The significance of isolated proteinuria in pediatric patients is uncertain. Therefore, we retrospectively studied all children evaluated for this urinary abnormality during the 6-year period from 1986 to 1992. Thirty-one patients (19 males), age 2 to 20 years, were identified as having isolated proteinuria that had persisted for a mean interval of 9.6 +/- 1.9 (SEM) months. The diagnosis was based upon the presence of a urine protein:creatinine ratio > 0.2 in an early-morning specimen. None of the patients had hematuria, edema, or azotemia. Seventeen children underwent a renal biopsy. There was no difference between the patients who were biopsied and those who were not with respect to age, magnitude of proteinuria, glomerular filtration rate (GFR), or serum albumin and cholesterol concentrations. The renal histopathology revealed focal segmental glomerulosclerosis (FSGS) (n = 8), membranous nephropathy (n = 1), postinfectious nephritis (n = 2), focal global glomerulosclerosis (FGGS) (n = 1), and normal kidney tissue (n = 5). Twelve of the patients who did not undergo a kidney biopsy and four of the five children with a normal renal biopsy were followed for at least 12 months; there was complete resolution of the proteinuria in 11 (69%) of these patients. The level of proteinuria did not predict the presence or absence of important kidney disease. However, if isolated proteinuria persists for more than 1 year, it is then unlikely to spontaneously remit and a renal biopsy is indicated to clarify the nature of any underlying glomerulopathy.(ABSTRACT TRUNCATED AT 250 WORDS)