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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. 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.

  4. 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

  5. Higher biomarker-calibrated protein intake is not associated with impaired renal function in postmenopausal women.

    PubMed

    Beasley, Jeannette M; Aragaki, Aaron K; LaCroix, Andrea Z; Neuhouser, Marian L; Tinker, Lesley F; Cauley, Jane A; Ensrud, Kristine E; Jackson, Rebecca D; Prentice, Ross L

    2011-08-01

    With aging, renal function tends to decline, as evidenced by reduced glomerular filtration rate. High-protein intake may further stress the kidneys by causing sustained hyperfiltration. To investigate whether dietary protein is associated with impaired renal function, we used data from 2 nested case-control studies within the Women's Health Initiative Observational Study (n = 2419). We estimated protein intake using a FFQ and estimated glomerular filtration rate (eGFR) from cystatin C. To account for the original study designs, inverse probability weights were applied. Self-reported energy and protein were calibrated using biomarkers of energy and protein intake. Associations between protein intake and renal function were estimated by weighted linear and logistic regression models. Average calibrated protein intake (mean ± SD) was 1.1 ± 0.2 g/(kg body weight·d).Twelve percent (n = 292) of women had impaired renal function. The odds of impaired renal function, defined as eGFR <60 mL/(min·1.73m(2)), was not associated with calibrated protein intake. When eGFR was modeled continuously, there was no association with calibrated protein when protein was expressed in absolute (g/d) or relative to energy (protein % energy/d), but protein relative to body weight [g/(kg body weight·d)] was associated with higher eGFR. There was no evidence for effect modification by age, BMI, or general health status. These data suggest higher protein intake is not associated with impaired renal function among postmenopausal women without a diagnosis of chronic kidney disease.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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,…

  15. 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.

  16. 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.

  17. Renal function assessment in heart failure.

    PubMed

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

    2017-03-01

    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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. [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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. Biomarkers of Renal Tumor Burden and Progression in TSC

    DTIC Science & Technology

    2013-09-01

    Renal lesions in TSC can cause significant morbidity and mortality. Most solid renal lesions of TSC are angiomyolipoma (AML), but some are...More power is needed to address clinical variables that impact urine composition. Assessment of renal function revealed CKD at substantially higher...frequencies in TSC than in the general population. TSC patients have approximately 15 times more CKD at 40-60 years of age, and those with TSC2 gene

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. [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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. [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.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. Residual renal function: a paradigm shift.

    PubMed

    Lowenstein, Jerome; Grantham, Jared J

    2017-03-01

    Residual renal function (RRF) in patients undergoing dialysis treatments is currently viewed as glomerular filtrate that has escaped tubular reabsorption. RRF has been quantified as a clearance of urea or creatinine, or urea + creatinine. A major paradigm shift has followed the recognition that a substantial number of organic anion retention solutes (possible "uremic toxins") are protein-bound and therefore are not readily filtered. These protein-bound aryl compounds are secreted by renal tubular organic anion transporters (OATs). This has led to the recognition that RRF in dialysis patients probably represents not only unreabsorbed glomerular filtrate but also a contribution of renal tubular transporters that secrete organic anions. Tubular secretion of hippurate, indoxyl sulfate, and p-cresol sulfate, protein-bound organic anions retained in the plasma of end-stage renal disease patients, can be quantified and used to evaluate the integrity of a function dependent on active solute transport. Here we propose a shift away from the exclusive "glomerulocentric" view of RRF as unreabsorbed glomerular filtrate and of the progression of renal disease as progressive glomerular loss. We expand the definition of RRF to include the combined renal and tubule functions remaining after a disease begins to destroy nephrons and proceeds to anuria. We propose renewed application of the first principles of renal physiology, articulated in the last century by Homer Smith, to the understanding and monitoring of RRF and progression of renal injury in patients during the sometimes long course of and at the end stage of chronic renal disease.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Biomarkers of delayed graft function as a form of acute kidney injury in kidney transplantation

    PubMed Central

    Malyszko, Jolanta; Lukaszyk, Ewelina; Glowinska, Irena; Durlik, Magdalena

    2015-01-01

    Renal transplantation ensures distinct advantages for patients with end-stage kidney disease. However, in some cases early complications can lead to allograft dysfunction and consequently graft loss. One of the most common early complications after kidney transplantation is delayed graft function (DGF). Unfortunately there is no effective treatment for DGF, however early diagnosis of DGF and therapeutic intervention (eg modification of immunosuppression) may improve outcome. Therefore, markers of acute kidney injury are required. Creatinine is a poor biomarker for kidney injury due principally to its inability to help diagnose early acute renal failure and complete inability to help differentiate among its various causes. Different urinary and serum proteins have been intensively investigated as possible biomarkers in this setting. There are promising candidate biomarkers with the ability to detect DGF. We focused on emerging biomarkers of DGF with NGAL is being the most studied followed by KIM-1, L-FABP, IL-18, and others. However, large randomized studies are needed to establish the value of new, promising biomarkers, in DGF diagnosis, prognosis and its cost-effectiveness. PMID:26175216

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. [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)

  5. 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

  6. 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

  7. 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

  8. 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.

  9. Pharmacokinetics of renally excreted drug dexpramipexole in subjects with impaired renal function

    PubMed Central

    He, Ping; Kerr, Doug; Marbury, Thomas; Ries, Daniel; Farwell, Wildon; Stecher, Scott; Dong, Yingwen; Wei, Dong; Rogge, Mark

    2014-01-01

    This phase I, open-label, single-dose study evaluated the pharmacokinetics, safety, and tolerability of renally excreted drug dexpramipexole in subjects with normal and impaired renal function, i.e. mild, moderate, severe renal impairment, or end-stage renal disease (ESRD) requiring hemodialysis when matched by age and sex. Dexpramipexole area under the curves (AUCs), but not Cmax, were significantly increased with the severity of renal impairment after a single dose administration. The geometric mean ratio of dose-normalized AUC(0–72) was 1.4, 1.7, 2.7, and 4.5, respectively, in mild, moderate, severe renal impairment, and ESRD subjects when compared to healthy subjects. There was a strong association between renal function (eGFR) and dexpramipexole CLr. The slope (90% confidence interval(CI)) of eGFR and renal clearance (CLr) in the regression model was 3.1 (2.4, 3.7). Dexpramipexole elimination in ESRD subjects during both dialysis and non-dialysis (i.e., interval between dialysis) was insignificant. Single 75 mg and 150 mg doses of dexpramipexole were well tolerated, and the safety profile was comparable across renal function groups. Extensive drug accumulation may occur with repeated dosing in patients with significant renal impairment. It is recommended that dexpramipexole not to be given to patients with severe renal impairment or in those with ESRD. PMID:24965504

  10. 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

  11. [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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. [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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  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.

  7. 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.

  8. [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.

  9. 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.

  10. 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.

  11. 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.

  12. [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.

  13. 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.

  14. 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.

  15. [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.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. [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.

  14. 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.

  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. 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.

  17. 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

  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

    2017-04-05

    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. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. [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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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)

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Effect of renal function on prognosis in chronic heart failure.

    PubMed

    Löffler, Adrián Ignacio; Cappola, Thomas P; Fang, James; Hetzel, Scott J; Kadlec, Andrew; Astor, Brad; Sweitzer, Nancy K

    2015-01-01

    Renal dysfunction (RD) is associated with increased mortality in heart failure (HF). The aim of this study was to identify whether worsened or improved renal function during mid-term follow-up is associated with worsened outcomes in patients with chronic HF. A total of 892 participants from a multicenter cohort study of chronic HF were followed over 3.1 ± 1.9 years of enrollment. Worsened and improved renal functions were tested with multivariate models as independent predictors of HF hospitalization and mortality. Although 12% of subjects experienced a ≥25% decrease in estimated glomerular filtration rate (eGFR), 17% experienced a ≥25% increase in eGFR, and there was stability of kidney function observed in the cohort as a whole. The quartile with the worst RD at any point in time had increased risk of HF hospitalization and mortality. Worsened eGFR was associated with HF outcomes in the unadjusted (hazard ratio = 1.71, 95% confidence interval 1.04 to 2.81, p = 0.035), but not the adjusted analysis. Improvement in eGFR was not associated with outcome (p = 0.453). In chronic HF, the severity of RD predicts risk of poor outcome better than changes in renal function during mid-term follow-up. This suggests that in patients with appropriately treated chronic HF, worsening renal function in itself does not yield useful prognostic information and may not reflect poor outcome.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  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. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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.

  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. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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...

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers.

    PubMed

    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

    2016-01-01

    We previously described early results of a nonchimeric operational tolerance protocol in human leukocyte antigen (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 eight enrollees were initially tolerant 1 year off immunosuppression. Biopsies of three others after total withdrawal showed Banff 1A acute cellular rejection without renal dysfunction. With longer follow-up including 5-year posttransplant biopsies, four of the five tolerant recipients remain without rejection while one developed Banff 1A without renal dysfunction. We now add seven new subjects (two operationally tolerant), and demonstrate time-dependent increases of circulating CD4(+) CD25(+++) CD127(-) FOXP3(+) Tregs versus losses of Tregs in nontolerant 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 posttransplant. The blood signature was validated by an external Immune Tolerance Network data set. Our approach to nonchimeric operational HLA-identical tolerance reveals association with Treg immunophenotypes and serial gene expression profiles.

  20. 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

  1. 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

  2. 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

  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. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  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. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  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. 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

  7. 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.

  8. 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

  9. 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.

  10. [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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. [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.

  17. 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

  18. 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.

  19. 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.

  20. Assessment of the efficacy of functional food ingredients-introducing the concept "kinetics of biomarkers".

    PubMed

    Verhagen, Hans; Coolen, Stefan; Duchateau, Guus; Hamer, Mark; Kyle, Janet; Rechner, Andreas

    2004-07-13

    Functional foods are "foods and beverages with claimed health benefits based on scientific evidence". Health claims need to be substantiated scientifically. The future of functional foods will heavily rely on proven efficacy in well-controlled intervention studies with human volunteers. In order to have the maximum output of human trials, improvements are needed with respect to study design and optimization of study protocols. Efficacy at realistic intake levels needs to be established in studies with humans via the use of suitable biomarkers, unless the endpoint can be measured directly. The human body is able to deal with chemical entities irrespective of their origin, and the pharmaceutical terms "absorption, distribution, metabolism and excretion" have their equivalent when biomarkers are concerned. Whereas only "diurnal variation" or "circadian rhythm" is sometimes considered, little attention is paid to "kinetics of biomarkers". "Kinetics of biomarkers" comprises "formation, distribution, metabolism and excretion". However, this is at present neither an established science nor common practice in nutrition research on functional foods. As a consequence, sampling times and matrices, for example, are chosen on the basis of historical practice and convenience (for volunteers and scientists) but not on the basis of in depth insight. The concept of kinetics of biomarkers is illustrated by a variety of readily comprehensible examples, such as malaria, cholesterol, polyphenols, glutathione-S-transferase alpha, F2-isoprostanes, interleukin-6, and plasma triacylglycerides.

  1. Effect of Organophosphate Compounds on Renal Function and Transport.

    DTIC Science & Technology

    1983-09-15

    cholinomimetic- induced diuresis , they do demonstrate a direct action of these compounds on renal cell electrolyte balance. Carter’s group did not examine the...Carrier. J. Friborg and 3. P. Onay, Vasodilators, intrarenal blood flow, and natriuresis in the dog. Amer. 3. Physiol., 221 (1971) 92- 98. 11. U.K...tylchol insestaraso activity. Diochem. Pharmacol., 7 (1961) 88-94. 19. 3.P. Hayslett, U. Kashgarian and F.H. Epstein, The diuresis of renal 17

  2. 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

  3. 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

  4. 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.

  5. 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

  6. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    PubMed

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  7. Parathyroid function in uremic children during periods of renal insufficiency, hemodialysis, and transplantation.

    PubMed

    Gruskin, A B; Root, A W; Duckett, G E; Baluarte, H J

    1976-11-01

    Function of the parathyroid gland was evaluated in children with renal insufficiency prior to and after imitation of hemodialysis, and again following renal transplantation. Serum levels of immunoreactive parathyroid hormone responded appropriately to increases or decreases of serum calcium concentrations in the three groups. Functional and histologic studies in the children with renal insufficiency demonstrated the cause of their elevated circulating levels of iPTH to be diffuse parathyroid hyperplasia. During hemodialysis, the serum concentration of calcium rose and that of iPTH decreased, when the calcium gradient between the dialysate and the blood favored movement of calcium into the body. During treatment with prednisolone (20 mg/kg intravenously) for reversal of renal transplant rejection, the serum concentration of calcium decreased and that of iPTH increased. These observations suggest that autonomy of the parathyroid gland rarely occurs in children with renal insufficiency, and that hemodialysis using a dialysate with a high concentration of calcium might assist in retarding the progression of renal osteodystrophy. Furthermore, if hyperparathyroidism contributes in part to growth failure in children with chronic renal disease, steroid-induced changes in cirulating iPTH following renal transplantation may inhibit growth.

  8. 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.

  9. Evaluation of renal function in the elderly, not as easy as it seems: a review.

    PubMed

    Ungar, Andrea; Iacomelli, Iacopo; Giordano, Antonella; Roberts, Anna Teresa; Rafanelli, Martina; Marchionni, Niccolò

    2015-08-01

    In the elderly assessment of renal function by glomerular filtration rate estimation is crucial for diagnostic, therapeutic and prognostic purposes. Our aim is to illustrate the different formulas available and their respective advantages and disadvantages.

  10. Preserving residual renal function in dialysis patients: an update on evidence to assist clinical decision making

    PubMed Central

    Jensen, Jens Dam; Peters, Christian Daugaard; Jespersen, Bente

    2011-01-01

    It has been documented that preservation of residual renal function in dialysis patients improves quality of life as well as survival. Clinical trials on strategies to preserve residual renal function are clearly lacking. While waiting for more results from clinical trials, patients will benefit from clinicians being aware of available knowledge. The aim of this review was to offer an update on current evidence assisting doctors in clinical practice. PMID:25949486

  11. Intra-Parenchymal Renal Resistive Index Variation (IRRIV) Describes Renal Functional Reserve (RFR): Pilot Study in Healthy Volunteers.

    PubMed

    Samoni, Sara; Nalesso, Federico; Meola, Mario; Villa, Gianluca; De Cal, Massimo; De Rosa, Silvia; Petrucci, Ilaria; Brendolan, Alessandra; Rosner, Mitchell H; Ronco, Claudio

    2016-01-01

    An increase of glomerular filtration rate after protein load represents renal functional reserve (RFR) and is due to afferent arteriolar vasodilation. Lack of RFR may be a risk factor for acute kidney injury (AKI), but is cumbersome to measure. We sought to develop a non-invasive, bedside method that would indirectly measure RFR. Mechanical abdominal pressure, through compression of renal vessels, decreases blood flow and activates the auto-regulatory mechanism which can be measured by a fall in renal resistive index (RRI). The study aims at elucidating the relationship between intra-parenchymal renal resistive index variation (IRRIV) during abdominal pressure and RFR. In healthy volunteers, pressure was applied by a weight on the abdomen (fluid-bag 10% of subject's body weight) while RFR was measured through a protein loading test. We recorded RRI in an interlobular artery after application of pressure using ultrasound. The maximum percentage reduction of RRI from baseline was compared in the same subject to RFR. We enrolled 14 male and 16 female subjects (mean age 38 ± 14 years). Mean creatinine clearance was 106.2 ± 16.4 ml/min/1.73 m(2). RFR ranged between -1.9 and 59.7 with a mean value of 28.9 ± 13.1 ml/min/1.73 m(2). Mean baseline RRI was 0.61 ± 0.05, compared to 0.49 ± 0.06 during abdominal pressure; IRRIV was 19.6 ± 6.7%, ranging between 3.1% and 29.2%. Pearson's coefficient between RFR and IRRIV was 74.16% (p < 0.001). Our data show the correlation between IRRIV and RFR. Our results can lead to the development of a "stress test" for a rapid screen of RFR to establish renal susceptibility to different exposures and the consequent risk for AKI.

  12. What physicians need to know about renal function in outpatients with heart failure.

    PubMed

    Waldum-Grevbo, Bård

    2015-01-01

    The majority of outpatients with heart failure (HF) have chronic kidney disease (CKD) as an important comorbidity. Both glomerular filtration rate and abnormal urinary albumin excretion are major predictors of outcome in HF patients. Despite this, patients with renal dysfunction have been systematically excluded from the large randomized HF trials. There is lack of evidence for optimal treatment in these cardiorenal patients and treatment nihilism may account in part for their bad prognosis. Identifying and monitoring the progression of renal disease and making an effort to preserve renal function should be an important task in the management of all patients with HF. In this review, the current understanding of the pathophysiology of renal dysfunction in outpatients with HF will be summarized. Furthermore, important principles of the identification and management of cardiorenal patients will be described in order to make the physician more capable of managing outpatients with HF and renal dysfunction.

  13. Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib

    PubMed Central

    Cebrián, Arancha; Gómez del Pulgar, Teresa; Méndez-Vidal, María José; Gonzálvez, María Luisa; Lainez, Nuria; Castellano, Daniel; García-Carbonero, Iciar; Esteban, Emilio; Sáez, Maria Isabel; Villatoro, Rosa; Suárez, Cristina; Carrato, Alfredo; Munárriz-Ferrándiz, Javier; Basterrechea, Laura; García-Alonso, Mirta; González-Larriba, José Luis; Perez-Valderrama, Begoña; Cruz-Jurado, Josefina; González del Alba, Aránzazu; Moreno, Fernando; Reynés, Gaspar; Rodríguez-Remírez, María; Boni, Valentina; Mahillo-Fernández, Ignacio; Martin, Yolanda; Viqueira, Andrea; García-Foncillas, Jesús

    2017-01-01

    Sunitinib is the currently standard treatment for metastatic renal cell carcinoma (mRCC). Multiple candidate predictive biomarkers for sunitinib response have been evaluated but none of them has been implemented in the clinic yet. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) in genes linked to mode of action of sunitinib and immune response as biomarkers for mRCC. This is a multicenter, prospective and observational study involving 20 hospitals. Seventy-five mRCC patients treated with sunitinib as first line were used to assess the impact of 63 SNPs in 31 candidate genes on clinical outcome. rs2243250 (IL4) and rs5275 (PTGS2) were found to be significantly associated with shorter cancer-specific survival (CSS). Moreover, allele C (rs5275) was associated with higher PTGS2 expression level confirming its functional role. Combination of rs5275 and rs7651265 or rs2243250 for progression free survival (PFS) or CSS, respectively, was a more valuable predictive biomarker remaining significant after correction for multiple testing. It is the first time that association of rs5275 with survival in mRCC patients is described. Two-SNP models containing this functional variant may serve as more predictive biomarkers for sunitinib and could suppose a clinically relevant tool to improve the mRCC patient management. PMID:28117391

  14. Acute thrombosis of a transplanted renal artery after gastric ulcer bleeding in a patient with a long-term well-functioning renal allograft

    PubMed Central

    Wu, Chung-Kuan; Leu, Jyh-Gang; Wei, Cheng-Chun; Hsieh, Shih-Chung

    2016-01-01

    Abstract Background: Acute thrombosis of a transplanted renal artery is a serious vascular complication following renal allograft transplantation, which usually occurs within the first month after transplantation and often results in graft loss. It rarely occurs beyond the first month, except in a rejected kidney or in a kidney with high-grade transplant renal artery stenosis. Result: A 65-year-old male with a history of type 2 diabetes mellitus, hypertension, pulmonary tuberculosis, and end-stage renal disease was previously treated with hemodialysis (HD). He received a kidney transplant and had a well-functioning graft for 2 years. He presented to our emergency department with gastric ulcer bleeding and received treatment involving an endoscopic submucosal epinephrine injection, a proton pump inhibitor, and blood transfusions. Nine days later, he complained of sudden lower abdominal pain and had acute anuric kidney failure. Renal ultrasonography revealed an absence of blood flow to the allograft kidney. Renal artery angiogram demonstrated complete occlusion of the transplanted renal artery. After thrombectomy and percutaneous transluminal angioplasty (PTA) with stent placement, 60% stenosis of the proximal renal artery with distal perfusion was noted. However, his graft function did not improve, and he received HD again. Histopathology of the transplanted kidney revealed ischemic tubular nephropathy with focal infarction without rejection. Conclusion: This is the first case of acute thrombosis of the transplanted renal artery following gastric ulcer bleeding in a patient with a long-term well-functioning graft kidney. PMID:27472705

  15. Impact of recovery of renal function on long-term mortality after coronary artery bypass grafting.

    PubMed

    Mehta, Rajendra H; Honeycutt, Emily; Patel, Uptal D; Lopes, Renato D; Shaw, Linda K; Glower, Donald D; Harrington, Robert A; Califf, Robert M; Sketch, Michael H

    2010-12-15

    Whether prognosis differs in acute renal failure (ARF) after coronary artery bypass grafting (CABG) in patients with and without recovery of renal function is not known. We studied patients who had CABG at Duke University Medical Center (1995 to 2008). ARF was defined as an increase in peak creatinine ≥50% after CABG or ≥0.7 mg/dl above baseline or need for new dialysis. Patients were categorized into 3 groups: (1) no ARF after CABG, (2) ARF after CABG and completely recovered renal function at day 7 (return of creatinine to no higher than baseline and no dialysis), or (3) ARF after CABG with no recovery of renal function at day 7 (creatinine no higher than baseline or new dialysis). Main outcome measurement was risk-adjusted long-term mortality (excluding death ≤7 days). ARF after CABG occurred in 2,083 of 10,415 patients (20%) and completely recovered in 703 (33.7%). Risk-adjusted mortality was highest in patients with ARF without recovery of renal function (hazard ratios 1.47, 95% confidence interval 1.34 to 1.62) and intermediate in those with ARF but completely recovered renal function (hazard ratios 1.21, 95% confidence interval 1.07 to 1.37, referent no-ARF group). Mortality was lower in patients with ARF compared to those without complete recovery of renal function (p = 0.0083). In conclusion, in patients with ARF after CABG, complete recovery of renal function was associated with significantly lower long-term mortality compared to those without such recovery, although this was significantly higher than in those without ARF. Thus, major emphasis should be on prevention of ARF in patients undergoing CABG.

  16. Relationship between renal function and extracorporeal membrane oxygenation use: a single-center experience.

    PubMed

    Gupta, Punkaj; Carlson, Jacob; Wells, Dennis; Selakovich, Patrick; Robertson, Michael J; Gossett, Jeffrey M; Fontenot, Eudice E; Steiner, Matthew B

    2015-04-01

    The effects of extracorporeal membrane oxygenation (ECMO) support on renal function in children with critical illness are unknown. The objective of this study was to investigate the impact of ECMO on renal function among children in different age groups. We performed a single-center retrospective observational study in critically ill children ≤ 18 years supported on ECMO for refractory cardiac or pulmonary failure (2006-2012). The patient population was divided into four age groups for the purpose of comparisons. The Acute Kidney Injury Network's (AKIN's) validated, three-tiered staging system for acute kidney injury was used to categorize the degree of worsening renal function. Data on patient demographics, baseline characteristics, renal function parameters, dialysis, ultrafiltration, duration of mechanical cardiac support, and mortality were collected. Comparisons of baseline characteristics, duration of mechanical cardiac support, and renal function were made between the four age groups. During the study period, 311 patients qualified for inclusion, of whom 289 patients (94%) received venoarterial (VA) ECMO, 12 (4%) received venovenous (VV) ECMO, and 8 (3%) received both VV and VA ECMO. A total of 109 patients (36%) received ultrafiltration on ECMO, 58 (19%) received hemodialysis, and 51 (16%) received peritoneal dialysis. There was a steady and sustained improvement in renal function in all age groups during the ECMO run, with the maximum and longest-sustained improvement occurring in the oldest age group. Proportions of patients in different AKIN stages remained similar in the first 7 days after ECMO initiation. We demonstrate that renal dysfunction improves early after ECMO support. Irrespective of the underlying disease process or patient age, renal function improves in children with pulmonary or cardiac failure who are placed on ECMO.

  17. RIFLE criteria and hepatic function in the assessment of acute renal failure in liver transplantation.

    PubMed

    Tinti, F; Umbro, I; Meçule, A; Rossi, M; Merli, M; Nofroni, I; Corradini, S Ginanni; Poli, L; Pugliese, F; Ruberto, F; Berloco, P B; Mitterhofer, A P

    2010-05-01

    Renal dysfunction in cirrhotic patients is primary related to disturbances of circulatory function, triggered by portal hypertension with chronic intrarenal vasoconstriction and hypoperfusion. Pretransplant renal function is an important factor implicated in the development of acute renal failure (ARF) after liver transplantation (OLT), but other factors mostly related to liver function seem to influence the development of ARF. The Acute Dialysis Quality Initiative workgroup developed the RIFLE classification to define ARF. We sought to evaluate the incidence of ARF among patients undergoing OLT, to evaluate the association of ARF with pre-OLT renal and hepatic functions, and to evaluate the influence of ARF on chronic kidney disease (CKD) at 1 month post-OLT. Clinical, renal, hepatic function, and donor risk index data of 24 patients who underwent deceased donor OLT were collected before transplantation, in the perioperative period and in the first month post-OLT. ARF occurred in 37.5% of patients with 56% developing the R grade and 44% the I grade; no patient showed the F grade. An association was observed between ARF and a higher Model for End-Stage Liver Disease (MELD) score and between ARF and a reduced pre-OLT serum albumin. No association was noted between ARF and other pre-OLT parameters. In cirrhotic patients serum creatinine is a bias for renal function assessment and the Modification of Diet in Renal Disease formula overestimates GFR. Post-OLT CKD was present in 6.7% of patients without ARF and in 44.4% of patients with ARF. The R grade developed more frequently among patients with viral cirrhosis. The association of ARF with MELD and hypoalbuminemia may be the result of a close relationship between renal and hepatic functions among cirrhotic patients. Post-OLT CKD may be the result of unrecognized, preexisting CKD and/or the effects of not fully resolved acute damage to an injured kidney.

  18. Cystatin C-Based Renal Function Changes After Antiretroviral Initiation: A Substudy of a Randomized Trial

    PubMed Central

    Gupta, Samir K.; Kitch, Douglas; Tierney, Camlin; Daar, Eric S.; Sax, Paul E.; Melbourne, Kathleen; Ha, Belinda; McComsey, Grace A.

    2014-01-01

    Background.  The effects of antiretrovirals on cystatin C-based renal function estimates are unknown. Methods.  We analyzed changes in renal function using creatinine and cystatin C-based estimating equations in 269 patients in A5224s, a substudy of study A5202, in which treatment-naive patients were randomized to abacavir/lamivudine or tenofovir/emtricitabine with open-label atazanavir/ritonavir or efavirenz. Results.  Changes in renal function significantly improved (or declined less) with abacavir/lamivudine treatment compared with tenofovir/emtricitabine using the Cockcroft-Gault formula (P = .016) and 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI; P = .030) and 2012 CKD-EPI cystatin C-creatinine (P = .025). Renal function changes significantly improved (or declined less) with efavirenz compared with atazanavir/ritonavir (P < .001 for all equations). Mean (95% confidence interval) renal function changes specifically for tenofovir/emtricitabine combined with atazanavir/ritonavir were −8.3 (−14.0, −2.6) mL/min with Cockcroft-Gault; −14.9 (−19.7, −10.1) mL/min per 1.732 with Modification of Diet in Renal Disease; −12.8 (−16.5, −9.0) mL/min per 1.732 with 2009 CKD-EPI; +8.9 (4.2, 13.7) mL/min per 1.732 with 2012 CKD-EPI cystatin C; and −1.2 (−5.1, 2.6) mL/min per 1.732 with 2012 CKD-EPI cystatin C-creatinine. Renal function changes for the other treatment arms were more favorable but similarly varied by estimating equation. Conclusions.  Antiretroviral-associated changes in renal function vary in magnitude and direction based on the estimating equation used. PMID:25734077

  19. Preoperative and postoperative cortical function of the kidney with staghorn calculi assessed by 99mtechnetium-dimercaptosuccinic acid renal scintigraphy.

    PubMed

    Kawamura, J; Itoh, H; Okada, Y; Higashi, Y; Yoshida, O; Fujita, T; Torizuka, K

    1983-09-01

    99mTechnetium dimercaptosuccinic acid renal scintigraphy, consisting of the cortical image and dimercaptosuccinic acid renal uptake rate, was used to assess preoperative and postoperative renal function in 55 patients with staghorn calculi. In 14 of 20 patients who had undergone extended pyelolithotomy and in 4 of 22 who had undergone nephrolithotomy there was an increase or no change in the postoperative dimercaptosuccinic acid renal uptake in the surgically treated kidney. However, there was no increase in the postoperative dimercaptosuccinic acid renal uptake in the patients who had undergone pyelolithotomy combined with nephrotomy or partial nephrectomy. Eight per cent of the preoperative dimercaptosuccinic acid renal uptake rate in the diseased kidney seems to be the absolute level for predicting the postoperative recovery of renal function. Dimercaptosuccinic acid renal images provide evidence of morphological changes in the cortex of the kidney with stones and the dimercaptosuccinic acid uptake rate is a useful adjunct for quantitative assessments of preoperative and postoperative residual cortical function.

  20. Effect of carotid occlusion and of perfusion pressure on renal function in conscious dogs.

    PubMed

    Gross, R; Kirchheim, H; Ruffmann, K

    1981-06-01

    We studied the effect of bilateral common carotid occlusion (implanted pneumatic cuffs) on renal blood flow (electromagnetic flowmeter) and renal function (implanted ureteral catheter) in nine chronically instrumented, conscious dogs on a high sodium diet (14 mmol/kg body weight per day). By means of suprarenal aortic constriction (pneumatic cuff) the influence of renal perfusion pressure was investigated. There was no change in renal blood flow or glomerular filtration rate (inulin clearance) with either reflexly increasing (+49.6%) or constant renal perfusion pressure. Carotid occlusion caused an increase of urine output by 80.5% and of sodium excretion by 85.3% due to a fall in fractional sodium reabsorption (-0.9%) when renal perfusion pressure was allowed to rise. Neither an increase of diuresis or sodium excretion nor an antinatriuresis was observed when renal perfusion pressure was kept constant during carotid occlusion. We conclude that, in conscious dogs at rest, the moderate sympathetic activation associated with carotid occlusion is too small to induce renal sympathetic vasoconstriction or antinatriuresis. The "carotid sinus polyuria" is a pressure-diuresis.

  1. PGRMC1 Is a Novel Potential Tumor Biomarker of Human Renal Cell Carcinoma Based on Quantitative Proteomic and Integrative Biological Assessments

    PubMed Central

    Wang, Xixi; Zhang, Peng; Lu, Weiliang; Yu, Yamei; Deng, Shi; Yang, Hanshuo; Zhu, Hongxia; Xu, Ningzhi; Liang, Shufang

    2017-01-01

    Progesterone receptor membrane component 1 (PGRMC1) is widely observed with an elevated level in multiple human cancers. However, the roles of PGRMC1 in renal cancer are not clear and merit further study. In this report, we made a systematic, integrative biological assessment for PGRMC1 in renal cell carcinoma (RCC) by a quantitative proteomic identification, immunohistochemical detection, and its clinic pathologic significance analysis. We found that PGRMC1 abundance is increased by 3.91-fold in RCC tissues compared with its autologous para-cancerous tissues by a quantitative proteome identification. To validate the proteomic result with more confidence, 135 clinic RCC tissues were recruited to measure PGRMC1 abundance by immunohistochemical staining, and 63.7% RCC samples (n = 86) showed a higher abundance of PGRMC1 than the noncancerous counterparts. And the elevated PGRMC1 level was related to the tumor malignancy degree and overall survival of RCC patients. Meanwhile the average serum PGRMC1 concentration for RCC patients (n = 18) was significantly increased by 1.67 fold compared with healthy persons. Moreover an exogenous elevated abundance of PGRMC1 by plasmid transfections significantly enhanced cell proliferation of renal cancer cells in vitro. Our findings demonstrate PGRMC1, which promotes RCC progression phenotypes in vitro and in vivo, is a novel potential biomarker and therapeutic target for RCC. PMID:28107520

  2. Cefepime-Induced Non-Convulsive Status Epilepticus in a Patient with Normal Renal Function

    PubMed Central

    Park, Hyeon-Mi; Noh, Young; Yang, Ji Won; Shin, Dong Hoon; Lee, Yeong-Bae

    2016-01-01

    Cefepime-induced encephalopathy including nonconvulsive status epilepticus has been known to develop in the patients with renal impairment. However, we report a 74-year-old woman with normal renal function who developed stuporous mental status during cefepime administration. Electroencephalogram (EEG) revealed 2 Hz rhythmic sharp-and-waves continuously, which suggested nonconvulsive status epilepticus (NCSE). After cefepime discontinuation, clinical symptoms recovered gradually and EEG findings showed only background slowing without epileptiform discharges. Cefepime-induced NCSE could be developed even in the patients with normal renal function, when they are elderly. Therefore, clinicians should be aware of the possibility of cefepime-induced NCSE when prescribing cefepime even to the patients with normal renal function. PMID:28101482

  3. Metformin-Associated Lactic Acidosis in a Patient with Normal Renal Function.

    PubMed

    Omar, Ahmed; Ellen, Ruth; Sorisky, Alexander

    2016-08-01

    We report a case of metformin-associated lactic acidosis (MALA) in the setting of normal renal function and review the relevant medical literature. A 77-year-old female diagnosed with type 2 diabetes mellitus previously treated with insulin and gliclazide MR was started on metformin. A few weeks later, she was found to have lactic acidosis. Renal function was normal, and no severe underlying illness was identified. Metformin was discontinued, and lactate levels normalized within 4 days, suggesting metformin was a reversible precipitant of the lactic acidosis. MALA can occur in the absence of renal impairment, systemic hypoperfusion or severe liver disease. A possible mechanism is a genetically determined alteration in metformin pharmacokinetics. Metformin is beneficial and safe in patients with normal renal function, but the development of MALA, although rare, should be kept in mind to prevent potentially life-threatening toxicity.

  4. Deregulated MicroRNAs in Biliary Tract Cancer: Functional Targets and Potential Biomarkers

    PubMed Central

    Beyreis, Marlena; Wagner, Andrej; Pichler, Martin; Neureiter, Daniel

    2016-01-01

    Biliary tract cancer (BTC) is still a fatal disease with very poor prognosis. The lack of reliable biomarkers for early diagnosis and of effective therapeutic targets is a major demanding problem in diagnosis and management of BTC. Due to the clinically silent and asymptomatic characteristics of the tumor, most patients are diagnosed at an already advanced stage allowing only for a palliative therapeutic approach. MicroRNAs are small noncoding RNAs well known to regulate various cellular functions and pathologic events including the formation and progression of cancer. Over the last years, several studies have shed light on the role of microRNAs in BTC, making them potentially attractive therapeutic targets and candidates as biomarkers. In this review, we will focus on the role of oncogenic and tumor suppressor microRNAs and their direct targets in BTC. Furthermore, we summarize and discuss data that evaluate the diagnostic power of deregulated microRNAs as possible future biomarkers for BTC. PMID:27957497

  5. Green tea inhibited the elimination of nephro-cardiovascular toxins and deteriorated the renal function in rats with renal failure

    PubMed Central

    Peng, Yu-Hsuan; Sweet, Douglas H.; Lin, Shiuan-Pey; Yu, Chung-Ping; Lee Chao, Pei-Dawn; Hou, Yu-Chi

    2015-01-01

    Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound nephro-cardiovascular toxins, which are not efficiently removed through hemodialysis. The renal excretions of IS and PCS were mediated by organic anion transporters (OATs) such as OAT1 and OAT3. Green tea (GT) is a popular beverage containing plenty of catechins. Previous pharmacokinetic studies of teas have shown that the major molecules present in the bloodstream are the glucuronides/sulfates of tea catechins, which are putative substrates of OATs. Here we demonstrated that GT ingestion significantly elevated the systemic exposures of endogenous IS and PCS in rats with chronic renal failure (CRF). More importantly, GT also significantly increased the levels of serum creatinine (Cr) and blood urea nitrogen (BUN) in CRF rats. Mechanism studies indicated that the serum metabolites of GT (GTM) inhibited the uptake transporting functions of OAT1 and OAT3. In conclusion, GT inhibited the elimination of nephro-cardiovascular toxins such as IS and PCS, and deteriorated the renal function in CRF rats. PMID:26552961

  6. The effect of radiopharmaceutical choice on the determination of relative renal function in rats with unilateral renal obstruction

    SciTech Connect

    Taylor, A.; Lallone, R.

    1984-01-01

    A significant divergence of GFR and ERPF within a single kidney could lead to different estimates of relative renal function depending on which radiopharmaceutical is administered. To address this question, the authors studied adult male Sprague-Dawley rats with unilateral ureteral obstruction by giving each animal an intravenous injection of 10 ..mu..Ci of I-125 iothalamate (GFR), I-131 hippurate (ERPF), and TC-99m DMSA and measuring the 30 minute clearance (renal uptake and urine excretion) of each agent. Normal control animals were sham operated; 25 experimental animals were subjected to permanent unilateral ureteral occlusion and studied at 6 hours, 1, 3, 7 and 14 days. Acute ureteral obstruction impaired the clearance of iothalamate to a much greater degree than OIH or DMSA at 6 hours and 1 day (rho<.005) and 3 days (rho<.05). The decline in DMSA clearance reflected ERPF more closely than GFR. In evaluating renal disease, one should consider the functional parameter reflected by the radiopharmaceutical as well as the underlying disease state.

  7. Reliability of predicted renal function in Japanese patients on cisplatin therapy.

    PubMed

    Yajima, A; Ogawa, C; Yatabe, M; Kondo, N; Saito, S; Suzuki, Y; Uesawa, Y

    2013-09-01

    Cisplatin, cis-Dichlorodiammine platinum (II) (CDDP) remains a major antineoplastic drug for the treatment of solid tumors. Its chief dose-limiting side effect is nephrotoxicity. To make a safe and effective dosing regimen of a drug excreted mainly by the renal route, evaluation of patients' renal function is essential. Creatinine clearance (CLcr) or glomerular filtration rate (GFR) is considered to be a standard renal-function test. Several equations have been used in clinical settings, to predict CLcr and GFR using serum creatinine concentration. We carried out a retrospective analysis of the correlation between 24-hour CLcr measured by a urine collection method; and the predicted CLcr and GFR estimated by various equations such as Jelliffe, Yasuda, Orita, Mawer, Mawer, MDRD and modified MDRD, and Cockcroft-Gault. This study used data from Japanese head-and-neck cancer patients, before and after chemotherapy with CDDP. Slopes of regression lines of scatter plots between measured CLcr and predicted renal function in post-CDDP patients were less compared to pre-CDDP patients. On the other hand, Y-intercepts were noted in the scatter plots on renal function from all equations. These results suggest that evaluation of renal function using predictive formulae may have been over-/under-estimated after CDDP administration.

  8. Usefulness of basic renal function tests in decision-making in children with loss of renal parenchyma and/or dilation of the urinary tract.

    PubMed

    García Nieto, Víctor M; Luis Yanes, Maria Isabel; Arango Sancho, Pedro; Sotoca Fernandez, Jorge V

    2016-01-01

    Basic renal function tests such as maximum urine osmolality and urinary elimination of albumin and N-acetyl-glucosaminidase often reveal abnormalities in clinical cases involving hyperpressure in the urinary tract or loss of renal parenchyma. However, in all the available algorithms dedicated to the study of children with urinary tract infection or dilation, the benefit of using these functional parameters is not mentioned. In this review, we provide information about the practical usefulness of assessing the basic renal function parameters. From these data, we propose an algorithm that combines morphological and functional parameters to make a reasoned case for voiding cystourethrography.

  9. Extrarenal citrulline disposal in mice with impaired renal function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The endogenous synthesis of arginine, a semiessential amino acid, relies on the production of citrulline by the gut and its conversion into arginine by the kidney in what has been called the "intestinal-renal axis" for arginine synthesis. Although the kidney is the main site for citrulline disposal,...

  10. Systematic expression analysis of the mitochondrial complex III subunits identifies UQCRC1 as biomarker in clear cell renal cell carcinoma

    PubMed Central

    Ellinger, Jörg; Gromes, Arabella; Poss, Mirjam; Brüggemann, Maria; Schmidt, Doris; Ellinger, Nadja; Tolkach, Yuri; Dietrich, Dimo; Kristiansen, Glen; Müller, Stefan C.

    2016-01-01

    Mitochondrial dysfunction is common in cancer, and the mitochondrial electron transport chain is often affected in carcinogenesis. So far, few is known about the expression of the mitochondrial complex III (ubiquinol-cytochrome c reductase complex) subunits in clear cell renal cell carcinoma (ccRCC). In this study, the NextBio database was used to determine an expression profile of the mitochondrial complex III subunits based on published microarray studies. We observed that five out of 11 subunits of the complex III were downregulated in at least three microarray studies. The decreased mRNA expression level of UQCRFS1 and UQCRC1 in ccRCC was confirmed using PCR. Low mRNA levels UQCRC1 were also correlated with a shorter period of cancer-specific and overall survival. Furthermore, UQCRFS1 and UQCRC1 were also decreased in ccRCC on the protein level as determined using Western blotting and immunohistochemistry. UQCRC1 protein expression was also lower in ccRCC than in papillary and chromophobe subtypes. Analyzing gene expression and DNA methylation in The Cancer Genome Atlas cohort revealed an inverse correlation of gene expression and DNA methylation, suggesting that DNA hypermethylation is regulating the expression of UQCRC1 and UQCRFS1. Taken together, our data implicate that dysregulated UQCRC1 and UQCRFS1 are involved in impaired mitochondrial electron transport chain function. PMID:27845902

  11. Sodium Thiosulfate Ameliorates Oxidative Stress and Preserves Renal Function in Hyperoxaluric Rats

    PubMed Central

    Bijarnia, Rakesh K.; Bachtler, Matthias; Chandak, Prakash G.; van Goor, Harry; Pasch, Andreas

    2015-01-01

    Background Hyperoxaluria causes crystal deposition in the kidney, which leads to oxidative stress and to injury and damage of the renal epithelium. Sodium thiosulfate (STS, Na2S2O3) is an anti-oxidant, which has been used in human medicine for decades. The effect of STS on hyperoxaluria-induced renal damage is not known. Methods Hyperoxaluria and renal injury were induced in healthy male Wistar rats by chronic exposure to ethylene glycol (EG, 0.75%) in the drinking water for 4 weeks. The treatment effects of STS, NaCl or Na2SO4 were compared. Furthermore, the effects of STS on oxalate-induced oxidative stress were investigated in vitro in renal LLC-PK1 cells. Results Chronic EG exposure led to hyperoxaluria, oxidative stress, calcium oxalate crystalluria and crystal deposition in the kidneys. Whereas all tested compounds significantly reduced crystal load, only STS-treatment maintained tissue superoxide dismutase activity and urine 8-isoprostaglandin levels in vivo and preserved renal function. In in vitro studies, STS showed the ability to scavenge oxalate-induced ROS accumulation dose dependently, reduced cell-released hydrogen peroxide and preserved superoxide dismutase activity. As a mechanism explaining this finding, STS was able to directly inactivate hydrogen peroxide in cell-free experiments. Conclusions STS is an antioxidant, which preserves renal function in a chronic EG rat model. Its therapeutic use in oxidative-stress induced renal-failure should be considered. PMID:25928142

  12. Targeting complement activation in brain-dead donors improves renal function after transplantation.

    PubMed

    Damman, Jeffrey; Hoeger, Simone; Boneschansker, Leo; Theruvath, Ashok; Waldherr, Ruediger; Leuvenink, Henri G; Ploeg, Rutger J; Yard, Benito A; Seelen, Marc A

    2011-05-01

    Kidneys recovered from brain-dead donors have inferior outcomes after transplantation compared to kidneys from living donors. Since complement activation plays an important role in renal transplant related injury, targeting complement activation in brain-dead donors might improve renal function after transplantation. Brain death (BD) was induced in Fisher rats by inflation of an epidurally placed balloon catheter and ventilated for 6h. BD animals were treated with soluble complement receptor 1 (sCR1) 1h before or 1h after BD. Kidney transplantation was performed and 7 days after transplantation animals were sacrificed. Plasma creatinine and urea were measured at days 0, 1, 3, 5 and 7 after transplantation. Renal function was significantly better at day 1 after transplantation in recipients receiving a sCR1 pre-treated donor kidney compared to recipients of a non-treated donor graft. Also treatment with sCR1, 1h after the diagnosis of BD, resulted in a better renal function after transplantation. Gene expression of IL-6, IL-1beta and TGF-beta were significantly lower in renal allografts recovered from treated donors. This study shows that targeting complement activation, during BD in the donor, leads to an improved renal function after transplantation in the recipient.

  13. Cyclosporine-associated renal arteriopathy resulting in loss of allograft function

    SciTech Connect

    Sommer, B.G.; Innes, J.T.; Whitehurst, R.M.; Sharma, H.M.; Ferguson, R.M.

    1985-06-01

    Cyclosporine-associated arteriopathy was the cause of graft loss in 40 percent of all allografts that failed in a series of 200 consecutive cadaveric renal transplants. Arteriopathy was diagnosed by biopsy and renal uptake of indium 111m labeled platelets in the face of acute renal deterioration. A moderate thrombocytopenia and microangiopathic picture of hemolytic uremia was also present on peripheral blood smear. Immunofluorescence and histologic characteristics of the allograft biopsy specimens failed to show evidence for acute rejection: immunoglobulin M, immunoglobulin A, immunoglobulin G, C1q, C3, and C4 were not present, and there was no evidence of an interstitial or vascular mononuclear cellular infiltrate. Two clinical presentations have been described. In Group I (seven patients), anuria occurred rapidly within the first 2 weeks after transplantation. In Group II (nine patients) renal function gradually diminished 1 to 5 months after starting cyclosporine therapy. Fifteen of the 16 recipients had progressive and irreversible loss of renal function which was pathologically associated with fibrin deposition, intimal proliferation, and thrombotic occlusion of the cortical interlobular and arcuate arteries, with subsequent focal glomerular ischemia and cortical infarction. One recipient with rapid loss of renal function received an intraarterial allograft infusion of streptokinase and subsequent systemic heparinization, which resulted in return of normal allograft function. The syndrome of cyclosporine-associated arteriopathy has been linked to a lack of or reduced amounts of prostacyclin-stimulating factor or prostacyclin.

  14. Risk Factors for Renal Functional Decline in Chronic Hepatitis B Patients Receiving Oral Antiviral Agents.

    PubMed

    Shin, Jung-Ho; Kwon, Hee Jin; Jang, Hye Ryoun; Lee, Jung Eun; Gwak, Geum-Youn; Huh, Wooseong; Jung, Sin-Ho; Lee, Joon Hyeok; Kim, Yoon-Goo; Kim, Dae Joong; Oh, Ha Young

    2016-01-01

    Renal functional decline that is frequently seen during chronic hepatitis B (CHB) treatment can exert adverse effects on overall prognosis. It, however, is difficult to distinguish vulnerable patients who may experience renal dysfunction because most previous CHB studies were conducted in relatively healthy individuals. In this retrospective observational study, renal functional decline in CHB patients receiving oral antiviral agents for more than 6 months was analyzed and risk factors of chronic kidney disease (CKD) progression were determined. Renal functional decline was defined when the estimated glomerular filtration rate (eGFR) decreased by more than 25% from baseline and rapid CKD progression was defined as eGFR decreased by more than 5 mL/min/1.73 m2/y among patients who experienced renal functional decline. A total of 4178 patients were followed up for a median 23 months. Antiviral agents included lamivudine (17.0%), adefovir (3.7%), entecavir (70.4%), telbivudine (0.6%), tenofovir (4.0%), or clevudine (4.3%). Renal functional decline occurred in 706 (16.9%) patients. Based on multivariate Cox regression analysis, age, hypertension, diabetes, history of liver or kidney transplantation, underlying underlying CKD, and simultaneous administration of diuretics increased the hazard ratio for renal functional decline; however, clevudine reduced risk. The eGFR significantly increased over time in patients receiving telbivudine or clevudine compared with lamivudine. Among the 3175 patients followed up for more than 1 year, 407 (12.8%) patients experienced rapid CKD progression. Patients with rapid CKD progression showed lower serum albumin, higher total bilirubin, and prolonged prothrombin time compared with patients with stable renal function, but hepatitis B envelope antigen positivity and hepatitis B virus deoxyribonucleic acid level did not differ between the control and rapid CKD progression groups. Age, diabetes, kidney transplantation, underlying CKD, and

  15. Abnormalities of sodium excretion and other disorders of renal function in fulminant hepatic failure.

    PubMed Central

    Wilkinson, S P; Arroyo, V A; Moodie, H; Blendis, L M; Williams, R

    1976-01-01

    Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis). PMID:964682

  16. Vicarious liver visualization in solitary functioning kidney with technetium-99m ethylenedicysteine renal scintigraphy

    PubMed Central

    Jain, Tarun Kumar; Phulsunga, Rohit Kumar; Gupta, Nitin; Sood, Ashwani; Bhattacharya, Anish; Mittal, Bhagwant Rai

    2015-01-01

    We present a case of 3-year-old boy who was incidentally diagnosed to have single left kidney on ultrasonography. Dynamic technetium-99m ethylenedicysteine renal scintigraphy was acquired for assessing the existing kidney function showed the tracer localization in bilateral renal fossae during the entire study. The single-photon emission computerized tomography/computerized tomography study revealed activity in the right renal fossa to be in the enlarged right lobe of the liver, which was mimicking as impaired functioning right kidney in planar images. The hybrid imaging helped in accurate delineation of tracer uptake by confirming it to be the false appearance of the right kidney in planar imaging. This case report also highlights the possible mechanism of renal tracer uptake in the liver parenchyma. PMID:26170576

  17. [Volume Homeostasis and Renal Function in Rats Exposed to Simulated and Actual Microgravity

    NASA Technical Reports Server (NTRS)

    Tucker, Bryan J.

    1993-01-01

    This project has investigated mechanisms that influence alterations in compartmental fluid and electrolyte balance in microgravity and evaluates countermeasures to control renal fluid and electrolyte losses. Determining the alterations due to space flight in fluid compartments and renal function is an important component in understanding long term adaptation to spaceflight and the contribution to post-flight orthostatic intolerance. Four definition phase studies and two studies examining neuro-humoral and vascular mechanisms have been completed.

  18. Ultrasonic parameters of renal calculi and gall bladder stones as a function of density.

    PubMed

    Agarwal, R

    1998-01-01

    In this investigation, ultrasonic parameters of complex renal calculi and gall bladder stones, in vitro are measured using a double-probe contact by pulse-echo technique. Due to the variation in the chemical composition of the stones, a large variation in the value of ultrasonic parameters is found. A correlation between ultrasonic parameters and various renal calculi and gall bladder stone pathologies are also discussed. The ultrasonic parameters are found to vary as a function of density of the specimen used.

  19. Hemodynamic and neurochemical determinates of renal function in chronic heart failure.

    PubMed

    Gilbert, Cameron; Cherney, David Z I; Parker, Andrea B; Mak, Susanna; Floras, John S; Al-Hesayen, Abdul; Parker, John D

    2016-01-15

    Abnormal renal function is common in acute and chronic congestive heart failure (CHF) and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with chronic CHF (ejection fraction; 23 ± 8%) underwent right heart catheterization, measurements of glomerular filtration rate (GFR; inulin) and renal plasma flow (RPF; para-aminohippurate), and radiotracer estimates of renal sympathetic activity. A subset (26 without, 36 with CHF) underwent acute pharmacological intervention with dobutamine or nitroprusside. We explored the relationship between baseline and drug-induced hemodynamic changes and changes in renal function. In CHF, there was an inverse relationship among right atrial mean pressure (RAM) pressure, RPF, and GFR. By contrast, mean arterial pressure (MAP), cardiac index (CI), and measures of renal sympathetic activity were not significant predictors. In those with CHF there was also an inverse relationship among the drug-induced changes in RAM as well as pulmonary artery mean pressure and the change in GFR. Changes in MAP and CI did not predict the change in GFR in those with CHF. Baseline values and changes in RAM pressure did not correlate with GFR in those without CHF. In the CHF group there was a positive correlation between RAM pressure and renal sympathetic activity. There was also an inverse relationship among RAM pressure, GFR, and RPF in patients with chronic CHF. The observation that acute reductions in RAM pressure is associated with an increase in GFR in patients with CHF has important clinical implications.

  20. Effect of renal function on risedronate pharmacokinetics after a single oral dose

    PubMed Central

    Mitchell, D Y; St Peter, J V; Eusebio, R A; Pallone, K A; Kelly, S C; Russell, D A; Nesbitt, J D; Thompson, G A; Powell, J H

    2000-01-01

    Aims To determine the relationship between risedronate pharmacokinetics and renal function. Methods Risedronate was administered to adult men and women (n = 21) with various degrees of renal function (creatinine clearance 15–126 ml min−1) as a single oral dose of 30 mg. Serum samples were obtained for 72 h after dosing, and urine samples were collected for 72 h after dosing and then periodically for 6 weeks. Risedronate concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Risedronate serum concentration-time and urinary excretion rate-time profiles were analysed simultaneously using nonlinear regression. Results Renal clearance and volume of distribution were linearly related to creatinine clearance (r2 = 0.854, P < 0.001; and r2 = 0.317, P < 0.01, respectively). Decreases in predicted renal clearance and volume of distribution of 82 and 69%, respectively, were observed when creatinine clearance decreased from 120 to 20 ml min−1. A 64% decrease in predicted oral clearance was observed when creatinine clearance decreased from 120 to 20 ml min−1 (P = 0.064). Iohexol clearance, a predictor of renal function, produced similar results to those observed with creatinine clearance. Risedronate was well tolerated by the study population. Conclusions Risedronate renal clearance was significantly related to a decrease in renal function. There was a consistent reduction in oral clearance with a decrease in creatinine clearance. However, based on the regression analysis, generally no dosage adjustment appears to be necessary for most patients with mild or moderate renal impairment (creatinine clearance > 20 ml min−1). PMID:10718776

  1. Cigarette smoking reduced renal function deterioration in hypertensive patients may be mediated by elevated homocysteine

    PubMed Central

    Cai, Qingqing; Peng, Guicheng; Zhang, Kun; Chen, Weiqing; Wang, Jingfeng; Huang, Hui

    2016-01-01

    Elevated homocysteine (HCY) and smoking are both important risk factors for hypertensive patients. However, whether they have crossing effect on renal function deterioration of hypertensive patients and what is the underlying mechanism are unclear. In the present study, 3033 participants diagnosed as essential hypertension with estimated glomerular filtration rate (eGFR)> 30 ml/min/1.73 m2 from southern China were enrolled in this cross-sectional study. We collected the demographic and clinical data. In addition, the mediation effects were analyzed. The results showed that, comparing with non-smokers, smokers had significant higher levels of HCY (13.10 (11.20−16.87) vs. 11.00 (8.90−13.40) umol/L, P < 0.001) and lower eGFR (79.71 (66.83−91.05) vs. 82.89 (69.80−95.85) ml/min/1.73m2, P < 0.001). HCY levels and smoking were independently associated with decreased eGFR. Meanwhile, eGFR levels were significantly negatively correlated with HCY (P < 0.001), and this correlation might be stronger in current smokers. Current smoker consuming over 20 cigarettes per day would accelerate early renal function deterioration (OR = 1.859, P = 0.019). The mediation effects analysis further showed that the association between smoking and renal function deterioration was mediated by HCY. And elevated HCY was accounted for 56.94% of the estimated causal effect of smoking on renal function deterioration in hypertensive patients. Our findings indicated that cigarette smoking was associated with renal function deterioration in hypertensive patients, and the association between cigarette smoking and renal function deterioration was probably mediated by elevated HCY. Therefore, HCY-lowering therapy may be beneficial for renal function deterioration in hypertensive smoking patients. PMID:27852066

  2. Assessment of renal function in workers previously exposed to cadmium.

    PubMed Central

    Elinder, C G; Edling, C; Lindberg, E; Kågedal, B; Vesterberg, O

    1985-01-01

    Cadmium induced renal effects were examined in 60 workers (58 men, 2 women) previously exposed to cadmium. Tubular damage in the form of beta 2-microglobulinuria was found in 40%, and urinary albumin and orosomucoid increased significantly with increasing urinary cadmium and increasing relative clearance of beta 2-microglobulin. It is suggested that increased albumin excretion is secondary to the tubular damage. In no case was typical glomerular proteinuria found that could be related to cadmium. Histories of renal stones were more common among the workers with high urinary cadmium concentrations. The glomerular filtration rate was measured in 17 of the workers who had pronounced tubular dysfunction. The average glomerular filtration rate for these men was less than the age adjusted predicted value (mean = 84%). Furthermore, there was a significant (p less than 0.05) correlation (r = -0.47) between tubular reabsorption loss and a decreased glomerular filtration rate. PMID:3904816

  3. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in healthy geriatric cats fed reduced protein foods enriched with fish oil, L-carnitine, and medium-chain triglycerides.

    PubMed

    Hall, J A; Yerramilli, M; Obare, E; Yerramilli, M; Yu, S; Jewell, D E

    2014-12-01

    The purpose of this study was to determine whether feeding cats reduced protein and phosphorus foods with added fish oil, L-carnitine, and medium-chain triglycerides (MCT) altered serum biomarkers of renal function. Thirty-two healthy cats, mean age 14.0 (8.3-19.6) years, were fed control food or one of two experimental foods for 6 months. All foods had similar concentrations of moisture, protein, and fat (approximately 8.0%, 26.5%, and 20.0%, respectively). Both experimental foods contained added fish oil (1.5%) and L-carnitine (500 mg/kg). Experimental-food 2 also contained increased MCT (10.5% from coconut oil), 1.5% added corn oil, and reduced animal fat. Glomerular filtration rate (GFR), serum biochemistries, renal function biomarkers including serum creatinine (sCr) and symmetrical dimethylarginine (SDMA), and plasma metabolomic profiles were measured at baseline, and at 1.5, 3, and 6 months. Body composition was determined by dual-energy X-ray absorptiometry. Although both experimental foods altered plasma fatty acids, carnitine and related metabolites, and lysophospholipid concentrations, there were no changes in renal function biomarkers. There was, however, a benefit in using SDMA versus sCr to assess renal function in older cats with less total lean mass. Compared with cats <12 years, those >15 years had lower total lean mass (P < 0.01), lower GFR (P = 0.04), and lower sCr concentrations (P < 0.01). However, SDMA concentrations (P < 0.01) were higher in older cats. This study shows that in cats, serum SDMA concentration is more highly correlated with GFR than sCr concentration, and, unlike sCr, which declines with age because of muscle wasting, SDMA increases as GFR declines with age.

  4. Omapatrilat normalizes renal function curve in spontaneously hypertensive rats

    PubMed Central

    Morazo, Paloma; Fortepiani, Lourdes A; Clara Ortíz, M; Atucha, Noemí M; García-Estañ, Joaquín

    2001-01-01

    Background The present study was designed to analyze the chronic renal response to omapatrilat, a new vasopeptidase inhibitor, in spontaneously hypertensive rats (SHR). To that end, the renal and blood pressure response to a 4-day salt loading protocol was analyzed and the respective chronic renal curves constructed. Results In non treated animals, and under normal sodium intake (around 2 mEq/day), mean arterial pressure (MAP), was significantly higher in the SHR as compared with the controls (WKY). After increasing salt intake (8 times normal), MAP did not change significantly in any group and the animals reached a normal sodium balance in four days. In a second group of animals, omapatrilat was given orally for 15 days at the dose of 40 mg/kg/day in the drinking water. In these omapatrilat-treated animals, and under normal sodium intake, MAP was significantly lower in both groups, although the antihypertensive effect was much greater in the SHR, so that the MAP of the SHR group was completely normalized and similar to the WKY-treated group. The subsequent elevation of sodium intake did not significantly elevate MAP in any group and the animals could manage the sodium excess as well as the non treated groups. Conclusions These results indicate that chronic treatment with omapatrilat normalizes blood pressure in SHR without affecting adversely the renal ability to eliminate a sodium load. Chronic treatment with omapatrilat resets the chronic pressure natriuresis relationship of the SHR to a normal level, thus without altering the normal salt-independence of this arterial hypertension model. PMID:11592920

  5. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    SciTech Connect

    Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Gonzalez-De Alba, Cesar; Froines, John R.; Espinosa-Fematt, Jorge A.

    2015-09-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  6. Electrochemical detection of methyl nicotinate biomarker using functionalized anodized titania nanotube arrays

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Dhiman; Smith, York R.; Misra, Mano; Mohanty, Swomitra K.

    2015-02-01

    Sensing and detection of volatile organic compounds (VOCs) from exhaled breath is a possible method for early diagnosis of several pulmonary diseases. The use of solid-state TiO2 nanotube array sensors for VOC sensing applications has been of great interest. In this study, titania nanotubular arrays (TNAs) were synthesized through electrochemical anodization and used for the electrochemical detection of methyl nicotinate biomarker vapor. Functionalization of the TNA with cobalt was found to be necessary for methyl nicotinate detection. Titanium dioxide films synthesized through high temperature oxidation and functionalized with cobalt were also compared with cobalt functionalized TNA. The ordered TNA demonstrated itself to be an effective substrate for cobalt deposition and subsequent biomarker detection over thin titanium dioxide films. Surface analysis of the cobalt functionalized TNA by x-ray photoelectron spectroscopy (XPS) studies observed cobalt deposits exist as cobalt hydroxide on the surface. Exposure of the sensor surface to methyl nicotinate vapor results in the reduction of cobalt hydroxide to cobalt metal on the surface. Two mechanisms have been proposed to describe the binding of the nicotinate biomarker to cobalt functionalized TNA consistent with the XPS studies and band theory.

  7. The Gomez' equations and renal hemodynamic function in kidney disease research.

    PubMed

    Bjornstad, Petter; Škrtić, Marko; Lytvyn, Yuliya; Maahs, David M; Johnson, Richard J; Cherney, David Z I

    2016-09-07

    Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease. A major challenge in preventing DKD is the difficulty in identifying high-risk patients at an early, pre-clinical stage. Albuminuria and eGFR as measures of renal function in DKD research and clinical practice are limited by regression of one-third of patients with microalbuminuria to normoalbuminuria and eGFR is biased and imprecise in the normal-elevated range. Moreover, existing methods that are used to assess renal function do not give detailed insight into the location of the renal hemodynamic effects of pharmacological agents at the segmental level. To gain additional information about the intrarenal circulation in-vivo in humans, mathematical equations were developed by Gomez et al in the 1950s. These equations used measurements of GFR, renal blood flow (RBF), effective renal plasma flow (ERPF), renal vascular resistance (RVR), hematocrit and serum protein to calculate afferent and efferent arteriolar resistances, glomerular hydrostatic pressure and filtration pressure. Although indirect and based on physiological assumptions, these techniques have the potential to improve researchers' ability to identify early pre-clinical changes in renal hemodynamic function in patients with a variety of conditions including DKD, thereby offering tremendous potential in mechanistic human research studies. In this review, we focus on the application of Gomez' equations and summarize the potential and limitations of this technique in DKD research. We also summarize illustrative data derived from Gomez' equations in patients with type 1 (T1D) and type 2 diabetes (T2D) and hypertension.

  8. SDF-1/CXCR4 signaling preserves microvascular integrity and renal function in chronic kidney disease.

    PubMed

    Chen, Li-Hao; Advani, Suzanne L; Thai, Kerri; Kabir, M Golam; Sood, Manish M; Gibson, Ian W; Yuen, Darren A; Connelly, Kim A; Marsden, Philip A; Kelly, Darren J; Gilbert, Richard E; Advani, Andrew

    2014-01-01

    The progressive decline of renal function in chronic kidney disease (CKD) is characterized by both disruption of the microvascular architecture and the accumulation of fibrotic matrix. One angiogenic pathway recently identified as playing an essential role in renal vascular development is the stromal cell-derived factor-1α (SDF-1)/CXCR4 pathway. Because similar developmental processes may be recapitulated in the disease setting, we hypothesized that the SDF-1/CXCR4 system would regulate microvascular health in CKD. Expression of CXCR4 was observed to be increased in the kidneys of subtotally nephrectomized (SNx) rats and in biopsies from patients with secondary focal segmental glomerulosclerosis (FSGS), a rodent model and human correlate both characterized by aberration of the renal microvessels. A reno-protective role for local SDF-1/CXCR4 signaling was indicated by i) CXCR4-dependent glomerular eNOS activation following acute SDF-1 administration; and ii) acceleration of renal function decline, capillary loss and fibrosis in SNx rats treated with chronic CXCR4 blockade. In contrast to the upregulation of CXCR4, SDF-1 transcript levels were decreased in SNx rat kidneys as well as in renal fibroblasts exposed to the pro-fibrotic cytokine transforming growth factor β (TGF-β), the latter effect being attenuated by histone deacetylase inhibition. Increased renal SDF-1 expression was, however, observed following the treatment of SNx rats with the ACE inhibitor, perindopril. Collectively, these observations indicate that local SDF-1/CXCR4 signaling functions to preserve microvascular integrity and prevent renal fibrosis. Augmentation of this pathway, either purposefully or serendipitously with either novel or existing therapies, may attenuate renal decline in CKD.

  9. Associations of Perfusate Biomarkers and Pump Parameters With Delayed Graft Function and Deceased Donor Kidney Allograft Function.

    PubMed

    Parikh, C R; Hall, I E; Bhangoo, R S; Ficek, J; Abt, P L; Thiessen-Philbrook, H; Lin, H; Bimali, M; Murray, P T; Rao, V; Schröppel, B; Doshi, M D; Weng, F L; Reese, P P

    2016-05-01

    Hypothermic machine perfusion (HMP) is increasingly used in deceased donor kidney transplantation, but controversy exists regarding the value of perfusion biomarkers and pump parameters for assessing organ quality. We prospectively determined associations between perfusate biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1, IL-18 and liver-type fatty acid-binding protein [L-FABP]) and pump parameters (resistance and flow) with outcomes of delayed graft function (DGF) and 6-mo estimated GFR (eGFR). DGF occurred in 230 of 671 (34%) recipients. Only 1-h flow was inversely associated with DGF. Higher NGAL or L-FABP concentrations and increased resistance were inversely associated with 6-mo eGFR, whereas higher flow was associated with higher adjusted 6-mo eGFR. Discarded kidneys had consistently higher median resistance and lower median flow than transplanted kidneys, but median perfusate biomarker concentrations were either lower or not significantly different in discarded compared with transplanted kidneys. Notably, most recipients of transplanted kidneys with isolated "undesirable" biomarker levels or HMP parameters experienced acceptable 6-mo allograft function, suggesting these characteristics should not be used in isolation for discard decisions. Additional studies must confirm the utility of combining HMP measurements with other characteristics to assess kidney quality.

  10. Acute renal failure.

    PubMed

    Bellomo, Rinaldo

    2011-10-01

    Acute renal failure (now acute kidney injury) is a common complication of critical illness affecting between 30 and 60% of critically ill patients. The development of a consensus definition (RIFLE--risk, injury, failure, loss, end-stage system) has allowed standardization of reporting and epidemiological work. Multicenter multinational epidemiological studies indicate that sepsis is now the most common cause of acute renal failure in the intensive care unit (ICU) followed by cardiac surgery-associated acute kidney injury. Unfortunately, our understanding of the pathogenesis of acute renal failure in these settings remains limited. Because of such limited understanding, no reproducibly effective therapies have been developed. In addition the diagnosis of acute renal failure still rests upon the detection of changes in serum creatinine, which only occur if more than 50% of glomerular filtration is lost and are often delayed by more than 24 hours. Such diagnostic delays make the implementation of early therapy nearly impossible. In response to these difficulties, there has been a concerted effort to use proteomics to identify novel early biomarkers of acute renal failure. The identification and study of neutrophil gelatinase- associated lipocalin has been an important step in this field. Another area of active interest and investigation relates to the role of intravenous fluid resuscitation and fluid balance. Data from large observational studies and randomized, controlled trials consistently indicate that a positive fluid balance in patients with acute renal failure represents a major independent risk factor for mortality and provides no protection of renal function. The pendulum is clearly swinging away from a fluid-liberal approach to a fluid-conservative approach in these patients. Finally, there is a growing appreciation that acute renal failure may identify patients who are at increased risk of subsequent chronic renal dysfunction and mortality, opening the way

  11. Multiple biomarkers biosensor with just-in-time functionalization: Application to prostate cancer detection.

    PubMed

    Parra-Cabrera, C; Samitier, J; Homs-Corbera, A

    2016-03-15

    We present a novel lab-on-a-chip (LOC) device for the simultaneous detection of multiple biomarkers using simple voltage measurements. The biosensor functionalization is performed in-situ, immediately before its use, facilitating reagents storage and massive devices fabrication. Sensitivity, limit of detection (LOD) and limit of quantification (LOQ) are tunable depending on the in-chip flown sample volumes. As a proof-of-concept, the system has been tested and adjusted to quantify two proteins found in blood that are susceptible to be used combined, as a screening tool, to diagnose prostate cancer (PCa): prostate-specific antigen (PSA) and spondin-2 (SPON2). This combination of biomarkers has been reported to be more specific for PCa diagnostics than the currently accepted but rather controversial PSA indicator. The range of detection for PSA and SPON2 could be adjusted to the clinically relevant range of 1 to 10 ng/ml. The system was tested for specificity to the evaluated biomarkers. This multiplex system can be modified and adapted to detect a larger quantity of biomarkers, or different ones, of relevance to other specific diseases.

  12. MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma

    PubMed Central

    Trevisani, Francesco; Ghidini, Michele; Larcher, Alessandro; Lampis, Andrea; Lote, Hazel; Manunta, Paolo; Alibrandi, Maria Teresa Sciarrone; Zagato, Laura; Citterio, Lorena; Dell'Antonio, Giacomo; Carenzi, Cristina; Capasso, Giovambattista; Rugge, Massimo; Rigotti, Paolo; Bertini, Roberto; Cascione, Luciano; Briganti, Alberto; Salonia, Andrea; Benigni, Fabio; Braconi, Chiara; Fassan, Matteo; Hahne, Jens Claus; Montorsi, Francesco; Valeri, Nicola

    2016-01-01

    Background: A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease has important health, social and economic impact and no predictive biomarkers are currently available. MicroRNAs (miRs) are small non-coding RNAs implicated in several pathological processes. Methods: Primary objective of our study was to define miRs whose deregulation is predictive of CKD in patients treated with RN. Ribonucleic acid from formalin-fixed paraffin embedded renal parenchyma (cortex and medulla isolated separately) situated >3 cm from the matching RCC was tested for miR expression using nCounter NanoString technology in 71 consecutive patients treated with RN for RCC. Validation was performed by RT–PCR and in situ hybridisation. End point was post-RN CKD measured 12 months post-operatively. Multivariable logistic regression and decision curve analysis were used to test the statistical and clinical impact of predictors of CKD. Results: The overexpression of miR-193b-3p was associated with high risk of developing CKD in patients undergoing RN for RCC and emerged as an independent predictor of CKD. The addition of miR-193b-3p to a predictive model based on clinical variables (including sex and estimated glomerular filtration rate) increased the sensitivity of the predictive model from 81 to 88%. In situ hybridisation showed that miR-193b-3p overexpression was associated with tubule-interstitial inflammation and fibrosis in patients with no clinical or biochemical evidence of pre-RN nephropathy. Conclusions: miR-193b-3p might represent a useful biomarker to tailor and implement surveillance strategies for patients at high risk of developing CKD following RN. PMID:27802451

  13. Delayed redo pyeloplasty fails to recover lost renal function after failed pyeloplasty: Early sonographic changes that correlate with a loss of differential renal function

    PubMed Central

    Chung, Doo Yong; Hong, Chang Hee; Im, Young Jae; Lee, Yong Seung; Kim, Sang Woon

    2015-01-01

    Purpose To evaluate changes in differential renal function (DRF), as a functional outcome, in children who underwent redo pyeloplasty for management of failed pyeloplasty and to examine the factors that affect functional outcomes. Materials and Methods Between January 2002 and November 2010, a total of 18 patients who underwent redo pyeloplasty for persistent ureteropelvic junction obstruction after failed pyeloplasty were enrolled in this study. We assessed perioperative factors and evaluated changes in renal cortical thickness (RCT), renal function, and hydronephrosis by use of serial ultrasound and diuretic renography. Results The mean follow-up period was 44.83±28.86 months. After redo pyeloplasty, prevention of further functional deterioration was observed in only 12 of the 18 patients. After dividing the patients according to this observation, we discovered significant differences in both change in DRF (dDRF) and change in RCT (dRCT) (difference between before and after initial pyeloplasty) between the two groups (p<0.001). Additionally, we noted a significant positive correlation between dRCT and dDRF. All patients showed improvements in hydronephrosis grade and relief of symptoms compared with before redo pyeloplasty. Conclusions Redo pyeloplasty should be considered in cases of failed pyeloplasty to preserve renal function and obtain relief from symptoms. If patients show severe deterioration of DRF or a decrease in RCT after initial pyeloplasty, preservation of DRF in these patients after redo pyeloplasty could be difficult. Therefore, redo pyeloplasty should be performed before severe deterioration of DRF or decrease in RCT. PMID:25685304

  14. Split renal function in patients with hypertension following continued captopril treatment

    SciTech Connect

    Aburano, T.; Takayama, T.; Nakajima, K.; Tonami, N.; Hisada, K.; Yasuhara, S.; Miyamori, I.; Takeda, R.

    1985-05-01

    The three different methods to evaluate the alterations of split renal function following continued captopril treatment were studied in patients with hypertension. Five patients had unilateral and 2 had bilateral renal artery stenosis, and 13 had normal renal arteries. The studies were performed the day prior to receiving captopril (baseline), and 6th or 7th day following continued captorpril treatment (37.5mg or 75mg/day): Split effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) after injections of I-131 iodohippuran and Tc-99m DTPA were measured respectively by the methods using kidney counting corrected for depth and dose, described by Schlegel and Gates. And Tc-99m DMSA uptake was also evaluated qualitatively. In most of patients with renal artery stenosis, split GFR and Tc-99m DMSA uptake in the affected kidney were markedly decreased 6th or 7th day following continued captorpril treatment. These findings suggest that the captopril induced alterations of split renal function may be of importance for the diagnosis of renovascular hypertension. For this purpose, split GFR determination and Tc-99m DMSA study are more useful than split ERPF determination.

  15. Kidney function changes with aging in adults: comparison between cross-sectional and longitudinal data analyses in renal function assessment.

    PubMed

    Chung, Sang M; Lee, David J; Hand, Austin; Young, Philip; Vaidyanathan, Jayabharathi; Sahajwalla, Chandrahas

    2015-12-01

    The study evaluated whether the renal function decline rate per year with age in adults varies based on two primary statistical analyses: cross-section (CS), using one observation per subject, and longitudinal (LT), using multiple observations per subject over time. A total of 16628 records (3946 subjects; age range 30-92 years) of creatinine clearance and relevant demographic data were used. On average, four samples per subject were collected for up to 2364 days (mean: 793 days). A simple linear regression and random coefficient models were selected for CS and LT analyses, respectively. The renal function decline rates per year were 1.33 and 0.95 ml/min/year for CS and LT analyses, respectively, and were slower when the repeated individual measurements were considered. The study confirms that rates are different based on statistical analyses, and that a statistically robust longitudinal model with a proper sampling design provides reliable individual as well as population estimates of the renal function decline rates per year with age in adults. In conclusion, our findings indicated that one should be cautious in interpreting the renal function decline rate with aging information because its estimation was highly dependent on the statistical analyses. From our analyses, a population longitudinal analysis (e.g. random coefficient model) is recommended if individualization is critical, such as a dose adjustment based on renal function during a chronic therapy.

  16. Validation of functional imaging as a biomarker for radiation treatment response.

    PubMed

    Jentsch, C; Beuthien-Baumann, B; Troost, E G C; Shakirin, G

    2015-07-01

    Major advances in radiotherapy techniques, increasing knowledge of tumour biology and the ability to translate these advances into new therapeutic approaches are important goals towards more individualized cancer treatment. With the development of non-invasive functional and molecular imaging techniques such as positron emission tomography (PET)-CT scanning and MRI, there is now a need to evaluate potential new biomarkers for tumour response prediction, for treatment individualization is not only based on morphological criteria but also on biological tumour characteristics. The goal of individualization of radiotherapy is to improve treatment outcome and potentially reduce chronic treatment toxicity. This review gives an overview of the molecular and functional imaging modalities of tumour hypoxia and tumour cell metabolism, proliferation and perfusion as predictive biomarkers for radiation treatment response in head and neck tumours and in lung tumours. The current status of knowledge on integration of PET/CT/MRI into treatment management and bioimage-guided adaptive radiotherapy are discussed.

  17. Mesenchymal Stem Cells (MSC) Prevented the Progression of Renovascular Hypertension, Improved Renal Function and Architecture

    PubMed Central

    Oliveira-Sales, Elizabeth B.; Maquigussa, Edgar; Semedo, Patricia; Pereira, Luciana G.; Ferreira, Vanessa M.; Câmara, Niels O.; Bergamaschi, Cassia T.; Campos, Ruy R.; Boim, Mirian A.

    2013-01-01

    Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C) is a renin-angiotensin-system (RAS)-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP) and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC) (2×105 cells/animal) were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K-1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. The treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1β, TNF-α angiotensinogen, ACE, and Ang II receptor AT1 were elevated, whereas AT2 levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. In conclusion, MSC therapy in the 2K-1C model (i) prevented the progressive increase of AP, (ii) improved renal morphology and microvascular rarefaction, (iii) reduced fibrosis, proteinuria and inflammatory cytokines, (iv) suppressed the intrarenal RAS, iv) decreased sympathetic hyperactivity in anesthetized animals and v) MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future. PMID:24223811

  18. Inflammation compromises renal dopamine D1 receptor function in rats

    PubMed Central

    Chugh, Gaurav; Lokhandwala, Mustafa F.

    2009-01-01

    We tested the effects of inflammation on renal dopamine D1 receptor signaling cascade, a key pathway that maintains sodium homeostasis and blood pressure during increased salt intake. Inflammation was produced by administering lipopolysaccharide (LPS; 4 mg/kg ip) to rats provided without (normal salt) and with 1% NaCl in drinking water for 2 wk (high salt). Control rats had saline injection and received tap water. We found that LPS increased the levels of inflammatory cytokines, interleukin-6, and tumor necrosis factor-α in the rats given either normal- or high-salt intake. Also, these rats had higher levels of oxidative stress markers, malondialdehyde and nitrotyrosine, and lower levels of antioxidant enzyme superoxide dismutase in the renal proximal tubules (RPTs). The nuclear levels of transcription factors NF-κB increased and Nrf2 decreased in the RPTs in response to LPS in rats given normal and high salt. Furthermore, D1 receptor numbers, D1 receptor proteins, and D1 receptor agonist (SKF38393)-mediated 35S-GTPγS binding decreased in the RPTs in these rats. The basal activities of Na-K-ATPase in the RPTs were similar in control and LPS-treated rats given normal and high salt. SKF38393 caused inhibition of Na-K-ATPase activity in the primary cultures of RPTs treated with vehicle but not in the cultures treated with LPS. Furthermore, LPS caused an increase in blood pressure in the rats given high salt but not in the rats given normal salt. These results suggest that LPS differentially regulates NF-κB and Nrf2, produces inflammation, decreases antioxidant enzyme, increases oxidative stress, and causes D1 receptor dysfunction in the RPTs. The LPS-induced dysfunction of renal D1 receptors alters salt handling and causes hypertension in rats during salt overload. PMID:19794106

  19. Renal function and glomerular hemodynamics in male endotoxemic rats.

    PubMed

    Lugon, J R; Boim, M A; Ramos, O L; Ajzen, H; Schor, N

    1989-10-01

    The renal effects of a single intravenous dose of two different E. coli lipopolysaccharides (LPS 0111:B4 and LPS 0127:B8), at the same dose of 100 micrograms/kg, were evaluated in euvolemic Munich-Wistar (MW) rats by whole kidney clearance techniques and micropuncture studies. Following LPS infusion, a significant decrease (8%) in mean BP was observed only in the LPS 0127:B8 treated group. Inulin clearance fell 57% (LPS 0111:B4), P less than 0.01, and 38% (LPS 0127:B8), P less than 0.01. Para-aminohippuric (PAH) clearance decreased 31% (P less than 0.01) and total effective renal vascular resistance rose 70% (P less than 0.03) in response to LPS 0111:B4. No significant change in PAH clearance was noted in the LPS 0127:B8 group. Superficial single nephron glomerular filtration rate (SNGFR) was reduced 69% (LPS 0111:B4), P less than 0.03, and 33% (LPS 0127:B8), P less than 0.02. Superficial glomerular plasma flow fell 48% (LPS 0111:B4), P less than 0.03, and 24% (LPS 0127:B8), P less than 0.03. Both lipopolysaccharides were associated with an increase in afferent arteriolar resistance (RA) which accounted for a reduction in the glomerular capillary hydraulic pressure (PGC). There was no change in the proximal tubular pressure in either group and, therefore, the net transcapillary hydraulic pressures were reduced. No measurable change in the ultrafiltration coefficient. Kf, was observed in either group. In a second set of protocols, the effect of prior administration of indomethacin or captopril on LPS 0111:B4 action was investigated. A significant decrease in BP occurred when animals were pretreated with captopril. Both indomethacin and captopril prevented the renal effects of LPS 0111:B4.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Correlation analysis between four serum biomarkers of liver fibrosis and liver function in infants with cholestasis

    PubMed Central

    TANG, NING; ZHANG, YAPING; LIU, ZEYU; FU, TAO; LIANG, QINGHONG; AI, XUEMEI

    2016-01-01

    The aim of the present study was to investigate the correlation between four serum biomarkers of liver fibrosis and liver function in infants with cholestasis. A total of 30 infants with cholestasis and 20 healthy infants were included in the study. Biochemical assays based on the initial rate method and colorimetric assays were conducted to determine the levels of liver function markers in the serum [such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), γ-glutamyl transferase (γ-GT), cholinesterase (CHE) and total bile acids (TBA)] and four serum biomarkers of liver fibrosis were measured using radioimmunoassays [hyaluronic acid (HA), procollagen type III (PCIII), laminin (LN) and collagen type IV (cIV)]. The serum levels of ALT, AST, TBIL, DBIL, IBIL, γ-GT and TBA in the infants with cholestasis were significantly higher compared to the healthy infants (P<0.01); the serum levels of CHE in the infants with cholestasis were significantly lower compared to the healthy infants (P<0.01). The serum levels of HA, PCIII, and cIV in the infants with cholestasis were significantly higher compared to the healthy infants (P<0.01). Correlation analyses between liver function and the four biomarkers of liver fibrosis showed that HA was positively correlated with AST and γ-GT (P<0.05) and negatively correlated with ALT, CHE and TBA (P<0.05). cIV was positively correlated with γ-GT (P<0.05) and negatively correlated with CHE (P<0.05). In conclusion, statistically significant differences were identified for the liver function markers (ALT, AST, TBIL, DBIL, IBIL, γ-GT and TBA) and the biomarkers HA, PCIII and cIV of liver fibrosis between infants with cholestasis and healthy infants. Thus, the serum levels of HA, cIV, γ-GT and CHE are sensitive markers for cholestatic liver fibrosis in infants. PMID:27347413

  1. Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI

    DTIC Science & Technology

    2015-09-01

    AWARD!NUMBER:!!!!W81XWH-14-1-0318 ! ! TITLE:!!! Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State...PAGES 19a. NAME OF RESPONSIBLE PERSON 19b. TELEPHONE NUMBER (Include area code) September 2015 Annual 1 Sep 2014 - 31 Aug 2015 Genetic and Diagnostic...functional MRI (fMRI); clinical outcome; genomic; hertitability; genetic control; pleitropy U U U UU 10 USAMRMC Our overarching strategy is to exploit

  2. Reduced cytosolic carboxypeptidase 6 (CCP6) level leads to accumulation of serum polyglutamylated DNAJC7 protein: A potential biomarker for renal cell carcinoma early detection

    PubMed Central

    Li, Yi; Zhu, Xiaoxiao; Ding, Juan; Ren, Shuangchun; Zhao, Heping; Wu, Song; Tian, Yong; Wang, Guo-Qing

    2016-01-01

    Renal cell carcinoma (RCC) is frequently diagnosed at advanced stages of disease, although early diagnosis has much favorable prognosis. This study assessed aberrant expression of cytosolic carboxypeptidase 6 (CCP6) leading to accumulation of serum polyglutamylated DNAJC7 as a biomarker for early RCC detection. A total of 835 RCCs, 143 chronic nephritis, 170 kidney stones and 415 health controls were collected for qRT-PCR, immunohistochemistry and Western blot analysis of CCP6 expression and mass spectrometry of DNAJC7 and polyglutamylated DNAJC7. The data showed that CCP6 expression was significantly decreased in 30 RCC tissues and that mass spectrometric and pull-down analysis identified DNAJC7 as a substrate of CCP6 and showed upregulated polyglutamylated-DNAJC7 (polyE-DNAJC7) in sera of RCC patients. The electrochemiluminescence immunoassay of large-scale serum samples from multi-institutes further confirmed the remarkable increase of polyE-DNAJC7 in 805 RCCs compared to that of 385 healthy controls (p < 0.001), 128 patients with chronic nephritis (p < 0.001), and 153 with kidney stone (p < 0.001). Serum level of DNAJC7-polyE protein was also associated with advanced RCC stage and grade in 805 patients. The data from the current study for the first time demonstrated increased serum polyglutamylated DNAJC7 as a potential biomarker for RCC early detection and association with advanced tumor stages and grade, which provides support of further polyglutamylation research in RCC. PMID:26993597

  3. Functional renal failure and haemorrhagic gastritis associated with endotoxaemia in cirrhosis.

    PubMed Central

    Clemente, C; Bosch, J; Rodés, J; Arroyo, V; Mas, A; Maragall, S

    1977-01-01

    Forty-three patients with cirrhosis and ascites, 21 with normal renal function, 10 with a progressive functional renal failure (FRF), and 12 with a steady FRF, were investigated for the presence of endotoxaemia by the Limulus lysate test. Endotoxaemia was found in nine patients with FRF and in none of the 21 with normal renal function (P less than 0-01). A positive Limulus test was almost exclusively associated with a progressive FRF (eight of 10 patients) and all but one of them died. Renal function improved as endotoxaemia disappeared in the survivor. Endotoxaemia was also associated with haemorrhage due to acute erosions of the gastric mucosa, being present in six of the seven patients who had this complication. Intravascular coagulation was not found in any patient. The Limulus test was positive in the ascitic fluid in 18 of 21 patients tested, although only two of them had peritonitis. These results suggest that endotoxaemia may play a critical role in the development of progressive renal failure and haemorrhagic gastritis in cirrhosis, and emphasise the potential risk of procedures involving reinfusion of ascitic fluid. PMID:301485

  4. DNA Damage Response Assessments in Human Tumor Samples Provide Functional Biomarkers of Radiosensitivity

    PubMed Central

    Willers, Henning; Gheorghiu, Liliana; Liu, Qi; Efstathiou, Jason A.; Wirth, Lori J.; Krause, Mechthild; von Neubeck, Cläre

    2015-01-01

    Predictive biomarkers are urgently needed for individualization of radiation therapy and treatment with radiosensitizing anti-cancer agents. Genomic profiling of human cancers will provide us with unprecedented insight into the mutational landscape of genes directly or indirectly involved in the response to radiation-induced DNA damage. However, to what extent this wealth of structural information about the cancer genome will produce biomarkers of sensitivity to radiation remains to be seen. Investigators are increasingly studying the subnuclear accumulation (i.e., foci) of proteins in the DNA damage response (DDR), such as γ-H2AX, 53BP1, or RAD51, as a surrogate of treatment sensitivity. Recent findings from preclinical studies have demonstrated the predictive potential of DDR foci by correlating foci with clinically relevant endpoints such as tumor control probability. Therefore, pre-clinical investigations of DDR foci responses are increasingly moving into cells and tissues from patients, which is the major focus of this review. The advantage of using DDR foci as functional biomarkers is that they can detect alterations in DNA repair due to various mechanisms. Moreover, they provide a global measurement of DDR network function without needing to know the identities of all the components, many of which remain unknown. Foci assays are thus expected to yield functional insight that may complement or supersede genomic information, thereby giving radiation oncologists unique opportunities to individualize cancer treatments in the near future. PMID:26384272

  5. In search of biomarkers in psychiatry: EEG-based measures of brain function.

    PubMed

    McLoughlin, Gráinne; Makeig, Scott; Tsuang, Ming T

    2014-03-01

    Current clinical parameters used for diagnosis and phenotypic definitions of psychopathology are both highly variable and subjective. Intensive research efforts for specific and sensitive biological markers, or biomarkers, for psychopathology as objective alternatives to the current paradigm are ongoing. While biomarker research in psychiatry has focused largely on functional neuroimaging methods for identifying the neural functions that associate with psychopathology, scalp electroencephalography (EEG) has been viewed, historically, as offering little specific brain source information, as scalp appearance is only loosely correlated to its brain source dynamics. However, ongoing advances in signal processing of EEG data can now deliver functional EEG brain-imaging with distinctly improved spatial, as well as fine temporal, resolution. One computational approach proving particularly useful for EEG cortical brain imaging is independent component analysis (ICA). ICA decomposition can be used to identify distinct cortical source activities that are sensitive and specific to the pathophysiology of psychiatric disorders. Given its practical research advantages, relatively low cost, and ease of use, EEG-imaging is now both feasible and attractive, in particular for studies involving the large samples required by genetically informative designs to characterize causal pathways to psychopathology. The completely non-invasive nature of EEG data acquisition, coupled with ongoing advances in dry, wireless, and wearable EEG technology, makes EEG-imaging increasingly attractive and appropriate for psychiatric research, including the study of developmentally young samples. Applied to large genetically and developmentally informative samples, EEG imaging can advance the search for robust diagnostic biomarkers and phenotypes in psychiatry.

  6. An Active Learning Exercise to Facilitate Understanding of Nephron Function: Anatomy and Physiology of Renal Transporters

    ERIC Educational Resources Information Center

    Dirks-Naylor, Amie J.

    2016-01-01

    Renal transport is a central mechanism underlying electrolyte homeostasis, acid base balance and other essential functions of the kidneys in human physiology. Thus, knowledge of the anatomy and physiology of the nephron is essential for the understanding of kidney function in health and disease. However, students find this content difficult to…

  7. Clinical and kinomic analysis identifies peripheral blood mononuclear cells as a potential pharmacodynamic biomarker in metastatic renal cell carcinoma patients treated with sunitinib

    PubMed Central

    Thomas-Schoemann, Audrey; Rangarajan, Savithri; Naji, Faris; Puszkiel, Alicja; Huillard, Olivier; Saidu, Nathaniel; Golmard, Lisa; Alexandre, Jerome; Goldwasser, Francois; Blanchet, Benoit; Vidal, Michel

    2016-01-01

    Background Sunitinib is a protein tyrosine kinase (PTK) inhibitor that has immune-modulating properties. In this context, peripheral blood mononuclear cells (PBMC), mainly constituted by lymphocytes, could be a perfect surrogate tissue for identifying and assaying pharmacodynamic biomarkers of sunitinib. In this study, we investigated the changes in lymphocytes count as pharmacodynamic biomarker in metastatic renal cell carcinoma (mRCC) patients under sunitinib therapy. Thereafter, we studied the ex vivo effect of sunitinib and SU12262 (active metabolite) on PBMC from naïve mRCC patients using a high throughput kinomic profiling method. Methods The prognostic value of total lymphocytes count between Day 0 and Day 21 (expressed as a ratio D21/D0) was retrospectively investigated in 88 mRCC patients under sunitinib therapy. PTK PamChip® microarrays were used to explore prospectively the ex vivo effect of sunitinib and SU12662 on PTK activity in PBMC from 21 naïve mRCC patients. Results In this retrospective study, D21/D0 lymphocytes ratio (Hazard Ratio, 1.83; CI95%, 1.24-2.71; p=0.0023) was independently associated with PFS. Interestingly, kinomic analysis showed that D21/D0 lymphocytes ratio and Heng prognostic model was statistically associated with the ex vivo sunitinib and SU12662 effect in PBMC. Conclusion The present study highlights that D21/D0 total lymphocytes ratio could be a promising pharmacodynamic biomarker in mRCC patients treated with sunitinib. Additionally, it paves the way to investigate the kinomic profile in PBMC as a prognostic factor in a larger cohort of mRCC patients under sunitinib therapy. PMID:27589830

  8. The rise of renal pathology in nephrology: structure illuminates function.

    PubMed

    D'Agati, Vivette D; Mengel, Michael

    2013-06-01

    This review chronicles historical landmarks in the rise of renal pathology from the mid-20th century. Major technical advances followed the advent of percutaneous kidney biopsy in 1951, including applications of thin serial sections, special stains, immunofluorescence, and electron microscopy. Inspired by the 1961 Ciba Symposium, renal pathologists and nephrologists collaborated on detailed clinical-pathologic studies, and the publication of Robert Heptinstall's textbook in 1966 offered the first modern synthesis of these emerging entities. By 2000, refinements in morphology-based diagnosis had outstripped knowledge of pathogenesis. The last decade has witnessed an explosion of new insights into the cause of kidney disease fueled by advances in molecular diagnostics, such as genetic screening, transcriptomics, and proteomics. We are entering an era of personalized medicine in which more precise mechanism-based diagnosis is fostering the design of targeted therapies in the individual patient. Only the continued partnering of pathologists and nephrologists can meet the challenge of integrating molecular diagnostics into pathogenesis-based therapy.

  9. Prenatal programming-effects on blood pressure and renal function.

    PubMed

    Ritz, Eberhard; Amann, Kerstin; Koleganova, Nadezda; Benz, Kerstin

    2011-03-01

    Impaired intrauterine nephrogenesis-most clearly illustrated by low nephron number-is frequently associated with low birthweight and has been recognized as a powerful risk factor for renal disease; it increases the risks of low glomerular filtration rate, of more rapid progression of primary kidney disease, and of increased incidence of chronic kidney disease or end-stage renal disease. Another important consequence of impaired nephrogenesis is hypertension, which further amplifies the risk of onset and progression of kidney disease. Hypertension is associated with low nephron numbers in white individuals, but the association is not universal and is not seen in individuals of African origin. The derangement of intrauterine kidney development is an example of a more general principle that illustrates the paradigm of plasticity during development-that is, that transcription of the genetic code is modified by epigenetic factors (as has increasingly been documented). This Review outlines the concept of prenatal programming and, in particular, describes its role in kidney disease and hypertension.

  10. [Side effects analyses in consideration of renal function for S-1-administered patients].

    PubMed

    Iwai, Mina; Kimura, Michio; Yoshimura, Tomoaki; Yasuda, Tadashi

    2011-06-01

    Although many analyses of S-1 side effects are reported, there are no reports where the analyses of side effects were performed in consideration of renal function, which is an important index of medication dose. Therefore, we investigated side effects in consideration of renal function. The subjects were 163 patients administered S-1 at the Department of Surgery of Ogaki Municipal Hospital, between October 2008 and December 2009. The frequency and severity of side effects were high and serious in the groupwhose creatinine clearance was low. A significant difference was observed among 3 groups with regard to thrombocytopenia and dehydration. In conclusion, we think that pharmacists must take renal function into consideration when administering medication, to keepclose medicinal guidance, and to actively observe progress.

  11. Renal function in congenital anomalies of the kidney and urinary tract.

    PubMed

    Kemper, M J; Müller-Wiefel, D E

    2001-11-01

    Congenital anomalies of the kidneys and urinary tract are a major cause of chronic and end-stage renal failure in children. The molecular mechanisms having been elaborated, there is now growing evidence that kidney function is to a large extent determined genetically at an early stage. Assessment of kidney function is an important tool in clinical medicine and is feasible in utero. Postnatally, determination of absolute glomerular filtration rate and also of split and excretory renal function play an important role in the determination of treatment and prognosis. This is supplemented by other biochemical, molecular and interventional prognostic factors, which are of help in preservation of kidney survival by minimizing modulating factors. If chronic or terminal renal failure ensues in childhood or even in early infancy, however, improved medical care has led to encouraging results, ultimately influencing the motivation in the care of children with congenital anomalies of the kidney and urinary tract.

  12. Hydroxyethylstarch impairs renal function and induces interstitial proliferation, macrophage infiltration and tubular damage in an isolated renal perfusion model

    PubMed Central

    Hüter, Lars; Simon, Tim-Philipp; Weinmann, Lenard; Schuerholz, Tobias; Reinhart, Konrad; Wolf, Gunter; Amann, Kerstin Ute; Marx, Gernot

    2009-01-01

    Introduction The aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours. Methods Infusion of either 10% HES 200/0.5, 6% HES 130/0.42 or Ringer's lactate (RL) was performed to achieve an haematocrit of 20% in eight kidneys from four animals per group. Physiological and pathophysiological parameters were determined (including N-acetyl-beta-aminoglucosidase as a marker for lysosomal tubular damage). Histological investigations and immunohistological stainings of the kidneys were performed. Results Initially after haemodilution, HES 130/0.42 and HES 200/0.5 reduced urine output compared with RL (P < 0.01). After six hours, N-acetyl-beta-aminoglucosidase was significantly higher in HES 200/0.5 (81 ± 23 U/L) compared with HES 130/0.42 (38 ± 12 U/L) and RL (21 ± 13 U/L; P < 0.001). Osmotic nephrosis-like lesions (OL) of the tubuli were present in all groups showing a significantly lower number of OL in RL (1.1 ± 0.4; P = 0.002) compared with both HES groups (HES 200/0.5 = 2.1 ± 0.6; HES 130/0.42 = 2.0 ± 0.5). Macrophage infiltration was significantly higher in HES 200/0.5 compared with HES 130/0.42 (1.3 ± 1.0 vs. 0.2 ± 0.04; P = 0.044). There was a significant increase in interstitial cell proliferation in the HES 200/0.5 group vs. HES 130/0.42 (18.0 ± 6.9 vs. 6.5 ± 1.6; P = 0.006) with no significant difference in RL (13.5 ± 4.0). Conclusions We observed impaired diuresis and sodium excretion by HES and identified renal interstitial proliferation, macrophage infiltration and tubular damage as potential pathological mechanisms of HES-induced adverse effects on renal function using an isolated porcine renal perfusion model. Furthermore, we demonstrated that 10% HES 200/0.5 had more of a pro-inflammatory effect compared with 6% HES 130/0.42 and caused more pronounced tubular damage than 6% HES 130/0.42 and

  13. Functional aspects of silent ureteral stones investigated with MAG-3 renal scintigraphy

    PubMed Central

    2014-01-01

    Background To investigate functional aspects of silent ureteral stones with special focus on obstruction and its relationship to renal anatomy. The present study is the first investigation of renal excretory function in patients with silent ureteral stones. Methods Patients with primarily asymptomatic ureteral stones underwent a mercapto-acetyltriglycine (MAG-3) renal scintigraphy prior to treatment, in addition to anatomic evaluation of renal units and serum creatinine levels. The primary outcome measure was the presence or absence of obstruction. Secondary outcome measures were kidney anatomy, grade of hydronephrosis, location of stones, stone size, and serum creatinine levels. Results During a ten-year period, 14 patients (median age 52.6 years; range 37.3 to 80.7 years) were included in the study. The relative frequency of primarily asymptomatic ureteral stones among all patients treated for ureteral stones in the study period was 0.7%. Eleven renal units showed some degree of hydronephrosis while 3 kidneys were not dilated. On the MAG-3 scan, 7 patients had an obstruction of the ureter, 5 had no obstruction, and 2 had dysfunction of the kidney. A statistically significant correlation was established between the grade of obstruction and stone size (p = 0.02). Conclusions At the time of presentation, only 64.3% of the patients revealed an obstruction in the stone-bearing renal unit. The degree of hydronephrosis and renal function were very diverse in this subgroup of patients with ureteral stones. The onset of ureterolithiasis and the chronological sequence of obstruction remain unclear in patients who have never experienced symptoms due to their stones. PMID:24397735

  14. Renal functional reserve is impaired in patients with systemic sclerosis without clinical signs of kidney involvement

    PubMed Central

    Livi, R; Teghini, L; Pignone, A; Generini, S; Matucci-Cerinic, M; Cagnoni, M

    2002-01-01

    Objective: To evaluate the functional response of the kidney to an amino acid challenge (the so called renal functional reserve (RFR)) in patients with systemic sclerosis (SSc) with no clinical sign of renal involvement. Methods: Before and after an intravenous amino acid load (Freamine III Baxter, 8.5% solution, 4.16 ml/min for two hours), glomerular filtration rate (GFR, as creatinine clearance), effective renal plasma flow (ERPF, as para-aminohyppurate clearance), and calculated total renal vascular resistance (TRVR) were measured in 21 patients with SSc with apparently normal renal function and 10 normal controls. Results: In basal conditions, patients had lower ERPF (403.5 (SD 43.8) v 496.4 (SD 71.3) ml/min, p<0.0002) and higher TRVR (10 822 (SD 2044) v 8874 (SD 1639) dyne/sxcm-5, p<0.014) than controls. The RFR, evaluated as the percentage increase of GFR after the amino acid load, was significantly reduced in patients with SSc (SSc +1.9 (SD18.6)%, controls +34.8 (SD 13.9)%; p<0.0002). However, the response of patients was not uniform. Multiple regression analysis showed that the RFR was inversely dependent on the patients' mean arterial pressure at admission and basal GFR (R2=65%, p<0.0001). Conclusions: Most patients with SSc cannot increase renal filtration under the challenge of a protein overload. This defective renal response to the amino acid load test sustains the concept of the prevalence of vasoconstrictor over vasodilating factors in the kidney of these patients. PMID:12117672

  15. Endotoxemia and the effects of dopamine on renal functions of neonatal piglets.

    PubMed

    Chin, Anthony; O'Conner, Linh Nguyen; Radhakrishnan, Jayant; Fornell, Linda; John, Eunice

    2002-01-01

    In this study, we observed the effects of moderate and high doses of dopamine on the renal functions of neonatal piglets during endotoxic shock. We found that fluid therapy alone was better at maintaining cardiac index and preventing elevation of systemic vascular resistance, than dopamine at 10 and at 20 microg/kg/min. Furthermore, urine output and glomerular filtration rate were reduced by dopamine. Following endotoxin administration dopamine decreased SVR and maintained a CI better than fluid alone. However, in spite of a better CI, greater deterioration in renal functions occurred in the dopamine groups as compared to the fluid group.

  16. Aortic Blood Flow Reversal Determines Renal Function: Potential Explanation for Renal Dysfunction Caused by Aortic Stiffening in Hypertension.

    PubMed

    Hashimoto, Junichiro; Ito, Sadayoshi

    2015-07-01

    Aortic stiffness determines the glomerular filtration rate (GFR) and predicts the progressive decline of the GFR. However, the underlying pathophysiological mechanism remains obscure. Recent evidence has shown a close link between aortic stiffness and the bidirectional (systolic forward and early diastolic reverse) flow characteristics. We hypothesized that the aortic stiffening-induced renal dysfunction is attributable to altered central flow dynamics. In 222 patients with hypertension, Doppler velocity waveforms were recorded at the proximal descending aorta to calculate the reverse/forward flow ratio. Tonometric waveforms were recorded to measure the carotid-femoral (aortic) and carotid-radial (peripheral) pulse wave velocities, to estimate the aortic pressure from the radial waveforms, and to compute the aortic characteristic impedance. In addition, renal hemodynamics was evaluated by duplex ultrasound. The estimated GFR was inversely correlated with the aortic pulse wave velocity, reverse/forward flow ratio, pulse pressure, and characteristic impedance, whereas it was not correlated with the peripheral pulse wave velocity or mean arterial pressure. The association between aortic pulse wave velocity and estimated GFR was independent of age, diabetes mellitus, hypercholesterolemia, and antihypertensive medication. However, further adjustment for the aortic reverse/forward flow ratio and pulse pressure substantially weakened this association, and instead, the reverse/forward flow ratio emerged as the strongest determinant of estimated GFR (P=0.001). A higher aortic reverse/forward flow ratio was also associated with lower intrarenal forward flow velocities. These results suggest that an increase in aortic flow reversal (ie, retrograde flow from the descending thoracic aorta toward the aortic arch), caused by aortic stiffening and impedance mismatch, reduces antegrade flow into the kidney and thereby deteriorates renal function.

  17. [Dose estimation for renal-excretion drugs in neonates and infants based on physiological development of renal function].

    PubMed

    Suzuki, Shinya; Murayama, Yuka; Sugiyama, Erika; Sekiyama, Masao; Sato, Hitoshi

    2009-07-01

    We established dose estimation formulae for renal-excretion drugs using the glomerular filtration rate (GFR), tubular secretion clearance (Sc), and unbound fraction of drug in plasma (fp) as a renal function index of physiological development in neonates and infants not more than 2 years of age. A dose ratio of (DC/DA)=clearance ratio of (CLC/CLA) congruent with(fpC.GFRC)/(fpA.GFRA) for neonates and infants/adults was applied to drugs with fp.GFR>Sc, while DC/DA=CLC/CLA congruent with(beta.BSAC+fpC.GFRC)/(beta.BSAA+fpA.GFRA) was applied to drugs with Sc>fp.GFR using the coefficient of each drug (beta) and body surface area (BSA). Validity of the estimation formulae was investigated in drugs with fp.GFR>Sc such as vancomycin (VCM), arbekacin (ABK), fosfomycin (FOM) and norfloxacin (NFLX), and in drugs with Sc>fp.GFR such as digoxin (DGX) and amoxicillin (AMPC). First, we compared the clearance ratio (CLC/ CLA) of VCM, ABK, and DGX estimated by our method with those calculated using the Japanese population clearance values and those estimated allometrically (BSAC/BSAA). Next, we compared the established doses of all drugs investigated with the doses for neonates and infants calculated from the conventional dose estimation methods for children and our estimation formulae, and evaluated our method. As a result, favorable consistency was observed in the CL ratio for all drugs, and the doses of VCM, FOM, NFLX and AMPC calculated from our estimation formulae approximated the established doses. In conclusion, the validity of the dose estimation method using pharmacokinetic factors related to physiological development (i.e., GFR, fp, Sc) for renal-excretion drugs in neonates and infants was demonstrated.

  18. Soy provides modest benefits on endothelial function without affecting inflammatory biomarkers in adults at cardiometabolic risk

    PubMed Central

    Reverri, Elizabeth J.; LaSalle, Colette D.; Franke, Adrian A.; Steinberg, Francene M.

    2015-01-01

    Scope Systemic inflammation, endothelial dysfunction, and oxidative stress are involved in the pathogenesis of the metabolic syndrome (MetS). Epidemiological evidence supports an association between whole soy food consumption and reduced risk of cardiovascular disease (CVD). The objective of this randomized, controlled, crossover study was to evaluate the effects of soy nut consumption on inflammatory biomarkers and endothelial function and to assess whether isoflavone metabolism to secondary products, equol and/or O-desmethylangolensin (ODMA), modifies these responses. Methods and Results n=17 adults at cardiometabolic risk were randomly assigned to the order of two snack interventions, soy nuts and macronutrient-matched control snack, for four weeks each, separated by a two week washout period. Outcome measures included biomarkers of inflammation, oxidative stress, and glycemic control (ELISA and clinical analyzers), endothelial function and arterial stiffness (peripheral arterial tonometry (PAT)), and isoflavone metabolites (LC-MS/MS). Results revealed that consuming soy nuts improved arterial stiffness as assessed by the augmentation index using PAT (P=0.03), despite lack of improvement in inflammatory biomarkers. Addition of equol and/ODMA production status as covariates did not significantly change these results. Conclusions Soy nuts when added to a usual diet for one month provide some benefit on arterial stiffness in adults at cardiometabolic risk. PMID:25351805

  19. The Landscape of Protein Biomarkers Proposed for Periodontal Disease: Markers with Functional Meaning

    PubMed Central

    Rosa, Nuno; Correia, Maria José; Arrais, Joel P.; Costa, Nuno; Oliveira, José Luís; Barros, Marlene

    2014-01-01

    Periodontal disease (PD) is characterized by a deregulated inflammatory response which fails to resolve, activating bone resorption. The identification of the proteomes associated with PD has fuelled biomarker proposals; nevertheless, many questions remain. Biomarker selection should favour molecules representing an event which occurs throughout the disease progress. The analysis of proteome results and the information available for each protein, including its functional role, was accomplished using the OralOme database. The integrated analysis of this information ascertains if the suggested proteins reflect the cell and/or molecular mechanisms underlying the different forms of periodontal disease. The evaluation of the proteins present/absent or with very different concentrations in the proteome of each disease state was used for the identification of the mechanisms shared by different PD variants or specific to such state. The information presented is relevant for the adequate design of biomarker panels for PD. Furthermore, it will open new perspectives and help envisage future studies targeted to unveil the functional role of specific proteins and help clarify the deregulation process in the PD inflammatory response. PMID:25057495

  20. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  1. [A 100-year perspective on renal function and hypertension. Anti-renin therapy has made hypertensive renal failure a rarity].

    PubMed

    Bergström, G; Herlitz, H; Himmelmann, A; Ljungman, S; Aurell, M

    1999-11-24

    One hundred years ago, in 1898, Professor Robert Tigerstedt, Karolinska institutet, Sweden, discovered renin. The subsequent elaboration in 1960 of the renin-angiotensin-aldosterone system signalled the start of modern hypertension research. The kidney takes part in blood pressure regulation in a number of ways. Indications are that increased renovascular resistance due to increased renin-angiotensin activity is of importance for the barostatic function of the kidneys and for the pathogenesis of human hypertension. Several commonly used, efficacious and well tolerated antihypertensive agents act by blocking the renin-angiotensin system, thus normalising kidney function. A number of current large-scale trials--utilising ACE inhibitors and angiotensin receptor antagonists--will, it is hoped, elucidate the proper role of 'anti-renin therapy' in the treatment of hypertension. Thanks to effective modern management of hypertension, renal failure due to hypertensive kidney disease is rare in Sweden today.

  2. Structural and functional alterations in Malpighian tubules as biomarkers of environmental pollution: synopsis and prospective.

    PubMed

    Giglio, Anita; Brandmayr, Pietro

    2017-03-06

    Although a number of biomarkers of pollutant exposure have been identified in invertebrate species, little is known about the effect on Malpighian tubules playing an essential role in excretion and osmoregulation. Analyses of structural and functional alterations on this organ can be useful to predict the effects at the organism and population level in monitoring studies of environmental pollution. The aim of the present review is to provide a synthesis of existing knowledge on cellular damages induced by xenobiotics in Malpighian tubules both under laboratory and field conditions. We compared studies of exposure to pesticides and heavy metals as mainly environmental contaminants from anthropogenic activities. This report provided evidence that the exposure to xenobiotics has an effect on this organ and reinforces the need for further research integrating molecular biomarkers with analysis on Malpighian tubules. Copyright © 2017 John Wiley & Sons, Ltd.

  3. A review about biomarkers for the investigation of vascular function and impairment in diabetes mellitus

    PubMed Central

    Derosa, Giuseppe; Maffioli, Pamela

    2016-01-01

    The aim of this review was to analyze the main biomarkers of vascular function and impairment in patients with type 2 diabetes. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched. We concluded that proatherogenic adhesion molecules (soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and soluble E selectin) and inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α) were elevated in type 2 diabetes mellitus. Their increased expression and release contribute to the accelerated atherogenesis typical of these patients. For these reasons, the early identification of high levels of these biomarkers will help to establish new strategies to reduce cardiovascular complications. PMID:27877049

  4. A review about biomarkers for the investigation of vascular function and impairment in diabetes mellitus.

    PubMed

    Derosa, Giuseppe; Maffioli, Pamela

    2016-01-01

    The aim of this review was to analyze the main biomarkers of vascular function and impairment in patients with type 2 diabetes. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched. We concluded that proatherogenic adhesion molecules (soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and soluble E selectin) and inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α) were elevated in type 2 diabetes mellitus. Their increased expression and release contribute to the accelerated atherogenesis typical of these patients. For these reasons, the early identification of high levels of these biomarkers will help to establish new strategies to reduce cardiovascular complications.

  5. Influence of Parasite Load on Renal Function in Mice Acutely Infected with Trypanosoma cruzi

    PubMed Central

    Parreira, Ricardo Cambraia; Miguel, Renata Botelho; de Paula Rogerio, Alexandre; Oliveira, Carlo Jose Freire; Chica, Javier Emilio Lazo

    2013-01-01

    Background Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Despite the vast number of studies evaluating the pathophysiological mechanisms of the disease, the influence of parasite burden on kidney lesions remains unclear. Thus, the main goal of this work was to evaluate the effect of T. cruzi infection on renal function and determine whether there was a correlation between parasite load and renal injury using an acute experimental model of the disease. Methodology/Principal Findings Low, medium and high parasite loads were generated by infecting C57BL/6 mice with 300 (low), 3,000 (medium) or 30,000 (high) numbers of “Y” strain trypomastigotes. We found that mice infected with T. cruzi trypomastigotes show increased renal injury. The infection resulted in reduced urinary excretion and creatinine clearance. We also observed a marked elevation in the ratio of urine volume to kidney and body weight, blood urea nitrogen, chloride ion, nitric oxide, pro- and anti-inflammatory cytokines and the number of leukocytes in the blood and/or renal tissues of infected mice. Additionally, we observed the presence of the parasite in the cortical/medullary and peri-renal region, an increase of inflammatory infiltrate and of vascular permeability of the kidney. Overall, most renal changes occurred mainly in animals infected with high parasitic loads. Conclusions/Significance These data demonstrate that T. cruzi impairs kidney function, and this impairment is more evident in mice infected with high parasitic loads. Moreover, these data suggest that, in addition to the extensively studied cardiovascular effects, renal injury should be regarded as an important indicator for better understanding the pan-infectivity of the parasite and consequently for understanding the disease in experimental models. PMID:23951243

  6. Health status, renal function, and quality of life after multiorgan failure and acute kidney injury requiring renal replacement therapy

    PubMed Central

    Faulhaber-Walter, Robert; Scholz, Sebastian; Haller, Herrmann; Kielstein, Jan T; Hafer, Carsten

    2016-01-01

    Background Critically ill patients with acute kidney injury (AKI) in need of renal replacement therapy (RRT) may have a protracted and often incomplete rehabilitation. Their long-term outcome has rarely been investigated. Study design Survivors of the HANnover Dialysis OUTcome (HANDOUT) study were evaluated after 5 years for survival, health status, renal function, and quality of life (QoL). The HANDOUT study had examinded mortality and renal recovery of patients with AKI receiving either standard extendend or intensified dialysis after multi organ failure. Results One hundred fifty-six former HANDOUT participants were analyzed. In-hospital mortality was 56.4%. Five-year survival after AKI/RRT was 40.1% (86.5% if discharged from hospital). Main causes of death were cardiovascular complications and sepsis. A total of 19 survivors presented to the outpatient department of our clinic and had good renal recovery (mean estimated glomerular filtration rate 72.5±30 mL/min/1.73 m2; mean proteinuria 89±84 mg/d). One person required maintenance dialysis. Seventy-nine percent of the patients had a pathological kidney sonomorphology. The Charlson comorbidity score was 2.2±1.4 and adjusted for age 3.3±2.1 years. Numbers of comorbid conditions averaged 2.38±1.72 per patient (heart failure [52%] > chronic kidney disease/myocardial infarction [each 29%]). Median 36-item short form health survey (SF-36™) index was 0.657 (0.69 physical health/0.66 mental health). Quality-adjusted life-years after 5 years were 3.365. Conclusion Mortality after severe AKI is higher than short-term prospective studies show, and morbidity is significant. Kidney recovery as well as general health remains incomplete. Reduction of QoL is minor, and social rehabilitation is very good. Affectivity is heterogeneous, but most patients experience emotional well-being. In summary, AKI in critically ill patients leads to incomplete rehabilitation but acceptable QoL after 5 years. PMID:27284261

  7. Effect of urinary stone disease and its treatment on renal function

    PubMed Central

    Mehmet, Necmettin Mercimek; Ender, Ozden

    2015-01-01

    Urolithiasis is a common disease that affects urinary tract in all age groups. Both in adults and in children, stone size, location, renal anatomy, and other factors, can influence the success of treatment modalities. Recently, there has been a great advancement in technology for minimally invasive management of urinary stones. The epoch of open treatment modalities has passed and currently there are much less invasive treatment approaches, such as percutaneous nephrolithotomy, ureteroscopy, shockwave lithotripsy, and retrograde internal Surgery. Furthermore, advancement in imaging technics ensures substantial knowledge that permit physician to decide the most convenient treatment method for the patient. Thus, effective and rapid treatment of urinary tract stones is substantial for the preservation of the renal function. In this review, the effects of the treatment options for urinary stones on renal function have been reviewed. PMID:25949941

  8. Pharmacologic strategies to preserve renal function in acute decompensated heart failure.

    PubMed

    Kumar, Sachin; Taylor, David O

    2015-02-01

    Over a million patients get hospitalized with the diagnosis of acute decompensated heart failure which poses an insurmountable financial burden on the health care system. Heart failure alone incurs over 30 billion dollars with half the cost spent towards acute hospitalizations. Majority of the treatment strategies have focused towards decongesting patients which often comes with the cost of worsening renal function. Renal dysfunction in the setting of acute decompensated heart failure portends worse morbidity and mortality. Recently, there has been a change in the focus with shift towards therapies attempting to conserve renal function. In the past decade, we have witnessed several large randomized controlled trials testing the established as well as emerging therapies in this subset of population with mixed results. This review intends to provide a comprehensive overview of the pharmacologic therapies commonly utilized in the management of acute decompensated heart failure and the body of evidence supporting these strategies.

  9. In vivo maturation of functional renal organoids formed from embryonic cell suspensions.

    PubMed

    Xinaris, Christodoulos; Benedetti, Valentina; Rizzo, Paola; Abbate, Mauro; Corna, Daniela; Azzollini, Nadia; Conti, Sara; Unbekandt, Mathieu; Davies, Jamie A; Morigi, Marina; Benigni, Ariela; Remuzzi, Giuseppe

    2012-11-01

    The shortage of transplantable organs provides an impetus to develop tissue-engineered alternatives. Producing tissues similar to immature kidneys from simple suspensions of fully dissociated embryonic renal cells is possible in vitro, but glomeruli do not form in the avascular environment. Here, we constructed renal organoids from single-cell suspensions derived from E11.5 kidneys and then implanted these organoids below the kidney capsule of a living rat host. This implantation resulted in further maturation of kidney tissue, formation of vascularized glomeruli with fully differentiated capillary walls, including the slit diaphragm, and appearance of erythropoietin-producing cells. The implanted tissue exhibited physiologic functions, including tubular reabsorption of macromolecules, that gained access to the tubular lumen on glomerular filtration. The ability to generate vascularized nephrons from single-cell suspensions marks a significant step to the long-term goal of replacing renal function by a tissue-engineered kidney.

  10. In Vivo Maturation of Functional Renal Organoids Formed from Embryonic Cell Suspensions

    PubMed Central

    Benedetti, Valentina; Rizzo, Paola; Abbate, Mauro; Corna, Daniela; Azzollini, Nadia; Conti, Sara; Unbekandt, Mathieu; Davies, Jamie A.; Morigi, Marina; Benigni, Ariela; Remuzzi, Giuseppe

    2012-01-01

    The shortage of transplantable organs provides an impetus to develop tissue-engineered alternatives. Producing tissues similar to immature kidneys from simple suspensions of fully dissociated embryonic renal cells is possible in vitro, but glomeruli do not form in the avascular environment. Here, we constructed renal organoids from single-cell suspensions derived from E11.5 kidneys and then implanted these organoids below the kidney capsule of a living rat host. This implantation resulted in further maturation of kidney tissue, formation of vascularized glomeruli with fully differentiated capillary walls, including the slit diaphragm, and appearance of erythropoietin-producing cells. The implanted tissue exhibited physiologic functions, including tubular reabsorption of macromolecules, that gained access to the tubular lumen on glomerular filtration. The ability to generate vascularized nephrons from single-cell suspensions marks a significant step to the long-term goal of replacing renal function by a tissue-engineered kidney. PMID:23085631

  11. Comparison of Renal Function between Robot-Assisted and Open Partial Nephrectomy as Determined by Tc 99m-DTPA Renal Scintigraphy

    PubMed Central

    2016-01-01

    We compared postoperative renal function impairment between patients undergoing robot-assisted partial nephrectomy (RAPN) and those undergoing open partial nephrectomy (OPN) by using Tc-99m diethylenetriaminepentaacetic acid (DTPA) renal scintigraphy. Patients who underwent partial nephrectomy by a single surgeon between 2007 and 2013 were eligible and were matched by propensity score, based on age, tumor size, exophytic properties of tumor, and location relative to the polar lines. Of the 403 patients who underwent partial nephrectomy, 114 (28%) underwent RAPN and 289 (72%) underwent OPN. Mean follow-up duration was 35.2 months. Following propensity matching, there were no significant differences between the two groups in tumor exophytic properties (P = 0.818) or nephrometry score (P = 0.527). Renal ischemic time (24.4 minutes vs. 17.8 minutes, P < 0.001) was significantly longer in the RAPN group than in the OPN group, while the other characteristics were similar. Multivariate analysis showed that greater preoperative renal unit function (P = 0.011) and nephrometry score (P = 0.041) were independently correlated with a reduction in glomerular filtration rate. The operative method did not correlate with renal function impairment (P = 0.704). Postoperative renal function impairment was similar between patients who underwent OPN and those who underwent RAPN, despite RAPN having a longer ischemic time. PMID:27134496

  12. Comparison of Renal Function between Robot-Assisted and Open Partial Nephrectomy as Determined by Tc 99m-DTPA Renal Scintigraphy.

    PubMed

    Lee, Chanwoo; Kwon, Taekmin; Yoo, Sangjun; Jung, Jaeyoon; Lee, Chunwoo; You, Dalsan; Jeong, In Gab; Kim, Choung-Soo

    2016-05-01

    We compared postoperative renal function impairment between patients undergoing robot-assisted partial nephrectomy (RAPN) and those undergoing open partial nephrectomy (OPN) by using Tc-99m diethylenetriaminepentaacetic acid (DTPA) renal scintigraphy. Patients who underwent partial nephrectomy by a single surgeon between 2007 and 2013 were eligible and were matched by propensity score, based on age, tumor size, exophytic properties of tumor, and location relative to the polar lines. Of the 403 patients who underwent partial nephrectomy, 114 (28%) underwent RAPN and 289 (72%) underwent OPN. Mean follow-up duration was 35.2 months. Following propensity matching, there were no significant differences between the two groups in tumor exophytic properties (P = 0.818) or nephrometry score (P = 0.527). Renal ischemic time (24.4 minutes vs. 17.8 minutes, P < 0.001) was significantly longer in the RAPN group than in the OPN group, while the other characteristics were similar. Multivariate analysis showed that greater preoperative renal unit function (P = 0.011) and nephrometry score (P = 0.041) were independently correlated with a reduction in glomerular filtration rate. The operative method did not correlate with renal function impairment (P = 0.704). Postoperative renal function impairment was similar between patients who underwent OPN and those who underwent RAPN, despite RAPN having a longer ischemic time.

  13. Renal sympathetic denervation in patients with hypertension and chronic kidney disease: does improvement in renal function follow blood pressure control?

    PubMed

    Kiuchi, Márcio Galindo; Chen, Shaojie; Andrea, Bruno Rustum; Kiuchi, Tetsuaki; Carreira, Maria Angela Magalhães de Queiroz; Graciano, Miguel Luis; Lugon, Jocemir Ronaldo

    2014-11-01

    Twenty-seven patients with resistant hypertension and chronic kidney disease were treated by renal sympathetic denervation (RSD) and followed for 12 months. Patients were retrospectively divided into controlled and uncontrolled blood pressure (BP) groups. Increases in mean estimated glomerular filtration rate (eGFR) were found at months 1, 3, 6, and 12 in the controlled group (P < .0001, for every time point). The mean change in eGFR after 12 months was 18.54 ± 8.15 mL/min/1.73 m(2) higher in the controlled group (P=.0318). In patients in the controlled group with baseline eGFR < 45 mL/min/1.73 m(2), responders (with an increase in eGFR > 6.2%) corresponded to 50% at 6 months and 83% at 12 months. In the patients with baseline eGFR ≥ 45 mL/min/1.73 m(2), all patients were labeled as responders at months 6 and 12. Median albumin:creatinine ratio after 12 months was lower than baseline only in the controlled group (P = .0003). Our results suggest that patients with this profile who reached BP control by RSD also experienced a significant improvement in renal function.

  14. Supranormal renal function in unilateral hydronephrosis: does it represent true hyperfunction?

    PubMed

    Maenhout, Annelies; Ham, Hamphrey; Ismaili, K; Hall, M; Dierckx, R A; Piepsz, A

    2005-12-01

    The existence of supranormal differential renal function in unilateral hydronephrosis remains controversial. While some authors consider it as fact, others believe that it is just a technical artifact. Within our department, chromium-51 ethylene diamine tetra-acetic acid (Cr-EDTA) renal clearance is systematically performed in conjunction with technetium-99m mercaptoacetyltriglycine (MAG3) renograms to derive an absolute single kidney glomerular filtration rate (SKGFR). Our data allows us to ascertain whether supranormal differential renal function in unilateral hydronephrosis might be due to hypofunction of the contralateral kidney. Children with marked unilateral hydronephrosis were selected from a large database of MAG3 diuretic(s) renograms. We excluded patients with posterior urethral valves, duplex anomalies, neurogenic bladder, solitary kidney, and those who underwent any previous urological surgery. We also excluded children who had an early furosemide injection (F0 procedure), selecting only those having received furosemide at the end of the renogram (F+20 test). Seventy-three patients (92 renograms) fulfilled these criteria. Differential renal function was calculated using the integral method. Hydronephrotic kidney with a relative uptake > or =55% was defined as supranormal. Six renograms (four patients) demonstrated supranormal relative function on the hydronephrotic side. However, the SKGFR of these kidneys was in all cases within the range of normal values, while the contralateral side demonstrated borderline low SKGFR. Increased relative function on the side of the hydronephrotic kidney is relatively infrequent. When it occurs, it may be related to a borderline hypofunction of the contralateral kidney.

  15. /sup 99m/Tc-glucoheptonate for quantitation of differential renal function

    SciTech Connect

    Ziessman, H.A.; Balseiro, J.; Fahey, F.H.; Le, T.V.; Dubiansky, V.

    1987-05-01

    Differential renal function was calculated by using /sup 99m/Tc-glucoheptonate (Tc-GH) in 51 patients. Computer-acquired background-corrected individual renal function was calculated by using both the 1-3-min uptake counts and the 2-4-hr delayed static counts. The degree of correlation between the two was high (r = .96). An equally high correlation was noted in 16 children who were 12 years old or younger, in 15 patients with renal size disparity greater than 60/40%, and in six patients with abnormal creatinine clearances. Ten patients had a 30-min dynamic /sup 99m/Tc-DTPA study followed immediately by the injection of Tc-GH and acquisition of delayed static images 2-4 hr later. A high degree of correlation (r = .99) was seen between the 1-3-min differential function obtained by using Tc-DTPA and the 2-4-hr delayed differential function obtained by using Tc-GH. This study shows that Tc-GH is a clinically useful and valid tool for calculation of differential renal function and that Tc-GH combines many of the best aspects of Tc-DTPA and Tc-DMSA.

  16. Cerebral Small Vessel Disease and Renal Function: Systematic Review and Meta-Analysis

    PubMed Central

    Makin, Stephen D.J.; Cook, F.A.B.; Dennis, Martin S.; Wardlaw, Joanna M.

    2015-01-01

    Background The small vessel disease (SVD) that appears in the brain may be part of a multisystem disorder affecting other vascular beds such as the kidney and retina. Because renal failure is associated with both stroke and white matter hyperintensities we hypothesised that small vessel (lacunar) stroke would be more strongly associated with renal failure than cortical stroke. Therefore, we performed a systematic review and meta-analysis to establish first if lacunar stroke was associated with the renal function, and second, if cerebral small vessel disease seen on the MRI of patients without stroke was more common in patients with renal failure. Methods We searched Medline and EMBASE for studies in adults with cerebral SVD (lacunar stroke or white matter hyper intensities (WMH) on Magnetic Resonance Imaging (MRI)), in which renal function was assessed (estimated glomerular filtration rate (eGFR) or proteinuria). We extracted data on SVD diagnosis, renal function, demographics and comorbidities. We performed two meta-analyses: first, we calculated the odds of renal impairment in lacunar (small vessel) ischaemic stroke compared to other ischaemic stroke subtypes (non-small vessel disease); and second, we calculated the odds of renal impairment in non-stroke individuals with WMH on MRI compared to individuals without WMH. We then performed a sensitivity analysis by excluding studies with certain characteristics and repeating the meta-analysis calculation. Results After screening 11,001 potentially suitable titles, we included 37 papers reporting 32 studies of 20,379 subjects: 15 of stroke patients and 17 of SVD features in non-stroke patients. To diagnose lacunar stroke, 13/15 of the studies used risk factor-based classification (none used diffusion-weighted MRI). 394/1,119 (35%) of patients with lacunar stroke had renal impairment compared with 1,443/4,217 (34%) of patients with non-lacunar stroke, OR 0.88, (95% CI 0.6-1.30). In individuals without stroke the

  17. Urinary biomarkers of kidney diseases in HIV-infected children.

    PubMed

    Perazzo, Sofia; Soler-García, Ángel A; Hathout, Yetrib; Das, Jharna R; Ray, Patricio E

    2015-06-01

    A significant number of children infected with the human immunodeficiency virus 1 (HIV-1) virus all over the world are at risk of developing renal diseases that could have a significant impact on their treatment and quality of life. It is necessary to identify children undergoing the early stages of these renal diseases, as well as the potential renal toxicity that could be caused by antiretroviral drugs, in order to prevent the development of cardiovascular complications and chronic renal failure. This article describes the most common renal diseases seen in HIV-infected children, as well as the value and limitations of the clinical markers that are currently being used to monitor their renal function and histological damage in a noninvasive manner. In addition, we discuss the progress made during the last 10 years in the discovery and validation of new renal biomarkers for HIV-infected children and young adults. Although significant progress has been made during the early phases of the biomarkers discovery, more work remains to be done to validate the new biomarkers in a large number of patients. The future looks promising, however, the new knowledge needs to be integrated and validated in the context of the clinical environment where these children are living.

  18. The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats.

    PubMed

    Jahn, Matheus Parmegiani; Gomes, Luana Ferreira; Jacob, Maria Helena Vianna Metello; da Rocha Janner, Daiane; Araújo, Alex Sander da Rosa; Belló-Klein, Adriane; Ribeiro, Maria Flávia Marques; Kucharski, Luiz Carlos

    2011-05-01

    Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β(1) (TGF-β(1)) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β(1), as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β(1) and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood.

  19. Longitudinal renal function in pediatric heart transplant recipients: 20-years experience.

    PubMed

    Gupta, Punkaj; Rettiganti, Mallikarjuna; Gossett, Jeffrey M; Gardner, Megan; Bryant, Janet C; Noel, Tommy R; Knecht, Kenneth R

    2015-03-01

    This study was initiated to assess the temporal trends of renal function, and define risk factors associated with worsening renal function in pediatric heart transplant recipients in the immediate post-operative period. We performed a single-center retrospective study in children ≤18 yr receiving OHT (1993-2012). The AKIN's validated, three-tiered AKI staging system was used to categorize the degree of WRF. One hundred sixty-four patients qualified for inclusion. Forty-seven patients (28%) were classified as having WRF after OHT. Nineteen patients (11%) required dialysis after heart transplantation. There was a sustained and steady improvement in renal function in children following heart transplantation in all age groups, irrespective of underlying disease process. The significant factors associated with risk of WRF included body surface area (OR: 1.89 for 0.5 unit increase, 95% CI: 1.29-2.76, p = 0.001) and use of ECMO prior to and/or after heart transplantation (OR: 3.50, 95% CI: 1.51-8.13, p = 0.004). Use of VAD prior to heart transplantation was not associated with WRF (OR: 0.50, 95% CI: 0.17-1.51, p = 0.22). On the basis of these data, we demonstrate that worsening renal function improves early after orthotopic heart transplantation.

  20. Renal Function and Diuretic Therapy in Infants and Children. Part i

    ERIC Educational Resources Information Center

    Loggie, Jennifer M. H.; And Others

    1975-01-01

    Included in the review are a description of the anatomic and functional development of the human kidney, a comparison of the renal physiology of the infant and adult, and a discussion of the pediatric clinical pharmacology of the most commonly used diuretic agents. (DB)

  1. Renal Function of Rats in Response to 37 Days of Head-Down Tilt

    NASA Technical Reports Server (NTRS)

    Wang, Tommy J.; Wade, Charles E.; Dalton, Bonnie P. (Technical Monitor)

    2001-01-01

    Spaceflight induces changes in human renal function, suggesting similar changes may occur in rats. Since rats continue to be the prime mammalian model for study in space, the effects of chronic microgravity on rat renal function should be clarified. Acute studies in rats using the ground-based microgravity simulation model, head-down tilt (HDT), have shown increases in glomerular filtration rate (GFR), electrolyte excretion, and a diuresis. However, long term effects of HDT have not been studied extensively. This study was performed to elucidate rat renal function following long-term simulated microgravity. Chronic exposure to HDT will cause an increase in GFR and electrolyte excretion in rats, similar to acute exposures, and lead to a decrease in the fractional excretion of filtered electrolytes. Experimental animals (HDT, n=10) were tail-suspended for 37 days and renal function compared to ambulatory controls (AMB, n=10). On day 37 of HDT, GFR, osmolal clearance, and electrolyte excretion were decreased, while plasma osmolality and free water clearance were increased. Urine output remained similar between groups. The fractional excretion of the filtered electrolytes was unchanged except for a decrease in the percentage of filtered calcium excreted. Chronic exposure to HDT results in decreased GFR and electrolyte excretion, but the fractional excretion of filtered electrolytes remained primarily unaffected.

  2. Can focused US with a diagnostic US contrast agent favorably affect renal function?

    PubMed

    Sica, Domenic A

    2009-12-01

    Focused ultrasonography (US) with simultaneous administration of a US microbubble contrast agent was used to transiently increase the glomerular filtration rate while altering the sieving properties of glomeruli in normal rabbits. In its current form, this process has very limited application potential to states of abnormal renal function.

  3. The effect of thymoquinone on the renal functions following ischemia-reperfusion injury in the rat

    PubMed Central

    Hammad, Fayez T; Lubbad, Loay

    2016-01-01

    Introduction: The aim of this study was to investigate the effect of thymoquinone, an antioxidant phytochemical compound found in the plant Nigella sativa, on the alterations in renal functional parameters following warm renal ischemia-reperfusion injury (IRI) in the rat. Methods: Wistar rats underwent left renal ischemia for 35 minutes. Group-TQ (n=15) received thymoquinone 10 mg/kg/day (dissolved in a vehicle (corn oil) orally by gavage starting 4 days prior to IRI and continued 6 days thereafter when the hemodynamic and tubular renal functions of the right and left kidneys were measured using clearance techniques. Group-Vx (n=15) underwent similar protocol but received only the vehicle. Results: IRI affected all hemodynamic and tubular parameters in the affected kidney. Thymoquinone attenuated the IRI-related alteration in renal functions so when the left ischemic kidney in Group-TQ and Group-Vx were compared, the left RBF and GFR were significantly higher in Group-TQ (2.02±0.39 vs. 1.27±0.21, P=0.04 and 0.33±0.08 vs. 0.18±0.03, P=0.03, respectively). Thymoquinone also improved left renal FENa (1.59±0.28 vs. 2.40±0.35, P=0.04). In addition, it decreased the gene expressions of KIM-1, NGAL, TNF-α, TGF-β1 and PAI-1 (143±20 vs. 358±49, 16±3 vs. 34±6, (1.1±0.2 vs. 2.8±0.4, 1.6±0.1 vs. 2.8±0.1, and 2.4±0.3 vs. 5.8±1.0, P<0.05 for all). Conclusion: Thymoquinone ameliorated the IRI effect on the hemodynamic and tubular renal functional parameters as well as the expression of some kidney injury markers and pro-inflammatory and pro-fibrotic cytokines indicating a renoprotective effect of this agent on the IRI-induced renal dysfunction with potential clinical implications. PMID:28078054

  4. Disposition of cefpodoxime proxetil in healthy volunteers and patients with impaired renal function.

    PubMed Central

    St Peter, J V; Borin, M T; Hughes, G S; Kelloway, J S; Shapiro, B E; Halstenson, C E

    1992-01-01

    The disposition of cefpodoxime in 24 subjects with various degrees of renal function after administration of a single oral dose of 200 mg of cefpodoxime proxetil (equivalent to 200 mg of cefpodoxime activity) was studied. Subjects were assigned to one of four groups (six per group): group I, normal renal function (creatinine clearance [CLCR], greater than ml/min); group II, mild renal impairment (CLCR, 50 to 80 ml/min); group III, moderate renal impairment (CLCR, 30 to 49 ml/min); or group IV, severe renal impairment (CLCR, 5 to 29 ml/min). Although cefpodoxime terminal elimination half-life in group I (2.55 +/- 0.25 h [mean +/- standard deviation]) was not significantly different from that in group II (3.53 +/- 0.74 h), the half-life values for group III (5.90 +/- 1.67 h) and group IV (9.80 +/- 1.21 h) were significantly prolonged compared with those of group I. The mean absorption rate constant was similar among groups and ranged from 0.68 to 0.85 h-1. All groups exhibited absorption lag-times which were comparable (0.30 to 0.41 h), and the apparent volume of distribution was similar among groups. Cefpodoxime apparent total body clearance (CLP/F) values in groups II, III, and IV (132 +/- 29, 112 +/- 41, and 55.7 +/- 9.9 ml/min, respectively) were significantly lower than that in group I (238 +/- 44 ml/min). Cefpodoxime CLP/F was positively correlated with CLCR (r2 = 0.79; P less than 0.05): CLP/F = (1.9 CLCR) + 18.4. Renal clearance also declined with decreasing renal function. Adjustments in cefpodoxime organism and on the site and severity of infection. Simulated plasma concentration-time data from this study suggest that 200 mg of cefpodoxime proxetil administered every 12 to 24 h to subjects with CLcr between 30 and 49 ml/min and 200-mg dose taken every 24 h by subjects with CLcr between 5 and 29 ml/min will maintain cefpodoxime concentration in plasma similar to those in subjects with normal renal function who receive a standard dosage mg every 12 h. PMID

  5. Osseous metastases from renal cell carcinoma: embolization and surgery for restoration of function. Work in progress

    SciTech Connect

    Rowe, D.M.; Becker, G.J.; Rabe, F.E.; Holden, R.W.; Richmond, B.D.; Wass, J.L.; Sequeira, F.W.

    1984-03-01

    Five patients underwent preoperative embolization of osseous metastases from renal cell carcinoma. The group consisted of four men and one woman who ranged in age from 46 to 79 years. The lesions were located in the pubic ramus and acetabulum, proximal femur, femoral midshaft, proximal humerus, and proximal tibia. All embolizations were performed within 24 hours of surgery. The internal fixation and tumor curettage was accomplished with estimated perioperative blood loss ranging from 10 ml to 1,250 ml. All patients had significant restoration of function following surgery. The authors suggest that preoperative embolization is an important and efficacious adjunct in the management of hypervascular renal cell osseous metastases.

  6. Use of 99mTc-mercaptoacetyltriglycine to evaluate renal function in horses.

    PubMed

    Woods, P R; Drost, W T; Clarke, C R; Rodebush, C J

    2000-01-01

    Ten healthy horses were injected intravenously with 99mTc-MAG3 and the disappearance of radioactivity from the blood was measured. The total body clearance (Cl(B)) and elimination half-life (t1/2(beta)) were 7.9 +/- 1.5 ml/kg/minute and 32.8 +/- 4.1 minutes, respectively. The disappearance of 99mTc-MAG3 from the blood of 2 horses with compromised renal function was also measured. The data suggest that 99mTc-MAG3 is a useful and clinically applicable radiopharmaceutical for measurement of effective renal blood flow in the horse.

  7. Effect of the duration of bladder overdistention on renal function and morphology in rats.

    PubMed

    Meng, Hong-Zhou; Cao, Min; Xiang, Jian-Jian; Zhou, Xie-Lai; Yin, Hong-Ping; Jin, Bai-Ye; Chen, Zhao-Dian; Jin, Xiao-Dong

    2013-06-01

    The aim of this study was to investigate the influence of the duration of bladder overdistention (DOBO) on kidney structure and function in rats. Bladder overdistention was induced in male Sprague-Dawley rats by an infusion of saline. Forty rats were divided into five groups: DOBO 1, 2, 4 or 8 h groups and the control. Renal function was evaluated using serum creatinine (SCr) and blood urea nitrogen (BUN). Apoptotic indices and morphologic changes of the kidney were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining and transmission electron microscopy (TEM). Compared with the control, rats undergoing 2, 4 or 8 h of overdistention showed significant, time-dependent increases in SCr (12.375 vs. 23.125, 34.375 and 51.500 μmol/l, respectively), BUN (6.980 vs. 18.689, 25.184 and 32.079 mmol/l, respectively), renal size (1.041 vs. 1.472, 1.484 and 1.634 cm(3), respectively) and renal pelvis separation (0.000 vs. 0.223, 0.320, 0.308 and 0.277 cm, respectively; P<0.01). In the rats, 2, 4 and 8 h of overdistention elicited time-dependent increases in the blood flow rate in the main renal artery (MRA; 44.827 vs. 49.082, 59.688 and 67.123 cm(3)/sec, control vs. DOBO 2, 4 and 8 h), the interlobar renal artery (IRA; 32.095 vs. 39.16 and 51.745 cm(3)/sec, control vs. DOBO 4 and 8 h) and the segmental renal artery (SRA; 21.171 vs. 24.355 and 25.358 cm(3)/sec, control vs. DOBO 4 and 8 h; P<0.01). TUNEL results showed that prolonged overdistention increased the apoptotic index of renal cells significantly (1.15, 1.77, 3.40, 5.34 and 13.91% for control and DOBO 1, 2, 4 and 8 h, respectively; P<0.01) and TEM indicated that prolonged overdistention resulted in ultrastructural injuries of increased severity. DOBO plays a significant role in the functional and structural impairment of the rat kidney. With increasing duration, the hemodynamic changes, cell apoptosis and ultrastructural injuries of the kidney are more evident, all of

  8. FDA Approval Summary: Nivolumab in Advanced Renal Cell Carcinoma After Anti-Angiogenic Therapy and Exploratory Predictive Biomarker Analysis.

    PubMed

    Xu, James Xunhai; Maher, V Ellen; Zhang, Lijun; Tang, Shenghui; Sridhara, Rajeshwari; Ibrahim, Amna; Kim, Geoffrey; Pazdur, Richard

    2017-03-01

    On November 23, 2015, the U.S. Food and Drug Administration approved nivolumab (OPDIVO, Bristol-Myers Squibb Company) for patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. The approval was based on efficacy and safety data demonstrated in an open-label, randomized study of 821 patients with advanced RCC who progressed after at least one anti-angiogenic therapy. Patients were randomized to nivolumab or everolimus and followed for disease progression. The primary end point was overall survival. Subsequent therapies, including everolimus for patients who developed progressive disease on the nivolumab arm, were allowed, but no cross-over was permitted. The median overall survival was 25.0 months on the nivolumab arm and 19.6 months on everolimus arm (hazard ratio: 0.73; 95% confidence interval: 0.60-0.89). The confirmed response rates were 21.5% versus 3.9%; median durations of response were 23.0 versus 13.7 months, and median times to response were 3.0 versus 3.7 months in the nivolumab and everolimus arms, respectively. A statistically significant improvement in progression-free survival was not observed in this trial. The safety profile of nivolumab in renal cell cancer was similar to that in other disease settings. However, the incidence of immune-mediated nephritis appeared to be higher in patients with RCC. The Oncologist 2017;22:311-317 IMPLICATIONS FOR PRACTICE: The overall benefit/risk profile demonstrated in trial CA209025 supported the approval of nivolumab as an additional treatment option for patients with advanced renal cell carcinoma after anti-angiogenic therapy. The use of nivolumab in patients who had received vascular endothelial growth factor-targeted therapy resulted in a 5.4 month improvement in median overall survival compared with the everolimus arm. This difference is statistically significant and clinically meaningful.

  9. Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function.

    PubMed

    Correia-Costa, Liane; Sousa, Teresa; Morato, Manuela; Cosme, Dina; Afonso, Joana; Areias, José C; Schaefer, Franz; Guerra, António; Afonso, Alberto C; Azevedo, Ana; Albino-Teixeira, António

    2016-09-01

    Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8-9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H2O2, myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H2O2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H2O2 were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P for linear trend=0·003). We conclude that oxidant status and NO are increased in relation to fat accumulation and, even in young children, they translate into higher values of cardiometabolic risk markers and affect renal function.

  10. Combined therapy with melatonin and exendin-4 effectively attenuated the deterioration of renal function in rat cardiorenal syndrome

    PubMed Central

    Chen, Kuan-Hung; Chen, Chih-Hung; Wallace, Christopher Glenn; Chen, Yen-Ta; Yang, Chih-Chao; Sung, Pei-Hsun; Chiang, Hsin-Ju; Chen, Yi-Ling; Chua, Sarah; Yip, Hon-Kan; Cheng, Jiin-Tsuey

    2017-01-01

    This study tested the hypothesis that combined therapy with melatonin (Mel) and exendin-4 (Ex4) would be superior to either therapy alone for preventing the deterioration of renal function in cardiorenal syndrome (CRS). Male adult Sprague Dawley rats (n = 48) were randomly and equally divided into sham-control (SC), chronic kidney disease (CKD; induced by 5/6 nephrectomy), CRS (CKD + dilated cardiomyopathy, DCM; induced by doxorubicin 7 mg/kg i.p. every 5 days, 4 doses), CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 µg/kg/day) and CRS-Mel-Ex4. They were euthanized by day 60 after CRS induction. By day 60, plasma creatinine level, urine protein/creatinine ratio and kidney injury histopathology score were highest in CRS, lowest in SC, and progressively decreased from CKD, CRS-Mel, CRS-Ex4 to CRS-Mel-Ex4 (all P<0.0001). The kidney protein expressions of inflammation (TNF-α/NF-κB/MMP-9/iNOS/RANTES), oxidative stress (NOX-1/NOX-2/NOX-4/oxidized protein), apoptosis (cleaved caspase-3/cleaved PARP/Bax), DNA-damaged marker (γ-H2AX) and fibrosis (p-mad3/TFG-β) showed identical patterns of creatinine level, whereas kidney protein expressions of GLP-1R showed a progressive increase from SC to CRS-Mel-Ex4 (all P<0.0001). Cellular expressions of inflammatory (CD14/CD68), DNA/kidney-damaged (γ-H2AX/KIM-1) and podocyte/renal tubule dysfunction signaling (β-catenin/Wnt1/Wnt4) biomarkers in kidney tissue exhibited an identical pattern of creatinine level (all P<0.0001). Podocyte components (podocin/dystroglycan/p-cadherin/synatopodin) were highest in SC, lowest in CRS, and significantly progressively increased from CKD to CRS-Mel-Ex4 (all P<0.0001). In conclusion, combined Mel-Ex4 therapy was superior to either one alone in preserving renal-function and kidney architectural integrity in the setting of CRS. PMID:28337255

  11. Effects of fasting during Ramadan on renal function of patients with chronic kidney disease.

    PubMed

    Mbarki, Houda; Tazi, Nada; Najdi, Adil; Tachfouti, Nabil; Arrayhani, Mohamed; Sqalli, Tarik

    2015-03-01

    Fasting during Ramadan is prohibited when an individual's health is endangered. Little work has been published in this direction in patients with chronic kidney disease (CKD). We aimed to evaluate the impact of fasting during Ramadan on the renal function of patients with CKD, adjusting for the initial degree of renal impairment. We prospectively studied 60 patients with CKD (35 females; mean age 45.6 ± 15.8 years). All study patients were older than 15 years, being followed-up at the nephrology clinic for more than six months, having a stable CKD during the preceding six months and who had fasted during Ramadan the previous year. Patients who had a medical contra-indication for fasting were excluded from the study [severe or resistant arterial hypertension, insulin-requiring diabetes, acute renal failure (ARF), active renal disease, repetitive urolithiasis or terminal chronic renal failure]. Statistical analysis was performed in collaboration with the epidemiology lab at the Fez Medical School using the SPSS software version 17. Three of the study patients developed ARF in the first week and four of them at the end of the month of the study period. The risk of developing ARF was significantly higher for patients with baseline creatinine clearance of <60 mL/min/1.73 m 2 . However, the small sample size does not allow us to draw any firm conclusions on fasting during Ramadan in stable CKD patients. Studies on larger numbers of patients are recommended.

  12. Technetium-99m dimercaptosuccinic acid uptake in long-term catheterized kidney. Comparison with renal function

    SciTech Connect

    Higashihara, E.; Tokuda, H.; Kishi, H.; Niijima, T.; Okada, Y.; Nishikawa, J.; Iio, M.

    1988-04-01

    We studied 23 long-term catheterized kidneys in 14 patients. The uptake of /sup 99m/Tc acid (/sup 99m/Tc-DMSA) was measured at one- and two-hour intervals after injection, and the uptake was corrected for variations in renal depth. These values were compared with inulin, creatinine, and para-amino hippurate (PAH) clearances which were measured in each kidney by collecting urine through long-term catheterization. Correlation coefficient was obtained between PAH clearance corrected for the body surface area and the two-hour uptake of /sup 99m/Tc-DMSA. The correlation coefficients between the two-hour uptake of /sup 99m/Tc-DMSA and the clearance values are not significantly different from those between the one-hour uptake and the clearance values. Corrections of the uptake for variations in renal depth did not improve the correlation coefficients. The results show that /sup 99m/Tc-DMSA is an excellent method to estimate the renal plasma flow and the one-hour uptake without correction for renal depth is clinically sufficient to evaluate the split renal function.

  13. Effects of positive acceleration /+Gz/ on renal function and plasma renin in normal man

    NASA Technical Reports Server (NTRS)

    Epstein, M.; Shubrooks, S. J., Jr.; Fishman, L. M.; Duncan, D. C.

    1974-01-01

    The effects of positive radial centrifugation (+Gz) on plasma resin activity (PRA) and renal function were assessed in 15 normal male subjects under carefully controlled conditions of Na, K, and water intake. Twenty minutes of +2.0 Gz resulted in significant decreases in the mean rate of sodium excretion and creatine clearance and in a doubling of PRA in seven sodium-depleted subjects (10 meq Na intake). In eight sodium-replete subjects (200 mq Na intake), 30 min of +2.0 Gz was also associated with a decrease in the mean rate of sodium excretion. As a consequence of a concurrent decrease in creatine clearance, the fractional excretion of sodium during centrifugation did not differ from control, suggesting that the changes in Na excretion were mediated primarily by renal hemodynamic factors, although enhanced renal tubular sodium reabsorption may also have played a role.

  14. Effects of taurine and housing density on renal function in laying hens*

    PubMed Central

    Ma, Zi-li; Gao, Yang; Ma, Hai-tian; Zheng, Liu-hai; Dai, Bin; Miao, Jin-feng; Zhang, Yuan-shu

    2016-01-01

    This study investigated the putative protective effects of supplemental 2-aminoethane sulfonic acid (taurine) and reduced housing density on renal function in laying hens. We randomly assigned fifteen thousand green-shell laying hens into three groups: a free range group, a low-density caged group, and a high-density caged group. Each group was further divided equally into a control group (C) and a taurine treatment group (T). After 15 d, we analyzed histological changes in kidney cells, inflammatory mediator levels, oxidation and anti-oxidation levels. Experimental data revealed taurine supplementation, and rearing free range or in low-density housing can lessen morphological renal damage, inflammatory mediator levels, and oxidation levels and increase anti-oxidation levels. Our data demonstrate that taurine supplementation and a reduction in housing density can ameliorate renal impairment, increase productivity, enhance health, and promote welfare in laying hens. PMID:27921400

  15. Effect of carbon nanoparticles on renal epithelial cell structure, barrier function, and protein expression

    PubMed Central

    BLAZER-YOST, BONNIE L.; BANGA, AMIRAJ; AMOS, ADAM; CHERNOFF, ELLEN; LAI, XIANYIN; LI, CHENG; MITRA, SOMENATH; WITZMANN, FRANK A.

    2011-01-01

    To assess effects of carbon nanoparticle (CNP) exposure on renal epithelial cells, fullerenes (C60), single-walled carbon nanotubes (SWNT), and multi-walled carbon nanotubes (MWNT) were incubated with a confluent renal epithelial line for 48 h. At low concentrations, CNP-treated cells exhibited significant decreases in transepithelial electrical resistance (TEER) but no changes in hormone-stimulated ion transport or CNP-induced toxicity or stress responses as measured by lactate dehydrogenase or cytokine release. The changes in TEER, manifested as an inverse relationship with CNP concentration, were mirrored by an inverse correlation between dose and changes in protein expression. Lower, more physiologically relevant, concentrations of CNP have the most profound effects on barrier cell function and protein expression. These results indicate an impact of CNPs on renal epithelial cells at concentrations lower than have been previously studied and suggest caution with regard to increasing CNP levels entering the food chain due to increasing environmental pollution. PMID:21067278

  16. Effects of taurine and housing density on renal function in laying hens.

    PubMed

    Ma, Zi-Li; Gao, Yang; Ma, Hai-Tian; Zheng, Liu-Hai; Dai, Bin; Miao, Jin-Feng; Zhang, Yuan-Shu

    This study investigated the putative protective effects of supplemental 2-aminoethane sulfonic acid (taurine) and reduced housing density on renal function in laying hens. We randomly assigned fifteen thousand green-shell laying hens into three groups: a free range group, a low-density caged group, and a high-density caged group. Each group was further divided equally into a control group (C) and a taurine treatment group (T). After 15 d, we analyzed histological changes in kidney cells, inflammatory mediator levels, oxidation and anti-oxidation levels. Experimental data revealed taurine supplementation, and rearing free range or in low-density housing can lessen morphological renal damage, inflammatory mediator levels, and oxidation levels and increase anti-oxidation levels. Our data demonstrate that taurine supplementation and a reduction in housing density can ameliorate renal impairment, increase productivity, enhance health, and promote welfare in laying hens.

  17. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    PubMed Central

    Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Alba, Cesar Gonzalez-De; Froines, John R.; Espinosa-Fematt, Jorge A.

    2016-01-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero is associated with an increase in respiratory symptoms and diseases in adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that exposure to arsenic during early childhood or in utero was associated with impairment in the lung function in children and suggested that this adverse effect could be due to a chronic inflammatory response to the metalloid. Therefore, a cross-sectional study was designed in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their As levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the Soluble Receptor for Advanced Glycation Endproducts (sRAGE) sputum level was significantly lower and Matrix Metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsenic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/Tissue Inhibitor of Metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. PMID:26048584

  18. Sexual hormones modulate compensatory renal growth and function.

    PubMed

    Azurmendi, Pablo J; Oddo, Elisabet M; Toledo, Jorge E; Martin, Rodolfo S; Ibarra, Fernando R; Arrizurieta, Elvira E

    2013-01-01

    The role played by sexual hormones and vasoactive substances in the compensatory renal growth (CRG) that follows uninephrectomy (uNx) is still controversial. Intact and gonadectomized adult Wistar rats of both sexes, with and without uNx, performed at 90 days age, were studied at age 150 days. Daily urine volume, electrolyte excretion and kallikrein activity (UKa) were determined. Afterwards, glomerular filtration rate and blood pressure were measured, the kidneys weighed and DNA, protein and RNA studied to determine nuclei content and cell size. When the remnant kidney weight at age 150 days was compared with the weight of the kidney removed at the time of uNx, male uNx rats showed the greatest CRG (50%) while growth in the other uNx groups was 25%, 15% and 19% in orchidectomized, female and ovariectomized rats, respectively. The small CRG observed in the uNx female rats was accompanied by the lowest glomerular filtration value, 0.56 ± 0.02 ml/ min/g kwt compared, with the other uNx groups, p < 0.05. Cell size (protein or RNA/DNA) was similar for all the groups except for uNx orchidectomized rats. In this group the cytoplasmatic protein or RNA content was lower than in the other groups while DNA (nuclei content) was similar. Some degree of hyperplasia was determined by DNA content in the uNx groups. Male sexual hormones positively influenced CRG and its absence modulated cell size. Female sexual hormones, instead, did not appear to stimulate CRG. The kallikrein kinin system may not be involved in CRG.

  19. Diffuse renal parenchyma uptake with bone scintigraphy in a patient with paroxysmal nocturnal hemoglobinuria and normal kidney function.

    PubMed

    Balink, Hans; Hoogendoorn, Mels; Hemmelder, Marc

    2014-03-01

    A 41-year-old woman with a Harrington spondylodesis presented with lower back pain. Bone scintigraphy showed diffusely increased parenchymal uptake in both kidneys. She reported 2 previous periods of dark, almost black, urine. Additional flow cytometric analysis confirmed the diagnosis of paroxysmal nocturnal hemoglobinuria. The increased renal parenchyma uptake is very probably due to paroxysmal nocturnal hemoglobinuria-related renal hemosiderosis. Remarkably, the patient did not develop any abnormality of renal function.

  20. Oncogenic functions of secreted Frizzled-related protein 2 in human renal cancer.

    PubMed

    Yamamura, Soichiro; Kawakami, Kazumori; Hirata, Hiroshi; Ueno, Koji; Saini, Sharanjot; Majid, Shahana; Dahiya, Rajvir

    2010-06-01

    The secreted Frizzled-related proteins (sFRP) are modulators of the Wnt signaling pathway, which is involved in embryonic development and tumor progression. The functions of sFRP2 have not been studied in renal cancer. Transient transfection of sFRP2 promoted cell growth in renal carcinoma cells, whereby the largest effect was observed in A498 cells. To further study the functions of sFRP2 gene in renal carcinoma cells, we established A498 renal cancer cell lines, which stably expressed sFRP2. Stably expressed sFRP2 significantly promoted cell proliferation in vitro and in vivo tumor growth. The stably expressed sFRP2 cells were also found to have reduced UV-induced apoptosis and increased G(2) phase of the cell cycle. The phosphorylation level at Ser(33/37)/Thr(41) of beta-catenin was lower in the stable sFRP2 cell lines compared with the control cell line. sFRP2 significantly activated T-cell factor/lymphoid enhancer factor transcriptional activity. In the stable sFRP2 cell line, expression of c-Fos, Bcl2, Bcl-w, cyclin B2, and cyclin E2 genes was significantly increased and p53 expression was decreased. This is the first report documenting that sFRP2 activates the canonical Wnt pathway and promotes cell growth by evoking diverse signaling cascades in renal cancer cells. This study may provide better strategies for the management of renal cancer through regulation of sFRP2 pathways.

  1. Control of arterial pressure and renal function during glucocorticoid excess in dogs.

    PubMed

    Hall, J E; Morse, C L; Smith, M J; Young, D B; Guyton, A C

    1980-01-01

    This study was designed to investigate the long-term effects of glucocorticoids on the control of mean arterial pressure (MAP) and renal function. Infusion of 10 mg/day of methylprednisolone (MP), a glucocorticoid with minimal mineralocorticoid activity, for 10 days in six intact conscious dogs maintained on a sodium intake of 78 mEq/day resulted in a decrease in MAP from 98 +/- 1 to 89 +/- 2 mm Hg, a decrease in sodium iothalamate space to 89 +/- 2% of control, and a marked increase in glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and urinary sodium excretion. Chronic infusion of MP at doses of 2--800 mg/day in four dogs maintained on low (5 mEq/day) or high sodium intakes (160--223 mEq/day) also caused increases in GFR and ERPF, as well as natriuresis and decreased sodium iothalamate space, while causing either no change or a slight reduction in MAP. To determine whether glucocorticoids potentiate the chronic effects of angiotensin II (AII) on MAP and renal function, MP was infused in dogs undergoing AII infusion (5 ng/kg/min). During AII hypertension, chronic infusion of 5 or 10 mg/day of MP also resulted in a marked renal vasodilation, natriuresis, and reductions in sodium iothalamate space, while causing small reductions in MAP. Thus, we found no evidence that chronic glucocorticoid excess causes hypertension in dogs, or that glucocorticoids potentiate the blood pressure or renal effects of AII. Instead, glucocorticoids tended to reduce MAP, probably because of chronic renal vasodilation, increased excretion of sodium, and volume depletion.

  2. Markers of Renal Disease and Function Are Associated with Systemic Inflammation in HIV

    PubMed Central

    Gupta, Samir K; Kitch, Douglas; Tierney, Camlin; Melbourne, Kathleen; Ha, Belinda; McComsey, Grace A

    2015-01-01

    Objectives Both renal disease and systemic inflammation predict non-AIDS events and overall mortality in HIV-infected patients. Here we sought to determine the relationships between renal disease and circulating inflammation markers. Methods We performed a secondary analysis of AIDS Clinical Trials Group study A5224s to determine if markers of renal disease [urine protein/creatinine (uPCR); urine albumin/creatinine (uACR); estimated glomerular filtration rate, eGFR, using CKD-EPI creatinine and cystatin C-creatinine] were associated with markers of systemic inflammation [high sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, soluble receptors of TNF-α (sTNFRI and II), soluble vascular cellular and intercellular adhesion molecules]. We correlated these renal and inflammatory markers prior to antiretroviral initiation and at 96 weeks of therapy. Results We found that estimated eGFR (using CKD-EPI cystatin C-creatinine), uPCR, and uACR were significantly correlated with most assessed markers of systemic inflammation prior to antiretroviral initiation. uPCR and eGFR (using CKD-EPI cystatin C-creatinine), but not uACR, remained significantly correlated with most of the assessed inflammatory markers after 96 weeks of ART. Most of these correlations, although statistically significant, were under 0.50. eGFR using CKD-EPI creatinine was much less frequently associated with inflammation markers and only significantly correlated with sTNFR1 at Week 0 and with sTNFRI and II at Week 96. Conclusions Renal disease and function are associated with systemic inflammation in HIV both before and after ART. Systemic inflammation may partially explain the relationships between proteinuria, albuminuria, and reduced renal function and future adverse outcomes. PMID:25990642

  3. Magnetic resonance imaging biomarkers of gastrointestinal motor function and fluid distribution

    PubMed Central

    Khalaf, Asseel; Hoad, Caroline L; Spiller, Robin C; Gowland, Penny A; Moran, Gordon W; Marciani, Luca

    2015-01-01

    Magnetic resonance imaging (MRI) is a well established technique that has revolutionized diagnostic radiology. Until recently, the impact that MRI has had in the assessment of gastrointestinal motor function and bowel fluid distribution in health and in disease has been more limited, despite the novel insights that MRI can provide along the entire gastrointestinal tract. MRI biomarkers include intestinal motility indices, small bowel water content and whole gut transit time. The present review discusses new developments and applications of MRI in the upper gastrointestinal tract, the small bowel and the colon reported in the literature in the last 5 years. PMID:26600972

  4. Current Stem Cell Biomarkers and Their Functional Mechanisms in Prostate Cancer

    PubMed Central

    Zhang, Kaile; Zhou, Shukui; Wang, Leilei; Wang, Jianlong; Zou, Qingsong; Zhao, Weixin; Fu, Qiang; Fang, Xiaolan

    2016-01-01

    Currently there is little effective treatment available for castration resistant prostate cancer, which is responsible for the majority of prostate cancer related deaths. Emerging evidence suggested that cancer stem cells might play an important role in resistance to traditional cancer therapies, and the studies of cancer stem cells (including specific isolation and targeting on those cells) might benefit the discovery of novel treatment of prostate cancer, especially castration resistant disease. In this review, we summarized major biomarkers for prostate cancer stem cells, as well as their functional mechanisms and potential application in clinical diagnosis and treatment of patients. PMID:27447616

  5. Renal function impairment induced by change in posture in patients with cirrhosis and ascites.

    PubMed Central

    Bernardi, M; Santini, C; Trevisani, F; Baraldini, M; Ligabue, A; Gasbarrini, G

    1985-01-01

    The assumption of upright posture by patients with liver cirrhosis leads to striking activation of adrenergic and renin-angiotensin systems. The tilting-induced modifications in renal function of eight healthy controls and 14 untreated patients with liver cirrhosis and ascites were related to plasma concentrations of noradrenaline, renin activity and aldosterone. All patients had preserved renal blood perfusion. All parameters were evaluated during bed rest for two hours and in the sitting posture for one hour. Basal plasma renin activity (0.1 greater than p greater than 0.05), aldosterone and noradrenaline concentrations (p less than or equal to 0.01) were raised in cirrhotics. The renal function tests (creatinine clearance, filtered sodium, tubular rejection fraction, urinary sodium excretion) were significantly reduced in cirrhosis. Under basal conditions, in cirrhotic patients tubular rejection fraction and urinary sodium excretion were inversely related to both noradrenaline and aldosterone concentrations. After tilting, the noradrenaline and aldosterone integrated outputs (sigma delta) were significantly greater in cirrhosis. All renal function tests significantly decreased in cirrhotics, whereas creatinine clearance only significantly decreased in controls. Patient's tubular rejection fraction of sodium and sodium excretion were related to sigma delta aldosteronaemia (r = -0.72; p less than 0.01), but no longer to sigma delta plasma noradrenaline. PMID:3891534

  6. Renal function and endocrine responses to arm exercise in euhydrated individuals with spinal cord injury.

    PubMed

    Kawasaki, Takashi; Nakamura, Takeshi; Sasaki, Yusuke; Sakamoto, Keiko; Ito, Tomoyuki; Goto, Masaki; Shimomatsu, Tomoya; Tajima, Fumihiro

    2012-04-01

    This study investigated the renal and endocrine responses to arm exercise in persons with spinal cord injury (SCI) under euhydration conditions (ad libitum drinking of water) and determined the physiological effects of exercise on renal function in these subjects. Eleven SCI (spinal lesions between T6 and L1, American Spinal Injury Association impairment scale A) and 14 able-bodied (AB) persons first rested for 1 h in a sitting position, before undergoing 2-h arm-crank ergometer exercise at 60% of maximum oxygen consumption followed by a 2-h recovery period. On another day, all subjects participated in a time control study (5 h of rest condition in sitting position). Urine and blood samples were collected hourly. There were no differences in mean blood pressure between the two groups. SCI patients showed attenuated increase in plasma adrenaline and increase in plasma aldosterone compared with AB controls, but similar changes in human atrial natriuretic polypeptide, plasma renin activity and plasma antidiuretic hormone following the exercise. Creatinine clearance, osmolal clearance, free water clearance and fractional excretion of Na(+) did not change during exercise in any of the subjects. These findings suggested that activated aldosterone and attenuated adrenaline responses during exercise in SCI could be due to adaptation to disordered sympathetic nervous system triggered to maintain renal function. The results showed no exercise-related adverse effects on renal function in hydrated subjects with SCI.

  7. Necrotizing and crescentic glomerulonephritis presenting with preserved renal function in patients with underlying multisystem autoimmune disease: a retrospective case series

    PubMed Central

    Tanna, Anisha; Randone, Olga; Tam, Frederick W. K.; Tarzi, Ruth M.; Levy, Jeremy B.; Griffith, Megan; Lightstone, Liz; Cook, H. Terence; Cairns, Tom; Pusey, Charles D.

    2015-01-01

    Objective. Necrotizing and crescentic GN usually presents with rapidly declining renal function, often in association with multisystem autoimmune disease, with a poor outcome if left untreated. We aimed to describe the features of patients who have presented with these histopathological findings but minimal disturbance of renal function. Methods. We conducted a retrospective review (1995–2011) of all adult patients with native renal biopsy–proven necrotizing or crescentic GN and normal serum creatinine (<120 μmol/l) at our centre. Results. Thirty-eight patients were identified. The median creatinine at presentation was 84 μmol/l and the median proportion of glomeruli affected by necrosis or crescents was 32%. Clinicopathological diagnoses were ANCA-associated GN (74%), LN (18%), anti-GBM disease (5%) and HScP (3%). Only 18% of cases had pre-existing diagnoses of underlying multisystem autoimmune disease, although the majority (89%) had extra-renal manifestations accompanying the renal diagnosis. All patients received immunosuppression and most had good long-term renal outcomes (median duration of follow-up 50 months), although two progressed to end-stage renal disease within 3 years. We estimate that renal biopsy had an important influence on treatment decisions in 82% of cases. Conclusion. Necrotizing and crescentic GN may present in patients with no or only minor disturbance of renal function. This often occurs in patients with underlying systemic autoimmune disease; early referral for biopsy may affect management and improve long-term outcomes in these cases. PMID:25431483

  8. Eligibility for Statin Treatment in Korean Subjects with Reduced Renal Function: An Observational Study

    PubMed Central

    Moon, Byung Sub; Kim, Jongho; Kim, Ji Hyun; Hyun, Young Youl; Park, Se Eun; Oh, Hyung-Geun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Lee, Kyu-Beck; Kim, Hyang; Park, Sung-Woo

    2016-01-01

    Background The purpose of this study was to investigate the relationship between statin eligibility and the degree of renal dysfunction using the Adult Treatment Panel (ATP) III and the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines in Korean adults. Methods Renal function was assessed in 18,746 participants of the Kangbuk Samsung Health Study from January 2011 to December 2012. Subjects were divided into three groups according to estimated glomerular filtration rate (eGFR): stage 1, eGFR ≥90 mL/min/1.73 m2; stage 2, eGFR 60 to 89 mL/min/1.73 m2; and stages 3 to 5, eGFR <60 mL/min/1.73 m2. Statin eligibility in these groups was determined using the ATP III and ACC/AHA guidelines, and the risk for 10-year atherosclerotic cardiovascular disease (ASCVD) was calculated using the Framingham Risk Score (FRS) and Pooled Cohort Equation (PCE). Results There were 3,546 (18.9%) and 4,048 (21.5%) statin-eligible subjects according to ATP III and ACC/AHA guidelines, respectively. The proportion of statin-eligible subjects increased as renal function deteriorated. Statin eligibility by the ACC/AHA guidelines showed better agreement with the Kidney Disease Improving Global Outcomes (KDIGO) recommendations compared to the ATP III guidelines in subjects with stage 3 to 5 chronic kidney disease (CKD) (κ value, 0.689 vs. 0.531). When the 10-year ASCVD risk was assessed using the FRS and PCE, the mean risk calculated by both equations significantly increased as renal function declined. Conclusions The proportion of statin-eligible subjects significantly increased according to worsening renal function in this Korean cohort. ACC/AHA guideline showed better agreement for statin eligibility with that recommended by KDIGO guideline compared to ATP III in subjects with CKD. PMID:27586450

  9. Decreased Renal Function Is a Risk Factor for Subclinical Coronary Atherosclerosis in Korean Postmenopausal Women

    PubMed Central

    Yun, Bo Hyon; Chon, Seung Joo; Cho, Si Hyun; Choi, Young Sik; Lee, Byung Seok

    2016-01-01

    Objectives Decreased renal function is associated with increased cardiovascular risk. Our study was planned to verify the association of decreased renal function and subclinical coronary atherosclerosis in postmenopausal women. Methods We performed a retrospective review of 251 Korean postmenopausal women who visited the health promotion center for a routine health checkup. Estimated glomerular filtration rate (eGFR) was used to show renal function, which was estimated by calculated using the Cockcroft-Gault (CG) and the modification of diet in renal disease (MDRD) formulas. Coronary atherosclerosis was assessed by 64-row multidetector computed tomography. Results Women with reduced eGFR (< 60 mL/minute/1.73 m2) had significantly higher brachial-ankle pulse wave velocity (baPWV) than women with normal eGFR (≥ 60 mL/minute/1.73 m2). The eGFR was negatively correlated with baPWV (r = -0.352, P < 0.001), significantly. The eGFR was lower in women with coronary atherosclerosis than in normal control women, markedly. Reduced eGFR was significantly associated with the presence of coronary atherosclerosis (odds ratio [OR] = 7.528, 95% confidence interval [CI] = 2.728-20.772, P < 0.001). Conclusions Decreased eGFR was closely associated with increased arterial stiffness and coronary atherosclerosis in postmenopausal women. Evaluating subclinical atherosclerosis by screening the renal function in postmenopausal women may be helpful screening high risk group and considering starting menopausal hormone therapy before atherosclerosis development. PMID:28119897

  10. Urinary iodine, thyroid function, and thyroglobulin as biomarkers of iodine status.

    PubMed

    Pearce, Elizabeth N; Caldwell, Kathleen L

    2016-09-01

    The accurate assessment of population iodine status is necessary to inform public health policies and clinical research on iodine nutrition, particularly the role of iodine adequacy in normal neurodevelopment. Urinary iodine concentration (UIC) directly reflects dietary iodine intake and is the most common indicator used worldwide to assess population iodine status. The CDC established the Ensuring the Quality of Iodine Procedures program in 2001 to provide laboratories that measure urinary iodine with an independent assessment of their analytic performance; this program fosters improvement in the assessment of UIC. Clinical laboratory tests of thyroid function (including serum concentrations of the pituitary hormone thyrotropin and the thyroid hormones thyroxine and triiodothyronine) are sometimes used as indicators of iodine status, although such use is often problematic. Even in severely iodine-deficient regions, there is a great deal of intraindividual variation in the ability of the thyroid to adapt. In most settings and in most population subgroups other than newborns, thyroid function tests are not considered sensitive indicators of population iodine status. However, the thyroid-derived protein thyroglobulin is increasingly being used for this purpose. Thyroglobulin can be measured in either serum or dried blood spot (DBS) samples. The use of DBS samples is advantageous in resource-poor regions. Improved methodologies for ascertaining maternal iodine status are needed to facilitate research on developmental correlates of iodine status. Thyroglobulin may prove to be a useful biomarker for both maternal and neonatal iodine status, but validated assay-specific reference ranges are needed for the determination of iodine sufficiency in both pregnant women and neonates, and trimester-specific ranges are possibly needed for pregnant women. UIC is currently a well-validated population biomarker, but individual biomarkers that could be used for research, patient care

  11. Renal function related to different treatment modalities for malignant germ cell tumours.

    PubMed Central

    Aass, N.; Fosså, S. D.; Aas, M.; Lindegaard, M. W.

    1990-01-01

    The renal function was evaluated with 131I-Hippuran clearance in 171 patients with malignant germ cell tumours. Assessments were performed before treatment and at three fixed times afterwards within 5 years. The patients were treated with surgery only (20 patients), infra-diaphragmatic radiotherapy only (median midplane dose 36 Gy) (48 patients), cisplatin-based chemotherapy (total cisplatin dose 500-850 mg) plus surgery (64 patients), cisplatin-based chemotherapy (total cisplatin dose greater than 850 mg) with or without surgery (23 patients) or cisplatin-based chemotherapy (total cisplatin dose 500-850 mg) plus infra-diaphragmatic radiotherapy (16 patients). No renal impairment was observed for patients treated with surgery only. In patients who received radiotherapy no change of the renal function occurred during the first year post-treatment. Three to five years after treatment discontinuation a statistically significant reduction within the normal range was observed in patients who were greater than 40 years at the time of irradiation. Cisplatin-based chemotherapy led to a statistically significant irreversible renal impairment for all the three groups. The greatest reduction was seen in patients who received the highest total cisplatin dose or who were treated with irradiation in addition to chemotherapy. The clinical significance of the observed nephrotoxicity is still unknown. PMID:2173944

  12. Ischemic Postconditioning and Subanesthetic S(+)-Ketamine Infusion: Effects on Renal Function and Histology in Rats

    PubMed Central

    de Resende, Marco A. C.; Pantoja, Alberto V.; Barcellos, Bruno M.; Reis, Eduardo P.; Consolo, Thays D.; Módolo, Renata P.; Domingues, Maria A. C.; Assad, Alexandra R.; Cavalcanti, Ismar L.; Castiglia, Yara M. M.; Módolo, Norma S. P.

    2015-01-01

    Background. Ischemic postconditioning (IP) in renal Ischemia reperfusion injury (IRI) models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI). The present study investigated the effects of IP and IP associated with subanesthetic S(+)-ketamine in ischemia-reperfusion-induced AKI. Methods. Forty-one Wistar rats were randomized into four groups: CG (10), control; KG (10), S(+)-ketamine infusion; IPG (10), IP; and KIPG (11), S(+)-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL), creatinine, and blood urea nitrogen (BUN). Tubular damage was evaluated by renal histology. Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG), whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG. Conclusions. No synergic effect of the use of subanesthetic S(+)-ketamine and IP on AKI was observed in this rat model. PMID:26413552

  13. Functional connectivity classification of autism identifies highly predictive brain features but falls short of biomarker standards

    PubMed Central

    Plitt, Mark; Barnes, Kelly Anne; Martin, Alex

    2014-01-01

    Objectives Autism spectrum disorders (ASD) are diagnosed based on early-manifesting clinical symptoms, including markedly impaired social communication. We assessed the viability of resting-state functional MRI (rs-fMRI) connectivity measures as diagnostic biomarkers for ASD and investigated which connectivity features are predictive of a diagnosis. Methods Rs-fMRI scans from 59 high functioning males with ASD and 59 age- and IQ-matched typically developing (TD) males were used to build a series of machine learning classifiers. Classification features were obtained using 3 sets of brain regions. Another set of classifiers was built from participants' scores on behavioral metrics. An additional age and IQ-matched cohort of 178 individuals (89 ASD; 89 TD) from the Autism Brain Imaging Data Exchange (ABIDE) open-access dataset (http://fcon_1000.projects.nitrc.org/indi/abide/) were included for replication. Results High classification accuracy was achieved through several rs-fMRI methods (peak accuracy 76.67%). However, classification via behavioral measures consistently surpassed rs-fMRI classifiers (peak accuracy 95.19%). The class probability estimates, P(ASD|fMRI data), from brain-based classifiers significantly correlated with scores on a measure of social functioning, the Social Responsiveness Scale (SRS), as did the most informative features from 2 of the 3 sets of brain-based features. The most informative connections predominantly originated from regions strongly associated with social functioning. Conclusions While individuals can be classified as having ASD with statistically significant accuracy from their rs-fMRI scans alone, this method falls short of biomarker standards. Classification methods provided further evidence that ASD functional connectivity is characterized by dysfunction of large-scale functional networks, particularly those involved in social information processing. PMID:25685703

  14. The reflex effects of changes in carotid sinus pressure upon renal function in dogs.

    PubMed Central

    Karim, F; Poucher, S M; Summerill, R A

    1984-01-01

    In chloralose-anaesthetized and artificially ventilated dogs, the carotid sinuses were vascularly isolated and perfused with arterial blood. Mean aortic pressure was held constant at 100 +/- 2 mmHg (mean +/- S.E. of mean, n = 19) by means of a pressure bottle connected to the aorta. Both vagus nerves were sectioned in the neck and propranolol hydrochloride (0.5 mg kg-1) was administered every 30 min. The left renal blood flow was measured by an electromagnetic flowmeter (wrap-round probe), glomerular filtration rate by creatinine clearance and urinary sodium by flame photometry. Decreasing pressure in the isolated carotid sinuses from 186 +/- 10 to 63 +/- 5 mmHg resulted in significant decreases in renal blood flow from 281 +/- 35 to 177 +/- 30 ml min-1 100 g-1 renal mass; glomerular filtration rate from 40.0 +/- 7.8 to 12.3 +/- 4.4 ml min-1 100 g-1; urine flow from 0.31 +/- 0.05 to 0.12 +/- 0.03 ml min-1 100 g-1 and sodium excretion from 21.7 +/- 7.2 to 8.2 +/- 3.0 mumol min-1 100 g-1. Increasing carotid sinus pressure back to 188 +/- 11 mmHg resulted in increases in all the variables to values not significantly different from their initial values. Tying renal sympathetic nerves at low carotid sinus pressure (73 +/- 11 mmHg) caused an increase in all of the variables. After denervation there was no response to changes in carotid sinus pressure. These results show that changes in carotid sinus pressure can result in significant reflex effects on renal function and that these effects are mediated by renal sympathetic nerves. PMID:6492002

  15. The association of blood pressure levels and change in renal function in hypertensive and nonhypertensive subjects.

    PubMed

    Rosansky, S J; Hoover, D R; King, L; Gibson, J

    1990-10-01

    We compared the changes in serum creatinine levels over time after a mean follow-up of 9.8 years in essential hypertensive (EH, n = 56) and control (n = 59) male veteran subjects. All subjects had normal serum creatinine levels (62 to 124 mumol/L) and "normal" urinalysis results on entry into the study. Subjects with comorbid renal diagnoses and diabetes mellitus were eliminated from the analysis. Although not statistically significant, the rate of change in the serum creatinine concentration over time was greater in the EH cohort compared with the control cohort (1.08 +/- 4.8 vs 0.027 +/- 3.5 mumol/L per year). The difference was especially marked in black EH subjects vs black control subjects (1.60 +/- 6.2 mumol/L per year vs -0.21 +/- 3.3 mumol/L per year). When age, race, body mass index, and a diagnosis of EH were entered into a logistic regression analysis, EH subjects had a statistically significantly greater rate of decline in renal function than did control subjects (1.5 +/- 8.3 mumol/L per year). When mean time-averaged systolic blood pressure for each subject was also included in the logistic regression analysis, only systolic time-averaged blood pressure was statistically significant (0.063 +/- 0.029 mumol/L per year). We conclude that in the absence of clinically detected parenchymal renal disease, EH subjects have a greater rate of decline in renal function than do nonhypertensive subjects. Time-averaged blood pressure is predictive of the change in serum creatinine concentration not only in EH subjects but also in nonhypertensive subjects. Thus, preservation of renal function may require a blood pressure lower than the currently accepted normotensive range.

  16. Functional Biomarkers: an Approach to Bridge Pharmacokinetics and Pharmacodynamics in Pediatric Clinical Trials.

    PubMed

    Kearns, Gregory L; Artman, Michael

    2015-01-01

    Over the past 30 years, much has been learned about the impact of development on drug disposition (i.e., pharmacokinetics). This is not true concerning drug action (i.e., pharmacodynamics). As a consequence, in clinical therapeutics and the drug development process, assumptions are often times made that a specific systemic drug exposure that is associated with desired drug action in adults will produce the same response in children. A review of the literature would suggest that this assumption may, in some cases, be an errant one. The relative paucity of information concerning developmental pharmacodynamics is associated with the challenge of assessing and quantitating drug response in vivo in infants and children. An approach to overcome these difficulties has been the evolution of biomarkers that are functional in nature in that they are capable of measuring drug response in both a time and age dependent fashion. The purpose of this review is to illustrate how functional biomarkers capable of assessing drug response/ effect in the developing child are developed and being evaluated for their clinical utility.

  17. Percutaneous Access: Acute Effects on Renal Function and Structure in a Porcine Model

    NASA Astrophysics Data System (ADS)

    Handa, Rajash K.; Willis, Lynn R.; Evan, Andrew P.; Connors, Bret A.; Ying, Jun; Fat-Anthony, William; Wind, Kelli R.; Johnson, Cynthia D.; Blomgren, Philip M.; Estrada, Mark C.; Paterson, Ryan F.; Kuo, Ramsay L.; Kim, Samuel C.; Matlaga, Brian R.; Miller, Nicole L.; Watkins, Stephanie L.; Handa, Shelly E.; Lingeman, James E.

    2007-04-01

    Percutaneous nephrolithotomy (PCNL) involves gaining access into the urinary collecting system to remove kidney stones. Animal studies demonstrated that a reduction in renal filtration and perfusion in both kidneys, and a decline in tubular organic anion transport in the treated kidney characterizes the acute (hours) functional response to unilateral percutaneous access. The acute morphologic and histological changes in the treated kidney were consistent with blunt trauma and ischemia. Only tubular organic anion transport remained depressed during the late (3-day) response to the access procedure. Human studies revealed an acute decline in glomerular function and bilateral renal vasoconstriction following unilateral PCNL. Therefore, percutaneous access is not a benign procedure, but is associated with acute functional and structural derangements.

  18. The mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.

    PubMed

    Dowling, N Maritza; Johnson, Sterling C; Gleason, Carey E; Jagust, William J

    2015-01-15

    Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imaging markers of neural function, and cognition has not been described. Using a statistical mediation model, we examined relationships between cerebrospinal fluid (CSF) analytes (hyperphosphorylated tau (p-Tau(181p)), β-amyloid peptides 1-42 (Aβ(1-42)), total tau (t-Tau), and their ratios); change in cognitive function; and change in [18F]fluorodeoxyglucose (FDG) uptake using positron emission tomography (PET). We hypothesized that a) abnormal CSF protein values at baseline, result in cognitive declines by decreasing neuronal glucose metabolism across time, and b) the role of altered glucose metabolism in the assumed causal chain varies by brain region and the nature of CSF protein alteration. Data from 412 individuals participating in Alzheimer's Disease Neuroimaging (ADNI) cohort studies were included in analyses. At baseline, individuals were cognitively normal (N = 82), or impaired: 241 with mild cognitive impairment, and 89 with Alzheimer's disease. A parallel-process latent growth curve model was used to test mediational effects of changes in regional FDG-PET uptake over time in relation to baseline CSF biomarkers and changes in cognition, measured with the 13-item Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-Cog). Findings suggested a causal sequence of events; specifically, FDG hypometabolism acted as a mediator between antecedent CSF biomarker alterations and subsequent cognitive impairment. Higher baseline concentrations of t-Tau, and p-Tau(181p) were more predictive of decline in cerebral glucose metabolism than lower baseline concentrations of Aβ(1-42). FDG-PET changes appeared to mediate t-Tau or t-Tau/Aβ(1-42)-associated cognitive change across all brain

  19. Alterations of the renal function and oxidative stress in renal tissue from rats chronically treated with aluminium during the initial phase of hepatic regeneration.

    PubMed

    Mahieu, Stella; Millen, Néstor; González, Marcela; Contini, María del Carmen; Elías, María Mónica

    2005-09-01

    Various indices of renal functions during the early stage of hepatic injury were studied in rats chronically treated with aluminum (Al) lactate. Tubular and hemodynamic parameters were analyzed four days after producing a 65% partial hepatectomy (PH). Water and sodium balances were also studied. Oxidative stress and the activity of Na-K-ATPase were determined in renal tissue. The rats were distributed in four groups: control, Al, PH, Al+PH. Al did not modify the hemodynamic renal functions and the PH-group reduced the glomerular filtrate rate (GFR). The Al + PH group presented a decrease in the renal blood flow and accentuated the GFR fall as compared with PH. The fractional excretion (FE) of water and sodium increased in the PH group. The rats chronically treated with Al and then submitted to the PH protocol developed a further increase in FE of water but a reduction in FE of sodium. Both PH and Al promoted an increase in the aldosterone. PH and Al induced a similar increase of the lipoperoxidation status with reduction of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px). The data indicated that Al is an inhibitor of catalase. The GSH and GSH-Px activity in the Al + PH group demonstrated a synergic effect of Al and PH. This work demonstrates that rats treated chronically with Al and submitted to another injury (such as hepatic damage) can aggravate renal functions, probably by increasing the oxidative state, at least in kidneys.

  20. Thalamic functional connectivity predicts seizure laterality in individual TLE patients: application of a biomarker development strategy.

    PubMed

    Barron, Daniel S; Fox, Peter T; Pardoe, Heath; Lancaster, Jack; Price, Larry R; Blackmon, Karen; Berry, Kristen; Cavazos, Jose E; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas

    2015-01-01

    Noninvasive markers of brain function could yield biomarkers in many neurological disorders. Disease models constrained by coordinate-based meta-analysis are likely to increase this yield. Here, we evaluate a thalamic model of temporal lobe epilepsy that we proposed in a coordinate-based meta-analysis and extended in a diffusion tractography study of an independent patient population. Specifically, we evaluated whether thalamic functional connectivity (resting-state fMRI-BOLD) with temporal lobe areas can predict seizure onset laterality, as established with intracranial EEG. Twenty-four lesional and non-lesional temporal lobe epilepsy patients were studied. No significant differences in functional connection strength in patient and control groups were observed with Mann-Whitney Tests (corrected for multiple comparisons). Notwithstanding the lack of group differences, individual patient difference scores (from control mean connection strength) successfully predicted seizure onset zone as shown in ROC curves: discriminant analysis (two-dimensional) predicted seizure onset zone with 85% sensitivity and 91% specificity; logistic regression (four-dimensional) achieved 86% sensitivity and 100% specificity. The strongest markers in both analyses were left thalamo-hippocampal and right thalamo-entorhinal cortex functional connection strength. Thus, this study shows that thalamic functional connections are sensitive and specific markers of seizure onset laterality in individual temporal lobe epilepsy patients. This study also advances an overall strategy for the programmatic development of neuroimaging biomarkers in clinical and genetic populations: a disease model informed by coordinate-based meta-analysis was used to anatomically constrain individual patient analyses.

  1. Live-Animal Imaging of Renal Function by Multiphoton Microscopy

    PubMed Central

    Dunn, Kenneth W.; Sutton, Timothy A.; Sandoval, Ruben M.

    2015-01-01

    Intravital microscopy, microscopy of living animals, is a powerful research technique that combines the resolution and sensitivity found in microscopic studies of cultured cells with the relevance and systemic influences of cells in the context of the intact animal. The power of intravital microscopy has recently been extended with the development of multiphoton fluorescence microscopy systems capable of collecting optical sections from deep within the kidney at subcellular resolution, supporting high-resolution characterizations of the structure and function of glomeruli, tubules, and vasculature in the living kidney. Fluorescent probes are administered to an anesthetized, surgically prepared animal, followed by image acquisition for up to 3 hr. Images are transferred via a high-speed network to specialized computer systems for digital image analysis. This general approach can be used with different combinations of fluorescent probes to evaluate processes such as glomerular permeability, proximal tubule endocytosis, microvascular flow, vascular permeability, mitochondrial function, and cellular apoptosis/necrosis. PMID:23042524

  2. Hormonally-regulated functions in crustaceans as biomarkers of environmental pollution.

    PubMed

    Fingerman, M; Jackson, N C; Nagabhushanam, R

    1998-10-01

    The effects of organic and inorganic contaminants on functions regulated by hormones in crustaceans are being investigated with increasing frequency because several of these phenomena show promise of being useful biomarkers of environmental contamination. Heavy metals and organic compounds have been found in studies with crustaceans to negatively affect hormonally-regulated functions, specifically reproduction, molting, blood glucose level, and pigmentary effectors. Neurotransmitters, including 5-hydroxytryptamine and dopamine, have been identified as being involved in stimulating or inhibiting release of specific crustacean neurohormones such as the pigment-dispersing and pigment-concentrating ones involved in color changes. The effects of pollutants on at least some of these hormonally-regulated processes appear due at least in part to impacting release of a neurohormone, possibly by affecting release of the neurotransmitter that normally stimulates release of that particular neurohormone.

  3. Comparison between the effects of indapamide and hydrochlorothiazide on creatinine clearance in patients with impaired renal function and hypertension.

    PubMed

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

    1995-01-01

    The long-term effects of indapamide or hydrochlorothiazide on blood pressure and renal function were examined in patients 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 while 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.

  4. Molecular clock is involved in predictive circadian adjustment of renal function

    PubMed Central

    Zuber, Annie Mercier; Centeno, Gabriel; Pradervand, Sylvain; Nikolaeva, Svetlana; Maquelin, Lionel; Cardinaux, Léonard; Bonny, Olivier; Firsov, Dmitri

    2009-01-01

    Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e., distal convoluted tubule (DCT) and connecting tubule (CNT) and the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf, and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, αENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms, and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function. PMID:19805330

  5. Evaluation of renal function with contrast MRI: mathematical modeling and error analysis

    NASA Astrophysics Data System (ADS)

    Rusinek, Roza

    1999-05-01

    Dynamic MR imaging with contrast media is increasingly used to provide a safe and noninvasive assessment of renal function. Following intravenous injection of a paramagnetic tracer such as Gd-DPTA, the time course of MR signal is measured in arterial blood and in the kidneys. We use mathematical modeling and Monte Carlo trials to evaluate errors in computed renal parameters such as mean transit time (sigma) m as a function of injected dose. The model assumes that tracer concentration in the renal compartments is the result of convolution of the arterial curve and unit response functions. Results indicate that (sigma) m is not a monotonic function of the dose: instead it reaches a minimum for 2.5 - 3.5 ml of 500 mmol/l solution of Gd-DPTA and it rapidly increases for doses lower than 1 ml. These results can help optimize MR protocol and establish the feasibility of MR measurements using reduced doses of Gd-DPTA.

  6. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease.

    PubMed

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.

  7. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

    PubMed

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

    2016-03-01

    The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

  8. Ertapenem-Induced Encephalopathy in a Patient With Normal Renal Function

    PubMed Central

    Sutton, S. Scott; Jumper, Mark; Cook, Sean; Edun, Babatunde; Wyatt, Michael D.

    2017-01-01

    Drug-induced neurotoxicity is a rare adverse reaction associated with ertapenem. Encephalopathy is a type of neurotoxicity that is defined as a diffuse disease of the brain that alters brain function or structure. We report a patient with normal renal function who developed ertapenem-induced encephalopathy manifesting as altered mental status, hallucinations, and dystonic symptoms. The patient’s symptoms improved dramatically following ertapenem discontinuation, consistent with case reports describing ertapenem neurotoxicity in renal dysfunction. Since clinical evidence strongly suggested ertapenem causality, we utilized the Naranjo Scale to estimate the probability of an adverse drug reaction to ertapenem. Our patient received a Naranjo Scale score of 7, suggesting a probable adverse drug reaction, with a reasonable temporal sequence to support our conclusion. PMID:28203577

  9. Use of endovascular stents in atherosclerotic renovascular stenosis: blood pressure and renal function changes in hypertensive patients.

    PubMed

    Tagle, Rodrigo; Acevedo, Monica; Xu, Meng; Pohl, Marc; Vidt, Donald

    2007-08-01

    Atherosclerotic renal artery stenosis may result in hypertension and ischemic nephropathy. Renal artery endovascular stenting has emerged as current therapy; however, the percentage of patients who benefit from this procedure is still not well established. The authors studied 116 hypertensive patients with atherosclerotic renovascular stenosis who underwent successful renal artery stenting for the first time. At 1 year, there was a significant overall decrease in blood pressure in the group after stenting; however, there was no change in renal function. Also, no significant change in the number of antihypertensive drugs was noted. Blood pressure improved in 55% of the patients, worsened in 14%, and remained unchanged in 31%. Renal function improved in 16% of the patients, worsened in 30%, and remained stable in 54%. In relation to blood pressure control, patients with resistant or difficult-to-control hypertension showed the most improvement in blood pressure control after stenting.

  10. Renal function in the fetus and neonate - the creatinine enigma.

    PubMed

    Kastl, Justin T

    2017-04-01

    The use of serum creatinine levels to estimate glomerular function in infants is admittedly fraught with inherent inaccuracies which are both physiological and methodological in nature. This characteristic can understandably reduce the neonatal clinician's confidence in the ability of serum creatinine levels to provide useful information relevant to their patients' medical care. The aim of this review is to provide further insight into the peculiarities of serum creatinine trends in both premature and term infants with special focus on the maturational and developmental changes occurring in the kidney during this crucial time-period. Though newer markers of glomerular function are gaining increasing traction in the clinical realm, the most prominent of which is currently cystatin C, creatinine nonetheless remains an important player in the scientific evolution of glomerular filtration rate (GFR) estimation. Not only do its limitations provide a level of distinction for newer markers of GFR, but its advantages persist in refining the precision of newer GFR formulae which incorporate multiple patient characteristics.

  11. Function and Regulation of MicroRNAs and Their Potential as Biomarkers in Paediatric Liver Disease

    PubMed Central

    Calvopina, Diego A.; Coleman, Miranda A.; Lewindon, Peter J.; Ramm, Grant A.

    2016-01-01

    MicroRNAs (miRNAs) are short non-coding RNAs involved in biological and pathological processes of every cell type, including liver cells. Transcribed from specific genes, miRNA precursors are processed in the cytoplasm into mature miRNAs and as part of the RNA-induced silencing complex (RISC) complex binds to messenger RNA (mRNA) by imperfect complementarity. This leads to the regulation of gene expression at a post-transcriptional level. The function of a number of different miRNAs in fibrogenesis associated with the progression of chronic liver disease has recently been elucidated. Furthermore, miRNAs have been shown to be both disease-and tissue-specific and are stable in the circulation, which has led to increasing investigation on their utility as biomarkers for the diagnosis of chronic liver diseases, including those in children. Here, we review the current knowledge on the biogenesis of microRNA, the mechanisms of translational repression and the use of miRNA as circulatory biomarkers in chronic paediatric liver diseases including cystic fibrosis associated liver disease, biliary atresia and viral hepatitis B. PMID:27801781

  12. [Pharmacodynamics of vecuronium in the kidney transplant recipient and the patient with normal renal function].

    PubMed

    Takita, K; Goda, Y; Kawahigashi, H; Okuyama, A; Kubota, M; Kemmotsu, O

    1993-02-01

    Pharmacodynamics of vecuronium were evaluated in seven kidney transplant recipients and compared with seven patients with normal renal function. Vecuronium 0.12 mg.kg-1 was used for the initial dose and 0.03 mg.kg-1 for the second dose for each patient under general anesthesia with either isoflurane, sevoflurane or halothane plus nitrous oxide after induction by thiamylal. The effect of vecuronium was evaluated by a muscle relaxation monitor. The time to the maximum blockade (onset time) and the time of 25% recovery of the first twitch height (duration time) were measured after each administration of vecuronium in patients of both groups. The onset times after the initial and second doses were similar in both groups (180.0 +/- 15.5 sec for recipients versus 185.7 +/- 14.9 sec for patients of normal renal function). However, duration was significantly longer in recipients than in patients of normal renal function. Durations after the initial and second doses were 130 +/- 19 min for the initial dose and 86 +/- 12 min for the second dose in recipients, whereas they were 51 +/- 5 min and 37 +/- 5 min in patients of normal renal function. The prolonged durations of vecuronium in the kidney transplant recipient were speculated to be mainly due to delayed elimination of the drug and effect of cyclosporin, an immunosuppressive agent in the recipients. These results suggest that the titrated administration of vecuronium by keen monitoring of muscle relaxation is needed in the kidney transplant recipient to avoid unnecessary prolongation in duration of action.

  13. Interactions Among Drinking and Ground Water Contaminants on Renal and Hepatic Function

    DTIC Science & Technology

    1988-07-25

    inulin . The change was more pronounced in the saline group, because the MCA + oil group had a somewhat diminished GFR. There were no significant effects...flow rate were not affected by MCA, VDC or the combined treatment. ftEMALES VDC decreased GFR, assessed as clearance of inulin , in both saline and MCA...apparently disparate, they are in agreement with the known relationship between renal function assessed by inulin clearance and lack of clearance of

  14. Renal function is associated with indicators of arsenic methylation capacity in Bangladeshi adults

    PubMed Central

    Peters, Brandilyn A.; Hall, Megan N.; Liu, Xinhua; Slavkovich, Vesna; Ilievski, Vesna; Alam, Shafiul; Siddique, Abu B.; Islam, Tariqul; Graziano, Joseph H.; Gamble, Mary V.

    2016-01-01

    Background Arsenic (As) methylation capacity in epidemiologic studies is typically indicated by the proportions of inorganic As (%InAs), monomethylarsonic acid (%MMA), and dimethylarsinic acid (%DMA) in urine as a fraction of total urinary As. The relationship between renal function and indicators of As methylation capacity has not been thoroughly investigated. Objectives Our two aims were to examine (1) associations between estimated glomerular filtration rate (eGFR) and %As metabolites in blood and urine, and (2) whether renal function modifies the relationship of blood %As metabolites with respective urinary %As metabolites. Methods: In a cross-sectional study of 375 As-exposed Bangladeshi adults, we measured blood and urinary As metabolites, and calculated eGFR from plasma cystatin C. Results In covariate-adjusted linear models, a one ml/min/1.73 m2 increase in eGFR was associated with a 0.39% increase in urinary %InAs (p<0.0001) and a mean decrease in urinary %DMA of 0.07 (p=0.0005). In the 292 participants with measurable blood As metabolites, the associations of eGFR with increased blood %InAs and decreased blood %DMA did not reach statistical significance. eGFR was not associated with urinary or blood %MMA in covariate-adjusted models. For a given increase in blood %InAs, the increase in urinary %InAs was smaller in those with reduced eGFR, compared to those with normal eGFR (p=0.06); this effect modification was not observed for %MMA or %DMA. Conclusions Urinary excretion of InAs may be impaired in individuals with reduced renal function. Alternatively, increased As methylation capacity (as indicated by decreased urinary %InAs) may be detrimental to renal function. PMID:26476787

  15. The Gingival Crevicular Fluid as a Source of Biomarkers to Enhance Efficiency of Orthodontic and Functional Treatment of Growing Patients

    PubMed Central

    Capelli, Jonas

    2017-01-01

    Gingival crevicular fluid (GCF) is a biological exudate and quantification of its constituents is a current method to identify specific biomarkers with reasonable sensitivity for several biological events. Studies are being performed to evaluate whether the GCF biomarkers in growing subjects reflect both the stages of individual skeletal maturation and the local tissue remodeling triggered by orthodontic force. Present evidence is still little regarding whether and which GCF biomarkers are correlated with the growth phase (mainly pubertal growth spurt), while huge investigations have been reported on several GCF biomarkers (for inflammation, tissue damage, bone deposition and resorption, and other biological processes) in relation to the orthodontic tooth movement. In spite of these investigations, the clinical applicability of the method is still limited with further data needed to reach a full diagnostic utility of specific GCF biomarkers in orthodontics. Future studies are warranted to elucidate the role of main GCF biomarkers and how they can be used to enhance functional treatment, optimize orthodontic force intensity, or prevent major tissue damage consequent to orthodontic treatment. PMID:28232938

  16. The Gingival Crevicular Fluid as a Source of Biomarkers to Enhance Efficiency of Orthodontic and Functional Treatment of Growing Patients.

    PubMed

    de Aguiar, Mariana Caires Sobral; Perinetti, Giuseppe; Capelli, Jonas

    2017-01-01

    Gingival crevicular fluid (GCF) is a biological exudate and quantification of its constituents is a current method to identify specific biomarkers with reasonable sensitivity for several biological events. Studies are being performed to evaluate whether the GCF biomarkers in growing subjects reflect both the stages of individual skeletal maturation and the local tissue remodeling triggered by orthodontic force. Present evidence is still little regarding whether and which GCF biomarkers are correlated with the growth phase (mainly pubertal growth spurt), while huge investigations have been reported on several GCF biomarkers (for inflammation, tissue damage, bone deposition and resorption, and other biological processes) in relation to the orthodontic tooth movement. In spite of these investigations, the clinical applicability of the method is still limited with further data needed to reach a full diagnostic utility of specific GCF biomarkers in orthodontics. Future studies are warranted to elucidate the role of main GCF biomarkers and how they can be used to enhance functional treatment, optimize orthodontic force intensity, or prevent major tissue damage consequent to orthodontic treatment.

  17. H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

    SciTech Connect

    MCClay, Joseph L.; Adkins, Daniel E.; Isern, Nancy G.; O'Connell, Thomas M.; Wooten, Jan B.; Zedler, Barbara K.; Dasika, Madhukar S.; Webb, B. T.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Murrelle, Edward L.; Leppert, Mark F.; van den Oord, Edwin J.

    2010-06-04

    Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious and growing public health concern. The major environmental risk factor for COPD is tobacco smoking, but the biological mechanisms underlying COPD are not well understood. In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 adults without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Two of the three urinary metabolites positively associated with baseline lung function, i.e. hippurate and formate, are often related to gut microflora. This suggests that the microbiome composition is variable between individuals with different lung function. Alternatively, the nature and origins of all three associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of lung disease or disease risk.

  18. Are plasma citrulline and glutamine biomarkers of intestinal absorptive function in patients with short bowel syndrome?

    PubMed

    Luo, Menghua; Fernández-Estívariz, Concepción; Manatunga, Amita K; Bazargan, Niloofar; Gu, Li H; Jones, Dean P; Klapproth, Jan-Michael; Sitaraman, Shanthi V; Leader, Lorraine M; Galloway, John R; Ziegler, Thomas R

    2007-01-01

    Sensitive biomarkers for intestinal absorptive function would be clinically useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is produced almost exclusively by the gut, which is also a major site of Gln metabolism. The goals of this study were to examine whether plasma Cit and Gln concentrations are biomarkers of residual small intestinal length and nutrient absorptive functions in adult SBS patients followed prospectively. We studied 24 stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a double-blind, randomized trial of individualized dietary modification +/- recombinant human growth hormone (GH). During a baseline week, intestinal absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate, sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and Gln concentrations determined. Individualized dietary modification and treatment with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days, then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4 and continued as tolerated for 24 weeks. Repeat plasma amino acid determination and nutrient absorption studies were performed at weeks 4 and 12. Residual small bowel length at baseline was positively correlated with baseline plasma Cit (r = 0.467; p = .028). However, no significant correlations between absolute Cit or Gln concentrations and the percent absorption of nutrient substrates at any time point were observed. Similarly, no correlation between the change in Cit or GLN concentration and the change in % nutrient absorption was observed (baseline vs weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned completely from PN, respectively. However, baseline plasma Cit or Gln did not predict PN weaning at these time points. We concluded that plasma Cit (but not Gln) concentrations appeared

  19. Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients

    PubMed Central

    Sood, Siddharth; Yu, Lijia; Visvanathan, Kumar; Angus, Peter William; Gow, Paul John; Testro, Adam Gareth

    2016-01-01

    AIM To investigate whether a novel immune function biomarker QuantiFERON-Monitor (QFM) can identify cirrhotic patients at greatest risk of infection. METHODS Adult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47 (52%) transplanted on the day of their QFM. The remaining 44 (48%) were monitored for infections until transplant, death, or census date of 1st February 2014. RESULTS Cirrhotic patients express a median QFM significantly lower than healthy controls (94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely immunosuppressed. Several factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient’s immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13 (29.5%) experienced a pre-transplant infection a median 20 d (range 2-182) post-test. QFM < 214 IU/mL was associated with HR = 4.1 (P = 0.01) for infection. A very low QFM < 30 IU/mL was significantly associated (P = 0.003) with death in three patients who died while awaiting transplantation (HR = 56.6). CONCLUSION QFM is lower in cirrhotics, allowing objective determinations of an individual’s unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection. PMID:28050238

  20. Plasma aldosterone and glomerular filtration in hypertensive patients with preserved renal function.

    PubMed

    Roldán, Julián; Morillas, Pedro; Castillo, Jesús; Andrade, Helder; Guillén, Silvia; Núñez, Daniel; Quiles, Juan; Bertomeu, Vicente

    2010-01-01

    There is increasing interest in the role of aldosterone in the pathophysiology of hypertension, cardiovascular disease and deteriorating renal function. The aim of this study was to investigate the relationship between aldosterone and the glomerular filtration rate (GFR) in hypertensive patients with preserved renal function. The study involved 186 consecutive hypertensive patients with a GFR >60 mL/min. The GFR was determined using the Modification of Diet in Renal Disease (MDRD) equation and the patients' plasma aldosterone levels were measured. Patients with a GFR between 60-89 mL/min had a significantly higher plasma aldosterone level than those with a GFR >90 mL/min (20.02 ng/dL vs. 15.3 ng/dL; P< .05). Multivariate analysis showed that the plasma aldosterone level was independently associated with the GFR (B=-7.36; P< .001). In hypertensive patients with preserved kidney function, the plasma aldosterone level was observed to increase as the GFR decreased.

  1. MicroRNAs in renal fibrosis

    PubMed Central

    Chung, Arthur C.-K.; Lan, Hui Y.

    2015-01-01

    MicroRNAs (miRNAs) are endogenous short non-coding RNAs that regulate most of important cellular processes by inhibiting gene expression through the post-transcriptional repression of their target mRNAs. In kidneys, miRNAs have been associated in renal development, homeostasis, and physiological functions. Results from clinical and experimental animal studies demonstrate that miRNAs play essential roles in the pathogenesis of various renal diseases. Chronic kidney diseases (CKD) is characterized by renal fibrosis. Transforming growth factor beta (TGF-β) is recognized as a major mediator of renal fibrosis because it is able to stimulate the accumulation of extracellular matrix (ECM) proteins to impair normal kidney function. Recently, emerging evidence demonstrate the relationship between TGF-β signaling and miRNAs expression during renal diseases. TGF-β regulates expression of several microRNAs, such as miR-21, miR-192, miR-200, miR-433, and miR-29. MiR-21, miR-192, and miR-433 which are positively induced by TGF-β signaling play a pathological role in kidney diseases. In contrast, members in both miR-29 and miR-200 families which are inhibited by TGF-β signaling protect kidneys from renal fibrosis by suppressing the deposition of ECM and preventing epithelial-to-mesenchymal transition, respectively. Clinically, the presence of miRNAs in blood and urine has been examined to be early biomarkers for detecting renal diseases. From experimental animal studies of CKD, targeting microRNAs also provides evidence about therapeutic potential of miRNAs during renal diseases. Now, it comes to the stage to examine the exact mechanisms of miRNAs during the initiation and progression of renal diseases. Therefore, determining the function of miRNAs in renal fibrosis may facilitate the development of both early diagnosis and treatment of renal diseases. PMID:25750628

  2. Postnatal development of renal function: micropuncture and clearance studies in the dog

    PubMed Central

    Horster, Michael; Valtin, Heinz

    1971-01-01

    Postnatal renal development was studied in dogs between 2 and 77 days. Single, superficial nephrons were evaluated by micropuncture, concurrently with measurements of total renal function and morphometric analyses in the same animals. Glomerular filtration rate for the entire kidney increased linearly from 0.13 ml/min per g kidney weight at 2 days to 0.91 at 77 days. Extraction of p-aminohippurate increased from about 20 to 80%, and renal plasma flow per g kidney weight, measured as Cpah/Epah, increased threefold during the same period. Filtration fraction increased to the mature value during the first half of the postnatal period studied. The clearance of urea per unit of renal mass increased with age, whereas the fraction of filtered urea reabsorbed declined during the early part of the postnatal period. The pattern of fractional urea reabsorption may be due mainly to increased medullary recycling of urea and to a rise in the reabsorption of water from the medullary collecting duct. Urine osmolality was higher than plasma from birth onward and rose with age. Osmolal equality of collecting duct fluid and medullary interstitium reflected mature vasopressin (ADH)-induced water permeability. The rise in urinary concentration was predominantly due to increasing medullary sequestration of urea. Glomerular filtration rate of the superficial nephron increased from 3.2 nl/min at 21 days, when subcapsular nephrons were uniformly patent, to 23.1 at 77 days. Despite this rise in filtered load, fractional reabsorption of sodium and water in superficial proximal tubules was constant and at the mature level from the onset of intratubular perfusion. Changes in arterial plasma protein concentration, in filtration fraction, and in the hydrostatic pressure gradient between proximal tubule and peritubular capillary may interact to maintain glomerulotubular balance. The data, together with results of an accompanying morphological study, demonstrate a sequence of coordinated changes

  3. Impact of contrast-enhanced ultrasound in patients with renal function impairment

    PubMed Central

    Girometti, Rossano; Stocca, Tiziano; Serena, Elena; Granata, Antonio; Bertolotto, Michele

    2017-01-01

    AIM To investigate the role of contrast enhanced ultrasound (CEUS) in evaluating patients with renal function impairment (RFI) showing: (1) acute renal failure (ARF) of suspicious vascular origin; or (2) suspicious renal lesions. METHODS We retrospectively evaluated patients addressed to CEUS over an eight years period to rule-out vascular causes of ARF (first group of 50 subjects) or assess previously found suspicious renal lesions (second group of 41 subjects with acute or chronic RFI). After preliminary grey-scale and color Doppler investigation, each kidney was investigated individually with CEUS, using 1.2-2.4 mL of a sulfur hexafluoride-filled microbubble contrast agent. Image analysis was performed in consensus by two readers who reviewed digital clips of CEUS. We calculated the detection rate of vascular abnormalities in the first group and performed descriptive statistics of imaging findings for the second group. RESULTS In the first group, CEUS detected renal infarction or cortical ischemia in 18/50 patients (36%; 95%CI: 23.3-50.9) and 1/50 patients (2%; 95%CI: 0.1-12), respectively. The detection rate of infarction was significantly higher (P = 0.0002; McNemar test) compared to color Doppler ultrasonography (10%). No vascular causes of ARF were identified in the remaining 31/50 patients (62%). In the second group, CEUS detected 41 lesions on 39 patients, allowing differentiation between solid lesions (21/41; 51.2%) vs complex cysts (20/41; 48.8%), and properly addressing 15/39 patients to intervention when feasible based on clinical conditions (surgery and cryoablation in 13 and 2 cases, respectively). Cysts were categorized Bosniak II, IIF, III and IV in 8, 5, 4 and 3 cases, respectively. In the remaining two patients, CEUS found 1 pseudolesion and 1 subcapsular hematoma. CONCLUSION CEUS showed high detection rate of renal perfusion abnormalities in patients with ARF, influencing the management of patients with acute or chronic RFI and renal masses

  4. GC-MS metabolomics-based approach for the identification of a potential VOC-biomarker panel in the urine of renal cell carcinoma patients.

    PubMed

    Monteiro, Márcia; Moreira, Nathalie; Pinto, Joana; Pires-Luís, Ana S; Henrique, Rui; Jerónimo, Carmen; Bastos, Maria de Lourdes; Gil, Ana M; Carvalho, Márcia; Guedes de Pinho, Paula

    2017-04-04

    The analysis of volatile organic compounds (VOCs) emanating from biological samples appears as one of the most promising approaches in metabolomics for the study of diseases, namely cancer. In fact, it offers advantages, such as non-invasiveness and robustness for high-throughput applications. The purpose of this work was to study the urinary volatile metabolic profile of patients with renal cell carcinoma (RCC) (n = 30) and controls (n = 37) with the aim of identifying a potential specific urinary volatile pattern as a non-invasive strategy to detect RCC. Moreover, the effect of some confounding factors such as age, gender, smoking habits and body mass index was evaluated as well as the ability of urinary VOCs to discriminate RCC subtypes and stages. A headspace solid-phase microextraction/gas chromatography-mass spectrometry-based method was performed, followed by multivariate data analysis. A variable selection method was applied to reduce the impact of potential redundant and noisy chromatographic variables, and all models were validated by Monte Carlo cross-validation and permutation tests. Regarding the effect of RCC on the urine VOCs composition, a panel of 21 VOCs descriptive of RCC was defined, capable of discriminating RCC patients from controls in principal component analysis. Discriminant VOCs were further individually validated in two independent samples sets (nine RCC patients and 12 controls, seven RCC patients with diabetes mellitus type 2) by univariate statistical analysis. Two VOCs were found consistently and significantly altered between RCC and controls (2-oxopropanal and, according to identification using NIST14, 2,5,8-trimethyl-1,2,3,4-tetrahydronaphthalene-1-ol), strongly suggesting enhanced potential as RCC biomarkers. Gender, smoking habits and body mass index showed negligible and age-only minimal effects on the urinary VOCs, compared to the deviations resultant from the disease. Moreover, in this cohort, the urinary volatilome did

  5. Architecture of the human renal inner medulla and functional implications

    PubMed Central

    Wei, Guojun; Rosen, Seymour; Dantzler, William H.

    2015-01-01

    The architecture of the inner stripe of the outer medulla of the human kidney has long been known to exhibit distinctive configurations; however, inner medullary architecture remains poorly defined. Using immunohistochemistry with segment-specific antibodies for membrane fluid and solute transporters and other proteins, we identified a number of distinctive functional features of human inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop descending thin limbs (DTLs) lie alongside descending and ascending vasa recta (DVR, AVR) within vascular bundles. These vascular bundles are continuations of outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at the margins of coalescing collecting duct (CD) clusters, thereby forming two regions, the vascular bundle region and the CD cluster region. Although AQP1 and urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR, respectively, their expression declines with depth below the outer medulla. Transcellular water and urea fluxes likely decline in these segments at progressively deeper levels. Smooth muscle myosin heavy chain protein is also expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated capillaries abut CDs along their entire length, paralleling ascending thin limbs (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however, in humans this architecture rarely occurs. Thus INSs are relatively infrequent in the human inner medulla, unlike in the rodent where they are abundant. UT-B is expressed within the papillary epithelium of the lower inner medulla, indicating a transcellular pathway for urea across this epithelium. PMID:26290371

  6. Effects of environmental levels of cadmium, lead and mercury on human renal function evaluated by structural equation modeling

    PubMed Central

    Trzeciakowski, Jerome P.; Gardiner, Lesley; Parrish, Alan R.

    2014-01-01

    A relationship between exposure to heavy metals, including lead and cadmium, and renal dysfunction has long been suggested. However, modeling of the potential additive, or synergistic, impact of metals on renal dysfunction has proven to be challenging. In these studies, we used structural equation modeling (SEM), to investigate the relationship between heavy metal burden (serum and urine levels of lead, cadmium and mercury) and renal function using data from the NHANES database. We were able to generate a model with goodness of fit indices consistent with a well-fitting model. This model demonstrated that lead and cadmium had a negative relationship with renal function, while mercury did not contribute to renal dysfunction. Interestingly, a linear relationship between lead and loss of renal function was observed, while the maximal impact of cadmium occurred at or above serum cadmium levels of 0.8 µg/L. The interaction of lead and cadmium in loss of renal function was also observed in the model. These data highlight the use of SEM to model interaction between environmental contaminants and pathophysiology, which has important implications in mechanistic and regulatory toxicology. PMID:24769258

  7. Effects of environmental levels of cadmium, lead and mercury on human renal function evaluated by structural equation modeling.

    PubMed

    Trzeciakowski, Jerome P; Gardiner, Lesley; Parrish, Alan R

    2014-07-03

    A relationship between exposure to heavy metals, including lead and cadmium, and renal dysfunction has long been suggested. However, modeling of the potential additive, or synergistic, impact of metals on renal dysfunction has proven to be challenging. In these studies, we used structural equation modeling (SEM), to investigate the relationship between heavy metal burden (serum and urine levels of lead, cadmium and mercury) and renal function using data from the NHANES database. We were able to generate a model with goodness of fit indices consistent with a well-fitting model. This model demonstrated that lead and cadmium had a negative relationship with renal function, while mercury did not contribute to renal dysfunction. Interestingly, a linear relationship between lead and loss of renal function was observed, while the maximal impact of cadmium occurred at or above serum cadmium levels of 0.8 μg/L. The interaction of lead and cadmium in loss of renal function was also observed in the model. These data highlight the use of SEM to model interaction between environmental contaminants and pathophysiology, which has important implications in mechanistic and regulatory toxicology.

  8. The determination of relative renal function in a pediatric population using Tc-99m DTPA and Tc-99m DMSA

    SciTech Connect

    Rosen, P.R.; Kuruc, A.; Treves, S.T.

    1985-05-01

    Three methods for evaluating relative renal function in a pediatric population were compared. The clinical and nuclear medicine data of 73 patients were reviewed. Pertinent data included patient age, serum creatinine and the referral diagnosis (reflux, hypertension, obstructive uropathy). Time activity curves for renal regions of interest (ROI) were obtained by renography with Tc-99m DTPA, and deconvolved by an externally detected blood pool curve Furosemide was then administered to evaluate the renal collecting system (if indicated). This was followed by DMSA administration. Relative function was determined in 3 ways: 1) Accumulated renal DTPA activity 60-120 sec. following injection. 2) Amplitude of the tubular phase of the deconvolved renal curve and, 3) Accumulated Tc-99m DMSA activity in renal ROI 4 or 24 hrs. post-injection. Regression analysis revealed: 1) The basic relationship of relative functional data obtained by all three methods was not affected by creatinine, age or other factors. 2) The relationship between the three methods is linear and highly correlated. 3) The DMSA values may be predicted from either method of analyzing the DTPA study using appropriate predictor equations. The authors conclude that Tc-99m DMSA, due to its higher cost and more radiation exposure should not be used for the routine evaluation of relative renal function.

  9. Recursive feature elimination for biomarker discovery in resting-state functional connectivity.

    PubMed

    Ravishankar, Hariharan; Madhavan, Radhika; Mullick, Rakesh; Shetty, Teena; Marinelli, Luca; Joel, Suresh E; Ravishankar, Hariharan; Madhavan, Radhika; Mullick, Rakesh; Shetty, Teena; Marinelli, Luca; Joel, Suresh E; Joel, Suresh E; Shetty, Teena; Marinelli, Luca; Mullick, Rakesh; Ravishankar, Hariharan; Madhavan, Radhika

    2016-08-01

    Biomarker discovery involves finding correlations between features and clinical symptoms to aid clinical decision. This task is especially difficult in resting state functional magnetic resonance imaging (rs-fMRI) data due to low SNR, high-dimensionality of images, inter-subject and intra-subject variability and small numbers of subjects compared to the number of derived features. Traditional univariate analysis suffers from the problem of multiple comparisons. Here, we adopt an alternative data-driven method for identifying population differences in functional connectivity. We propose a machine-learning approach to down-select functional connectivity features associated with symptom severity in mild traumatic brain injury (mTBI). Using this approach, we identified functional regions with altered connectivity in mTBI. including the executive control, visual and precuneus networks. We compared functional connections at multiple resolutions to determine which scale would be more sensitive to changes related to patient recovery. These modular network-level features can be used as diagnostic tools for predicting disease severity and recovery profiles.

  10. Uncoupling of PUMA Expression and Apoptosis Contributes to Functional Heterogeneity in Renal Cell Carcinoma - Prognostic and Translational Implications.

    PubMed

    Zhou, Xiaoguang; Li, Jielin; Marx, Christina; Tolstov, Yanis; Rauch, Geraldine; Herpel, Esther; Macher-Goeppinger, Stephan; Roth, Wilfried; Grüllich, Carsten; Pahernik, Sascha; Hohenfellner, Markus; Duensing, Stefan

    2015-12-01

    Renal cell carcinoma (RCC) is characterized by a profound disruption of proapoptotic signaling networks leading to chemo- and radioresistance. A key mediator of DNA damage-induced apoptosis is the BH3-only protein PUMA. Given its central role in proapoptotic signaling, we analyzed a series of more than 600 precision-annotated primary RCC specimens for PUMA protein expression. We found a reduced expression of PUMA in 22.6% of RCCs analyzed. Unexpectedly, however, PUMA deficiency was not associated with more aggressive tumor characteristic as expected. Instead, a reduced PUMA expression was associated with a lower TNM stage, lower histopathologic grade, and more favorable cancer-specific patient survival. A direct correlation in a separate patient cohort revealed a profound disconnection between PUMA expression and apoptosis as exemplified by the fact that the tumor with the highest level of apoptotic cells was PUMA deficient. In a series of in vitro studies, we corroborated these results and discovered the highest propensity to undergo apoptosis in an RCC cell line with virtually undetectable PUMA expression. At the same time, PUMA expression was not necessarily associated with stronger apoptosis induction, which underscores the striking functional heterogeneity of PUMA expression and apoptosis in RCC. Collectively, our findings suggest that PUMA-independent mechanisms of cell death exist and may play an important role in suppressing malignant progression. They underscore the functional heterogeneity of RCCs and suggest that PUMA expression alone may not be a suitable predictive biomarker. A better understanding of alternative proapoptotic pathways, however, may help to design novel therapeutic strategies for patients with advanced RCC.

  11. Retracted: Identification of Novel Biomarkers for Pancreatic Cancer Using Integrated Transcriptomics With Functional Pathways Analysis.

    PubMed

    Zhang, Xuan; Tong, Pan; Chen, Jinyun; Pei, Zenglin; Zhang, Xiaoyan; Chen, Weiping; Xu, Jianqing; Wang, Jin

    2016-02-22

    Retraction: 'Identification of Novel Biomarkers for Pancreatic Cancer Using Integrated Transcriptomics With Functional Pathways Analysis' by Zhang, X., Tong, P., Chen, J., Pei, Z., Zhang, X., Chen, W., Xu, J. and Wang, J. The above article from the Journal of Cellular Physiology, published online on 10 March 2016 in Wiley Online Library as Early View (http://onlinelibrary.wiley.com/enhanced/doi/10.1002/jcp.25353/), has been retracted by agreement between Gary Stein, the journal's Editor-in-Chief, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation at the University of Texas, MD Anderson Cancer Center, which confirmed that the article was submitted and approved for publication by Dr. Jin Wang without acknowledgement of NIH funding received or the consent and authorship of Dr. Ann Killary and Dr. Subrata Sen, with whom the manuscript was originally drafted.

  12. Introduction: History and Problems of Compensatory Adaptation of Renal Functions and of Compensatory Hypertrophy of the Kidney

    PubMed Central

    Peters, Georges

    1978-01-01

    The history of observations and experimental work on compensatory changes following the loss of renal mass, and the historical reasons for the distinction between the concepts of compensatory adaptation (of renal functions) and of compensatory hypertrophy (of nephrons) are outlined. While the effector mechanisms of both types of compensatory changes are being elucidated at a rapid pace, many questions concerning the primary changes initiating these events, the control mechanisms implied and the interrelationship between functional adaptation and hypertrophy remain unanswered. PMID:366923

  13. Increased curvature of hollow fiber membranes could up-regulate differential functions of renal tubular cell layers.

    PubMed

    Shen, Chong; Meng, Qin; Zhang, Guoliang

    2013-08-01

    Tissue engineering devices as in vitro cell culture systems in scaffolds has encountered the bottleneck due to their much lower cell functions than real tissues/organs in vivo. Such situation has been improved in some extent by mimicking the cell microenvironments in vivo from either chemical or physical ways. However, microenvironmental curvature, commonly seen in real tissues/organs, has never been manipulated to regulate the cell performance in vitro. In this regard, this paper fabricated polysulfone membranes with or without polyethylene glycol modification to investigate the impact of curvature on two renal tubular cells. Regardless the varying membrane curvatures among hollow fiber membranes of different diameters and flat membrane of zero curvature, both renal cells could well attach at 4 h of seeding and form similar confluent layers at 6 days on each membrane. Nevertheless, the renal cells on hollow fibers, though showing confluent morphology as those on flat membranes, expressed higher renal functions and, moreover, the renal functions significantly increased with the membrane curvature among hollow fibers. Such upregulation on functions was unassociated with mass transport barrier of hollow fibers, because the cultures on lengthwise cut hollow fibers without mass transfer barrier showed same curvature effect on renal functions as whole hollow fibers. It could be proposed that the curvature of hollow fiber membrane approaching to the large curvature in kidney tubules increased the mechanical stress in the renal cells and thus might up-regulate the renal cell functions. In conclusion, the increase of substrate curvature could up-regulate the cell functions without altering the confluent cell morphology and this finding will facilitate the design of functional tissue engineering devices.

  14. A CASE OF CALCIPHYLAXIS IN A PATIENT WITH HYPOPARATHYROIDISM AND NORMAL RENAL FUNCTION

    PubMed Central

    Erdel, Blake L.; Juneja, Rattan; Evans-Molina, Carmella

    2014-01-01

    Objective To present the case of a patient with a history of thyroid cancer, post-surgical hypoparathyroidism, chronic calcitriol use, and normal renal function who presented with painful skin lesions secondary to calciphylaxis. Methods We describe the history, biochemistry, histopathology, evaluation, and management of this patient. Results A 47 year-old female with hypoparathyroidism, chronically treated with calcitriol and calcium, presented with exquisitely painful skin ulcerations. Four months prior to the onset of symptoms, she had initiated warfarin therapy for atrial fibrillation. Review of laboratory data from the past year revealed elevated calcium and phosphorus levels. A diagnosis of calciphylaxis was made based upon pathologic evaluation of a skin biopsy. Management included titration of calcitriol and calcium to maintain serum calcium and phosphate levels in the low normal range. Sodium thiosulfate was administered at a dose of 25 mg IV three times a week with some resolution in the patient's pain. Unfortunately, the patient battled recurrent bacteremia and sepsis, presumably related to her calciphylaxis wounds, and ultimately succumbed to complications from sepsis. Conclusion While calciphylaxis is typically associated with renal insufficiency and secondary hyperparathyroidism, we highlight the case of a patient with normal renal function and hypoparathyroidism. Patients treated with chronic calcitriol should have serum calcium and phosphorus monitored closely and may benefit from non-calcium based phosphate binders if hyperphosphatemia becomes unavoidable. This is especially important in the presence of other risk factors for calciphylaxis including warfarin use. PMID:24518186

  15. Protection of renal function by green tea extract during Plasmodium berghei infection.

    PubMed

    Somsak, Voravuth; Jaihan, Ubonwan; Srichairatanakool, Somdet; Uthaipibull, Chairat

    2013-12-01

    Impairment of renal function from oxidative stress during malaria infection is one of the leading causes of death in endemic areas. Since blood urea nitrogen and creatinine levels in plasma can be used as markers for monitoring renal damage, this study investigated the effect of green tea extract on reduction of blood urea nitrogen and creatinine levels during malaria infection using Plasmodium berghei ANKA infected mice as in vivo model. For in vivo testing, ICR mice were infected with 1 × 10(7) parasitized erythrocytes and green tea extract was subsequently administered orally twice a day for 10 consecutive days. Parasitemia was estimated by standard microscopy, and blood urea nitrogen and creatinine levels in plasma were also measured. It was found that parasitemia kept increasing until animal death, and is strongly correlated with high blood urea nitrogen and creatinine. The highest levels of blood urea nitrogen and creatinine in plasma were found on day 10 after infection. However, blood urea nitrogen and creatinine levels in plasma were reduced and decreased significantly (p<0.01) in green tea extract treated mice, compared with untreated group. It can be concluded that green tea extract can protect and maintain renal function during malaria infection, and this extract can be developed for use as a supplement and combination therapy.

  16. Pharmacokinetics of cefotetan in normal subjects and patients with impaired renal function.

    PubMed Central

    Ohkawa, M; Hirano, S; Tokunaga, S; Motoi, I; Shoda, R; Ikeda, A; Sugata, T; Sawaki, M; Shimamura, M; Okasho, A; Kuroda, K

    1983-01-01

    The elimination kinetics of cefotetan (YM09330), a new parenteral semisynthetic cephamycin derivative, were studied in eight healthy volunteers and 41 patients with renal insufficiency after the administration of a single 500-mg dose intravenously. Concentrations of cefotetan in serum and urine were determined by both bioassay and high-pressure liquid chromatography. The pharmacokinetic parameters for cefotetan were calculated on the basis of a two-compartment open model. Serum concentrations of cefotetan immediately after administration were approximately 180 micrograms/ml in all subjects regardless of function; however, serum concentrations during the beta-phase increased directly with the degree of renal impairment. The mean serum half-life during the beta-phase was 3.0 h in normal subjects as compared with 13.1 h in hemodialysis patients. There was a linear correlation (P less than 0.0001) between the elimination rate constant of cefotetan and creatinine clearance. The mean cumulative urinary recovery of cefotetan in the 24-h urine was 83.3% of the administered dose in normal subjects and decreased with reduced renal function. PMID:6572490

  17. Mesenchymal stem cell therapy promotes the improvement and recovery of renal function in a preclinical model

    PubMed Central

    Urt-Filho, Antônio; Oliveira, Rodrigo Juliano; Hermeto, Larissa Correa; Pesarini, João Renato; de David, Natan; Cantero, Wilson de Barros; Falcão, Gustavo; Marks, Guido; Antoniolli-Silva, Andréia Conceição Milan Brochado

    2016-01-01

    Abstract Acute renal failure (ARF) is an extremely important public health issue in need of novel therapies. The present study aimed to evaluate the capacity of mesenchymal stem cell (MSC) therapy to promote the improvement and recovery of renal function in a preclinical model. Wistar rats were used as the experimental model, and our results show that cisplatin (5mg/kg) can efficiently induce ARF, as measured by changes in biochemical (urea and creatinine) and histological parameters. MSC therapy performed 24h after the administration of chemotherapy resulted in normalized plasma urea and creatinine levels 30 and 45d after the onset of kidney disease. Furthermore, MSC therapy significantly reduced histological changes (intratubular cast formation in protein overload nephropathy and tubular hydropic degeneration) in this ARF model. Thus, considering that current therapies for ARF are merely palliative and that MSC therapy can promote the improvement and recovery of renal function in this model system, we suggest that innovative/alternative therapies involving MSCs should be considered for clinical studies in humans to treat ARF. PMID:27275667

  18. Effects of tenoxicam on renal function and the disposition of inulin and p-aminohippurate in healthy volunteers and patients with chronic renal failure.

    PubMed Central

    Freestone, S; McAuslane, J A; Prescott, L F

    1991-01-01

    1. The effects of tenoxicam on renal function were studied in 10 patients with chronic renal failure (creatinine clearance 46.7 +/- 11.9 ml min-1 1.73 m-2) and eight healthy volunteers. A parallel treatment control group of eight healthy volunteers received placebo. Tenoxicam was given orally in a dose of 40 mg daily for 2 days followed by 20 mg daily for a further 8 days. Renal function was assessed by measurement of the renal clearances of inulin and p-aminohippurate (PAH) using the single injection technique before and during administration of tenoxicam. 2. In the healthy volunteers there were no changes in glomerular filtration rate, effective renal plasma flow, or the urinary excretion of N-acetylglucosaminidase and beta 2-microglobulin on the 3rd and 10th days of treatment with tenoxicam. The mean urinary excretion of prostaglandins E2 and 6-keto F1 alpha decreased during treatment but there was great individual variation and the differences were not statistically significant. Tenoxicam had no effect on the half-life, clearance, volume of distribution or urinary recovery of inulin and PAH. 3. There was no significant change in the clearance of inulin and creatinine after treatment with tenoxicam for 10 days in the patients with chronic renal failure. However, in this group there was a significant increase in plasma creatinine on the 3rd and 6th days with a return to pretreatment levels by the 10th day. The administration of tenoxicam for 10 days was associated with a small but significant increase in the plasma half-life and volume of distribution of inulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1958445

  19. The Effects of Long-Term Chaetomellic Acid A Administration on Renal Function and Oxidative Stress in a Rat Model of Renal Mass Reduction

    PubMed Central

    Nogueira, António; Oliveira, Maria Manuel; Pires, Carlos André; Colaço, Bruno

    2017-01-01

    Purpose. This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in a model of renal mass reduction. Methods. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment (n = 14); RMR + CAA: RMR rats treated with CAA (n = 13); SO: SO rats without treatment (n = 13); and SO + CAA: SO rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months. Results. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity (p < 0.05) and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAA administration significantly increased catalase and GR activity (p < 0.05) and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio. No significant differences were found between the RMR groups in any of the parameters of renal function. However, CAA administration slightly improves some parameters of renal function. Conclusions. These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress. PMID:28326323

  20. Conversion from a calcineurin inhibitor-based immunosuppressive regimen to everolimus in renal transplant recipients: effect on renal function and proteinuria.

    PubMed

    Morales, J; Fierro, A; Benavente, D; Zehnder, C; Ferrario, M; Contreras, L; Herzog, C; Buckel, E

    2007-04-01

    New immunosuppressive agents are being actively researched to avoid complications of chronic allograft nephropathy (CAN), calcineurin inhibitor (CNI) nephrotoxicity, and posttransplantation cancer. The family of mTOR inhibitors offers a unique immunosuppressive opportunity to avoid CNI toxicity and reduce the incidence of malignancy. Nevertheless, increasing data have demonstrated that sirolimus (SRL), the first mTOR introduced in the treatment of solid organ transplant recipients, induces proteinuria, an adverse event that could produce deterioration of long-term renal function. In this short-term study of patients followed for 1 to 16 months, we examined changes in renal function and proteinuria among renal transplant recipients converted from a CNI-based regimen to an everolimus (EVL)-based one, a recently introduced mTOR inhibitor. Our data showed that renal function can be optimized after conversion to EVL by up to 42% in recipients showing CAN grade 1 or 2, or CNI nephrotoxicity. Importantly, patients who improved their creatinine clearance did not show increased proteinuria measured in a voided specimen as the ratio of urinary protein and creatinine concentration (P/C). These results, if confirmed with long-term follow-up and a larger number of patients, would allow us to consider EVL as a promising agent for maintenance immunosuppressive regimens in kidney transplantation.

  1. Biomarkers in the assessment of acute and chronic kidney diseases in the dog and cat.

    PubMed

    Cobrin, A R; Blois, S L; Kruth, S A; Abrams-Ogg, A C G; Dewey, C

    2013-12-01

    In both human and veterinary medicine, diagnosing and staging renal disease can be difficult. Measurement of glomerular filtration rate is considered the gold standard for assessing renal function but methods for its assessment can be technically challenging and impractical. The main parameters used to diagnose acute and chronic kidney disease include circulating creatinine and urea concentrations, and urine-specific gravity. However, these parameters can be insensitive. Therefore, there is a need for better methods to diagnose and monitor patients with renal disease. The use of renal biomarkers is increasing in human and veterinary medicine for the diagnosis and monitoring of acute and chronic kidney diseases. An ideal biomarker would identify site and severity of injury, and correlate with renal function, among other qualities. This article will review the advantages and limitations of renal biomarkers that have been used in dogs and cats, as well as some markers used in humans that may be adapted for veterinary use. In the future, measuring a combination of biomarkers will likely be a useful approach in the diagnosis of kidney disorders.

  2. Crystal structure of folliculin reveals a hidDENN function in genetically inherited renal cancer.

    PubMed

    Nookala, Ravi K; Langemeyer, Lars; Pacitto, Angela; Ochoa-Montaño, Bernardo; Donaldson, Jane C; Blaszczyk, Beata K; Chirgadze, Dimitri Y; Barr, Francis A; Bazan, J Fernando; Blundell, Tom L

    2012-08-01

    Mutations in the renal tumour suppressor protein, folliculin, lead to proliferative skin lesions, lung complications and renal cell carcinoma. Folliculin has been reported to interact with AMP-activated kinase, a key component of the mammalian target of rapamycin pathway. Most cancer-causing mutations lead to a carboxy-terminal truncation of folliculin, pointing to a functional importance of this domain in tumour suppression. We present here the crystal structure of folliculin carboxy-terminal domain and demonstrate that it is distantly related to differentially expressed in normal cells and neoplasia (DENN) domain proteins, a family of Rab guanine nucleotide exchange factors (GEFs). Using biochemical analysis, we show that folliculin has GEF activity, indicating that folliculin is probably a distantly related member of this class of Rab GEFs.

  3. Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

    PubMed

    Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M

    2014-01-01

    Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

  4. [Renal functioning and human body liquids during 5-day dry immersion].

    PubMed

    Noskov, V B; Larina, I M; Pastushkova, L Kh; Dobrokhotov, I V; Valeeva, O A; Coupe, M; Custaud, M -A; Novoselova, A M

    2011-01-01

    Renal function and body composition, including liquids, were investigated in 14 essentially healthy male subjects during simulation of some spaceflight effects by 5-d dry immersion (DI). Noninvasive measurement of water spaces of organism was performed with the methods of bio-impedance analysis (BIA). Increase of renal excretion of liquids and appearance of negative water balance were observed. BIA revealed reductions of total body and extracellular liquids and a decrease of circulating plasma volume. This means, that DI induced hypohydration of organism. In the post-DI period, the hydration status regained its baseline level fairly soon. Lean body mass slightly decreased; adipose mass, on the contrary, exceeded baseline values. Moreover, the experiment evidenced technical impossibility to obtain valid impedansimetry data in DI.

  5. Chromogranin A Regulates Renal Function by Triggering Weibel–Palade Body Exocytosis

    PubMed Central

    Chen, Yuqing; Mahata, Manjula; Rao, Fangwen; Khandrika, Srikrishna; Courel, Maite; Fung, Maple M.; Zhang, Kuixing; Stridsberg, Mats; Ziegler, Michael G.; Hamilton, Bruce A.; Lipkowitz, Michael S.; Taupenot, Laurent; Nievergelt, Caroline; Mahata, Sushil K.; O'Connor, Daniel T.

    2009-01-01

    Chromogranin A (CHGA), a protein released from secretory granules of chromaffin cells and sympathetic nerves, triggers endothelin-1 release from endothelial cells. CHGA polymorphisms associate with an increased risk for ESRD, but whether altered CHGA–endothelium interactions may explain this association is unknown. Here, CHGA led to the release of endothelin-1 and Weibel–Palade body exocytosis in cultured human umbilical vein endothelial cells. In addition, CHGA triggered secretion of endothelin-1 from glomerular endothelial cells and TGF-β1 from mesangial cells cocultured with glomerular endothelial cells. In humans, plasma CHGA correlated positively with endothelin-1 and negatively with GFR. GFR was highly heritable in twin pairs, and common promoter haplotypes of CHGA predicted GFR. In patients with progressive hypertensive renal disease, a CHGA haplotype predicted rate of GFR decline. In conclusion, these data suggest that CHGA acts through the glomerular endothelium to regulate renal function. PMID:19520754

  6. Detection of Impaired Sympathetic Cerebrovascular Control Using Functional Biomarkers Based on Principal Dynamic Mode Analysis

    PubMed Central

    Saleem, Saqib; Tzeng, Yu-Chieh; Kleijn, W. Bastiaan; Teal, Paul D.

    2017-01-01

    This study sought to determine whether models of cerebrovascular function based on Laguerre-Volterra kernels that account for nonlinear cerebral blood flow (CBF) dynamics can detect the effects of functional cerebral sympathetic blockade. We retrospectively analyzed continuous beat-to-beat blood pressure, middle cerebral blood velocity, and partial-pressure of end-tidal CO2 (PETCO2) recordings from eighteen healthy individuals who were treated with either an oral dose of the α1-adrenergic receptor blocker Prazosin or a placebo treatment. The global principal dynamic modes (PDMs) were analyzed using Laguerre-Volterra kernels to examine the nonlinear system dynamics. Our principal findings were: (1) very low frequency (<0.03 Hz) linear components of first-order kernels for BP and PETCO2 are mutually coupled to CBF dynamics with the ability to separate individuals between control and blockade conditions, and (2) the gains of the nonlinear functions associated with low-pass and ≈0.03 Hz global PDMs for the BP are sensitive to sympathetic blockade. Collectively these results suggest that very low frequency global PDMs for BP may have potential utility as functional biomarkers of sympathetic neurovascular dysfunction which can occur in conditions like autonomic failure, stroke and traumatic brain injury. PMID:28119628

  7. Renal endothelial function is associated with the anti-proteinuric effect of ACE inhibition in 5/6 nephrectomized rats.

    PubMed

    Vettoretti, Simone; Vavrinec, Peter; Ochodnicky, Peter; Deelman, Leo E; De Zeeuw, Dick; Henning, Rob H; Buikema, Hendrik

    2016-05-01

    In healthy rats, the physiological variation of baseline endothelial function of intrarenal arteries correlates with the severity of renal damage in response to a subsequent specific renal injury. However, whether such a variation in endothelial function may also condition or predict the variable response to angiotensin-converting enzyme-inhibiting treatment in these individuals has not been addressed before. To study this, 5/6 nephrectomy was performed to induce renal injury and chronic kidney disease in a group of healthy Wistar rats. At the time of nephrectomy, interlobar arteries were obtained from the extirpated right kidney and studied in vitro for endothelium-dependent relaxation to acetylcholine. Six weeks thereafter, treatment with lisinopril was started (n = 11) and continued for 9 wk. Proteinuria (metabolic cages) and systolic blood pressure (SBP; tail cuff) were evaluated weekly, and these were analyzed in relation to renal endothelial function at baseline. 5/6 Nephrectomy induced an increase in SBP and progressive proteinuria. Treatment with lisinopril reduced SBP and slowed proteinuria, albeit to a variable degree among individuals. The acetylcholine-induced renal artery dilation at baseline negatively correlated with lisinopril-induced reduction of proteinuria (r(2) = 0.648, P = 0.003) and with the decrease in SBP (r(2) = 0.592, P = 0.006). Our data suggest that angiotensin-converting enzyme-inhibitor attenuates the progression of renal damage the most in those individuals with decreased basal renal endothelial-mediated vasodilation.

  8. Prospective Randomized Trial Comparing Hepatic Venous Outflow and Renal Function after Conventional versus Piggyback Liver Transplantation

    PubMed Central

    Brescia, Marília D’Elboux Guimarães; Massarollo, Paulo Celso Bosco; Imakuma, Ernesto Sasaki; Mies, Sérgio

    2015-01-01

    Background This randomized prospective clinical trial compared the hepatic venous outflow drainage and renal function after conventional with venovenous bypass (n = 15) or piggyback (n = 17) liver transplantation. Methods Free hepatic vein pressure (FHVP) and central venous pressure (CVP) measurements were performed after graft reperfusion. Postoperative serum creatinine (Cr) was measured daily on the first week and on the 14th, 21st and 28th postoperative days (PO). The prevalence of acute renal failure (ARF) up to the 28th PO was analyzed by RIFLE-AKIN criteria. A Generalized Estimating Equation (GEE) approach was used for comparison of longitudinal measurements of renal function. Results FHVP-CVP gradient > 3 mm Hg was observed in 26.7% (4/15) of the patients in the conventional group and in 17.6% (3/17) in the piggyback group (p = 0.68). Median FHVP-CVP gradient was 2 mm Hg (0–8 mmHg) vs. 3 mm Hg (0–7 mm Hg) in conventional and piggyback groups, respectively (p = 0.73). There is no statistically significant difference between the conventional (1/15) and the piggyback (2/17) groups regarding massive ascites development (p = 1.00). GEE estimated marginal mean for Cr was significantly higher in conventional than in piggyback group (2.14 ± 0.26 vs. 1.47 ± 0.15 mg/dL; p = 0.02). The conventional method presented a higher prevalence of severe ARF during the first 28 PO days (OR = 3.207; 95% CI, 1.010 to 10.179; p = 0.048). Conclusion Patients submitted to liver transplantation using conventional or piggyback methods present similar results regarding venous outflow drainage of the graft. Conventional with venovenous bypass technique significantly increases the harm of postoperative renal dysfunction. Trial Registration ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01707810 PMID:26115520

  9. The effects of stimulating carotid chemoreceptors on renal haemodynamics and function in dogs.

    PubMed Central

    Karim, F; Poucher, S M; Summerill, R A

    1987-01-01

    1. Dogs were anaesthetized with chloralose and artificially ventilated. The carotid chemoreceptors were stimulated by changing the perfusion of vascularly isolated carotid sinus regions from arterial to venous blood. The mean carotid sinus pressure and the mean arterial blood pressure were held constant at 124 +/- 3 and 122 +/- 3 mmHg, respectively. Both vagosympathetic trunks were sectioned in the neck and propranolol (17 micrograms kg-1 min-1 I.V.) and gallamine triethiodide (0.2-2.0 mg kg-1 30 min-1 I.V.) were infused. Renal blood flow was measured by an electromagnetic flow probe, glomerular filtration rate by creatinine clearance, sodium excretion by flame photometry and solute excretion by osmometry. 2. In sixteen tests in thirteen dogs perfusion of the carotid sinus regions with venous blood resulted in significant decreases in renal blood flow from 271 +/- 24 to 198 +/- 21 ml min-1 100 g-1 renal mass; glomerular filtration rate from 41.0 +/- 4.8 to 22.1 +/- 3.1 ml min-1 100 g-1; filtration fraction from 0.25 +/- 0.02 to 0.19 +/- 0.02; urine flow from 0.48 +/- 1.0 to 0.21 +/- 0.03 ml min-1 100 g-1; sodium excretion from 18.1 +/- 4.1 to 12.9 +/- 4.2 mumol min-1 100 g-1; and osmolar excretion 327 +/- 42 to 171 +/- 26 mu osmol min-1 100 g-1. The right atrial pressure did not change significantly from 4.6 +/- 1.2 cmH2O. 3. In seven dogs, tying renal sympathetic nerves abolished all the responses except that of sodium excretion which was now reversed; sodium excretion increased from 68 +/- 19 to 116 +/- 38 mumol min-1 100 g-1 without significant change in right atrial pressure from 7.4 +/- 1.9 cmH2O. Crushing the carotid bodies, however, abolished all the responses. 4. The results show that carotid chemoreceptor stimulation can cause significant reflex effects on renal haemodynamics and function which are mediated via renal sympathetic nerves. They also show that the chemoreceptor stimulation can cause natriuresis in the absence of haemodynamic changes, in the

  10. A ratiometric fluorescent nanoprobe based on terbium functionalized carbon dots for highly sensitive detection of an anthrax biomarker.

    PubMed

    Chen, Hao; Xie, Yujie; Kirillov, Alexander M; Liu, Liangliang; Yu, Minghui; Liu, Weisheng; Tang, Yu

    2015-03-25

    A ratiometric fluorescent nanoprobe based on terbium functionalized carbon dots (CDs) was designed to detect dipicolinic acid (DPA) as an anthrax biomarker with high selectivity and sensitivity. CDs were generated by one-step synthesis using an ethylenediaminetetraacetic acid precursor, and served as a scaffold for coordination with Tb(3+) and a fluorescence reference.

  11. Early Changes in Clinical, Functional, and Laboratory Biomarkers in Workers at Risk of Indium Lung Disease

    PubMed Central

    Cummings, Kristin J.; Virji, M. Abbas; Trapnell, Bruce C.; Carey, Brenna; Healey, Terrance; Kreiss, Kathleen

    2015-01-01

    Rationale Occupational exposure to indium compounds, including indium–tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood. Objectives To determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities. Methods Among indium–tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models. Measurements and Main Results Eighty-seven (93%) of 94 indium–tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 μg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥1.0 μg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 μg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures. Conclusions In indium–tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum biomarkers of lung

  12. Associations between biomarkers of joint metabolism, hand osteoarthritis, and hand pain and function

    PubMed Central

    Aslam, Imran; Perjar, Irina; Shi, Xiaoyan A.; Renner, Jordan B.; Kraus, Virginia B.; Golightly, Yvonne M.; Jordan, Joanne M.; Nelson, Amanda E.

    2014-01-01

    Objective To determine the associations between joint metabolism biomarkers and hand radiographic osteoarthritis (rOA, based on Kellgren Lawrence [KL] grade ≥2), symptoms, and function. Design Cross-sectional data were available for 663 participants (mean age 63 years, 63% white, 49% women). Three definitions of hand rOA were considered: 1) a composite measure involving at least 3 hand joints distributed bilaterally with 2 of 3 in the same joint group, including ≥1 distal interphalangeal joint, without metacarpophalangeal [MCP] swelling); 2) rOA in at least one joint of a group; and 3) number of joints with KL ≥2. We assessed hand symptoms and the 15-item AUSCAN (Likert format). We measured serum cartilage oligomeric matrix protein (sCOMP), hyaluronic acid (sHA),carboxy-terminal propeptide of type II collagen (sCPII), type II collagen degradation product (C2C), urinary C-terminal crosslinked telopeptide of type II collagen (uCTX-II), and urinary N-terminal crosslinked telopeptide (uNTX-1). Linear regression models were performed to assess associations between each biomarker with hand rOA, AUSCAN, and symptoms, adjusting for age, gender, race, current smoking/drinking status, BMI, and hip and knee rOA. Results In adjusted analyses, MCP (p<0.0001) and carpometacarpal rOA (p=0.003), and a higher number of hand joints with rOA (p=0.009), were associated with higher levels of sHA. Positive associations were seen between AUSCAN and hand symptoms and levels of sCOMP (p≤0.003) and sHA (p≤0.048). Conclusion Hand symptoms and higher AUSCAN scores were independently associated with higher levels of both sCOMP and sHA; hand rOA was associated only with sHA levels. PMID:24584914

  13. Efficacious response with low-dose indapamide therapy in the treatment of type II diabetic patients with normal renal function or moderate renal insufficiency and moderate hypertension.

    PubMed

    Madkour, Hosameldin; Ali, Kareim; Nosrati, Saeid; Massry, Shaul G

    2002-01-01

    We examined the efficacy of low daily dose (1.25 mg/day) of indapamide in the treatment of high blood pressure in patients with diabetes mellitus with normal renal function and those with moderate renal insufficiency (serum creatinine <1.5 mg/dl). The study was an open label one of four months duration. Twenty-eight patients were enrolled in the study and only 15 completed it. Within 2 weeks of therapy, systolic blood pressure fell from 173 +/- 4.5 to 144 +/- 2.0 mm Hg and diastolic blood pressure from 96 +/- 2.1 to 80 +/- 1.8 mm Hg (p < 0.01) and blood pressure remained at these levels throughout the study. The results show that low dose indapamide is effective in the treatment of moderate hypertension in patients with diabetes mellitus who have normal renal function or moderate renal insufficiency. Therefore, this dose of 1.25 mg/day is recommended for the treatment of such patients.

  14. End-Stage Renal Disease After Renal Surgery in Patients with Normal Preoperative Kidney Function: Balancing Surgical Strategy and Individual Disorders at Baseline.

    PubMed

    Capitanio, Umberto; Larcher, Alessandro; Terrone, Carlo; Antonelli, Alessandro; Volpe, Alessandro; Fiori, Cristian; Furlan, Maria; Dehò, Federico; Minervini, Andrea; Serni, Sergio; Porpiglia, Francesco; Trevisani, Francesco; Salonia, Andrea; Carini, Marco; Simeone, Claudio; Montorsi, Francesco; Bertini, Roberto

    2016-10-01

    Although nephron-sparing surgery (NSS) has demonstrated benefit in terms of renal function preservation, it is unclear whether NSS might also decrease the risk of end-stage renal disease (ESRD) relative to radical nephrectomy (RN). In the current paper, we aimed to report the rate and the predictors of ESRD after surgery, accounting for detailed individual baseline characteristics and comorbidities. A multi-institutional collaboration among five European tertiary care centers allowed study of 2027 patients with normal preoperative renal function and a clinically localized T1abN0M0 renal mass. Cox regression analyses were used to predict the risk of ESRD (defined as the onset of a postoperative estimated glomerular filtration rate <15ml/min per 1.73 m(2)) after adjusting for the individual baseline risk of developing chronic kidney disease. Univariable ESRD rates at 5 and 10 yr of follow-up were virtually equivalent for patients who underwent NSS (1.5% and 2.5%, respectively) versus RN (1.9% and 2.7%, respectively; hazard ratio [HR]: 0.8; 95% confidence interval [CI], 0.4-1.6). However, diabetes, smoking, uncontrolled hypertension, and other comorbidities were consistently more frequent in the NSS group relative to their RN counterparts. After adjusting for detailed baseline individual characteristics, NSS was shown to have an independent protective effect relative to RN (HR: 0.4; 95% CI, 0.2-0.8; p=0.02) at multivariable analyses.

  15. Development of fluorescent tracers for the real-time monitoring of renal function

    NASA Astrophysics Data System (ADS)

    Poreddy, Amruta R.; Asmelash, Bethel; Debreczeny, Martin P.; Fitch, Richard M.; Freskos, John N.; Galen, Karen P.; Gaston, Kimberly R.; Kostelc, James G.; Kumar, Rana; Marzan, Tim A.; Neumann, William L.; Rajagopalan, Raghavan; Schoenstein, Tasha M.; Shieh, Jeng-Jong; Wilcox, J. Micah; Wojdyla, Jolette K.; Dorshow, Richard B.

    2011-03-01

    Accurate measurement of glomerular filtration rate (GFR) at the bedside is highly desirable in order to assess renal function in real-time, which is currently an unmet clinical need. In our pursuit to develop exogenous fluorescent tracers as GFR markers, various hydrophilic derivatives of 3,6-diaminopyrazine-2,5-dicarboxylic acid with varying molecular weights and absorption/emission characteristics were synthesized. These include polyhydroxyalkyl based small molecules and poly(ethylene glycol) (PEG) substituted moderate molecular weight compounds, which were further sub-grouped into analogs having blue excitation with green emission, and relatively longer wavelength analogs having green excitation with orange emission. Lead compounds were identified in each of the four classes on the basis of structure- activity relationship studies, which included in vitro plasma protein binding, in vivo urine recovery of administered dose, and in vivo optical monitoring. The in vivo optical monitoring experiments with lead candidates have been correlated with plasma pharmacokinetic (PK) data for measurement of clearance and hence GFR. Renal clearance of these compounds, occurring exclusively via glomerular filtration, was established by probenecid blocking experiments. The renal clearance property of all these advanced candidates was superior to that of the iothalamate, which is currently an accepted standard for the measurement of GFR.

  16. Induction of renal and hepatic mixed function oxidases in the hamster and guinea pig.

    PubMed

    Smith, J H; Rush, G F; Hook, J B

    1986-02-01

    A marked species difference exists in the induction of renal and hepatic mixed function oxidase (MFO) activity between rats and rabbits. However, little is known about MFO induction in these organs from other laboratory animals. Male Golden Syrian hamsters and male Hartley guinea pigs were administered phenobarbital (PB) or beta-napthoflavone (BNF) at 70 and 40 mg/kg, respectively, as daily i.p. injections for 4 days. Polybrominated biphenyl (PBB) (Firemaster BP-6) was given as a single i.p. injection (50 mg/kg). Hamster hepatic microsomal ethoxyresorufin-O-deethylase (EROD) and benzphetamine-N-demethylase (BPND) were selectively induced by BNF and PB, respectively. PBB administration induced both hamster hepatic EROD and BPND. In contrast, hepatic microsomal MFO activity from the guinea pig was inducible by PB, PBB and BNF. Renal microsomal MFO activity in both species was inducible by BNF and PBB as arylhydrocarbon hydroxylase and EROD were induced approximately 10-fold. On the other hand, hamster BPND was induced by PB whereas guinea pig MFO activity was unaffected. Total renal cytochrome P-450 content was not affected by any of these inducers in either species. These data demonstrate selective patterns of induction in both hamster and guinea pig liver and kidney suggesting the involvement of multiple forms of cytochrome P-450.

  17. Cordyceps militaris Treatment Preserves Renal Function in Type 2 Diabetic Nephropathy Mice

    PubMed Central

    Yu, Sung-Hsun; Dubey, Navneet Kumar; Li, Wei-Shan; Liu, Ming-Che; Chiang, Han-Sun; Leu, Sy-Jye; Shieh, Ying-Hua; Tsai, Feng-Chou; Deng, Win-Ping

    2016-01-01

    Diabetic nephropathy is derived from long-term effects of high blood glucose on kidney function in type 2 diabetic patients. Several antidiabetic drugs and herbal medications have failed to prevent episodes of DN. Hence, this study aimed to further investigate the renal injury-reducing effect of antidiabetic CmNo1, a novel combination of powders of fruiting bodies and mycelia of Cordyceps militaris. After being administered with streptozotocin-nicotinamide and high-fat-diet, the diabetic nephropathy mouse model displayed elevated blood glucose and renal dysfunction markers including serum creatinine and kidney-to-body weight ratio. These elevated markers were significantly mitigated following 8 weeks CmNo1 treatment. Moreover, the chronic hyperglycemia-induced pathological alteration in renal tissue were also ameliorated. Besides, immunohistochemical study demonstrated a substantial reduction in elevated levels of carboxymethyl lysine, an advanced glycation end product. Elevated collagenous deposition in DN group was also attenuated through CmNo1 administration. Moreover, the enhanced levels of transforming growth factor-β1, a fibrosis-inducing protein in glomerulus were also markedly dampened. Furthermore, auxiliary risk factors in DN like serum triglycerides and cholesterol were found to be increased but were decreased by CmNo1 treatment. Conclusively, the results suggests that CmNo1 exhibit potent and efficacious renoprotective action against hyperglycemia-induced DN. PMID:27832180

  18. Cordyceps militaris Treatment Preserves Renal Function in Type 2 Diabetic Nephropathy Mice.

    PubMed

    Yu, Sung-Hsun; Dubey, Navneet Kumar; Li, Wei-Shan; Liu, Ming-Che; Chiang, Han-Sun; Leu, Sy-Jye; Shieh, Ying-Hua; Tsai, Feng-Chou; Deng, Win-Ping

    2016-01-01

    Diabetic nephropathy is derived from long-term effects of high blood glucose on kidney function in type 2 diabetic patients. Several antidiabetic drugs and herbal medications have failed to prevent episodes of DN. Hence, this study aimed to further investigate the renal injury-reducing effect of antidiabetic CmNo1, a novel combination of powders of fruiting bodies and mycelia of Cordyceps militaris. After being administered with streptozotocin-nicotinamide and high-fat-diet, the diabetic nephropathy mouse model displayed elevated blood glucose and renal dysfunction markers including serum creatinine and kidney-to-body weight ratio. These elevated markers were significantly mitigated following 8 weeks CmNo1 treatment. Moreover, the chronic hyperglycemia-induced pathological alteration in renal tissue were also ameliorated. Besides, immunohistochemical study demonstrated a substantial reduction in elevated levels of carboxymethyl lysine, an advanced glycation end