Obinutuzumab in Recurrent Focal Segmental Glomerulosclerosis After Pediatric Kidney Transplantation: A Case Report

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Introduction: Recurrence of immuno-mediated forms of FSGS after kidney transplant occurs in about 30% of cases and is often associated with poor outcome. Currently, standardized therapeutic protocols are not available. Possible options are plasmapheresis, rituximab, cyclosporine, and immunoadsorption. We describe a pediatric FSGS recurrence treated with the 2nd generation humanized anti-CD20 antibody obinutuzumab. Case Description: A 3 years-old child with multidrug-resistant FSGS underwent a related-donor kidney transplant. Twelve hours after anastomosis, he developed a severe anuric FSGS recurrence (Fig.1a), treated with high doses of steroids, cyclosporine, rituximab, and plasmapheresis, with poor response. About 3 weeks later, obinutuzumab was given as rescue therapy. One week after drug infusion, proteinuria became sub-nephrotic (48 mg/dL), and kidney function normalized (Fig.1a). After about 7 months on plasmapheresis and standard immunosuppression, proteinuria was absent with a subsequent reduction in plasmapheresis' frequency. A complete and lasting depletion of total CD19+ and memory CD19+CD27+ B cells was maintained for more than 12 months after obinutuzumab infusion (Fig.1b). About one year after transplant, plasmapheresis was discontinued. One month later, in parallel with B-cell reappearance, low-grade proteinuria reappeared (Fig.1a). Therefore, a second rituximab infusion associated with plasmapheresis was planned.Figure 1.: a) Clinical course of patient after kidney transplantation; dashed line represents the normal range of proteinuria. b) Multicolor flow cytometry analysis of circulating total CD19+ B cells and memory CD19+CD27+ B cells; dashed line represents the cut-off of CD19+ B cell recovery. RTX, rituximab; OBI, oobinumumab; Tx, transplantation.Discussion: To our knowledge, this is the first case of pediatric post-transplant FSGS recurrence treated with obinutuzumab, which determined remission and long-lasting B-cell depletion. Further clinical trials are needed to establish the real efficacy of this approach.

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