Regulation of ROMK and channel-inducing factor (CHIF) in acute renal failure due to ischemic reperfusion injury

Abstract

Listen

Translate article

Acute renal failure caused by ischemia followed by reperfusion is often associated with severe hyperkalemia. The present study was undertaken to characterize the effects of renal ischemia and reperfusion on plasma potassium (K) and on the gene expression of channel-inducing factor (CHIF), a putative K channel regulator, and of ROMK, the distal nephron secretory K channel. The following groups of rats were studied: (1) sham operated (sham); (2) after one hour of ischemia by bilateral renal artery clamping (I), and after one hour of ischemia; (3) one hour of reperfusion (I-R 1 h); (4) 24 hours of reperfusion (I-R 24 h); (5) 48 hours of reperfusion (I-R 48 h); and (6) 72 hours reperfusion (I-R 72 h). The expression of CHIF and ROMK was examined by Northern blot hybridization in renal cortex, medulla, and papilla and in the colon. The abundance of ROMK protein was determined in the renal cortex and medulla by immunoblotting. Maximal plasma creatinine and potassium levels after ischemia and reperfusion were 470 +/- 16 micromol/L, P < 0.0001 versus sham, and 9.65 +/- 0.33 mmol/L, P < 0.0001 versus sham, respectively. The expression of CHIF was significantly down-regulated in the medulla and papilla, with a maximal decrease of 80% at 48 to 72 hours. In contrast, a most significant increase in CHIF mRNA expression (250% of baseline) was noted in the colon after 24 to 48 hours of reperfusion. ROMK expression was reduced in the cortex and was completely abolished in the medulla at 48 to 72 hours of reperfusion. Ischemia and reperfusion injury significantly decreased ROMK protein abundance to 10% of control in the medullary fractions. These results suggest that down-regulation of renal CHIF and ROMK may contribute at least partly to the hyperkalemia of acute renal failure after ischemia and reperfusion, while CHIF up-regulation in the colon may act as a compensatory mechanism of maintaining K balance via increased K secretion.