1. Chronic kidney disease and cardiovascular disease CKD is a major but poorly recognised and under-treated risk factor for cardiovascular disease. It can be categorised in to 5 stages according to GFR and the presence of markers of kidney damage. Stage 3 CKD, the subject of this proposal, is defined by a glomerular filtration rate (GFR) of 30-59 ml/min/1.73m2. There is a graded inverse relationship between cardiovascular risk and GFR which is independent of age, sex and other risk factors. There is also a graded association between albuminuria and cardiovascular risk and in patients with both low GFR and albuminuria, risk is increased with a multiplicative association. While the cardiovascular risk of end stage CKD is extreme, in public health terms the burden resides in early stage (CKD stages 1-3) disease, which is more prevalent affecting almost 1 in 7 of the entire population, including approximately 4% of those aged 40-59 and more than 40% of those over 70 years. Thus, CKD is a potentially important risk factor for cardiovascular disease in the general population. Although the risks of myocardial infarction and other manifestations of coronary artery disease are increased in CKD, there is a much greater increase in the incidence of heart failure and sudden cardiac death in stages 3-5. This is almost certainly a reflection of the very high prevalence of myocardial disease; left ventricular hypertrophy (LVH) often accompanied by magnetic resonance imaging evidence of fibrosis is present in over 30% of patients with stage 2 (GFR 60-89) and stage 3 CKD and in 80% of patients at the start of renal replacement therapy. To date, the only prospective trial to examine the prognostic benefit of drug therapy in this high risk group is the recently presented SHARP trial. This showed a reduction in occlusive vascular events associated with LDL lowering with simvastatin and ezetimibe. The Birmingham CRIB-2 study (see below) published in 2010 provided evidence that mineralocorticoid receptor blockade with spironolactone exerts beneficial effects on intermediate end points of strong prognostic value including LV mass and arterial stiffness. That work provides the basis for this application.