Patients with sickle cell disease (SCD) may develop kidney dysfunction from childhood. The purpose of this study was to examine the value of serum cystatin C as a marker for glomerular filtration rate (GFR) in children with SCD, as compared to serum creatinine and creatinine clearance (CrCl). Twenty children (ages 9-21, ten males) with SCD with and without albuminuria were studied. The mean serum cystatin for the whole group was 0.89 mg/l (0.5-1.7 mg/l). Mean serum cystatin C was significantly different among the children with proteinuria (n=4), microalbuminuria (n=5), and without albuminuria (n=11) (1.25 mg/l, 0.84 mg/l, and 0.78 mg/l, respectively). The mean GFR derived from serum cystatin was significantly different among these subgroups, becoming abnormal in the proteinuric cohort (63 ml/min per 1.73 m(2)), in contrast to 94 for the microalbuminuric, and 103 for the normal subgroups. Serum creatinine (mean: 0.58 mg/dl, range: 0.3-1.1) did not change significantly with the level of albuminuria. Mean CrCl remained normal to increased within the subgroups, (133 ml/min per 1.73 m(2) for those with proteinuria, 144 for those with microalbuminuria, and 163 for the normal subgroup). We conclude that serum cystatin C correlates with the level of albuminuria and may be a reliable method to measure renal function in SCD.