Genotoxic damage in end-stage renal disease

End-stage renal disease (ESRD) patients are at increased risk for cardiovascular events and cancer, possibly due to genomic instability associated with renal disease and/or its therapy. Prognostic biomarkers of genomic instability may prove useful for initiating appropriate intervention strategies. We conducted a case-control study, performing the single-cell gel electrophoresis assay (circulating leukocytes) and the micronucleus cytome assay (buccal epithelial cells). Cases (ESRD patients; n = 55) were on weekly/fortnightly dialysis therapy and controls (n = 39) were healthy adults. The patients had significantly elevated levels of DNA damage and micronucleated cells. DNA damage showed higher validity and sensitivity than did chromosome damage, for discriminating patients from controls. The patient group showed significant increases in cell proliferation, cytokinetic defects, and cell death, and a decrease in repair index. Correlations were seen between genetic damage and both time-onmedication and time-on-dialysis; between condensed chromatin cells and sex; and between pyknotic cells and dietary pattern. Following stratification by age, gender, and dialysis frequency, significantly elevated DNA damage and MN frequency were seen in the fortnightly dialysis patients, perhaps due to accumulated uremic toxicants. DNA and chromosome damage may be useful prognostic biomarkers for initiating timely interventions against co-morbidities in ESRD patients.