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Research Paper|Volume 7, Issue 10|pp 766—775

Telomere length, cardiovascular risk and arteriosclerosis in human kidneys: an observational cohort study

Katrien De Vusser1,2, Nicky Pieters3, Bram Janssen3, Evelyne Lerut4,5, Dirk Kuypers1,2, Ina Jochmans1,6, Diethard Monbaliu1,6, Jacques Pirenne1,6, Tim Nawrot3,7, Maarten Naesens1,2
  • 1Department of Microbiology and Immunology, KU Leuven – University of Leuven, Leuven, Belgium
  • 2Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
  • 3Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium
  • 4Department of Imaging and Pathology, KU Leuven – University of Leuven, Leuven, Belgium
  • 5Department of Pathology, University Hospitals Leuven, Leuven, Belgium
  • 6Department of Abdominal Transplantation Surgery, University Hospitals Leuven, Leuven, Belgium
  • 7Department of Public Health and Primary Care, KU Leuven – University of Leuven, Leuven, Belgium
Received: August 13, 2015Accepted: September 20, 2015Published: September 30, 2015
https://doi.org/10.18632/aging.100814

Copyright: © 2015 De Vusser et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background Replicative senescence, associated with telomere shortening, plays an important role in aging and cardiovascular disease. The relation between telomere length, cardiovascular risk, and renal disease is unknown. Methods Our study consisted of a cohort of 257 kidney donors for transplantation, divided into a test and a validation cohort. We used quantitative RT‐PCR to measure relative telomere length (log T/S ratio) in peripheral blood leucocytes, and in kidney biopsies performed prior to implantation. The association between leucocyte and intrarenal telomere length, cardiovascular risk factors, and renal histology, was studied using multiple regression models, adjusted for calendar age, gender and other donor demographics. Results Subjects with intrarenal arteriosclerosis had significantly shorter leucocyte telomere length compared with patients without arteriosclerosis (log T/S ratio ‐0.3 ± 0.4 vs. 0.1 ± 0.2 with vs. without arteriosclerosis; p = 0.0008). Intrarenal arteriosclerosis was associated with shorter telomere length, independent of gender, calendar age, history of hypertension and history of cardiovascular events. For each increase of one standard deviation of the log T/S ratio, the odds for intrarenal arteriosclerosis decreased with 64% (Odds ratio 0.36; 95% CI 0.17‐0.77; p = 0.02). In accordance with leucocyte telomere length, shorter intrarenal telomere length associated significantly with the presence of renal arteriosclerosis (log T/S ratio ‐0.04 ± 0.06 vs. 0.08 ± 0.01 with vs. without arteriosclerosis, p = 0.007), and not with other histological lesions. Interpretation We demonstrate that arteriosclerosis in smaller intrarenal arteries is associated with shorter telomere length. Our study suggests a central role of replicative senescence in the progression of renovascular disease, independent of calendar age.