The long-term outcome of 20 preterm infants with extremely low birth weight and acute renal failure in the neonatal period was studied retrospectively over an 18-year period. Those with progressive renal disease are compared with those with normal renal function. Current mean age is 7.5+/-4.6 years (range 3.2-18.5 years). Nine patients showed deterioration in renal function (low GFR group). Increasing proteinuria, as determined by random urine protein/creatinine ratio (Up/c), correlated with deterioration in renal function ( r=0.8, P<0.0001). Prominent risk factors for progression were Up/c >0.6 at 1 year of age [100% sensitivity, 75% positive predictive value (PPV), P<0.01], serum creatinine >0.6 mg/dl at 1 year of age (75% sensitivity, 80% PPV, P<0.01), and a tendency to obesity with body mass index >85th percentile (89% sensitivity, PPV 67%, P=0.03). Loss of renal mass and nephrocalcinosis were not prognostic indicators. This report begins to identify important clinical parameters that should lead to closer surveillance and potential treatment interventions for preservation of renal function in a growing population of surviving low birth weight individuals.