Background: There is paucity of information on rituximab-associated hypogammaglobulinemia (HGG) and its potential infectious consequences in children treated for idiopathic nephrotic syndrome (INS). Methods: A survey was distributed by the European Society Pediatric Nephrology to its members. It addressed the screening and management practices of pediatric nephrology units for recognizing and treating RTX-associated HGG and its morbidity and mortality. Eighty-four centers which had treated an overall 1328 INS children with RTX responded. Results: The majority of centers administered several courses of RTX and continued concomitant immunosuppressive therapy. Sixty-five percent of centers routinely screened children for HGG prior to RTX infusion, 59% during, and 52% following RTX treatment. Forty-seven percent had observed HGG prior to RTX administration, 61% during and 47% >9 months following treatment in 121, 210, and 128 subjects respectively. Thirty-three severe infections were reported among the cohort of 1328 RTX-treated subjects, of whom 3 children died. HGG had been recognized in 30/33 (80%) of them. Conclusions: HGG in steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) children is probably multifactorial and can be observed prior to RTX administration in children with SDNS/FRNS. Persistent HGG lasting >9 months from RTX infusion is not uncommon and may increase the risk of severe infections in this cohort. We advocate for the obligatory screening for HGG in children with SDNS/FRNS prior to, during, and following RTX treatment. Further research is necessary to identify risk factors for developing both HGG and severe infections before recommendations are made for its optimal management. Graphical

Background: Idiopathic nephrotic syndrome (INS) is the most common cause of nephrotic syndrome in children. A hallmark of the disease is the rapid remission of proteinuria following a high dose of steroids. Recurrent disease or steroid dependence are common, leading to a high steroid burden and the introduction of steroid sparing therapy. Anti-CD20 antibodies have been increasingly used with excellent results in complicated INS. Nevertheless, their use can be limited by the occurrence of infusion-related reactions (IRRs). Methods: This report discusses further treatment options for children who are intolerant to RTX and presents the first report of a successful switch to obinutuzumab (OBI) for a child with difficult-to-treat steroid-dependent nephrotic syndrome (SDNS) and RTX intolerance who was unresponsive to a desensitization protocol. Results: A 12-year-old boy with SDNS since the age of 2, was treated with steroids, cyclophosphamide and cyclosporine A (CsA). Because of the prolonged use of calcineurin inhibitors, a course of rituximab (RTX) was planned. Unfortunately, during first infusion, the boy presented with IRR. A desensitization protocol following the first unsuccessful infusion also failed. Facing the risks of long-term cyclosporine therapy, a decision was made to switch to another type of anti-CD20 antibody. Obinutuzumab infusion with a modified premedication scheme was uneventful. Conclusions: Switching therapy to obinutuzumab may be considered an option in nephrotic children who are intolerant to RTX when alternative therapies have been exhausted. The addition of montelukast to premedication and employment of desensitization protocols may decrease the risk of infusion-related reactions to anti-CD20 agents.

Background/Objectives: Primary steroid-resistant nephrotic syndrome (SRNS) in children is an ominous diagnosis due to limited therapeutic options and poor prognosis. The younger the child, the greater the probability of a genetic etiology which is typically resistant to immunosuppressive therapy. International guidelines recommend genetic testing and a search for rare infectious causes in the youngest age group. When no identifiable etiology is found, an immunologic cause of SRNS is suspected, with few therapeutic options available, which lately have included anti-CD20 therapy for children > 7 years of age. This is the first report on the successful use of obinutuzumab in a very young child with primary SRNS. Methods: Two consecutive doses of obinutuzumab, a humanized anti-CD20 antibody (300 mg/m² BSA), were administered two weeks apart to a 24-month-old boy with severe, complicated SRNS which had been refractory to cyclosporin A and rituximab and in whom previous genetic testing and a search for multiple infectious causes had been negative. Results: Complete remission of severe nephrotic syndrome was achieved 2 months after the last infusion with, to date, sustained resolution of proteinuria and normal serum albumin levels without further use of IMS drugs and no severe adverse effects noted. Conclusions: Obinutuzumab may be a rescue option for severe, multidrug-resistant ISN, even in young children, when no other therapeutic options are available.