Long-term Outcome of Adult Patients With Membranous Nephropathy Treated With Rituximab.

Introduction: Rituximab (RTX) therapy has become the standard of care for treatment of membranous nephropathy (MN). However, data on hard outcomes such as end-stage kidney disease (ESKD) and loss of estimated glomerular filtration rate (eGFR), are lacking.

Methods: This was a retrospective study on all patients with MN treated with RTX between January 2000 and December 2022. The primary outcomes were ESKD and eGFR loss > 50%. Clinical outcomes were complete remission (CR), partial remission (PR) (reduction in baseline proteinuria ≥ 50% and proteinuria ≤ 3.5 g/24 h), and immunological remission (IR) (serum antiphospholipase A receptor antibody [PLA2R-Ab] depletion).

Results: A total of 159 patients were included (75.5% male, 87.4% White, median age: 58 years); 52.8% had previous immunosuppression (IS). Baseline serum creatinine was 1.50 (1.1-1.9) mg/dl, eGFR was 54.6 (37.4-72.5) ml/min per 1.73 m, proteinuria was 9.2 (6.7-11.9) g/24 h, and serum albumin was 2.7 (2.2-3.2) g/dl; Of the patients, 108 (75.5%) had PLA2R-Ab-associated MN (PLA2R-MN); and 140 of 159 (88.1%) attained CR or PR. Median (interquartile range [IQR]) time to CR and PR were 22.6 (15.5-37.4) and 6.8 (3.6-12.1) months, respectively. Failure to respond to RTX was observed in 11.9% of patients. Previous IS and interstitial fibrosis/tubular atrophy (IFTA) ≥ 25% were independent factors associated with failure to respond to RTX. Patients treated only with RTX with a median follow-up of 62.6 months; 7 of 159 (4.4%) developed ESKD with an estimated renal survival of 97% (95% confidence interval [CI]: 94%-100%) and 95.4% (95% CI: 91.2%-99%) at 5 and 10 years, respectively.

Conclusion: RTX treatment is associated with excellent long-term renal survival that compares favorably with historical survival rates using the cyclic corticosteroids/cyclophosphamide regimen.