- Hospital MaternoInfantil de la Vall dHebron, Barcelona, Spain Atm?? B

- Hospital MaternoInfantil de la Vall dHebron, Barcelona, Spain Atm?? B. 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, AZD-5904 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 abstract Open in a separate window A higher resolution version of the Graphical abstract is available as Supplementary information Supplementary Information The online version contains supplementary material available at 10.1007/s00467-023-05913-1. Keywords: Rituximab, Hypogammaglobulinemia, Nephrotic syndrome, Children Introduction Rituximab (RTX) is a monoclonal antibody against CD20, an antigen expressed on the surface of all circulating B cells excluding plasma cells. Licensed for the treatment of malignancies, vasculitis, and rheumatoid arthritis, it is used off label for the treatment of different autoimmune disease and has been used increasingly for the management of idiopathic nephrotic AZD-5904 syndrome (INS) mainly in children with poorly controlled steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) [1C3]. Recent randomized controlled trials have confirmed its efficacy for this indication, but paucity of data exist on its optimal dosage and short- and long-term safety [4C10]. Targeting B cells should be the rationale for using RTX in INS, nevertheless evidence exists that RTX can also impact T cells [11, 12]. Depletion of CD20-expressing B cells in the peripheral blood following RTX infusion is rapid and long lasting (several months). Though anti-CD20 antibodies were not expected to influence immunoglobulin levels, the association of RTX use and hypogammaglobulinemia (HGG) has been well established in adults, less so in the pediatric population [13, 14]. A number of risk factors including RTX dose, concomitant immunosuppressive (IMS) treatment, and pre-existing low immunoglobulin levels seem to play a role in its development [15C19]. The reported incidence in adults is relatively low, ranging from 14C20% in adults with malignancies to 3.5C4.2% in subjects with autoimmune diseases [18, 20C22]. The clinical significance of this acquired HGG is not fully known but recent publications have shown an increased risk of infections following its use in adults and AZD-5904 children [18, 19, 23]. Due to the paucity of data on the incidence of HGG and its consequences in RTX-treated children with INS, a survey was undertaken by the Glomerulonephritis Working Group (WG) of the European Society Pediatric Nephrology (ESPN) addressing the screening and management practices in place in pediatric nephrology centers for the recognition and treatment of this complication and its potential association with severe infections. Materials and methods An online survey was distributed by the Glomerulonephritis WG to all ESPN members by email. The survey was web based and developed in the English language. It assessed three domains: AZD-5904 center policy for administration of RTX (dose, number of courses, co-administrated drugs, CD19/20 monitoring), screening policy for HGG defined as serum levels below age-standardized reference ranges (prior, during and after 9 months after RTX infusion), its management with IgG replacement therapy (IGRT), and RTX-associated morbidity and mortality (center observations on the number of patients with severe infections requiring hospitalization, HIF3A data on individual etiology and outcome). The survey consisted.