Edwards, Nicola Catherine (2011)
Ph.D. thesis, University of Birmingham.
This thesis examined whether patients with early stage chronic kidney disease (CKD) have abnormalities of arterial stiffness and cardiac function. Aldosterone is known to promote inflammation and fibrosis in the arteries, heart and kidney. Treatment with spironolactone, which blocks aldosterone at the mineralocorticoid receptor might be effective at reducing such injury. To address these hypotheses, I performed an observational study in patients with early stage CKD without known cardiovascular disease and healthy volunteers. Aortic stiffness and myocardial structure and function were assessed using cardiac MRI and echocardiography. I demonstrated reductions in aortic distensibility, increased ventricular and arterial stiffness and impairment of markers of left ventricular systolic and diastolic function in CKD. I complemented this work by performing a randomised double blind controlled trial examining the effect of spironolactone on intermediate prognostic markers of cardiovascular function. Spironolactone reduced arterial stiffness and left ventricular mass and improved markers of systolic and diastolic function independent of changes in blood pressure. Spironolactone was well tolerated with low rates of hyperkalaemia and renal dysfunction. These findings support a role for spironolactone in reducing aldosterone mediated cardiovascular injury in early stage CKD. A clinical outcome study evaluating spironolactone in CKD is now required
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