Kuan-Ting Chen1, Yi-No Kang2,3,4, Yen-Chung Lin5,6,7,8, I-Lin Tsai9, Wei-Chiao Chang10,11,12,13, Te-Chao Fang5,6,7, Mai-Szu Wu14,7,8,15, Chih-Chin Kao16,6,7,8. 1. Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan. 2. Institute of Health Policy and Management, College of Public Health, National Taiwan University, Taipei, Taiwan. 3. Evidence-Based Medicine Center, Wan Fang Hospital, Taipei Medical University. 4. Cochrane Taiwan, Taipei Medical University. 5. Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan. 6. Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 7. Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 8. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 9. Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 10. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan. 11. Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan. 12. Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 13. Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. 14. Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 121008@h.tmu.edu.tw. 15. Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. 16. Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan 121008@h.tmu.edu.tw.
Abstract
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; P=0.001) and all-cause mortality (relative risk, 0.44; 95% confidence interval, 0.30 to 0.66; P<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; P=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.
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; P=0.001) and all-cause mortality (relative risk, 0.44; 95% confidence interval, 0.30 to 0.66; P<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; P=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.
Authors: Jonathan A C Sterne; Jelena Savović; Matthew J Page; Roy G Elbers; Natalie S Blencowe; Isabelle Boutron; Christopher J Cates; Hung-Yuan Cheng; Mark S Corbett; Sandra M Eldridge; Jonathan R Emberson; Miguel A Hernán; Sally Hopewell; Asbjørn Hróbjartsson; Daniela R Junqueira; Peter Jüni; Jamie J Kirkham; Toby Lasserson; Tianjing Li; Alexandra McAleenan; Barnaby C Reeves; Sasha Shepperd; Ian Shrier; Lesley A Stewart; Kate Tilling; Ian R White; Penny F Whiting; Julian P T Higgins Journal: BMJ Date: 2019-08-28
Authors: Fabian Hammer; Uwe Malzahn; Julian Donhauser; Christoph Betz; Markus P Schneider; Clemens Grupp; Nils Pollak; Stefan Störk; Christoph Wanner; Vera Krane Journal: Kidney Int Date: 2019-01-31 Impact factor: 10.612
Authors: David M Charytan; Robert Padera; Alexander M Helfand; Michael Zeisberg; Xingbo Xu; Xiaopeng Liu; Jonathan Himmelfarb; Angeles Cinelli; Raghu Kalluri; Elisabeth M Zeisberg Journal: Int J Cardiol Date: 2014-07-06 Impact factor: 4.164
Authors: David M Charytan; Jonathan Himmelfarb; T Alp Ikizler; Dominic S Raj; Jesse Y Hsu; J Richard Landis; Amanda H Anderson; Adriana M Hung; Rajnish Mehrotra; Shailendra Sharma; Daniel E Weiner; Mark Williams; Marcelo DiCarli; Hicham Skali; Paul L Kimmel; Alan S Kliger; Laura M Dember Journal: Kidney Int Date: 2018-11-23 Impact factor: 10.612
Authors: Thaminda Liyanage; Toshiharu Ninomiya; Vivekanand Jha; Bruce Neal; Halle Marie Patrice; Ikechi Okpechi; Ming-hui Zhao; Jicheng Lv; Amit X Garg; John Knight; Anthony Rodgers; Martin Gallagher; Sradha Kotwal; Alan Cass; Vlado Perkovic Journal: Lancet Date: 2015-03-13 Impact factor: 79.321
Authors: Luca Di Lullo; Antonio Gorini; Domenico Russo; Alberto Santoboni; Claudio Ronco Journal: Cardiorenal Med Date: 2015-07-15 Impact factor: 2.041