Safety and cardiovascular effects of mineralocorticoid receptor antagonists for patients receiving hemodialysis: a systematic review and meta-analysis

Abstract

Introduction Cardiovascular disease is an important factor in the mortality and morbidity of patients with end-stage renal disease receiving hemodialysis. Although mineralocorticoid receptor antagonists may have potential benefits on the cardiovascular system, their safety for patients on hemodialysis remains unclear, considering the differences between the results of already performed clinical trials. Methods MEDLINE, EMBASE, Cochrane, ClinicalTrials.gov and PubMed databases were searched for relevant clinical trials. The Cochrane Collaboration assessment tool was employed to evaluate the quality of the randomized controlled trials. Revman 5.3 was used to perform the meta-analysis. Results Eleven studies (n¼379) were included in the systematic review and five randomized controlled trials were included in the meta-analysis (n¼248). Mineralocorticoid antagonists (MRAs) did not increase predialysis potassium levels significantly (0.11, 95% confidence interval À0.03 to 0.25, p ¼ 0.11). However, the studies included in this review reported inconsistently with respect to effects of mineralocorticoid receptor antagonists on blood pressure, left ventricular ejection fraction and left ventricular hypertrophy, and quantitative analysis was not performed due to insufficient data. One trial showed that the mineralocorticoid receptor antagonists were associated with decreased carotid intima-media thickness and other articles concluded that mineralocorticoid receptor antagonists had no effect on aortic stiffness. Conclusion It is safe to use low dose mineralocorticoid receptor antagonists on patients receiving hemodialysis, at the end of each session of hemodialysis, and close monitoring of serum potassium levels and possible side effects is necessary. The cardiovascular actions still need to be explored and large scale RCTs are in progress.

Association of Mineralocorticoid Receptor Antagonists With the Mortality and Cardiovascular Effects in Dialysis Patients: A Meta-analysis

“…We noticed that previous published meta-analyses omitted important trials (e.g., there are only five RCTs in Zhao’s work ( Zhao et al, 2016 )), Zhao’s conclusion that MRA did not increase potassium levels significantly, this is consistent with our result. However, they did not analyze the effect of MRA on serum potassium in patients with different dialysis methods, we did a subgroup analysis specifically for this question.…”

“…Notably, the risk/benefit ratio of MRAs in dialysis patients is less well defined, owing to concerns that their cardioprotective actions may be counteracted by excess risk of hyperkalemia ( Georgianos et al, 2017 ). Moreover, patients with end-stage renal disease often experience multiple complications, consequently, mineralocorticoid receptor antagonists (MRA) should be considered for complete blockade of the renin-angiotensin-aldosterone system (RAAS) ( Zhao et al, 2016 ). MRA, including eplerenone and spironolactone, have been shown effective in patients with hypertension and HFrEF ( Pitt et al, 1999 ; Zannad et al, 2011 ).…”

Intestinal Mineralocorticoid Receptor Contributes to Epithelial Sodium Channel–Mediated Intestinal Sodium Absorption and Blood Pressure Regulation

“…From a clinical perspective, a direct association between intestinal MR and BP has not been established to date; however, several interesting studies have assessed the efficiency and safety of MR antagonists in dialysis patients 40, 41. In some, but not all, of these studies, BP improvement was observed using MR antagonists.…”