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)

Acute tubular necrosis (ATN) is associated with hyperkalemia. We have shown that the medulla is the main site of impaired sodium (Na+)/potassium (K+) pump activity in ATN. CHIF, a gene that evokes K+ conductance in oocytes, is regulated in the colon by aldosterone and in the kidney by K+ intake. It is assumed that CHIF has a role in K+ homeostasis. To characterize the impaired K+ handling in ATN, the effect of impaired renal function on CHIF mRNA expression in the kidney and colon was studied. Three groups of rats with glycerol-induced ATN were studied: (1) control group, (2) moderate-ATN group, and (3) severe-ATN group. Serum creatinine levels in the control group were 45+/-2.1 micromol/L; in the moderate-ATN group, 224.8+/-16.9 micromol/L; and in the severe-ATN group, 376.5+/-15.9 micromol/L. In the group with severe ATN, significant hyperkalemia (P < 0.001 v control group) was noted. The expression of CHIF mRNA in relative units (percentage of control) in the moderate-ATN group, in the medulla, papilla, and colon, was 16.3%+/-5.6% (P < 0.001), 94.2%+/-9.3% (P=not significant ), and 165.9%+/-11.1% (P < 0.001); and in the severe-ATN group was 11.1%+/-6.4% (P < 0.001), 73.7%+/-4% (P < 0.001), and 310.8%+/-27.3% (P < 0.001), respectively. These results show that (1) in both moderate and severe ATN, CHIF mRNA is dramatically reduced in the medulla, (2) in severe ATN, CHIF mRNA expression decreases in the papilla, and (3) CHIF mRNA is upregulated in direct relationship to the severity of ATN and to the levels of aldosterone in the colon. These results suggest that the hyperkalemia that occurs in severe ATN stems at least in part from the downregulation of CHIF mRNA in the kidney medulla and papilla. The compensatory increase in colonic CHIF mRNA is not sufficient to maintain normal serum K+ levels.
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PMID:Role of down-regulated CHIF mRNA in the pathophysiology of hyperkalemia of acute tubular necrosis. 977 21