Cardio-Renal Syndrome clinical trials

Comparing the Effects of Spironolactone With Chlortalidone on LV Mass in Patients With CKD

In stage 3 chronic kidney disease (CKD) the risk of death due to cardiovascular causes is high and greatly exceeds the risk of progression to end stage renal failure. This high cardiovascular risk is predominantly due to sudden cardiac death and heart failure, manifestations of left ventricular hypertrophy and fibrosis. Aldosterone appears to play an important role in the causation of this myocardial disease both by direct inflammatory and fibrotic myocardial effects and via increased arterial stiffness due to hypertrophy, inflammation, and fibrosis within the media of large arteries. Levels of aldosterone are high in CKD despite sodium overload and treatment with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) drugs due to the twin phenomena of aldosterone escape and breakthrough. In a previous British Heart Foundation funded study, Birmingham investigators showed that the addition of the mineralocorticoid receptor blocker (MRB) spironolactone to background therapy with ACE inhibitors or ARBs caused reductions in the prognostically important parameters of arterial stiffness and LV mass. Because spironolactone therapy was also associated with significant falls in arterial pressure it remains possible that these effects were mediated simply by blood pressure reduction. In this multi-centre, randomised controlled study, the effects of treatment with spironolactone on LV mass and arterial stiffness in patients with stage 3 CKD on established ACE or ARB therapy will be compared to those of chlortalidone, a control anti-hypertensive agent. Early stage chronic kidney disease is highly prevalent and new, cost effective treatment strategies are required to reduce cardiovascular risk. This study is designed to provide the rationale for a larger study of morbidity and mortality with MRB therapy in early stage CKD.