DNA Damage in End-Stage Renal Disease Patients. Assessment by In Vitro Comet Assay and by Cell-Free DNA Quantification

Abstract

Inflammation is a common feature in end stage renal disease (ESRD) that might contribute to increase DNA damage. ESRD patients present increased circulating cell-free DNA (cfDNA) and different types of DNA injury. The underlying inflammatory process in ESRD may be associated with increased genomic damage and cfDNA contributing to further enhance inflammation. We analyzed the degree of genomic damage in ESRD patients under hemodialysis therapy, using the comet assay and cfDNA quantification. ESRD patients presented significantly higher C-reactive protein (CRP) and cell damaged DNA. The cfDNA correlated with age and inflammatory stage. Nine out of 39 patients died during the one year follow-up period and presented significantly higher cfDNA, than those who persisted alive. At lower CRP values, the increased DNA damage is still within the cell, and at higher CRP the damaged DNA is released in to plasma. The higher degree of genomic damage in ESRD might be a consequence of inflammation and aging, and may contribute to increase cancer and cardiovascular mortality risk. Our data suggest that the comet assay is more sensitive for low-grade inflammatory conditions, while cfDNA appears as a good biomarker for more severe inflammatory conditions, and as a biomarker for the outcome of ESRD patients.