P1439DO PATIENTS ON DIALYSIS AGE FASTER THAN HEALTHY ADULTS BASED ON TELOMERE LENGTH; A BIOLOGICAL MARKER OF AGEING AND MORTALITY?
Authors: Muthuppalaniappan Vasantha , McCafferty Kieran , Yaqoob Muhammad 
Published: June 2020

Abstract

Background and Aims
Telomere length (TL) is an emerging novel biomarker of ageing and survival. Telomere shortening to a critical limit is associated with replicative senescence and cell death; a process accelerated by oxidative stress and chronic inflammation. This process is often observed among patients with end stage kidney disease (ESKD). This predisposes them to increased morbidity and mortality in comparison to their normal counterparts when matched for age and gender. The exact reason for premature ageing in this cohort remains poorly understood and there is a need for further investigations into biomarkers of ageing to help understand the process. The aim of the study was to investigate if patients with ESKD in comparison to healthy controls had an increased biological age based on telomere length measurements.

Method
This was a single centre prospective, observational, cohort study among eligible dialysis patients and healthy controls. The healthy control group consisted of potential living donors. Patients were recruited as per the study protocol. Recruited patients on HD had their blood sampled prior to their mid-week dialysis session while potential live donors and PD patients had their blood sampled at outpatient clinics. Whole blood was immediately isolated for peripheral blood mononuclear cells (PBMC). Genomic DNA was extracted from PBMC to measure relative telomere length (rTL) by quantitative real-time polymerase chain reaction according to the modified Cawthon protocol. Baseline demographic data and 1-year mortality were obtained from electronic patient records.

Results
A total of 336 patients (125 patients on HD, 114 patients on PD and 100 healthy controls) had their baseline rTL measured between the period of December 2015 to July 2018. Inter assay CV for rTL assay was 4.86%. Mean age of the dialysis cohort was 54.3 with an age range between 23-83 years. Mean age of control cohort was 44.5 with an age range between 20-75years. There were 87 and 56 females in the dialysis and control cohort respectively. Age was significantly associated with TL in a multivariate regression model in both the dialysis (p&lt;0.001) and control group (p&lt;0.001). There was no significant difference in mean TL between gender in the healthy cohort in our study p=0.778. However, mean TL was higher in females than in males among dialysis patients, p=0.007. Mean TL of control and dialysis group was 2.23 ± 0.33 and 2.11 ± 0.34 respectively. The difference in TL between the groups was significant, p=0.006. However, a multivariate analysis of TL adjusted for age and gender was not significant, p=0.875. This was due to the control cohort consisting of younger recruits in comparison to the dialysis cohort. TL was not significantly different between HD and PD patients. There were 10 deaths in 365 days with no loss of follow up throughout the study period. All the deaths were in the dialysis cohort. There was no significant association found between TL and mortality outcomes but the direction of effect i.e shorter TL was associated with increased risk of death.

Conclusion
This study failed to show any difference between TL between dialysis patients and controls to demonstrate that patients on dialysis age faster. This does not preclude current evidence suggesting that dialysis patients do have an accelerated ageing in comparison to healthy cohort but merely that our study has shown that TL may not be the ideal biomarker of ageing to demonstrate this difference. In fact, increasing animal studies have found that the rate of change in TL over a period of time is a better representation of ageing. The study also identified no association between TL and 1-year mortality as there were only 10 deaths within the 1 year of follow up. This may be largely due to a short duration of follow up and it may be interesting to evaluate TL and 5-year mortality data in this cohort in future.