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The association between hypogammaglobulinemia severity and infection risk in rituximab-treated patients with childhood-onset idiopathic nephrotic syndrome

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Abstract

Background

Hypogammaglobulinemia is a major adverse effect from rituximab. However, the association between rituximab-induced hypogammaglobulinemia and infection frequency is unknown.

Methods

Patients who received rituximab for complicated nephrotic syndrome between February 2006 and October 2020 were enrolled in this retrospective observational study. Infections requiring antibacterial or antiviral agents or hospitalization were identified, and the characteristics of infections were compared according to infection type.

Results

One hundred and forty patients were enrolled. Fifty infection events were detected in 36 patients, 45 infection events in 32 patients required hospitalization, and 1 severe infection event required intensive care unit admission. In eight patients who developed severe hypogammaglobulinemia (serum IgG level < 200 mg/dL) for more than 1 year after rituximab treatment, eight infections occurred in six patients; six of these infections did not occur during the period of severe hypogammaglobulinemia. Febrile neutropenia accounted for 54.2% (13/24) of all infections among the patients with hypogammaglobulinemia. The incidence of infections was 0.028 (95% confidence interval = 0.017–0.448), 0.071 (95% [CI] = 0.041–0.114), and 0.096 (95% [CI] = 0.019–0.282) patient-years in patients with normal serum IgG levels and those with mild and severe hypogammaglobulinemia, respectively. Immunoglobulin replacement therapy was not administered to any patients except for the treatment of infection.

Conclusions

Our results showed no statistically significant association between hypogammaglobulinemia severity and infection rate. In addition, the frequency of infection was relatively low even in patients with severe hypogammaglobulinemia, suggesting that immunoglobulin replacement therapy may not be necessary for rituximab-treated patients with severe hypogammaglobulinemia.

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Data availability

The data from this study are available from the corresponding author upon reasonable request.

Code availability

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Acknowledgements

The authors would like to thank Dr. Chie Nagata at the National Center for Child Health and Development for her advice on statistical analysis. The authors would also like to express their gratitude to Drs. Shuichi Ito and Kenji Ishikura for their contributions to our clinical practice.

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Authors and Affiliations

  1. Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-853, Japan

    Yuta Inoki, Kentaro Nishi, Mai Sato, Masao Ogura & Koichi Kamei

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  1. Yuta Inoki
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Contributions

All authors are physicians who treated the patients in this study. Yuta Inoki conducted the study, collected the clinical and laboratory data, and wrote the manuscript; Kentaro Nishi, Mai Sato, and Masao Ogura reviewed and edited the manuscript; Koichi Kamei, the corresponding author, supervised the work and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Koichi Kamei.

Ethics declarations

Ethics approval

The study was approved by the Ethics Committee of the National Center for Child Health and Development (approval number: 2021–169).

Consent to participate

Informed consent regarding participation was exempted in accordance with the principles of the Declaration of Helsinki and the ethical guidelines issued by the Ministry of Health, Labor, and Welfare, Japan.

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Informed consent for publication was exempted in accordance with the guidelines.

Conflict of interest

Koichi Kamei has obtained research funding from Public Foundation of Vaccination Research Center, the Terumo Foundation for Life Sciences and Arts, and Taiju Life Social Welfare Foundation; donations from Chugai Pharmaceutical Co. Ltd., Astellas Pharma Inc., Ono Pharmaceutical Co., Teijin Pharma Ltd., Shionogi Co. Ltd., and Otsuka Pharmaceutical Co. Ltd.; and lecture fees from Tanabe Mitsubishi Pharma, Baxter Ltd., and Zenyaku Kogyo Co. Ltd. All other authors have no potential conflicts of interests to disclose.

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Inoki, Y., Nishi, K., Sato, M. et al. The association between hypogammaglobulinemia severity and infection risk in rituximab-treated patients with childhood-onset idiopathic nephrotic syndrome. Pediatr Nephrol 38, 451–460 (2023). https://doi.org/10.1007/s00467-022-05652-9

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  • DOI: https://doi.org/10.1007/s00467-022-05652-9

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