Molecular Basis of the Pelvi-Ureteric Junction Obstruction in Children with Hydronephrosis

Abstract

ABSTRACT: Background: Pelvi-Ureteric Junction Obstruction (PUJO) represents a significant cause of congenital hydronephrosis that can lead to progressive renal damage if untreated. While the condition is well-characterized clinically, its molecular pathogenesis remains poorly understood. This study aimed to identify key genetic alterations in PUJO through comprehensive transcriptomic analysis. Methods: We conducted a prospective study from January 2016 to December 2023 involving 9 pediatric patients (18 tissue samples) undergoing Anderson-Hynes pyeloplasty. Paired samples were collected from stenotic PUJ segments and adjacent normal ureteral tissue. RNA sequencing was performed followed by bioinformatic analysis to identify differentially expressed genes (DEGs) and pathway enrichment. Clinical parameters including demographics, presentation, and postoperative outcomes were systematically recorded. Results: The cohort showed male predominance (3.5:1 ratio) with mean age 40.22±32.61 months and left-sided predominance (77.8%). Key clinical presentations included abdominal distension (55.6%) and urinary tract infections (33.3%). Postoperative complications occurred in 22.2% cases. Transcriptomic analysis revealed 590 significant DEGs (292 upregulated, 298 downregulated), with notable enrichment in neuroactive ligand-receptor interactions (141 genes) and olfactory transduction pathways (50 genes). Chromosomal analysis identified 29 enriched regions, particularly on chromosomes 19, 17, and 9. Key dysregulated genes included KRT8 (upregulated) and SEMA3F (downregulated), implicating defects in smooth muscle differentiation and ureteral development. Conclusion: This first Bangladeshi transcriptomic study of PUJO identifies distinct molecular signatures involving neural signaling, ion transport, and developmental pathways. The findings provide novel insights into PUJO pathogenesis and potential biomarkers for early diagnosis. These results establish a foundation for developing targeted therapies to prevent renal damage in affected children.