Genetic testing in children with nephrolithiasis and nephrocalcinosis.

Area of Science:

• Pediatric Nephrology
• Clinical Genetics
• Medical Diagnostics

Background:

• Genetic kidney diseases are increasingly diagnosable through accessible, low-cost genetic testing.
• Nephrolithiasis/nephrocalcinosis (NL/NC) in children necessitates effective diagnostic strategies.
• Understanding genetic contributions to pediatric NL/NC is crucial for improved patient care.

Purpose of the Study:

• To determine the diagnostic yield of genetic testing in children with NL/NC.
• To identify predictors associated with a positive genetic diagnosis in this pediatric population.
• To evaluate the utility of genetic panels in diagnosing kidney stone and calcification conditions.

Main Methods:

• Retrospective multicenter cross-sectional study of children aged ≤21 years with NL/NC.
• Utilized the Invitae Nephrolithiasis Panel for genetic analysis between January 2019 and September 2021.
• Employed bivariate and multiple logistic regression to identify predictors of genetic diagnosis.

Main Results:

• Genetic testing yielded a diagnosis in 32% of pediatric NL/NC cases (29% NL, 40% NC).
• Definite, probable, or possible diagnoses were established in up to one-third of patients.
• Low serum bicarbonate was a significant predictor, increasing the odds of a genetic diagnosis by 8.7 times (p=0.02).
• Variants were identified across 28 genes, revealing 20 distinct genetic conditions.

Conclusions:

• Genetic testing demonstrates high diagnostic yield for pediatric NL/NC, identifying explanatory variants in a substantial proportion of cases.
• The findings support the integration of genetic testing into clinical practice for children with NL/NC.
• Identifying specific clinical features, such as low serum bicarbonate, can aid in predicting the likelihood of a genetic diagnosis.