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)

Adult patients deficient in carnitine palmitoyltransferase II (CPT II) cannot generate sufficient amounts of energy, which results in rhabdomyolysis and acute renal failure (ARF). Its genetic basis has been recognized; but histopathologic changes, especially electron microscopic changes, have scarcely been described. The study subject is a patient with ARF caused by repetitive nontraumatic rhabdomyolysis. The acylcarnitine profile of serum and enzyme assay on skin fibroblasts confirmed the diagnosis of CPT II deficiency. Renal biopsy specimens were examined microscopically and immunohistochemically. The histological diagnosis was interstitial nephritis with acute tubular necrosis caused by rhabdomyolysis. Myoglobin in tubules was detected by means of immunohistochemistry and electron microscopy. The genetic structure of CPT II was analyzed in the patient and his family. Eight pairs of polymerase chain reaction (PCR) primers were designed to cover the coding region. Each PCR-amplified gene product was subjected to DNA sequencing, which unveiled heterozygosity at the CPT II locus consisting of a deletion of cytosine and thymine at codon 408, resulting in a stop signal at 420, as well as a mutation of arginine to cysteine at codon 631. The frame shift at 408 has never been described before. DNA sequencing of the family showed the deletion mutation from the mother and the point mutation from the father. We describe renopathological findings in a patient with CPT II deficiency associated with rhabdomyolysis, which suggested the pathological role of myoglobin casts in the development of tubular necrosis. Genetic analysis of the patient identified a novel variant of the CPT II gene.
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PMID:Carnitine palmitoyltransferase II deficiency due to a novel gene variant in a patient with rhabdomyolysis and ARF. 1575 83

The HNK-1 carbohydrate epitope is a 3-sulfo-glucuronyl residue attached to lactosamine structures on glycoproteins, proteoglycans, or glycolipids mostly expressed in the nervous system. Here, using monoclonal antibodies against the sulfated HNK-1 carbohydrate epitope, we first examined its distribution in developing and adult kidneys, then its expression in kidneys with tubular necrosis and renal neoplasms. This HNK-1 epitope was expressed in the human, rabbit, and rat, but not mouse kidney. It was detected within a subset of epithelial cells in the renal vesicle and in comma- and S-shaped bodies during early stages of nephrogenesis. In ureteral bud derivatives, the epitope was present transiently in the area where the collecting duct fused with the nephron. In the adult kidney, expression of the HNK-1 epitope became mainly restricted to the thin ascending loop of Henle where this epitope was carried by heparan- and chondro-proteoglycan. In pathological conditions, HNK-1 epitope expression increased dramatically in proximal epithelial tubule cells in kidneys with acute tubular necrosis. In tumors, the HNK-1 epitope was expressed in the epithelial component of nephroblastomas and in a subgroup of papillary renal cell carcinomas. These data suggest that molecules carrying the sulfated HNK-1 carbohydrate epitope may play an important role in critical stages of renal development and in the physiology of thin ascending loop of Henle.
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PMID:Sulfated HNK-1 epitope in developing and mature kidney: a new marker for thin ascending loop of Henle and tubular injury in acute tubular necrosis. 1640 97

Narthecium ossifragum, a perennial herb of the lily family, causes toxic renal tubular necrosis in several ruminant species. 3-Methoxy-2(5H)-furanone (3M2F) has been identified as a nephrotoxin present in N. ossifragum extracts. We studied effects of three different 3M2F-containing fractions isolated from N. ossifragum and synthetic 3M2F on the porcine kidney cell line LLC-PK1. In some of the experiments, we included the glioma cell lines U251 and BT4Cn to compare the effects of the toxin on LLC-PK1 cells to the effect on these cell lines. The synthetic 3M2F was shown to be only mildly toxic, and the most purified fraction from N. ossifragum showed the highest degree of toxicity in our studies. When monolayer cultures were exposed to increasing amounts of 3M2F-containing extract, a dose-dependent increase in cell death was observed. Similarly, reduced neutral red uptake and 3H-thymidine uptake (DNA synthesis) was observed. There was increased apoptotic activity in the LLC-PK1 cells with increasing concentration of 3M2F-containing extract. Multicellular three-dimensional spheroids from LLC-PK1 cells stopped fluid transport, showed degenerative changes and collapsed totally 6 h after extract exposure. Our findings indicate junctional damage, reduced cellular endocytosis and DNA-synthesis as well as induction of apoptosis as possible mechanisms for the acute tubular necrosis observed in ruminant species.
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PMID:Effects of 3-methoxy-2(5H)-furanone-containing extracts from Narthecium ossifragum (L.) Huds. on renal tubular cells in vitro. 1714 20

In patients with cirrhosis, acute renal failure is due to prerenal failure (a result of decreased renal perfusion) and tubular necrosis. There are 3 main causes of prerenal failure: 'true hypovolemia' (which complicates hemorrhage, gastrointestinal or renal fluid losses), sepsis, and type 1 hepatorenal syndrome (HRS). Prerenal failure may also be due to the administration of non-steroidal antiinflammatory drugs, or intravascular radiocontrast agents. Prerenal failure is reversible after restoration of renal blood flow. Treatments target the cause of hypoperfusion, and fluid replacement is used to treat 'non-HRS' prerenal failure. In patients with type 1 HRS with very low short-term survival rate, liver transplantation is the ideal treatment. Systemic vasoconstrictor therapy with terlipressin (combined with intravenous human albumin), noradrenaline (combined with albumin and furosemide) or midodrine (combined with octreotide and albumin) may improve renal function in patients with type 1 HRS waiting for liver transplantation. MARS (for Molecular Adsorbent Recirculating System) and the transjugular intrahepatic portosystemic shunt may also improve renal function in these patients. In patients with cirrhosis, acute tubular necrosis is mainly due to an ischemic insult to the renal tubules. Studies are needed on the natural course and treatment (e.g., renal-replacement therapy) of acute tubular necrosis in patients with cirrhosis.
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PMID:Diagnosis and treatment of acute renal failure in patients with cirrhosis. 1722

Envenomation by the sea anemone Phyllodiscus semoni causes fulminant dermatitis and, rarely, acute renal failure in humans. Here, we investigated whether the venom extracted from the nematocysts (PsTX-T) was nephrotoxic when administered intravenously in rats and whether PsTX-T induced activation of the complement system. Although small dose of PsTX-T induced acute tubular necrosis in rats resembling pathology seen in patients, kidneys displayed glomerular injury with glomerular endothelial damage, thrombus formation, mesangiolysis, and partial rupture of glomerular basement membrane, accompanied by severe tubular necrosis at 24 hours after administration of 0.03 mg of PsTX-T per animal, similar to the glomerular findings typical of severe hemolytic uremic syndrome. The early stage injury was accompanied by specific PsTX-T binding, massive complement C3b, and membrane attack complex deposition in glomeruli in the regions of injury and decreased glomerular expression of complement regulators. A pathogenic role for complement was confirmed by demonstrating that systemic complement inhibition reduced renal injury. The isolated nephrotoxic component, a 115-kd protein toxin (PsTX-115), was shown to cause identical renal pathology. The demonstration that PsTX-T and PsTX-115 were highly nephrotoxic acting via induction of complement activation suggests that inhibition of complement might be used to prevent acute renal damage following envenomation by P. semoni.
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PMID:A protein toxin from the sea anemone Phyllodiscus semoni targets the kidney and causes a severe renal injury with predominant glomerular endothelial damage. 1760 Jan 20

Acute renal failure that is associated with macroscopic hematuria (ARF-MH) is a widely known complication of IgA nephropathy (IgAN). Although spontaneous recovery of renal function after cessation of MH has been described, no long-term outcome studies have been performed. The outcome of patients who had biopsy-proven IgAN and presented an ARF-MH episode in the period 1975 through 2005 was studied. Thirty-six episodes of ARF-MH that occurred in 32 patients were identified. A complete recovery of baseline renal function after cessation of MH was observed in 27 (group 1); in the remaining nine episodes (25%; group 2), estimated GFR (eGFR) did not reach the baseline value. Final eGFR was 89 +/- 28 ml/min per 1.73 m(2) in group 1 patients and 38 +/- 12 ml/min per 1.73 m(2) in group 2 patients (P = 0.0005). The duration of MH was significantly longer in group 2 patients: 33.7 +/- 25.3 versus 15.4 +/- 18.4 d (P = 0008). A high proportion of tubules that were filled by red blood cell casts and had signs of acute tubular necrosis were the most striking histologic abnormalities. In conclusion, a significant proportion (25%) of ARF-MH in IgAN did not recover the baseline renal function after the disappearance of MH. Duration of MH longer than 10 d, age >50 yr, decreased baseline eGFR, absence of previous episodes of MH, and the severity of tubular necrosis were significant risk factors for an incomplete recovery of renal function.
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PMID:Factors that determine an incomplete recovery of renal function in macrohematuria-induced acute renal failure of IgA nephropathy. 1769 87

Military use of depleted uranium (DU) has renewed interest in the toxicology of this metal. In this study, the nephrotoxicity of single exposure DU was assessed with and without pre-exposure stress. Adult male Sprague-Dawley rats (n=288) were administered a single IM dose of 0, 0.1, 0.3 or 1.0 mg/kg DU. Corticosterone concentrations (ng/ml, mean+/-SD) were 763.65+/-130.94 and 189.80+/-90.81 for swim stressed and unstressed rats. Serum and kidney uranium concentration, hematocrit, chemistry, and renal histology were assessed on sacrifice days 1, 3, 7 and 30 post-DU-dosing. Dose related increases in serum and kidney uranium were noted. DU concentration peaked day 1 in the kidney and days 3-7, in the serum. Dose-related elevations of Cr and BUN concentrations were seen on days 3 and 7. A decline in serum albumin coincided with Cr and BUN suggesting protein losing nephropathy. Dose related acute tubular necrosis and proliferative glomulonephritis were seen. Tubular regeneration in low dose rats was almost complete by day 30. High dose rats had extensive tubular necrosis and delayed regeneration with focal residual chronic interstitial nephritis and cortical scarring. Glomular changes were reversed in all treatment groups by day 30. Stress exposure had no impact on any measured renal parameter.
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PMID:Temporal clinical chemistry and microscopic renal effects following acute uranyl acetate exposure. 1809 45

Escherichia coli strains producing Shiga toxins (Stxs) colonize the lower gastrointestinal tract and cause watery diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome (HUS). HUS is characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Oliguria associated with acute tubular necrosis and microangiopathic thrombosis has been reported as the most common cause of renal failure in Argentinean children. Our study was undertaken to obtain a model of HUS in rats that was similar to the clinical and renal histopathology findings described in humans. Rats were intraperitoneally inoculated with culture supernatant from recombinant E. coli expressing Stx2. Glomerular filtrate volume evaluated from clearance of creatinine resulted in a progressive reduction (from 53% at 24 h to 90% at 48 h). Urine volume increased significantly at 24 h but returned to normal levels at 48 h. Evidence of thrombocytopenia, anemia and leukocytosis was documented. Macroscopic analysis revealed a hyperemic peritoneal face with intestinal water accumulation. The kidneys were friable and congestive. Histopathological analysis showed glomerular and tubular necrosis as well as microangiopathic thrombosis. Our findings indicated vascular damage and kidney lesions similar to those described in humans with HUS.
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PMID:Development of an experimental hemolytic uremic syndrome in rats. 1825 62

Cephaloridine (CER) is a classical beta-lactam antibiotic that has long served as a model drug for the study of cephalosporin antibiotic-induced acute tubular necrosis. In the present study, we analyzed gene expression profiles in the kidney of rats given subtoxic and toxic doses of CER to identify gene expression alterations closely associated with CER-induced nephrotoxicity. Male Fischer 344 rats were intravenously injected with CER at three different dose levels (150, 300, and 600 mg/kg) and sacrificed after 24 h. Only the high dose (600 mg/kg) caused mild proximal tubular necrosis and slight renal dysfunction. Microarray analysis identified hundreds of genes differentially expressed in the renal cortex following CER exposure, which could be classified into two main groups that were deregulated in dose-dependent and high dose-specific manners. The genes upregulated dose dependently mainly included those involved in detoxification and antioxidant defense, which was considered to be associated with CER-induced oxidative stress. In contrast, the genes showing high dose-specific (lesion-specific) induction included a number of genes related to cell proliferation, which appeared to reflect a compensatory response to CER injury. Of the genes modulated in both manners, we found many genes reported to be associated with renal toxicity by other nephrotoxicants. We could also predict potential transcription regulators responsible for the observed gene expression alterations, such as Nrf2 and the E2F family. Among the candidate gene biomarkers, kidney injury molecule 1 was markedly upregulated at the mildly toxic dose, suggesting that this gene can be used as an early and sensitive indicator for cephalosporin nephrotoxicity. In conclusion, our transcriptomic data revealed several characteristic expression patterns of genes associated with specific cellular processes, including oxidative stress response and proliferative response, upon exposure to CER, which may enhance our understanding of the molecular mechanisms behind cephalosporin antibiotic-induced nephrotoxicity.
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PMID:Transcriptomic analysis of nephrotoxicity induced by cephaloridine, a representative cephalosporin antibiotic. 1850 Jul 88

The distinction between T-cell-mediated rejection (TCMR) and other causes of kidney transplant dysfunction such as tubular necrosis requires biopsy. Subclinical rejection (SCR), an established risk factor for chronic allograft dysfunction, can only be diagnosed by protocol biopsy. A specific non-invasive biomarker to monitor immunological graft status would facilitate diagnosis and treatment of common transplantation-related complications. To identify possible markers, we measured urinary mRNA levels of several cytolytic proteins by quantitative PCR. Our cohort of 70 renal transplant recipients had biopsy proven type I and type II TCMR, acute tubular necrosis, SCR, calcineurin inhibitor-toxicity, cytomegalovirus infection, and stable graft function with normal histology. Granzyme A (GzmA) mRNA was significantly higher in subclinical and acute cellular rejection compared to patients with stable grafts or those with tubular necrosis with 80% sensitivity and up to 100% specificity. Granzyme B and perforin mRNA levels could significantly discriminate acute rejection from stable or tubular necrosis, but were not significantly elevated during SCR. Importantly, only GzmA mRNA remained below detection limits from grafts that were stable and most with tubular necrosis. Hence, the presented data indicate that urinary GzmA mRNA levels may entail a diagnostic non-invasive biomarker to distinguish patients with subclinical and acute cellular rejection from those with tubular necrosis or stable grafts.
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PMID:Urinary granzyme A mRNA is a biomarker to diagnose subclinical and acute cellular rejection in kidney transplant recipients. 2072 May 22


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