Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease: Efficacy and Safety

Abstract

Mineralocorticoid receptor antagonists (MRAs) that block aldosterone's effects on both epithelial and non-epithelial receptors have become a mainstay of therapy for chronic heart failure. Given that cardiovascular events remain the leading cause of death for patients with end-stage renal disease (ESRD), the question of whether these MRAs can be employed in dialysis patients arises. This review summarizes the rationale for blocking aldosterone in patients with chronic and end-stage kidney disease and surveys the data on both the efficacy and safety of using MRAs in the ESRD population. A small but growing body of literature suggests that use of MRAs by ESRD patients is associated with lower blood pressure, reduced left ventricular (LV) mass, and improved LV ejection fraction. Recently, a large randomized trial found an overall 3-year mortality rate of 6.4% in ESRD patients on spironolactone 25 mg daily vs. 19.7% in ESRD patients on no MRA therapy (p = 0.002), without a significantly increased risk of hyperkalemia.

Minoxidil for Treatment of Resistant Hypertension in Chronic Kidney Disease––A Retrospective Cohort Analysis

“…The PATHWAY‐2 study excluded patients with an estimated GFR <45 mL/min, as other studies have . Nevertheless, recent data from small‐scale studies suggest that mineralocorticoid receptor antagonists are beneficial and safe in chronic kidney disease, but larger trials (the Aldosterone Antagonist Chronic Hemodialysis Interventional Survival Trial [ALCHEMIST]; NCT01848639) are currently underway to confirm these preliminary data . In our study, spironolactone was used only once (at discharge), which is mainly because of the mean estimated GFR 34 mL/min and the subsequent risk of hyperkalemia.…”

“…41 Nevertheless, recent data from small-scale studies suggest that mineralocorticoid receptor antagonists are beneficial and safe in chronic kidney disease, but larger trials (the Aldosterone Antagonist Chronic Hemodialysis Interventional Survival Trial [ALCHEMIST]; NCT01848639) are currently underway to confirm these preliminary data. 42 In our study, spironolactone was used only once (at discharge), which is mainly because of the mean estimated GFR 34 mL/min and the subsequent risk of hyperkalemia. The approach to consequently avoid sodium retention could not be applied to our whole cohort, especially since 27.7% of our patients had end-stage renal disease with limited residual diuresis, which compromises the use of any diuretics.…”

Management of heart failure in patients with end-stage kidney disease on maintenance dialysis: a practical guide

“…However, aldosterone levels increase as eGFR decreases, so patients with CKD and ESKD have inappropriately high levels of aldosterone despite increased ECV, contributing to left ventricular hypertrophy and inflammatory effects. Small randomized controlled trials have shown that in patients with ESKD, the addition of MRAs is associated with decreased left ventricular mass (Bomback, 2016).…”

The role of aldosterone in kidney diseases and hypertension. Is it worth using mineralocorticoid receptor antagonists in clinical practice?

“…The incidence of life-threateninghyperkalemia was (potassium level > 6.5 mmol/L) 1.9% and gynecomastia occurred in 10% of the spironolactone patients [40]. The future perspective of spironolactone treatment in hemodialyzed patients will be available soon as a result of another new study -AL-CHEMIST study (Aldosterone Antagonist Chronic www.ah.viamedica.pl Hemodialysis Interventional Survival Trial, ALCHE-MIST) [41]. Moreover, in many studies benefits of aldosterone antagonists in peritoneal dialysis patients were confirmed.…”