Telomere shortening and haemodialysis.
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).


CONCLUSIONS
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.
Boxall
Mark C
MC
Institute of Human Genetics and Institute for Ageing and Health, University of Newcastle upon Tyne, and Renal Unit, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK.
Goodship
Timothy H J
TH
Brown
Alison L
AL
Ward
Michael C
MC
von Zglinicki
Thomas
T
D000447:Aldehydes / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D011237:Predictive Value of Tests; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods*; D016615:Telomere / Q000235:genetics* / Q000473:pathology*
D000447:Aldehydes; D008315:Malondialdehyde; D002097:C-Reactive Protein