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

Sachit Anand1, Anjali Srivastava1, Ajay Verma1

  • 1Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India.

International Journal of Molecular Sciences
|July 15, 2026
PubMed

Insights

Boys with posterior urethral valves (PUV) show higher global DNA methylation levels. This epigenetic alteration is linked to chronic kidney disease (CKD) severity and kidney scarring in these patients.

Area of Science:

  • Epigenetics
  • Pediatric Nephrology
  • Urology

Background:

  • Posterior urethral valves (PUV) are a common cause of congenital urinary tract obstruction in male infants.
  • PUV can lead to progressive chronic kidney disease (CKD) and kidney scarring, even after surgical correction.
  • The role of DNA methylation, an epigenetic mechanism, in the pathogenesis of PUV-associated CKD is not well understood.

Purpose of the Study:

  • To compare global DNA methylation levels, specifically 5-methylcytosine content (5-mC%), in peripheral blood between boys with PUV and healthy controls.
  • To investigate the association between global 5-mC% and kidney function (glomerular filtration rate), CKD stage, and kidney scarring in boys with PUV.

Main Methods:

  • A cross-sectional study involving 45 boys with PUV and 45 age-matched male controls.
  • Global DNA methylation (5-mC%) was quantified using an ELISA-based assay on peripheral blood samples.
  • Kidney function and scarring were assessed using nuclear scintigraphy; CKD staging was performed according to established criteria.

Main Results:

  • Global 5-mC% was significantly elevated in boys with PUV compared to controls (median 0.4336 vs. 0.3732, p < 0.001).
  • Within the PUV cohort, global 5-mC% demonstrated a positive correlation with CKD severity and a logarithmic association with CKD stage (R² = 0.8012).
  • Boys with kidney scarring exhibited higher global 5-mC% than controls (p < 0.001).

Conclusions:

  • Systemic global DNA methylation is altered in boys with posterior urethral valves.
  • Elevated global 5-mC% may serve as a potential biomarker for CKD progression and kidney scarring in PUV patients.
  • Further longitudinal research employing locus-specific methylation analysis is warranted to elucidate the precise mechanisms involved.

Keywords:
DNA methylationchronic kidney diseasecongenital anomalies of the kidney and urinary tractepigeneticsposterior urethral valves

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