Mineralocorticoid Receptor Antagonists—Use in Chronic Kidney Disease

Abstract

Mineralocorticoid receptor antagonists (MRA) are drugs with a potentially broad spectrum of action. They have been reported to have healing effects in many diseases, such as chronic heart failure, hypertension, or nephrotic syndrome. Numerous studies suggest that mineralocorticoid receptor activation is pathogenic and a progression factor of chronic kidney disease (CKD); however, results of studies on the use of MRA in the treatment of CKD are inconclusive. Current guidelines recommend against the use of MRA in patients with advanced CKD. Although, there is growing interest on their use in this population due to treatment benefits. In this review, we summarize studies which were purposed to evaluate the impact of MRA therapy on CKD patients. Despite many benefits of this treatment e.g., reducing cardiovascular mortality or alleviating proteinuria, steroidal MRA (such as spironolactone or eplerenone) have a low safety profile. They often lead to hyperkalemia complications which are dangerous in patients with CKD, and diabetic nephropathy, especially in hemodialysis patients. Studies on recently developed nonsteroidal MRA showed that they have fewer side effects. In our review, we discuss steroidal and nonsteroidal MRA treatment effects on the estimated glomerular filtration rate (eGFR), proteinuria, the cardiovascular system, and hyperkalemia in CKD patients. We present new content and recent publications in this field.

Efficacy and Safety of Finerenone in Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

“…Although finerenone was associated with a higher overall risk of hyperkalemia than placebo, a markedly lower incidence of hyperkalemia and lower mean change of potassium concentrations were observed in the finerenone than in the spironolactone group (Pitt et al, 2013;Kintscher et al, 2021). Since our data showed that finerenone increased kalemia by 0.17 mmol/L, finerenone should not be afraid of the risk of hyperkalemia because of the potential benefits of taking it (Baran et al, 2021). However, Randomized Aldactone Evaluation Study (RALES) cautions us about what also might come following the publication of impactful results from controlled trials (Moura-Neto and Ronco, 2021).…”

Results from a Phase 1 Study Assessing the Pharmacokinetics of the Aldosterone Synthase Inhibitor Baxdrostat in Participants with Varying Degrees of Renal Function

“…Reducing aldosterone activity in these patients may therefore delay the progression of CKD by reducing BP and preventing renal fibrosis 22 . Spironolactone and eplerenone, older MR antagonists, have been shown to induce changes in biomarkers associated with an improvement in the progression of CKD, presumably due to their anti‐inflammatory and antifibrotic effects; however, they are not approved for the treatment of CKD and use is not recommended in advanced CKD 8 . Finererone, a newer nonsteroidal MR antagonist, is approved for use in patients with diabetic kidney disease, but had a modest effect on BP, 10 whereas a phase 2 study of baxdrostat in patients with resistant hypertension demonstrated a significant reduction in systolic BP 15 .…”

The Effect of Aldosterone on Cardiorenal and Metabolic Systems

“…Patients treated with the MR antagonist and ACEI/ARB showed lower albuminuria compared with those treated with ACEI/ARB alone [ 126 ]. MR antagonists may contribute to the beneficial effect on the kidney by reducing proteinuria and suppressing CKD progression.…”