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A step-by-step, multidisciplinary strategy to maximize the yield of genetic testing in pediatric patients with chronic kidney diseases

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An Editorial Commentary to this article was published on 19 March 2024

Abstract

Background

The use of genetic testing in pediatric patients with chronic kidney diseases (CKD) has increased exponentially in the past few years, particularly with the emergence of novel sequencing techniques. However, the genetic yield remains unexpectedly low in nephrology, with an impact on diagnosis, prognosis and treatment. Moreover, the increasing diversity of genetic testing possibilities can be seen as an obstacle by clinicians, in the absence of a strong background in genetics. Here, we propose a step-by-step, multidisciplinary strategy for the diagnostic evaluation of pediatric patients with CKD, and appropriate genetic test selection to maximize the yield of genetic testing.

Methods

A total of 126 pediatric patients were enrolled in a retrospective file analysis. Genetic testing techniques used included phenotype-associated next-generation panel sequencing (N = 41), Sanger and SNaPshot sequencing (N = 3) and/or whole exome sequencing (N = 2).

Results

Overall genetic yield reached 63% and genetic testing significantly impacted patient management in 70%. The distribution of kidney diseases among patients was balanced and matched previously described pediatric cohorts in terms of glomerulopathies, tubulopathies and ciliopathies. Genetic analyses led to significant treatment modifications, kidney biopsy sparing and personalized nephroprotection, as well as tailored genetic counseling. Of note, the evaluation of Human Phenotype Ontology term accuracy in the cohort showed that causal mutations were precisely identified in 85% of the patients at most.

Conclusion

Here we suggest a step-by-step, multidisciplinary strategy to maximize the yield of genetic testing in pediatric patients with CKD. This approach optimizes patient care while avoiding unnecessary treatments or procedures.

Graphical Abstract

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Data availability

The datasets generated during and/or analysed during the current study are not publicly available due to European privacy laws (GDPR), but are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Pediatric Nephrology, Centre Hospitalier de Luxembourg, 4 Rue Barblé, L1210, Luxembourg, Luxembourg

    Ancuta Caliment, Olil Van Reeth & Olivier Niel

  2. Center of Human Genetics, Institut de Pathologie Et de Génétique, Gosselies, Belgium

    Charlotte Hougardy & Karin Dahan

  3. Laboratoire National de Santé, 1 Rue Louis Rech, L3555, Dudelange, Luxembourg

    Karin Dahan

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  1. Ancuta Caliment
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Caliment, A., Van Reeth, O., Hougardy, C. et al. A step-by-step, multidisciplinary strategy to maximize the yield of genetic testing in pediatric patients with chronic kidney diseases. Pediatr Nephrol (2024). https://doi.org/10.1007/s00467-024-06299-4

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