Genetic Basis of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)

Abstract

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are a leading cause of pediatric chronic kidney disease (CKD), with a diverse range of clinical manifestations and underlying genetic causes. Objective: This study aims to investigate the genetic basis of CAKUT in pediatric patients, identifying key mutations and exploring their association with clinical outcomes such as renal impairment and extra-renal features. Methods: This cross-sectional study was conducted at District Headquarter Hospital Mardan from May 2024 to May 2025. A total of 55 pediatric patients diagnosed with CAKUT were enrolled in this study. Genetic screening was performed using whole exome sequencing (WES) and. -

targeted gene sequencing for known CAKUT-related genes (HNF1B, PAX2, RET, EYA1). Clinical data, including renal function and associated comorbidities, were collected from medical records. Results: Mutations in HNF1B were identified in 12 patients (21.8%), with renal hypodysplasia observed in 8 (66.7%) of these cases. Mutations in PAX2 were found in 8 patients (14.5%), with vesicoureteral reflux (VUR) present in 6 (75%) of these cases. RET mutations were detected in 5 patients (9.1%), while EYA1 mutations (copy number variations) were found in 4 patients (7.3%). However, 26 patients (47.3%) did not have mutations in the targeted genes. Logistic regression analysis revealed that HNF1B mutations were significantly associated with renal impairment (OR = 5.2, 95% CI: 1.5–18.3, p = 0.01), and PAX2 mutations were significantly associated with VUR (OR = 3.5, 95% CI: 1.2–10.5, p = 0.02). Conclusion: This study underscores the important role of genetic mutations in the development of CAKUT, particularly in relation to renal hypodysplasia and VUR. Early genetic screening can aid in the diagnosis and prognosis of CAKUT, and the identification of mutations in genes like HNF1B and PAX2 may help guide clinical management