What question did this study set out to answer?

To evaluate the safety and efficacy of combined anti-CD20 and anti-CD38 therapy in posttransplant FSGS recurrence.

January 22, 2026Transplantation Direct0 citationsOpen Access

Combined Anti-CD20/Anti-CD38 Therapy in Posttransplant Focal Segmental Glomerulosclerosis Recurrence: A Retrospective, International, Multicenter Study

PCPaolo CravediIcahn School of Medicine at Mount Sinai UMUmberto MaggioreUniversity of Parma GMGabriele MortariIstituto Giannina Gaslini

Key Points

To evaluate the safety and efficacy of combined anti-CD20 and anti-CD38 therapy in posttransplant FSGS recurrence.
Retrospective analysis of 16 patients with FSGS recurrence posttransplant
Patients received either anti-CD20 plus anti-CD38 monoclonal antibodies or anti-CD38 alone
Evaluation of remission status and adverse events over a median follow-up of 11 months
Complete remission achieved in 5 patients, partial remission in 11
13 patients remained in remission at last follow-up
Overall kidney function improved after treatment
Significant decline in serum IgM levels post-treatment, with no severe adverse events reported

Abstract

Background. Focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation is a leading cause of allograft failure and remains difficult to treat. Standard therapies, including plasma exchange (PEX) and rituximab, are often ineffective and poorly tolerated. Growing evidence implicates immune-mediated circulating factors, such as IgG and IgM autoantibodies, in disease pathogenesis. Given the central role of memory B cells and plasma cells in antibody production, we tested the safety/efficacy profile of a combined B-cell and plasma cell–depleting approach with rituximab and daratumumab in patients with posttransplant FSGS recurrence. Methods. This is a retrospective analysis of a multicenter, international cohort of sixteen patients (median age 37 y) with biopsy-proven FSGS recurrence posttransplant who received anti-CD20 plus anti-CD38 monoclonal antibodies or anti-CD38 alone. The majority of patients were resistant to common therapies, including rituximab and PEX. Results. The treatment achieved complete or partial remission in 5 and 11 patients, respectively. Five experienced proteinuria relapse, and 4 responded to repeated daratumumab alone. At the last follow-up (median 11 2–18 mo), 13 patients are still in remission and PEX was discontinued in all but 3 cases. Overall, kidney function improved after treatment, and no severe acute or chronic adverse events were reported. Serological analysis revealed a significant decline in IgM, but not in IgG, after treatment. Conclusions. Despite the retrospective, nonrandomized design, the temporal association between treatment and remission supports an effect of anti-CD38 monoclonal antibody alone or in combination with anti-CD20. Treatment is safe and may confer enhanced efficacy over standard approaches. Prospective, mechanistic studies are warranted to validate these findings and delineate the immunopathogenesis of FSGS recurrence.

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