非甾体盐皮质激素受体拮抗剂治疗慢性肾脏病的疗效及安全性的meta分析

doi:10.3760/cma.j.cn441417-20241220-13007

摘要/Abstract

摘要：

目的　用meta分析法评估非甾体盐皮质激素受体拮抗剂（mineralocorticoid receptor antagonists，MRAs）治疗慢性肾脏病的疗效及安全性，为临床应用提供循证医学证据。方法　检索PubMed、Embase、Web of Science、Scopus、the Cochrane Library、中国知网、万方数据知识服务平台、维普资讯中文期刊服务平台、中国生物医学文献数据库从建库到2024年10月关于非甾体MRAs治疗慢性肾脏病的随机对照试验，对纳入的原始研究进行质量评价及数据提取，采用RevMan 5.4软件进行meta分析。结果　共纳入10篇文献，涉及16 365例患者。meta分析结果显示，非甾体MRAs组的尿白蛋白肌酐比（urinary albumin-to-creatinine ratio，UACR）的降低幅度大于安慰剂组［加权平均差（weighted mean difference，WMD）=-0.35（-0.41，-0.28），P<0.000 01］，估算肾小球滤过率（estimated glomerular filtration rate，eGFR）的降低幅度大于安慰剂组［WMD=-3.26（-4.86，-1.67），P<0.000 1］，eGFR下降≥30%和终末期肾病（end stage renal disease，ESRD）比例低于安慰剂组［风险比（risk ratio，RR）=0.85（0.78，0.93），P=0.000 3；RR=0.80（0.65，0.99），P=0.04］。从安全性来看，非甾体MRAs组心血管事件的发生率低于安慰剂组［RR=0.88（0.81，0.95），P=0.002］。虽然非甾体MRAs组的血清钾浓度升高幅度大于安慰剂组［WMD=0.17（0.14，0.21），P<0.000 01］，高钾血症比例高于安慰剂组［RR=2.01（1.81，2.23），P<0.000 01］，但两组之间不良事件的发生率相当［RR=1.00（0.98，1.01），P=0.68］。结论　非甾体MRAs有助于降低UACR，可改善慢性肾脏病患者的肾功能恶化，有显著的心肾保护作用。与安慰剂组相比，非甾体MRAs组发生高钾血症的风险较高，但总体不良事件风险无明显差异。

关键词: 盐皮质激素受体拮抗剂, 非奈利酮, 阿帕利酮, 艾沙利酮, 慢性肾脏病, meta分析

Abstract:

Objective　To evaluate the efficacy and safety of non-steroidal mineralocorticoid receptor antagonists (MRAs) in the treatment of chronic kidney disease by meta-analysis, and to provide evidence-based medical evidences for clinical application. Methods　The PubMed, Embase, Web of Science, Scopus, the Cochrane Library, CNKI, Wanfang Data, VIP Database, and China Biology Medicine database were searched for randomized controlled trials on non-steroidal MRAs for the treatment of chronic kidney disease from the establishment of the databases to October 2024. The quality evaluation and data extraction of the included original studies were conducted, and RevMan 5.4 software was used for meta-analysis. Results　A total of 10 articles were included, involving 16 365 patients. The results of the meta-analysis showed that the decrease degree of urinary albumin-to-creatinine ratio (UACR) in the non-steroidal MRA group was greater than that in the placebo group [weighted mean difference (WMD)= -0.35 (-0.41, -0.28), P<0.000 01], and the decrease degree of estimated glomerular filtration rate (eGFR) was greater than that in the placebo group [WMD=-3.26 (-4.86, -1.67), P<0.000 1], the proportions of eGFR decrease ≥30% and end-stage renal disease (ESRD) were lower than those in the placebo group [risk ratio (RR) =0.85 (0.78, 0.93), P=0.000 3; RR=0.80 (0.65, 0.99), P=0.04]. In terms of safety, the incidence of cardiovascular events in the non-steroidal MRA group was lower than that in the placebo group [RR=0.88 (0.81, 0.95), P=0.002]. Although the increase degree of serum potassium concentration in the non-steroidal MRA group was greater than that in the placebo group [WMD=0.17 (0.14, 0.21), P<0.000 01], and the proportion of hyperkalemia was higher than that in the placebo group [RR=2.01 (1.81, 2.23), P<0.000 01]. However, the incidence of adverse events was comparable between the two groups [RR=1.00 (0.98, 1.01), P=0.68]. Conclusions　Non-steroidal MRAs help to reduce the UACR, improve the renal function deterioration in chronic kidney disease patients, and have significant cardiorenal protective effects. Compared with the placebo group, the non-steroidal MRA group has a higher risk of hyperkalemia, but there is no significant difference in overall risk of adverse events.

Key words: Mineralocorticoid receptor antagonists, , Finerenone, , Apararenone, , Esaxerenone, , Chronic kidney disease, , Meta-analysis

李昕萌刘倩倩边左珺刘云启.

非甾体盐皮质激素受体拮抗剂治疗慢性肾脏病的疗效及安全性的meta分析 [J]. 国际医药卫生导报, 2025, 31(13): 2141-2148.

Li Xinmeng, Liu Qianqian, Bian Zuojun, Liu Yunqi.

Efficacy and safety of non-steroidal mineralocorticoid receptor antagonists in the treatment of chronic kidney disease: a meta-analysis [J]. International Medicine and Health Guidance News, 2025, 31(13): 2141-2148.

参考文献

[1]Xie Y, Bowe B, Mokdad AH, et al. Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016[J]. Kidney Int, 2018, 94(3):567-581. DOI: 10.1016/j.kint.2018.04.011.

[2]Agarwal R, Kolkhof P, Bakris G, et al. Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine[J]. Eur Heart J, 2021, 42(2):152-161. DOI: 10.1093/eurheartj/ehaa736.

[3]Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial[J]. Eur Heart J, 2013, 34(31):2453-2463. DOI: 10.1093/eurheartj/eht187.

[4]Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial[J]. JAMA, 2015, 314(9):884-894. DOI: 10.1001/jama.2015.10081.

[5]Filippatos G, Anker SD, Böhm M, et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease[J]. Eur Heart J, 2016, 37(27):2105-2114. DOI: 10.1093/eurheartj/ehw132.

[6]Sato N, Ajioka M, Yamada T, et al. A randomized controlled study of finerenone vs. eplerenone in Japanese patients with worsening chronic heart failure and diabetes and/or chronic kidney disease[J]. Circ J, 2016, 80(5):1113-1122. DOI: 10.1253/circj.CJ-16-0122.

[7]Katayama S, Yamada D, Nakayama M, et al. A randomized controlled study of finerenone versus placebo in Japanese patients with type 2 diabetes mellitus and diabetic nephropathy[J]. J Diabetes Complications, 2017, 31(4):758-765. DOI: 10.1016/j.jdiacomp.2016.11.021.

[8]Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes[J]. N Engl J Med, 2020, 383(23):2219-2229. DOI: 10.1056/NEJMoa2025845.

[9]Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes[J]. N Engl J Med, 2021, 385(24):2252-2263. DOI: 10.1056/NEJMoa2110956.

[10]Wada T, Inagaki M, Yoshinari T, et al. Apararenone in patients with diabetic nephropathy: results of a randomized, double-blind, placebo-controlled phase 2 dose-response study and open-label extension study[J]. Clin Exp Nephrol, 2021, 25(2):120-130. DOI: 10.1007/s10157-020-01963-z.

[11]Ito S, Kashihara N, Shikata K, et al. Esaxerenone (CS-3150) in patients with type 2 diabetes and microalbuminuria (ESAX-DN): phase 3 randomized controlled clinical trial[J]. Clin J Am Soc Nephrol, 2020, 15(12):1715-1727. DOI: 10.2215/CJN.06870520.

[12]Bakris G, Pergola PE, Delgado B, et al. Effect of KBP-5074 on blood pressure in advanced chronic kidney disease: results of the BLOCK-CKD study[J]. Hypertension, 2021, 78(1):74-81. DOI: 10.1161/HYPERTENSIONAHA.121.17073.

[13]Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions[J]. Cochrane Database Syst Rev, 2019, 10(10):ED000142. DOI: 10.1002/14651858.ED000142.

[14]李昕萌,刘倩倩,刘云启.慢性肾脏病进展的危险因素及延缓策略[J].国际医药卫生导报,2024,30(11):1766-1770. DOI:10.3760/cma.j.issn.1007-1245.2024.11.002.

[15]Schmieder RE, Schutte R, Schumacher H, et al. Mortality and morbidity in relation to changes in albuminuria, glucose status and systolic blood pressure: an analysis of the ONTARGET and TRANSCEND studies[J]. Diabetologia, 2014, 57(10):2019-2029. DOI: 10.1007/s00125-014-3330-9.

[16]Lattenist L, Lechner SM, Messaoudi S, et al. Nonsteroidal mineralocorticoid receptor antagonist finerenone protects against acute kidney injury-mediated chronic kidney disease: role of oxidative stress[J]. Hypertension, 2017, 69(5):870-878. DOI: 10.1161/HYPERTENSIONAHA.116.08526.

[17]Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury[J]. J Cardiovasc Pharmacol, 2014, 64(1):69-78. DOI: 10.1097/FJC.0000000000000091.

[18]Collard D, Brouwer TF, Olde Engberink RHG, et al. Initial estimated glomerular filtration rate decline and long-term renal function during intensive antihypertensive therapy: a post hoc analysis of the SPRINT and ACCORD-BP randomized controlled trials[J]. Hypertension, 2020, 75(5):1205-1212. DOI: 10.1161/HYPERTENSIONAHA.119.14659.

[19]Ito S, Shikata K, Nangaku M, et al. Efficacy and safety of esaxerenone (CS-3150) for the treatment of type 2 diabetes with microalbuminuria: a randomized, double-blind, placebo-controlled, phase II trial[J]. Clin J Am Soc Nephrol, 2019, 14(8):1161-1172. DOI: 10.2215/CJN.14751218.

[20]Grune J, Beyhoff N, Smeir E, et al. Selective mineralocorticoid receptor cofactor modulation as molecular basis for finerenone's antifibrotic activity[J]. Hypertension, 2018, 71(4):599-608. DOI: 10.1161/HYPERTENSIONAHA.117.10360.

[21]Grune J, Beyhoff N, Smeir E, et al. Selective mineralocorticoid receptor cofactor modulation as molecular basis for finerenone's antifibrotic activity[J]. Hypertension, 2018, 71(4):599-608. DOI: 10.1161/HYPERTENSIONAHA.117.10360.

[22]Chen W, Zheng L, Wang J, et al. Overview of the safety, efficiency, and potential mechanisms of finerenone for diabetic kidney diseases[J]. Front Endocrinol (Lausanne), 2023, 14:1320603. DOI: 10.3389/fendo.2023.1320603.

[23]Yang P, Shen W, Chen X, et al. Comparative efficacy and safety of mineralocorticoid receptor antagonists in heart failure: a network meta-analysis of randomized controlled trials[J]. Heart Fail Rev, 2019, 24(5):637-646. DOI: 10.1007/s10741-019-09790-5.

[24]Ndumele CE, Neeland IJ, Tuttle KR, et al. A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: a scientific statement from the American Heart Association[J]. Circulation, 2023, 148(20):1636-1664. DOI: 10.1161/CIR.0000000000001186.

[25]American Diabetes Association Professional Practice Committee. 11. Chronic kidney disease and risk management: standards of care in diabetes-2024[J]. Diabetes Care, 2024, 47(Suppl 1):S219-S230. DOI: 10.2337/dc24-S011.

[26]«中华内科杂志»编辑委员会,盐皮质激素受体拮抗剂临床应用共识专家组.盐皮质激素受体拮抗剂临床应用多学科中国专家共识(2022)[J].中华内科杂志,2022,61(9):981-999. DOI:10.3760/cma.j.cn112138-20220622- 00472.