Comparative effects of nabumetone, sulindac, and ibuprofen on renal function.
OBJECTIVE
Nonsteroidal antiinflammatory drugs (NSAID) have been associated with hemodynamically mediated acute renal failure. There appear to be differences among NSAID in producing this effect. We compare renal effects of ibuprofen, sulindac, and nabumetone.


METHODS
Seventeen women over age 56 receiving hydrochlorothiazide and fosinopril for hypertension 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 ibuprofen for 1 month with intervening 2 week control periods. After each period renal function was assessed by inulin and para-aminohippurate clearances and urinary prostaglandins were measured.


RESULTS
No overall statistical differences among the NSAID were observed. However, there were clinically meaningful differences during ibuprofen therapy: 4 patients developed a clinically significant decrease in renal function; during sulindac therapy one of these also developed a clinically significant decrease in renal function. During nabumetone there were 0 episodes of clinically significant decrease in renal function. Using Gomez equations, glomerular hydrostatic pressure and afferent and efferent arteriolar resistances were estimated. None changed overall during any intervention. However, the 4 patients who developed decreased renal function while taking ibuprofen were analyzed separately. Glomerular hydrostatic pressure decreased 15%; afferent arteriolar resistance increased 85%. These changes were associated with marked decreases in vasodilatory prostaglandins compared to patients receiving ibuprofen who did not develop decreases in renal function.


CONCLUSIONS
There are differences in effect on renal function among NSAID. These can be correlated with specific alterations in suppression of the cyclooxygenase system cascade and related to changes in the hemodynamic control of glomerular filtration.
Cook
M E
ME
Section of Nephrology, LSU Medical School, New Orleans 70112, USA.
Wallin
J D
JD
Thakur
V D
VD
Kadowitz
P J
PJ
McNamara
D B
DB
Garcia
M M
MM
Lipani
J A
JA
Poland
M
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002074:Butanones / Q000494:pharmacology*; D018592:Cross-Over Studies; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008875:Middle Aged; D000077430:Nabumetone; D011453:Prostaglandins / Q000378:metabolism; D013467:Sulindac / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D004573:Electrolytes; D011453:Prostaglandins; D013467:Sulindac; D013929:Thromboxane B2; D000077430:Nabumetone; D007052:Ibuprofen