Mineralocorticoid Receptor Antagonists and Cardiovascular Health with Kidney Failure.
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ABSTRACT:
SUBMITTER: Soomro QH
PROVIDER: S-EPMC8216618 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
Publications
Mineralocorticoid Receptor Antagonists and Cardiovascular Health with Kidney Failure.
Soomro Qandeel H QH Charytan David M DM
Clinical journal of the American Society of Nephrology : CJASN 20210601 6
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| S-EPMC7769027 | biostudies-literature
Project description:BackgroundDiabetic kidney disease (DKD) is a common disorder with multiple serious clinical implications, including an increased risk of end-stage kidney disease (ESKD), cardiovascular complications, heart failure, onset or worsening of hypertension, and premature death. Patients with DKD frequently require dialysis or kidney transplantation to manage their ESKD.SummaryUpregulation of the renin-angiotensin-aldosterone system is an important contributor to kidney disease progression, as highlighted by the results of trials evaluating angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with albuminuria. Increasing evidence suggests the existence of a multidirectional network that involves aldosterone, the mineralocorticoid receptor (MR), and the Ras-related C3 botulinum toxin substrate 1 (Rac1) as driving forces in the generation of reactive oxygen species and oxidative stress-induced injury in the initiation of interstitial nephritis and eventual fibrosis in chronic kidney disease and DKD. The MR is a key element of this triangle, as highlighted by the beneficial effect of MR antagonists in preventing or reducing aldosterone- or Rac1-related effects in basic science studies, and the improved patient outcomes observed in clinical studies.Key messagesAldosterone can promote kidney disease in diabetes via the MR and via MR-independent actions through Rac1. However, the MR remains a key element of this triangle, with clinical data supporting the use of MR antagonists in delaying the progression of kidney disease in diabetes.
| S-EPMC10273909 | biostudies-literature
Project description:Mineralocorticoid receptor antagonists (MRA) improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and reduce risk of heart failure (HF) hospitalization in patients with heart failure with preserved ejection fraction (HFpEF). However, the benefit and risks of MRA use are not clear in HF patients and chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We conducted a systematic review evaluating the efficacy and safety of MRA in patients with HF and CKD. PubMed, Embase, and Cochrane Central databases were searched for relevant studies on patients with HF and reduced renal function (defined as eGFR <60 mL/min/1.73 m2). Seven studies with 5,522 patients were included. We found 3 studies in patients with HFrEF, 1 study with HFpEF, and 2 in acute HF and 1 with mixed patient population of HF. Post hoc analyses from randomized controlled trials demonstrated reduction of risk in the primary end point (adverse cardiovascular outcomes and/or all-cause mortality and/or HF hospitalization) with MRA use in the CKD subgroup (eGFR 30 to 60 mL/min/1.73 m2) despite a greater risk of hyperkalemia and higher rates of drug discontinuation. In 3 observational studies, propensity score matching was performed to compare patients treated with and without MRA and did not identify benefits, but conclusions from these studies were limited due to residual confounding and concern for bias. In conclusion, benefits of MRA use in HF appear to be consistent in patients with reduced renal function (eGFR 30 to 60 mL/min/1.73 m).
| S-EPMC7977068 | biostudies-literature
Project description:Rationale & objectiveTo comprehensively summarize the efficacy of mineralocorticoid receptor antagonists (MRAs) to improve kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD).Study designRelevant studies were identified from Medline and Scopus databases from their inception up to August 2023.Setting & study populationsPatients with nondialysis or dialysis CKD.Selection criteria for studiesSystematic reviews and meta-analyses (SR-MAs) of randomized controlled trials (RCTs) that investigated the efficacy of MRAs on kidney and CV outcomes in patients with nondialysis or dialysis CKD were included in this study.Data extractionCharacteristics of studies and participants, and treatment effects were extracted.Analytic approachEfficacy of MRAs was qualitatively summarized according to types of patients and MRAs.ResultsForty SR-MAs were included. When compared with placebo/usual care, steroidal MRAs (sMRAs) provided significant benefit in decreasing all-cause (pooled RRs of 0.38 [0.22-0.65] to 0.87 [0.77-0.98]) and CV mortality (pooled RRs of 0.34 [0.15-0.75] to 0.46 [0.28-0.76]) only in patients treated with dialysis, when compared with placebo. Nonsteroidal MRAs (nsMRAs) significantly lowered composite CV events in both nondialysis CKD (pooled RRs of 0.86 [0.79-0.94] to 0.92 [0.85-0.99]) and patients with diabetic kidney disease (DKD) (pooled RRs of 0.86 [0.78-0.95] to 0.88 [0.81-0.96]). In addition, nsMRAs showed significant benefit in reducing composite kidney outcomes in patients with either nondialysis CKD or DKD when compared with placebo. However, this efficacy was lower than sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with DKD. Moreover, both sMRAs and nsMRAs significantly increased the risk of hyperkalemia in patients with nondialysis CKD and DKD.LimitationsThe comparison between nsMRAs and SGLT2i is based on network meta-analyses. Consequently, additional head-to-head RCTs are necessary to confirm the advantages of SGLT2i over nsMRAs.ConclusionssMRAs offer benefits in reducing all-cause and cardiovascular mortality and composite CV events in patients treated with dialysis. nsMRAs improve kidney outcomes in patients with nondialysis CKD and DKD but increase hyperkalemia risk.
| S-EPMC11803877 | biostudies-literature
Project description:Aldosterone, a hormone synthesized by the adrenal cortex, plays a crucial role in regulating sodium and potassium levels in the kidneys through interaction with the mineralocorticoid receptor (MR) in the distal tubules and collecting ducts. While aldosterone aids in maintaining fluid balance by promoting sodium reabsorption and potassium secretion, elevated levels can lead to inflammation, oxidative stress, and organ damage. Experimental evidence highlights aldosterone's involvement in renal inflammation, collagen deposition, and fibrosis, often exacerbating the effects of therapies like angiotensin-converting enzyme inhibitors (ACEIs) by increasing proteinuria and vascular damage. Conversely, mineralocorticoid receptor antagonists (MRAs) show promise in mitigating these harmful effects. This review integrates current knowledge on aldosterone and MRAs, emphasizing their roles in renal health from both clinical and experimental perspectives. Additionally, the novel drug finerenone has shown favorable renal and cardiovascular outcomes in patients with diabetes and chronic kidney disease (CKD), warranting exploration of its potential use in other disease populations in future research.
| S-EPMC11384348 | biostudies-literature
Project description: Not available
| S-EPMC5779066 | biostudies-literature
Project description:Diabetic kidney disease (DKD) is one of the major causes of end-stage renal disease (ESRD). To evaluate the efficacy and safety of different types of mineralocorticoid receptor antagonists (MRAs) in diabetic kidney disease patients, we conducted this network meta-analysis by performing a systematic search in PubMed, MEDLINE, EMBASE, Web of Science, the Cochrane Library, and Clinicaltrials.gov. A total of 12 randomized clinical trials with 15,492 patients applying various types of MRAs covering spironolactone, eplerenone, finerenone, esaxerenone, and apararenone were included. The efficacy outcomes were the ratio of urine albumin creatine ratio (UACR) at posttreatment vs. at baseline, change in posttreatment estimated glomerular filtration (eGFR) vs. at baseline, and change in posttreatment systolic blood pressure (SBP) vs. at baseline. The safety outcome was the number of patients suffering from hyperkalemia. High-dose finerenone (MD -0.31, 95% CI: -0.52, -0.11), esaxerenone (MD -0.54, 95% CI: -0.72, -0.30), and apararenone (MD -0.63, 95% CI: -0.90, -0.35) were associated with a superior reduction in proteinuria in patients with DKD. Regarding the change in eGFR, the results of all drugs were similar, and finerenone may have potential superiority in protecting the kidney. Compared with placebo, none of the treatments was associated with a higher probability of controlling systolic blood pressure during treatment. Moreover, spironolactone, esaxerenone, and 20 mg of finerenone presented a higher risk of hyperkalemia. This Bayesian network meta-analysis was the first to explore the optimal alternative among MRAs in the treatment of DKD and revealed the superiority of 20 mg of finerenone among MRAs in treating DKD. Systematic Review Registration: PROSPERO, identifier (CRD42022313826).
| S-EPMC9523214 | biostudies-literature
Project description:BackgroundPerceived risks of hyperkalemia and acute renal insufficiency may limit use of mineralocorticoid receptor antagonist (MRA) therapy in patients with heart failure, especially those with diabetes mellitus or chronic kidney disease.Methods and resultsUsing clinical registry data linked to Medicare claims, we analyzed patients hospitalized with heart failure between 2005 and 2013 with a history of diabetes mellitus or chronic kidney disease. We stratified patients by MRA use at discharge. We used inverse probability-weighted proportional hazards models to assess associations between MRA therapy and 30-day, 1-year, and 3-year mortality, all-cause readmission, and readmission for heart failure, hyperkalemia, and acute renal insufficiency. We performed interaction analyses for differential effects on 3-year outcomes for reduced, borderline, and preserved ejection fraction. Of 16 848 patients, 12.3% received MRA therapy at discharge. Higher serum creatinine was associated with lower odds of MRA use (odds ratio, 0.66; 95% confidence interval, 0.61-0.71); serum potassium was not (odds ratio, 1.00; 95% confidence interval, 0.90-1.11). There was no mortality difference between groups. MRA therapy was associated with greater risks of readmission for hyperkalemia and acute renal insufficiency and lower risks of long-term all-cause readmission. Patients on MRA therapy with borderline or preserved ejection fraction had greater risks of readmission for hyperkalemia (P=0.02) and acute renal insufficiency (P<0.001); patients with reduced ejection fraction did not.ConclusionsAmong patients with heart failure and diabetes mellitus or chronic kidney disease, MRA use was associated with lower risk of all-cause readmission despite greater risk of hyperkalemia and acute renal insufficiency.
| S-EPMC5779000 | biostudies-literature
Project description:AimsGuideline-directed medical therapy (GDMT) including beta-blockers and renin-angiotensin system inhibitors is shown to reduce mortality risk in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). However, there is little evidence about the efficacy of additional administration of mineralocorticoid receptor antagonists (MRAs) with GDMT in patients ≥80 years presenting with HF. We aimed to investigate the prognostic impact of GDMT with MRA in relation to the age of patients with HF.Methods and resultsThis observational study included patients admitted for HF with reduced LVEF who were discharged alive; among them, 224 patients were ≥80 years, and 661 patients were <80 years. Both populations were divided into three groups depending on whether they received GDMT with or without MRA or single/no GDMT drugs (GDMT+MRA+, GDMT+MRA-, or non-GDMT, respectively). The primary endpoint was all-cause mortality. In patients ≥80 years, all-cause mortality was the lowest in the GDMT+MRA+ group (log-rank trend, P = 0.034), and no significant differences were observed between the GDMT+MRA- and non-GDMT groups. Multivariate Cox regression analysis revealed that GDMT+MRA+ was superior to GDMT+MRA-, even after adjusting for parameters at discharge (hazard ratio: 0.32, 95% confidence interval: 0.11-0.99). In patients <80 years, GDMT reduced all-cause mortality; however, additional MRA was not associated with an improved outcome.ConclusionsThe results of this study suggest that additional MRA to GDMT at discharge is one of the therapeutic options for elderly HF patients with reduced LVEF. This finding is not well documented in previous clinical trials.
| S-EPMC7524245 | biostudies-literature
Project description: Not available
| S-EPMC7341785 | biostudies-literature