Effects of two nonsteroidal anti-inflammatory drugs, indomethacin and oxaprozin, on the kidney.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to cause sodium retention and to decrease glomerular filtration rate (GFR). We studied the effects of two such drugs, indomethacin and oxaprozin, a new propionic acid derivative, on renal function of awake, normal human subjects during sustained water diuresis. Although neither drug had a long-term effect on GFR or sodium clearance (CNa), indomethacin (six subjects) but not oxaprozin (seven subjects) transiently reduced GFR and CNa. Given over the short term, oxaprozin caused a reduction in GFR from 113.7 +/- 5.7 to 99.8 +/- 4.7 ml/min (p < 0.01) and CNa from 0.84 +/- 0.07 to 0.61 +/- 0.08 ml/min (p < 0.005). The results were much the same when an additional dose of indomethacin was given to subjects who had been receiving the drug for a week. Inference from clearance data at a time when urinary osmolality (Uosm) remained constant but urine flow per GFR (V/GFR) fell suggests that both drugs stimulated proximal tubular sodium and fluid resorption. Both suppressed renin and aldosterone levels comparably and reduced potassium excretion transiently, but only indomethacin caused a sustained change in serum potassium concentration; serum potassium rose from 4.32 +/- 0.10 to 4.56 +/- 0.11 mEq/l (p < 0.05) after 1 wk. These disparate findings suggest that prostaglandin synthesis inhibition may not be the sole mechanism of action of NSAIDs.
D000450:Aldosterone / Q000652:urine; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D007671:Kidney Concentrating Ability / Q000187:drug effects; D008297:Male; D000077431:Oxaprozin; D010080:Oxazoles / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D011453:Prostaglandins / Q000502:physiology; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D010080:Oxazoles; D011422:Propionates; D011453:Prostaglandins; D000450:Aldosterone; D012964:Sodium; D012083:Renin; D000077431:Oxaprozin; D007213:Indomethacin