Genetic testing in children with nephrolithiasis and nephrocalcinosis.

Background: Diagnosing genetic kidney disease has become more accessible with low-cost, rapid genetic testing. The study objectives were to determine genetic testing diagnostic yield and examine predictors of genetic diagnosis in children with nephrolithiasis/nephrocalcinosis (NL/NC). Methods: This...

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Publicado en:Pediatric Nephrology Vol. 38; no. 8; pp. 2615 - 2623
Autores principales: Gefen, Ashley M., Sethna, Christine B., Cil, Onur, Perwad, Farzana, Schoettler, Megan, Michael, Mini, Angelo, Joseph R., Safdar, Adnan, Amlie-Wolf, Louise, Hunley, Tracy E., Ellison, Jonathan S., Feig, Daniel, Zaritsky, Joshua
Formato: research tables/charts Journal Article
Publicado: Springer Nature Aug2023
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Aug2023
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00467-023-05879-0
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        atl: Genetic testing in children with nephrolithiasis and nephrocalcinosis.
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        au:
          Gefen, Ashley M.
          Sethna, Christine B.
          Cil, Onur
          Perwad, Farzana
          Schoettler, Megan
          Michael, Mini
          Angelo, Joseph R.
          Safdar, Adnan
          Amlie-Wolf, Louise
          Hunley, Tracy E.
          Ellison, Jonathan S.
          Feig, Daniel
          Zaritsky, Joshua
        affil: Division of Nephrology, Department of Pediatrics, Cohen Children's Medical Center, 269-01 76th Ave, 11040, Queens, NY, USA
      sug:
        subj:
          Urolithiasis Diagnosis
          Nephrocalcinosis Diagnosis
          Genetic Screening
          Human
          Retrospective Design
          Cross Sectional Studies
          Multicenter Studies
          Child
          Adolescence
          Logistic Regression
          Odds Ratio
          Confidence Intervals
          Descriptive Statistics
          Funding Source
          Child: 6-12 years
          Adolescent: 13-18 years
      ab: Background: Diagnosing genetic kidney disease has become more accessible with low-cost, rapid genetic testing. The study objectives were to determine genetic testing diagnostic yield and examine predictors of genetic diagnosis in children with nephrolithiasis/nephrocalcinosis (NL/NC). Methods: This retrospective multicenter cross-sectional study was conducted on children ≤ 21 years old with NL/NC from pediatric nephrology/urology centers that underwent the Invitae Nephrolithiasis Panel 1/1/2019–9/30/2021. The diagnostic yield of the genetic panel was calculated. Bivariate and multiple logistic regression were performed to assess for predictors of positive genetic testing. Results: One hundred and thirteen children (83 NL, 30 NC) from 7 centers were included. Genetic testing was positive in 32% overall (29% NL, 40% NC) with definite diagnoses (had pathogenic variants alone) made in 11.5%, probable diagnoses (carried a combination of pathogenic variants and variants of uncertain significance (VUS) in the same gene) made in 5.4%, and possible diagnoses (had VUS alone) made in 15.0%. Variants were found in 28 genes (most commonly HOGA1 in NL, SLC34A3 in NC) and 20 different conditions were identified. Compared to NL, those with NC were younger and had a higher proportion with developmental delay, hypercalcemia, low serum bicarbonate, hypophosphatemia, and chronic kidney disease. In multivariate analysis, low serum bicarbonate was associated with increased odds of genetic diagnosis (β 2.2, OR 8.7, 95% CI 1.4–54.7, p = 0.02). Conclusions: Genetic testing was high-yield with definite, probable, or possible explanatory variants found in up to one-third of children with NL/NC and shows promise to improve clinical practice.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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