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)

Prothrombin has remarkable affinity for calcium oxalate crystals. It is produced in renal tubular cells and is detected as a urinary form of prothrombin F1. The aim of this basic study was (1) to isolate prothrombin mRNA from normal human and rat kidneys; (2) to confirm expression level changes in stone-forming rat kidneys; and (3) to analyze the DNA sequence of renal prothrombin. The aim of the clinical investigation was to measure the serum levels of renal prothrombin in clinical cases of various urologic diseases. The expression of prothrombin mRNA in human kidneys and male Wistar rat kidneys was investigated using reverse transcription-PCR, with prothrombin (F1, F2, and thrombin) primers. Renal prothrombin levels were measured in the sera of patients with renal cell carcinoma, renal transplant donors, patients with chronic renal failure, and renal transplant recipients, using an enzyme-linked immunosorbent assay. Expression of cyclophilin as well as prothrombin mRNA could be detected. Prothrombin mRNA expression levels seemed to be increased in stone-forming rats. The DNA sequence of renal prothrombin differed from that of liver prothrombin at three points. Repeated measurements of renal prothrombin showed that values were high during the acute tubular necrosis period and tended to decrease with the recovery of renal function. Prothrombin mRNA expression could be confirmed in human and rat kidneys, as well as in stone-forming rat kidneys. Serum concentration measurements can be considered useful for assessment of recovery from acute tubular necrosis after renal transplantation and for diagnosis of acute rejection.
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PMID:Gene expression of prothrombin in human and rat kidneys: basic and clinical approach. 1054 Dec 74

Acute renal failure (ARF) occurs frequently in hospitalised patients, and is associated with significant morbidity and mortality. The most common and generalised forms of acute renal failure are pre-renal conditions and intra-renal acute tubular necrosis (ATN). Pre-renal ARF in its pure state should be entirely reversible by restoring renal perfusion, but in some cases ATN has already occurred. ATN remains a more vexing problem, and is seen most often with hypotension, perioperative or systemic inflammatory stresses, radiocontrast administration, and exposure to nephrotoxins. Among the available pharmacological options for prevention or treatment of ATN, there is a remarkable lack of definitive evidence supporting specific therapy in any setting. Although loop diuretics, mannitol, and dopamine are frequently used for prevention and/or treatment of ATN, clinical studies have failed to prove value. Other drugs with theoretical value, specifically atrial natriuretic peptide analogues, adenosine blockers, and calcium antagonists, have been insufficiently studied to recommend use. Other pharmacological options may arise in the future. Ensuring adequate intravascular fluid volume remains the only approach to managing ATN which can be considered relatively effective and safe. Given the abundant theoretical basis for the prevention and treatment of ATN with drugs, well conducted clinical studies with relevant outcome measures are clearly warranted.
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PMID:An evaluation of pharmacological strategies for the prevention and treatment of acute renal failure. 1071

It was reported that reactive oxygen metabolites play an important role in the pathogenesis of several renal diseases including glomerulonephritis, ischemia and acute tubular necrosis. However, the effect of oxidants and protective effect of sex steroid hormones on Na+/glucose cotransporter of renal proximal tubular cells is not yet elucidated. In the present study, we examined the effect of sex steroid hormones against tert-butyl hydroperoxide (t-BHP)-induced alteration of Na+/glucose cotransporter activity in primary cultured rabbit renal proximal tubule cells (PTCs). t-BHP inhibited alpha-methyl-D-glucopyranoside (alpha-MG) uptake in a dose-dependent manner. t-BHP-induced inhibition of alpha-MG uptake was due not to Km but to the decrease of Vmax. 0.5 mM t-BHP-induced inhibition of alpha-MG uptake was significantly blocked by estradiol-17beta, but not by progesterone and testosterone. This protective effect was not blocked by estrogen receptor antagonist or transcription and translation inhibitor. In addition, 0.5 mM t-BHP increased [3H]-arachidonic acid (AA) release and Ca2+ uptake. These effects of t-BHP were also significantly blocked by estradiol-17beta, but not by progesterone and testosterone. Protective efficacy of estradiol-17beta on t-BHP-induced inhibition of alpha-MG uptake is exhibited between antioxidants and iron chelators. In conclusion, estradiol-17beta, but not progesterone and testosterone, partially prevented t-BHP-induced inhibition of alpha-MG uptake through its antioxidant activity dependent upon phenol structures and inhibition of AA release and Ca2+ influx.
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PMID:Effects of sex hormones on Na+/glucose cotransporter of renal proximal tubular cells following oxidant injury. 1152 8

Perchloroethylene (PCE) is an unsaturated chlorinated hydrocarbon in the form of a colorless, volatile liquid that is used as an industrial organic solvent for metal degreasing and for dry cleaning. The majority of cases of PCE intoxication have occurred by chronic inhalation, and PCE has been implicated previously in the development of mild renal dysfunction. However, the acute effects of PCE on the kidney are not well characterized, and the authors know of no reports of renal biopsy findings in the human. Here the case of a 32-year-old man who manifested by semicomatose state and oliguric acute renal failure requiring dialysis after accidental ingestion of 75 g of PCE is presented. A renal biopsy performed on the 19th day after ingestion showed features characteristic of severe acute tubular necrosis: aggregations of triangular or rhomboid crystals in the tubular lumens. A von Kossa stain showed that the crystal deposits were strongly positive for calcium. After 5 hemodialyses and conservative treatment, renal function gradually returned to normal.
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PMID:ARF requiring hemodialysis after accidental perchloroethylene ingestion. 1261 4

Many aspects of calcium oxalate (CaOx) deposition in renal transplant biopsies are not known. Review of all renal transplant biopsies performed in a 7-year period showed that CaOx deposition could be classified into three groups. Group I: Seven biopsies within a month post-transplant displayed rare CaOx foci against a background of acute tubular necrosis or acute cell-mediated rejection. At follow-up, five grafts functioned well and two failed due to chronic allograft nephropathy. CaOx in this context was an incidental finding secondary to a sudden excretion of an end-stage renal disease-induced increased body burden of CaOx. Group II: Two biopsies performed 2 and 10 months post-transplant showed rare CaOx foci against a background of chronic allograft nephropathy, leading to graft loss. CaOx in this context reflected nonspecific parenchymal deposition due to chronic renal failure regardless of causes. Group III: One biopsy with recurrent PH1 characterized by marked CaOx deposition associated with severe tubulointerstitial injury and graft loss 6 months post-transplant. There were two previously reported cases in which CaOx deposition in the renal allografts was due the antihypertensive drug naftidrofuryl oxalate or increased intestinal absorption of CaOx. CaOx deposition in renal allografts can be classified in different categories with distinctive morphologic features and clinical implications.
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PMID:Calcium oxalate deposition in renal allografts: morphologic spectrum and clinical implications. 1526 37

Accumulated oxalate will be excreted after renal transplantation, creating an increased risk of tubular precipitation, especially in the presence of allograft dysfunction. We evaluated calcium oxalate (CaOx) deposition in renal allograft biopsies with early dysfunction, its association with acute tubular necrosis (ATN) and graft survival. We studied 97 renal transplant patients, submitted to a graft biopsy within 3 months post-transplant, and reanalyzed them after 10 years. We analyzed renal tissue under polarized light and quantified CaOx deposits. CaOx deposits were detected in 52.6% of the patients; 26.8% were of mild and 25.8% of moderate intensity. The deposits were more frequent in biopsies performed within 3 weeks post-transplant (82.4 vs. 63.0%, p < 0.05) and in allografts with more severe renal dysfunction (creatinine 5.6 mg/dL vs. 3.4 mg/dL, p < 0.001). ATN incidence was also higher in patients with CaOx deposits (47% vs. 24%, p < 0.001). Twelve-year graft survival was strikingly worse in patients with CaOx deposits compared to those free of deposits (49.7 vs. 74.1%, p = 0.013). Our study shows a high incidence of CaOx deposits in kidney allografts with early dysfunction, implying an additional risk for acute tubular injury, with a negative impact on graft survival.
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PMID:Early presence of calcium oxalate deposition in kidney graft biopsies is associated with poor long-term graft survival. 1564 92

Ethylene glycol (EG) is nephrotoxic due to its metabolism. Many studies suggest that the toxicity is due to oxalate accumulation, but others have conversely suggested that toxicity results from effects of metabolites such as glycolaldehyde or glyoxylic acid on proximal tubule cells. In vivo studies have indicated that accumulation of calcium oxalate monohydrate (COM) corresponds closely with development of toxicity in renal tissue. The present studies were therefore designed to clarify the roles of various metabolites in the mechanism for EG toxicity in vitro by comparing the relative cytotoxicity of EG metabolites using three measures of cell death, ethidium homodimer uptake, lactate dehydrogenase (LDH) release and the conversion of the tetrazolium salt XTT to a colorimetric dye. Human proximal tubule cells in culture were incubated in physiologic buffers for 6h at 37 degrees C with COM (147-735microg/ml, an oxalate equivalence of 1-5mM), glycolate (5-25mM), glyoxylate (0.2-5mM) and glycolaldehyde (0.2-2mM). To assess the effects of acidity on the cytotoxicity, incubations were carried out at pH 6-7.4. The results show that COM dose-dependently increased LDH release and ethidium homodimer uptake, while the other metabolites did not. Conversely, COM had no effect on the XTT assay, while high concentrations of glycolaldehyde and glyoxylate decreased XTT activity, but the latter only at acidic pH. The correlation between the uptake of ethidium homodimer and the release of LDH suggest that COM is cytotoxic to human kidney cells in culture, while the XTT assay does not validly measure cytotoxicity in this system. These results indicate that COM, and not glyoxylate or glycolaldehyde, is the toxic metabolite responsible for the acute tubular necrosis and renal failure that is observed in EG-poisoned patients.
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PMID:Calcium oxalate, and not other metabolites, is responsible for the renal toxicity of ethylene glycol. 1768 74

A young man presented to the emergency department with mental status changes, severe metabolic acidosis, and oliguria. Acute ethylene glycol intoxication was diagnosed. The patient suffered clinical brain death three days after admission despite intensive care and continuous hemodiafiltration. The patient died one month after admission. Autopsy revealed acute tubular necrosis of the kidneys with significant calcium oxalate depositions. The brain was markedly softening and with chronic meningoencephalitis and dural sinus thrombosis. We considered that the amount and the persistence of the calcium oxalate deposition in the kidney may afford a best clue to the postmortem diagnosis of ethylene glycol poisoning even in the chronic stage.
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PMID:Brain death with calcium oxalate deposition in the kidney: clue to the diagnosis of ethylene glycol poisoning. 1769 92

Renal injury is known to trigger upregulation of many intracellular signal proteins, but those most sensitive in responding to renal injury remain debatable. We used gene microarray analysis to compare gene expression in rat kidneys subjected to early ischemia-reperfusion injury (30 min of renal ischemia and 3 hr of reperfusion) with non-ischemic kidneys as controls. Among 31,100 genes analyzed, microarray analysis revealed 21 genes with >3-fold increase in expression in ischemic kidneys compared to control non-ischemic kidneys. These upregulated genes included heat shock protein 70 (43-fold), heat shock protein 27 (12-fold), heme oxygenase-1 (10-fold), kidney injury molecule-1 (8-fold), and several subtypes of S100 calcium-binding proteins (3.1- to 7.5-fold). Following a prolonged reperfusion period (48 hr) after 30 min of ischemia, acute tubular necrosis was obvious in the S3 segment of proximal tubules of ischemic kidneys. Injured proximal tubules showed upregulated expression of heat shock protein 70 by immunohistochemistry and by Western blotting. These data suggest that heat shock proteins (eg, heat shock protein 70, heat shock protein 27, and heme oxygenase-1) are crucial for renal cell response to ischemic injury and that heat shock protein 70 is a highly sensitive intracellular marker of ischemia-reperfusion injury.
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PMID:Heat shock protein expression is highly sensitive to ischemia-reperfusion injury in rat kidneys. 1831 83

An 11-year-old male developed systemic calciphylaxis during induction therapy for acute lymphoblastic leukemia. His predisposing conditions were hypercalcemia, supplements for pamidronate-induced hypocalcemia and hypophosphatemia and renal insufficiency. He died of cardiorespiratory arrest on the 20th day of induction treatment. Autopsy revealed extensive calcium deposits in the heart, lungs and kidneys. He had diffused alveolar damage, acute tubular necrosis, chronic pancreatitis and marked hepatic steatosis. Systemic calcium deposition may progress rapidly in children with hypercalcemia of malignancy. Since pamidronate reduces mineral resorption from tissues, calcium and phosphate replacements increase systemic mineral deposits. Thus, mineral supplements should be considered only to combat symptoms.
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PMID:Systemic calciphylaxis. 1849 73


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