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

Abstract Purpose:In primary membranous nephropathy (PMN), treatment includes tailored immunosuppressive protocols to reduce renal 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. We aimed 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 two 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: Mean post-treatment follow-up period was 46.9 ± 11.9 months. Initial mean proteinuria was 5.9 ± 3 g/day, decreasing to 2.1 ± 2.5 g/day by 12 months and to 2 ± 2.4 g/day by 24 months post-treatment. All achieved remission following treatment. Of these, 41% and 59% attained complete (CR) and partial remission (PR), respectively. The median time to remission was 6.68 months, with an average duration of sustained remission noted at 26.5 months. Sixteen patients (72.7%) experienced relapse, necessitating additional RTX doses after 20.1 (50±4) months. Serious adverse events were documented in 3 patients (13.6%). Conclusion: Our 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. This approach might be a effective and safe treatment protocols.