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Diagnostic and clinical utility of genetic testing in children with kidney failure

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Abstract

Background

Genetic kidney disease is well established as an important cause of pediatric kidney failure, and genetic testing might increase diagnostic accuracy, but evidence is limited. This study was conducted to determine the diagnostic yield and clinical impact of genetic testing for children with kidney failure.

Methods

Patients who were diagnosed with kidney failure before 19 years of age at Children’s Hospital of Fudan University from 2009 to 2018 and received next-generation sequencing (NGS) were enrolled. The results for likely pathogenic variants in genes known to cause chronic kidney disease (CKD) were analyzed.

Results

A molecular diagnosis was identified in 39.9% (75/188) of children with kidney failure. Specific subtype of clinical category was discerned in 54 (72.0%) patients, kidney disease was reclassified in 7 (9.3%) patients, the unknown etiology of 5 (6.7%) patients was molecularly diagnosed, and the clinical diagnoses of the other 9 (12.0%) patients were confirmed. In addition, genetic diagnosis was considered to have contributed to clinical management, including negating the need for kidney biopsy (26/75, 34.7%), avoiding immunosuppressive therapy (24/75, 32.0%), changing surveillance (48/75, 64.0%), guiding specific treatment (21/75, 28.0%), and guiding peri-transplant management and options for kidney transplantation (12/75, 16.0%). Furthermore, cascade testing was subsequently offered to 34.7% (26/75) of families.

Conclusions

Genetic testing identified a molecular diagnosis in nearly 40% of children with kidney failure. Our results confirm that in children with kidney failure, genetic testing can not only establish a specific molecular diagnosis, but has a significant impact on clinical management.

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Availability of data and materials

All data generated or analyzed are included in this paper.

Code availability

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Acknowledgements

We thank all patients and their families who contributed to this study. We thank the coordinators of the Chigene (Beijing) Translational Medical Research Center Co. Ltd., WuXi NextCODE in Shanghai, and MyGenostics Co. Ltd. in Beijing, for sequencing technology support.

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Author notes

  1. Jing Chen, Fang Lin and Yihui Zhai contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, China

    Jing Chen, Fang Lin, Yihui Zhai, Chunyan Wang, Jia Rao, Jiaojiao Liu, Jialu Liu, Minghui Yu, Qian Shen & Hong Xu

  2. Clinical Genetic Center, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, China

    Bingbing Wu

  3. Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institutes of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

    Duan Ma

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  1. Jing Chen
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Contributions

J. Chen, F. Lin, Y. Zhai, Q. Shen, and H. Xu contributed to the research design; B. Wu, D. Ma, and H. Xu provided administrative, technical, and material support; F. Lin, C. Wang, J. Rao, Jiaojiao Liu, Jialu Liu, and M. Yu contributed to data acquisition; J. Chen, F. Lin, and Y. Zhai contributed to data analysis and interpretation; J. Chen, F. Lin, and M. Yu contributed to statistical analysis; J. Chen and Q. Shen drafted the manuscript; Q. Shen and H. Xu contributed critical revisions of the manuscript; Q. Shen and H. Xu contributed supervision and mentorship; and all authors approved the final version of the report.

Corresponding authors

Correspondence to Qian Shen or Hong Xu.

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This study was approved by the Ethical Review Committee of the Children’s Hospital of Fudan University.

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All authors declare no competing interests.

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Chen, J., Lin, F., Zhai, Y. et al. Diagnostic and clinical utility of genetic testing in children with kidney failure. Pediatr Nephrol 36, 3653–3662 (2021). https://doi.org/10.1007/s00467-021-05141-5

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