Shustin L, Wald H, Popovtzer M M
Nephrology Service, Hadassah University Hospital, Jerusalem, Israel.
Am J Kidney Dis. 1998 Oct;32(4):600-4. doi: 10.1016/s0272-6386(98)70023-x.
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.
急性肾小管坏死（ATN）与高钾血症相关。我们已经表明，髓质是ATN中钠（Na +）/钾（K +）泵活性受损的主要部位。CHIF是一种在卵母细胞中引发K +电导的基因，在结肠中受醛固酮调节，在肾脏中受K +摄入量调节。据推测，CHIF在K +稳态中起作用。为了表征ATN中受损的K +处理情况，研究了肾功能受损对肾脏和结肠中CHIF mRNA表达的影响。研究了三组甘油诱导的ATN大鼠：（1）对照组，（2）中度ATN组，和（3）重度ATN组。对照组血清肌酐水平为45±2.1微摩尔/升；中度ATN组为224.8±16.9微摩尔/升；重度ATN组为376.5±15.9微摩尔/升。在重度ATN组中，观察到明显的高钾血症（与对照组相比，P <0.001）。中度ATN组中，髓质、乳头和结肠中CHIF mRNA的相对单位表达（对照组的百分比）分别为16.3%±5.6%（P <0.001）、94.2%±9.3%（P无统计学意义）和165.9%±11.1%（P <0.001）；重度ATN组分别为11.1%±6.4%（P <0.001）、73.7%±4%（P <0.001）和310.8%±27.3%（P <0.001）。这些结果表明：（1）在中度和重度ATN中，髓质中CHIF mRNA显著降低；（2）在重度ATN中，乳头中CHIF mRNA表达降低；（3）CHIF mRNA上调与ATN的严重程度和结肠中醛固酮水平直接相关。这些结果表明，重度ATN中出现的高钾血症至少部分源于肾髓质和乳头中CHIF mRNA的下调。结肠中CHIF mRNA的代偿性增加不足以维持正常的血清K +水平。
