Mineralocorticoid Receptor Antagonists in ESKD

Agarwal, Adhish; Cheung, Alfred K.

doi:10.2215/cjn.13221019

Cited by 12 publications

(19 citation statements)

References 11 publications

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“…In addition, ESRD is characterized by excess aldosterone despite extracellular volume expansion, a phenomenon that is associated with increased mortality 11 . Aldosterone breakthrough, which describes discordantly elevated aldosterone levels during angiotensin‐converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy, is particularly relevant in patients with ESRD 12 . Therefore, treatment with MRAs may be particularly beneficial in HF patients with ESRD.…”

Section: Introductionmentioning

confidence: 99%

The effects of mineralocorticoid receptor antagonists on cardiovascular outcomes in patients with end‐stage renal disease and heart failure

Lin

et al. 2022

European J of Heart Fail

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Aims Mineralocorticoid receptor antagonists (MRAs) have been shown to provide survival benefits in patients with heart failure; however, MRA use in patients with chronic kidney disease has been limited by safety concerns. The effects of MRAs on outcomes in patients with end‐stage renal disease (ESRD) and heart failure remain unknown. The aim of this study was to evaluate the effects of MRAs on cardiovascular outcomes in patients with heart failure under maintenance dialysis in a real‐world setting. Methods and results A retrospective cohort study was conducted by collecting data from the Taiwan National Health Insurance Research Database (NHIRD). Patients diagnosed with heart failure and ESRD and who started maintenance dialysis between 1 January 2001 and 31 December 2013 were identified. Patients were grouped according to MRA prescription. The outcomes of interest included cardiovascular (CV) death, hospitalization for heart failure (HHF), all‐cause mortality, acute myocardial infarction (AMI), ischaemic stroke, any coronary revascularization procedures, and new‐onset hyperkalaemia. Propensity score matching was performed at a 1:3 ratio between MRA users and non‐users to minimize selection bias. A total of 50 872 patients who satisfied our inclusion and exclusion criteria were identified. After 1:3 matching, 2176 patients were included in the MRA group, and 6528 patients were included in the non‐MRA group. The risk of CV death was significantly lower among patients who received MRAs than those who did not (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.80–0.95), as was the risk of all‐cause mortality (HR 0.88, 95% CI 0.83–0.94). Reductions in the risks of CV death and all‐cause mortality were more prominent among patients undergoing haemodialysis and those with coronary artery disease. Conclusions In patients undergoing regular dialysis who are diagnosed with heart failure, the use of MRAs is associated with lower risks of all‐cause mortality and CV death. The benefits of MRA treatment in heart failure may persist in patients with ESRD. Further investigations through randomized controlled trials are needed to assess the efficacy and safety of MRAs in this high‐risk population.

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Section: Introductionmentioning

confidence: 99%

The effects of mineralocorticoid receptor antagonists on cardiovascular outcomes in patients with end‐stage renal disease and heart failure

Lin

et al. 2022

European J of Heart Fail

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“…While results from ACHIEVE are not yet available, results outlining the type and efficiency of MRAs recommended for use in ESKD would be of great value. Finerenone requires further study regarding its role, performance, and safety profile in the context of ESKD (29).…”

Section: Acute Kidney Injurymentioning

confidence: 99%

Administration of finerenone in chronic kidney disease

et al. 2022

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Spironolactone is a first-generation and non-selective mineralocorticoid receptor antagonist (MRA). It is extensively well-studied and recommended due to increased accessibility for patients. Unfortunately, it is often discontinued in several cases due to its association with hyperkalemia. The apparent benefit of eplerenone over spironolactone is its mineralocorticoid receptor (MR) selectivity. However, it is also characterized by low-potency and higher cost compared to spironolactone. The high adverse-effect profile of spironolactone and eplerenone has led to the innovation of novel medications such as non-steroidal MRAs. Among these medications, finerenone is the most advanced agent. Finerenone is associated with decreased proteinuria, reduced risk of hyperkalemia and increased preservation of renal function with comparable benefit in heart failure compared to selective and nonselective MRAs. The nonsteroidal structure of finerenone affects mineralocorticoid receptor binding, lipophilicity and polarity which have potent effects on distribution, the degree of attachment to blood proteins, transportation, and tissue diffusion.

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“…MR are intracellular receptors and act as nuclear transcription factors ("genomic" effect) or have rapid non-genomic effects through secondary cell signaling mechanisms [38][39][40]. They are expressed in many tissues, including the kidney, heart, vasculature, nervous and immune system.…”

Section: Mineralocorticoids and The Mineralocorticoid Receptors (Mr)mentioning

confidence: 99%

Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease

et al. 2021

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Diabetes mellitus is a global health issue and main cause of chronic kidney disease. Both diseases are also linked through high cardiovascular morbidity and mortality. Diabetic kidney disease (DKD) is present in up to 40% of diabetic patients; therefore, prevention and treatment of DKD are of utmost importance. Much research has been dedicated to the optimization of DKD treatment. In the last few years, mineralocorticoid receptor antagonists (MRA) have experienced a renaissance in this field with the development of non-steroidal MRA. Steroidal MRA have known cardiorenal benefits, but their use is limited by side effects, especially hyperkalemia. Non-steroidal MRA still block the damaging effects of mineralocorticoid receptor overactivation (extracellular fluid volume expansion, inflammation, fibrosis), but with fewer side effects (hormonal, hyperkalemia) than steroidal MRA. This review article summarizes the current knowledge and newer research conducted on MRA in DKD.

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Mineralocorticoid Receptor Antagonists in ESKD

Cited by 12 publications

References 11 publications

The effects of mineralocorticoid receptor antagonists on cardiovascular outcomes in patients with end‐stage renal disease and heart failure

The effects of mineralocorticoid receptor antagonists on cardiovascular outcomes in patients with end‐stage renal disease and heart failure

Administration of finerenone in chronic kidney disease

Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease

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