Combination of B-cell-guided rituximab and low-dose tacrolimus for primary membranous nephropathy: a retrospective cohort study

Background B-cell-targeted therapy with rituximab (RTX) has become a first-line option for primary membranous nephropathy (PMN), but current regimens incur substantial medical costs, and some patients show suboptimal responses. The combination of RTX with immunosuppressants has garnered increasing interest, yet its efficacy and optimal dosing remain unclear. This study compared the efficacy and safety of B-cell-guided RTX combined with low-dose tacrolimus (TAC) versus standard RTX monotherapy for the treatment of PMN. Methods This retrospective analysis included 116 patients diagnosed with PMN between December 2022 and December 2024. All participants were diagnosed based on clinical evaluation and renal biopsy pathology. Of these patients, 57 finally received B-cell-guided RTX combined with low-dose TAC (observation group), while 38 received RTX monotherapy (standard group). In the observation group, RTX dosage was adjusted based on B-lymphocyte counts until B-cell depletion was achieved, accompanied by long-term oral low-dose TAC (0.02 mg/kg/day). Follow-up was conducted monthly after treatment to monitor peripheral blood lymphocyte subsets. RTX was re-administered if CD19+ B-lymphocytes rebounded to 5 cells/μL and the patient had not achieved complete remission. The standard group received two 1 g doses of administered 2 weeks apart. Over a 6-months follow-up, remission rates, incidence of adverse events, and treatment costs were compared between the two regimens. Results The overall remission rate in the observation group was 71.93%, with complete and partial remission rates of 31.58% and 40.35%, respectively. In the standard group, the overall remission rate was 68.42%, with complete and partial remission rates of 26.32% and 42.1%, respectively; none of these differences were statistically significant ( P 0.05). Multi-factor Logistic regression analysis identified non-use of renin-angiotensin system inhibitors (RASi) as an independent risk factor for non-remission (OR = 9.113, 95% CI: 1.010, 82.259, P = 0.049), while higher baseline albumin levels served as a protective factor for remission (OR = 0.862, 95% CI: 0.747, 0.995, P = 0.042). The observation group received a significantly lower total dose of RTX (0.3 ± 0.16g vs. 2 g, t = 73.19, P = 0.000) and had reduced immunosuppressive therapy costs (5608.77 ± 2053.41 CNY vs. 26,000 CNY, t = 74.973, P = 0.000), resulting in average savings of approximately 20,391.23 CNY per patient. During treatment, no serious adverse events occurred in the observation group, whereas four serious adverse events were reported in the standard group. Non-serious adverse events totaled 12 in the observation group and 18 in the standard group. Overall safety was significantly higher in the observation group (χ 2 = 12.656, P = 0.001). Conclusion B-cell-guided RTX combined with low-dose TAC effectively induces clinical remission in patients with PMN, with a lower total RTX dose, improved safety profile, and better cost-effectiveness.