COMPARATIVE EFFECTS OF NABUMETONE, SULINDAC, AND IBUPROFEN ON RENAL-FUNCTION

Objective, Nonsteroidal antiinflammatory drugs (NSAID) have been assoc iated with hemodynamically mediated acute renal failure. There appear to be differences among NSAID in producing this effect. We compare ren al effects of ibuprofen, sulindac, and nabumetone. Methods, Seventeen women over age 56 receiving hydrochlorothiazide and fosinopril for hyp ertension who had osteoarthritis requiring NSAID received 3 different NSAID to evaluate potential varying renal effects, In an investigator blinded randomized study, patients received nabumetone, sulindac, or i buprofen for 1 month with intervening 2 week control periods, After ea ch period renal function was assessed by inulin and para-aminohippurat e clearances and urinary prostaglandins were measured. Results, No ove rall statistical differences among the NSAID were observed. However, t here were clinically meaningful differences during ibuprofen therapy: 4 patients developed a clinically significant decrease in renal functi on; during sulindac therapy one of these also developed a clinically s ignificant decrease in renal function. During nabumetone there were 0 episodes of clinically significant decrease in renal function. Using G omez equations, glomerular hydrostatic pressure and afferent and effer ent arteriolar resistances were estimated. None changed overall during any intervention. However, the 4 patients who developed decreased ren al function while taking ibuprofen were analyzed separately. Glomerula r hydrostatic pressure decreased 15%; afferent arteriolar resistance i ncreased 85%. These changes were associated with marked decreases in v asodilatory prostaglandins compared to patients receiving ibuprofen wh o did not develop decreases in renal function. Conclusion. There are d ifferences in effect on renal function among NSAID. These can be corre lated with specific alterations in suppression of the cyclooxygenase s ystem cascade and related to changes in the hemodynamic control of glo merular filtration.