Global DNA Methylation in Children with Posterior Urethral Valves: Association with Kidney Function and Kidney Scarring.

Posterior urethral valves (PUV) cause congenital urinary tract obstruction and often lead to chronic kidney disease (CKD) despite treatment; however, DNA methylation remains underexplored in PUV. This cross-sectional study aimed to compare peripheral-blood global DNA methylation, measured as 5-methylcytosine content (5-mC%), between boys with PUV and age-matched male controls, and to assess its association with kidney function, CKD stage, and kidney scarring. The study included 45 boys with PUV and 45 age-matched boys as controls. Peripheral-blood global 5-mC% was quantified using an ELISA-based assay. Glomerular filtration rate and kidney scarring were assessed by nuclear scintigraphy, and PUV patients were categorized according to CKD stage and scarring status. Statistical comparisons were performed using the Kruskal-Wallis test followed by Dunn's test, with exploratory trend analysis used to evaluate the association between global 5-mC% and CKD severity. Global 5-mC content was significantly higher in PUV patients than in controls (median 5-mC%: 0.4336 vs. 0.3732, p < 0.001). Within the PUV cohort, global 5-mC% increased with CKD severity (p < 0.05) and showed a logarithmic association with CKD stage (R2 = 0.8012). Patients with kidney scarring also had significantly higher global 5-mC% than controls (p < 0.001), although differences across individual CKD stages and scarring subgroups were not statistically significant. These findings suggest altered systemic global 5-mC content in boys with PUV and support larger, longitudinal studies incorporating locus-specific methylation profiling.