Telomere Shortening and Haemodialysis

Abstract

Background: Increased oxidative stress is a well described feature of haemodialysis (HD). This is secondary to an increase in the production of reactive oxygen species and impaired antioxidant mechanisms. Telomeres are the specialized ends of eukaryotic chromosomes and consist of tandemly repeated DNA sequences. Telomeres shorten with each cell division and it is well known that telomere length in peripheral blood mononuclear cells (PBMCs) decreases with age. Telomere shortening rate is increased by oxidative stress. In this study we have examined a possible relationship between oxidative stress and telomere shortening in haemodialysis. Methods: 20 control subjects, 20 non-diabetic and 18 diabetic HD patients were studied. Peripheral blood mononuclear cell telomere length, plasma malondialdehyde plus 4-hydroxyalkenal (MDA+4-HAE) concentration (a marker of oxidative stress) and C-reactive protein (CRP) concentration were measured. Results: MDA+4-HAE and CRP were significantly higher in the HD patients (CRP, controls 7.5 ± 1.5, HD patients 16.4 ± 3.1 mg/l, p < 0.05). There was no difference in mean telomere length between the HD patients and controls (control, 8,283 ± 179 bp; non-diabetic HD, 7,966 ± 160 bp; diabetic HD, 8,033 ± 197 bp) but age adjusted residual telomere length was inversely associated with the length of time on dialysis (r = –0.35, p = 0.03). Conclusion: These results suggest that length of time on dialysis is independently associated with increased telomere shortening in HD patients. We hypothesise that this reflects cumulative DNA exposure to oxidative stress.