Subcutaneous Daratumumab in Recurrent Posttransplant Focal Segmental Glomerulosclerosis: A Report of 2 Cases

Recurrent primary focal segmental glomerulosclerosis (FSGS) after kidney transplantation requires prolonged treatment, often with unsatisfactory results. We report 2 cases of FSGS recurrence that achieved remission with subcutaneous daratumumab and propose novel mechanisms of its action that demonstrate efficacy in this disease. The first patient was a 51-year-old woman who experienced early FSGS recurrence 1 month after transplantation. With regular biweekly plasma exchange, her daily proteinuria was 1-1.5 g, and the estimated glomerular filtration rate was 43 mL/min/1.73 m². Although 2 doses of rituximab depleted CD19/20 B lymphocytes, they were ineffective in reducing proteinuria, leading to the reintroduction of plasma exchange. Based on histological persistence of FSGS at the 1-year surveillance biopsy, subcutaneous daratumumab treatment was initiated, which led to a rapid decrease in proteinuria and disease remission. The second patient was a 25-year-old woman with a second relapse of FSGS 7 years after transplantation, which was immune adsorption dependent as rituximab was ineffective in inducing remission. A kidney biopsy performed 2 years later showed persistence of FSGS as well as chronic active antibody-mediated rejection. Daratumumab treatment was initiated using the chronic active antibody-mediated rejection treatment protocol. With this treatment, daily proteinuria decreased from 6 g to 0.3-0.5 g, and immune adsorption was discontinued. In conclusion, daratumumab shows promise in controlling recurrent FSGS in selected kidney transplant recipients with potential mechanisms beyond plasma and natural killer cells.