Telomere attrition is associated with inflammation, low fetuin-A levels and high mortality in prevalent haemodialysis patients
Article first published online: 7 DEC 2007
© 2007 Blackwell Publishing Ltd
Journal of Internal Medicine
Volume 263, Issue 3, pages 302–312, March 2008
How to Cite
Carrero, J. J., Stenvinkel, P., Fellström, B., Qureshi, A. R., Lamb, K., Heimbürger, O., Bárány, P., Radhakrishnan, K., Lindholm, B., Soveri, I., Nordfors, L. and Shiels, P. G. (2008), Telomere attrition is associated with inflammation, low fetuin-A levels and high mortality in prevalent haemodialysis patients. Journal of Internal Medicine, 263: 302–312. doi: 10.1111/j.1365-2796.2007.01890.x
- Issue published online: 7 DEC 2007
- Article first published online: 7 DEC 2007
- telomere length
Introduction. Chronic kidney disease (CKD) predisposes to a 10- to 20-fold increased cardiovascular risk. Patients undergo accelerated atherogenesis and vascular ageing. We investigated whether telomere attrition, a marker of cell senescence, contributes to this increased mortality risk.
Methods. This is a cross-sectional study in prevalent haemodialysis patients [n = 175; 98 Males; median (range) age: 66 (23–86) years]. Biochemical markers of oxidative stress and inflammatory status were measured in relation to the patient’s leucocyte telomere length. Overall mortality was assessed after a median of 31 (range 2–42) months.
Results. Telomere length was shorter in CKD men, despite women being older (average ± SD 6.41 ± 1.23 vs. 6.96 ± 1.48 kb, P = 0.002). Telomere length was associated with age (rho = −0.18, P = 0.01), fetuin-A (rho = 0.26, P = 0.0004), high-sensitivity C-reactive protein (rho = −0.21, P = 0.005) and IL-6 (rho = −0.17, P = 0.02). In a multivariate logistic regression (pseudo r2 = 0.14), telomere length was associated with age >65 years (odds ratio: 2.11; 95% CI: 1.10, 4.06), sex (2.01; 1.05, 3.86), fetuin-A (1.85; 0.97, 3.50) and white blood cell count (2.04; 1.02, 4.09). Receiver operating characteristic curves identified a telomere length < 6.28 kb as a fair predictor of mortality. Finally, reduced telomere length was associated with increased mortality, independently of age, gender and inflammation (likelihood ratio 41.6, P < 0.0001), but dependently on fetuin-A levels.
Conclusion. Age and male gender seem to be important contributors to reduced telomere length in CKD patients, possibly via persistent inflammation. Reduced telomere length also contributes to the mortality risk of these patients through pathways that could involve circulating levels of fetuin-A.