The mechanisms of action of aldosterone include upregulation of Angiotensin 1 receptors and direct effects on fibroblast collagen synthesis as well as decreased matrix metallo-proteinase secretion. An anti-fibrotic effect of MRB therapy may be of major importance. After myocardial infarction, circulating markers of collagen turnover and fibrosis were reduced by MRB therapy and in the RALES study myocardial collagen turnover was significantly reduced by spironolactone and the fall in the marker of this index was related to the mortality benefit. In CKD stages 2 and 3, data from CRIB-2 showed that spironolactone improves myocardial diastolic function and collagen turnover. .