Short-term indomethacin administration does not impair excretion of acute potassium load in humans.
Maintenance treatment with prostaglandin synthesis inhibitors often causes some degree of hyperkalemia, indicating impaired potassium (K) excretion. Hypoaldosteronism probably is a mediating factor, but it is unknown whether these drugs also impair renal K excretion directly. Indomethacin, for example, stimulates NaCl reabsorption in Henle's loop, and thus may impair K excretion by decreasing distal NaCl delivery. We therefore studied the effect of 1 day administration of indomethacin (50 mg tid) on the excretion of a single oral KCl (1 mmol kg-1 body weight) in six healthy volunteers taking a 40 mmol sodium diet. To allow analysis of renal sodium handling, clearance studies were performed during water loading. In this acute setting, indomethacin had no effect on plasma K, and did not decrease plasma aldosterone. However, indomethacin clearly reduced NaCl excretion. Nonetheless, the excretion of the K load was entirely normal. Excretion of the K load was accompanied by increased clearance of phosphate and uric acid, and natriuresis. Data derived from the maximal free water clearance were compatible with increased delivery to and decreased reabsorption from the diluting segment. Occurrence of these effects was not prevented by indomethacin, although overall NaCl excretion remained less than observed without indomethacin. Indomethacin reduced prostaglandin E2 excretion substantially. Apparently, in normal man indomethacin does not impair K excretion directly, even though it greatly reduces NaCl excretion. Moreover, the effects of K on renal NaCl handling, probably contributing to the excretion of a K load, are not dependent on renal prostaglandins.
Van Buren
M
M
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
Van Rijn
H J
HJ
Koomans
H A
HA
D000284:Administration, Oral; D000328:Adult; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced* / Q000378:metabolism; D007213:Indomethacin / Q000008:administration & dosage / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011189:Potassium Chloride / Q000008:administration & dosage
D011189:Potassium Chloride; D011188:Potassium; D007213:Indomethacin