sulindac and Nephritis--Interstitial

Nonsteroidal anti-inflammatory drugs inhibit cyclo-oxygenase activity and thereby reduce prostaglandin synthesis. Studies in humans have used these cyclo-oxygenase inhibitors to examine the role of prostaglandins in controlling renal function. Although short-term studies have demonstrated reductions in effective renal plasma flow, glomerular filtration rate, urinary sodium excretion, and plasma renin activity, long-term administration of nonsteroidal anti-inflammatory drugs does not result in significant or clinically important changes in renal function in normal human subjects. If healthy volunteers are placed on low-sodium diets or treated with diuretics, both renal hemodynamics and salt and water excretion can become prostaglandin-dependent. Studies in normal subjects suggest that sulindac, a nonsteroidal anti-inflammatory drug that undergoes biotransformation in the kidney, does not inhibit renal prostaglandin synthesis or urinary sodium excretion under basal conditions but may impair furosemide-stimulated prostaglandin synthesis and changes in renal function. Doses of sulindac that spare basal renal cyclo-oxygenase do inhibit extrarenal cyclo-oxygenase. The mechanism responsible for this biochemical selectivity of sulindac is not related to a differential sensitivity of the renal cyclo-oxygenase to the active metabolite of sulindac, sulindac sulfide. Sulindac sulfide, in concentrations as low as 1 nM, was equipotent to indomethacin as an inhibitor of prostaglandin E2 synthesis in primary cultures of three renal cell lines. Appropriate clinical use of all nonsteroidal anti-inflammatory drugs, including sulindac, requires careful consideration of risk factors that predispose to nephrotoxicity and careful monitoring when administered to patients at risk.

Topics: Anti-Inflammatory Agents; Arachidonic Acid; Arachidonic Acids; Body Water; Electrolytes; Humans; Kidney; Nephritis, Interstitial; Prostaglandins; Renin; Sulindac

Topics: Acute Kidney Injury; Aged; Cholestasis; Female; Humans; Indenes; Nephritis, Interstitial; Sulindac

Topics: Arthritis, Rheumatoid; Female; Humans; Indenes; Kidney; Middle Aged; Nephritis, Interstitial; Sulindac