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.
