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Title: Arterial Stiffness and Chronic Kidney Disease
Author: Tomlinson, Laurie
ISNI:       0000 0004 2688 625X
Awarding Body: University of Brighton and Sussex
Current Institution: University of Brighton
Date of Award: 2009
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Introduction: Chronic kidney disease (CKD) common, particularly in the elderly, and is linked to an increased risk of cardiovascular disease (CVD). This is partly explained by joint risk factors such as hypertension and diabetes but novel risk factors such as arterial stiffness, arterial calcification and endothelial dysfunction may play a role. Our aims were 1) to prospectively investigate whether aortic stiffness was linked with rate of decline of renal dysfunction, 2) to investigate the associations of arterial stiffness in patients with moderate renal dysfunction, and 3) to investigate whether aortic stiffness was linked with adverse outcomes. Secondary aims were to explore the links between 24 hour ambulatory blood pressure (BP) monitoring (24h ABPM), aortic stiffness, and the novel CV risk factors asymmetric dimethylarginine (ADMA) and Fetuin-A. Methods: This is an observational study of 133 patients with CKD stages 3-4 (estimated GFR 15-60mUmin). At baseline subjects underwent full assessment of CV risk, measurement of arterial stiffness, Fetuin-A, ADMA, and 24h ABPM. Patients were then followed-up with repeat of arterial stiffness measurements 6- monthly. Change in renal function and clinical events were recorded. Major results: Renal function is a determinant of aortic stiffness independent of other well-described factors. Aortic stiffness is closely linked to deterioration in renal function and predicts cardiovascular events within this cohort. There is a high prevalence of ambulatory hypotension during 24h ABPM in older patients with CKD, and a large difference in BP between clinic and home measurements. The BP difference is associated with aortic stiffness, and is suggestive of a causal relationship. A rise in BP at night is associated with increased aortic stiffness, as is the related measure of postural hypotension. ADMA levels are related to change in renal function, while Fetuin-A is related to change in aortic stiffness. Conclusion: In this predominantly elderly cohort of patients with CKD stages 3 and 4, aortic stiffness is associated with baseline and change in renal fundion, CV risk and BP pattems. This highlights the close links between macro- and microvascular disease and suggests that knowledge of aortic stiffness may be crucial in further understanding the pathophysiology and treatment of renal disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available