thesis

Progression of coronary artery disease in patients with end stage renal disease

Abstract

Coronary artery disease is highly prevalent in the end stage renal disease population. For the general population, there are guidelines for managing coronary artery disease, however there are no clear consensus guidelines for patients with end stage renal disease. Renal transplantation is superior to dialysis in terms of both patient survival and quality of life. A significant proportion of potential renal transplant candidates are at high risk of coronary artery disease; they need to be scrutinized and aggressively treated for risk factors in order to maintain the graft and survival benefit that has been created by organ donation. In addition, clinicians also need to consider the risk of cardiovascular disease for dialysis patients not undergoing transplantation. In terms of pathophysiological processes, there is growing evidence of a varied and significant effect of chemokines on cardiovascular disease; of particular interest are MCP-1, CCL15 and CCL18. There also exists established data demonstrating that the non-invasive investigation of measuring carotid intimal media thickness appears to be predictive of cardiovascular mortality in patients with end stage renal disease. Whilst coronary angiography is considered the gold standard investigation for diagnosing and treating coronary artery disease, it is an invasive procedure and therefore not without complication and is an expensive resource. This work examines the effect of elective coronary angiography on glomerular filtration rate in patients with advanced chronic kidney disease and has demonstrated that coronary angiography performed in a timely fashion did not accelerate the decline in renal function. In addition this work examines the cardiac survival of potential transplant patients undergoing coronary angiography and intervention and has demonstrated that a thorough approach to diagnosing and intervening on angiographically significant coronary artery disease was associated with a low incidence of cardiac mortality and morbidity. Finally, this work has demonstrated higher chemokine levels in patients with progressive coronary artery disease compared to patients without progressive coronary artery disease, and shows that a significant proportion of patients with normal coronary angiograms at initial screening have no evidence of angiographically progressive disease over a 3 year period. These results can be applied when performing cardiac risk stratification in an end stage renal failure population. In addition this work provides some evidence to support chemokines as appealing targets for novel therapies in the future

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