Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.590049
Title: The role of calcification regulatory proteins in the arterial stiffening of chronic kidney disease stages 3 & 4
Author: Ford, Martin
Awarding Body: University of Brighton
Current Institution: University of Brighton
Date of Award: 2012
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Abstract:
Background: Chronic Kidney Disease (CKD) is common and is associated with an increased cardiovascular morbidity and mortality which is not completely explained by traditional risk factors. Non-traditional risk factors include arterial stiffening and calcification. Several calcification regulatory proteins (CaRP) are implicated in arterial stiffening. Fetuin-A may be important in inhibiting mineralisation via physicochemical interaction with calcium and phosphate, and can form circulating CalciProtein Particles (CPP) in pro-calcific states. Osteoprotegerin (OPG) & Receptor Activator of Nuclear Factor K-B Ligand (RANKL) control bone resorption and are also expressed in the vasculature. They may be important in vascular calcification. Fibroblast growth factor 23 (FGF-23) promotes urinary phosphate excretion and is also thought to be implicated in vascular disease. This study tests the hypotheses that these CaRP are associated with aortic stiffening in pre-dialysis CKD, and that CaRP and/or arterial stiffening are associated with outcomes. Method: 200 CKD stage 3 & 4 subjects were enrolled in this study. Subjects underwent annual measurement of aortic stiffness with carotid-femoral pulse wave velocity (C-F PWV) and CaRP were measured. Outcomes measures were C-F PWV and high sensitivity troponin T (hs-cTnT), a recently introduced biomarker of adverse cardiovascular outcome assessed at baseline, rate of change of C-F PWV, rate of change of renal function and survival. Major Results: OPG and CPP were independently associated with arterial stiffness. OPG, RANKL and FGF-23 were associated with hs-cTnT, independently of other recognised risk factors. Neither CaRP nor arterial stiffness were associated with rate of change of renal function. OPG:RANKL was associated with adverse survival in addition to hs-cTnT. C-F PWV increased across the follow up period and was independently associated with the combined end point of renal and patient survival in a time dependent manner. Conclusion: This study provides epidemiological evidence of the association between CaRP and a variety of cardiovascular measurements and outcomes including arterial stiffness, stiffening and survival. Arterial stiffness was associated with the combined outcome of death or progression of renal disease. Evidence of an association between arterial stiffness and either progression of renal disease or survival alone could not be proven.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.590049  DOI: Not available
Keywords: A000 Medicine
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