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Genotoxic damage in end-stage renal disease.

G Gandhi1, T Mehta1, P Contractor1

  • 1Department of Human Genetics, Guru Nanak Dev University, Amritsar, 143 005, India.

Mutation Research. Genetic Toxicology and Environmental Mutagenesis
|September 26, 2018
PubMed
Summary

Genomic instability biomarkers, including DNA damage, are elevated in end-stage renal disease (ESRD) patients undergoing dialysis. These markers can help identify patients needing timely interventions for associated health risks.

Keywords:
Buccal cytomeComet assayDialysisMicronucleus

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Area of Science:

  • Biomarkers
  • Genomics
  • Renal Disease

Background:

  • End-stage renal disease (ESRD) patients face higher risks of cardiovascular events and cancer.
  • Genomic instability may contribute to these comorbidities in ESRD.
  • Prognostic biomarkers for genomic instability could guide interventions.

Purpose of the Study:

  • To investigate genomic instability in ESRD patients on dialysis.
  • To evaluate DNA damage and chromosome damage as potential biomarkers.
  • To correlate genetic damage with clinical factors in ESRD.

Main Methods:

  • Case-control study comparing ESRD patients (n=55) and healthy controls (n=39).
  • Assays used: single-cell gel electrophoresis (leukocytes) and micronucleus cytome assay (buccal cells).
  • Evaluated DNA damage, chromosome damage, cell proliferation, and cell death.

Main Results:

  • ESRD patients exhibited significantly higher DNA damage and micronucleated cells compared to controls.
  • DNA damage was more sensitive and valid than chromosome damage for distinguishing patients.
  • Increased cell proliferation, cytokinetic defects, cell death, and decreased repair index were observed in patients.
  • Genetic damage correlated with medication duration, dialysis duration, sex, and dietary patterns.
  • Fortnightly dialysis patients showed elevated DNA damage and micronucleus frequency, possibly due to uremic toxicants.

Conclusions:

  • Elevated DNA and chromosome damage in ESRD patients indicate genomic instability.
  • These damage markers show potential as prognostic indicators for ESRD comorbidities.
  • Timely interventions can be initiated based on these biomarkers.