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Updated: Jul 30, 2026
Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
Regulation of ROMK and channel-inducing factor (CHIF) in acute renal failure due to ischemic reperfusion injury
D Gimelreich1, M M Popovtzer, H Wald
1Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Acute renal failure following ischemia-reperfusion causes hyperkalemia. Down-regulation of renal channel-inducing factor (CHIF) and ROMK channels contributes to this, while colon CHIF up-regulation may compensate for potassium balance.
Area of Science:
- Nephrology
- Physiology
- Molecular Biology
Background:
- Acute renal failure (ARF) post-ischemia-reperfusion often leads to severe hyperkalemia.
- Understanding potassium regulation during ARF is crucial for patient management.
Purpose of the Study:
- To investigate the impact of renal ischemia-reperfusion on plasma potassium levels.
- To characterize changes in gene expression of channel-inducing factor (CHIF) and ROMK potassium channels in the kidney and colon.
Main Methods:
- Rats underwent sham operation, ischemia, or 1-72 hours of reperfusion.
- CHIF and ROMK gene expression analyzed via Northern blot in renal tissues and colon.
- ROMK protein abundance assessed by immunoblotting in renal cortex and medulla.
Main Results:
- Ischemia-reperfusion significantly elevated plasma creatinine and potassium levels.
- Renal CHIF expression decreased significantly in the medulla and papilla.
- Colon CHIF mRNA expression increased, while renal ROMK expression and protein abundance were markedly reduced, particularly in the medulla.
Conclusions:
- Down-regulation of renal CHIF and ROMK likely contributes to hyperkalemia in ARF.
- Up-regulation of CHIF in the colon may represent a compensatory mechanism for potassium homeostasis.
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