Aims: To evaluate the efficacy of long-term repeated rituximab treatment in refractory PLA2R-Ab-related membranous nephropathy (MN). Materials & methods: Rituximab was administered at a single dose of 375 mg/m2 and repeated if peripheral B-cell levels were >5/ul in 46 patients with refractory PLA2R-Ab-related MN. Results: The median frequency of rituximab treatment was 3 (IQR 2.0-4.0). A total of 32 (32/46) patients achieved remission (completed remission [CR] or partial remission [PR]) over a median time of 17.0 months, and 10 patients eventually progressed to CR. The proportion of serum PLA2R-Ab depletion was 73.91% (34/46) over a median time of 9 months. Antibody depletion preceded proteinuria remission. Conclusions: Long-term repeated rituximab treatment achieved high kidney and immunological response rates in refractory PLA2R-Ab related MN, and antibody depletion was a prerequisite for proteinuria remission.
Keywords: B cells; PLA2R-Ab; immunotherapy; membranous nephropathy; nephrotic syndrome; refractory; rituximab; treatment response.
Membranous nephropathy (MN) is the leading cause of proteinuria in adults and is mainly manifested as edema. Phospholipase 2 receptor (PLA2R) antibody is detected in 70–80% of patients with MN. Its main treatments are immunosuppressive therapies. The efficacy of traditional immunosuppressant drugs including steroids and alkylating and calcineurin inhibitors in reducing proteinuria have been confirmed; however, several adverse events such as diabetes mellitus, infections, cancer and kidney injury have been reported. Rituximab, a monoclonal antibody against CD20 on B cells, has been verified to be effective, safer and better tolerated in MN. However, the optimal rituximab regimen for MN has not yet been established. Here, we use B-cell-driven long-term repeated rituximab regimen and determine its exciting efficacy for refractory MN.