Renal effects of nonsteroidal anti-inflammatory drugs in chronic glomerular disease

In contrast to a variety of clinical conditions characterized by ineffective circulatory volume, chronic glomerular disease is not usually associated with increased circulating levels of vasoconstrictor hormones. However, a reduction in glomerular prostacyclin production can possibly account for the prostaglandin dependence of renal function in these patients by virtue of the enhanced constrictor effects of angiotensin II on glomerular arterioles and mesangium. The reduction of renal function induced by a nonselective cyclo-oxygenase inhibitor is inversely related to the basal prostacyclin production. Increased renal synthesis of vasoconstrictor thromboxane A2, as noted in patients with systemic lupus erythematosus, might contribute to the cyclo-oxygenase dependence of renal function. Aspirin as well as a variety of structurally unrelated nonsteroidal anti-inflammatory drugs reduce renal function in systemic lupus erythematosus patients. However, the functional consequences of renal cyclo-oxygenase inhibition are partially attenuated in patients with lupus nephritis vis-à-vis other forms of chronic glomerular disease because of concomitant suppression of enhanced glomerular thromboxane A2 production. Animal data consistent with a prevailing functional significance of vasodilator prostaglandins have also been reported. Short-term administration of sulindac at the recommended dosage is relatively safe in patients with chronic glomerular disease because of selective sparing of glomerular cyclo-oxygenase activity. The long-term consequences of selective versus nonselective cyclo-oxygenase inhibition remain to be established in humans. The beneficial effects of a combination of aspirin and dipyridamole in slowing the deterioration of renal function in patients with membranoproliferative glomerulonephritis does provide a rationale for exploring the effects of low-dose aspirin (i.e., 0.5 to 1.0 mg/kg per day), which most effectively suppresses platelet thromboxane A2 production without interfering with renal prostacyclin synthesis.