A single-center experience of Obinutuzumab in children with refractory kidney disease

Background This is a retrospective review of children with refractory kidney disease treated with Obinutuzumab. Sparse published data exist in children with nephrotic syndrome and refractory membranous nephropathy treated with Obinutuzumab. Methods The study included all children who received Obinutuzumab and one Ofatumumab. Demographic data, etiology, biopsy results, therapies, eGFR (ml/min/1.73), first AM urine protein/creatinine, follow-up time, and side effects were noted. Clinical response was defined as AM Urine protein/creatinine < 0.3 and/or > 30% improvement in eGFR. Results 46 infusions were given in 29 patients. Etiology: 22 primary nephrotic syndrome (76%), (SDNS 59% and SRNS 41%, 2 were post kidney txp), 5 (17%) chronic GN (C3GN, Lupus nephritis, IgAN, C1QN), and 2 (7%) AIN/AKI. Biopsy diagnosis was obtained in 25 (86%). Failed therapies : all with steroids, Rituximab = 20 (69%), CNI = 19 (66%), MMF = 17(59%), Cytoxan = 7(30%). Twenty-three (82%) had complete remission of the primary nephropathy, and 73% were off all medications. eGFR improved from 49 to 64. Adverse events : 1 had a severe reaction and was unable to get the infusion, 3 patients had infections needing hospitalization (varicella, PCP pneumonia, and septic shock). Follow-up time : 3 to 44 months. Post infusion, all patients were off steroids, except 2 txp patients. Time to relapse was significantly longer with obinutuzumab vs rituximab (19 mos vs 10 mos). Conclusions Obinutuzumab was well tolerated and associated with a high and sustained remission rate in children with various resistant nephropathies. Significant reductions in proteinuria and improvement in eGFR were observed.