Abstract
[Truncated] Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease (CVD) and this may relate to the complex interplay of traditional, novel and renal specific cardiovascular risk factors, such as hypertension, insulin resistance (IR), inflammation and dyslipidaemia. The relative contribution and significance of IR in predicting cardiovascular outcomes in CKD is largely unknown and may be driven directly by IR or indirectly through its effect on metabolic risk factors which are also seen in the metabolic syndrome (MetS). The dyslipidaemia of CKD, in the absence of IR, may be phenotypically similar to that seen in IR states and the MetS, which can worsen as IR progresses with declining renal function. IR is prevalent in CKD and has been shown as an independent predictor of future cardiovascular events. IR is associated with hypertension, dyslipidaemia, inflammation, increased oxidative stress, decreased adipocytokines and fibrinolysis, all of which may impact on cardiovascular risk. Vascular function studies which assess endothelial dysfunction (ED) and arterial stiffness can be used as surrogate markers for cardiovascular risk and shown to provide important prognostic information in patients with CKD. Modulation of IR in patients with CKD has the potential to improve vascular function and thereby reduce CVD risk in this population.
This thesis tests the principal hypothesis that IR directly or indirectly through its effects on metabolic risk factors such as dyslipidaemia mediates the increased risk for CVD in patients with CKD, and that this risk is potentially modified by treatment with an insulin sensitiser. To address the aims of this thesis, 3 separate studies were conducted. Study 1 was a case-control study which examines renal dyslipidaemia as it relates to IR and aims to define the underlying lipoprotein kinetic abnormalities. Study 2 was a cross-sectional study which examines the association between IR, vascular function and dyslipidaemia in CKD. It also aims to define the prevalence of MetS and examine the association between IR, MetS and vascular function. Study 3 was an interventional study to assess the effect of an insulin sensitiser, rosiglitazone (RSG), on measures of vascular function including endothelial function, systemic arterial compliance (SAC) and arterial stiffness in patients with stage 3-4 CKD.
This thesis tests the principal hypothesis that IR directly or indirectly through its effects on metabolic risk factors such as dyslipidaemia mediates the increased risk for CVD in patients with CKD, and that this risk is potentially modified by treatment with an insulin sensitiser. To address the aims of this thesis, 3 separate studies were conducted. Study 1 was a case-control study which examines renal dyslipidaemia as it relates to IR and aims to define the underlying lipoprotein kinetic abnormalities. Study 2 was a cross-sectional study which examines the association between IR, vascular function and dyslipidaemia in CKD. It also aims to define the prevalence of MetS and examine the association between IR, MetS and vascular function. Study 3 was an interventional study to assess the effect of an insulin sensitiser, rosiglitazone (RSG), on measures of vascular function including endothelial function, systemic arterial compliance (SAC) and arterial stiffness in patients with stage 3-4 CKD.
Original language | English |
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Qualification | Doctor of Philosophy |
Publication status | Unpublished - 2012 |