Aim: To evaluate the efficacy of single-dose oral mizoribine (MZB) pulse therapy given twice weekly for frequently relapsing steroid-dependent nephrotic syndrome (FR-SDNS).
Methods: The subjects were 8 patients with FR-SDNS with a median age of 6.9 years old (range 3.1 - 18.0 y). The study was performed as a Phase II trial. The MZB dose was adjusted to achieve a peak blood level of 3 - 5 μg/ml (3.9 - 15.9 mg/kg/d, maximum dose: 750 mg) using a single dose given twice weekly before a meal. The therapeutic benefits of MZB pulse therapy were assessed based on a comparison of the incidence of relapse and the required daily dosage of prednisolone (PSL) in the 12 months prior to and following therapy.
Results: The incidence of relapse after therapy was significantly lower than that before therapy (2.5 ± 1.4 vs. 4.3 ± 0.5, p < 0.01) and the required daily dosage of prednisolone (PSL) after therapy was lower than that before therapy (0.48 ± 0.23 vs. 0.52 ± 0.32 mg/kg/d, not significant). However, this therapy was not effective for 3 out of 4 patients treated with cyclosporine. During follow-up, discontinuation of PSL was possible in 4 of 5 patients who showed a decreased rate of relapse after therapy. The peak blood concentration of MZB in these patients was significantly higher than that in 3 patients who did not show a decreased rate of relapse (3.95 ± 0.11 vs. 3.05 ± 0.21 μg/ml, p < 0.01). No adverse effects were observed in any patients.
Conclusion: Our results show that single-dose oral MZB pulse therapy is effective in decreasing the frequency of relapse in some pediatric patients with FR-SDNS. A peak concentration of MZB of ~3.8 - 4.0 μg/ ml may be required for FR-SDNS therapy.