Article(id=1324050734974640148, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324050669933572771, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202512358, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1766592000000, receivedDateStr=2025-12-25, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793607894890, onlineDateStr=2026-11-02, pubDate=1778342400000, pubDateStr=2026-05-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793607894890, onlineIssueDateStr=2026-11-02, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793607894890, creator=13701087609, updateTime=1793607894890, updator=13701087609, issue=Issue{id=1324050669933572771, tenantId=1146029695717560320, journalId=1227665162245664772, year='2026', volume='53', issue='9', pageStart='1537', pageEnd='1728', issueExtLink='null', onlineDate='null', pubDate='1778342400000', pubDateStr='2026-05-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793607879384, creator='13701087609', updateTime=1793670100562, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1324311644528050975, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324050669933572771, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1324311644528050976, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324050669933572771, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1543, endPage=1548, ext={EN=ArticleExt(id=1324050735385681941, articleId=1324050734974640148, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Longitudinal association between chronic kidney disease and the risk of new onset knee osteoarthritis based on CHARLS data, columnId=1240413921954295836, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the longitudinal association of baseline chronic kidney disease (CKD) status and estimated glomerular filtration rate (eGFR) levels with the risk of incident knee osteoarthritis (KOA) among middle-aged and older Chinese adults, and to provide epidemiological evidence for the pathological crosstalk of the “kidney-bone axis”.

Methods

This study utilized longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS, 2011—2018). A total of 4 182 participants aged 45 years and older, free of KOA at baseline and with complete covariate data, were included. Missing data were handled using multiple imputation. The association between baseline CKD [defined as eGFR <60 ml/ (min·1.73m2) ] and incident KOA was analyzed using Kaplan-Meier survival curves and multivariatble Cox proportional hazards regression models. Restricted cubic spline (RCS) modeling was employed to examine the dose-response relationship between eGFR levels and KOA risk. Subgroup analyses and lag analyses were conducted to verify the robustness of the results.

Results

During an average follow-up of 4 years, the cumulative incidence of incident KOA was significantly higher in the CKD group compared to the non-CKD group (Log-rank P<0.001). Multivariable Cox regression analysis demonstrated that, after adjusting for demographics, lifestyle factors, body mass index (BMI), and chronic comorbidities, baseline CKD remained an independent risk factor for incident KOA [hazard ratio (HR) =1.82, 95% confidence interval (CI) : 1.30-2.55, P<0.001]. RCS analysis revealed no significant linear or non-linear dose-response relationship between baseline eGFR levels and KOA risk in the total population (P for overall association =0.348), suggesting a pathological threshold effect of renal function on KOA. Sensitivity analyses confirmed the robustness of these findings.

Conclusion

CKD is an independent risk factor for incident KOA among middle-aged and older Chinese adults, characterized by a potential pathogenic threshold effect at an eGFR of <60 ml/ (min·1.73m2). Integrated management of joint health in CKD patients should be prioritized, employing early screening to achieve comprehensive prevention and treatment of “kidney-bone/joint” comorbidities.

, authors=En-yan XUE1, 2, Tian-ci GUO1, 2, Wei-yong WU1, 2, Bo-wen SONG1, 2, Chen GUO1, 2, Ai-feng LIU1, 2, authorsList=En-yan XUE, Tian-ci GUO, Wei-yong WU, Bo-wen SONG, Chen GUO, Ai-feng LIU, authorCompany=null, correspAuthors=Ai-feng LIU, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1324050736945963042, articleId=1324050734974640148, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=基于CHARLS数据的慢性肾脏病与新发膝骨关节炎风险的纵向关联研究, columnId=1228016567632462653, journalTitle=现代预防医学, columnName=流行病与统计方法, runingTitle=null, highlight=null, articleAbstract=
目的

探讨中国中老年人群基线慢性肾脏病(chronic kidney disease,CKD)状态及肾小球滤过率(estimated glomerular filtration rate,eGFR)水平与新发膝关节骨关节炎(knee osteoarthritis,KOA)风险的纵向关联,验证“肾-骨轴”病理串扰在流行病学层面的体现。

方法

基于中国健康与养老追踪调查2011—2018年纵向数据,纳入基线无KOA且相关协变量完整的45岁及以上受访者4 182名。采用多重插补法处理缺失数据。应用Kaplan-Meier生存曲线及多因素Cox比例风险回归模型分析基线CKD[eGFR<60 ml/(min·1.73m2)]与新发KOA的关联。采用限制性立方样条(restricted cubic splines,RCS)模型分析eGFR水平与KOA风险的剂量-反应关系。进行亚组分析及滞后分析以验证结果稳健性。

结果

平均4年的随访期间,CKD组新发KOA累积发病率显著高于非CKD组(Log-rank P<0.001)。Cox回归分析显示,在调整了人口学特征、生活方式、身体质量指数(body mass index,BMI)及慢性病共病等混杂因素后,基线CKD是新发KOA的独立危险因素,CKD患者发生KOA的风险是非CKD人群的1.82倍(HR=1.82,95% CI:1.30~2.55,P<0.001)。RCS分析显示,全人群中基线eGFR水平与KOA风险之间未见显著的线性或非线性剂量-反应关系(总趋势 P=0.348),提示肾功能对KOA的影响具有病理阈值效应特征。敏感性分析证实上述结果稳健。

结论

CKD是中国中老年人新发KOA的独立危险因素,其致病风险可能存在以eGFR<60 ml/(min·1.73m2)为界点的阈值效应。应重视CKD患者的关节健康管理,通过早期筛查实现“肾-骨/关节”共病的综合防治。

, authors=薛恩炎1, 2, 郭天赐1, 2, 吴维勇1, 2, 宋博文1, 2, 国琛1, 2, 刘爱峰1, 2, authorsList=薛恩炎, 郭天赐, 吴维勇, 宋博文, 国琛, 刘爱峰, authorCompany=null, correspAuthors=刘爱峰, authorNote=

薛恩炎(1999—),男,博士在读,研究方向:中医骨伤科学

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刘爱峰,E-mail:
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薛恩炎(1999—),男,博士在读,研究方向:中医骨伤科学

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薛恩炎(1999—),男,博士在读,研究方向:中医骨伤科学

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Front Nutr, 2025, 12: 1533966., articleTitle=Body roundness index and the risk of knee osteoarthritis:evidence from the China Health and Retirement Longitudinal Study, refAbstract=null)], funds=[Fund(id=1324050748958449761, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, awardId=82474538, language=CN, fundingSource=国家自然科学基金面上项目(82474538), fundOrder=null, country=null), Fund(id=1324050749033947234, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, awardId=4042502041, language=CN, fundingSource=天津中医药大学第一附属医院创新团队培育计划项目(4042502041), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1324050737281507363, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, xref=1., ext=[AuthorCompanyExt(id=1324050737289895972, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, companyId=1324050737281507363, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China), AuthorCompanyExt(id=1324050737294090277, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, companyId=1324050737281507363, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.天津中医药大学第一附属医院,天津 300381)]), AuthorCompany(id=1324050737382170662, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, xref=2., ext=[AuthorCompanyExt(id=1324050737390559271, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, companyId=1324050737382170662, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.中医国家临床医学研究中心,天津 300381)])], figs=[ArticleFig(id=1324050745997271126, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, language=EN, label=Figure 1, caption=Kaplan-Meier survival curve for CKD and new-onset KOA, figureFileSmall=VTkez55UMQN+ZWZZKdr8DQ==, figureFileBig=TTy9cvJXtMALC3q+t2kxiQ==, tableContent=null), ArticleFig(id=1324050746399924311, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, language=CN, label=图1, caption=CKD与新发KOA的K-M生存曲线, figureFileSmall=VTkez55UMQN+ZWZZKdr8DQ==, figureFileBig=TTy9cvJXtMALC3q+t2kxiQ==, tableContent=null), ArticleFig(id=1324050748232835161, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, language=EN, label=Figure 2, caption=Dose-response relationship between baseline eGFR levels and risk of incident KOA, figureFileSmall=vlxP99SjrGRdBCC02EECsw==, figureFileBig=Kj4EyDw8tedx4NE4N7Xb8A==, tableContent=null), ArticleFig(id=1324050748312526938, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, language=CN, label=图2, caption=基线 eGFR 水平与新发 KOA 风险的剂量-反应关系

注:模型调整了年龄、性别、教育程度、婚姻状况、居住地、吸烟、饮酒、BMI 及慢性病共病数量;横坐标为eGFR[ml/(min·1.73m2)],纵坐标为风险比(HR,对数标度);实线表示 HR 的点估计值,虚线及阴影区域表示95%置信区间;水平虚线表示参照水平(HR=1)。

, figureFileSmall=vlxP99SjrGRdBCC02EECsw==, figureFileBig=Kj4EyDw8tedx4NE4N7Xb8A==, tableContent=null), ArticleFig(id=1324050748379635803, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, language=EN, label=Figure 3, caption=Subgroup analysis of the association between CKD and the risk of incident KOA, figureFileSmall=omEIgRNFofPUZzR2M7yxzg==, figureFileBig=9NSqPYtIkm+L7Fz2kdE/Zw==, tableContent=null), ArticleFig(id=1324050748463521884, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, language=CN, label=图3, caption=CKD与新发KOA风险关联的分层分析, figureFileSmall=omEIgRNFofPUZzR2M7yxzg==, figureFileBig=9NSqPYtIkm+L7Fz2kdE/Zw==, tableContent=null), ArticleFig(id=1324050748534825053, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, language=EN, label=Table 1, caption=

Baseline characteristics of CKD patients and non-CKD patients [(),n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总计 (n=4 182)非CKD组 (n=3 934)CKD组 (n=248)统计量t/χ2值P值
年龄(岁)57.7 ±8.7757.5 ±8.5861.3 ±10.69-5.56<0.001
性别1.100.293
男性2 099 (50.2)1 966 (50.0)133 (53.6)
女性2 083 (49.8)1 968 (50.0)115 (46.4)
婚姻状况4.710.030
已婚3 810 (91.1)3 594 (91.4)216 (87.1)
单身/离异/丧偶372 (8.9)340 (8.6)32 (12.9)
吸烟状况3.500.062
不吸烟2 454 (58.7)2 323 (59.1)131 (52.8)
吸烟1 727 (41.3)1 610 (40.9)117 (47.2)
饮酒状况0.760.384
不饮酒2 511 (60.1)2 369 (60.3)142 (57.3)
饮酒1 668 (39.9)1 562 (39.7)106 (42.7)
教育水平2.080.555
文盲1 061 (25.4)1 002 (25.5)59 (23.8)
小学1 607 (38.4)1 504 (38.2)103 (41.5)
中学975 (23.3)924 (23.5)51 (20.6)
高中及以上539 (12.9)504 (12.8)35 (14.1)
居住地0.980.323
农村2 677 (64.0)2 526 (64.2)151 (60.9)
城市1 505 (36.0)1 408 (35.8)97 (39.1)
BMI4.810.186
正常2 235 (62.9)2 119 (63.2)116 (58.3)
低体重204 (5.7)187 (5.6)17 (8.5)
超重950 (26.7)891 (26.6)59 (29.6)
肥胖164 (4.6)157 (4.7)7 (3.5)
体力活动0.660.718
低活跃482 (28.3)451 (28.1)31 (31.3)
中等活跃192 (11.3)180 (11.2)12 (12.1)
高活跃1 029 (60.4)973 (60.7)56 (56.6)
慢性病数量(种)33.19<0.001
02 079 (49.7)1 995 (50.7)84 (33.9)
11 229 (29.4)1 147 (29.2)82 (33.1)
≥2874 (20.9)792 (20.1)82 (33.1)
eGFR[ml/(min·1.73m2)]93.43 ±14.1294.50 ±12.6376.57 ±22.9112.13<0.001
), ArticleFig(id=1324050748648071262, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, language=CN, label=表1, caption=

CKD患者与非CKD患者人群的基线特征[(),n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总计 (n=4 182)非CKD组 (n=3 934)CKD组 (n=248)统计量t/χ2值P值
年龄(岁)57.7 ±8.7757.5 ±8.5861.3 ±10.69-5.56<0.001
性别1.100.293
男性2 099 (50.2)1 966 (50.0)133 (53.6)
女性2 083 (49.8)1 968 (50.0)115 (46.4)
婚姻状况4.710.030
已婚3 810 (91.1)3 594 (91.4)216 (87.1)
单身/离异/丧偶372 (8.9)340 (8.6)32 (12.9)
吸烟状况3.500.062
不吸烟2 454 (58.7)2 323 (59.1)131 (52.8)
吸烟1 727 (41.3)1 610 (40.9)117 (47.2)
饮酒状况0.760.384
不饮酒2 511 (60.1)2 369 (60.3)142 (57.3)
饮酒1 668 (39.9)1 562 (39.7)106 (42.7)
教育水平2.080.555
文盲1 061 (25.4)1 002 (25.5)59 (23.8)
小学1 607 (38.4)1 504 (38.2)103 (41.5)
中学975 (23.3)924 (23.5)51 (20.6)
高中及以上539 (12.9)504 (12.8)35 (14.1)
居住地0.980.323
农村2 677 (64.0)2 526 (64.2)151 (60.9)
城市1 505 (36.0)1 408 (35.8)97 (39.1)
BMI4.810.186
正常2 235 (62.9)2 119 (63.2)116 (58.3)
低体重204 (5.7)187 (5.6)17 (8.5)
超重950 (26.7)891 (26.6)59 (29.6)
肥胖164 (4.6)157 (4.7)7 (3.5)
体力活动0.660.718
低活跃482 (28.3)451 (28.1)31 (31.3)
中等活跃192 (11.3)180 (11.2)12 (12.1)
高活跃1 029 (60.4)973 (60.7)56 (56.6)
慢性病数量(种)33.19<0.001
02 079 (49.7)1 995 (50.7)84 (33.9)
11 229 (29.4)1 147 (29.2)82 (33.1)
≥2874 (20.9)792 (20.1)82 (33.1)
eGFR[ml/(min·1.73m2)]93.43 ±14.1294.50 ±12.6376.57 ±22.9112.13<0.001
), ArticleFig(id=1324050748727763039, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, language=EN, label=Table 2, caption=

Cox proportional hazards regression analysis of the association between CKD and the risk of incident KOA

, figureFileSmall=null, figureFileBig=null, tableContent=
变量Model 1 (未调整)Model 2 (部分调整)Model 3 (完全调整)
HR(95%CI)P值HR(95%CI)P值HR(95%CI)P值
CKD
否———
是1.86(1.34~2.59)<0.0011.95(1.39~2.72)<0.0011.82(1.30~2.55)<0.001
), ArticleFig(id=1324050748811649120, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050734974640148, language=CN, label=表2, caption=

CKD与新发KOA风险关联的Cox比例风险回归分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变量Model 1 (未调整)Model 2 (部分调整)Model 3 (完全调整)
HR(95%CI)P值HR(95%CI)P值HR(95%CI)P值
CKD
否———
是1.86(1.34~2.59)<0.0011.95(1.39~2.72)<0.0011.82(1.30~2.55)<0.001
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基于CHARLS数据的慢性肾脏病与新发膝骨关节炎风险的纵向关联研究
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薛恩炎 1, 2 , 郭天赐 1, 2 , 吴维勇 1, 2 , 宋博文 1, 2 , 国琛 1, 2 , 刘爱峰 1, 2
现代预防医学 | 流行病与统计方法 2026,53(9): 1543-1548
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现代预防医学 |流行病与统计方法 2026 , 53 (9) : 1543 -1548
基于CHARLS数据的慢性肾脏病与新发膝骨关节炎风险的纵向关联研究
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薛恩炎1, 2, 郭天赐1, 2, 吴维勇1, 2, 宋博文1, 2, 国琛1, 2, 刘爱峰1, 2
作者信息
  • 1.天津中医药大学第一附属医院,天津 300381
  • 2.中医国家临床医学研究中心,天津 300381
通讯作者:
刘爱峰,E-mail:
作者简介:

薛恩炎(1999—),男,博士在读,研究方向:中医骨伤科学

Longitudinal association between chronic kidney disease and the risk of new onset knee osteoarthritis based on CHARLS data
En-yan XUE1, 2, Tian-ci GUO1, 2, Wei-yong WU1, 2, Bo-wen SONG1, 2, Chen GUO1, 2, Ai-feng LIU1, 2
Affiliations
  • First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
出版时间: 2026-05-10 doi: 10.20043/j.cnki.MPM.202512358
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目的

探讨中国中老年人群基线慢性肾脏病(chronic kidney disease,CKD)状态及肾小球滤过率(estimated glomerular filtration rate,eGFR)水平与新发膝关节骨关节炎(knee osteoarthritis,KOA)风险的纵向关联,验证“肾-骨轴”病理串扰在流行病学层面的体现。

方法

基于中国健康与养老追踪调查2011—2018年纵向数据,纳入基线无KOA且相关协变量完整的45岁及以上受访者4 182名。采用多重插补法处理缺失数据。应用Kaplan-Meier生存曲线及多因素Cox比例风险回归模型分析基线CKD[eGFR<60 ml/(min·1.73m2)]与新发KOA的关联。采用限制性立方样条(restricted cubic splines,RCS)模型分析eGFR水平与KOA风险的剂量-反应关系。进行亚组分析及滞后分析以验证结果稳健性。

结果

平均4年的随访期间,CKD组新发KOA累积发病率显著高于非CKD组(Log-rank P<0.001)。Cox回归分析显示,在调整了人口学特征、生活方式、身体质量指数(body mass index,BMI)及慢性病共病等混杂因素后,基线CKD是新发KOA的独立危险因素,CKD患者发生KOA的风险是非CKD人群的1.82倍(HR=1.82,95% CI:1.30~2.55,P<0.001)。RCS分析显示,全人群中基线eGFR水平与KOA风险之间未见显著的线性或非线性剂量-反应关系(总趋势 P=0.348),提示肾功能对KOA的影响具有病理阈值效应特征。敏感性分析证实上述结果稳健。

结论

CKD是中国中老年人新发KOA的独立危险因素,其致病风险可能存在以eGFR<60 ml/(min·1.73m2)为界点的阈值效应。应重视CKD患者的关节健康管理,通过早期筛查实现“肾-骨/关节”共病的综合防治。

慢性肾脏病  /  膝骨关节炎  /  肾小球滤过率  /  纵向队列研究  /  中国健康与养老追踪调查
Objective

To investigate the longitudinal association of baseline chronic kidney disease (CKD) status and estimated glomerular filtration rate (eGFR) levels with the risk of incident knee osteoarthritis (KOA) among middle-aged and older Chinese adults, and to provide epidemiological evidence for the pathological crosstalk of the “kidney-bone axis”.

Methods

This study utilized longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS, 2011—2018). A total of 4 182 participants aged 45 years and older, free of KOA at baseline and with complete covariate data, were included. Missing data were handled using multiple imputation. The association between baseline CKD [defined as eGFR <60 ml/ (min·1.73m2) ] and incident KOA was analyzed using Kaplan-Meier survival curves and multivariatble Cox proportional hazards regression models. Restricted cubic spline (RCS) modeling was employed to examine the dose-response relationship between eGFR levels and KOA risk. Subgroup analyses and lag analyses were conducted to verify the robustness of the results.

Results

During an average follow-up of 4 years, the cumulative incidence of incident KOA was significantly higher in the CKD group compared to the non-CKD group (Log-rank P<0.001). Multivariable Cox regression analysis demonstrated that, after adjusting for demographics, lifestyle factors, body mass index (BMI), and chronic comorbidities, baseline CKD remained an independent risk factor for incident KOA [hazard ratio (HR) =1.82, 95% confidence interval (CI) : 1.30-2.55, P<0.001]. RCS analysis revealed no significant linear or non-linear dose-response relationship between baseline eGFR levels and KOA risk in the total population (P for overall association =0.348), suggesting a pathological threshold effect of renal function on KOA. Sensitivity analyses confirmed the robustness of these findings.

Conclusion

CKD is an independent risk factor for incident KOA among middle-aged and older Chinese adults, characterized by a potential pathogenic threshold effect at an eGFR of <60 ml/ (min·1.73m2). Integrated management of joint health in CKD patients should be prioritized, employing early screening to achieve comprehensive prevention and treatment of “kidney-bone/joint” comorbidities.

Chronic kidney disease  /  Knee osteoarthritis  /  Glomerular filtration rate  /  Longitudinal cohort study  /  China Health and Retirement Longitudinal Study
薛恩炎, 郭天赐, 吴维勇, 宋博文, 国琛, 刘爱峰. 基于CHARLS数据的慢性肾脏病与新发膝骨关节炎风险的纵向关联研究. 现代预防医学, 2026 , 53 (9) : 1543 -1548 . DOI: 10.20043/j.cnki.MPM.202512358
En-yan XUE, Tian-ci GUO, Wei-yong WU, Bo-wen SONG, Chen GUO, Ai-feng LIU. Longitudinal association between chronic kidney disease and the risk of new onset knee osteoarthritis based on CHARLS data[J]. Modern Preventive Medicine, 2026 , 53 (9) : 1543 -1548 . DOI: 10.20043/j.cnki.MPM.202512358
膝关节骨关节炎(knee osteoarthritis, KOA)是一种以关节软骨进行性退变、慢性滑膜炎症以及病理性软骨下骨重塑为特征的慢性关节疾病[1],也是导致全球中老年人慢性疼痛和肢体致残的主要原因之一。最新对2021年全球疾病负担的研究结果显示,全球膝骨关节炎患者累积已超过3.747亿,预计到2045年患者将达到6.581亿[2]。在中国,随着人口老龄化进程的加速,KOA给医疗系统和社会经济带来的负担尤为沉重,流行病学调查显示,我国KOA的患病率已经高达18%,随着年龄增长,患病率显著增加,60岁以上人群患病率达到了50%,受累人数庞大且呈逐年上升趋势[3]。尽管既往研究已证实高龄、肥胖、女性、关节损伤及遗传因素等是KOA的重要危险因素[4-8],但这些传统因素尚不足以完全解释其发病机制。近年来,越来越多的证据提示KOA并非单纯的“磨损性”疾病,而是一种与全身代谢稳态密切相关的复杂病理过程[9],探索其潜在的代谢性危险因素及共病机制已成为当前研究的热点。
与此同时,慢性肾脏病(chronic kidney disease,CKD)作为另一大全球性公共卫生挑战,其流行态势同样严峻。流行病学调查显示,中国CKD的患病率已达8.2%,并呈快速攀升趋势[10]。近年来,“肾-骨轴”这一概念在代谢性骨病研究中备受关注[11]。传统医学理论素有“肾主骨”之经典理论[12],而现代医学研究也证实,肾脏与骨骼系统之间存在复杂的内分泌调节和代谢串扰[13]。CKD患者常伴随矿物质与骨代谢异常、钙磷代谢紊乱、维生素D缺乏及全身性慢性炎症状态[14-16],这些病理生理改变不仅影响全身骨骼矿化,更能破坏膝关节软骨下骨的重塑平衡与微环境稳态,进而加速膝骨关节炎的发生和进展[17]。
然而,目前关于CKD与KOA关联的研究较少,且多集中于膝关节置换术后并发症的研究,缺乏基于人群的大样本纵向队列证据。此外,基线肾功能水平[如估算肾小球滤过率(estimated glomerulare filtration rate,eGFR]与KOA发病风险之间是否存在明确的剂量-反应关系,也鲜有研究,这限制了我们对疾病周期风险梯度的认识。基于此,本研究利用具有全国代表性的中国健康与养老追踪调查(China Health and Retirement Longitudinal Study,CHARLS)数据,旨在通过前瞻性队列设计,验证“肾-骨轴”理论在KOA流行病学中的体现。本研究将系统分析基线CKD状态对新发KOA风险的影响,并进一步利用限制性立方样条(restricted cubic splines,RCS)模型探索eGFR水平与KOA风险的量效关系,旨在为KOA的早期危险因素筛查、跨学科综合防治提供新的流行病学依据。
本研究数据来源于CHARLS。该调查是一项覆盖中国28个省份、具有全国代表性的中老年人群纵向调查[18]。本研究以2011年基线调查为起点,选取2013、2015及2018年作为随访节点。纳入标准:(1)基线年龄 ≥ 45岁;设定该年龄截点主要基于以下两点考量:一是,CHARLS的研究设计旨在代表中国45岁及以上的中老年人群,以系统反映老龄化进程中的健康特征;二是,原发性KOA具有显著的年龄依赖性,其发病率在45岁以后呈指数级上升;(2)具有完整的肾功能血液检测数据(血肌酐)及相关协变量数据。排除标准:(1)基线已确诊关节炎或报告患有膝关节疼痛者;(2)随访期间失访或缺乏有效结局数据者。最终纳入分析4 182人。排除的3 220名失访者(失访率43.5%)与纳入人群在性别、受教育程度及居住地等核心基线特征上的标准化均值差(standardized mean difference,SMD)均小于0.2,提示样本缩减未引入明显的系统性选择偏倚。尽管失访组的平均年龄略高于纳入组(SMD=0.248),鉴于本研究在多变量模型中已对年龄进行了充分调整,该差异不太可能引入严重的系统性偏倚。所有受访者均已签署知情同意书,CHARLS项目已获得北京大学生物医学伦理委员会批准。
采用2009年CKD流行病学合作组(CKD-EPI)公式计算eGFR[19]。该公式已被证实在不同人群中具有良好的适用性,具体计算公式如下:
公式中Scr为血肌酐值(mg/dl),Age为年龄(岁)。κ 值:女性为0.7,男性为0.9。α 值:女性为-0.329,男性为-0.411。min(Scr/κ, 1) 表示 Scr/κ 与1之间的较小值,max(Scr/κ, 1)表示Scr/κ与1之间的较大值。
依据KDIGO指南,CKD定义为eGFR<60ml/(min·1.73m2)[20]。本研究将CKD作为二分类变量(是/否),eGFR作为连续变量纳入分析。
研究结局为随访期间新发的KOA。依据CHARLS问卷,若受访者在随访期间自我报告被医生诊断为关节炎(arthritis)且伴有膝关节疼痛(knee pain),则定义为发生KOA事件。随访时间定义为从基线调查至首次确诊KOA、失访或随访结束(2018年)的时间间隔。
基线收集的潜在混杂因素:(1)人口学特征:年龄、性别、受教育程度(文盲、小学、中学、高中及以上)、婚姻状况(已婚、单身/离异/丧偶)、居住地(城市/农村)。(2)生活方式:吸烟状况、饮酒状况、体力活动[依据国际体力活动问卷标准,根据代谢当量(METs)将受访者的体力活动水平分为三类:低活跃、中等活跃和高活跃[21]]。(3)健康状况:身体质量指数[(body mass index,BMI),分为低体重、正常、超重/肥胖]、慢性病共病数量(0种、1种、≥2种),其中慢性病包括高血压、糖尿病、心脏病、脑卒中、肺部疾病等10种常见疾病。
通过R(版本4.3.3)软件进行统计分析。符合正态分布的连续变量以(均数±标准差)表示,组间比较采用t检验;分类变量以频数(百分比)表示,组间比较采用χ2检验。为最大程度减少信息损失,采用多重插补法对缺失协变量及eGFR进行插补(插补次数m=5),并基于插补后的数据集进行汇总分析。采用Kaplan-Meier法绘制生存曲线,并用Log-rank检验比较CKD组与非CKD组的KOA累积发病率差异。构建多因素Cox比例风险回归模型计算风险比及其95%置信区间,采用RCS模型分析eGFR水平与KOA风险的剂量-反应关系,节点设为3个。随后按年龄、性别、BMI等特征进行亚组分析,并进行交互作用检验以评估结果的稳健性。双侧检验,检验水准α=0.05。
本研究共纳入4 182名受访者,其中基线患有CKD者248例(5.93%)。如表1所示,CKD组平均年龄显著高于非CKD组(61.3岁 vs. 57.5岁,P<0.001),单身/离异/丧偶比例更高(12.9% vs. 8.6%,P=0.022),其余人口学及生活方式特征差异无统计学意义(P>0.05)。
如图1所示,Kaplan- Meier曲线显示,CKD组新发KOA累积发病率显著高于非CKD组(Log-rank P<0.001)。Cox回归分析提示,在完全调整混杂因素后(模型3),CKD仍是新发KOA的独立危险因素(HR=1.82, 95%CI:1.30~2.55,P<0.001)。见表2。
RCS分析显示,调整混杂因素后基线eGFR与新发KOA风险未见显著的整体关联(总趋势P= 0.348,非线性P=0.479),见图2。结合表2结果提示,肾功能对KOA发病的影响呈现“病理阈值效应”,即当肾功能下降至临床诊断标准[eGFR<60ml/(min·1.73m2)]时,才会触发显著的关节损害风险。
亚组分析结果显示,在不同年龄(<60岁/≥60岁)、性别、BMI分组、婚姻状况及生活方式分层中,CKD与KOA的关联方向基本一致。交互作用检验显示,各分层因素与CKD之间无显著交互作用(交互P值均大于0.05),表明CKD对KOA的危害效应在不同特征人群中具有良好的稳健性。见图3。
通过两项敏感性分析进一步验证了结果的稳健性:(1)滞后分析(剔除随访前2年内发病者)显示关联依然显著(HR=1.72, 95%CI: 1.19~2.47);(2)基于未插补的完全个案数据(n=3 688)重新分析,结果(HR=1.89, 95%CI: 1.32~2.71)与主模型高度一致,表明本研究结果稳健。
本研究基于具有全国代表性的CHARLS纵向队列数据,首次在中国中老年人群中证实了CKD是新发KOA的独立危险因素。研究发现,基线患有CKD的受访者在随访期间发生KOA的风险增加了82%。然而,RCS分析并未发现基线eGFR水平与KOA风险存在显著的线性或非线性剂量-反应关系。这一结果提示,肾功能受损对关节健康的危害可能并非呈连续的渐进式特征,而是具有明确的病理阈值效应,即只有当肾功能下降至临床诊断标准时,才会触发显著的关节损害风险。
本研究结果与部分国外队列研究结论一致。例如,终末期肾病长期透析的患者发生骨关节炎的风险显著增加[22]。然而,既往研究多聚焦于严重肾衰竭患者,而本研究发现,即便是在普通社区人群中,eGFR的下降也与骨关节健康密切相关,这提示“肾-骨”轴的病理联系可能在疾病早期即已建立。
CKD增加KOA风险的潜在机制可能涉及多条通路。首先,全身性慢性炎症状态可能是连接二者的核心桥梁。CKD患者常伴有循环中促炎因子(如TNF-α、IL-6)水平升高[23],这些炎症因子可破坏关节软骨基质的代谢平衡,加速软骨降解[24]。其次,矿物质骨代谢异常在肾功能下降早期即可出现,维生素D缺乏及继发性甲状旁腺功能亢进可能导致软骨下骨微结构破坏,进而引发关节软骨的生物力学失衡[25]。此外,CKD患者常伴随尿毒症性肌病和肌肉减少症,膝关节周围肌肉力量的下降削弱了对关节的保护作用,增加了机械磨损风险[26]。尽管本研究因数据限制未能在统计学上完全验证上述中介路径,但既往基础研究已为这些机制提供了理论支持。
本研究具有重要的临床与公共卫生意义。首先,结果强调了在CKD患者管理中关注骨关节健康的重要性。临床医生在诊治CKD患者(尤其是老年患者)时,不应仅关注心血管并发症,还应早期筛查关节疼痛症状。其次,eGFR与KOA的关系提示,保护肾功能可能产生维持关节健康的效应。建议将适度运动、控制炎症及改善骨代谢纳入CKD患者的综合干预策略,以降低KOA的发生风险。
此外,本研究存在一定局限性。第一,KOA的诊断主要基于受访者的自我报告及疼痛症状,缺乏X线或MRI影像学确诊数据,虽然该定义方式在CHARLS相关研究中被广泛应用[27],但仍无法完全排除类风湿性关节炎等其他炎症性关节病变造成的结局错分风险。然而,考虑到中老年人群中KOA的患病率远高于类风湿性关节炎,这种潜在偏差对核心结论的影响可能有限。第二,受限于CHARLS数据库的设计,本研究未能获取详细的膳食营养素数据。CHARLS仅采用简化的食物频率问卷记录饮食习惯,缺乏具体的摄入量及营养成分分析数据,这使得我们无法精准计算钙、磷及维生素D等对‘肾-骨轴’及软骨代谢至关重要的微量营养素摄入水平。尽管既往多项基于CHARLS的高质量研究均因数据限制未将膳食纳入调整[27-28],且我们在模型中已充分调整了BMI、高血压及糖尿病等能够反映长期营养代谢状态的替代指标,但仍需谨慎解读可能存在的残余混杂影响。”第三,由于数据限制,未能深入分析CKD具体分期对KOA严重程度的影响。
综上所述,本前瞻性队列研究证实CKD是中国中老年人群新发KOA的独立危险因素,且肾功能受损对关节健康的危害呈现以eGFR<60 ml/(min·1.73m2)为界点的“病理阈值效应”。本研究为“肾-骨轴”病理串扰假说提供了流行病学证据。在临床实践中,建议打破单病种管理壁垒,将关节健康筛查纳入CKD患者的常规管理,通过早期识别与综合干预,延缓“肾-关节”共病的进展。
  • 国家自然科学基金面上项目(82474538)
  • 天津中医药大学第一附属医院创新团队培育计划项目(4042502041)
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2026年第53卷第9期
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doi: 10.20043/j.cnki.MPM.202512358
  • 接收时间:2025-12-25
  • 首发时间:2026-11-02
  • 出版时间:2026-05-10
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  • 收稿日期:2025-12-25
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国家自然科学基金面上项目(82474538)
天津中医药大学第一附属医院创新团队培育计划项目(4042502041)
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    1.天津中医药大学第一附属医院,天津 300381
    2.中医国家临床医学研究中心,天津 300381

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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