Renal effects of oral prostaglandin supplementation after ibuprofen in diabetic subjects: A double-blind, placebo-controlled, multicenter trial

Prostaglandins of the E series (PGE) are known to contribute to the maintenance of renal hemodynamics in subjects with chronic renal insufficiency. Agents that block PGE synthesis, nonsteroidal anti-inflammatory agents (NSAID), are widely used by people with renal insufficiency. This study was undertaken in subjects with renal insufficiency secondary to diabetes to evaluale the acute effects of a PGE₁ analog, misoprostol, on NSAID-induced changes in RBF, as calculated by para-aminohippurate clearance, and GFR, as calculated by inulin clearance. Sodium excretion was also assessed. Twenty-five fasting subjects with a mean age of 56 ± 4 yr received 800 mg of ibuprofen orally. A concomitant dose of either a placebo (PL) or 200 μg of misoprostol was also given. This was followed in 1 h by either a placebo or an additional 200-μg dose of misoprostol. Measurements for the determination of RBF, GFR, blood pressure, and fractional excretion of sodium were performed every 30 min for the next 5 h. The greatest reduction in both GFR (-25 ± 7 mL/min per 1.73 m² PL versus -10 ± 4 mL/min per 1.73 m², misoprostol ΔGFR; P < 0.05) and RBF (-48 ± 21 mL/min per 1.73 m² PL versus -15 ± 8 mL/min per 1.73 m², M ΔRBF; P < 0.05) occurred approximalely 2 h after the NSAID dose. No significant differences were noted in blood pressure, fractional excretion of sodium, or other measured parameters between groups during the entire study. Gastrointestinal upset was the most common side effect observed in both groups. It was concluded that the PGE₁ analog misoprostol blunts the acute renal hemodynamic effects of NSAID. Its use for the long-term preservation of renal function in this population, however, remains to be established.