This prospective cohort study (n=70, ages 1–18, Greater Toronto Area, Canada, June 2018–December 2023) evaluated the incidence of and risk factors for hypogammaglobulinemia, hematological complications, B cell repopulation, and relapses in children with nephrotic syndrome treated with rituximab.
Post-rituximab, 68% had any hypogammaglobulinemia, 32% had severe (IgG <3 g/L), and 46% had prolonged (≥12 months) hypogammaglobulinemia. Risk factors for prolonged hypogammaglobulinemia included younger age (OR 1.13), European ethnicity (OR 6.37), lower pre-treatment IgG (OR 1.63), and longer maintenance immunosuppression (OR 1.27). Hematological complications included anemia (16%), neutropenia (21%), and thrombocytopenia (3%); 17% had documented infections. All children had complete B cell depletion, with median repopulation at 6.3 months.
- Single-center prospective cohort limits generalizability; immunoglobulin and B cell data were only collected at the study institution, potentially missing results from outside facilities. - The ethnicity finding (European OR 6.37) may reflect baseline IgG differences by race rather than a true independent effect, which the study acknowledges but cannot fully disentangle. - No control group without rituximab, making it difficult to attribute all hematological or immunological changes solely to rituximab.
Screen children receiving rituximab for nephrotic syndrome for hypogammaglobulinemia—especially those who are younger, of European ethnicity, have low pre-treatment IgG, or are on prolonged immunosuppression, as nearly half will develop prolonged IgG deficiency. Monitor for neutropenia (1 in 5) and infections (1 in 6) and plan B cell monitoring with expected repopulation around 6 months post-treatment.
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