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Nephrology, Dialysis, Transplantation :... Oct 2023Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis),... (Meta-Analysis)
Meta-Analysis
The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis.
BACKGROUND AND OBJECTIVES
Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), direct renin inhibitors (DRIs), or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or chronic kidney disease (CKD) progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS
This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33 048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects.
RESULTS
There were 208 AKI events in 2690 patients on ACEi + ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23-1.39). There were 304 hyperkalemia events in 2818 patients on ACEi + ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32-2.94). A non-steroidal MRA + ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81-1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84-2.28). A steroidal MRA + ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67).
CONCLUSION
Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.
Topics: Adult; Humans; Renin-Angiotensin System; Diabetic Nephropathies; Hyperkalemia; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Acute Kidney Injury; Diabetes Mellitus
PubMed: 37309038
DOI: 10.1093/ndt/gfad101 -
Annals of Medicine and Surgery (2012) Oct 2023The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease.... (Review)
Review
BACKGROUND AND OBJECTIVES
The incidence of morbidity and mortality in patients with type 2 diabetes mellitus is substantially correlated with cardiovascular disease and chronic kidney disease. The current guidelines recommend the use of renin-angiotensin system blockers, but recent studies probed into the effects of finerenone to mitigate the risk of cardiorenal events. This meta-analysis was performed to demonstrate the effects of finerenone on cardiorenal events, comprising cardiovascular mortality, heart failure, change in estimated glomerular filtration rate, and serum potassium levels.
METHODS
After screening with our eligibility criteria, 350 articles were identified with an initial literature search on multiple databases, including PubMed, Science Direct, and Cochrane Central. Seven randomized controlled trials with a total of 15 462 patients (=8487 in the finerenone group; =6975 in the control group) were included.
RESULTS
Patients receiving finerenone were at a reduced risk for cardiovascular mortality [HR: 0.84 (0.74, 0.95)], heart failure [OR: 0.79 (0.68, 0.92)], decrease in estimated glomerular filtration rate by 40% [OR: 0.82 (0.74, 0.91)] and by 57% [OR: 0.70 (0.59, 0.82)]; and a higher incidence of moderate hyperkalemia [OR: 2.25 (1.78, 2.84)].
CONCLUSION
Finerenone, owing to its better mineralocorticoid affinity, and a much lower risk of adverse effects, promises to be a much better alternative than other renin-angiotensin system blockers available for the treatment of chronic kidney disease patients with type 2 diabetes. Further trials should be conducted to provide more definitive evidence to assess the safety and efficacy of finerenone compared to spironolactone and eplerenone.
PubMed: 37811017
DOI: 10.1097/MS9.0000000000001180 -
International Journal of Retina and... Jun 2022Mineralocorticoid receptor antagonists (MRAs) are widely used for chronic central serous chorioretinopathy (cCSCR), but their effectiveness remains unclear. This...
BACKGROUND
Mineralocorticoid receptor antagonists (MRAs) are widely used for chronic central serous chorioretinopathy (cCSCR), but their effectiveness remains unclear. This research was conducted to evaluate the efficacy of this drugs for cCSCR.
METHODS
This is a review of randomized clinical trials (RCT) comparing MRAs to placebo in adults with cCSCR, using the effects of MRAs on best-corrected visual acuity (BCVA) and adverse events as primary outcomes and the effects of MRAs on anatomical parameters as secondary outcomes: central subfield thickness (CST), subretinal fluid height (SFH) and central choroidal thickness (CCT). Our all-language online search included Medline (via PubMed), Central, Embase, Lilacs, Ibecs, and RCT registers platforms, as late as May 2021. We used the Cochrane risk-of-bias tool (version 2) to assess the methodological quality of each study and synthesized the results in meta-analyses using a random-effects model.
RESULTS
The search identified 302 records, five of which were eligible, totaling 225 cCSCR patients (aged 45-62 years; M/F ratio 3.1:1) treated for 1 to 12 months with spironolactone (50 mg/day) or eplerenone (50 mg/day) vs. placebo. Moderate-certainty evidence suggests MRAs result in little to no improvement in BCVA compared to placebo (SMD 0.22; 95% CI - 0.04 to 0.48; studies = 5; comparisons = 6; participants = 218; I = 0%). Very low-certainty evidence suggests that, when compared to placebo, MRAs have a very uncertain impact on adverse effects (no meta-analysis was performed), and CST (MD 18.1; 95% CI - 113.04 to 76.84; participants = 145; studies = 2; I = 68%). MRAs also result in little to no difference in SFH (SMD - 0.35; 95% CI - 0.95 to 0.26; studies = 5; comparisons = 6; participants = 221; I = 76%; moderate certainty) and CCT (MD - 21.23; 95% CI - 64.69 to 22.24; participants = 206; studies = 4; comparisons = 5; I = 85%; low certainty).
CONCLUSION
MRAs have little to no effect on BCVA. Evidence for adverse events and CST is very uncertain. MRAs also have little to no effect on SFH and CCT. These findings should be considered when prescribing MRAs for cCSCR. This research was previous registration in the PROSPERO platform (CRD42020182601).
PubMed: 35672807
DOI: 10.1186/s40942-022-00385-1 -
Eye (London, England) Apr 2021We performed a systematic review and meta-analysis to assess the efficacy and safety of the mineralocorticoid receptor antagonist (MRA) treatment for central serous... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We performed a systematic review and meta-analysis to assess the efficacy and safety of the mineralocorticoid receptor antagonist (MRA) treatment for central serous chorioretinopathy (CSC).
METHODS
We searched the PubMed, Embase, and the Cochrane Library to identify relevant clinical studies published prior to March 2020. The primary outcome was change in best-corrected visual acuity (BCVA), and the secondary outcomes included the subretinal fluid (SRF), subfoveal choroidal thickness (SFCT), and central macular thickness (CMT).
RESULTS
Five randomized controlled trials (RCT) and four cohort studies met the inclusion criteria with a total of 352 eyes. The MRA treatment was not superior to placebo in BCVA at 1 month (WMD = -0.06, 95% CI -0.15-0.02, P = 0.15, I = 86%), 3 months (WMD = -0.04, 95% CI -0.14-0.06, P = 0.44, I = 77%) and 6 months (WMD = -0, 95% CI -0.05-0.05, P = 0.92, I = 0%). The MRA treatment resulted in significant reduction than the placebo in the SRF (WMD = -60.64, 95% CI -97.91 to -23.37, P = 0.001, I = 49%), SFCT (WMD = -39.15, 95% CI -52.58 to -25.72, P < 0.001, I = 0%), and CMT (WMD = -60.75, 95% CI -97.85 to -23.65, P = 0.01, I = 53%).
CONCLUSIONS
Our meta-analysis shows that the MRA treatment can improve anatomical structure in CSC patients, but it is not effective for achieving BCVA gain. The applicant of the MRA is safe and have no severe effect.
Topics: Central Serous Chorioretinopathy; Humans; Mineralocorticoid Receptor Antagonists; Subretinal Fluid; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity
PubMed: 33414535
DOI: 10.1038/s41433-020-01338-4 -
Journal of Nephrology May 2023Mineralocorticoid receptor antagonists (MRAs) were shown to delay chronic kidney disease (CKD) progression in patients with hypertension and/or heart failure (HF) and... (Review)
Review
BACKGROUND
Mineralocorticoid receptor antagonists (MRAs) were shown to delay chronic kidney disease (CKD) progression in patients with hypertension and/or heart failure (HF) and proteinuria.
OBJECTIVE
We conducted a systematic literature review on real-world evidence to identify the literature gaps related to the efficacy and safety outcomes of MRAs administered to CKD patients.
RESULTS
A total of 751 records were identified of which, 23 studies (26 publications) were analyzed. Studies included heterogeneous populations, including the overall CKD, CKD and diabetes, CKD and HF, and CKD and a history of cardiovascular disease. Most of the studies were small and non-rigorous, resulting in a notable lack of evidence in these populations. In the overall CKD population, steroidal MRAs resulted in a significant or sustained eGFR reduction but no efficacy in delaying progression to end-stage kidney disease. No cardiovascular protection was found. Results for all-cause mortality and hospitalization for HF were inconsistent; however, the longest follow-up studies indicate similar or lower incidence for spironolactone non-users. Most results consistently reported a higher incidence of hyperkalemia among patients on steroidal MRAs in all CKD stages, and side effects led to high discontinuation rates in the real-world setting.
CONCLUSIONS
Despite the limited availability of evidence on the effectiveness and safety of steroidal MRAs in CKD patients and subgroups with diabetes, HF or history of cardiovascular disease, MRAs were shown to have a limited effect on renal and cardiovascular outcomes. Gaps in the evidence regarding the efficacy and safety of MRAs are particularly relevant in diabetic CKD patients; therefore, further research is warranted.
Topics: Humans; Mineralocorticoid Receptor Antagonists; Cardiovascular Diseases; Mineralocorticoids; Renal Insufficiency, Chronic; Heart Failure; Diabetic Nephropathies
PubMed: 36422853
DOI: 10.1007/s40620-022-01492-w -
Diabetology & Metabolic Syndrome Nov 2023Diabetes is a complicated, chronic condition that requires ongoing medical attention as well as multiple risk-reduction measures beyond glucose control. The prevalence... (Review)
Review
BACKGROUND
Diabetes is a complicated, chronic condition that requires ongoing medical attention as well as multiple risk-reduction measures beyond glucose control. The prevalence of chronic kidney disease (CKD) is highly variable in different parts of the world due to various environmental, ethnic, socioeconomic, and rural-urban differences. Diabetes is the leading cause of CKD. This study aimed to estimate the global prevalence of CKD and its associated factors among type 2 diabetes(T2DM) patients, provide scientific evidence for a better understanding of the burden of CKD among diabetes mellitus type 2 patients, and design interventional strategies.
METHODS
Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist guideline was followed for this review and meta-analysis. The electronic databases (Pub Med, Cochrane Library, Google Scholar, and grey literature) were searched to retrieve articles by using keywords. Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument was used to assess the quality of studies. The meta-analysis was conducted using STATA 17 software. The Meta logistic regression was computed to present the pooled prevalence and Odds ratio (OR) of the determinate factors with a 95% confidence interval (CI).
RESULTS
In this systematic review and meta-analysis 20 studies were done in 13 different countries. The pooled magnitude of chronic kidney disease among type 2 DM patients was 27% (95% CI 21%, 33%). The prevalence of chronic kidney disease differs across countries, with the maximum in the USA and the lowest in the United Arab Emirates. Patients with CKD have an elevated risk of severe renal and cardiovascular morbidity and mortality. Renin-angiotensin system inhibitors, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide 1 receptor agonists, and, more recently, non-steroidal mineralocorticoid receptor antagonists are among the medications that have been demonstrated to slow the progression of CKD. In this systematic review and meta-analysis increased age, obesity, having a history of type 2 diabetes mellitus, smoking history, presence of hypertension, and cardiac heart disease were factors significantly associated with the presence of chronic kidney disease among type 2 diabetic patients.
CONCLUSIONS
The prevalence of chronic kidney disease among type 2 diabetes mellitus patients was high based on the included 20 articles. The review reported that old age, hypertension, cardiac disease, smoking, obesity, and duration of diabetes mellitus was predictor variable for chronic kidney disease among type 2 diabetic patients. Therefore, in order to lower the morbidity and mortality from chronic kidney disease among type 2 diabetic patients, it is advised to develop both preventive and curative intervention strategies, such as raising awareness, creating a supportive environment, and prescribing appropriate medication at an early stage.
PubMed: 38012781
DOI: 10.1186/s13098-023-01202-x -
BMC Nephrology Sep 2016Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypertension and proteinuria are critically involved in the progression of chronic kidney disease. Despite treatment with renin angiotensin system inhibition, kidney function declines in many patients. Aldosterone excess is a risk factor for progression of kidney disease. Hyperkalaemia is a concern with the use of mineralocorticoid receptor antagonists. We aimed to determine whether the renal protective benefits of mineralocorticoid antagonists outweigh the risk of hyperkalaemia associated with this treatment in patients with chronic kidney disease.
METHODS
We conducted a meta-analysis investigating renoprotective effects and risk of hyperkalaemia in trials of mineralocorticoid receptor antagonists in chronic kidney disease. Trials were identified from MEDLINE (1966-2014), EMBASE (1947-2014) and the Cochrane Clinical Trials Database. Unpublished summary data were obtained from investigators. We included randomised controlled trials, and the first period of randomised cross over trials lasting ≥4 weeks in adults.
RESULTS
Nineteen trials (21 study groups, 1 646 patients) were included. In random effects meta-analysis, addition of mineralocorticoid receptor antagonists to renin angiotensin system inhibition resulted in a reduction from baseline in systolic blood pressure (-5.7 [-9.0, -2.3] mmHg), diastolic blood pressure (-1.7 [-3.4, -0.1] mmHg) and glomerular filtration rate (-3.2 [-5.4, -1.0] mL/min/1.73 m(2)). Mineralocorticoid receptor antagonism reduced weighted mean protein/albumin excretion by 38.7 % but with a threefold higher relative risk of withdrawing from the trial due to hyperkalaemia (3.21, [1.19, 8.71]). Death, cardiovascular events and hard renal end points were not reported in sufficient numbers to analyse.
CONCLUSIONS
Mineralocorticoid receptor antagonism reduces blood pressure and urinary protein/albumin excretion with a quantifiable risk of hyperkalaemia above predefined study upper limit.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Disease Progression; Glomerular Filtration Rate; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Patient Dropouts; Proteinuria; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Risk Assessment
PubMed: 27609359
DOI: 10.1186/s12882-016-0337-0 -
Cureus Jul 2023The purpose of this study is to assess the safety and efficacy of finerenone therapy in type 2 diabetes mellitus (T2DM) patients with cardiovascular and chronic renal... (Review)
Review
A Systematic Review and Meta-Analysis on the Efficacy and Safety of Finerenone Therapy in Patients with Cardiovascular and Chronic Kidney Diseases in Type 2 Diabetes Mellitus.
The purpose of this study is to assess the safety and efficacy of finerenone therapy in type 2 diabetes mellitus (T2DM) patients with cardiovascular and chronic renal diseases. This meta-analysis assesses the efficacy and safety of finerenone in the treatment of diabetic kidney disease (DKD). A comprehensive search of PubMed, Embase, and Google Scholar databases was performed to identify relevant randomized controlled trials (RCTs). To quantify the effects of finerenone, the analysis included the estimation of aggregated mean differences (MDs) and relative risks (RRs), as well as 95% confidence intervals (CIs). This meta-analysis included seven double-blind trials with patients suffering from chronic kidney disease (CKD) and T2D. Participants received finerenone or a placebo was assigned at random. The primary efficacy outcomes were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, kidney failure, a sustained 57% decrease in the estimated glomerular filtration rate from baseline over four weeks, or renal death. Among the 39,995 patients included in the analysis, finerenone treatment was associated with a lower risk of cardiovascular and renal-related mortality compared to placebo (RR = 0.86 (0.80, 0.93), p = 0.0002; I-squared statistic (I ) = 0%) and (RR = 0.56 (0.17, 1.82), p = 0.34; I= 0%). In addition, finerenone treatment was associated with a marginally reduced risk of serious adverse events (RR = 0.95 (0.92, 0.97), p = 0.0001; I= 0%), although no significant difference in the overall risk of adverse events was observed between the two groups (RR = 1.00 (0.99, 1.01), p = 0.56; I= 0%). This study's findings suggest that finerenone administration can reduce the risk of end-stage kidney disease, renal failure, cardiovascular mortality, and hospitalization. Patients with both T2DM and CKD are therefore advised to consider finerenone therapy.
PubMed: 37575756
DOI: 10.7759/cureus.41746 -
BMC Cardiovascular Disorders Jan 2016The aim of this study was to systematically assess the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) for patients with heart failure (HF) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The aim of this study was to systematically assess the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) for patients with heart failure (HF) and diabetes mellitus (DM).
METHODS
We conducted a comprehensive search for controlled studies that evaluated the efficacy and safety of MRAs in patients with DM and HF. Medline, Embase and Cochrane databases were searched. Two reviewers independently identified citations, extracted data and evaluated quality. Risk estimations were abstracted and pooled where appropriate.
RESULTS
Four observational studies were included. MRAs use was associated with reduced mortality compared with controls (RR = 0.78; 95% CI: 0.69-0.88; I(2) = 0%; P < 0.001). Increased risk of developing hyperkalaemia was observed in those patients taking MRAs (RR = 1.74; 95% CI: 1.27-2.38; I(2) = 0%; P = 0.0005).
CONCLUSIONS
The current cumulative evidence suggests that MRAs can improve clinical outcomes but increase the risk of hyperkalaemia in patients with DM and HF.
TRIAL REGISTRATION
PROSPERO CRD42015025690 .
Topics: Comorbidity; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Mortality; Risk Factors; Treatment Outcome
PubMed: 26822790
DOI: 10.1186/s12872-016-0198-2 -
Clinical Journal of the American... Jun 2021Patients with kidney failure have a high risk of cardiovascular disease due to cardiac remodeling, left ventricular fibrosis, and hyperaldosteronism, all of which can be... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Patients with kidney failure have a high risk of cardiovascular disease due to cardiac remodeling, left ventricular fibrosis, and hyperaldosteronism, all of which can be potentially mitigated by mineralocorticoid receptor antagonists. However, because of the fear of hyperkalemia, the use of mineralocorticoid receptor antagonists in patients with kidney failure is limited in current clinical practice, and few studies have investigated the efficacy and safety. Thus, we aimed to determine the benefits and side effects of mineralocorticoid receptor antagonists in patients with kidney failure treated with dialysis.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
This is a systematic review and meta-analysis of randomized controlled trials published from 2005 to 2020 that compared the effect of mineralocorticoid receptor antagonists with either placebo or no treatment in patients with kidney failure. Two reviewers independently searched the PubMed, EMBASE, and Cochrane databases for all published studies, extracted data, assessed the risk of bias, and rated the quality of evidence. A meta-analysis was conducted on 14 eligible randomized controlled trials, and a total of 1309 patients were included.
RESULTS
High-quality evidence suggested that mineralocorticoid receptor antagonists are associated with lower cardiovascular mortality (relative risk, 0.41; 95% confidence interval, 0.24 to 0.70; =0.001) and all-cause mortality (relative risk, 0.44; 95% confidence interval, 0.30 to 0.66; <0.001), and the risk of hyperkalemia was comparable with that of control group (relative risk, 1.12; 95% confidence interval, 0.91 to 1.36; =0.29). However, no significant decrease in nonfatal cardiovascular events and stroke was observed, and there was no significant improvement in BP or cardiac performance parameters, including left ventricular ejection fraction and left ventricular mass index.
CONCLUSIONS
Our meta-analysis suggests that mineralocorticoid receptor antagonists might improve clinical outcomes of patients with kidney failure without significant increase in the risk of hyperkalemia.
Topics: Cardiovascular Diseases; Humans; Kidney Failure, Chronic; Mineralocorticoid Receptor Antagonists; Renal Dialysis; Treatment Outcome
PubMed: 34117083
DOI: 10.2215/CJN.15841020