Table 1.

Rationales for combined therapy with MRBs and other RAAS inhibitors

Use of MRBs with ACEIs or ARBS
1.Aldosterone “escape” or “breakthrough” (6, 8, 46)
2.Beneficial effects of MRBs can be demonstrated even in the absence of elevated systemic circulating aldosterone levels (42)
3.Upregulation or activation of mineralocorticoid receptors at the target organ level implies that tissue damage can occur even with normal systemic levels of aldosterone (19, 25, 47)
4.MRBs, ACEIs, and ARBs reduce oxidative stress and generation of reactive oxygen species (20, 21, 33, 34, 49, 50)
Use of MRBs with ARBs Rather than ACEIs
5.The specificity of ARBs may be permissive of beneficial effects of angiotensin II mediated through non-AT-1 receptor pathways; ACEIs reduce angiotensin II generation and would not necessarily favor non-AT-1 receptor effects (48)
6.There may be beneficial effects of individual ARBs that are not explained by class effects or inhibition of AT-1 receptors (49, 50)
7.Current cost differential between ARBs and ACEIs does not favor using ARBs alone as a first-line therapy in CKD (51)
  • ACEI, angiotensin-converting enzyme inhibitor; ARBs, angiotensin receptor blockers; AT-1, angiotensin II type-1 receptor; CKD, chronic kidney disease; MRBs, mineralocorticoid receptor blockers; RAAS, renin-angiotensin-aldosterone system.