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Kidney Week

Abstract: PO1991

Genetic Testing and Biomarkers as Predictive Tools for Congenital Anomalies of Kidney and Urinary Tract (CAKUT)

Session Information

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology


  • Harris, Meredith, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Erkan, Elif, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Kaufman, Kenneth, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States

Cincinnati Children’s Hospital is 1 of ~5 centers offering fetal interventions (FI) (amnioinfusions/amnioshunts) & infant hemodialysis (HD) for oligo/anhydramnios (OA), increasing survival from 17 to 50%. As a result of this unique surviving Congenital Anomalies of Kidney & Urinary Tract (CAKUT) population, more investigation into genetics & biomarkers in severe CAKUT needs to be performed, particularly in our growing bilateral multicystic dysplastic kidney (bMCDK) population (fatal at most centers). We hypothesize identification of novel genetic mutations & biomarkers will aid in determination of the clinical course of infants & mechanisms of nephrogenesis.


Inclusion criteria for severe CAKUT are women undergoing FI for OA or infants starting HD by 1 month of life. We obtained amniotic fluid (AF) during FI and blood from the mother, father, & infant for trios whole exome sequencing (WES). We performed ELISA testing on AF of 4 renal tubular biomarkers produced by fetal kidneys and validated in AF (NGAL, Cystatin c, Uromodulin and ET-1). Controls are 2nd trimester AF from infants without CAKUT.


We enrolled 18 families-6 with bMCDK & obtained 8 AF samples (2 bMCDK). We performed WES on 5 trios (4 bMCDK) & 3 singletons (1 bMCDK). We identified 4 strong candidate genes (Table).
Biomarker testing included 8 AF samples & 10 controls. All 4 biomarkers are significantly lower in severe CAKUT than controls & are lower in bMCDK than bladder obstruction, likely as the bMCDK population has less renal endowment. Biomarkers are lower in those with intrauterine demise compared to liveborn.


In patients with severe CAKUT, we detected 4 strong candidate genes, 3 implicated in embryo development. This population is enriched for genetic variants, likely due to severity of presentation. We validated 4 biomarkers in AF with correlations to diagnosis & survival. WES & biomarker testing are promising techniques to predict the course of severe CAKUT prenatally. Our goal is to develop a polygenic risk score to predict disease severity in utero based on genetic & biomarker data in this unique population.

Genetic Variants in Bilateral MCDK Families
GeneChromosomeVariantMCDK FamilyVariant FrequencyPredicted TolerancePathwayGene FunctionSyndromes affiliated with genePotential Biomarkers
FRAS14G to A SNVF1, F20.0037%1/5IntegrinOrganogenesisFraser Syndromeintegrin α3β1
NSUN72De novo frameshiftF2N/aN/aRNA methylation transferaseMitochondrial rRNA processingFamilial restrictive cardiomyopathyNone
MTMR322C to T SNVF30.0000040%2/5Protein Tyrosine Phosphatase, mTORCilia Signaling, AutophagyCharcot-Marie-Tooth, Lupus Nephritis, IgA nephropathyLow molecular weight protein-tyrosine phosphatase
CEP1626A to G SNVF1, F20.0009%1/5Axonemal Microtubule BindingCiliogenesis,
Organelle Biogenesis
Seckel Syndrome, Orofacial Digital SyndromeNone


  • Other NIH Support