延缓慢性肾脏病进展临床管理指南（2025年版）

指南肾脏内科· 其他肾脏疾病 · 2025 · 中国研究型医院学会

一、指南制定背景

慢性肾脏病(chronic kidney disease，CKD)已成为全球范围内重大公共卫生问题，对人类健康构成严重威胁并带来沉重疾病负担。根据“全球疾病负担(global burden of disease,GBD)”研究，2021年全球CKD的患病人数高达6.74亿，占全球总人口的8.0% ${}^{[1]}$ 。2021年CKD导致了4 450万伤残调整生命年(disability-adjusted life-years，DALYs)和3 560万早死损失生命年(years of life lost,YLL)，且与2010年相比呈显著增长趋势。随着全球老龄化趋势加剧，以及糖尿病、高血压等慢性疾病患病率持续增长，预计到2050年CKD3~5期的患病率在全球许多地区将超过$$10\%^{[2]}\circ$$

我国CKD的防控形势尤为严峻。GBD数据显示，2017年我国CKD患病人数已达1.3亿，位居全球之首[3]。后续一项系统回顾分析研究显示，2020年这一数字可能已上升至1.6亿[4]。值得注意的是，目前中国CKD患者虽以早期阶段为主，但CKD3期患者比例较大。第6次中国慢性病及危险因素监测结果显示，我国CKD1~2期、3期和4~5期患者分别约占73.3%、25.0%和1.8%，CKD3期患者占了1/4。我国CKD防治具有知晓率低、治疗率低和控制率低“三低”特点。随着CKD向中晚期进展，相关合并症和并发症负担将逐渐加重。而一旦发展为终末期肾病(end-stage kidney disease，ESKD)，患者需依赖血液透析、腹膜透析或肾移植等肾脏替代治疗以维持生命。这不仅严重影响患者的生活质量，也给家庭、社会及公共卫生体系带来沉重负担[6]。因此，延缓CKD进展对于降低ESKD患病率和病死率，改善患者生存质量具有十分重要的意义。

延缓CKD进展策略需综合考虑患者的个体差异，以患者为中心进行全面管理。治疗目标不仅包括肾脏保护以降低ESKD发生率，还应涵盖合并症和并发症的管理，以降低患者病死率和提高生活质量。近年来健康生活方式在CKD管理中的重要性日益受到重视[7]，而众多药物不断问世也为CKD治疗提供了更多有效手段。在延缓CKD进展方面，除了经典基础用药血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitor,ACEI)/血管紧张素II受体拮抗剂(angiotensin II receptor blocker,ARB)外，钠-葡萄糖共转运蛋白2抑制剂(sodium-glucose cotransporter-2 inhibitor,SGLT2i)、非甾体盐皮质激素受体拮抗剂(nonsteroidal mineralocorticoid receptor antagonist,nsMRA)和胰高血糖素样肽-1受体激动剂(glucagon-like peptide-1 receptor agonists,GLP-1RA)等新型药物已在CKD治疗中得到应用。此外，可能有助于延缓特定人群CKD进展的新药，如血管紧张素受体脑啡肽酶抑制剂(angiotensin receptor neprilysin inhibitor，ARNI)、内皮素受体拮抗剂(endothelin receptor antagonist,ERA)等也在一些临床试验中显示出令人鼓舞的价值 ${}^{[8-10]}$ 。

本指南旨在结合最新的循证医学证据和专家临床实践经验，以有效延缓非透析CKD患者疾病进展为目标，制定符合我国国情的CKD临床管理规范，最终造福广大肾病患者。

二、指南制定方法

本指南由中国研究型医院学会发起，邀请肾脏病学及相关领域的权威专家共同组建了一支多学科的指南工作组。本指南已在国际实践指南注册与透明化平台(practice guideline registration for transparency,PREPARE)注册，注册号为PREPARE-2024CN1168。指南的制定严格遵循世界卫生组织(World Health Organization,WHO)发布的《WHO指南制订手册》(第二版)和中华医学会发布的《制订/修订<临床诊疗指南>的基本方法及程序》。

本指南主要面向肾脏病诊疗管理的临床医学工作者，包括肾脏专科医师、内科医师、全科医师、护理工作者、临床药师以及基层医疗卫生人员。推荐意见的应用目标人群为未接受透析治疗的成年CKD患者。

本指南的证据检索涵盖了国际和国内重要数据库中近10年间收录的有关CKD临床管理的文献，包括PubMed、Embase、Cochrane Library、UpToDate、改善全球肾脏病预后组织(Kidney Disease:Improving Global Outcomes,KDIGO)官方网站、美国心脏病学和肾脏病学会官方网站、欧洲心脏病学和肾脏病学会官方网站、谷歌学术、万方医学网、中国知网和百度学术等。为确保证据的时效性，检索工作持续更新至2024年10月，并于同年补充检索了部分内容。

本指南采用牛津证据分级系统对证据质量和推荐强度进行分级[13]。证据等级及推荐强度见表1。

基于国内外循证证据，结合我国临床实践和患者偏好，指南工作组撰写了证据阐述并初拟了推荐意见。为提升指南的科学性和实用性，工作组通过多轮意见反馈和讨论会，广泛征集专家意见，并对指南内容进行了细致的修订，形成最终推荐意见。本指南发表后，工作组计划每年对新证据进行动态评估，并在3~5年内更新推荐意见，以保持指南内容的前沿性和适用性。

三、CKD患者的进展风险评估和临床管理目标

1.CKD的诊断:CKD是由多种原因引起的肾脏结构和/或功能异常，持续时间超过3个月的慢性疾病。CKD的诊断标准为以下7项肾损伤或肾功能降低指标中任何一项的异常持续超过3个月:(1)肾功能降低[估算肾小球滤过率(estimated glomerular filtration rate, eGFR)<60 ml· $\min^{-1}\cdot$ (1.73 $\,m^{2}$ ) ${}^{-1}$ ];(2)白蛋白尿[尿白蛋白/肌酐比值(albumin-to-creatinine ratio,ACR≥30 mg/g(或≥3 mg/mmol)];(3)尿沉渣异常;(4)肾小管功能异常引起的电解质及其他异常;(5)肾组织学异常;(6)肾影像学异常;(7)肾移植病史 ${}^{[14]}$ 。在肾损伤或肾功能异常持续时间不明确的情况下，应进行临床评估以区分CKD、急性肾损伤(acute kidney injury,AKI,即肾功能改变在2~7d内发生)和急性肾脏病(肾结构或肾功能出现异常≤3个月)。

表12009版牛津证据分级系统

|推荐强度|证据水平|定义(以治疗/预防为例)| |---|---|---| |A|1a 1b 1c|纳入一致性较高的随机对照试验的系统评价| |A|1a 1b 1c|置信区间较窄的单个随机对照试验| |A|1a 1b 1c|“全或无”证据(实施治疗前,所有患者均死亡;实施治疗后,有患者能存活。或实施治疗前,部分患者死亡; 实施治疗后,无患者死亡)| |B|2a 2b 2c 3a 3b|纳入一致性较高的队列研究的系统评价| |B|2a 2b 2c 3a 3b|单个队列研究(或低质量随机对照试验)| |B|2a 2b 2c 3a 3b|生态学研究| |B|2a 2b 2c 3a 3b|纳入一致性较高的病例对照研究的系统评价| |B|2a 2b 2c 3a 3b|单个病例对照研究| |C|4|病例系列(或低质量队列研究或病例对照研究)| |D|5|专家意见|

2.CKD进展风险评估:

四、延缓 CKD进展的方法

(一)延缓 CKD进展的综合性管理策略

(二)改善生活方式和纠正急性可逆性因素

1.调整饮食:

2.运动和控制体重:

3.戒烟:

4.纠正可逆性因素:

(三)积极控制原发病

(四)积极控制CKD进展相关的危险因素

推荐意见

16.推荐积极控制与CKD进展相关的主要危险因素，包括但不限于高血压、高血糖和蛋白尿。(推荐强度A，证据等级1a)

影响CKD进展的因素是多方面的，包括CKD的原发病因、eGFR水平、尿白蛋白水平、AKI、肾脏病理活动指数、高血压、高血糖、血脂异常、高尿酸、贫血、吸烟、肥胖、CVD史和持续暴露于肾毒性药物等[75]。其中，高血压、高血糖和蛋白尿是CKD进展最常见且重要的危险因素，它们与CKD并发症、CVD的发生以及不良预后风险密切相关[75]，需要积极进行临床干预。此外，CKD患者的感染风险增高，而感染又可能增加患者贫血、循环功能障碍、肾脏损伤或死亡等风险[76]，因此，积极防控感染也是延缓CKD进展的重要策略。其他一些自身免疫性疾病引起的肾脏活动性病变也是非常重要的可逆转因素，应依据病情变化，及时采取针对性治疗措施。

1.严格管控高血压:

推荐意见

17.建议大多数非透析 CKD患者的血压控制目标为<130/80 mmHg,对于可耐受且肾功能稳定的患者,可进一步降低收缩压至 120 mmHg;年龄≥65岁的非透析CKD患者,如能耐受,血压可逐渐降至<140/90 mmHg。(推荐强度A,证据等级1a)

高血压既是 CKD的始动因素，又是 CKD进展的主要危险因素之一,还是 CKD患者发生 CVD的高危因素,与 CKD

患者的不良肾脏预后和心血管结局密切相关。2019年数据显示，我国与高血压相关的CKD患病人数约为558万，死亡人数达7.026万，导致169万DALYs[77]。第六次中国慢性病及危险因素监测结果显示，CKD患者高血压的知晓率和治疗率分别为52.9%和46.3%，控制率仅为24.5%[5]，在超重或肥胖、合并蛋白尿、较低eGFR水平和糖尿病患者中，血压控制情况尤其不佳 ${}^{[78]}$ 。

日本一项前瞻性集群随机试验(FROM-J)的事后分析[79]显示，将CKD患者血压控制在130/80mmHg以下可显著降低不良肾脏结局的风险，在合并蛋白尿的患者中获益更为显著。韩国的前瞻性CKD队列研究亦表明，非透析CKD患者在1年内收缩压控制达标的时间越长，eGFR下降幅度越小 ${}^{[80]}$ 。

尽管如此，不同指南推荐的CKD患者血压控制目标存在差异。KDIGO指南建议有高血压的CKD患者的血压控制目标为收缩压<120 mmHg,但支持这一目标与延缓CKD进展相关性的直接证据尚不充分。SPRINT强化降压研究[81]显示，与标准降压治疗(收缩压目标<140mmHg)相比，强化降压(收缩压目标<120mmHg)能降低25%的主要心血管事件风险，但CKD患者亚组结果显示，强化降压治疗与标准降压相比未能延缓 CKD进展或改善不良肾病结局。因此，在考虑患者的耐受性后，对大多数非透析 CKD患者，建议控制血压在130/80 mmHg以下，对于可耐受且肾功能稳定的患者，可进一步降低收缩压至 120 mmHg;年龄≥65岁的非透析CKD患者，如能耐受，血压可考虑逐渐降至<140/90 mmHg。

2.积极控制高血糖:

推荐意见

18.建议未接受透析治疗的CKD合并糖尿病患者使用个体化控糖目标:对大多数无低血糖风险且健康状态良好的患者，建议糖化血红蛋白(HbA1c)控制目标<6.5%;对发生过严重低血糖事件、预期寿命较短、合并严重大血管或微血管并发症的患者，建议HbA1c控制目标<8.0%。(推荐强度A，证据等级1a)

糖尿病是导致CKD患者严重健康问题的主要原因之一，包括心血管并发症和ESKD等[83]。血糖控制不佳与不良肾脏结局风险增加密切相关。我国与糖尿病相关的CKD患病人数在2019年约为3164万，死亡人数为7.603万,导致 213万 DALYs ${}^{[85]}$ 。而我国 CKD患者对糖尿病的知晓率、治疗率和控制率分别为 45.1%、 43.6%和$$42.3\%^{[5]}\circ$$

良好的血糖控制可有效延缓 CKD进展，改善临床预后。一项包含 11项 RCT研究的荟萃分析 ${}^{[ 86]}$ 发现，血糖控制达标(HbA1c<7.0%)可降低非致死性心肌梗死和微量白蛋白尿进展风险。多项 RCT研究比较了强化降糖治疗(HbA1c:<6.5%~<7.1%)与标准降糖治疗( HbA1c:<7.3%~<8.4%)对糖尿病患者临床结局的影响,

结果显示，使用强化降糖治疗可降低白蛋白尿和ESKD发生风险[87-92]。国内外的CKD管理和糖尿病管理指南[15,93-95]均建议应考虑年龄、病程和并发症等因素制定个体化控糖目标，达到最大治疗获益。KDIGO和美国糖尿病学会(American Diabetes Association,ADA)2022年联合发布了关于CKD患者糖尿病管理的共识报告 ${}^{[93]}$ ,KDIGO指南建议糖尿病合并CKD患者的HbA1c目标应为<6.5%~<8.0%;ADA则建议对于大多数无低血糖风险的非妊娠成年1型糖尿病(type 1 diabetes mellitus,T1DM)和 2型糖尿病(type 2 diabetes mellitus,T2DM)患者，起始HbA1c目标应为<7%，但对于预期寿命有限且治疗弊大于利的患者，更高的目标(即<8%)也是可以接受的。

3.积极治疗蛋白尿:

(五)延缓CKD进展的药物治疗

1.RAASi:肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system,RAAS)激活是 CKD进展的重要机制，也是心血管风险增加和心力衰竭发生发展的关键因素。RAASi包括ACEI/ARB、醛固酮受体拮抗剂(aldosterone receptor antagonist,ARA)/盐皮质激素受体阻断剂(mineralocorticoid receptor antagonist,MRA)、肾素抑制剂以及ARNI。其中ACEI/ARB是CKD临床治疗的经典基础用药 ${}^{[14,104-105]}$ 。

近年来大量RCT研究提示，RAASi在伴或不伴T2DM的CKD患者中均能延缓CKD进展和降低心血管事件风险，这类药物也已成为 CKD临床管理的基础用药 ${}^{[14,105]}$ 。

(1) ACEI/ARB:

2. SGLT2i:

28.推荐CKD患者(伴或不伴糖尿病)eGFR≥20ml· $\min^{-1}\cdot(1.73~m^{2})^{-1}$ 时使用SGLT2i治疗。(推荐强度A，证据等级1a)

29.推荐以下CKD患者优先启用SGLT2i治疗:①有中度及以上CKD进展风险的患者;②有发生心血管事件的高危因素;③伴心力衰竭(无论射血分数水平);④合并T2DM。(推荐强度A，证据等级1a)

30.SGLT2i治疗后患者eGFR下降≤30%无需中止治疗(推荐强度B,证据等级2b);如eGFR下降>30%则需注意检查患者有无容量不足或同时使用其他肾毒性药物，评估肾损伤的病因，如无法缓解，则建议减量或停药(推荐强度B,证据等级3a)。已使用SGLT2i的患者，eGFR下降到20ml·min-1·(1.73m2)-1以下建议可继续使用，直至患者不可耐受或需透析、肾移植(推荐强度C，证据等级4)。

31.建议反复发生低血糖事件的T2DM患者调整原有降糖方案。(推荐强度B，证据等级2b)

SGLT2i通过抑制近端小管对葡萄糖的重吸收，导致葡萄糖在尿液中蓄积(糖尿),由此产生的高渗透压引发渗透性利尿(增加尿量)，最终促进尿液排出多余的葡萄糖[105,125-126]。目前认为SGLT2i对CKD的肾脏保护机制主要包括:通过抑制SGLT2来恢复远端钠输送，以修复管球反馈和恢复正常传入张力，降低肾小球内压;降低血压和改善血管功能;减轻肾小管工作负荷和改善缺氧;增加代谢效应和激活转录因子以增加自噬作用等 ${}^{[127]}$ 。

最近一项荟萃分析(纳入13项试验，涉及超过9万例患者数据)显示，与安慰剂组相比，SGLT2i组患者的肾脏病进展风险下降37%(RR=0.63,95%CI0.58~0.69)，且无论患者是否合并糖尿病，以及无论CKD病因(糖尿病肾病，缺血性和高血压性肾病，肾小球疾病如IgA肾病、局灶节段性肾小球硬化等其他原因肾脏病)，经SGLT2i治疗，肾病进展风险降低程度类似。已有3项大型RCT探讨了SGLT2i对CKD患者(伴或不伴T2DM)肾脏结局和心血管风险的影响 ${}^{[27-29]}$ 。2019年CREDENCE研究 ${}^{[27]}$ 在4401例合并糖尿病的 CKD患者中评估了卡格列净的治疗效果，受试者 eGFR为30~90ml·min ${}^{-1}\cdot$ (1.73m ${}^2$ ) ${}^{-1}$ 。结果显示，卡格列净组的主要复合终点(ESKD、血肌酐水平翻倍、肾脏或心血管原因死亡)相对风险相比安慰剂组下降30%(HR=0.70,P<0.001),肾脏特异性复合终点相对风险下降34%(HR=0.66,P<0.001),ESKD相对风险下降 32%(HR=0.68,P=0.002),全因死亡结局阴性。DAPA-CKD研究 ${}^{[28]}$ 则首次在伴或不伴

T2DM的CKD患者(n=4304)中评估了达格列净的治疗结局，受试者eGFR为25~75ml·min-1·(1.73m2)-1。结果显示，与安慰剂组相比，达格列净组的主要复合结局(eGFR持续下降至少50%、肾衰竭、肾脏或心血管原因死亡)相对风险下降39%(HR=0.61,P<0.001)，肾脏特异性复合终点风险下降44%(HR=0.56,P<0.001)，心血管死亡或因心力衰竭住院风险下降29%(HR=0.71,P=0.009)，全因死亡风险下降31%(HR=0.68,P=0.004)。伴或不伴T2DM的CKD患者接受达格列净的治疗获益类似。EMPA-KIDNEY研究[29]评估了恩格列净对肾脏结局的影响，研究纳入6609例eGFR 20~<45 ml·min-1·(1.73 m2)-1，或eGFR 45~<90 ml·min-1·(1.73m2)-1且ACR≥200mg/g的CKD患者(伴或不伴T2DM)。结果表明，与安慰剂组相比，恩格列净组肾病进展和心血管原因死亡复合终点风险下降28%(HR=0.72,P<0.001)，在伴或不伴T2DM和不同基线eGFR的患者中观察到获益一致，但未能观察到心血管终点和全因死亡终点风险降低。

目前有5项大型RCT研究探讨了SGLT2i治疗心力衰竭患者(伴/不伴T2DM)的疗效结局，结果显示SGLT2i治疗明显降低心力衰竭恶化、住院和死亡风险[129-133]，其中两项RCT研究的受试者为射血分数≤40%的心力衰竭患者[129-130]，两项RCT研究则针对射血分数>40%的心力衰竭患者[131-132]。这些研究包含40.5%~50.2% CKD患者，次要肾脏终点结局提示SGLT2i治疗可显著改善心力衰竭患者的肾脏结局(延缓eGFR下降)，亚组分析提示合并CKD的心力衰竭患者接受SGLT2i治疗后的主要心力衰竭不良结局风险降低获益与总人群一致[129-130]。3项评估SGLT2i治疗CKD的临床研究包含10.1%~14.8%心力衰竭患者[27-29]，CREDENCE[27]和DAPA-CKD[28]研究分别观察到卡格列净组和达格列净组相比安慰剂组的心血管不良事件风险明显降低，EMPA-KIDNEY研究[29]观察到恩格列净组相比安慰剂组的心血管不良事件风险有降低趋势。

SGLT2i用药注意事项 ${}^{[134]}$ :①开始治疗后2~4周，部分患者会出现eGFR下降>10%的现象，如eGFR较基线下降<30%，不需要停用SGLT2i药物，但需监测eGFR变化。若2~4周内血肌酐水平升高≥30%，建议首先分析是否存在血容量不足或合并使用了其他肾毒性药物，并进行相应处理，如无法缓解，则建议减量或停药。进展至透析或肾移植者应停止 SGLT2i治疗 ${}^{[105]}$ 。②反复发生低血糖事件的T2DM患者,需调整原有降糖方案,减少联合使用胰岛素、磺胺类或格列奈类药物的剂量后再加用 SGLT2i。③SGLT2i与ACEI/ARB联合应用时,应当遵循个体化治疗原则,采用“序贯”给药方法，避免早期eGFR下降效应的叠加。

3. GLP-1RA:

4.中医药治疗:

(六)积极管理合并症、并发症，延缓CKD进展

1.CKD合并高血压:

2.CKD患者CVD风险管理:

推荐意见

41.推荐对CKD患者定期进行CVD风险评估，结合心血管-肾脏-代谢综合征(cardiovascular-kidney-metabolic syndrome，CKM)的分级管理策略进行早期管理，以预防和延缓心肾疾病的进展。(推荐强度A，证据等级1b)

心、肾作为控制机体有效循环和血流动力学稳定的两个重要器官，在生理功能上相互依存，在病理状态下相互影响[170-171],其中一个器官的急性或慢性功能障碍可诱发另一个器官的损伤或功能障碍 ${}^{[172]}$ 。数据显示,我国27.8%的住院CKD患者合并CVD。CKD患者中的CVD主要表现为心血管钙化、心脏结构及功能改变、心律失常、心力衰竭，甚至猝死 ${}^{[174-176]}$ ,而且随着eGFR下降，这些风险逐渐增加，大部分CKD患者因CVD而过早死亡的风险超过发展为肾衰竭的风险 ${}^{[177]}$ 。

值得注意的是，CKD患者常合并代谢危险因素如高血

糖、高血压、高血脂、肥胖等会进一步加剧CVD、CKD和T2DM的恶性循环，2023年美国心脏协会(AHA)由此提出了CKM的定义，进一步强调了CVD、肾脏疾病、T2DM和肥胖等之间的相互影响，旨在更好地指导临床重视心肾预后影响因素的综合管理。建议对所有患者尽早和全程监测风险因素，检测的频率和内容应根据CKM分期而调整。针对风险因素和CKM分期变化应尽早给予积极干预。

(1)积极防治动脉粥样硬化性CVD(atherosclerotic cardiovascular disease,ASCVD):

推荐意见

42.推荐CKD患者综合管理高血压、高血糖、高血脂和CKD-MBD，以降低ASCVD风险。(推荐强度A，证据等级1a)

43.推荐非透析CKD患者，尤其是年龄≥50岁且eGFR<60 ml·min-1·(1.73 m2)-1的患者，使用他汀类药物联合或不联合依折麦布治疗血脂异常，以持续降低低密度脂蛋白(low density lipoprotein,LDL)胆固醇水平，减少心血管事件的发生。(推荐强度A，证据等级1a)

44.CKD患者的ASCVD治疗应结合个体病情，制定包括药物干预和冠状动脉血运重建的个体化方案。(推荐强度B，证据等级2c)

45.CKD患者接受冠状动脉血运重建时，应充分评估造影剂相关肾病(contrast-induced nephropathy,CIN)风险，并采取预防措施如充分水化、使用低渗型造影剂及减少造影剂用量。(推荐强度A，证据等级2b)

ASCVD是CVD的主要病理基础。CKD人群存在与ASCVD风险增加相关的多种危险因素，包括一般危险因素如高血压、高血糖、高血脂，以及CKD特异性危险因素CKD-MBD。CKD-MBD会加速血管钙化，主要表现为大动脉及中小动脉内膜、中膜的钙质沉积和心脏瓣膜钙化，从而增加心血管事件风险。

2024年KDIGO指南[14]提出，在CKD患者中预防ASCVD应针对高血压、高血糖、高血脂、CKD-MBD等风险因素进行药物、饮食和生活方式干预。2023年AHA ${}^{[178]}$ 提出，对存在CKD、代谢危险因素和/或亚临床CVD的1~3级CKM患者应重视“生命八要素”管理，即4个健康行为(饮食、身体活动、戒烟、睡眠)和4个健康指标(体重、血胆固醇、血糖、血压)的管理 ${}^{[178]}$

CKD患者中的高血压、高血糖和CKD-MBD管理策略见本指南的相关章节阐述。

CKD患者的血脂异常主要表现为甘油三酯和LDL胆固醇水平较高，高密度脂蛋白(high density lipoprotein,HDL)胆固醇水平较低 ${}^{[179]}$ 。血脂异常不仅增加CKD患者发生CVD的风险，也与CKD进展风险显著增加相关 ${}^{[179-180]}$ 。他汀类药物是临床首选的调脂药物。一项纳入28项RCT的荟萃分析 ${}^{[181]}$ 评估了他汀类药物对非透析 CKD患者心血管事件的影响，结果显示，经他汀类药物治疗后，LDL胆固醇每

降低1mmol/L,首次主要血管事件风险降低21%(RR=0.79，95%CI0.77~0.81)。近年发表的研究报告证实了他汀类药物的总体安全性 ${}^{[ 182]}$ 。

在临床实际使用调脂药物时，应考虑CKD患者年龄、eGFR水平以及是否合并CVD、CVD风险进行个体化调整 ${}^{[14]}$ :年龄≥50岁、eGFR<60 ml·min ${}^{-1}$ ·(1.73 m ${}^{2}$ )- ${}^{1}$ 的 CKD患者(长期透析和肾移植患者除外)，推荐使用他汀类药物和/或联合依折麦布治疗;年龄≥50岁、eGFR≥60 ml·min-1.(1.73m2)-1的CKD患者，推荐使用他汀类药物治疗;年龄18~49岁、未接受长期透析或肾移植的CKD患者，伴如下一种或多种情况时推荐使用他汀类药物治疗:已知冠心病(心肌梗死或冠状动脉血运重建)、糖尿病、既往发生缺血性卒中、CVD风险预测模型评分预测冠心病10年死亡风险发生率或非致死性心肌梗死发生率≥10%。对于杂合子家族性高胆固醇血症患者，或需要进一步降低LDL水平的合并ASCVD患者，可以考虑在饮食调节和使用最大耐受剂量他汀类药物基础上添加前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin kexin type 9,PCSK-9)抑制剂 ${}^{[183]}$

CKD合并ASCVD患者的管理原则与非CKD患者相同，但需注意不同肾功能状态下药物剂量的调整和药物之间相互作用及其对肾功能潜在的不良影响:①调脂:CKD 1~2期患者使用他汀类药物无须减量;CKD3期患者使用阿托伐他汀、辛伐他汀、氟伐他汀、瑞舒伐他汀均无须减量，而普伐他汀应限制使用;CKD4期患者使用阿托伐他汀无须减量，辛伐他汀应减量使用，而氟伐他汀、瑞舒伐他汀、普伐他汀、PCSK-9抑制剂等均应限制使用。依折麦布在CKD患者中无须调整剂量。CKD患者使用他汀类药物治疗时应关注肌病风险的升高 ${}^{[184]}$ 。②抗栓:CKD患者使用抗血小板药物前应充分评估出血风险 ${}^{[185]}$ 。CKD 1~3b期患者建议使用低剂量阿司匹林作为二级预防用药，治疗过程中需密切监测肾功能变化，阿司匹林不能耐受的情况下，可考虑使用P2Y12抑制剂(氯吡格雷、替格瑞洛)14.186]。 CKD 3b~5期患者尽量避免使用阿司匹林和替格瑞洛[186],但必须使用时(如冠状动脉支架术后)，应在心脏科和肾脏科医师严密监测下，采用个体化剂量进行治疗。③改善心肌缺血:水溶性β受体阻滞剂(阿替洛尔)主要经肾脏清除，CKD患者需要调整剂量;脂溶性β受体阻滞剂(普萘洛尔、美托洛尔、卡维地洛)主要经肝脏代谢，CKD不需要调整剂量;水脂双溶性的β受体阻滞剂(比索洛尔)在轻中度肾功能不全时不需调整剂量，严重肾功能不全时需调整剂量 ${}^{[187]}$ 。其他改善心肌缺血药物如CCB类、硝酸酯类药物在CKD患者中无需调整剂量。

冠状动脉血运重建也是ASCVD的重要治疗手段，方式主要包括经皮冠状动脉介入治疗(percutaneous coronary intervention, PCI)、冠状动脉旁路移植术(coronary artery bypass grafting,CABG)和两者结合的杂交冠状动脉重建术(hybrid coronary revascularization, HCR $)^{[188]}$ 。 SYNTAX研究 ${}^{[ 189]}$ 是首个比较 PCI和 CABG的前瞻性 RCT研究

(n=1800)，其针对CKD人群和非CKD人群5年随访数据进行了分析，结果显示，CKD患者接受PCI(26.7%比10.8%，P<0.001)和CABG(21.2%比10.6%,P=0.005)后的病死率明显高于肾功能正常的患者;CKD患者中，接受PCI治疗后的主要不良心脑血管事件(major adverse cardiac and cerebrovascular event,MACCE)发生率明显高于接受CABG治疗患者(42.1%比31.5%,P=0.019);在合并糖尿病的CKD患者中，接受PCI治疗后的死亡、卒中、心肌梗死复合终点事件(47.9%比24.4%，P=0.005)和全因死亡率(40.9%比17.7%，P=0.004)明显高于接受CABG治疗患者。但大部分冠状动脉血运重建的RCT研究排除了CKD患者，支持血运重建方式选择的相关支持证据仍不足，临床需建立包括CVD专家的多学科团队，综合评估患者冠状动脉病变程度和个体临床特征后决定是否进行冠状动脉血运重建，并指导选择血运重建方式。一般来说，对于疾病表现更复杂的患者，建议使用CABG进行血运重建，而不是PCI。对于具有稳定型冠状动脉疾病且解剖结构适合两种手术的糖尿病患者，冠状动脉三支病变和左主干冠状动脉疾病中CABG的证据比使用PCI的证据更强。但在低疾病复杂性的左主干疾病中，CABG和PCI都可作为使用推荐 ${}^{[188]}$ 。

CIN是冠状动脉血运重建治疗的严重合并症，其发生与一系列因素相关，其中CKD是CIN最重要和最常见的危险因素，因此CKD患者尤需重视CIN的防治 ${}^{[ 190-191]}$ :①冠状动脉造影前对所有患者充分水化;②推荐使用等渗或低渗型造影剂;③尽量减少造影剂用量，造影剂总用量/eGFR<3.7;④未使用他汀类药物的患者，可在围手术期(术前2d+术后3d)短期给予他汀类药物治疗，如瑞舒伐他汀10 mg[192];⑤如预计造影剂用量>100 ml,左心室射血分数≤35%或美国纽约心脏病学会分级>2，应考虑使用生理盐水术前水化12h(1ml·kg-1·h-1),术后持续水化24h(0.5ml· $kg^{-1}\cdot h^{-1}$ );⑥不能实施标准水化治疗的重度CKD患者，可以考虑输注呋塞米联合水化治疗;⑦重度CKD患者可考虑术前6h预防性超滤，使液体置换率保持1L/h而总液体量无丢失，生理盐水静脉水化至术后24h;⑧不推荐重度CKD患者常规行预防性血液透析。

(2)个体化调整CKD合并心力衰竭患者的用药方案:

3.CKD合并糖尿病:

4.CKD合并贫血:

5.水电解质和酸碱失衡:

(1)CKD合并高钾血症:

(2)CKD合并代谢性酸中毒:

推荐意见

62.对合并代谢性酸中毒的CKD患者，考虑使用口服补碱治疗(碳酸氢钠或柠檬酸钠)以及饮食干预(低蛋白饮食或以植物性饮食为主)纠正酸中毒。严重酸中毒者(二氧化碳结合力<13mmol/L)需及时静脉补碱或透析治疗。(推荐强度C,证据水平4)

63.推荐治疗过程中积极监测血电解质和血压，注意可能同时合并存在的高钾血症，维持血清碳酸氢盐水平不超过正常上限(<26mmol/L)，且对血压控制、血钾或体液状态无不良影响。(推荐强度A，证据水平1c)

一项非设盲的RCT研究[76]在合并代谢性酸中毒的CKD患者(n=134)中比较了口服碳酸氢钠和标准治疗对肾脏结局的影响，结果显示，碳酸氢钠治疗的肌酐清除率下降速度较慢[1.88 ml·min-1·(1.73 m2)-1比 5.93 ml·min-1·(1.73 m2)-1,P<0.001],ESKD风险降低 87%(RR=0.13,P<0.001)。一项非随机分配的对照研究[277]在合并代谢性酸中毒的高血压肾病患者(n=59)中探讨了柠檬酸钠的治疗作用，结果显示，与未接受碱治疗组相比，柠檬酸钠治疗后肾损伤标志物(尿液排泄内皮素-1和N-乙酰-β-D葡萄糖胺酶)水平明显降低(P<0.001)，eGFR下降速度明显减慢(P<0.001)。一项开放标签RCT研究 ${}^{[ 278]}$ 在合并代谢性酸中毒的3~5期CKD患者(n=795)中比较了使用碳酸氢钠与常规治疗对患者的影响，结果显示碳酸氢钠组血肌酐水平翻倍的患者比例显著降低(6%比17%，P<0.001)。此外，碳酸氢钠组启动肾脏替代治疗的患者比例(6.9%比12.3%,P=0.016)

和全因死亡率(3.1%比6.8%，P=0.004)均低于常规治疗组。一些小型RCT研究[279-282]也证实，通过饮食干预(低蛋白饮食或以植物性饮食为主)纠正酸中毒与口服碳酸氢钠有类似的临床获益。

研究表明，口服碳酸氢钠与安慰剂相比并未显著降低CKD患者进展为肾衰竭的风险。一项Ⅲ期 RCT研究[285]纳入1 480例 CKD患者，受试者 eGFR为(29.2±6.3)ml·min ${}^{-1}\cdot$ (1.73 m ${}^{2}$ ) ${}^{-1}$ ,血清碳酸氢盐(17.5±1.4) mEq/L,采用新型胃肠道盐酸结合剂Veverimer或安慰剂治疗，结果发现Veverimer治疗组患者的血清碳酸氢盐水平高于安慰剂组，但CKD进展的复合终点(即ESKD、eGFR下降≥40%或因肾衰竭死亡)差异无统计学意义(HR=0.99,95%CI0.80~1.20,P=0.90)。虽然目前仍缺乏大型RCT研究证据明确口服补碱治疗和饮食干预在延缓合并酸中毒CKD患者肾病进展方面的作用，但基于这些干预措施可有效提高血清碳酸氢盐浓度，从而避免发展为严重酸中毒和延缓CKD进展的潜在获益。本指南建议对合并代谢性酸中毒的CKD患者，使用口服补碱治疗以及饮食干预以纠正酸中毒。治疗过程中应积极监测血电解质和血压，确保血清碳酸氢盐水平不超过正常上限(<26mmol/L)，且对血压控制、血钾或体液状态无不良影响。

6.CKD合并高尿酸血症:

推荐意见64.对合并高尿酸血症的CKD患者，建议避免摄入高嘌呤食物、多饮水、避免饮酒及富含果糖的饮料、避免应用可升高血尿酸的药物，全面筛查高尿酸血症相关的CVD风险并积极控制。(推荐强度A，证据水平1a)65.对于伴痛风的CKD患者，使用延缓CKD进展治疗药物后血尿酸水平仍未达标(血尿酸≥360μmol/L)，可加用别嘌醇、非布司他，谨慎使用苯溴马隆。(推荐强度C，证据水平4)66.对合并无症状高尿酸血症的CKD患者，可考虑优先选择同时有降低血尿酸水平作用的SGLT2i和ARB药物氯沙坦。(推荐强度C，证据水平4)67.急性痛风发作期的对症治疗，建议使用糖皮质激素或较低剂量秋水仙碱，谨慎使用NSAID。(推荐强度C，证据水平4)

高尿酸血症(正常嘌呤饮食下，非同日2次空腹血尿酸水平超过420μmol/L)在 CKD患者中常见，且随着肾功能的恶化而加重 ${}^{[286]}$ 。 CKD患者因肾脏排泄不良而容易发生高尿酸血症，相关的可能因素包括eGFR下降、使用利尿剂、肾血管阻力增加和合并胰岛素抵抗 ${}^{[287]}$ 。实验数据提示，尿酸本身可能通过一系列机制增加CKD进展风险，包括诱导内皮功能障碍、炎性反应、氧化应激和增强肾素-血管紧张素系统活性 ${}^{[287]}$ 。观察性研究提示，血尿酸水平升高与CKD进展风险增加相关 ${}^{[288-290]}$ 。

除肾功能下降导致尿酸排泄不良外，CKD患者可能还

存在导致血尿酸增加的其他因素，如高嘌呤饮食、饮酒以及合并某些疾病(如骨髓增生性疾病、溶血性贫血、银屑病、肿瘤化疗等)而导致尿酸生成过多;或因高血压、代谢综合征、遗传性疾病[尿酸盐转运蛋白1(URAT1)、葡萄糖转运子9(GLUT9)、ATP结合盒转运蛋白G2(ABCG2)]、合并使用药物(阿司匹林、利尿剂、钙调磷酸酶抑制剂、抗结核药等)而进一步加剧尿酸排泄不良[291]。临床管理中应重视对这些风险因素的防控。

降尿酸治疗药物主要包括黄嘌呤醇氧化酶抑制剂(别嘌醇、非布司他)和促尿酸排泄药物(苯溴马隆)。目前尚无充分的证据支持对无症状高尿酸血症CKD患者使用降尿酸治疗药物可延缓CKD进展。一项系统综述[292]包括12项RCT研究数据(1187例CKD或非CKD患者)，分析了降尿酸治疗对CKD进展和其他心血管终点事件的影响，结果提示，仍无法明确降尿酸治疗有降低血压、尿蛋白水平或其他心血管事件标志物的获益。一项安慰剂对照RCT研究在合并无症状高尿酸血症[血尿酸(490±110)μmol/L]的3~4期CKD患者(n=363)中分析了别嘌醇治疗后eGFR的变化情况。结果显示别嘌醇组和安慰剂组的eGFR均有所下降，变化幅度差异无统计学意义[组间均数差=-0.10ml· $\min^{-1}\cdot\left(1.73~m^{2}\right)^{-1}, P= 0.85$ ]。另一项在合并T1DM和无症状高尿酸血症的1~3期CKD患者中开展的RCT研究[294]也显示类似的结果。一项安慰剂对照RCT研究[295]在合并无症状高尿酸血症的3期CKD患者中分析了非布司他对肾脏结局的影响，结果显示非布司他组与安慰剂组的eGFR变化幅度差异无统计学意义[组间均数差=0.70ml·min-1·(1.73m2)-1，P=0.1]。苯溴马隆可能增加尿结晶和泌尿系结石风险，对泌尿系结石患者和肾功能不全的患者属于相对禁忌 ${}^{[296]}$ 。

近年来研究发现，SGLT2i可能通过促尿酸排泄、减少氧化应激和促进细胞自噬而降低血尿酸水平，因此合并无症状高尿酸血症的CKD患者可使用SGLT2i作为延缓CKD进展的一线治疗药物。一项双向交叉RCT研究[297]在无症状高尿酸血症患者(n=36)中探讨了在URAT1抑制剂维立诺雷(Verinurad)联合非布司他治疗方案基础上增加达格列净对疗效的影响，结果显示加入达格列净后血尿酸水平进一步降低(组间均数差=-62.3μmol/L,95% CI-82.8~-41.8)，但不影响尿液中尿酸水平(组间均数差=0.3 mg/h,95%CI-8.7~9.2)，提示达格列净与维立诺雷和非布司他联用有助于降低血尿酸水平，且对肾功能无不良影响。一项单中心回顾性研究 ${}^{[298]}$ 在晚期 CKD患者(n=31)中分析了达格列净治疗后的血尿酸水平变化，结果显示，服药3周和3个月后患者的血尿酸水平显著下降，尿酸排泄分数增加(均P<0.05)。在糖尿病患者和心力衰竭患者中的研究结果也显示SGLT2i治疗有降低血尿酸水平的额外作用 ${}^{[299-301]}$ 。一项回顾性队列研究 ${}^{[302]}$ 和3项观察性队列研究 ${}^{[303-305]}$ 则提示，在T2DM患者(CKD患者分别占25%、11.53%、2%、1.5%)中，与接受DPP-4抑制剂 ${}^{[\,302-303]}$ 或GLP-1RA ${}^{[\,304-305]}$ 治疗相比，接受SGLT2i治疗可降低痛风发生风险。

研究提示，ARB药物氯沙坦对血尿酸也有一定降低作用。一项RCT研究[306]在高血压患者(n=118)中比较了氯沙坦与其他ARB药物联合利尿剂治疗对血压控制和血尿酸水平的影响，结果提示相比其他ARB类药物，氯沙坦治疗在达到相同血压控制效果的同时，还可降低血尿酸水平(-38.90μmol/L比8.84μmol/L,P=0.01)。一项在症状性心力衰竭患者[n=3834,36%的患者eGFR≤60ml·min-1(1.73m2)^{-1}]中开展的双盲 RCT研究 ${}^{[307]}$ 提示，较大剂量氯沙坦(150mg/d)相比较小剂量(50mg/d)可进一步降低血尿酸水平(组间均数差=-23.87μmol/L,P<0.001)和新发高尿酸血症风险(RR=0.71,P=0.002)。

有痛风发作病史的CKD患者，建议在维持延缓CKD进展药物的基础上，加用别嘌醇、非布司他等降尿酸治疗药物。CKD患者急性痛风发作时，无需停用此前已使用的降尿酸治疗药物;如尚未使用降尿酸药物，则需在痛风缓解后适时给予降尿酸药物治疗。

急性痛风发作时需及时给予抗炎镇痛治疗[291]。推荐糖皮质激素作为治疗CKD患者急性痛风发作的首选药物。可通过口服、关节内注射、肌内注射、静脉注射等途径给药。单关节急性发作，可行关节内注射，以减少药物的全身反应，但应除外合并感染的患者。对于多关节或严重的急性痛风发作可使用中小剂量糖皮质激素[291]。NSAID因其肾毒性作用，不推荐作为治疗CKD患者急性痛风发作的首选药物。1~4期CKD患者痛风发作时可谨慎短期(≤5d)使用NSAID，应避免长期或大剂量使用。未透析治疗的5期CKD患者尽量避免使用NSAID。低剂量秋水仙碱的安全性优于NSAID。韩国的一项多中心病例对照研究 ${}^{[309]}$ 显示，合并高尿酸血症或慢性痛风的CKD患者(n=3085)使用秋水仙碱治疗可降低CKD进展风险。秋水仙碱有引起AKI的报告，用药过程中需监测肾功能变化，并需根据eGFR调整剂量，eGFR 35~49ml·min-1·(1.73m2)-1时每日最大剂量0.5mg;eGFR10~34ml·min-1·(1.73m2)-1时每次最大剂量0.5mg,隔天1次;eGFR<10ml·min-1·(1.73m2)-1时禁用。

7.合并CKD-MBD:

五、总结和展望

本指南聚焦延缓CKD进展，以循证证据为依据，以患者为中心，制定了从诊断、风险控制到治疗的全过程规范化CKD管理策略，旨在通过基于循证证据的CKD规范诊疗管理,达到延缓甚至阻滞 CKD进展的目标,改善 CKD患者预后。

随着CKD研究持续进展，新型药物和治疗手段不断问世,本指南工作组将对新的研究证据进行持续动态评价,并根据证据情况更新后续版本，以更好地指导临床医师开展诊疗工作,实现最大化延缓 CKD进展,造福广大患者的目的。

在延缓CKD进展领域，仍有很多问题有待进一步研究解决。如:(1)我国CKD人群的原发病因分布与欧美人群存在差异，需要基于大样本的流行病学调查数据进一步明确我国的CKD进展风险分层，结合地域差异，制定符合我国国情的CKD进展筛查流程;(2)运用机器学习和深度学习等方法，建立基于大数据和适合中国患者特征的CKD风险预测模型，更加精准发现疾病进展高风险患者;(3)聚焦促进CKD进展的关键机制，开展延缓CKD进展药物创新研究，特别是肾脏靶向性炎症和纤维化的小分子药物及细胞基因治疗研究;(4)践行CKD多学科管理理念，建立CKD多学科管理团队，提高CKD并发症诊治水平，改善患者远期预后;(5)进一步完善CKD患者健康管理教育模式，充分利用信息化手段提升患者对疾病的知晓率和规范治疗率，实现CKD患者住院、门诊、居家一体化管理;(6)重视新药上市后的疗效和安全性真实世界研究，在保证疗效和安全性的基础上探讨简化用药方案，减轻CKD患者的用药负担和降低药物相互作用。

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《延缓慢性肾脏病进展临床管理指南(2025年版)》专家组

顾问:陈江华(浙江大学医学院附属第一医院)

组长:刘必成(东南大学附属中大医院)、刘章锁(郑州大学第一附属医院)

执笔专家(按姓名汉语拼音字母表顺序排序):

陈崴(中山大学附属第一医院)、李贵森(四川省人民医院)、孙林(中南大学湘雅二医院)、王彬(东南大学附属中大医院)、徐钢(华中科技大学同济医学院附属同济医院)、姚丽(中国医科大学附属第一医院)、查艳(贵州省人民医院)

专家组成员(按姓名汉语拼音字母表顺序排序):

陈朝生(温州医科大学附属第一医院)、陈莉明(天津医科大学代谢病医院)、陈钦开(南昌大学第一附属医院)、陈崴(中山大学附属第一医院)、陈晓农(上海交通大学医学院附属瑞金医院)、程虹(首都医科大学附属北京安贞医院)、程震(东部战区总医院)、迟雁青(河北医科大学第三医院)、崔文鹏(吉林大学第二医院)、达静静(贵州省人民医院)、丁峰(上海交通大学医学院附属第九人民医院)、范秋灵(上海交通大学医学院附属第一人民医院)、顾乐怡(上海交通大学医学院附属仁济医院)、郭明好(新乡医学院第一附属医院)、韩飞(浙江大学医学院附属第一医院)、郝传明(复旦大学附属华山医院)、郝丽荣(深圳南方科技大学医院)、洪富源(福建省立医院)、胡波(暨南大学附属第一医院)、胡文博(青海省人民医院)、姜虹(浙江大学医学院附属第一医院)、蒋红利(西安交通大学第一附属医院)、孔耀中(佛山市第一人民医院)、李冰(海南医学院第二附属医院)、李贵森(四川省人民医院)、李寒(首都医科大学附属北京朝阳医院)、李华(浙江大学医学院附属邵逸夫医院)、李素华(新疆医科大学第一附属医院)、梁伟(武汉大学人民医院)、梁玉梅(湖南省人民医院)、廖晓辉(重庆医科大学附属第二医院)、刘必成(东南大学附属中大医院)、刘东伟(郑州大学第一附属医院)、刘宏(东南大学附属中大医院)、刘庆华(中山大学附属第一医院)、刘章锁(郑州大学第一附属医院)、陆晨(新疆医科大学第一附属医院)、罗萍(吉林大学第二医院)、罗群(宁波市

第二医院)、马坤岭(浙江大学医学院附属第二医院)、毛慧娟(江苏省人民医院)、彭艾(同济大学附属第十人民医院)、彭晖(中山大学附属第三医院)、彭张哲(中南大学湘雅医院)、任红旗(徐州医科大学附属淮海医院)、任萍萍(浙江大学医学院附属第一医院)、任野萍(深圳大学总医院)、宋岩(解放军总医院第一医学中心)、苏白海(四川大学华西医院)、隋满姝(哈尔滨医科大学附属第一医院)、孙东(徐州医科大学附属医院)、孙脊峰(空军军医大学第二附属医院)、孙林(中南大学湘雅二医院)、孙世仁(空军军医大学西京医院)、田娜(宁夏医科大学总医院)、万建新(福建医科大学附属第一医院)、王保兴(河北医科大学第三医院)、王彬(东南大学附属中大医院)、王彩丽(内蒙古科技大学包头医学院第一附属医院)、王德光(安徽医科大学第二附属医院)、王惠明(武汉大学人民医院)、王俭勤(兰州大学第二医院)、王恺(南开大学生命科学学院)、王立华(天津医科大学第二医院)、王莉(四川省人民医院)、王凉(南京医科大学附属无锡市人民医院)、王沛(郑州大学第一附属医院)、吴永贵(安徽医科大学第一附属医院)、肖湘成(中南大学湘雅医院)、徐钢(华中科技大学同济医学院附属同济医院)、徐岩(青岛大学附属医院)、燕宇(北京大学人民医院)、杨莉(北京大学第一医院)、杨敏(常州市第一人民医院)、杨向东(山东大学齐鲁医院)、杨晓萍(石河子大学第一附属医院)、姚丽(中国医科大学附属第一医院)、叶智明(广东省人民医院)、袁静(浙江大学医学院附属第一医院)、曾彩虹(东部战区总医院)、曾春雨(陆军军医大学大坪医院)、曾锐(华中科技大学同济医学院附属同济医院)、查艳(贵州省人民医院)、张浩(中南大学湘雅三医院)、张玉强(海军军医大学附属长征医院)、赵景宏(陆军军医大学第二附属医院)、郑可(北京协和医院)、钟爱民(江西省人民医院)、周丽丽(南方医科大学南方医院)、周晓玲(宁夏医科大学总医院)、周晓霜(山西省人民医院)、周怡(中山大学附属第一医院)、朱永俊(海南医学院第一附属医院)、邹洪斌(吉林大学第二医院)

参考文献

[1]GBD 2021 Diseases and Injuries Collaborators. Global incidence, prevalence, years lived with disability(YLDs),disability-adjusted life-years(DALYs), and healthy life expectancy(HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations,1990-2021: a systematic analysis for the Global Burden of Disease Study 2021[J]. Lancet, 2024, 403(10440): 2133-2161.DOI: 10.1016/S0140-6736(24)00757-8.

[2]Chesnaye NC, Ortiz A, Zoccali C, et al. The impact of population ageing on the burden of chronic kidney disease[J]. Nat Rev Nephrol, 2024, 20(9): 569-585. DOI:10.1038/s41581-024-00863-9.

[3]GBD Chronic Kidney Disease Collaboration. Global,regional, and national burden of chronic kidney disease,1990-2017: a systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet, 2020, 395(10225):709-733.DOI: 10.1016/S0140-6736(20)30045-3.

[4]Liyanage T, Toyama T, Hockham C, et al. Prevalence of chronic kidney disease in Asia: a systematic review and analysis[J]. BMJ Glob Health, 2022, 7(1): e007525. DOI:10.1136/bmjgh-2021-007525.

[5]Wang L, Xu X, Zhang M, et al. Prevalence of chronic kidney

disease in China: results from the Sixth China Chronic Disease and Risk Factor Surveillance[J]. JAMA Intern Med,2023, 183(4): 298-310. DOI: 10.1001/jamainternmed.2022.6817.

[6]Zhang L, Zhao MH, Zuo L, et al. China Kidney Disease Network(CK-NET) 2015 annual data report[J]. Kidney Int Suppl(2011),2019,9(1):e1-e81.DOI:10.1016/j.kisu.2018.11.001.

[7]Liu J,Shi Y,Diao Y,et al.Strategies to improve long-term outcomes for patients with chronic kidney disease in China[J]. Kidney Dis(Basel),2023,9(4):265-276.DOI:10.1159/000530022.

[8]杨倩，杜鹃，胡继佳，等.ARNI在慢性肾脏病合并高血压患者中的应用[J].国际泌尿系统杂志,2023,43(3):556-559.DOI:10.3760/cma.j.cn431460-20210922-00142.

[9]Chung E, Badve SV, Heerspink H, et al. Endothelin receptor antagonists in kidney protection for diabetic kidney disease and beyond?[J]. Nephrology(Carlton),2023,28(2):97-108.DOI:10.1111/nep.14130.

[10]张会健，李贵森.IgA肾病补体靶向治疗研究进展[J]内科理论与实践,2023,18(3):197-200.DOI:10.16138/j.1673-6087.2023.03.013.

[11]World Health Organization. WHO handbook for guideline development[M]. 2nd Edition. Geneva: World Health Organization,2014.

[12]蒋朱明，詹思延，贾晓巍，等.制订/修订《临床诊疗指南》的基本方法及程序[J].中华医学杂志,2016,96(4):250-253.DOI:10.3760/cma.j.issn.0376-2491.2016.04.004.

[13]Oxford centre for evidence-based medicine: levels of evidence(March 2009)[DB/OL].(2009-3)[2024-11-20].https://www. cebm. ox.ac.uk/resources/levels- of-evidence/oxford- centre- for- evidence- based- medicine-levels-of-evidence-march-2009.

[14]Kidney Disease: Improving Global Outcomes(KDIGO)CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease[J]. Kidney Int,2024, 105(4S): S117-S314. DOI:10.1016/j.kint.2023.10.018.

[15]中华预防医学会肾脏病预防与控制专业委员会.中国慢性肾脏病早期评价与管理指南[J].中华内科杂志，2023,62(8):902-930.DOI:10.3760/cma.j.cn112138-20221013-00755.

[16] Levey AS,Inker LA, Matsushita K,et al.GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration[J]. Am J Kidney Dis,2014,64(6):821-835.DOI:10.1053/j.ajkd.2014.07.030.

[17]Matsushita K,Chen J,Sang Y,et al.Risk of end-stage renal disease in Japanese patients with chronic kidney disease increases proportionately to decline in estimated glomerular filtration rate[J]. Kidney Int, 2016, 90(5):1109-1114.DOI:10.1016/j.kint.2016.08.003.

[18]Inker LA, Lambers Heerspink HJ, Mondal H, et al. GFR decline as an alternative end point to kidney failure in clinical trials: a meta-analysis of treatment effects from 37 randomized trials[J]. Am J Kidney Dis, 2014, 64(6):848-859.DOI:10.1053/j.ajkd.2014.08.017.

[19]Lambers Heerspink HJ, Tighiouart H, Sang Y,et al.GFR decline and subsequent risk of established kidney outcomes: a meta-analysis of 37 randomized controlled

trials[J]. Am J Kidney Dis, 2014, 64(6): 860-866. DOI: 10.1053/j.ajkd.2014.08.018.

[20]Norris KC, Smoyer KE, Rolland C, et al. Albuminuria,serum creatinine, and estimated glomerular filtration rate as predictors of cardio-renal outcomes in patients with type 2 diabetes mellitus and kidney disease: a systematic literature review[J].BMC Nephrol,2018,19(1):36.DOI:10.1186/s12882-018-0821-9.

[21]Lambers Heerspink HJ, Gansevoort RT. Albuminuria is an appropriate therapeutic target in patients with CKD: the pro view[J]. Clin J Am Soc Nephrol, 2015, 10(6): 1079-1088.DOI:10.2215/CJN.11511114.

[22]Kidney Disease: Improving Global Outcomes(KDIGO).KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease[J]. Kidney Int Suppl,2013,3(1):1-150.DOI:10.1038/kisup.2012.73.

[23]Jafar TH, Schmid CH, Landa M, et al. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data[published correction appears in Ann Intern Med, 2002, 137(4): 299][J]. Ann Intern Med,2001, 135(2):73-87.DOI: 10.7326/0003-4819-135-2-200107170-00007.

[24]Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy[J]. N Engl J Med,2001,345(12): 861-869. DOI: 10.1056/NEJMoa 011161.

[25]Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes[J]. N Engl J Med, 2001, 345(12): 851-860. DOI: 10.1056/NEJMoa011303.

[26]Mann JF, Schmieder RE, Dyal L,et al. Effect of telmisartan on renal outcomes: a randomized trial[J]. Ann Intern Med,2009,151(1): 1-10, W1-2. DOI: 10.7326/0003-4819-151-1-200907070-00122.

[27]Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy[J]. N Engl J Med,2019,380(24):2295-2306.DOI:10.1056/NEJMoa1811744.

[28]Heerspink H, Stefansson BV, Correa-Rotter R, et al.Dapagliflozin in patients with chronic kidney disease[J].N Engl J Med,2020, 383(15): 1436-1446. DOI: 10.1056/NEJMoa2024816.

[29]The EMPA-KIDNEY Collaborative Group, Herrington WG,Staplin N, et al. Empagliflozin in patients with chronic kidney disease[J]. N Engl J Med, 2023, 388(2): 117-127.DOI:10.1056/NEJMoa2204233.

[30]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.

[31]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.

[32]Gerstein HC,Sattar N,Rosenstock J,et al.Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes[J].N Engl J Med,2021,385(10):896-907.DOI:10.1056/

NEJMoa2108269.

[33]Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease(AWARD-7): a multicentre, open-label, randomised trial[J]. Lancet Diabetes Endocrinol,2018,6(8):605-617.DOI:10.1016/S2213-8587(18)30104-9.

[34]Adair KE, Bowden RG. Ameliorating chronic kidney disease using a whole food plant-based diet[J]. Nutrients,2020,12(4):1007.DOI:10.3390/nu12041007.

[35]Molina P, Gavela E, Vizcaino B, et al. Optimizing diet to slow CKD progression[J]. Front Med(Lausanne),2021,8:654250.DOI: 10.3389/fmed.2021.654250.

[36]Kim H, Caulfield LE, Garcia-Larsen V, et al. Plant-based diets and incident CKD and kidney function[J]. Clin J Am Soc Nephrol,2019,14(5):682-691.DOI:10.2215/CJN.12391018.

[37]Amir S, Kim H, Hu EA, et al. Adherence to plant-based diets and risk of CKD progression and all-cause mortality:findings from the Chronic Renal Insufficiency Cohort(CRIC) study[J].Am J Kidney Dis,2024,83(5):624-635.DOI:10.1053/j.ajkd.2023.09.020.

[38]Oh KH,Kang M,Kang E,et al.The KNOW-CKD study: what we have learned about chronic kidney diseases[J]. Kidney Res Clin Pract, 2020, 39(2): 121-135. DOI: 10.23876/j.krcp.20.042.

[39]Kalantar-Zadeh K, Kramer HM, Fouque D. High-protein diet is bad for kidney health: unleashing the taboo[J].Nephrol Dial Transplant,2020,35(1):1-4.DOI:10.1093/ndt/gfz216.

[40]Friedman AN. High-protein diets: potential effects on the kidney in renal health and disease[J]. Am J Kidney Dis,2004,44(6):950-962.DOI:10.1053/j.ajkd.2004.08.020.

[41]Hostetter TH, Meyer TW, Rennke HG,et al. Chronic effects of dietary protein in the rat with intact and reduced renal mass[J]. Kidney Int,1986,30(4):509-517.DOI:10.1038/ki.1986.215.

[42]Yan B,Su X,Xu B,et al.Effect of diet protein restriction on progression of chronic kidney disease: a systematic review and meta-analysis[J]. PLoS One, 2018, 13(11):e0206134.DOI:10.1371/journal.pone.0206134.

[43]Rhee CM,Ahmadi SF, Kovesdy CP,et al. Low-protein diet for conservative management of chronic kidney disease: a systematic review and meta-analysis of controlled trials[J]. J Cachexia Sarcopenia Muscle, 2018, 9(2): 235-245.DOI:10.1002/jcsm.12264.

[44]Hahn D, Hodson EM, Fouque D. Low protein diets for non-diabetic adults with chronic kidney disease[J].Cochrane Database Syst Rev, 2018, 10(10): CD001892.DOI:10.1002/14651858.CD001892.pub4.

[45]Obeid W,Hiremath S, Topf JM. Protein restriction for CKD:time to move on[J]. Kidney360, 2022, 3(9): 1611-1615.DOI: 10.34067/KID.0001002022.

[46]Lew QJ,Jafar TH, Koh HW,et al. Red meat intake and risk of ESRD[J].J Am Soc Nephrol,2017,28(1):304-312.DOI:10.1681/ASN.2016030248.

[47]McMahon EJ,Campbell KL,Bauer JD,et al.Altered dietary salt intake for people with chronic kidney disease[J].Cochrane Database Syst Rev,2021,6(6):CD010070.DOI:10.1002/14651858.CD010070.pub3.

[48]Xiao B, Huang J, Chen L, et al. Ultra-processed food consumption and the risk of incident chronic kidney disease: a systematic review and meta-analysis of cohort studies[J]. Ren Fail,2024,46(1):2306224.DOI:10.1080/0886022X.2024.2306224.

[49]Prospective Studies Collaboration, Whitlock G,Lewington S, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies[J]. Lancet, 2009, 373(9669): 1083-1096.DOI:10.1016/S0140-6736(09)60318-4.

[50]Herrington WG, Smith M, Bankhead C, et al. Body-mass index and risk of advanced chronic kidney disease:Prospective analyses from a primary care cohort of 1.4 million adults in England[J]. PLoS One, 2017, 12(3):e0173515.DOI:10.1371/journal.pone.0173515.

[51]谢霄玲，苗鑫蕾，唐桂敏，等.肥胖与慢性肾脏病的关联:一项回顾性队列研究[J].中华内分泌代谢杂志,2024,40(9):752-757.DOI:10.3760/cma.j.cn311282-20231115-00170.

[52]曾芷青，马钰，杨超，等.中国成年人BMI和腰围与慢性肾脏病发病风险的关联研究[J].中华流行病学杂志，2024,45[7]:903-913.DOI:10.3760/cma.j.cn112338-20240227-00085.

[53]Look AHEAD Research Group. Effect of a long-term behavioural weight loss intervention on nephropathy in overweight or obese adults with type 2 diabetes: a secondary analysis of the Look AHEAD randomised clinical trial[J]. Lancet Diabetes Endocrinol, 2014, 2(10):801-809.DOI:10.1016/S2213-8587(14)70156-1.

[54]Perl J, Karaboyas A, Morgenstern H, et al. Association between changes in quality of life and mortality in hemodialysis patients: results from the DOPPS[J].Nephrol Dial Transplant, 2017, 32(3): 521-527. DOI:10.1093/ndt/gfw233.

[55]Afsar B,Siriopol D,Aslan G,et al.The impact of exercise on physical function, cardiovascular outcomes and quality of life in chronic kidney disease patients: a systematic review[J]. Int Urol Nephrol, 2018, 50(5): 885-904. DOI:10.1007/s11255-018-1790-4.

[56]Kanbay M, Copur S, Yildiz AB, et al. Physical exercise in kidney disease: a commonly undervalued treatment modality[J]. Eur J Clin Invest,2024,54(2):e14105.DOI:10.1111/eci.14105.

[57]Battaglia Y,Baciga F,Bulighin F,et al. Physical activity and exercise in chronic kidney disease: consensus statements from the Physical Exercise Working Group of the Italian Society of Nephrology[J].J Nephrol,2024,37(7): 1735-1765.DOI: 10.1007/s40620-024-02049-9.

[58]Heiwe S, Jacobson SH. Exercise training for adults with chronic kidney disease[J]. Cochrane Database Syst Rev,2011,2011(10): CD003236. DOI: 10.1002/14651858.CD003236.pub2.

[59]Hellberg M, Hoglund P, Svensson P, et al. Randomized controlled trial of exercise in CKD-the RENEXC study[J]Kidney Int Rep, 2019, 4(7): 963-976. DOI: 10.1016/j.ekir:2019.04.001.

[60]Bohm M, Schumacher H, Werner C, et al. Association between exercise frequency with renal and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk[J]. Cardiovasc

Diabetol, 2022, 21(1): 12. DOI: 10.1186/s12933- 021-01429-w.

[61]Xia J,Wang L,Ma Z,et al.Cigarette smoking and chronic kidney disease in the general population: a systematic review and meta-analysis of prospective cohort studies[J]. Nephrol Dial Transplant, 2017, 32(3): 475-487. DOI:10.1093/ndt/gfw452.

[62]Nakamura K, Nakagawa H, Murakami Y, et al. Smoking increases the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease[J].Kidney Int, 2015, 88(5): 1144-1152. DOI: 10.1038/ki.2015.212.

[63]王雪，史可香，余灿清，等.中国10个地区成年人慢性肾脏病流行情况及其生活方式影响因素[J].中华流行病学杂志,2023,44(3):386-392.DOI:10.3760/cma.j.cn112338-20220801-00680.

[64]Mehran R, Dangas GD, Weisbord SD. Contrast-associated acute kidney injury[J]. N Engl J Med, 2019, 380(22):2146-2155.DOI:10.1056/NEJMra1805256.

[65]Cashion W, Weisbord SD. Radiographic contrast media and the kidney[J]. Clin J Am Soc Nephrol, 2022, 17(8):1234-1242.DOI: 10.2215/CJN.16311221.

[66]Perazella MA. Onco-nephrology: renal toxicities of chemotherapeutic agents[J]. Clin J Am Soc Nephrol, 2012,7(10):1713-1721.DOI:10.2215/CJN.02780312.

[67]Clifford KM, Selby AR, Reveles KR, et al. The risk and clinical implications of antibiotic-associated acute kidney injury: a review of the clinical data for agents with signals from the Food and Drug Administration's Adverse Event Reporting System(FAERS) database[J].Antibiotics(Basel),2022,11(10):1367.DOI:10.3390/antibiotics11101367.

[68]中国中西医结合学会,中华中医药学会,中华医学会.中草药相关肾损伤中西医结合诊疗指南[DB/OL].(2023-05-31)[2024-11-20].https://www.cacm.org.cn/wp-content/uploads/2023/06/中草药相关肾损伤中西医结合诊疗指南.pdf.

[69]Molitoris BA. Low-flow acute kidney injury: the pathophysiology of prerenal azotemia, abdominal compartment syndrome, and obstructive uropathy[J]. Clin JAm Soc Nephrol,2022,17(7):1039-1049.DOI:10.2215/CJN.15341121.

[70]Batte A, Shahrin L, Claure-Del Granado R, et al. Infections and acute kidney injury: a global perspective[J].Semin Nephrol, 2023, 43(5): 151466. DOI: 10.1016/j.semnephrol.2023.151466.

[71]Zhang L, Long J, Jiang W, et al. Trends in chronic kidney disease in China[J].N Engl J Med,2016,375(9):905-906.DOI:10.1056/NEJMc1602469.

[72]Yang C, Wang H, Zhao X, et al. CKD in China: evolving spectrum and public health implications[J]. Am J Kidney Dis,2020,76(2):258-264.DOI:10.1053/j.ajkd.2019.05.032.

[73]吴宇,周晶晶,姜世敏,等.慢性肾脏病病因构成及变化趋势分析[J].中华健康管理学杂志,2021,15(5):442-445.DOI:10.3760/cma.j.cn115624-20210309-00115.

[74]Zhang L,Zhao MH,Zuo L,et al.China Kidney Disease Network(CK-NET) 2016 annual data report[J]. Kidney Int Suppl(2011),2020,10(2):e97-e185.DOI:10.1016/j.kisu.2020.09.001.

[75]Webster AC, Nagler EV, Morton RL,et al. Chronic kidney disease[J]. Lancet, 2017, 389(10075): 1238-1252. DOI:10.1016/S0140-6736(16)32064-5.

[76]Cheikh Hassan HI, Tang M, Djurdjev O, et al. Infection in advanced chronic kidney disease leads to increased risk of cardiovascular events, end-stage kidney disease and mortality[J]. Kidney Int, 2016, 90(4): 897-904. DOI: 10.1016/j.kint.2016.07.013.

[77]Bu Y, Liu Y, Zhou M, et al. The burden of hypertension-related chronic kidney disease- China,2010-2019[J]. China CDC Wkly, 2024, 6(14): 282-288.DOI: 10.46234/ccdcw2024.055.

[78]Yan Z, Wang Y, Li S, et al. Hypertension control in adults with CKD in China: baseline results from the Chinese Cohort Study of Chronic Kidney Disease(C-STRIDE)[J].Am J Hypertens,2018,31(4):486-494.DOI:10.1093/ajh/hpx222.

[79]Tsuchida-Nishiwaki M, Uchida HA, Takeuchi H, et al.Association of blood pressure and renal outcome in patients with chronic kidney disease; a post hoc analysis of FROM-J study[J]. Sci Rep, 2021, 11(1): 14990. DOI:10.1038/s41598-021-94467-z.

[80]Park CH, Kim HW, Joo YS, et al. Findings from the KNOW-CKD study indicate that higher systolic blood pressure time in target range is associated with a lower risk of chronic kidney disease progression[J]. Kidney Int,2024,105(4):835-843.DOI:10.1016/j.kint.2023.12.008.

[81]SPRINT Research Group, Wright JT, Williamson JD,et al.A randomized trial of intensive versus standard blood-pressure control[published correction appears in N Engl J Med, 2017, 377(25): 2506. DOI: 10.1056/NEJMx170008][J]. N Engl J Med, 2015, 373(22):2103-2116.DOI:10.1056/NEJMoa1511939.Erratum in:N Engl J Med, 2017, 377(25): 2506. DOI: 10.1056/NEJMx170008.

[82]高血压肾病诊治中国专家共识组成员.高血压肾病诊断和治疗中国专家共识(2022)[J].中华高血压杂志，2022,30(4):307-317.DOI:10.16439/j.issn.1673-7245.2022.04.003.

[83]Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011[DB/OL]. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. https://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf(accessed 8 April 2017).

[84]Jung HH. Evaluation of serum glucose and kidney disease progression among patients with diabetes[J]. JAMA Netw Open, 2021, 4(9): e2127387. DOI: 10.1001/jamanetworkopen.2021.27387.

[85]Pan X, Lin X, Huang X, et al. The burden of diabetes-related chronic kidney disease in China from 1990 to 2019[J].Front Endocrinol(Lausanne),2022,13:892860.DOI: 10.3389/fendo.2022.892860.

[86]Ruospo M, Saglimbene VM, Palmer SC, et al. Glucose targets for preventing diabetic kidney disease and its progression[J]. Cochrane Database Syst Rev,2017,6(6):CD010137.DOI:10.1002/14651858.CD010137.pub2.

[87]Abraira C,Emanuele N,Colwell J,et al. Glycemic control and complications in type II diabetes. Design of a

feasibility trial. VA CS Group(CSDM)[J]. Diabetes Care,1992, 15(11): 1560-1571. DOI: 10.2337/diacare. 15.11.1560.

[88]Action to Control Cardiovascular Risk in Diabetes Study Group,Gerstein HC,Miller ME,et al.Effects of intensive glucose lowering in type 2 diabetes[J]. N Engl J Med,2008,358(24):2545-2559.DOI:10.1056/NEJMoa 0802743.

[89]Duckworth W,Abraira C, Moritz T,et al. Glucose control and vascular complications in veterans with type 2 diabetes[J].N Engl J Med,2009,360(2):129-139.DOI:10.1056/NEJMoa0808431.

[90]Gaede P, Vedel P, Parving HH, et al. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study[J]. Lancet, 1999, 353(9153): 617-622.DOI: 10.1016/S0140-6736(98)07368-1.

[91]ADVANCE Collaborative Group, Patel A, MacMahon S,et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes[J]. N Engl J Med, 2008,358(24):2560-2572.DOI:10.1056/NEJMoa0802987.

[92]Crasto W, Jarvis J, Khunti K, et al. Multifactorial intervention in individuals with type 2 diabetes and microalbuminuria: the Microalbuminuria Education and Medication Optimisation(MEMO) study[J]. Diabetes Res Clin Pract,2011,93(3):328-336.DOI:10.1016/j.diabres.2011.05.008.

[93]de Boer IH, Khunti K, Sadusky T, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association(ADA) and Kidney Disease: Improving Global Outcomes(KDIGO)[J].Kidney Int,2022,102(5):974-989.DOI:10.1016/j.kint.2022.08.012.

[94]中华医学会肾脏病学分会专家组.糖尿病肾脏疾病临床诊疗中国指南[J].中华肾脏病杂志,2021,37(3):255-304.DOI:10.3760/cma.j.cn441217-20201125-00041.

[95]American Diabetes Association Professional Practice Committee. Standards of care in diabetes-2024[J].Diabetes Care,2024,47 Suppl 1:S1-S321.

[96]Gansevoort RT, Matsushita K, van der Velde M, et al.Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts[J]. Kidney Int, 2011, 80(1): 93-104. DOI: 10.1038/ki.2010.531.

[97]Inker LA, Levey AS, Pandya K, et al. Early change in proteinuria as a surrogate end point for kidney disease progression: an individual patient meta-analysis[J]. Am J Kidney Dis, 2014, 64(1): 74-85. DOI: 10.1053/j. ajkd.2014.02.020.

[98]Heerspink HJ, Kropelin TF, Hoekman J, et al. Drug-induced reduction in albuminuria is associated with subsequent renoprotection: a meta-analysis[J]. J Am Soc Nephrol, 2015, 26(8): 2055-2064. DOI: 10.1681/ASN.2014070688.

[99]Coresh J, Heerspink H, Sang Y, et al. Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies[J]. Lancet Diabetes Endocrinol, 2019, 7(2): 115-127. DOI: 10.1016/S2213-

8587(18)30313-9.

[100] Kidney Disease: Improving Global Outcomes(KDIGO)Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases[J]. Kidney Int,2021,100[4S]: S1-S276. DOI:10.1016/j.kint.2021.05.021.

[101]Tang C,Chen P,Si FL,et al.Time-varying proteinuria and progression of IgA nephropathy: a cohort study[J]. Am J Kidney Dis,2024,84(2):170-178.e1.DOI: 10.1053/j.ajkd.2023.12.016.

[102]Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes[J]. N Engl J Med,2012,367(23): 2204-2213. DOI: 10.1056/NEJMoa1208799.

[103]Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk(the ONTARGET study): a multicentre,randomised, double-blind, controlled trial[J]. Lancet,2008, 372(9638): 547-553. DOI: 10.1016/S0140-6736(08)61236-2.

[104]Kidney Disease: Improving Global Outcomes(KDIGO)Blood Pressure Work Group. KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease[J]. Kidney Int, 2021, 99(3S):S1-S87.DOI:10.1016/j.kint.2020.11.003.

[105]Kidney Disease: Improving Global Outcomes(KDIGO)Diabetes Work Group. KDIGO 2022 clinical practice guideline for diabetes management in chronic kidney disease[J]. Kidney Int,2022,102(5S): S1-S127. DOI:10.1016/j.kint.2022.06.008.

[106]Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group(Gruppo Italiano di Studi Epidemiologici in Nefrologia)[J]. Lancet, 1997, 349(9069):1857-1863.

[107]Maschio G, Alberti D, Janin G, et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group[J]. N Engl J Med, 1996,334(15): 939-945. DOI: 10.1056/NEJM199604113341502.

[108] Maschio G, Alberti D, Locatelli F, et al. Angiotensin-converting enzyme inhibitors and kidney protection: the AIPRI trial. The ACE Inhibition in Progressive Renal Insufficiency(AIPRI) Study Group[J]. J Cardiovasc Pharmacol, 1999, 33 Suppl 1: S16-S20; discussion S41-S43.DOI: 10.1097/00005344-199900001-00004.

[109]Hou FF, Xie D, Zhang X, et al. Renoprotection of Optimal Antiproteinuric Doses(ROAD) study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency[J].J Am Soc Nephrol, 2007, 18(6):1889-1898.DOI: 10.1681/ASN.2006121372.

[110]Jafar TH, Stark PC, Schmid CH, et al. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease[J]. Kidney Int, 2001, 60(3): 1131-1140.DOI:10.1046/j.1523-1755.2001.0600031131.x.

[111]Gerstein HC, Mann JF, Pogue J, et al. Prevalence and determinants of microalbuminuria in high-risk diabetic

and nondiabetic patients in the Heart Outcomes Prevention Evaluation Study. The HOPE Study Investigators[J]. Diabetes Care, 2000, 23 Suppl 2: B35-B39.

[112]Cinotti GA, Zucchelli PC, Collaborative Study Group, et al.Effect of lisinopril on the progression of renal insufficiency in mild proteinuric non-diabetic nephropathies[J]. Nephrol Dial Transplant, 2001, 16(5):961-966.DOI:10.1093/ndt/16.5.961.

[113]Hou FF,Zhang X,Zhang GH,et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency[J]. N Engl J Med, 2006, 354(2): 131-140. DOI: 10.1056/NEJMoa053107.

[114]Tang S,Ho K,Ko W,et al. Management of chronic kidney disease: a Hong Kong consensus recommendation[J].Hong Kong Med J,2024,30(6):478-487.DOI:10.12809/hkmj2311309.

[115]Leon SJ, Whitlock R, Rigatto C, et al. Hyperkalemia-related discontinuation of renin- angiotensin-aldosterone system inhibitors and clinical outcomes in CKD: a population-based cohort study[J].Am J Kidney Dis,2022, 80(2): 164-173.e1. DOI: 10.1053/j.ajkd.2022.01.002.

[116] Singhania G,Ejaz AA, McCullough PA,et al. Continuation of chronic heart failure therapies during heart failure hospitalization- a review[J]. Rev Cardiovasc Med, 2019,20(3):111-120.DOI:10.31083/j.rcm.2019.03.562.

[117]王玉，赵明辉.再谈盐皮质激素受体拮抗剂在慢性肾脏病治疗中的应用[J].中华肾脏病杂志，2021,37(10):854-857. DOI: 10.3760/cma. j.cn441217-20201203-00130.

[118]Amazit L, Le Billan F, Kolkhof P,et al. Finerenone impedes aldosterone-dependent nuclear import of the mineralocorticoid receptor and prevents genomic recruitment of steroid receptor coactivator-1[J]. J Biol Chem,2015,290(36):21876-21889.DOI:10.1074/jbc.M115.657957.

[119]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.

[120]Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis[J]. Eur Heart J, 2022, 43(6): 474-484.DOI:10.1093/eurheartj/ehab777.

[121]Li P,An Y,Zheng H,et al. Finerenone in Chinese patients with type 2 diabetes and chronic kidney disease: a FIDELITY analysis[J]. Kidney In Rep, 2024, 9(4 Suppl):S221.DOI:10.1016/j.ekir.2024.02.449.

[122]Marx N, Federici M, Schütt K, et al. 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes[J]. Eur Heart J, 2023, 44(39): 4043-4140.DOI: 10.1093/eurheartj/ehad192.

[123]Sarafidis P, Iatridi F, Ferro C, et al. Mineralocorticoid receptor antagonist use in chronic kidney disease with type 2 diabetes: a clinical practice document by the European Renal Best Practice(ERBP) board of the European Renal Association(ERA)[J]. Clin Kidney J,2023,

16(11):1885-1907.DOI:10.1093/ckj/sfad139.

[124] Mc Causland FR, Vaduganathan M, Claggett BL, et al.Finerenone and kidney outcomes in patients with heart failure: the FINEARTS-HF trial[J].J Am Coll Cardiol,2025,85(2):159-168.DOI:10.1016/j.jacc.2024.10.091.

[125]张瀚桢,郝传明.钠-葡萄糖共转运蛋白2抑制剂在非糖尿病肾脏疾病中的肾脏保护机制研究进展[J].中华肾脏病杂志,2022,38(4):359-363.DOI:10.3760/cma.j.cn441217-20211210-00052.

[126]Lv J,Guo L,Wang R,et al.Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in nondiabetic patients with chronic kidney disease: a review of recent evidence[J]. Kidney Dis(Basel),2023,9(5):326-341.DOI:10.1159/000530395.

[127]Sen T, Heerspink H. A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors[J]. Cell Metab, 2021, 33(4): 732-739. DOI: 10.1016/j.cmet.2021.02.016.

[128]Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials[J]. Lancet, 2022, 400(10365): 1788-1801.DOI:10.1016/S0140-6736(22)02074-8.

[129]McMurray J,Solomon SD,Inzucchi SE,et al.Dapagliflozin in patients with heart failure and reduced ejection fraction[J].N Engl J Med,2019,381(21):1995-2008.DOI:10.1056/NEJMoa1911303.

[130]Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure[J]. N Engl J Med,2020, 383(15): 1413-1424. DOI: 10.1056/NEJMoa2022190.

[131]Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction[J]. N Engl J Med,2021,385(16):1451-1461.DOI: 10.1056/NEJMoa 2107038.

[132]Solomon SD,McMurray J,Claggett B,et al.Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction[J].N Engl J Med,2022,387(12):1089-1098.DOI:10.1056/NEJMoa2206286.

[133]Bhatt DL, Szarek M, Pitt B, et al. Sotagliflozin in patients with diabetes and chronic kidney disease[J]. N Engl J Med,2021,384(2): 129-139.DOI: 10.1056/NEJMoa 2030186.

[134]《钠-葡萄糖转运体2抑制剂在慢性肾脏病患者临床应用的中国专家共识(2023年版)》专家组.钠-葡萄糖转运体2抑制剂在慢性肾脏病患者临床应用的中国专家共识(2023年版)[J].中华肾脏病杂志,2023,39(11):879-888.DOI:10.3760/cma.j.cn441217-20230625-00633.

[135]Thomas MC. The potential and pitfalls of GLP-1 receptor agonists for renal protection in type 2 diabetes[J].Diabetes Metab, 2017, 43 Suppl 1: 2S20-22S27. DOI:10.1016/S1262-3636[17]30069-1.

[136]Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome[J]. N Engl J Med, 2015, 373(23): 2247-2257.DOI: 10.1056/NEJMoa1509225.

[137]Muskiet M, Tonneijck L, Huang Y,et al. Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA

randomised, placebo-controlled trial[J]. Lancet Diabetes Endocrinol,2018,6(11):859-869.DOI:10.1016/S2213-8587(18)30268-7.

[138]Marso SP, Daniels GH, Brown-Frandsen K, et al.Liraglutide and cardiovascular outcomes in type 2 diabetes[J]. N Engl J Med, 2016, 375(4): 311-322. DOI:10.1056/NEJMoa1603827.

[139]Mann J,Orsted DD, Brown-Frandsen K, et al. Liraglutide and renal outcomes in type 2 diabetes[J]. N Engl J Med,2017,377(9):839-848.DOI:10.1056/NEJMoa1616011.

[140]Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes[J].N Engl J Med,2016,375(19):1834-1844.DOI:10.1056/NEJMoa1607141.

[141]Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes[J].N Engl J Med,2017,377(13):1228-1239.DOI:10.1056/NEJMoa1612917.

[142]Gerstein HC,Colhoun HM,Dagenais GR,et al.Dulaglutide and cardiovascular outcomes in type 2 diabetes(REWIND):a double-blind, randomised placebo-controlled trial[J]. Lancet, 2019, 394(10193): 121-130.DOI: 10.1016/S0140-6736(19)31149-3.

[143]Gerstein HC,Colhoun HM,Dagenais GR,et al.Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial[J]. Lancet, 2019, 394(10193): 131-138. DOI: 10.1016/S0140-6736(19)31150-X.

[144]Sattar N, Lee M, Kristensen SL, et al. Cardiovascular,mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials[J]. Lancet Diabetes Endocrinol, 2021, 9(10): 653-662. DOI: 10.1016/S2213-8587(21)00203-5.

[145]Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes[J]. N Engl J Med,2024,391(2): 109-121.DOI: 10.1056/NEJMoa2403347.

[146]《中成药治疗优势病种临床应用指南》标准化项目组.中成药治疗慢性肾脏病3~5期(非透析)临床应用指南[2020年)[J].中国中西医结合杂志,2021,41(3):261-272.DOI:10.7661/j.cjim.20210114.257.

[147]Burnier M, Pruijm M, Wuerzner G,et al. Drug adherence in chronic kidney diseases and dialysis[J]. Nephrol Dial Transplant, 2015, 30(1): 39-44. DOI: 10.1093/ndt/gfu015.

[148]Bailie GR,Eisele G,Liu L,et al. Patterns of medication use in the RRI-CKD study: focus on medications with cardiovascular effects[J]. Nephrol Dial Transplant, 2005,20(6):1110-1115.DOI:10.1093/ndt/gfh771.

[149]Cardone KE, Bacchus S, Assimon MM, et al.Medication-related problems in CKD[J]. Adv Chronic Kidney Dis,2010,17(5):404-412.DOI:10.1053/j.ackd.2010.06.004.

[150]Dorks M, Allers K, Schmiemann G, et al. Inappropriate medication in non-hospitalized patients with renal insufficiency: a systematic review[J]. J Am Geriatr Soc,2017,65(4):853-862.DOI:10.1111/jgs.14809.

[151] Long CL, Raebel MA, Price DW, et al. Compliance with dosing guidelines in patients with chronic kidney disease

[J]. Ann Pharmacother, 2004, 38(5): 853-858. DOI: 10.1345/aph.1D399.

[152]Bots SH, Onland-Moret NC, Tulevski II, et al. Heart failure medication dosage and survival in women and men seen at outpatient clinics[J]. Heart,2021,107(21):1748-1755.DOI: 10.1136/heartjnl-2021-319229.

[153]Santema BT, Ouwerkerk W, Tromp J, et al. Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational,cohort study[J]. Lancet, 2019, 394(10205): 1254-1263.DOI: 10.1016/S0140-6736(19)31792-1.

[154]董婷，李建中，吴声，等.苏州社区老年人慢性肾脏病筛查及共病分析[J].中华老年医学杂志,2021,40(12):1583-1588. DOI: 10.3760/cma.j.issn.0254-9026.2021.12.023.

[155]Robles NR, Cerezo I, Hernandez-Gallego R. Renin-angiotensin system blocking drugs[J]. J Cardiovasc Pharmacol Ther, 2014, 19(1): 14-33. DOI: 10.1177/1074248413501018.

[156]Filippatos TD, Tsimihodimos V, Elisaf MS. Mechanisms of blood pressure reduction with sodium-glucose co- transporter 2(SGLT2) inhibitors[J]. Expert Opin Pharmacother,2016,17(12):1581-1583.DOI:10.1080/14656566.2016.1201073.

[157]Wright JT, Bakris G, Greene T, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial[J]. JAMA, 2002, 288(19): 2421-2431.DOI:10.1001/jama.288.19.2421.

[158]Baker WL, Smyth LR, Riche DM, et al. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis[J].J Am Soc Hypertens,2014,8(4):262-275.e9.DOI:10.1016/j.jash.2014.01.007.

[159]Weber MA, Mansfield TA, Cain VA, et al. Blood pressure and glycaemic effects of dapagliflozin versus placebo in patients with type 2 diabetes on combination antihypertensive therapy: a randomised, double-blind,placebo-controlled, phase 3 study[published correction appears in Lancet Diabetes Endocrinol, 2016, 4(3): e3.DOI: 10.1016/S2213-8587(15)00467-2][J]. Lancet Diabetes Endocrinol, 2016,4(3):211-220.DOI:10.1016/S2213-8587(15)00417-9.

[160]Tikkanen I, Narko K,Zeller C,et al.Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension[J]. Diabetes Care, 2015, 38(3): 420-428.DOI:10.2337/dc14-1096.

[161]Zinman B, Wanner C, Lachin JM, et al. Empagliflozin,cardiovascular outcomes, and mortality in type 2 diabetes[J]. N Engl J Med, 2015, 373(22): 2117-2128. DOI: 10.1056/NEJMoa1504720.

[162]Bohm M, Fitchett D, Ofstad AP, et al. Heart failure and renal outcomes according to baseline and achieved blood pressure in patients with type 2 diabetes: results from EMPA-REG OUTCOME[J].J Hypertens,2020,38(9):1829-1840.DOI:10.1097/HJH.0000000000002492.

[163]Heerspink HJ, Provenzano M, Vart P,et al. Dapagliflozin and blood pressure in patients with chronic kidney disease and albuminuria[J]. Am Heart J,2024,270:125-135.DOI:10.1016/j.ahj.2024.02.006.

[164]Packer M, Claggett B, Lefkowitz MP, et al. Effect of neprilysin inhibition on renal function in patients with type 2 diabetes and chronic heart failure who are receiving target doses of inhibitors of the renin-angiotensin system: a secondary analysis of the PARADIGM-HF trial[J]. Lancet Diabetes Endocrinol,2018,6(7):547-554.DOI:10.1016/S2213-8587(18)30100-1.

[165]Mc Causland FR, Lefkowitz MP, Claggett B, et al.Angiotensin-neprilysin inhibition and renal outcomes in heart failure with preserved ejection fraction[J].Circulation,2020,142(13):1236-1245.DOI:10.1161/CIRCULATIONAHA.120.047643.

[166]Chang HY,Feng AN,Fong MC,et al.Sacubitril/valsartan in heart failure with reduced ejection fraction patients: Real world experience on advanced chronic kidney disease,hypotension, and dose escalation[J]. J Cardiol, 2019,74(4):372-380.DOI:10.1016/j.jjcc.2019.03.010.

[167] Hsieh HL,Chen CY,Chen CH,et al.Renal protective effect of sacubitril/valsartan in patients with heart failure[J].Sci Rep,2021,11(1):4593.DOI:10.1038/s41598-021-84118-8.

[168]Freeman MW, Halvorsen YD, Marshall W, et al. Phase 2 trial of baxdrostat for treatment-resistant hypertension[J].N Engl J Med,2023,388(5):395-405.DOI:10.1056/NEJMoa2213169.

[169]Laffin LJ, Rodman D, Luther JM, et al. Aldosterone synthase inhibition with lorundrostat for uncontrolled hypertension: the target-HTN randomized clinical trial[J].JAMA,2023,330(12):1140-1150.DOI:10.1001/jama.2023.16029.

[170]Goffredo G, Barone R, Di Terlizzi V, et al. Biomarkers in cardiorenal syndrome[J].J Clin Med,2021,10(15):3433.DOI:10.3390/jcm10153433.

[171]Ajibowo AO, Okobi OE, Emore E, et al. Cardiorenal syndrome: a literature review[J]. Cureus, 2023, 15(7):e41252.DOI:10.7759/cureus.41252.

[172]House AA, Anand I, Bellomo R, et al. Definition and classification of cardio-renal syndromes: workgroup statements from the 7th ADQI Consensus Conference[J].Nephrol Dial Transplant, 2010, 25(5): 1416-1420. DOI:10.1093/ndt/gfq136.

[173]Wang F,Yang C,Long J,et al. Executive summary for the 2015 annual data report of the China Kidney Disease Network(CK-NET)[J]. Kidney Int, 2019, 95(3): 501-505.DOI:10.1016/j.kint.2018.11.011.

[174]Park M,Hsu CY,Li Y,et al.Associations between kidney function and subclinical cardiac abnormalities in CKD[J].J Am Soc Nephrol,2012,23(10):1725-1734.DOI:10.1681/ASN.2012020145.

[175]Foley RN, Parfrey PS, Kent GM,et al. Long-term evolution of cardiomyopathy in dialysis patients[J]. Kidney Int,1998, 54(5): 1720-1725. DOI: 10.1046/j. 1523-1755.1998.00154.x.

[176]Suzuki T, Agarwal SK, Deo R, et al. Kidney function and sudden cardiac death in the community: the Atherosclerosis Risk in Communities(ARIC) study[J].Am Heart J,2016,180:46-53.DOI:10.1016/j.ahj.2016.07.004.

[177]Chronic Kidney Disease Prognosis Consortium,Matsushita K, van der Velde M, et al. Association of

estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis[J]Lancet, 2010, 375(9731): 2073-2081. DOI: 10.1016/S0140-6736(10)60674-5.

[178] Ndumele CE, Rangaswami J, Chow SL, et al.Cardiovascular-kidney-metabolic health: a presidential advisory from the American Heart Association[published correction appears in Circulation, 2024,149(13): e1023.DOI: 10.1161/CIR.0000000000001241][J].Circulation,2023,148(20):1606-1635.DOI:10.1161/CIR.0000000000001184.

[179]Schiffrin EL,Lipman ML,Mann JF.Chronic kidney disease:effects on the cardiovascular system[J]. Circulation, 2007,116(1): 85-97. DOI: 10.1161/CIRCULATIONAHA. 106.678342.

[180]Lee C, Park JT, Chang TI, et al. Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: results from the KNOW-CKD[J]Nutr Metab Cardiovasc Dis,2022,32(2):410-419.DOI:10.1016/j.numecd.2021.09.037.

[181]Cholesterol Treatment Trialists'(CTT) Collaboration,Herrington WG, Emberson J, et al. Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials[J]. Lancet Diabetes Endocrinol, 2016, 4(10): 829-839. DOI:10.1016/S2213-8587(16)30156-5.

[182]Collins R, Reith C,Emberson J,et al. Interpretation of the evidence for the efficacy and safety of statin therapy[J]Lancet, 2016, 388(10059): 2532-2561. DOI: 10.1016/S0140-6736(16)31357-5.

[183]Kosmas CE, Bousvarou MD, Papakonstantinou EJ, et al.Novel pharmacological therapies for the management of hyperlipoproteinemia(a)[J]. Int J Mol Sci, 2023, 24(17):13622.DOI:10.3390/ijms241713622.

[184]中国血脂管理指南修订联合专家委员会.中国血脂管理指南(2023年)[J].中华心血管病杂志,2023,51(3):221-255.DOI:10.3760/cma.j.cn112148-20230119-00038.

[185]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.抗血小板治疗中国专家共识[J].中华心血管病杂志，2013, 41(3): 183-194. DOI: 10.3760/cma.j.issn.0253-3758.2013.03.004.

[186]霍勇,王拥军,谷涌泉,等.常用口服抗血小板药物不耐受及低反应性人群诊疗专家共识[J].中华心血管病杂志(网络版),2021,4(1):1-13.DOI:10.3760/cma.j.cn116031.2021.1000076.

[187]应用β肾上腺素能受体阻滞剂规范治疗冠心病中国专家共识组.应用β肾上腺素能受体阻滞剂规范治疗冠心病的中国专家共识[J].中国循环杂志,2020,35[2]:108-123.DOI:10.3969/j.issn.1000-3614.2020.02.002.

[188]中国冠状动脉杂交血运重建专家共识(2022)编写组.中国冠状动脉杂交血运重建专家共识(2022)[J].中华胸心血管外科杂志，2022,38(7):385-395.DOI:10.3760/cma.j.cn112434-20220507-00152.

[189]Milojevic M,Head SJ,Mack MJ,et al.The impact of chronic kidney disease on outcomes following percutaneous coronary intervention versus coronary artery bypass grafting in patients with complex coronary artery disease: five-year follow-up of the SYNTAX trial[J]

EuroIntervention, 2018, 14(1): 102-111. DOI: 10.4244/EIJ-D-17-00620.

[190] Lawton JS,Tamis-Holland JE,Bangalore S,et al.2021 ACC/AHA/SCAI guideline for coronary artery revascularization: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines[J].Circulation,2022,145(3):e4-e17.DOI:10.1161/CIR.0000000000001039.

[191]Neumann FJ, Sousa-Uva M,Ahlsson A, et al.2018 ESC/EACTS guidelines on myocardial revascularization[J]. Eur Heart J,2019,40(2):87-165.DOI:10.1093/eurheartj/ehy394.

[192]Li J,Li Y,Xu B,et al. Short-term rosuvastatin therapy prevents contrast-induced acute kidney injury in female patients with diabetes and chronic kidney disease: a subgroup analysis of the TRACK-D study[J]. J Thorac Dis,2016,8(5):1000-1006.DOI:10.21037/jtd.2016.03.26.

[193]Tokmakova MP,Skali H, Kenchaiah S,et al.Chronic kidney disease, cardiovascular risk, and response to angiotensin-converting enzyme inhibition after myocardial infarction:the Survival And Ventricular Enlargement(SAVE) study[J].Circulation,2004,110(24):3667-3673.DOI:10.1161/01.CIR.0000149806.01354.BF.

[194]Bowling CB, Sanders PW, Allman RM, et al. Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: insights from the SOLVD treatment trial[J]. Int J Cardiol, 2013, 167(1): 151-156.DOI:10.1016/j.ijcard.2011.12.056.

[195]SOLVD Investigators, Yusuf S, Pitt B, et al. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions[J]. N Engl J Med,1992, 327(10): 685-691. DOI: 10.1056/NEJM199209033271003.

[196] Torp-Pedersen C, Kober L, Carlsen J. Angiotensin-converting enzyme inhibition after myocardial infarction:the trandolapril cardiac evaluation study[J]. Am Heart J,1996, 132(1 Pt 2 Su): 235-243. DOI: 10.1016/s0002-8703(96)90559-1.

[197]Anand IS, Bishu K, Rector TS, et al. Proteinuria, chronic kidney disease, and the effect of an angiotensin receptor blocker in addition to an angiotensin-converting enzyme inhibitor in patients with moderate to severe heart failure[J].Circulation,2009,120(16):1577-1584.DOI:10.1161/CIRCULATIONAHA.109.853648.

[198] Desai AS, Swedberg K, McMurray JJ, et al. Incidence and predictors of hyperkalemia in patients with heart failure:an analysis of the CHARM program[J].J Am Coll Cardiol,2007, 50(20): 1959-1966. DOI: 10.1016/j.jacc.2007.07.067.

[199]Granger CB, McMurray JJ, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-alternative trial[J]. Lancet, 2003, 362(9386): 772-776.DOI: 10.1016/S0140-6736(03)14284-5.

[200]Shah SR, Ali A, Ikram S. Sotagliflozin and decompensated heart failure: results of the SOLOIST-WHF trial[J]. Expert Rev Clin Pharmacol,2021,14(5):523-525.DOI:10.1080/

17512433.2021.1908123.

[201]Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators[J]. N Engl J Med, 1999, 341(10): 709-717. DOI: 10.1056/NEJM 199909023411001.

[202]Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms[J]N Engl J Med, 2011, 364(1): 11-21. DOI: 10.1056/NEJMoa1009492.

[203]Ghali JK, Wikstrand J, Van Veldhuisen DJ, et al. The influence of renal function on clinical outcome and response to beta-blockade in systolic heart failure:insights from Metoprolol CR/XL Randomized Intervention Trial in Chronic HF(MERIT-HF)[J]. J Card Fail,2009, 15(4): 310-318. DOI: 10.1016/j. cardfail.2008.11.003.

[204]Castagno D, Jhund PS, McMurray JJ, et al. Improved survival with bisoprolol in patients with heart failure and renal impairment: an analysis of the cardiac insufficiency bisoprolol study II(CIBIS-II) trial[J]. Eur J Heart Fail,2010,12(6):607-616.DOI:10.1093/eurjhf/hfq038.

[205]Krum H, Roecker EB, Mohacsi P,et al. Effects of initiating carveditol in patients with severe chronic heart failure:results from the COPERNICUS study[J]. JAMA, 2003,289(6):712-718.DOI:10.1001/jama.289.6.712.

[206]Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial[J]. Lancet,2001, 357(9266): 1385-1390. DOI: 10.1016/s0140-6736(00)04560-8.

[207]Cohen-Solal A, Kotecha D, van Veldhuisen DJ, et al.Efficacy and safety of nebivolol in elderly heart failure patients with impaired renal function: insights from the SENIORS trial[J]. Eur J Heart Fail, 2009, 11(9): 872-880.DOI:10.1093/eurjhf/hfp104.

[208]Damman K, Gori M, Claggett B, et al. Renal effects and associated outcomes during angiotensin-neprilysin inhibition in heart failure[J]. JACC Heart Fail, 2018, 6(6):489-498.DOI:10.1016/j.jchf.2018.02.004.

[209]Voors AA,Mulder H, Reyes E,et al. Renal function and the effects of vericiquat in patients with worsening heart failure with reduced ejection fraction: insights from the VICTORIA(Vericiguat Global Study in Subjects with HFrEF) trial[J]. Eur J Heart Fail,2021,23(8): 1313-1321.DOI: 10.1002/ejhf.2221.

[210]国家心血管病中心,国家心血管病专家委员会心力衰竭专业委员会，中国医师协会心力衰竭专业委员会，等.国家心力衰竭指南2023[J].中华心力衰竭和心肌病杂志，2023,7(4): 215-311. DOI: 10.3760/cma. j. issn. 101460-20231209-00052.

[211]Neuen BL, Young T, Heerspink H, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis[J].Lancet Diabetes Endocrinol, 2019, 7(11): 845-854. DOI:10.1016/S2213-8587(19)30256-6.

[212]Babitt JL, Lin HY. Mechanisms of anemia in CKD[J]. J Am Soc Nephrol, 2012, 23(10): 1631-1634. DOI: 10.1681/ASN.2011111078.

[213]Inker LA, Grams ME, Levey AS, et al. Relationship of estimated GFR and albuminuria to concurrent laboratory abnormalities: an individual participant data meta-analysis in a global consortium[J]. Am J Kidney Dis, 2019,73(2):206-217.DOI:10.1053/j.ajkd.2018.08.013.

[214]Thorp ML, Johnson ES,Yang X,et al. Effect of anaemia on mortality, cardiovascular hospitalizations and end-stage renal disease among patients with chronic kidney disease[J]. Nephrology(Carlton), 2009, 14(2): 240-246. DOI:10.1111/j.1440-1797.2008.01065.x.

[215]Hoshino J, Muenz D, Zee J, et al. Associations of hemoglobin levels with health-related quality of life,physical activity, and clinical outcomes in persons with stage 3-5 nondialysis CKD[J]. J Ren Nutr, 2020, 30(5):404-414.DOI:10.1053/j.jrn.2019.11.003.

[216]Minutolo R, Provenzano M, Chiodini P, et al. New-onset anemia and associated risk of ESKD and death in non-dialysis CKD patients: a multicohort observational study[J]. Clin Kidney J, 2022, 15(6): 1120-1128. DOI:10.1093/ckj/sfac004.

[217]Awan AA, Walther CP, Richardson PA, et al. Prevalence,correlates and outcomes of absolute and functional iron deficiency anemia in nondialysis-dependent chronic kidney disease[J]. Nephrol Dial Transplant, 2021, 36(1):129-136.DOI:10.1093/ndt/gfz192.

[218]Macdougall IC, Bock AH, Carrera F, et al. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia[J]. Nephrol Dial Transplant,2014,29(11):2075-2084.DOI:10.1093/ndt/gfu201.

[219]Tessitore N, Solero GP, Lippi G, et al. The role of iron status markers in predicting response to intravenous iron in haemodialysis patients on maintenance erythropoietin[J]. Nephrol Dial Transplant, 2001, 16(7): 1416-1423.DOI:10.1093/ndt/16.7.1416.

[220]Fishbane S, Kowalski EA, Imbriano LJ, et al. The evaluation of iron status in hemodialysis patients[J].J Am Soc Nephrol,1996,7(12):2654-2657.DOI:10.1681/ASN.V7122654.

[221] Fishbane S, Shapiro W, Dutka P, et al. A randomized trial of iron deficiency testing strategies in hemodialysis patients[J]. Kidney Int,2001,60(6):2406-2411.DOI:10.1046/j.1523-1755.2001.00077.x.

[222]Macdougall IC, Tucker B, Thompson J, et al. A randomized controlled study of iron supplementation in patients treated with erythropoietin[J]. Kidney Int, 1996, 50(5):1694-1699.DOI:10.1038/ki.1996.487.

[223]Batchelor EK, Kapitsinou P, Pergola PE, et al. Iron deficiency in chronic kidney disease: updates on pathophysiology, diagnosis, and treatment[J]. J Am Soc Nephrol, 2020, 31(3): 456-468. DOI: 10.1681/ASN.2019020213.

[224]Pisani A, Riccio E, Sabbatini M, et al. Effect of oral liposomal iron versus intravenous iron for treatment of iron deficiency anaemia in CKD patients: a randomized trial[J]. Nephrol Dial Transplant, 2015, 30(4): 645-652.DOI: 10.1093/ndt/gfu357.

[225]O'Lone EL, Hodson EM, Nistor I, et al. Parenteral versus oral iron therapy for adults and children with chronic kidney disease[J]. Cochrane Database Syst Rev, 2019,

2(2): CD007857. DOI: 10.1002/14651858. CD007857.pub3.

[226]Agarwal R, Kusek JW, Pappas MK. A randomized trial of intravenous and oral iron in chronic kidney disease[J].Kidney Int, 2015, 88(4): 905-914. DOI: 10.1038/ki.2015.163.

[227]Chung EY, Palmer SC, Saglimbene VM, et al.Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis[J]Cochrane Database Syst Rev,2023,2(2):CD010590.DOI:10.1002/14651858.CD010590.pub3.

[228]Liu B, Chen N, Zhao J, et al. Efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection for the treatment of renal anemia in Chinese hemodialysis patients: a randomized, open-label, parallel-group,noninferiority phase III trial[J]. Chronic Dis Transl Med,2022,8(2):134-144.DOI:10.1002/cdt3.23.

[229]Chen N, Xing C, Niu J, et al. Darbepoetin alfa injection versus epoetin alfa injection for treating anemia of Chinese hemodialysis patients with chronic kidney failure: a randomized, open-label, parallel-group, non-inferiority phase III trail[J]. Chronic Dis Transl Med,2022,8(1):59-70.DOI:10.1002/cdt3.13.

[230]钱家麒,陈楠,梅长林,等.持续性红细胞生成素受体激活剂静脉给药在慢性肾脏病透析患者中纠正贫血的疗效、安全性和耐受性[J].中华肾脏病杂志，2012,28(11):847-852. DOI: 10.3760/cma. j.issn.1001-7097.2012.11.006.

[231]Saglimbene VM, Palmer SC, Ruospo M, et al. Continuous erythropoiesis receptor activator(CERA) for the anaemia of chronic kidney disease[J]. Cochrane Database Syst Rev,2017,8(8): CD009904.DOI: 10.1002/14651858.CD009904.pub2.

[232]Zhang P, Jiang Y, Xu C, et al. Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial[J]. EClinicalMedicine, 2023,65:102273.DOI:10.1016/j.eclinm.2023.102273.

[233]Locatelli F, Choukroun G, Truman M, et al. Once-monthly continuous erythropoietin receptor activator(C.E.R.A.) in patients with hemodialysis-dependent chronic kidney disease: pooled data from phase III trials[J]. Adv Ther,2016,33(4):610-625.DOI:10.1007/s12325-016-0309-6.

[234]Lin T,Yang A, Qiu H,et al. Pegmolesatide for the treatment of anemia in NDD-CKD patients: a multicenter randomized active-controlled phase 3 trial[J]. J Am Soc Nephrol, 2022, 33(11S): 247. DOI: 10.1681/ASN.20223311S1247c.

[235]中国研究型医院学会肾脏病学专业委员会.罗沙司他治疗肾性贫血中国专家共识[J].中华医学杂志,2022,102(24):1802-1810. DOI: 10.3760/cma.j.cn112137-20220129-00220.

[236]Zhang L, Hou J, Li J, et al. Roxadustat for the treatment of anemia in patients with chronic kidney diseases: a meta-analysis[J]. Aging(Albany NY), 2021, 13(13):17914-17929.DOI:10.18632/aging.203143.

[237]Chen N, Hao C, Liu BC, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis[J]. N Engl J Med, 2019, 381(11): 1011-1022. DOI: 10.1056/NEJMoa1901713.

[238]Akizawa T, Yamaguchi Y, Otsuka T, et al. A phase 3,

multicenter, randomized, two-arm, open-label study of intermittent oral dosing of roxadustat for the treatment of anemia in Japanese erythropoiesis-stimulating agent-naive chronic kidney disease patients not on dialysis[J]. Nephron, 2020, 144(8): 372-382. DOI: 10.1159/000508100.

[239]Fishbane S, El-Shahawy MA, Pecoits-Filho R, et al.Roxadustat for treating anemia in patients with CKD not on dialysis: results from a randomized phase 3 study[J].J Am Soc Nephrol, 2021, 32(3): 737-755. DOI: 10.1681/ASN.2020081150.

[240]Shutov E,Sutowicz W,Esposito C,et al. Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: a phase 3, randomized, double-blind,placebo-controlled study(ALPS)[J]. Nephrol Dial Transplant,2021,36(9):1629-1639.DOI:10.1093/ndt/gfab057.

[241]Akizawa T, Iwasaki M, Otsuka T, et al. Phase 3 study of roxadustat to treat anemia in non-dialysis-dependant CKD[J].Kidney Int Rep,2021,6(7):1810-1828.DOI:10.1016/j.ekir.2021.04.003.

[242]Barratt J, Andric B, Tataradze A, et al. Roxadustat for the treatment of anaemia in chronic kidney disease patients not on dialysis: a phase 3, randomized, open-label, active-controlled study(DOLOMITES)[published correction appears in Nephrol Dial Transplant, 2022, 37(4): 805][J].Nephrol Dial Transplant, 2021, 36(9): 1616-1628. DOI:10.1093/ndt/gfab191.

[243]Yu XQ,Ye ZM,Liang XL,et al.A phase 3 multicenter,randomized, double-blind, placebo-controlled study of enarodustat for the treatment of renal anemia in Chinese non-dialysis CKD patients[J/OL].(2023-11-02)[2025-01-21]. 2023 ASN: TH-PO1147. https://www.asn-online. org/education/kidneyweek/2023/program-abstract.aspx?controlId=3976799.

[244]Akizawa T, Nangaku M, Yamaguchi T, et al. A phase 3 study of enarodustat in anemic patients with CKD not requiring dialysis: the SYMPHONY ND study[J]. Kidney Int Rep,2021,6(7):1840-1849.DOI:10.1016/j.ekir.2021.04.037.

[245] Qu W, Yao L, Liu X, et al. Effects of sodium-glucose co-transporter 2 inhibitors on hemoglobin levels: a meta-analysis of randomized controlled trials[J]. Front Pharmacol,2021,12:630820.DOI:10.3389/fphar.2021.630820.

[246] Wang X, Fu R, Liu H, et al. The effects of sodium glucose co-transporter(SGLT) 2 inhibitors on hematocrit levels: a systematic review and meta-analysis of randomized controlled trials[J]. Ann Palliat Med, 2021, 10(6): 6467-6481.DOI:10.21037/apm-21-1022.

[247]Wilding JP, Woo V, Rohwedder K, et al. Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years[J]. Diabetes Obes Metab,2014,16(2):124-136.DOI:10.1111/dom.12187.

[248]Koshino A, Schechter M, Chertow GM, et al. Dapagliflozin and anemia in patients with chronic kidney disease[J].NEJM Evid,2023,2(6): EVIDoa2300049.DOI: 10.1056/EVIDoa2300049.

[249]Oshima M, Neuen BL, Jardine MJ, et al. Effects of canagliflozin on anaemia in patients with type 2 diabetes

and chronic kidney disease: a post-hoc analysis from the CREDENCE trial[J]. Lancet Diabetes Endocrinol, 2020,8(11):903-914.DOI:10.1016/S2213-8587(20)30300-4.

[250]Packer M. How can sodium-glucose cotransporter 2 inhibitors stimulate erythrocytosis in patients who are iron-deficient? Implications for understanding iron homeostasis in heart failure[J]. Eur J Heart Fail, 2022,24(12):2287-2296.DOI:10.1002/ejhf.2731.

[251]Korgaonkar S, Tilea A, Gillespie BW, et al. Serum potassium and outcomes in CKD: insights from the RRI-CKD cohort study[J]. Clin J Am Soc Nephrol, 2010, 5(5):762-769.DOI:10.2215/CJN.05850809.

[252]Collins AJ, Pitt B, Reaven N, et al. Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes[J]. Am J Nephrol, 2017, 46(3): 213-221. DOI:10.1159/000479802.

[253]Adamczak M, Surma S. Metabolic acidosis in patients with CKD: epidemiology, pathogenesis, and treatment[J]Kidney Dis(Basel),2021,7(6):452-467.DOI:10.1159/000516371.

[254]Melamed ML, Raphael KL. Metabolic acidosis in CKD: a review of recent findings[J]. Kidney Med, 2021, 3(2):267-277.DOI:10.1016/j.xkme.2020.12.006.

[255]Dobre M,Yang W,Chen J,et al. Association of serum bicarbonate with risk of renal and cardiovascular outcomes in CKD: a report from the Chronic Renal Insufficiency Cohort(CRIC) study[J]. Am J Kidney Dis,2013,62(4):670-678.DOI:10.1053/j.ajkd.2013.01.017.

[256]Raphael KL,Zhang Y,Wei G,et al.Serum bicarbonate and mortality in adults in NHANES III[J]. Nephrol Dial Transplant,2013,28(5):1207-1213.DOI:10.1093/ndt/gfs609.

[257]Navaneethan SD, Schold JD, Arrigain S, et al. Serum bicarbonate and mortality in stage 3 and stage 4 chronic kidney disease[J]. Clin J Am Soc Nephrol, 2011, 6(10):2395-2402.DOI: 10.2215/CJN.03730411.

[258]Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD[J]. Nephrol Dial Transplant,2009,24(4):1232-1237.DOI:10.1093/ndt/gfn633.

[259]Wesson DE, Buysse JM, Bushinsky DA. Mechanisms of metabolic acidosis-induced kidney injury in chronic kidney disease[J]. J Am Soc Nephrol, 2020, 31(3): 469-482.DOI:10.1681/ASN.2019070677.

[260]Bandak G, Sang Y, Gasparini A, et al. Hyperkalemia after initiating renin-angiotensin system blockade: the Stockholm Creatinine Measurements(SCREAM) project[J].J Am Heart Assoc,2017,6[7):e005428.DOI:10.1161/JAHA.116.005428.

[261]Pecoits-Filho R, Fliser D, Tu C, et al. Prescription of renin-angiotensin-aldosterone system inhibitors(RAASi)and its determinants in patients with advanced CKD under nephrologist care[J].J Clin Hypertens(Greenwich),2019,21(7):991-1001.DOI:10.1111/jch.13563.

[262]Lazich I, Bakris GL. Prediction and management of hyperkalemia across the spectrum of chronic kidney disease[J].Semin Nephrol,2014,34(3):333-339.DOI:10.1016/j.semnephrol.2014.04.008.

[263]Savarese G, Vasko P, Jonsson A, et al. The Swedish heart failure registry: a living, ongoing quality assurance and research in heart failure[J]. Ups J Med Sci, 2019, 124(1):65-69.DOI:10.1080/03009734.2018.1490831.

[264]Jun M, Jardine MJ, Perkovic V, et al. Hyperkalemia and renin-angiotensin aldosterone system inhibitor therapy in chronic kidney disease: a general practice-based,observational study[J]. PLoS One, 2019, 14(3): e0213192.DOI:10.1371/journal.pone.0213192.

[265]Neuen BL, Oshima M, Agarwal R, et al. Sodium-glucose cotransporter 2 inhibitors and risk of hyperkalemia in people with type 2 diabetes: a meta-analysis of individual participant data from randomized, controlled trials[J].Circulation,2022,145(19):1460-1470.DOI:10.1161/CIRCULATIONAHA.121.057736.

[266]叶智明，蔡建芳，陈崴，等.高钾血症管理规范多科室合作全流程管理模式[J].中华肾脏病杂志，2024,40(3):245-254.DOI:10.3760/cma.j.cn441217-20231110-01109.

[267]中华医学会肾脏病学分会专家组.中国慢性肾脏病患者血钾管理实践专家共识[J].中华肾脏病杂志，2020,36(10):781-792.DOI:10.3760/cma.j.cn441217-20200721-00139.

[268] Noel JA, Bota SE, Petrcich W, et al. Risk of hospitalization for serious adverse gastrointestinal events associated with sodium polystyrene sulfonate use in patients of advanced age[J]. JAMA Intern Med, 2019, 179(8): 1025-1033.DOI:10.1001/jamainternmed.2019.0631.

[269]Laureati P, Xu Y, Trevisan M, et al. Initiation of sodium polystyrene sulphonate and the risk of gastrointestinal adverse events in advanced chronic kidney disease: a nationwide study[J]. Nephrol Dial Transplant, 2020,35(9):1518-1526.DOI:10.1093/ndt/gfz150.

[270]Nasir K,Ahmad A. Treatment of hyperkalemia in patients with chronic kidney disease: a comparison of calcium polystyrene sulphonate and sodium polystyrene sulphonate[J].J Ayub Med Coll Abbottabad,2014,26(4):455-458.

[271]Yu MY,Yeo JH, Park JS,et al. Long-term efficacy of oral calcium polystyrene sulfonate for hyperkalemia in CKD patients[J]. PLoS One, 2017, 12(3): e0173542. DOI: 10.1371/journal.pone.0173542.

[272]Spinowitz BS, Fishbane S, Pergola PE, et al. Sodium zirconium cyclosilicate among individuals with hyperkalemia: a 12-month phase 3 study[J]. Clin J Am Soc Nephrol, 2019, 14(6): 798-809. DOI: 10.2215/CJN.12651018.

[273]Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia[J]. N Engl J Med,2015,372(3):222-231.DOI:10.1056/NEJMoa1411487.

[274]李儒刚,黄洁平,旷双红,等.环硅酸锆钠散对慢性肾脏病严重高钾血症患者短期降钾效果的临床观察[J].国际医药卫生导报,2022,28(6):854-858.DOI:10.3760/cma.j.issn.1007-1245.2022.06.030.

[275]Fishbane S, Ford M, Fukagawa M, et al. A phase 3b,randomized, double-blind, placebo-controlled study of sodium zirconium cyclosilicate for reducing the incidence of predialysis hyperkalemia[J].J Am Soc Nephrol, 2019,30(9):1723-1733.DOI:10.1681/ASN.2019050450.

[276] de Brito-Ashurst I, Varagunam M, Raftery MJ, et al.

Bicarbonate supplementation slows progression of CKD and improves nutritional status[J]. J Am Soc Nephrol, 2009, 20(9): 2075-2084. DOI: 10.1681/ASN.2008111205.

[277]Phisitkul S, Khanna A, Simoni J, et al. Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR[J]. Kidney Int, 2010, 77(7): 617-623.DOI:10.1038/ki.2009.519.

[278]Di Iorio BR, Bellasi A, Raphael KL, et al. Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI study[J].J Nephrol,2019,32(6):989-1001.DOI:10.1007/s40620-019-00656-5.

[279]Goraya N, Munoz-Maldonado Y, Simoni J, et al. Fruit and vegetable treatment of chronic kidney disease-related metabolic acidosis reduces cardiovascular risk better than sodium bicarbonate[J]. Am J Nephrol, 2019, 49(6):438-448.DOI:10.1159/000500042.

[280]Goraya N,Simoni J,Jo CH,et al.A comparison of treating metabolic acidosis in CKD stage 4 hypertensive kidney disease with fruits and vegetables or sodium bicarbonate[J]. Clin J Am Soc Nephrol, 2013, 8(3): 371-381. DOI:10.2215/CJN.02430312.

[281]Goraya N,Simoni J,Jo CH,et al.Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate[J]. Kidney Int, 2014, 86(5): 1031-1038.DOI:10.1038/ki.2014.83.

[282]Noce A, Marrone G, Wilson Jones G, et al. Nutritional approaches for the management of metabolic acidosis in chronic kidney disease[J]. Nutrients,2021,13(8):2534.DOI:10.3390/nu13082534.

[283]Hultin S, Hood C, Campbell KL, et al. A systematic review and meta-analysis on effects of bicarbonate therapy on kidney outcomes[J]. Kidney Int Rep,2021,6(3):695-705.DOI:10.1016/j.ekir.2020.12.019.

[284]BiCARB study group. Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis(BiCARB):a pragmatic randomised, double-blind, placebo-controlled trial[J]. BMC Med, 2020, 18(1): 91. DOI: 10.1186/s12916-020-01542-9.

[285] Tangri N, Mathur VS, Bushinsky DA, et al. VALOR-CKD:a multicenter, randomized, double-blind placebo-controlled trial evaluating veverimer in slowing progression of CKD in patients with metabolic acidosis[J].J Am Soc Nephrol, 2024, 35(3): 311-320. DOI: 10.1681/ASN.0000000000000292.

[286]Sato Y, Feig DI, Stack AG, et al. The case for uric acid-lowering treatment in patients with hyperuricaemia and CKD[J]. Nat Rev Nephrol, 2019, 15(12): 767-775. DOI:10.1038/s41581-019-0174-z.

[287]Jalal DI, Chonchol M, Chen W, et al. Uric acid as a target of therapy in CKD[J]. Am J Kidney Dis, 2013, 61(1): 134-146.DOI:10.1053/j.ajkd.2012.07.021.

[288]Chonchol M, Shlipak MG, Katz R, et al. Relationship of uric acid with progression of kidney disease[J]. Am J Kidney Dis,2007, 50(2): 239-247. DOI: 10.1053/j.ajkd.2007.

05.013.

[289]Iseki K, Ikemiya Y, Inoue T, et al. Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort[J]. Am J Kidney Dis, 2004, 44(4):642-650.

[290]Hsu CY,Iribarren C,McCulloch CE,et al. Risk factors for end-stage renal disease: 25-year follow-up[J]. Arch Intern Med, 2009, 169(4): 342-350. DOI: 10.1001/archinternmed.2008.605.

[291]中国医师协会肾脏内科医师分会.中国肾脏疾病高尿酸血症诊治的实践指南(2017版)[J].中华医学杂志，2017，97(25):1927-1936.DOI:10.3760/cma.j.issn.0376-2491.2017.25.003.

[292]Sampson AL, Singer RF, Walters GD. Uric acid lowering therapies for preventing or delaying the progression of chronic kidney disease[J]. Cochrane Database Syst Rev,2017, 10(10): CD009460. DOI: 10.1002/14651858.CD009460.pub2.

[293]Badve SV, Pascoe EM, Tiku A, et al. Effects of allopurinol on the progression of chronic kidney disease[J]. N Engl J Med,2020,382(26):2504-2513.DOI:10.1056/NEJMoa 1915833.

[294]Doria A, Galecki AT, Spino C, et al. Serum urate lowering with allopurinol and kidney function in type 1 diabetes[J].N Engl J Med,2020,382(26):2493-2503.DOI:10.1056/NEJMoa1916624.

[295]Kimura K,Hosoya T,Uchida S,et al.Febuxostat therapy for patients with stage 3 CKD and asymptomatic hyperuricemia: a randomized trial[J]. Am J Kidney Dis,2018,72(6):798-810.DOI:10.1053/j.ajkd.2018.06.028.

[296]中华医学会内分泌学分会.中国高尿酸血症与痛风诊疗指南(2019)[J].中华内分泌代谢杂志，2020,36(1):1-13.DOI:10.3760/cma.j.issn.1000-6699.2020.01.001.

[297] Stack AG, Han D, Goldwater R, et al. Dapagliflozin added to verinurad plus febuxostat further reduces serum uric acid in hyperuricemia: the QUARTZ study[J]. J Clin Endocrinol Metab,2021,106(5):e2347-e2356.DOI:10.1210/clinem/dgaa748.

[298]Mori D,Kobayashi M, Wada M, et al. Effect of dapagliflozin on serum uric acid levels in patients with advanced chronic kidney disease[J]. Intern Med, 2024, 63(3): 353-357.DOI:10.2169/internalmedicine.1828-23.

[299]Rajasekar R, Sundaram SM, Raj CP, et al. Analysing uric acid levels to assess the effectiveness of dapagliflozin[J].Clin Nutr ESPEN, 2024, 59: 81-88. DOI: 10.1016/j.clnesp.2023.11.013.

[300]Doehner W, Anker SD, Butler J, et al. Uric acid and sodium- glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: the EMPEROR-reduced trial[J].Eur Heart J,2022,43(36):3435-3446.DOI:10.1093/eurheartj/ehac320.

[301]McDowell K, Welsh P, Docherty KF, et al. Dapagliflozin reduces uric acid concentration, an independent predictor of adverse outcomes in DAPA-HF[J]. Eur J Heart Fail,2022,24(6):1066-1076.DOI:10.1002/ejhf.2433.

[302]McCormick N, Yokose C, Wei J, et al. Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent gout flares and gout-primary emergency department visits and hospitalizations: a general population cohort study[J]. Ann Intern Med,

2023,176(8):1067-1080.DOI:10.7326/M23-0724.

[303]Chung MC, Hung PH, Hsiao PJ, et al. Association of sodium-glucose transport protein 2 inhibitor use for type 2 diabetes and incidence of gout in Taiwan[J].JAMA Netw Open,2021,4(11):e2135353.DOI:10.1001/jamanetworkopen.2021.35353.

[304]Fralick M, Chen SK, Patorno E, et al. Assessing the risk for gout with sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes: a population-based cohort study[J]. Ann Intern Med, 2020, 172(3): 186-194. DOI:10.7326/M19-2610.

[305]Lund LC, H@jlund M, Henriksen DP, et al. Sodium-glucose cotransporter-2 inhibitors and the risk of gout: a Danish population based cohort study and symmetry analysis[J].Pharmacoepidemiol Drug Saf,2021,30(10):1391-1395.DOI: 10.1002/pds.5252.

[306]Matsumura K, Arima H, Tominaga M, et al. Effect of losartan on serum uric acid in hypertension treated with a diuretic: the COMFORT study[J]. Clin Exp Hypertens,2015, 37(3): 192-196. DOI: 10.3109/10641963.2014.933968.

[307]Ferreira JP,Zannad F, Kiernan MS,et al. High- versus low-dose losartan and uric acid: an analysis from HEAAL[J].J Cardiol,2023,82(1):57-61.DOI:10.1016/j.jjcc.2023.04.005.

[308]Baker M, Perazella MA. NSAIDs in CKD: are they safe?[J].Am J Kidney Dis,2020,76(4):546-557.DOI:10.1053/j.ajkd.2020.03.023.

[309]Kim HW,Joo YS,Yun HR,et al. Colchicine use and the risk of CKD progression: a multicentre nested case-control study[J]. Rheumatology(Oxford), 2022, 61(11): 4314-4323.DOI:10.1093/rheumatology/keac077.

[310]Moe SM. Chronic kidney disease-mineral bone disorder[J].Perit Dial Int,2008,28(2 Suppl):5-10.DOI:10.1177/089686080802802S02.

[311]Yamada S, Nakano T. Role of chronic kidney disease(CKD)-mineral and bone disorder(MBD) in the pathogenesis of cardiovascular disease in CKD[J]. J Atheroscler Thromb, 2023, 30[8]: 835-850. DOI: 10.5551/jat.RV22006.

[312]国家肾脏疾病临床医学研究中心.中国慢性肾脏病矿物质和骨异常诊治指南概要[J].肾脏病与透析肾移植杂志，2019, 28(1): 52-57. DOI: 10.3969/j.issn.1006-298X.2019.01.012.

[313]Khan SR. Crystal-induced inflammation of the kidneys:results from human studies, animal models, and tissue-culture studies[J]. Clin Exp Nephrol, 2004, 8(2): 75-88.DOI: 10.1007/s10157-004-0292-0.

[314]Da J, Xie X, Wolf M, et al. Serum phosphorus and progression of CKD and mortality: a meta-analysis of cohort studies[J]. Am J Kidney Dis, 2015, 66(2): 258-265.DOI:10.1053/j.ajkd.2015.01.009.

[315]Zoccali C, Ruggenenti P, Perna A, et al. Phosphate may promote CKD progression and attenuate renoprotective effect of ACE inhibition[J]. J Am Soc Nephrol, 2011,22(10):1923-1930.DOI:10.1681/ASN.2011020175.

[316]Bellasi A, Mandreoli M, Baldrati L, et al. Chronic kidney disease progression and outcome according to serum phosphorus in mild-to-moderate kidney dysfunction[J].Clin J Am Soc Nephrol, 2011, 6(4): 883-891. DOI: 10.

2215/CJN.07810910.

[317]De Nicola L, Provenzano M, Chiodini P,et al. Epidemiology of low-proteinuric chronic kidney disease in renal clinics[J]. PLoS One, 2017, 12(2): e0172241. DOI: 10.1371/journal.pone.0172241.

[318]Kidney Disease: Improving Global Outcomes(KDIGO)CKD- MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation,prevention, and treatment of chronic kidney disease-mineral and bone disorder(CKD-MBD)[J]. Kidney Int Suppl[2011),2017,7(1):1-59.DOI:10.1016/j.kisu.2017.04.001.

[319]Shinaberger CS, Greenland S, Kopple JD, et al. Is controlling phosphorus by decreasing dietary protein intake beneficial or harmful in persons with chronic kidney disease?[J]. Am J Clin Nutr, 2008, 88(6): 1511-1518.DOI:10.3945/ajcn.2008.26665.

[320]Block GA, Wheeler DC, Persky MS, et al. Effects of phosphate binders in moderate CKD[J]. J Am Soc Nephrol,2012,23(8):1407-1415.DOI:10.1681/ASN.2012030223.

[321]Hill KM, Martin BR, Wastney ME, et al. Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease[J]. Kidney Int, 2013,83(5):959-966.DOI:10.1038/ki.2012.403.

[322]London GM, Guérin AP, Marchais SJ,et al. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality[J]. Nephrol Dial Transplant,2003,18(9):1731-1740.DOI:10.1093/ndt/gfg414.

[323]de Francisco AL, Leidig M, Covic AC, et al. Evaluation of calcium acetate/magnesium carbonate as a phosphate binder compared with sevelamer hydrochloride in haemodialysis patients: a controlled randomized study(CALMAG study) assessing efficacy and tolerability[J].Nephrol Dial Transplant, 2010, 25(11): 3707-3717. DOI:10.1093/ndt/gfq292.

[324] Di Iorio B, Bellasi A, Russo D, et al. Mortality in kidney disease patients treated with phosphate binders: a randomized study[J]. Clin J Am Soc Nephrol, 2012, 7(3):487-493.DOI: 10.2215/CJN.03820411.

[325] Di Iorio B, Molony D, Bell C, et al. Sevelamer versus calcium carbonate in incident hemodialysis patients:results of an open-label 24-month randomized clinical trial[J].Am J Kidney Dis,2013,62(4):771-778.DOI:10.1053/j.ajkd.2013.03.023.

[326]Chertow GM, Burke SK, Dillon MA, et al. Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients[J].Nephrol Dial Transplant, 1999, 14(12): 2907-2914. DOI:10.1093/ndt/14.12.2907.

[327]Chertow GM, Burke SK, Raggi P, et al. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients[J].Kidney Int,2002,

62(1):245-252.DOI:10.1046/j.1523-1755.2002.00434.x.

[328]Brandenburg VM, Schlieper G, Heussen N, et al.Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study[J]. Nephrol Dial Transplant, 2010, 25(8): 2672-2679.DOI:10.1093/ndt/gfq053.

[329] Hu L, Napoletano A, Provenzano M, et al. Mineral bone disorders in kidney disease patients: the ever-current topic[J].Int J Mol Sci,2022,23(20):12223.DOI:10.3390/ijms232012223.

[330]Coburn JW, Maung HM, Elangovan L,et al. Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4[J]. Am J Kidney Dis, 2004, 43(5):877-890.DOI:10.1053/j.ajkd.2004.01.012.

[331]Hamdy NA, Kanis JA, Beneton MN, et al. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure[J]. BMJ, 1995, 310(6976):358-363.DOI:10.1136/bmj.310.6976.358.

[332]Fishbane S, Chittineni H, Packman M, et al. Oral paricalcitol in the treatment of patients with CKD and proteinuria: a randomized trial[J]. Am J Kidney Dis,2009,54(4):647-652.DOI:10.1053/j.ajkd.2009.04.036.

[333]Wang AY,Fang F,Chan J,et al.Effect of paricalcitol on left ventricular mass and function in CKD--the OPERA trial[J].J Am Soc Nephrol, 2014, 25(1): 175-186. DOI: 10.1681/ASN.2013010103.

[334]Thadhani R, Appelbaum E, Pritchett Y,et al. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial[J].JAMA,2012,307(7):674-684.DOI:10.1001/jama.2012.120.

[335]Parfrey PS, Chertow GM, Block GA, et al. The clinical course of treated hyperparathyroidism among patients receiving hemodialysis and the effect of cinacalcet: the EVOLVE trial[J]. J Clin Endocrinol Metab, 2013, 98(12):4834-4844.DOI:10.1210/jc.2013-2975.

[336]Block GA, Bushinsky DA, Cheng S, et al. Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: a randomized clinical trial[J].JAMA, 2017, 317(2): 156-164. DOI: 10.1001/jama.2016.19468.

[337]Parfrey PS, Drüeke TB, Block GA, et al. The effects of cinacalcet in older and younger patients on hemodialysis:the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events(EVOLVE) trial[J]. Clin J Am Soc Nephrol, 2015, 10(5): 791-799. DOI: 10.2215/CJN.07730814.

[338]Zheng CM, Hsu YH, Wu CC, et al. Osteoclast-released Wnt-10b underlies cinacalcet related bone improvement in chronic kidney disease[J]. Int J Mol Sci, 2019, 20(11):2800.DOI:10.3390/ijms20112800.

表12009版牛津证据分级系统
推荐强度	证据水平	定义(以治疗/预防为例)
A	1a 1b 1c	纳入一致性较高的随机对照试验的系统评价
A	1a 1b 1c	置信区间较窄的单个随机对照试验
A	1a 1b 1c	“全或无”证据(实施治疗前,所有患者均死亡;实施治疗后,有患者能存活。或实施治疗前,部分患者死亡; 实施治疗后,无患者死亡)
B	2a 2b 2c 3a 3b	纳入一致性较高的队列研究的系统评价
B	2a 2b 2c 3a 3b	单个队列研究(或低质量随机对照试验)
B	2a 2b 2c 3a 3b	生态学研究
B	2a 2b 2c 3a 3b	纳入一致性较高的病例对照研究的系统评价
B	2a 2b 2c 3a 3b	单个病例对照研究
C	4	病例系列(或低质量队列研究或病例对照研究)
D	5	专家意见

表 2
CKD分期 $\begin{aligned}{\left[\, eGFR\,,ml\cdot min^{-1}\cdot\left(\, 1.73\, m^2\right)^{-1}\right)}\,\right]\end{aligned}$$	尿白蛋白分期	尿白蛋白分期	尿白蛋白分期
CKD分期 $\begin{aligned}{\left[\, eGFR\,,ml\cdot min^{-1}\cdot\left(\, 1.73\, m^2\right)^{-1}\right)}\,\right]\end{aligned}$$	A1 (ACR<30 mg/g 或 $<3 mg/ mmol$ , 正常或轻度增加)	A2 (ACR 30~299 mg/g 或 $3\sim 29 mg/ mmol$ , 中度增加)	A3 (ACR≥300 mg/g 或≥30 mg/mmol, 显著增加)
G1(eGFR≥90,正常或升高)	1	1	3
G2(eGFR 60~89,轻度减退)	1	1	3
G3a(eGFR 45~59,轻度至中度减退)	1	2	3
G3b(eGFR 30~44,中度至重度减退)	2	3	3
G4(eGFR 15~29,重度减退)	3	3	4+
G5(eGFR<15,肾衰竭)	4+	4+	4+

表2不同eGFR水平CKD患者的降糖药物使用注意事项
eGFR $$\left[{ ml}\cdot{ min}^{-1}\cdot(1.73\,{ m}^{2})^{-1}\right]$$	一线降糖治疗方案	增加药物以控制血糖
eGFR≥45	二甲双胍+SGLT2i	首选GLP-1RA;其他可选择降糖药物有DPP-4抑制剂、胰岛素、磺脲类药物、噻唑烷二酮、α-葡萄糖苷酶抑制剂
30≤eGFR<45	二甲双胍+SGLT2i,但二甲双胍需减少剂量	同上
20≤eGFR<30	停用二甲双胍,可使用SGLT2i	同上
15≤eGFR<20	SGLT2i不建议作为起始用药	同上
eGFR<15或透析	停用,若已使用SGLT2i可继续维持使用至透析或肾移植	较合适的降糖药物有DPP-4抑制剂、胰岛素、噻唑烷二酮;也可使用磺脲类药物和 $\alpha$ -葡萄糖苷酶抑制剂

引用 / 出处

中国研究型医院学会. 延缓慢性肾脏病进展临床管理指南（2025年版）[S/OL]. 2025.

延缓慢性肾脏病进展临床管理指南（2025年版）

一、指南制定背景

二、指南制定方法

三、CKD患者的进展风险评估和临床管理目标

2.CKD进展风险评估:

推荐意见

四、延缓 CKD进展的方法

(一)延缓 CKD进展的综合性管理策略

推荐意见

(二)改善生活方式和纠正急性可逆性因素

推荐意见

2.运动和控制体重:

推荐意见

3.戒烟:

推荐意见

4.纠正可逆性因素:

推荐意见

(三)积极控制原发病

推荐意见

(四)积极控制CKD进展相关的危险因素

3.积极治疗蛋白尿:

推荐意见

(五)延缓CKD进展的药物治疗

推荐意见

推荐意见

2. SGLT2i:

3. GLP-1RA:

推荐意见

4.中医药治疗:

推荐意见

(六)积极管理合并症、并发症，延缓CKD进展

推荐意见

1.CKD合并高血压:

推荐意见

2.CKD患者CVD风险管理:

(1)积极防治动脉粥样硬化性CVD(atherosclerotic cardiovascular disease,ASCVD):

推荐意见

3.CKD合并糖尿病:

推荐意见

4.CKD合并贫血:

推荐意见

5.水电解质和酸碱失衡:

推荐意见

(1)CKD合并高钾血症:

推荐意见

(2)CKD合并代谢性酸中毒:

7.合并CKD-MBD:

推荐意见

五、总结和展望

参考文献

相关指南

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