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Urine alpha 1-microglobulin-to-creatinine ratio and beta 2-microglobulin-to-creatinine ratio for detecting CAKUT with kidney dysfunction in children

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Abstract

Background

The leading cause of advanced chronic kidney disease (CKD) in children is congenital anomalies of the kidney and urinary tract (CAKUT). However, the most appropriate parameters of biochemical urine analysis for detecting CAKUT with kidney dysfunction are not known.

Methods

The present observational study analyzed data on children with CAKUT (stage 2–4 CKD) and the general pediatric population obtained from school urine screenings. The sensitivity and specificity of urine alpha 1-microglobulin-, beta 2-microglobulin-, protein-, and the albumin-to-creatinine ratios (AMCR, BMCR, PCR, ACR, respectively) in detecting CAKUT with kidney dysfunction were compared with those of the conventional urine dipstick, and the most appropriate of these four parameters were evaluated.

Results

In total, 77 children with CAKUT and 1712 subjects in the general pediatric population fulfilled the eligibility criteria. Conventional dipstick urinalysis was insufficient due to its low sensitivity; even when the threshold of proteinuria was +/−, its sensitivity was only 29.7% for stage 2 and 44.1% for stage 3 CKD. Among the four parameters assessed, the AMCR and BMCR were adequate for detecting CAKUT in children with stage 3–4 CKD (the respective sensitivity and specificity of the AMCR for detecting CAKUT in stage 3 CKD was 79.4% and 97.5% while that of BMCR was 82.4% and 97.5%). These data were validated using national cohort data.

Conclusion

AMCR and BMCR are superior to dipstick urinalysis, PCR, and ACR in detecting CAKUT with kidney dysfunction, particularly stage 3 CKD. However, for AMCR, external validation is required.

Graphical Abstract

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Data availability

The first author and the corresponding author have the study data, which can be provided on reasonable request.

Code availability

Not applicable.

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Acknowledgments

We confirm that the results presented in this article have not been published previously in their entirety or in part. The authors would like to thank all the hospitals, institutions, pediatricians, and the Tokyo Health Organization for their cooperation. The authors would also like to thank Katsumi Abe and Yoshihiko Morikawa for their assistance with coordinating and supervising data collection, and James Robert Valera for his assistance with editing this manuscript, and Yoshinobu Nagaoka, Ryoko Harada, Yuko Hamasaki, and all members of the Pediatric CKD Study Group in Japan in conjunction with the Committee of Measures for Pediatric CKD of the Japanese Society for Pediatric Nephrology for providing us with the data.

Funding

The present study was supported by a Health, Labour and Welfare Sciences Research Grant (H25-jisedai-ippan-003) and childhood-onset, rare and intractable kidney disease in Japan, research on rare and intractable diseases Health, Labour and Welfare Sciences Research Grants (20FC1028).

Author information

Authors and Affiliations

  1. Department of Nephrology, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Riku Hamada, Kaori Kikunaga & Masataka Honda

  2. Department of Pediatrics, Fussa Hospital, Tokyo, Japan

    Kaori Kikunaga & Takeshi Matsuyama

  3. Department of Pediatrics, Kitasato University School of Medicine, 1-15-1, Kitazato, Minami-ku, Sagamihara-shi, Kanagawa, 252-0374, Japan

    Kaori Kikunaga & Kenji Ishikura

  4. Teikyo Academic Research Center, Teikyo University, Tokyo, Japan

    Tetsuji Kaneko

  5. Clinical Research Support Center, Tokyo Metropolitan Children’s Medical Center, Tokyo, Japan

    Tetsuji Kaneko & Masako Tomotsune

  6. Department of Pediatrics, Minamitama Hospital, Tokyo, Japan

    Shojiro Okamoto

  7. Ichinomiya Medical Treatment and Habilitation Center, Aichi, Japan

    Osamu Uemura

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

    Koichi Kamei

  9. Department of Pediatrics, Shizuoka Children’s Hospital, Shizuoka, Japan

    Naohiro Wada

  10. Saitama Children’s Medical Center, Saitama, Japan

    Akira Oka

Authors
  1. Riku Hamada
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  2. Kaori Kikunaga
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  12. Masataka Honda
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Contributions

All authors made substantial contributions to the conception and design of the study; to the acquisition, analysis, and interpretation of the data; or to the drafting and critical revision of the manuscript for important intellectual content. RH conceptualized and designed the study and wrote the first draft. KK interpreted the data and reviewed and revised the manuscript. MH helped conceptualize and design the study, interpreted the data, and helped revise the manuscript. SO and TM helped conceptualize and design the study. MT, OU, KK, NW, and AO coordinated and supervised data collection at each site. KI also provided us with the data and critically reviewed the analyses and the manuscript. As the biostatistician, TK carried out the analyses and interpreted the data. Furthermore, all the authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Kaori Kikunaga.

Ethics declarations

Ethics approval

The study was approved by a central ethics board (Tokyo Metropolitan Children’s Medical Center approval number H25-33; Fussa Hospital approval number 1; and Tokyo Health Organization) before commencement.

Consent to participate

The study data were retrospective and based on information in the patients’ medical records and records of annual screenings. Informed consent was waived in accordance with the related guidelines. The study protocol was displayed publicly on the website of Tokyo Metropolitan Children’s Medical Center and Tokyo Health Organization in accordance with the guidelines.

Conflict of interest

The authors declare no competing interests.

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Hamada, R., Kikunaga, K., Kaneko, T. et al. Urine alpha 1-microglobulin-to-creatinine ratio and beta 2-microglobulin-to-creatinine ratio for detecting CAKUT with kidney dysfunction in children. Pediatr Nephrol 38, 479–487 (2023). https://doi.org/10.1007/s00467-022-05577-3

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  • DOI: https://doi.org/10.1007/s00467-022-05577-3

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