Telomere length is associated with increased risk of bleeding in patients on hemodialysis

Introduction Patients with end-stage kidney disease (ESKD) on hemodialysis (HD) have a high risk for bleeding complications. The tendency of bleeding events in ESKD patients is multifactorial and influenced by impaired platelet-vessel wall interaction, dysfunctional platelets, and treatment like anticoagulation therapy. Telomere length is a recognized surrogate parameter for biological and early vascular aging. Healthy persons have a chronological age-dependent telomere length approximately between 5 to 15 kb per diploid cell. Our aim is to elucidate the role of bleeding in association with biological aging, expressed by telomere length.

Method The Vienna Investigation of Atrial Fibrillation and Thromboembolism in Hemodialysis (VIVALDI) study is a prospective population-based cohort study of prevalent HD patients. Adult patients were recruited and followed-up for a maximum of 1350 days during which the occurrence of major bleeding events was recorded. The VIVALDI study was approved by the local ethics committees and all patients consented to participate in written form. The DNA from whole blood, sampled at baseline, was isolated and analyzed for average telomere length via qPCR-based method. The risk of major bleeding occurrence was calculated using competing risk regression with consideration of the competing endpoint all-cause death.

Results In 308 patients (193 males (62.7%) and 115 females (37.3%)) with ESKD and a median age of 67 years (25th to 75th percentile 56.4-76) years, the median telomere length was 1.51 kb (25th to 75th percentile (0.60 to 3.18kb). Major bleeding events occurred in 39 patients (incidence rate 5.7 per 100 patient-years). There was no relevant correlation between telomere length and chronological age (correlation coefficient of -0.117, p=0.040). Per 1kb increase in telomere length, the risk of major bleeding occurrence increased by 9% (SHR 1.094, 95% confidence interval 1.021-1.172, p=0.011) in a multivariable competing risk regression model adjusted for age, BMI, and anticoagulation use ([Fig. 1]). Compared to patients in the quartile with the shortest telomere lengths, patients in the second quartile had a 3.3-fold increased risk of major bleeding (95% CI 1.02-10.56, p=0.046), patients in the third quartile had a 3.4-fold increased risk (95%CI 1.09-10.77, p=0.036), and patients in the fourth quartile had a 3.1-fold increased risk of major bleeding (95%CI 0.98-10.1, p=0.053) ([Fig. 2]).

Fig. 1  Competing risk regression model of major bleeding risk occurrence

Fig. 2  Cumulative probability of major bleeding occurrence according to quartile of telomere leng

Conclusion In a cohort of patients with ESKD on HD and overall short telomere lengths, the risk of major bleeding increased with increasing telomere lengths.

Publikationsverlauf

Artikel online veröffentlicht:
26. Februar 2024