OBJECTIVES: Glomerular disease and renal failure cause substantial morbidity for patients with sickle cell disease (SCD). Proteinuria is an early manifestation of sickle nephropathy, but the prevalence of proteinuria and its clinical correlations in children with SCD are unknown. STUDY DESIGN: Data were collected prospectively on children with SCD for 10 years including physical measurements, laboratory test results, and clinical complications. Persistent proteinuria was defined as > or =1+ protein on urinalysis for at least 6 months. The glomerular filtration rate was estimated with serum creatinine concentration and height. Proteinuria was correlated with other variables by chi(2) analysis. RESULTS: Proteinuria occurred in 20 of 442 pediatric patients including 15 (6.2%) with sickle cell anemia. Proteinuria increased with age, affecting 12% of older teenagers with sickle cell anemia. Proteinuria was significantly associated with lower hemoglobin concentration, higher mean corpuscular volume, and higher leukocyte count. For children of some ages, proteinuria was associated with complications including stroke, acute chest syndrome, cholelithiasis, and hospitalizations. Glomerular filtration rate hyperfiltration occurred early in life, followed by normalization. CONCLUSIONS: Sickle nephropathy, manifested as persistent proteinuria, begins early in life, occurs in all forms of SCD, and is associated with severity of disease. Early detection of proteinuria may allow therapy to prevent progressive renal insufficiency.