Rituximab in idiopathic membranous nephropathy

Abstract

Selective depletion of B cells with the mAb rituximab may benefit the autoimmune glomerular disease idiopathic membranous nephropathy (IMN). Here, we describe our experience treating 100 consecutive IMN patients with persistent nephrotic syndrome with rituximab. We defined complete remission as persistent proteinuria <0.3 g/24 h and partial remission as persistent proteinuria <3 g/24 h, each also having >50% reduction in proteinuria from baseline. During a median follow-up of 29 months after rituximab administration, 65 patients achieved complete or partial remission. The median time to remission was 7.1 months. All 24 patients who had at least 4 years of follow-up achieved complete or partial remission. Rates of remission were similar between patients with or without previous immunosuppressive treatment. Four patients died and four progressed to ESRD. Measured GFR increased by a mean 13.2 (SD 19.6) ml/min per 1.73 m(2) among those who achieved complete remission. Serum albumin significantly increased and albumin fractional clearance decreased among those achieving complete or partial remission. Proteinuria at baseline and the follow-up duration each independently predicted the decline of proteinuria. Furthermore, the magnitude of proteinuria reduction significantly correlated with slower GFR decline (P=0.0001). No treatment-related serious adverse events occurred. In summary, rituximab achieved disease remission and stabilized or improved renal function in a large cohort of high-risk patients with IMN.

Figure 1.

Patient flow chart.

Figure 2.

Kaplan–Meier curves for the percentages of participants with IMN achieving complete remission, partial remission, or both. Data are in the study group as a whole (overall, upper panel) and among participants with or without treatment with other immunosuppressants before rituximab administration (first-line therapy, middle panel, and second-line therapy, lower panel, respectively). Twenty-seven of the patients with partial remission eventually achieved complete remission. Thus, in the group achieving the combined end point of partial or complete remission, these patients achieved both events. In this case, time to the first event (partial remission) was considered for survival analysis.

Figure 3.

Kaplan–Meier curves for the percentages of participants with IMN achieving complete remission, partial remission, or both within the subgroup of 18 patients who received a second course of rituximab because of disease relapse after initial complete or partial remission.

Figure 4.

Median 24-hour urinary protein excretion at baseline (month 0), at 3, 6, 9, and 12 months and at 6-monthly evaluations after rituximab administration in the study group as a whole (overall) and in different cohorts with homogeneous follow-up durations.

Figure 5.

Baseline and follow-up GFR, serum albumin, and albumin fractional clearance in the subgroup of participants with clearance evaluations. GFR, measured by the iohexol plasma clearance technique (upper panel), serum albumin levels (middle panel), and albumin fractional clearance (lower panel) at baseline and after rituximab infusion in 37 participants with IMN. Data are in the study group as a whole (overall) or in patients with complete remission, partial remission, or no remission considered separately. Data are mean ± SEM.