. This was followed by a high-throughput lentivirus screen, independently targeting 195 overexpressed transcripts identified in the gene array in four ccRCC cell lines. This revealed 31 ‘hits’ that contribute to ccRCC cell proliferation. Many of the hits identified are not only presented in the context of ccRCC for the first time, but several have not been previously linked to cancer. We further characterize the function of a group of hits in tumor cell invasion. Taken together these findings reveal pathways that may be critical in ccRCC tumorigenicity, and identifies novel candidate factors that could serve as targets for therapeutic intervention or diagnostic/prognostic biomarkers for patients with advanced ccRCC. PMID:24979721