Acute, usually reversible, renal failure has been observed in patients with normal or minimally altered glomeruli on renal biopsy. This review aims to examine the clinical features of acute renal failure in these patients and to evaluate factors that may contribute to the reduction in glomerular filtration rate (GFR). In an analysis of 79 cases affecting 75 patients reported in the English literature since 1966, with acute renal failure associated with minimal change disease or mild histopathological changes in glomeruli, the average age was 58 +/- 2 years (mean +/- 5 SEM), urine protein excretion 11.6 +/- 0.6 g/d, and serum albumin level 19 +/- 1 g/L (1.9 +/- 0.1 g/dL). Acute renal failure was documented an average of 29 +/- 5 days after onset of nephrotic syndrome, and persisted for 7 weeks in 62 episodes in the 58 patients in whom recovery of renal function occurred. Fourteen patients died of uremia or required chronic dialysis, and 3 were lost to follow-up. Although plasma volume depletion was sometimes cited as the cause of renal failure, objective signs of hypovolemia were not documented and most patients did not improve after treatment designed to correct volume deficits. In contrast, histopathological changes consistent with acute tubular necrosis (ATN) were observed in at least 60% of cases. Since the pathogenesis of acute renal failure in minimal change nephrotic syndrome is unknown, we evaluated hemodynamic determinants of GFR in patients with minimal change disease with normal or near-normal renal function, and in relevant animal models, to obtain insights into the effect of nephrotic syndrome on GFR. Although acute renal failure is uncommon, GFR is reduced concurrently with nephrotic syndrome in approximately 30% of children and adults. Absolute and effective blood volume and renal plasma flow are relatively well preserved. However, clinical and experimental observations suggest that the glomerular ultrafiltration coefficient may be reduced by as much as 50%. These findings, together with renal biopsy changes in cases with acute renal failure, suggest that severe reductions in GFR in some patients with minimal change nephrotic syndrome may result from an interaction between acute ischemic tissue injury and preexisting intrinsic renal abnormalities.