Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome

Abstract

Background: We designed a prospective and randomized trial of mizoribine (MZR) therapy combined with prednisolone (PSL) for idiopathic membranous nephropathy (IMN) with steroid-resistant nephrotic syndrome (SRNS). Methods: Patients with IMN were divided into 2 groups, and MZR combined with PSL was administered for 2 years. PSL was initially prescribed at 40 mg/day and tapered. MZR was given once-a-day at 150 mg and 3-times-a-day at 50 mg each to groups 1 and 2. Serum MZR concentrations from 0 to 4 h after administration were examined within one month of treatment. The concentration curve and peak serum level (Cmax) of MZR were estimated by the population pharmacokinetic (PPK) parameters of MZR. Results: At 2 years, 10 of 19 patients (52.6 %) in group 1 and 7 of 18 patients (38.9 %) in group 2 achieved complete remission (CR). The time-to-remission curve using the Kaplan–Meier technique revealed an increase in the cumulative CR rate in group 1, but no significant difference between the groups. Meanwhile, there was a significant difference in Cmax between groups 1 and 2 (mean ± SD: 1.20 ± 0.52 vs. 0.76 ± 0.39 μg/mL, p = 0.04), and Cmax levels in CR cases were significantly higher than those in non-CR cases. Receiver operating characteristic analysis showed that Cmax more than 1.1 µg/mL was necessary for CR in once-a-day administration. Conclusion: Administration of MZR once a day is useful when combined with PSL for treatment of IMN with SRNS. In addition, it is important to assay the serum concentration of MZR and to determine Cmax, and more than 1.1 µg/mL of Cmax is necessary for CR.