Congenital anomalies of the kidney and urinary tract (CAKUT) in critically ill infants: a multicenter cohort study

Leow, Esther Huimin; Lee, Jan Hau; Hornik, Christoph P.; Ng, Yong Hong; Hays, T. R.; Clark, Reese H.; Tolia, Veeral N.; Greenberg, Rachel G.

doi:10.1007/s00467-022-05542-0

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…Previously CAKUT and CHD have both been found as solitary anomalies or co-existing with other organ system malformations ( 3 , 4 , 7 , 8 , 27 – 31 ). Overall, 40%–60% of patients with a CAKUT or CHD have an additional extra-renal or extra-cardiac abnormality ( 7 , 8 , 27 – 30 ). CHD and CAKUT are known to co-occur in 25%–30% of affected individuals, more than any other concurrent organ system anomalies ( 7 , 8 , 31 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, additional structural malformations were identified just as commonly in those with environmental causes and no identifiable etiology for their presentation. Patients with CHD or CAKUT and additional organ system anomalies have higher morbidity and mortality, and thus our data may be biased, since hospital admission was among the selection criteria ( 27 , 29 ). Despite this possible skewing, these results still provide valuable information on what additional diagnostic work up should be considered, and suggest that hospitalized pediatric patients with both CAKUT and CHD should be evaluated for additional organ system malformations, most specifically in the musculoskeletal and nervous systems.…”

Section: Discussionmentioning

confidence: 99%

“…Previously CAKUT and CHD have both been found as solitary anomalies or co-existing with other organ system malformations (3,4,7,8,(27)(28)(29)(30)(31). Overall, 40%-60% of patients with a CAKUT or CHD have an additional extra-renal or extra-cardiac abnormality (7,8,(27)(28)(29)(30).…”

Section: Expanding the Phenotype Of Patients With Cakut And Chdmentioning

confidence: 99%

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Genomic sequencing has a high diagnostic yield in children with congenital anomalies of the heart and urinary system

et al. 2023

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BackgroundCongenital heart defects (CHD) and congenital anomalies of the kidney and urinary tract (CAKUT) account for significant morbidity and mortality in childhood. Dozens of monogenic causes of anomalies in each organ system have been identified. However, even though 30% of CHD patients also have a CAKUT and both organs arise from the lateral mesoderm, there is sparse overlap of the genes implicated in the congenital anomalies for these organ systems. We sought to determine whether patients with both CAKUT and CHD have a monogenic etiology, with the long-term goal of guiding future diagnostic work up and improving outcomes.MethodsRetrospective review of electronic medical records (EMR), identifying patients admitted to Rady Children's Hospital between January 2015 and July 2020 with both CAKUT and CHD who underwent either whole exome sequencing (WES) or whole genome sequencing (WGS). Data collected included demographics, presenting phenotype, genetic results, and mother's pregnancy history. WGS data was reanalyzed with a specific focus on the CAKUT and CHD phenotype. Genetic results were reviewed to identify causative, candidate, and novel genes for the CAKUT and CHD phenotype. Associated additional structural malformations were identified and categorized.ResultsThirty-two patients were identified. Eight patients had causative variants for the CAKUT/CHD phenotype, three patients had candidate variants, and three patients had potential novel variants. Five patients had variants in genes not associated with the CAKUT/CHD phenotype, and 13 patients had no variant identified. Of these, eight patients were identified as having possible alternative causes for their CHD/CAKUT phenotype. Eighty-eight percent of all CAKUT/CHD patients had at least one additional organ system with a structural malformation.ConclusionsOverall, our study demonstrated a high rate of monogenic etiologies in hospitalized patients with both CHD and CAKUT, with a diagnostic rate of 44%. Thus, physicians should have a high suspicion for genetic disease in this population. Together, these data provide valuable information on how to approach acutely ill patients with CAKUT and CHD, including guiding diagnostic work up for associated phenotypes, as well as novel insights into the genetics of CAKUT and CHD overlap syndromes in hospitalized children.

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