Treatment with microemulsified cyclosporine in children with frequently relapsing nephrotic syndrome

Background. We previously established a treatment protocol for conventional cyclosporine (Sandimmune, Novartis, Basel, Switzerland) in children with frequently relapsing nephrotic syndrome; similar to 50% of patients remained relapse free for 2 years, without serious adverse events. Recently, microemulsified cyclosporine (Neoral, Novartis), which has a more stable absorption profile than conventional cyclosporine, has been developed. We tested the hypothesis that microemulsified cyclosporine is at least as effective as conventional cyclosporine. Methods. To evaluate the safety and efficacy of microemulsified cyclosporine, a prospective, multicentre trial was conducted according to the previously established protocol, using microemulsified cyclosporine instead of conventional cyclosporine. The duration of treatment was 24 months. During the first 6 months, patients received microemulsified cyclosporine in a dose that maintained the trough level between 80 and 100 ng/mL of cyclosporine. For the next 18 months, the dose was adjusted to maintain a level between 60 and 80 ng/mL. Results. A total of 62 patients (median age, 5.4 years; 48 males, 14 females) were studied. The frequency of relapse decreased from 4.6 +/- 1.4 to 0.7 +/- 1.5 times per year (P < 0.0001). The probability of relapse-free survival at Month 24 was 58.1% (95% confidence interval, 45.8-70.3%). The probability of progression (to frequently relapsing nephrotic syndrome)-free survival at Month 24 was 88.5% (95% confidence interval, 80.4-96.5%). Cyclosporine nephrotoxicity was detected in only 8.6% of patients who underwent renal biopsy after 2 years of treatment. Antihypertensive agents were administered to 12.9% of the patients to control hypertension without severe sequelae. Conclusions. Microemulsified cyclosporine administered according to our treatment protocol is safe and effective in children with frequently relapsing nephrotic syndrome.