There is also accumulating evidence to suggest that the addition of MRBs to ACE inhibitors in CKD might have beneficial effects by slowing the otherwise progressive decline in renal function. Animal experiments have shown that aldosterone can mediate renal injury and that MRBs such as eplerenone effectively reduce this. MRBs remain effective in low aldosterone models of CKD probably reflecting the importance of local (paracrine) aldosterone synthesis. In humans, small studies have suggested that the addition of MRBs to ACE inhibitors or ARB reduces proteinuria and may slow the progression of renal disease. Thus, the widespread use of MRBs in CKD has been advocated and has even been termed 'renal aspirin'. Until the publication of the CRIB-2 trial however, little attention had been paid to the potentially beneficial effects of MRB therapy on the cardiovascular system in patients with CKD.