Diabetes Mellitus Attenuates Response to Anti-CD20 Therapy in Primary Membranous Nephropathy Despite Equivalent B-Cell Depletion

Background and Hypothesis Primary membranous nephropathy (MN) and diabetes mellitus (DM) are common comorbidities, yet the impact of DM on the response to anti-CD20 monoclonal antibody therapy in MN remains unclear. We hypothesized that despite comparable B-cell depletion, MN patients with comorbid DM would exhibit a reduced treatment response compared to non-diabetic MN patients. Methods In this retrospective cohort study, we included adults with primary MN who received at least one complete course of anti-CD20 antibody therapy. Propensity score matching (1:2) was applied based on age, sex, baseline eGFR, urinary protein and PLA2R antibody status. The primary outcome was remission (complete or partial) at 3,6,9,12 months. Secondary outcomes included immunological remission, B-cell depletion, and changes in renal parameters. Multivariable logistic regression, Kaplan-Meier analysis, and subgroup analyses were used to compare outcomes between MN patients with (MN+DM) and without diabetes (MN). Results After matching, 207 patients were included (72MN+DM, 135MN). B-cell depletion and immunological remission rates showed no statistically significant differences between groups over the 12-month follow-up period. However, MN patients had significantly higher overall remission rates at 9 months (94% vs. 77%; OR=4.55, 95% CI=1.52–12.50, P<0.01) and at 12 months (97% vs. 86%; OR=5.26, 95% CI=1.25–20.00, P<0.05). Subgroup analyses confirmed consistently poorer responses in diabetic patients across multiple strata. Safety profiles were similar between groups. Conclusion Despite equivalent B-cell depletion, MN with DM patients show a reduced response to anti-CD20 antibody therapy relative to non-diabetic patients, underscoring that tight glycemic control, early supplementary anti-CD20 dosing for poor response, and combined immunosuppressive regimens may enhance their clinical outcomes.