Long-term treatment of focal segmental glomerulosclerosis in children with cyclosporine given as a single daily dose.

Cyclosporine (CsA) has been successfully used for treatment of children with focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome (NS) for the last decade. Response rates of 50% to 100% have been reported using twice-daily dosing of 5 to 32 mg/kg/d, achieving trough blood levels of 70 to 500 ng/mL. Treatment has been associated with a high incidence of side effects, including nephrotoxicity, hypertension, gingival hyperplasia, and hirsutism. To determine whether once-daily low-dose CsA could minimize side effects and still induce remission, 21 children with biopsy-proven FSGS and NS, each treated with CsA, 4.6 +/- 0.8 mg/kg/d, with no predetermined target trough blood levels, were studied. Eleven of 21 children (52%) attained complete remission and 5 of 21 children (24%) attained partial remission, for a total response rate of 76%. Mean time to response was 2.8 +/- 0.8 months, and mean duration of therapy was 20.6 +/- 13.7 months. CsA dosage was tapered or stopped in 9 responders; 3 of these patients maintained remission at last follow-up 6 to 13 months later, and 6 patients relapsed at 1.5 to 18.7 months (mean, 8.7 months). Five of these 6 patients responded again when CsA therapy was restarted or the dosage was increased. Twelve of 16 responders were still being administered CsA at last follow-up 11 to 60 months (mean, 24.6 months) later. Five of 21 patients (24%) had no response to CsA during 2 to 27 months of therapy; 4 of these 5 patients developed end-stage renal disease after CsA therapy was stopped. Side effects of CsA therapy were minimal: 1 patient each developed new-onset hypertension or gingival hyperplasia, and no patient had hirsutism or nephrotoxicity. Single daily low-dose CsA appears to be effective for long-term treatment of children with FSGS and NS, with fewer side effects than twice-daily dosing.