Possible molecular basis for changes in potassium handling in acute renal failure.
Renal potassium excretion is diminished in acute renal failure (ARF). The gastrointestinal tract can compensate for deficient renal potassium excretion in many patients with ARF. For both impaired renal potassium excretion and gastrointestinal compensation in ARF, little is known about the role of potassium channels. We hypothesized that specific changes in the expression of the secretory renal outer medullary potassium channel (ROMK), and the potassium channel regulator, channel-inducing factor (CHIF), in kidney and colon could contribute to changes in potassium handling. Sprague-Dawley rats underwent uninephrectomy and 35 minutes of renal ischemia, followed by varying periods of reperfusion. Renal function, serum and urine potassium levels, and aldosterone levels were measured. The expression of messenger RNA (mRNA) for ROMK and CHIF in the kidney and CHIF in the colon were measured by Northern blot hybridization. Serum creatinine level was increased at 24 hours and started to decline at 48 hours of renal ischemia reperfusion injury (IRI). Serum potassium level was increased at 24 hours, further elevated at 48 hours of IRI, and returned to normal at 7 days of IRI. Urine potassium level was reduced at 24 and 48 hours. Northern blot analysis indicated that the expression of ROMK1 mRNA in the cortex or medulla remained unchanged at 24 hours but profoundly decreased (by 70% to 80%) at 48 hours (n = 4; P < 0.01). The expression of CHIF mRNA in the kidney cortex or medulla decreased by 25% to 30% at 24 hours and 35% to 40% at 48 hours of IRI (n = 4; P < 0.05 for each group). CHIF mRNA expression in the distal colon was moderately increased at 24 hours (approximately twofold) and significantly enhanced at 48 hours (more than threefold; P < 0.01; n = 4) of IRI. Serum aldosterone level was increased approximately threefold at 48 hours of IRI (P < 0.01; n = 6). In conclusion, (1) suppression of ROMK and CHIF in the kidney may contribute to decreased renal potassium excretion in ARF; (2) enhanced expression of CHIF in the distal colon in IRI could be an adaptive response to increase potassium excretion in the colon and help modify hyperkalemia in ARF; and (3) increased aldosterone levels, as a response to hyperkalemia, could be upregulating colonic CHIF.
Rabb
H
H
Division of Nephrology, Hennepin County Medical Center, University of Minnesota, Minneapolis 55415, USA. rabbx003@tc.umn.edu
Wang
Z
Z
Postler
G
G
Soleimani
M
M
D058186:Acute Kidney Injury / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
C094337:Fxyd4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D015221:Potassium Channels; D012333:RNA, Messenger; D011188:Potassium