Effects of oral prostaglandins on indomethacin-induced renal failure in patients with cirrhosis and ascites.

Nonsteroidal antiinflammatory drugs (NSAID), such as indomethacin, reduce production of renal prostaglandins and markedly impair renal function in patients with cirrhosis and ascites. To determine if simultaneous administration of oral prostaglandin analogs minimizes the renal impairment, 10 patients received indomethacin and either misoprostol or placebo in a double-blind, crossover study. Indomethacin reduced urinary sodium from 23 +/- 9 to 8 +/- 4 microEq/min in 4 hours. Misoprostol with indomethacin tended to prevent the fall in urinary sodium (from 35 +/- 15 to 46 +/- 21 microEq/min at 4 hours), but sodium excretion fell to the same level in both groups by 8 hours (6 +/- 3 microEq/min). Indomethacin reduced creatinine clearance in 4 hours by 49%; misoprostol plus indomethacin reduced creatinine clearance by only 34%. Misoprostol tended to minimize or delay the nephrotoxic effects of indomethacin, suggesting that more potent prostaglandin analogs may prevent the renal impairment induced by NSAID.