Telomere attrition is associated with inflammation, low fetuin-A levels and high mortality in prevalent haemodialysis patients

Carrero, J.J. et al. (2008) Telomere attrition is associated with inflammation, low fetuin-A levels and high mortality in prevalent haemodialysis patients. Journal of Internal Medicine, 263(3), pp. 302-312. (doi:10.1111/j.1365-2796.2007.01890.x)

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Abstract

<p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Shiels, Professor Paul
Authors: Carrero, J.J., Stenvinkel, P., Fellstrom, B., Qureshi, A.R., Lamb, K., Heimburger, O., Bárány, P., Radhakrishnan, K., Lindholm, B., Soveri, I., Nordfors, L., and Shiels, P.G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Internal Medicine
Publisher:Wiley-Blackwell Publishing Ltd.
ISSN:0954-6820
ISSN (Online):1365-2796
Published Online:07 December 2007

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