Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Traditional methods of noninvasively evaluating patients for renal injury do not accomplish the following tasks: reliably distinguish potentially treatable forms of acute renal failure from acute tubular necrosis; provide a sensitive indicator of early allograft rejection in renal transplant recipients, particularly those in the pediatric age group; provide an early warning of incipient drug-induced nephrotoxicity; or serve as an adequate screening test for renal injury due to exposure to occupational or environmental toxins, especially heavy metals. Because of this, considerable effort has been devoted to the development of assays to satisfy these needs. Three approaches include measurement in the urine of low-molecular-weight plasma proteins such as beta 2-microglobulin; a variety of kidney-derived enzymes, such as L-alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase; and specific renal antigens using immunologic detection. The first two of these have not proved to be adequately sensitive or specific, complicated by the frequent loss of activity associated with the physicochemical characteristics of the urine or the presence of pyuria. Despite this, useful information has been obtained. In particular, assays of beta 2-microglobulin urinary excretion and retinol binding protein appear to have clinical utility that should be pursued. Recent experience with a monoclonal antibody-based assay for a unique proximal tubular antigen, the adenosine deaminase binding protein, suggests that a battery of such assays, each directed against an antigen localized to a particular segment of the nephron, may be particularly useful.
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PMID:Noninvasive renal diagnostic studies. 290 37

Retinol binding protein (RBP) was analyzed in the sera and urines of 5 patients with hepato-renal syndrome (HRS), 4 with acute tubular necrosis (ATN), 20 liver cirrhosis patients with normal kidney function (NKF), 14 chronic renal failure (CRF) patients, and 19 healthy adults. All renal failure patients had high mean urine RBP (URBP): HRS, 8 mg/L; ATN, 11 mg/L; CRF, 8 mg/L respectively; p less than 0.001 vs the rest. Those with ATN and CRF had high mean serum RPB (SRBP): 146 and 149 mg/L, respectively, p less than 0.001 compared to the other groups. In HRS, in spite of renal failure, SRBP was very low (mean = 12 mg/L). The cirrhotics with NKF averaged less than 50% of the SRBP values of the healthy controls (16 vs 41 mg/L RBP, p less than 0.001); their RBP excretion was normal (mean URBP of 0.1 vs 0.06 mg/L in the control group). RBP analyses before and during HRS in two patients showed a marked increase in urine RBP during HRS (35- and 600-fold respectively) with practically unchanged serum levels. Impaired hepatic production and/or release is proposed to explain the low serum RBP in HRS, and a renal tubular injury or dysfunction to account for its high excretion. The RBP urinary loss could further compromise an already abnormal RBP metabolism and its serum levels. This combination (of low serum and high urine RBP), in the context of renal failure occurring in alcoholic liver cirrhosis, could help in the recognition of HRS.
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PMID:Analysis of serum and urinary retinol binding protein in hepato-renal syndrome. 356 46

Renal function in the early post-transplantation period depends largely on factors affecting the kidney prior to implantation. Function of the graft may be also disturbed by the most common complications of the early post-operative period such as acute graft rejection (AGR), acute tubular necrosis (ATN) and may be modified by nephrotoxic action of cyclosporine A (CsA). Evaluation of excretion of enzymes and low molecular weight proteins (LMWP) may help in the differentiation of these complications. Aim Comparison of the urinary excretion of markers of tubular injury in patients with AGR, ATN, or patients with stable graft function (SGF) was made and differences between groups and correlations between markers and cold ischemia time (CIT), warm ischemia time (WIT) and blood trough level of cyclosporine A (CsA0) were determined. Material and methods In 60 cadaveric renal allograft recipients in the early post-transplantation period urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and B isoenzyme (NAG-B), alanylaminopeptidase (AAP), gamma-glutamyltransferase (GGT), alpha and pi isoenzymes of glutathione S-transferase (alpha-GST, pi-GST), retinol binding protein (RBP) and beta2- microglobulin (beta2M), were analyzed. Results NAG and NAB-B activities were higher in ATN (P<0.05, P<0.01) and in AGR (P<0.005, P<0.02) than in SGF. Excretion of pi-GST was higher in AGR than in SGF (P<0.0002) or ATN (P<0.007). CIT and WIT in patients with ATN were higher (P<0.05) than in SGF group. In ATN patients, correlations of CIT with RBP (P<0.05) and pi-GST (P<0.05), and WIT with RBP (P<0.05), and pi-GST (P<0.001) were found. Conclusions High urinary NAG and NAG B excretion characterizes ATN and AGR patients. Evaluating urinary excretion of pi-GST may be helpful in differentiating AGR from ATN. However, taking into account ischemia time is necessary in interpreting the pi-GST value in early post transplant period.
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PMID:Enzymuria and low molecular weight protein excretion as the differentiating marker of complications in the early post kidney transplantation period. 1716 Apr 49

Ischemia/reperfusion injury and delayed graft function (DGF) following organ transplantation adversely affect graft function and survival. A large animal model has not been characterized. We developed a pig kidney allograft model of DGF and evaluated the cytoprotective effects of inhaled carbon monoxide (CO). We demonstrate that donor warm ischemia time is a critical determinant of DGF as evidenced by a transient (4-6 days) increase in serum creatinine and blood urea nitrogen following transplantation before returning to baseline. CO administered to recipients intraoperatively for 1 h restored kidney function more rapidly versus air-treated controls. CO reduced acute tubular necrosis, apoptosis, tissue factor expression and P-selectin expression and enhanced proliferative repair as measured by phosphorylation of retinol binding protein and histone H3. Gene microarray analyses with confirmatory PCR of biopsy specimens showed that CO blocked proinflammatory gene expression of MCP-1 and heat shock proteins. In vitro in pig renal epithelial cells, CO blocks anoxia-reoxygenation-induced cell death while promoting proliferation. This large animal model of DGF can be utilized for testing therapeutic strategies to reduce or prevent DGF in humans. The efficacy of CO on improving graft function posttransplant validates the model and offers a potentially important therapeutic strategy to improve transplant outcomes.
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PMID:Intraoperative administration of inhaled carbon monoxide reduces delayed graft function in kidney allografts in Swine. 2097 33

Ischemia-reperfusion injury (IRI) is inevitable during kidney transplantation leading to oxidative stress and inflammation. We previously reported that preoperative fasting in young-lean male mice protects against IRI. Since patients are generally of older age with morbidities possibly leading to a different response to fasting, we investigated the effects of preoperative fasting on renal IRI in aged-overweight male and female mice. Male and female F1-FVB/C57BL6-hybrid mice, average age 73 weeks weighing 47.2 grams, were randomized to preoperative ad libitum feeding or 3 days fasting, followed by renal IRI. Body weight, kidney function and survival of the animals were monitored until day 28 postoperatively. Kidney histopathology was scored for all animals and gene expression profiles after fasting were analyzed in kidneys of young and aged male mice. Preoperative fasting significantly improved survival after renal IRI in both sexes compared with normal fed mice. Fasted groups had a better kidney function shown by lower serum urea levels after renal IRI. Histopathology showed less acute tubular necrosis and more regeneration in kidneys from fasted mice. A mRNA analysis indicated the involvement of metabolic processes including fatty acid oxidation and retinol metabolism, and the NRF2-mediated stress response. Similar to young-lean, healthy male mice, preoperative fasting protects against renal IRI in aged-overweight mice of both genders. These findings suggest a general protective response of fasting against renal IRI regardless of age, gender, body weight and genetic background. Therefore, fasting could be a non-invasive intervention inducing increased oxidative stress resistance in older and overweight patients as well.
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PMID:Preoperative fasting protects against renal ischemia-reperfusion injury in aged and overweight mice. 2495 49

Determination of the protein composition of urine is a non-invasive method helping to diagnose renal lesions and evaluate therapeutic interventions. We present here five observations that highlight the performance and relevance of urine protein analysis combining selected glomerular and tubular protein measurements. Total urine protein level and measurements of urinary IgG, albumin, transferrin alpha-1 microglobulin and retinol binding protein were performed on a urine sample by immunonephelometry. The results were normalized for urine creatinine concentration and integrated in the MDI interpretation software that provides a "urine protein profile" (UPP). Sequential UPP were performed in two patients with drug-induced tubular toxicity. One resolved after drug withdrawal. The second concomitantly developped glomerular lesions and repeated UPP was warranted to follow evaluation of the distinct renal lesions. Two cases illustrate two distinct clinical situations in patients with multiple myeloma, respectively myeloma cast nephropathy and toxic acute tubular necrosis. Those differential diagnoses were early anticipated by UPP. In one case, UPP was in favour of the presence of large amount of urinary monoclonal light chain excretion before performing urine electrophoresis analysis and renal biopsy while this was not in the other case. In the last case, we compared sequential UPP, renal function and kidney biopsies in a patient with a diagnosis of membranous nephropathy, and demonstrated a good correlation between urine glomerular and tubular protein excretion and progression of the renal lesions. The use of the UPP in clinical practice, particularly through the accurate quantification of tubular markers, is a more efficient tool for the diagnosis and follow-up of renal diseases than the less sensitive semi-quantitative urine electrophoresis or combined assays of both total proteinuria and albuminuria.
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PMID:Interest of the combined measurement of selected urinary proteins in the diagnosis approach in nephrology. 2854 Aug 55

Tenofovir disoproxil fumarate (TDF) is a commonly used antiretroviral drug for HIV, rarely causing Fanconi syndrome and acute kidney injury. We retrospectively analyzed the clinico pathological presentation of 20 cases of tenofovir-induced tubulopathy, and investigated the renal expression of the megalin and cubilin proteins, as well as the mitochondrial respiratory chain activity. Estimated glomerular filtration rate (eGFR) before TDF exposure was 92 ml/min/1.73m2, decreasing to 27.5 ml/min/1.73m2 at the time of biopsy, with 30% of patients requiring renal replacement therapy. Proximal tubular expression of megalin and cubilin was altered in 19 and 18 cases, respectively, whereas it was preserved in patients exposed to TDF without proximal tubular dysfunction and in HIV-negative patients with acute tubular necrosis. Loss of megalin/cubilin was correlated with low eGFR and high urine retinol binding protein at the time of biopsy, low eGFR at last follow-up, and was more severe in patients with multifactorial toxicity. Patients with additional nephrotoxic conditions promoting tenofovir accumulation showed a lower eGFR at presentation and at last follow-up, and more severe lesions of acute tubular necrosis, than those with isolated tenofovir toxicity. Altered mitochondrial COX activity in proximal tubules was observed and may be an early cellular alteration in tenofovir nephrotoxicity. In conclusion, altered megalin/cubilin expression represents a distinctive feature in tenofovir-induced tubulopathy, and its severity is correlated with urine retinol binding protein loss and is associated with a poor renal prognosis. Concomitant exposure to other nephrotoxic conditions severely impacts the renal presentation and outcome.
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PMID:Decreased expression of megalin and cubilin and altered mitochondrial activity in tenofovir nephrotoxicity. 2930 6