Low-Dose Rituximab and Calcineurin Inhibitor Combination as an Effective Treatment Strategy in Relapsed Primary Membranous Nephropathy

Objective: In primary membranous nephropathy (PMN), treatment includes tailored immunosuppressive protocols to reduce progression risks, with relapse being a common challenge. Nevertheless, the existing body of literature on utilizing Rituximab (RTX) and calcineurin inhibitors (CNIs) in such cases is limited. The study aims to document the outcomes associated with the combined use of low-dose RTX and CNIs in the treatment of relapsed PMN patients with a moderate to high risk.

Methods: In this retrospective study, 22 relapsed PMN patients (22.7% female, average age 51.2 ± 12 years) were included. At the time of diagnosis, 27% (n = 6) were identified as high risk and 73% (n = 16) as moderate risk. The patients were treated with 2 doses of 500 mg RTX administered 15 days apart. Low-dose CNI was started (n = 2) or maintained (n = 20) combined with RTX therapy.

Results: The mean follow-up period was 46.9 ± 11.9 months. Initial proteinuria averaged 5.9 ± 3 g/day, decreasing to 2.1 ± 2.5 g/day at 12 months and 2 ± 2.4 g/day at 24 months post treatment. All patients achieved remission, with 41% attaining complete remission and 59% partial remission. The median time to remission was 6.68 months, and the average duration of sustained remission was 26.5 months.

Conclusion: The results suggest that the combination of low-dose RTX and CNI could be a viable and safe treatment option for relapsed PMN patients with a moderate to high risk. The synergistic impact of CNI and RTX may augment treatment effectiveness, enabling the use of reduced RTX dosages.

Cite this article as: Yanık AM, Berke İ, Aykent MB, et al. Low-dose rituximab and calcineurin inhibitor combination as an effective treatment strategy in relapsed primary membranous nephropathy. Turk J Nephrol. 2025;34(4):259-266.