Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028961 (oliguria)
 1,847 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary mutations in Tamm-Horsfall protein (THP/uromodulin) gene cause autosomal dominant kidney diseases characterized by juvenile-onset hyperuricemia, gout and progressive kidney failure, although the disease pathogenesis remains unclear. Here we show that targeted expression in transgenic mice of a mutation within the domain of 8 cysteines of THP in kidneys' thick ascending limb (TAL) caused unfolded protein response in younger (1-month old) mice and apoptosis in older (12-month old) mice. While the young mice had urine concentration defects and polyuria, such defects progressively reversed in the older mice to marked oliguria, highly concentrated urine, fibrotic kidneys and reduced creatinine clearance. Both the young and the old transgenic mice had significantly higher serum uric acid and its catabolic product, allantoin, than age-matched wild-type mice. This THP mutation apparently caused primary defects in TAL by compromising the luminal translocation and reabsorptive functions of NKCC2 and ROMK and secondary responses in proximal tubules by upregulating NHE3 and URAT1. Our results strongly suggest that the progressive worsening of kidney functions reflects the accumulation of the deleterious effects of the misfolded mutant THP and the compensatory responses. Transgenic mice recapitulating human THP/uromodulin-associated kidney diseases could be used to elucidate their pathogenesis and test novel therapeutic strategies.
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PMID:Point mutation in D8C domain of Tamm-Horsfall protein/uromodulin in transgenic mice causes progressive renal damage and hyperuricemia. 2914 99

We herein report a 46-year-old man with diabetes who developed acute kidney injury and oliguria after receiving vancomycin to treat his foot infection. Renal biopsy revealed typical features of advanced diabetic nephropathy as well as features of acute vancomycin nephrotoxicity. Several changes typical for acute vancomycin nephrotoxicity, but hitherto not adequately described, were seen. There was an element of acute tubulointerstitial injury associated with frequent tubular casts consisting of typical hyaline casts, pale glassy material suggestive of uromodulin, and distinctive features suggestive of vancomycin deposition. Coprecipitation of vancomycin and uromodulin was confirmed by immunostain. Electron microscopic study showed features supportive for the diagnosis of diabetic nephropathy and distinctive concentric appearance of vancomycin tubular casts within the fibrillary background of uromodulin. The patient's renal function improved rapidly after cessation of vancomycin and initiation of steroid therapy, suggesting that vancomycin-associated tubular injury is potentially reversible over time with proper management.
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PMID:Vancomycin nephrotoxicity: Vancomycin tubular casts with characteristic electron microscopic findings. 3187 55