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Background <p>Rituximab is increasingly used to treat childhood nephrotic syndrome, although its long-term effects are poorly understood. Our study aims to evaluate the incidence and risk factors for hypogammaglobulinemia, hematological complications, B cell repopulation, and relapses after rituximab treatment.</p> Methods <p>We included children (1–18 years of age) with nephrotic syndrome who were enrolled in a prospective cohort study (Greater Toronto Area, Canada) and received rituximab from June 2018 to December 2023. We collected all immunoglobulin, hematology, and microbiology results from our institution. The primary outcome was hypogammaglobulinemia (IgG ≥ 2 standard deviations below the age-specific mean), classified as severe (IgG &lt; 3 g/L) and/or prolonged (≥ 12 months). Secondary outcomes included other immunoglobulin and hematological parameters, B cell depletion, and relapses.</p> Results <p>Seventy children with nephrotic syndrome received rituximab treatment. Pre-existing hypogammaglobulinemia was present in 46% of the patients. After rituximab, 68% of the patients had any, 32% had severe, and 46% had prolonged hypogammaglobulinemia. Younger age (odds ratio [OR] 1.13, 95% CI 1.01–1.29), European ethnicity (OR 6.37, 95% CI 1.74–30.83), lower pre-treatment IgG (OR 1.63, 95% CI 1.24–2.31) and longer maintenance immunosuppression duration (OR 1.27, 95% CI 1.03–1.61) were risk factors for prolonged hypogammaglobulinemia post-rituximab. Post-rituximab, 16% of the children had anemia, 21% had neutropenia, and 3% had thrombocytopenia. Twelve children (17%) developed documented infections. All children experienced complete B cell depletion post-rituximab, with B cell repopulation at median 6.3 months. Older age, prior calcineurin inhibitor treatment, and steroid sensitivity were associated with longer time-to-B cell repopulation.</p> Conclusions <p>Prolonged hypogammaglobulinemia occurs in half of children with nephrotic syndrome post-rituximab. Younger age, European ethnicity, lower pre-treatment IgG, and longer maintenance immunosuppression use are associated with higher prolonged hypogammaglobulinemia risk.</p> Graphical abstract <p></p>

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Hypogammaglobulinemia and B cell repopulation after rituximab in childhood nephrotic syndrome

  • 期刊论文

  • 发表日期：

    2026年7月11日

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  • Cal H. Robinson,
  • Sophia Gorgiev,
  • Nowrin Aman,
  • Tonny H. M. Banh,
  • Josefina Brooke,
  • Valentina Bruno,
  • Vaneet Dhillon,
  • Mackenzie Garner,
  • Christoph Licht,
  • Ashlene McKay,
  • Damien Noone,
  • Rachel Pearl,
  • Seetha Radhakrishnan,
  • Keisha Rasool,
  • Nithiakishna Selvathesan,
  • Chia Wei Teoh,
  • Jovanka Vasilevska-Ristovska,
  • Rulan S. Parekh

摘要

Background

Rituximab is increasingly used to treat childhood nephrotic syndrome, although its long-term effects are poorly understood. Our study aims to evaluate the incidence and risk factors for hypogammaglobulinemia, hematological complications, B cell repopulation, and relapses after rituximab treatment.

Methods

We included children (1–18 years of age) with nephrotic syndrome who were enrolled in a prospective cohort study (Greater Toronto Area, Canada) and received rituximab from June 2018 to December 2023. We collected all immunoglobulin, hematology, and microbiology results from our institution. The primary outcome was hypogammaglobulinemia (IgG ≥ 2 standard deviations below the age-specific mean), classified as severe (IgG < 3 g/L) and/or prolonged (≥ 12 months). Secondary outcomes included other immunoglobulin and hematological parameters, B cell depletion, and relapses.

Results

Seventy children with nephrotic syndrome received rituximab treatment. Pre-existing hypogammaglobulinemia was present in 46% of the patients. After rituximab, 68% of the patients had any, 32% had severe, and 46% had prolonged hypogammaglobulinemia. Younger age (odds ratio [OR] 1.13, 95% CI 1.01–1.29), European ethnicity (OR 6.37, 95% CI 1.74–30.83), lower pre-treatment IgG (OR 1.63, 95% CI 1.24–2.31) and longer maintenance immunosuppression duration (OR 1.27, 95% CI 1.03–1.61) were risk factors for prolonged hypogammaglobulinemia post-rituximab. Post-rituximab, 16% of the children had anemia, 21% had neutropenia, and 3% had thrombocytopenia. Twelve children (17%) developed documented infections. All children experienced complete B cell depletion post-rituximab, with B cell repopulation at median 6.3 months. Older age, prior calcineurin inhibitor treatment, and steroid sensitivity were associated with longer time-to-B cell repopulation.

Conclusions

Prolonged hypogammaglobulinemia occurs in half of children with nephrotic syndrome post-rituximab. Younger age, European ethnicity, lower pre-treatment IgG, and longer maintenance immunosuppression use are associated with higher prolonged hypogammaglobulinemia risk.

Graphical abstract