Effect of oral mizoribine pulse therapy for frequently relapsing steroid-dependent nephrotic syndrome

Aim: To evaluate the efficacy of oral mizoribine (MZB) pulse therapy given twice a week for frequently relapsing steroid-dependent nephrotic syndrome (FR-SDNS). Subjects: 16 patients with FR-SDNS with a median age of 11.6 years (range 5.1-17.8 years) were enrolled in the study. This study was a Phase II trial. Methods: The dose of MZB was adjusted to achieve a peak blood level of about 3 mu g/ml (10.0 - 19.7 mg/kg/d, maximum total dose 750 mg) in two divided doses given 2 days a week before a meal. The therapeutic benefits of MZB pulse therapy were assessed based on a comparison of the incidence of relapse (times/year) and the required daily dosage of prednisolone (PSL) before and after therapy. Results: The incidence of relapse after therapy was significantly lower than that before therapy (2.4 +/- 1.6 vs. 3.4 +/- 1.1 times/year, p < 0.05), and the required daily dosage of PSL after therapy was lower than that before therapy (0.39 +/- 0.26 vs. 0.47 +/- 0.24 mg/kg/d; not significant). During the follow-up period, discontinuation of PSL was possible in 6 of 12 patients who showed a decreased rate of relapse after therapy. The age at entry into the study and the peak blood concentration of MZB of these patients were significantly higher than in four patients who did not show a decreased rate of relapse (12.3 +/- 4.3 vs. 7.9 +/- 2.6 years, p < 0.05; 3.00 +/- 0.93 vs. 1.97 +/- 0.36 mu g/ml, p < 0.005, respectively). No adverse effects were observed in any patients. Conclusion: Our results show that MZB pulse therapy is effective in decreasing the frequency of relapse and reducing the required PSL dosage in older pediatric patients with FR-SDNS.