Obinutuzumab for Recurrent FSGS After Kidney Transplantation: A Case of Durable Partial Remission

Introduction: While several therapeutic options are commonly used to treat recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation, none have demonstrated consistent efficacy. Emerging data suggest that Obinutuzumab, a novel B-cell-targeting agent, may be a promising alternative in resistant diseases. We present a case illustrating successful management of recurrent FSGS using Obinutuzumab in a patient with a complex clinical background and limited response to conventional therapies. Case Description: A 54-year-old woman with history of papillary urothelial carcinoma, hypertension, hypothyroidism, and end-stage kidney disease secondary to FSGS refractory to multiple therapies (corticosteroids, calcineurin inhibitors, rituximab, ACTH, plasmapheresis and the investigational agent abatacept) with infusion reactions noted to both rituximab and abatacept limiting their use. Within a week of deceased donor kidney transplantation, she developed nephrotic-range proteinuria. Allograft biopsy confirmed FSGS recurrence. She started plasmapheresis in addition to ARB and SGLT-2 inhibitor; she did not tolerate mineralocorticoid receptor antagonist. Obinutuzumab was initiated 4 months post-transplant, with a second course administered 6 months later. Plasmapheresis could not be discontinued but was weaned down to once weekly. Her urine protein/creatinine ratio stabilized at 0.5-0.8 g/g. Her course was complicated by BK nephropathy, with viremia peaking at 6.1 logIU/mL following the second Obinutuzumab infusion. Although SV40 staining was negative on repeat biopsy, we suspect BK viremia contributed to graft dysfunction, given that FSGS lesions were stable with less podocytopathy. Graft function subsequently stabilized as BK viremia declined to approximately ~2-3 logIU/mL (Figure). Discussion: Obinutuzumab offers enhanced antibody-dependent cytotoxicity and reduced complement activation compared to rituximab (Kant et al., 2022). Prospective studies are needed to define the optimal use of Obinutuzumab in post-transplant recurrent FSGS.