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

Abstract

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 m², 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.

Keywords: long-term outcome; membranous nephropathy; remission; rituximab.

Graphical abstract

Figure 1

Proportion of complete remission (blue), partial remission (dark red), reduction of proteinuria ≥ 50% (light orange), and nonresponse (green) over time.

Figure 2

Flowchart of patients with membranous nephropathy treated with rituximab included remission, failure, and end-stage kidney disease progression with therapy changes. ACTH, adrenocorticotropic hormone; RTX, rituximab.

Figure 3

Comparative of the Kaplan Meier plot for renal survival in months in patients with MN treated only with RTX after being included versus all patients in the cohort. MN, membranous nephropathy; RTX = rituximab.