Aldosterone Antagonists in Addition to Renin Angiotensin System Antagonists for Preventing the Progression of CKD: Editorial Summary of a Cochrane Review

Chronic kidney disease (CKD) is a public health challenge, as it has prevalence of 11% and the 14th-leading cause death worldwide (12.2 deaths per 100,000 people). Since 1990, from CKD have increased at higher rate than for any other except complications HIV infection.1Webster A.C. Nagler E.V. Morton R.L. et al.Chronic disease.Lancet. 2017; 389: 1238-1252Abstract Full Text PDF PubMed Scopus (1067) Google Scholar Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are standard care to delay progression earlier stages failure in patients with proteinuria irrespective primary disease; addition, these agents associated reduction cardiovascular risk.2No authors listed Randomised placebo-controlled trial effect ramipril on decline glomerular filtration risk terminal renal proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici Nefrologia).Lancet. 1997; 349: 1857-1863Abstract (1697) Scholar,3Palmer S.C. Mavridis D. Navarese E. al.Comparative efficacy safety blood pressure-lowering adults diabetes disease: network meta-analysis.Lancet. 2015; 385: 2047-2056Abstract (256) Incomplete suppression aldosterone by renin-angiotensin-aldosterone system blockade ACEIs ARBs (called ‘aldosterone escape phenomenon’) occurs 10%-40% cases worsening both diabetic nondiabetic disease, suggesting role antagonists preventing CKD.4Bomback A.S. Klemmer P.J. incidence implications breakthrough.Nat Clin Pract Nephrol. 2007; 3: 486-492Crossref (279) Addition may provide benefits (reduction effects patient-level outcomes such major events) but also be harms (hyperkalemia acute injury [AKI]). A Cochrane systematic review was published 2014.5Bolignano Palmer Navaneethan S.D. Strippoli G.F. Aldosterone chronic disease.Cochrane Database Syst Rev. 2014; 4: CD007004PubMed This identified 27 studies (1,549 participants) found that nonselective (spironolactone) combined an ACEI ARB (or both) significantly reduced proteinuria, had no significant estimated (eGFR), hyperkalemia gynecomastia. It data (kidney failure, death, events).5Bolignano An update this performed 6 years thereafter, when additional trials been people CKD, including new (the novel nonsteroidal mineralocorticoid antagonists, eg, finerenone esaxerenone) developed.6Bramlage P. Swift S.L. Thoenes M. al.Non-steroidal antagonism treatment disease.Eur J Heart Fail. 2016; 18: 28-37Crossref (45) included 18 (4,248 through January 7, 2020.7Chung E.Y. Ruospo Natale Bolignano addition renin 2020; 10: Studies were all randomized controlled quasi-randomized participants 1 4, defined KDOQI guideline,8Levey Coresh J. Balk al.National Kidney Foundation practice guidelines evaluation, classification, stratification.Ann Intern Med. 2003; 139: 137-147Crossref (3507) albuminuria proteinuria. Treatment summarized using random meta-analysis. Risk bias evaluated risk-of-bias tool certainty evidence ascertained GRADE.9Guyatt G.H. Oxman A.D. Schünemann H.J. al.GRADE guidelines: series articles Journal Clinical Epidemiology.J Epidemiol. 2011; 64: 380-382Abstract (1373) total 44 (5,745 review, which 23 21 proteinuric (IgA nephropathy, benign nephrosclerosis, membranous idiopathic glomerulonephritis, heart disease). For comparison between placebo, 22 (1,441 assessed (spironolactone), (925 selective (eplerenone), 4 (2,626 (finerenone esaxerenone), co-intervention both). median study follow-up duration 3 months none powered detect mortality, events. methodological domains unclear high most studies. uncertain (2 studies, 84 participants; ratio [RR], 3.00 [95% CI, 0.33-27.65]; very low-certainty evidence), (3 421 RR, 0.58 0.10-3.50]; events 1,067 0.95 0.26-3.56]; limitations few available reduce protein excretion (14 1,193 standardized mean difference [SMD], ?0.51 ?0.82 ?0.20]; evidence). However, difficult apply clinically, since heterogeneous measures necessitated use SMD, summarizes intervention each relative deviation observed study. example, SMD expresses level half lower placebo group, cannot translated into absolute In evidence, systolic pressure 911 difference, ?4.98 ?8.22 ?1.75] mm Hg) diastolic (13 875 ?1.04 ?2.82 0.73] Hg). eGFR 1,165 ?3.00 ?5.51 ?0.49] mL/min/1.73 m2, evidence) short-term data. antagonist selectivity eGFR, remain uncertain, only reported single each. probably increases (17 3,001 2.17 1.47-3.22]; moderate-certainty AKI (5 1,446 1.94 0.99-3.79]; gynecomastia (4 281 5.14 1.14-23.23]; similar antagonists. Gynecomastia compared diuretics, calcium channel blockers, alone, combination ARB, nitrates owing limited number reporting comparison. (1,066 eplerenone and/or mellitus. agent thought more less binding androgen impact urinary potassium levels, potent composite hospitalization, emergency presentation occurred higher-dose group secondary exploratory end point, there differences outcome N-terminal pro-B-type natriuretic peptide hyperkalemia.10Filippatos G. Anker Böhm al.A vs. mellitus 37: 2105-2114Crossref (152) risks uncertain. stage 1-4 increase hyperkalemia, AKI, underpowered short detected potential added therapy require further high-quality adequate power addressed concurrent potassium-binding agents. appear promising, recent FIDELIO-DKD showing 18% sustained decrease least 40%, causes) type 2 hyperkalemia.11Bakris G.L. Agarwal R. al.FIDELIO-DKD InvestigatorsEffect diabetes.N Engl 383: 2219-2229Crossref (178) Secondary showed 14% causes, nonfatal myocardial infarction, stroke, hospitalization we eagerly await results FIGARO-DKD trial, assess mortality disease.11Bakris