Steroidal and Non-steroidal Mineralocorticoid Receptor Antagonists in Cardiorenal Medicine

Rajiv Agarwal; Peter Kolkhof; George Bakris; Johann Bauersachs; Hermann Haller; Takashi Wada; Faiez Zannad

Disclosures

Eur Heart J. 2021;42(2):152-161. 

In This Article

Summary of the Development of Steroidal Mineralocorticoid Receptor Antagonists

The remarkable progress in the development of MRAs is summarized in Figure 1. Up to the 1970s, DOCA synthesis contributed to research on the physiology, pharmacology, and pathophysiology of MR agonists; progesterone was identified as a natural MRA; and parenteral and oral drugs were developed as MRA (outlined in the next section). This was followed by a ~30-year hiatus, after which lifesaving benefits of MRAs for patients with HFrEF[17] culminated in a Level 1A recommendation in clinical guidelines.[37] A critical unmet need exists to slow progression of CKD to ESKD, especially in patients with T2D. In CKD, use of steroidal MRAs in preclinical studies demonstrates benefit, but the associated side effects, including hyperkalaemia, persist as the main limitations for broad implementation in clinical use for CV and kidney protection.

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