Most nonsteroidal anti-inflammatory drugs are anti-proteinuric agents, especially if the patient is sodium-depleted. The decline in urinary protein excretion induced by these agents always markedly exceeds the decrease in glomerular filtration rate. Moreover, the remaining proteinuria appears to be more selective. Together, these findings suggest that the anti-proteinuric effect of nonsteroidal anti-inflammatory drugs is hemodynamically mediated. Nonsteroidal anti-inflammatory agents that reduce renal prostaglandin E2 excretion also decrease proteinuria, whereas sulindac decreases neither prostaglandin E2 nor protein excretion. In a retrospective study, it appeared that administration of indomethacin improved renal survival of nephrotic patients with an initial serum creatinine concentration of less than 110 mumol/liter. The anti-proteinuric effect of indomethacin itself or indomethacin-induced hemodynamic changes might explain this observation.