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

Abstract

BackgroundWe 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).MethodsPatients 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 (C max) of MZR were estimated by the population pharmacokinetic (PPK) parameters of MZR.ResultsAt 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 C max between groups 1 and 2 (mean ± SD: 1.20 ± 0.52 vs. 0.76 ± 0.39 μg/mL, p = 0.04), and C max levels in CR cases were significantly higher than those in non-CR cases. Receiver operating characteristic analysis showed that C max more than 1.1 µg/mL was necessary for CR in once-a-day administration.ConclusionAdministration 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 C max, and more than 1.1 µg/mL of C max is necessary for CR.

Immunosuppression therapy for idiopathic membranous nephropathy: systematic review with network meta-analysis

“…Rituximab was compared with non-immunosuppressive therapy (1 trial, 75 participants) [ 11 ]. Mizoribine was compared with steroid monotherapy (1 trial, 36 participants) [ 43 ] and also against different doses of mizoribine (1 trial, 37 participants) [ 66 ]. Azathioprine was compared with non-immunosuppressive therapy (2 trials, 23 participants) [ 24 , 25 ].…”

Herbal Medicine “Shulifenxiao” Formula for Nephrotic Syndrome of Refractory Idiopathic Membranous Nephropathy

“…It is well known that MN has a high spontaneous remission rate ( Saito et al, 2017 ), and it can be concluded that some patients achieve spontaneous remission. In order to exclude such potential spontaneous remission cases, we reviewed the proteinuria and serum albumin levels 6°months prior to the TCM treatment.…”

“…W. Chen et al ( Chen et al, 2013 ) reported a benefit of combining TAC with prednisone in treating 14 adults Chinese RIMN patients, that remission was attained in 11/14 patients (78.6%: CR 35.7% and PR 42.9%) at the end of follow-up. T. Saito et al ( Saito et al, 2017 ) treated 19 patients with Mizoribine (MZR) in combination with prednisolone, and CR was attained in only 10/19 (52.6%) patients after more than 2°years of treatment. F.B.…”

Membranous nephropathy in a Russian population

“…Монотерапию ГКС проводили в отдельных, редких случаях, в основном при противопоказаниях к назначению цитостатических препаратов. Одним из средств лечения больных МН является ритуксимаб, который применен в комбинации с цитостатиками или в качестве монотерапии в небольшой части случаев и имеет определенные перспективы [55][56][57] наряду с такролимусом, мизорибином и адренокортикотропным гормоном [58][59][60].…”