Effects of suprofen on the isolated perfused rat kidney.

Although suprofen has been associated with the development of acute renal failure in greater than 100 subjects, the mechanism of damage remains unclear. The direct nephrotoxic effects of a single dose of 15 mg of suprofen were compared in the recirculating isolated rat kidney perfused with cell-free buffer with or without the addition of 5 mg/dL of uric acid. There were no significant differences in renal sodium excretion, oxygen consumption, or urinary flow rates in kidneys perfused with suprofen compared with the drug-free control groups. In contrast, a significant decline in glomerular filtration rate was found after the introduction of suprofen to the kidney perfused with uric acid; no changes were found with suprofen in the absence of uric acid. A significant decrease in the baseline excretion rate of uric acid was found in rats given suprofen, compared with drug-free controls. However, the fractional excretion of uric acid was unchanged between the groups over the experimental period. In summary, suprofen causes acute declines in renal function, most likely by directly altering the intrarenal distribution of uric acid.