Inhibition of renal prostaglandin synthesis in man: methodological and clinical implications.

Integrity of renal prostaglandin synthesis is necessary to maintain renal cortical and medullary function in patients with kidney, heart and liver disease. A comparison of the biochemical effects of various non-steroidal anti-inflammatory drugs (NSAIDs) necessitates that renal prostaglandin synthesis, as reflected by urinary immunoreactive prostaglandin excretion, be assessed with proper attention to problems created by seminal fluid contamination, inadequate chromatographic separation of samples, and largely unknown cross reactivities of systemic eicosanoid metabolites with antibodies raised against primary prostaglandins. Most, but not all, clinical studies support the observation that conventional doses of sulindac, administered orally, do not inhibit renal prostaglandin synthesis or alter renal function. Caution is in order, however, about the use of any NSAID, including sulindac at conventional dosage, in patients with severe liver disease as the plasma levels of sulindac sulfide are increased and prolonged compared to patients with normal hepatic function. Furosemide-induced natriuresis is probably not prostaglandin-mediated, in contrast to increased in renal blood flow and renin release. Some NSAIDs can attenuate the efficacy of antihypertensive therapy. Inasmuch as sulindac does inhibit systemic vascular prostacyclin production, its lack of hypertensive effect vis-a-vis other NSAIDs argues in favor of the importance of intrarenal prostaglandin-dependent mechanisms in mediating the hemodynamic effects of non-selective cyclooxygenase inhibitors.