Effects of indomethacin and misoprostol on renal function in healthy volunteers

We have examined the effects on renal function of indomethacin and misoprostol, alone and in combination. Eight healthy volunteers took indomethacin 50 mg tds for one week, and indomethacin plus misoprostol (a synthetic PGE1 analogue) 200 micrograms qds for one week in a crossover design. A separate group (n = 5) took misoprostol alone for one week. 51Cr EDTA GFR rose significantly from baseline after the combination of indomethacin and misoprostol (from mean +/- SD 117 +/- 7.1 to 123 +/- 8.0 mls/min/1.73 m2, p = 0.05). When indomethacin alone was given 51Cr EDTA GFR did not change significantly (120 +/- 9.0 to 117 +/- 9.0 mls/min/1.73 m2). However in 4 of these subjects 51Cr EDTA GFR fell (range 7-19 mls/min/1.73 m2); in each of these the reduction was reversed when the indomethacin was given together with misoprostol. In the whole group the change in 51Cr EDTA GFR, from baseline, after indomethacin plus misoprostol was significantly different from that after indomethacin alone (+6 +/- 8 vs -3 +/- 5 mls/min/1.73 m2 p = 0.05). Misoprostol alone had no effect on GFR. We conclude that misoprostol and indomethacin in combination increase GFR in healthy volunteers, and further studies are now warranted to determine whether misoprostol is beneficial in the prophylaxis and treatment of NSAID-induced renal impairment.