Daratumumab for Treatment of Refractory Podocytopathy: A Case Report

Primary podocytopathies, manifesting as minimal change disease and primary focal and segmental glomerulosclerosis, previously had a debatable pathogenesis. However, with the recent discovery of antinephrin antibodies, these primary podocytopathies are now considered an antibody-mediated disease. As a result, the therapeutic approach targeting B-cells has become better justified. We present the case of a 30-year-old man who was evaluated for nephrotic syndrome and found to have minimal change disease on the kidney biopsy. He was initially treated with a prolonged course of steroids, achieving complete remission. But, shortly after starting the steroid tapering, the nephrotic syndrome relapsed, with a prolonged course of proteinuria that partially responded to the sequential resumption of corticosteroids, rituximab, calcineurin inhibitors, and obinutuzumab. A repeat kidney biopsy confirmed the primary podocytopathy with a histology of focal and segmental glomerulosclerosis, tip lesion. Then, the patient was treated with weekly subcutaneous daratumumab for 8 doses, resulting in improvement of proteinuria, albuminemia, and resolution of edema that was persistent for more than 2 years. A growing body of evidence supports the rationale of an anti-CD38 strategy in the treatment of immune-mediated kidney diseases resistant to anti-CD20 agents, highlighting the role of anti-B-cell therapy in primary podocytopathy.