Renal effects of drugs that inhibit prostaglandin synthesis

Abstract

The kidney synthesizes all known prostaglandins and thromboxanes, namely, PGE2, PGI2, PGF(2α), PGD2, and TxA2. The major physiologic functions of these products of arachidonate oxygenation are control of RBF and GFR, stimulation of renin secretion, and modulation of sodium and water excretion. Indomethacin, aspirin, and related drugs inhibit fatty acid cyclo-oxygenase and thereby inhibit prostaglandins synthesis. Indomethacin in conventional doses, reduces renal synthesis of prostaglandins by greater than 75% within 1 hour of parenteral administration. These inhibitory drugs exert few, if any, deleterious effects on renal function in normal man or conscious, normal animals. If animals are volume-depleted, vasoconstricted, or bile-duct-ligated, then indomethacin can significantly decrease RBF, GFR, and sodium and water excretion. Patients with severe liver disease and ascites, lupus erythematosus, primary glomerular disease with and without the nephrotic syndrome, and advanced congestive heart failure will often respond to prostaglandin-synthesis-inhibitors with reductions of GFR and decrements of salt excretion. Suppression of renal prostaglandin synthesis in patients with Bartter's syndrome exerts salutary changes in the clinical course.