Introduction: Recurrence of FSGS after kidney transplantation is a significant risk of early graft loss in patients who do not respond to therapy, including plasmapheresis (PLEX), optimization of calcineurin inhibitors, and depletion of B cells with anti-CD20 antibody. Rituximab induces B-cell destruction by complement-dependent cytotoxicity that can be impaired by complement inhibitory factors or complement depletion resulting in resistance to rituximab. Obinutuzumab, a second-generation anti-CD20 antibody, induces direct antibody-dependent cytotoxicity and phagocytosis. Overall, B-cell depletion and antibody half-life are higher with obinutuzumab than with rituximab, which translates into superior efficacy and tolerability. Data on obinutuzumab as an adjunct therapy for FSGS recurrence are limited to a few case reports. We present a patient with FSGS recurrence after transplantation who responded to a regimen of PLEX and obinutuzumab.
Methods: The patient was diagnosed with nephrotic syndrome (NS) at 22 months of age and failed to respond to corticosteroids. Kidney biopsy confirmed FSGS. Genetic testing showed variants of unknown significance in 4 genes associated with steroid-resistant NS and FSGS.  He failed to respond to tacrolimus and lipid apheresis at three years of age. He progressed to ESRD at 5.5 years of age.
Results: He received a haplotype match and a preemptive kidney transplant from his mother at six years of age. At the time of the transplant, his native kidneys were removed because of nephrotic range proteinuria. Induction was with thymoglobulin/methylprednisolone, and maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and corticosteroids. On post-transplant day 3, he developed nephrotic range proteinuria with urine protein-to-creatinine ratio (UPCR) of 42.1 mg/mg (normal < 0.2 mg/mg). Tacrolimus trough goal was increased, and daily PLEX was initiated on postoperative day five and continued for five days. The regimen was changed to triweekly PLEX, and after 13 treatments, he had achieved partial remission (UPCR 1.4 mg/mg). Serum creatinine rose to 1.7 mg/dl, and a kidney biopsy showed foot process effacement and acute tubular necrosis but no rejection. His viral studies were negative, and donor-specific antibody testing remained at zero. Tacrolimus's dose was reduced to standard dosing; his creatinine has come down to 0.6 mg/dl over time. Due to persistent proteinuria, he received obinutuzumab 375 mg/m2 on post-transplant day 40. Proteinuria gradually improved and subsequently resolved completely eight months after obinutuzumab administration. 
Conclusions: Although concomitant use of PLEX prevents a definite conclusion about the contribution of obinutuzumab to the treatment of post-transplant FSGS recurrence, the sustained remission is highly suggestive. A clinical trial is needed to evaluate the efficacy of obinutuzumab in managing FSGS recurrence after kidney transplantation.