Single-dose daily administration of cyclosporin A for relapsing nephrotic syndrome

Cyclosporin A (CsA) has been reported to be effective as a steroid-sparing agent in frequently relapsing nephrotic syndrome (FRNS). However, low efficacy has sometimes been observed in selected patients with steroid-dependent FRNS. We speculated that a low peak level of CsA in the blood might be the cause, and conducted a prospective pilot study on such steroid-dependent FRNS patients to examine whether single-dose daily administration of CsA would yield a sufficient peak blood level, and therefore a satisfactory steroid-sparing effect. Five children with steroid-dependent FRNS, aged 7-16 years, were enrolled in the study. All had been treated with prednisolone combined with twice daily CsA (T), which was subsequently replaced with the single-dose daily administration protocol (S), because of a poor steroid-sparing effect. Although the mean daily CsA dosage with the S protocol was significantly lower than with the T protocol (S 2.4+/-1.1 mg/kg per day vs. T 3.6+/-0.8 mg/kg per day, P<0.05), the mean peak blood level tended to be higher with the S protocol than the T protocol (S 764+/-122 ng/ml vs. T 358+/-250 ng/ml, P=0.1797) without mean trough blood level elevation. As a result, the minimum dose of prednisolone required for maintenance of clinical remission tended to be lower with the S than the T protocol (S 0.4+/-0.2 mg/kg on alternate days vs. T 0.6+/-0.4 mg/kg on alternate days, P=0.0656). No evidence of CsA nephrotoxicity was observed in a repeat renal biopsy performed 9 months after commencement of the S protocol in one patient. These clinical observations, although on a small number of patients and preliminary, suggest that single-dose daily administration of CsA might be an attractive protocol in selected patients with steroid-dependent FRNS in whom CsA administration by the conventional protocol is associated with a poor steroid-sparing effect.