Qi Chen1, Zi Wang2, Jingwei Zhou3, Zhenjie Chen1, Yan Li1, Shichao Li1, Hukang Zhao1, Sunil V Badve4,5, Jicheng Lv6. 1. Department of Nephrology, Dongzhimen Hospital, The First Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China. 2. Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University and Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China. 3. Department of Nephrology, Dongzhimen Hospital, The First Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China 13910634708@163.com jichenglv75@gmail.com. 4. Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia. 5. Department of Renal Medicine, St. George Hospital, Sydney, New South Wales, Australia. 6. Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University and Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China 13910634708@163.com jichenglv75@gmail.com.
Abstract
BACKGROUND AND OBJECTIVES: Several clinical practice guidelines noted the potential benefits of urate-lowering therapy on cardiovascular disease and CKD progression; however, the effect of this regimen remains uncertain. In this systematic review, we aimed to evaluate the efficacy of urate-lowering therapy on major adverse cardiovascular events, all-cause mortality, kidney failure events, BP, and GFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We systematically searched MEDLINE, Embase, and the Cochrane databases for trials published through July 2020. We included prospective, randomized, controlled trials assessing the effects of urate-lowering therapy for at least 6 months on cardiovascular or kidney outcomes. Relevant information was extracted into a spreadsheet by two authors independently. Treatment effects were summarized using random effects meta-analysis. RESULTS: We identified 28 trials including a total of 6458 participants with 506 major adverse cardiovascular events and 266 kidney failure events. Overall urate-lowering therapy did not show benefits on major adverse cardiovascular events (risk ratio, 0.93; 95% confidence interval, 0.74 to 1.18) and all-cause mortality (risk ratio, 1.04; 95% confidence interval, 0.78 to 1.39) or kidney failure (risk ratio, 0.97; 95% confidence interval, 0.61 to 1.54). Nevertheless, urate-lowering therapy attenuated the decline in the slope of GFR (weighted mean difference, 1.18 ml/min per 1.73 m2 per year; 95% confidence interval, 0.44 to 1.91) and lowered the mean BP (systolic BP: weighted mean difference, -3.45 mm Hg; 95% confidence interval, -6.10 to -0.80; diastolic BP: weighted mean difference, -2.02 mm Hg; 95% confidence interval, -3.25 to -0.78). There was no significant difference (risk ratio, 1.01; 95% confidence interval, 0.94 to 1.08) in the risk of adverse events between the participants receiving urate-lowering therapy and the control group. CONCLUSIONS: Urate-lowering therapy did not produce benefits on the clinical outcomes, including major adverse cardiovascular events, all-cause mortality, and kidney failure. Thus, there is insufficient evidence to support urate lowering in patients to improve kidney and cardiovascular outcomes.
BACKGROUND AND OBJECTIVES: Several clinical practice guidelines noted the potential benefits of urate-lowering therapy on cardiovascular disease and CKD progression; however, the effect of this regimen remains uncertain. In this systematic review, we aimed to evaluate the efficacy of urate-lowering therapy on major adverse cardiovascular events, all-cause mortality, kidney failure events, BP, and GFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We systematically searched MEDLINE, Embase, and the Cochrane databases for trials published through July 2020. We included prospective, randomized, controlled trials assessing the effects of urate-lowering therapy for at least 6 months on cardiovascular or kidney outcomes. Relevant information was extracted into a spreadsheet by two authors independently. Treatment effects were summarized using random effects meta-analysis. RESULTS: We identified 28 trials including a total of 6458 participants with 506 major adverse cardiovascular events and 266 kidney failure events. Overall urate-lowering therapy did not show benefits on major adverse cardiovascular events (risk ratio, 0.93; 95% confidence interval, 0.74 to 1.18) and all-cause mortality (risk ratio, 1.04; 95% confidence interval, 0.78 to 1.39) or kidney failure (risk ratio, 0.97; 95% confidence interval, 0.61 to 1.54). Nevertheless, urate-lowering therapy attenuated the decline in the slope of GFR (weighted mean difference, 1.18 ml/min per 1.73 m2 per year; 95% confidence interval, 0.44 to 1.91) and lowered the mean BP (systolic BP: weighted mean difference, -3.45 mm Hg; 95% confidence interval, -6.10 to -0.80; diastolic BP: weighted mean difference, -2.02 mm Hg; 95% confidence interval, -3.25 to -0.78). There was no significant difference (risk ratio, 1.01; 95% confidence interval, 0.94 to 1.08) in the risk of adverse events between the participants receiving urate-lowering therapy and the control group. CONCLUSIONS:Urate-lowering therapy did not produce benefits on the clinical outcomes, including major adverse cardiovascular events, all-cause mortality, and kidney failure. Thus, there is insufficient evidence to support urate lowering in patients to improve kidney and cardiovascular outcomes.
Authors: Benjamin R Szwejkowski; Stephen J Gandy; Sushma Rekhraj; John G Houston; Chim C Lang; Andrew D Morris; Jacob George; Allan D Struthers Journal: J Am Coll Cardiol Date: 2013-08-28 Impact factor: 24.094
Authors: Dinesh Khanna; John D Fitzgerald; Puja P Khanna; Sangmee Bae; Manjit K Singh; Tuhina Neogi; Michael H Pillinger; Joan Merill; Susan Lee; Shraddha Prakash; Marian Kaldas; Maneesh Gogia; Fernando Perez-Ruiz; Will Taylor; Frédéric Lioté; Hyon Choi; Jasvinder A Singh; Nicola Dalbeth; Sanford Kaplan; Vandana Niyyar; Danielle Jones; Steven A Yarows; Blake Roessler; Gail Kerr; Charles King; Gerald Levy; Daniel E Furst; N Lawrence Edwards; Brian Mandell; H Ralph Schumacher; Mark Robbins; Neil Wenger; Robert Terkeltaub Journal: Arthritis Care Res (Hoboken) Date: 2012-10 Impact factor: 4.794
Authors: Richard J Johnson; George L Bakris; Claudio Borghi; Michel B Chonchol; David Feldman; Miguel A Lanaspa; Tony R Merriman; Orson W Moe; David B Mount; Laura Gabriella Sanchez Lozada; Eli Stahl; Daniel E Weiner; Glenn M Chertow Journal: Am J Kidney Dis Date: 2018-02-27 Impact factor: 8.860
Authors: Kenneth G Saag; Andrew Whelton; Michael A Becker; Patricia MacDonald; Barbara Hunt; Lhanoo Gunawardhana Journal: Arthritis Rheumatol Date: 2016-08 Impact factor: 10.995
Authors: Marian Goicoechea; Soledad Garcia de Vinuesa; Ursula Verdalles; Eduardo Verde; Nicolas Macias; Alba Santos; Ana Pérez de Jose; Santiago Cedeño; Tania Linares; Jose Luño Journal: Am J Kidney Dis Date: 2015-01-13 Impact factor: 8.860
Authors: Michael M Givertz; Kevin J Anstrom; Margaret M Redfield; Anita Deswal; Haissam Haddad; Javed Butler; W H Wilson Tang; Mark E Dunlap; Martin M LeWinter; Douglas L Mann; G Michael Felker; Christopher M O'Connor; Steven R Goldsmith; Elizabeth O Ofili; Mitchell T Saltzberg; Kenneth B Margulies; Thomas P Cappola; Marvin A Konstam; Marc J Semigran; Steven E McNulty; Kerry L Lee; Monica R Shah; Adrian F Hernandez Journal: Circulation Date: 2015-04-14 Impact factor: 29.690
Authors: P Richette; M Doherty; E Pascual; V Barskova; F Becce; J Castañeda-Sanabria; M Coyfish; S Guillo; T L Jansen; H Janssens; F Lioté; C Mallen; G Nuki; F Perez-Ruiz; J Pimentao; L Punzi; T Pywell; A So; A K Tausche; T Uhlig; J Zavada; W Zhang; F Tubach; T Bardin Journal: Ann Rheum Dis Date: 2016-07-25 Impact factor: 19.103
Authors: Charles F Hayfron-Benjamin; Bert-Jan van den Born; Albert G B Amoah; Anke H Maitland-van der Zee; Karlijn A C Meeks; Erik J A J Beune; Kerstin Klipstein-Grobusch; Charles Agyemang Journal: JAMA Netw Open Date: 2021-10-01
Authors: Alicia Swee Yan Yip; Shariel Leong; Yao Hao Teo; Yao Neng Teo; Nicholas L X Syn; Ray Meng See; Caitlin Fern Wee; Elliot Yeung Chong; Chi-Hang Lee; Mark Y Chan; Tiong-Cheng Yeo; Raymond C C Wong; Ping Chai; Ching-Hui Sia Journal: Ther Adv Chronic Dis Date: 2022-03-23 Impact factor: 5.091
Authors: Christopher Jenkins; Jennifer H Hwang; Jeffrey B Kopp; Cheryl A Winkler; Sung Kweon Cho Journal: Front Pharmacol Date: 2022-08-23 Impact factor: 5.988