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

The toxicity of the anti-cancer drug cis-diamminedichloroplatinum (II) (cisplatin), at 2 to 40 mg per kg, was studied in the frog, Rana pipiens. The LD50 for the drug was approximately 17 mg per kg. Major non-nervous system toxicity occurred in the kidney. Renal failure was manifested as anasarca and increasing blood urea nitrogen (BUN). Histopathological changes included acute tubular necrosis and tubular dilatation, which were more severe at higher doses. Interstitial fibrosis occurred after prolonged survival after a single dose. Ultrastructurally, there was increased electron-dense material in tubular cells, but no specific changes in mitochondria or nuclear structures were seen. Gastro-intestinal toxicity was less severe than in other species and was more prominent at higher doses. Pathological changes consisted of epithelial nuclear atypia and apoptosis. By electron microscopy, there was increased separation of cell borders, depletion of chylomicrons and mucin granules and increases in electron-dense material. Again no specific mitochondrial or nuclear changes were seen. Relatively slight changes were seen in the liver, consisting of altered distribution of rough endoplasmic reticulum and dispersion of nuclear chromatin. Minimal pathology was demonstrated in the haematopoietic system or in the gonads. Thus toxicity of cisplatin in the frog is similar to that seen in mammals, including rodents and man.
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PMID:Toxicity of cis-diamminedichloroplatinum (II) (cisplatin) in the frog, Rana pipiens. 207 54

Nephrogenic fibrosing dermopathy (NFD) is a newly recognized cutaneous fibrosing disorder. To date the etiology, pathogenesis, and clinical course remains unknown. The majority of cases have been in renal dialysis or renal transplant patients. Only four cases have been reported in which patients had acute renal failure and never required dialysis. Currently, there is no effective treatment. A 65-year-old man was hospitalized for pneumonia. During hospitalization he developed acute renal failure secondary to acute tubular necrosis. The patient had woody indurated plaques on his upper extremities and trunk, and brown indurated plaques on his trunk. Histopathological examination revealed a spindle cell proliferation infiltrating through the dermis and subcutis with mild mucin deposition. Nephrogenic fibrosing dermopathy is a novel fibrosing disorder diagnosed clinically and histopatholigically. Currently no risk factors other than renal failure have been identified. Our patient is a unique example of NFD observed in acute renal failure secondary to acute tubular necrosis, never requiring dialysis. We also review the four other cases of acute NFD never requiring dialysis that have been reported in the literature.
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PMID:Nephrogenic fibrosing dermopathy in a patient with acute renal failure never requiring dialysis. 1642 79

Acute kidney injury (AKI) is characterized by acute tubular necrosis (ATN) which involves mainly proximal tubules. Past AKI is associated with higher risk of chronic kidney disease (CKD). The MUC1 mucin is a large glycoprotein responsible for epithelial protection and locates to convoluted distal tubules and collecting ducts. Since MUC1 activates the epithelial-mesenchymal transition (EMT) in carcinoma cells, we hypothesized that MUC1 could be involved in epithelial tubular cell plasticity, a process that not only accompanies epithelial repair, but also participates into kidney fibrosis, histological substratum of CKD. In cultured human proximal cells and in human kidney allograft biopsies, we observed MUC1 induction in proximal tubules displaying ATN. Transient MUC1 induction localized with mesenchymal and stem-cell markers and was associated in vitro with reduced anoikis. In a mouse ischemia-reperfusion (IR) model, Muc1 expression mitigates severe tubular injury, as WT displayed less ATN than Muc1 KO mice. But, WT mice displayed more severe kidney fibrosis than Muc1 KO 28days after ischemia. Besides, sustained Muc1 expression in WT was associated with less kidney M2 macrophages. Human kidney biopsies performed within the first week (W1) of transplantation in the context of IR showed MUC1 W1 induction associated with EMT markers. Protocol biopsies performed 3months after demonstrated sustained abnormal MUC1 induction in atrophic tubules within kidney fibrosis. Altogether these data showed that sustained abnormal MUC1 induction accompanies failing epithelial repair, chronic inflammation and kidney fibrosis. In conclusion, MUC1 exerts opposite effects during kidney response to IR: first protective and then harmful.
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PMID:Dual role of MUC1 mucin in kidney ischemia-reperfusion injury: Nephroprotector in early phase, but pro-fibrotic in late phase. 2836 75