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CD4 + and CD8 + T-lymphocyte number as predictive marker of relapse after rituximab treatment in childhood-onset refractory nephrotic syndrome

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Abstract

Background

Rituximab is a promising option for refractory idiopathic nephrotic syndrome. However, no simple predictive markers for relapse after rituximab have been established. To determine such markers, we investigated the relationship between CD4 + and CD8 + cell counts and relapse after rituximab administration.

Methods

We retrospectively investigated patients with refractory nephrotic syndrome who received rituximab followed by immunosuppressive as maintenance therapy. Patients were divided into no relapse in 2 years after rituximab treatment or relapse group. After rituximab treatment, CD4 + /CD8 + cell counts were measured monthly, at prednisolone discontinuation, and at B-lymphocyte recovery. To predict relapse, these cell counts were analyzed using receiver operating characteristic (ROC). Additionally, relapse-free survival was reevaluated based on the result of ROC analysis for 2 years.

Results

Forty-eight patients (18 in the relapse group) were enrolled. At prednisolone discontinuation (52 days after rituximab treatment), the relapse-free group showed significantly lower cell counts than the relapse group (median CD4 + cell count: 686 vs. 942 cells/µL, p = 0.006; CD8 + : 613 vs. 812 cells/µL, p = 0.005). In the ROC analysis, CD4 + cell count > 938 cell/µL and CD8 + cell count > 660 cells/µL could predict relapse in 2 years (sensitivity, 56% and 83%; specificity, 87% and 70%). The patient group with both lower CD4 + and CD8 + cell counts showed significantly longer 50% relapse-free survival (1379 vs. 615 days, p < 0.001 and 1379 vs. 640 days, p < 0.001).

Conclusions

Lower CD4 + and CD8 + cell counts in the early phase after rituximab administration may predict a lower risk of relapse.

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Availability of data and materials

The data that support the findings of this study are available from the corresponding author, Shuichi Ito, upon reasonable request.

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Acknowledgements

We would like to thank all participants and physicians for their contributions to this study. And the authors would like to thank Enago (www.enago.jp) for the English language review.

Funding

There was no external funding for this manuscript.

Author information

Authors and Affiliations

  1. Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan

    Toru Kanamori, Koichi Kamei, Mai Sato, Kentaro Nishi, Mika Okutsu, Sho Ishiwa, Masao Ogura, Mayumi Sako, Kenji Ishikura & Shuichi Ito

  2. Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan

    Toru Kanamori & Mika Okutsu

  3. Department of Pediatrics, Faculty of Medicine, Oita University, Oita, Japan

    Sho Ishiwa

  4. Department of Pediatrics, Kitasato University School of Medicine, Kanagawa, Japan

    Kenji Ishikura

  5. Department of Pediatrics, Yokohama City University Hospital, 22-2 Seto, Kanazawa-Ku, Yokohama, Kanagawa, 236-0027, Japan

    Shuichi Ito

Authors
  1. Toru Kanamori
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  2. Koichi Kamei
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  3. Mai Sato
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Contributions

All authors were physicians who provided treatment to the patients in this report. Toru Kanamori conducted the study, collected the clinical data, and prepared the manuscript; Mai Sato, Kentaro Nishi, Mika Okutsu, Sho Ishiwa, and Masao Ogura edited and reviewed the manuscript; Koichi Kamei revised the manuscript; Shuichi Ito oversaw the work as the corresponding author and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shuichi Ito.

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Conflict of interest

Kamei has received research funding from the Terumo Foundation for Life Sciences and Arts, Public Foundation of Vaccination Research Center, 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. Ishikura received grants from Asahi Kasei Pharma, Chugai Pharmaceutical Co., Ltd., Novartis Pharma, and Zenyaku Kogyo Co. Ltd. and lecture fees from Asahi Kasei Pharma, Chugai Pharmaceutical Co., Ltd., Zenyaku Kogyo Co., Ltd., and Novartis Pharma K.K. Ito received grants from Teijin Pharma Ltd, Astellas Pharma Inc., Pfizer Co. Ltd., and Tanabe Mitsubishi Pharma and lecture fees from Teijin Pharma Ltd and Sanofi Genzyme Co. Ltd.

Ethical approval and consent to participate

This study conformed to the principles of the Declaration of Helsinki and the ethical guidelines issued by the Ministry of Health, Labor, and Welfare in Japan. It was approved by the ethics committee of the NCCHD (approval number: 2403). Informed consent regarding participation was waived in accordance with the guidelines.

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Informed consent regarding publication was waived in accordance with the guidelines.

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Kanamori, T., Kamei, K., Sato, M. et al. CD4 + and CD8 + T-lymphocyte number as predictive marker of relapse after rituximab treatment in childhood-onset refractory nephrotic syndrome. Clin Exp Nephrol 27, 622–630 (2023). https://doi.org/10.1007/s10157-023-02343-z

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  • DOI: https://doi.org/10.1007/s10157-023-02343-z

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