Efficacy and safety assessment of mineralocorticoid receptor antagonists in patients with chronic kidney disease

Eur J Intern Med. 2023 Sep:115:114-127. doi: 10.1016/j.ejim.2023.05.038. Epub 2023 Jun 14.

Abstract

Background: The objective of our study is to evaluate the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) and determine the optimal MRA treatment regimen in patients with chronic kidney disease (CKD).

Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library from their inception to June 20, 2022. The composite kidney outcome, cardiovascular events, urinary albumin to creatinine ratio (UACR), estimated glomerular filtration rate (EGFR), serum potassium, systolic blood pressure (SBP), diastolic blood pressure (DBP), creatine and creatine clearance were included for analysis. We conducted pairwise meta-analyses and Bayesian network meta-analyses (NMA) and calculated the surface under the cumulative ranking curve (SUCRA).

Results: We included 26 studies with 15,531 participants. By pairwise meta-analyses, we found that MRA treatment could significantly reduce UACR in CKD patients with or without diabetes. Notably, compared to placebo, Finerenone was associated with a lower risk of composite kidney outcome and cardiovascular events. Data from NMA demonstrated an overt UACR reduction without increasing serum potassium by Apararenone, Esaxerenone, and Finerenone in CKD patients. Spironolactone decreased SBP and DBP but elevated CKD patients' serum potassium.

Conclusions: Compared to placebo, Apararenone, Esaxerenone, and Finerenone might ameliorate albuminuria in CKD patients without causing elevated serum potassium levels. Remarkably, Finerenone conferred a cardiovascular benefit, and Spironolactone lowered blood pressure in CKD patients.

Keywords: Cardiovascular event; Chronic kidney disease; Mineralocorticoid receptor antagonist; Serum potassium; The primary composite kidney outcome; Urinary albumin to creatinine ratio.

MeSH terms

  • Bayes Theorem
  • Cardiovascular Diseases* / drug therapy
  • Creatine / therapeutic use
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetic Nephropathies* / drug therapy
  • Humans
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Potassium
  • Renal Insufficiency, Chronic* / chemically induced
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / drug therapy
  • Spironolactone / therapeutic use

Substances

  • Mineralocorticoid Receptor Antagonists
  • esaxerenone
  • Spironolactone
  • apararenone
  • Creatine
  • Potassium