Genetic analysis and pregnancy outcomes of fetuses with kidney and urinary tract anomalies

Abstract Objective: To explore the genetic basis and pregnancy outcomes of congenital anomalies of the kidney and urinary tract (CAKUTs). Methods: We analyzed the ultrasonographic features, results of prenatal diagnostic tests (chromosomal karyotype analysis, chromosomal microarray analysis [CMA], and whole exome sequencing [WES]), and pregnancy outcomes of fetuses with CAKUTs. Results: The main ultrasonographic features of 1197 CAKUTs were hydronephrosis, multicystic dysplastic kidney, renal agenesis, and duplex kidney. Of 413 fetuses that underwent prenatal genetic tests, 80 (19.37%, 80/413) had clinically significant abnormal results, including 27 fetuses with chromosome abnormalities and 40 with pathogenic copy number variations (CNVs)/variations of uncertain significance (VOUSs). Of the 26 fetuses that underwent WES, 13 (50.00%, 13/26) had pathogenic/likely pathogenic point mutations. The incidence of genetic abnormalities was significantly lower for isolated CAKUTs (11.36%, 36/317) than for CAKUTs with additional anomalies (45.83%, 44/96; p < 0.05). The operation rate among live-born children with CAKUTs was 6.75% (51/755). The anteroposterior diameter (APD) of the renal pelvis in the third trimester could predict the necessity of postnatal surgery, and the sensitivity and specificity of APD ≥ 17.5 mm were 63.2% and 94.7%, respectively. Conclusions: The main geneetic causes of isolated CAKUT were copy number variations (CNVs) and genetic abnormalities. CMA has important value in CAKUT fetuses with normal karyotype and can increase the detection rate by 4%; WES can significantly improve the genetic detection rate of CAKUT fetuses. Fetuses with isolated urinary abnormalities have a good prognosis after birth.