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Abstract: FR-PO0718

Rituximab-Induced Hypogammaglobulinemia in Childhood Nephrotic Syndrome: Systematic Review and Meta Analysis

Session Information

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Chung, Zinnia, McMaster University Michael G DeGroote School of Medicine, Hamilton, Ontario, Canada
  • Chung, Jason, Western University Schulich School of Medicine & Dentistry, London, Ontario, Canada
  • Yu, Andrew, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
  • Chanchlani, Rahul, McMaster Children's Hospital, Hamilton, Ontario, Canada
Background

Rituximab, a chimeric anti-CD20 monoclonal antibody, is used as a steroid-sparing agent in complicated pediatric nephrotic syndrome. Hypogammaglobulinemia is a known side effect that can lead to severe infections and mortality, yet its incidence and risk factors remain unclear. This review aimed to determine the incidence of rituximab-induced hypogammaglobulinemia and related infections in children with nephrotic syndrome.

Methods

A systematic review of 5 databases from 1974-2024 was completed. Randomized and non-randomized studies with pediatric (<18 years) nephrotic syndrome patients receiving ≥1 rituximab dose were included. Hypogammaglobulinemia was defined by IgG levels >2 SD below the age-matched reference range.

Results

33 studies (n=3,495) were eligible for meta-analysis. The pooled incidence of hypogammaglobulinemia was 11.4% (95%CI: 6.4-19.5). Patients receiving rituximab had increased risk of hypogammaglobulinemia (RR: 1.81, 95%CI: 1.46-2.25). Meta-regression showed no significant effect of follow-up duration, age, sex, or cumulative dose. Of 517 hypogammaglobulinemia episodes, 93 (18%) infections occurred—4 fatal, 2 requiring ICU admission, 2 chronic, and 73 severe.

Conclusion

Hypogammaglobulinemia is a relatively common side effect of rituximab that can result in life threatening or chronic infections. The risk of hypogammaglobulinemia and infections should be weighed against the effectiveness of rituximab for nephrotic syndrome management.

Random effects meta-regression model for incidence of hypogammaglobinemia adjusting for follow-up, age, sex and cumulative dose of Rituximab
Random effects, z-distribution
 Point EstimateStandard Error95% Lower bound95% Upper boundZ-valueP-value
Intercept-4.914.553-13.824.02-1.0770.281
Follow-up-0.020.162-0.340.30-0.1300.896
Age0.080.210-0.330.500.4000.689
Sex (% male)0.020.060-0.100.140.3250.746
Cumulative dose0.0010.001-0.0010.0030.6410.522

Digital Object Identifier (DOI)