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Article(id=1149773880237192036, tenantId=1146029695717560320, journalId=1146123166801305609, issueId=1149773869357167407, articleNumber=null, orderNo=null, doi=10.12404/j.issn.1671-1815.2404785, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1719331200000, receivedDateStr=2024-06-26, revisedDate=1738771200000, revisedDateStr=2025-02-06, acceptedDate=null, acceptedDateStr=null, onlineDate=1752057054812, onlineDateStr=2025-07-09, pubDate=1746633600000, pubDateStr=2025-05-08, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1752057054812, onlineIssueDateStr=2025-07-09, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1752057054812, creator=13701087609, updateTime=1752057054812, updator=13701087609, issue=Issue{id=1149773869357167407, tenantId=1146029695717560320, journalId=1146123166801305609, year='2025', volume='25', issue='13', pageStart='5273', pageEnd='5704', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1752057052207, creator=13701087609, updateTime=1768456769392, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1218559268744253990, tenantId=1146029695717560320, journalId=1146123166801305609, issueId=1149773869357167407, language=EN, specialIssueTitle=, coverIllustrator=, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1218559268744253991, tenantId=1146029695717560320, journalId=1146123166801305609, issueId=1149773869357167407, language=CN, specialIssueTitle=, coverIllustrator=, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=5377, endPage=5383, ext={EN=ArticleExt(id=1149773880560153446, articleId=1149773880237192036, tenantId=1146029695717560320, journalId=1146123166801305609, language=EN, title=Association between Non-HDL-C to HDL-C ratio and Rapid Decline in Renal Function: A Longitudinal Cohort Study Based on CHARLS, columnId=1156262732384031076, journalTitle=Science Technology and Engineering, columnName=Papers·Medicine, runingTitle=null, highlight=null, articleAbstract=

In order to explore the relationship between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) and the risk of rapid decline in kidney function, data from the China health and retirement longitudinal study (CHARLS) conducted in 2011 and 2015 was utilized. It includes 4 055 participants aged 40 and above with a baseline estimated glomerular filtration rate (eGFR) of at least 60 mL/(min·1.73m2), calculated using serum creatinine and cystatin C levels. Rapid kidney function decline is defined as a decrease in eGFR of 3 mL/(min·1.73m2·a). A multivariable logistic regression model was used to investigate the association between NHHR and the risk of rapid kidney function decline. Additionally, restricted cubic spline and threshold effect analyses were used to evaluate the dose-response relationship. The results show that over the 4-year follow-up, 447 participants (11.02%) experienced rapid decline in kidney function. In the fully adjusted multivariable logistic regression model, those in the highest NHHR group (T3) faced a 1.94-fold increased risk of rapid kidney function decline compared to the lowest NHHR group (T1) (OR=1.94,95%CI:1.46~2.61). As a continuous variable, each unit increase in NHHR is associated with a 1.21-fold increase in risk (OR=1.21, 95%CI:1.08~1.36). The restricted cubic spline analysis demonstrates a near logarithmic curve saturation effect between NHHR and rapid kidney function decline (Pnonlinearity<0.05). It is concluded that with NHHR ≤3.52, the risk increases as NHHR rises, while NHHR >3.52 marks a saturation point. In conclusion, among middle-aged and elderly individuals, a higher NHHR is linked to a greater risk of rapid decline in kidney function, displaying a nonlinear relationship.

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为探究非高密度脂蛋白胆固醇(non-high density lipoprotein cholesterol, Non-HDL-C)与高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-C)比值NHHR与肾功能快速下降风险之间的关系。通过使用2011年和2015年中国健康与养老追踪调查(China health and retirement longitudinal study, CHARLS)数据,分析了4 055名年龄≥40岁并且基线估计肾小球滤过率(estimated glomerular filtration rate, eGFR)≥60 mL/(min·1.73m2)的参与者(根据血清肌酐和胱抑素C生成估计肾小球滤过率)。肾功能快速下降定义为eGFR下降≥3 mL/(min·1.73m2·a)。采用多因素logistic回归模型探究NHHR与肾功能快速下降的风险的相关性,同时采用限制性立方样条和阈值效应分析评估二者的剂量-效应关系。结果表明:在4年的随访期间,447名(11.02%)参与者肾功能快速下降。在完全调整的多因素Logistic回归模型中,NHHR最高组(T3)肾功能快速下降风险是NHHR最低组(T1)的1.94倍(OR=1.94,95%CI:1.46~2.61)。当NHHR作为连续变量时,NHHR每升高一个单位,肾功能快速下降风险增加1.21倍(OR=1.21,95%CI:1.08~1.36)。限制性立方样条结果显示,NHHR与肾功能快速下降呈现近似对数曲线的饱和效应关系(Pnonlinearity<0.05),拐点分析显示NHHR≤3.52时,随着NHHR升高,肾功能快速下降风险增加。当NHHR>3.52,肾功能快速下降风险趋于饱和。可见在中老年人中,较高的NHHR与纵向肾功能快速下降相关且存在非线性关系。

, correspAuthors=王茂泓, authorNote=null, correspAuthorsNote=
* 王茂泓(1970—),男,汉族,江西南昌人,博士,主任中医师,博士研究生导师。研究方向:中西医结合防治肾系疾病。E-mail:。
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郑航(1994—),男,汉族,山西长治人,博士研究生。研究方向:中西医结合防治肾系疾病。E-mail:。

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郑航(1994—),男,汉族,山西长治人,博士研究生。研究方向:中西医结合防治肾系疾病。E-mail:。

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郑航(1994—),男,汉族,山西长治人,博士研究生。研究方向:中西医结合防治肾系疾病。E-mail:。

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Saudi Journal of Kidney Diseases and Transplantation, 2021, 32(5): 1300-1309., articleTitle=Insulin resistance in nondiabetic chronic kidney disease patients, refAbstract=null)], funds=[Fund(id=1175114013626221471, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, awardId=82160879, language=CN, fundingSource=国家自然科学基金地区基金(82160879), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1175114009700352877, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, xref=1, ext=[AuthorCompanyExt(id=1175114009725518702, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, companyId=1175114009700352877, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1 Clinical Medical College, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China), AuthorCompanyExt(id=1175114009738101615, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, companyId=1175114009700352877, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1 江西中医药大学临床医学院, 南昌 330004)]), AuthorCompany(id=1175114009817793392, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, xref=2, ext=[AuthorCompanyExt(id=1175114009821987697, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, companyId=1175114009817793392, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2 The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China), AuthorCompanyExt(id=1175114009830376306, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, companyId=1175114009817793392, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2 江西中医药大学附属医院, 南昌 330006)])], figs=[ArticleFig(id=1175114012728640403, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=EN, label=Fig.1, caption=Flowchart of participant selection, figureFileSmall=x9/+ZkRFGuNZgkyFG2pQHg==, figureFileBig=daXy3RhQm/lfKKgJm8Gw1g==, tableContent=null), ArticleFig(id=1175114012795749268, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=CN, label=图1, caption=参与者筛选流程图, figureFileSmall=x9/+ZkRFGuNZgkyFG2pQHg==, figureFileBig=daXy3RhQm/lfKKgJm8Gw1g==, tableContent=null), ArticleFig(id=1175114012850275221, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=EN, label=Fig.2, caption=Restricted cubic spline curve for the association between NHHR and rapid eGFR decline, figureFileSmall=fE//GwEZRcZo4kxMeXO+VA==, figureFileBig=sbDDP6JA8AhNoAv57wForA==, tableContent=null), ArticleFig(id=1175114012908995478, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=CN, label=图2, caption=NHHR与eGFR快速下降的限制性立方样条曲线, figureFileSmall=fE//GwEZRcZo4kxMeXO+VA==, figureFileBig=sbDDP6JA8AhNoAv57wForA==, tableContent=null), ArticleFig(id=1175114012955132823, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=EN, label=Fig.3, caption=Subgroup analysis of NHHR and rapid eGFR decline, figureFileSmall=3cfa5FefFZOrn2V+CKujzQ==, figureFileBig=qYKC98G1fhQehfUW5bzAhg==, tableContent=null), ArticleFig(id=1175114013009658776, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=CN, label=图3, caption=NHHR与eGFR快速下降的亚组分析

P for interaction表示用于检验两个或多个变量之间交互作用的统计量;1 mmHg=133.32 Pa

, figureFileSmall=3cfa5FefFZOrn2V+CKujzQ==, figureFileBig=qYKC98G1fhQehfUW5bzAhg==, tableContent=null), ArticleFig(id=1175114013068379033, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=EN, label=Table 1, caption=

Baseline characteristics of participants

, figureFileSmall=null, figureFileBig=null, tableContent=
特征 总计 非肾功能快速下降组 肾功能快速下降组 P
参与者数量/人 4 055 3 608(89.0%) 447(11.0%) —
年龄/岁 59±9.0 58.9±9.0 59.7±9.7 0.084
性别 男性 1 863(45.9%) 1 661(46.0%) 202(45.2%) 0.773
女性 2 192(54.1%) 1 947(54.0%) 245(54.8%)
学历 小学或以上学历 3 695(91.1%) 3 284(91.0%) 411(91.9%) 0.719
中学学历 310(7.6%) 280(7.8%) 30(6.7%)
大学及以上学历 50(1.2%) 44(1.2%) 6(1.3%)
婚姻状况 已婚 3 441(84.9%) 3 071(85.1%) 370(82.2%) 0.217
单身 614(15.1%) 537(14.9%) 77(17.2%)
居住地区 城市 252(6.2%) 220(6.1%) 32(7.2%) 0.440
农村 3 803(93.8%) 3 388(93.9%) 415(92.8%)
吸烟情况 现在不吸烟 2 819(69.7%) 2 513(69.8%) 306(68.8%) 0.679
现在吸烟 1 224(30.3%) 1 085(30.2%) 139(31.2%)
饮酒情况 从不饮酒 2 712(66.9%) 2 410(66.8%) 302(67.6%) 0.367
少于每月1次 302(7.4%) 276(7.6%) 26(5.8%)
多于每月1次 1 041(25.7%) 922(25.6%) 119(26.6%)
BMI 消瘦 248(6.1%) 226(6.3%) 22(4.9%) 0.117
正常体重 3 358(82.8%) 2 994(2 994%) 364(81.4%)
超重/肥胖 449(11.1%) 388(6.3%) 61(13.60%)
血压 收缩压/mmHg 129.6±21.2 129.0±21.0 134.1±22.3 <0.001
舒张压/mmHg 75.3±12.0 75.0±11.9 77.4±12.1 <0.001
基线eGFR/[mL·min-1·(1.73 m2)-1] 88.3±14.5 87.1±13.7 97.6±17.5 <0.001
空腹血糖/(mg·dL-1) 108.7±32.6 107.9±30.1 114.9±47.9 <0.001
尿酸/(mg·dL-1) 4.3±1.2 4.3±1.2 4.4±1.3 0.078
无中风疾患 3 988(98.3%) 3 552(98.4%) 436(97.5%) 0.221
无心血管疾患 3 622(89.3%) 3 219(89.2%) 403(90.2%) 0.600
无肺部疾患 3 622(89.3%) 3 222(89.3%) 400(89.5%) 0.970
NHHR 3.0±1.4 3.0±1.4 3.6±1.6 <0.001
NHHR分组 NHHR-T1 1 352(33.3%) 1 261(35.0%) 91(20.4%) —
NHHR-T2 1 351(33.3%) 1 218(33.8%) 133(29.8%) —
NHHR-T3 1 352(33.3%) 1 129(31.3%) 223(49.9%) —
), ArticleFig(id=1175114013135487898, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=CN, label=表1, caption=

参与者的基线特征

, figureFileSmall=null, figureFileBig=null, tableContent=
特征 总计 非肾功能快速下降组 肾功能快速下降组 P
参与者数量/人 4 055 3 608(89.0%) 447(11.0%) —
年龄/岁 59±9.0 58.9±9.0 59.7±9.7 0.084
性别 男性 1 863(45.9%) 1 661(46.0%) 202(45.2%) 0.773
女性 2 192(54.1%) 1 947(54.0%) 245(54.8%)
学历 小学或以上学历 3 695(91.1%) 3 284(91.0%) 411(91.9%) 0.719
中学学历 310(7.6%) 280(7.8%) 30(6.7%)
大学及以上学历 50(1.2%) 44(1.2%) 6(1.3%)
婚姻状况 已婚 3 441(84.9%) 3 071(85.1%) 370(82.2%) 0.217
单身 614(15.1%) 537(14.9%) 77(17.2%)
居住地区 城市 252(6.2%) 220(6.1%) 32(7.2%) 0.440
农村 3 803(93.8%) 3 388(93.9%) 415(92.8%)
吸烟情况 现在不吸烟 2 819(69.7%) 2 513(69.8%) 306(68.8%) 0.679
现在吸烟 1 224(30.3%) 1 085(30.2%) 139(31.2%)
饮酒情况 从不饮酒 2 712(66.9%) 2 410(66.8%) 302(67.6%) 0.367
少于每月1次 302(7.4%) 276(7.6%) 26(5.8%)
多于每月1次 1 041(25.7%) 922(25.6%) 119(26.6%)
BMI 消瘦 248(6.1%) 226(6.3%) 22(4.9%) 0.117
正常体重 3 358(82.8%) 2 994(2 994%) 364(81.4%)
超重/肥胖 449(11.1%) 388(6.3%) 61(13.60%)
血压 收缩压/mmHg 129.6±21.2 129.0±21.0 134.1±22.3 <0.001
舒张压/mmHg 75.3±12.0 75.0±11.9 77.4±12.1 <0.001
基线eGFR/[mL·min-1·(1.73 m2)-1] 88.3±14.5 87.1±13.7 97.6±17.5 <0.001
空腹血糖/(mg·dL-1) 108.7±32.6 107.9±30.1 114.9±47.9 <0.001
尿酸/(mg·dL-1) 4.3±1.2 4.3±1.2 4.4±1.3 0.078
无中风疾患 3 988(98.3%) 3 552(98.4%) 436(97.5%) 0.221
无心血管疾患 3 622(89.3%) 3 219(89.2%) 403(90.2%) 0.600
无肺部疾患 3 622(89.3%) 3 222(89.3%) 400(89.5%) 0.970
NHHR 3.0±1.4 3.0±1.4 3.6±1.6 <0.001
NHHR分组 NHHR-T1 1 352(33.3%) 1 261(35.0%) 91(20.4%) —
NHHR-T2 1 351(33.3%) 1 218(33.8%) 133(29.8%) —
NHHR-T3 1 352(33.3%) 1 129(31.3%) 223(49.9%) —
), ArticleFig(id=1175114013219373979, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=EN, label=Table 2, caption=

Associations between baseline NHHR and rapid eGFR decline

, figureFileSmall=null, figureFileBig=null, tableContent=
指标参数 模型1 模型2 模型3
OR(95%CI) P OR(95%CI) P OR(95%CI) P
NNHR 1.49(1.35~1.65) <0.001 1.50(1.35~1.66) <0.001 1.21(1.08~1.36) 0.001
NNHR分组 NHHR-T1 参考 — 参考 — 参考 —
NHHR-T2 1.51(1.15~2.00) 0.004 1.53(1.16~2.02) 0.003 1.45(1.08~1.95) 0.014
NHHR-T3 2.74(2.12~3.55) <0.001 2.75(2.13~3.58) <0.001 1.94(1.46~2.61) <0.001
P for trend <0.001 — <0.001 — <0.001 —
), ArticleFig(id=1175114013282288540, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=CN, label=表2, caption=

基线NHHR与eGFR快速下降的相关性

, figureFileSmall=null, figureFileBig=null, tableContent=
指标参数 模型1 模型2 模型3
OR(95%CI) P OR(95%CI) P OR(95%CI) P
NNHR 1.49(1.35~1.65) <0.001 1.50(1.35~1.66) <0.001 1.21(1.08~1.36) 0.001
NNHR分组 NHHR-T1 参考 — 参考 — 参考 —
NHHR-T2 1.51(1.15~2.00) 0.004 1.53(1.16~2.02) 0.003 1.45(1.08~1.95) 0.014
NHHR-T3 2.74(2.12~3.55) <0.001 2.75(2.13~3.58) <0.001 1.94(1.46~2.61) <0.001
P for trend <0.001 — <0.001 — <0.001 —
), ArticleFig(id=1175114013353591709, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=EN, label=Table 3, caption=

Threshold effect analysis for the association between NHHR and rapid eGFR decline

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NHHR OR(95%CI) P
拐点(K) 3.520 —
NHHR<3.520 1.37(1.16~1.62) <0.001
NHHR≥3.520 1.02(0.92~1.13) 0.707
对数似然比检验 — 0.008
), ArticleFig(id=1175114013429089182, tenantId=1146029695717560320, journalId=1146123166801305609, articleId=1149773880237192036, language=CN, label=表3, caption=

NHHR与eGFR快速下降的阈值效应分析

, figureFileSmall=null, figureFileBig=null, tableContent=
NHHR OR(95%CI) P
拐点(K) 3.520 —
NHHR<3.520 1.37(1.16~1.62) <0.001
NHHR≥3.520 1.02(0.92~1.13) 0.707
对数似然比检验 — 0.008
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非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值和肾功能快速下降之间的关系: 基于中国健康与养老追踪调查的纵向队列数据
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郑航 1 , 王茂泓 2, * , 李雪 1 , 张珍珍 1
科学技术与工程 | 论文·医药、卫生 2025,25(13): 5377-5383
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科学技术与工程 | 论文·医药、卫生 2025, 25(13): 5377-5383
非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值和肾功能快速下降之间的关系: 基于中国健康与养老追踪调查的纵向队列数据
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郑航1 , 王茂泓2, * , 李雪1, 张珍珍1
作者信息
  • 1 江西中医药大学临床医学院, 南昌 330004
  • 2 江西中医药大学附属医院, 南昌 330006

    • 郑航(1994—),男,汉族,山西长治人,博士研究生。研究方向:中西医结合防治肾系疾病。E-mail:。

通讯作者:

* 王茂泓(1970—),男,汉族,江西南昌人,博士,主任中医师,博士研究生导师。研究方向:中西医结合防治肾系疾病。E-mail:。
Association between Non-HDL-C to HDL-C ratio and Rapid Decline in Renal Function: A Longitudinal Cohort Study Based on CHARLS
Hang ZHENG1 , Mao-hong WANG2, * , Xue LI1, Zhen-zhen ZHANG1
Affiliations
  • 1 Clinical Medical College, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
  • 2 The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China
出版时间: 2025-05-08 doi: 10.12404/j.issn.1671-1815.2404785
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摘要
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为探究非高密度脂蛋白胆固醇(non-high density lipoprotein cholesterol, Non-HDL-C)与高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-C)比值NHHR与肾功能快速下降风险之间的关系。通过使用2011年和2015年中国健康与养老追踪调查(China health and retirement longitudinal study, CHARLS)数据,分析了4 055名年龄≥40岁并且基线估计肾小球滤过率(estimated glomerular filtration rate, eGFR)≥60 mL/(min·1.73m2)的参与者(根据血清肌酐和胱抑素C生成估计肾小球滤过率)。肾功能快速下降定义为eGFR下降≥3 mL/(min·1.73m2·a)。采用多因素logistic回归模型探究NHHR与肾功能快速下降的风险的相关性,同时采用限制性立方样条和阈值效应分析评估二者的剂量-效应关系。结果表明:在4年的随访期间,447名(11.02%)参与者肾功能快速下降。在完全调整的多因素Logistic回归模型中,NHHR最高组(T3)肾功能快速下降风险是NHHR最低组(T1)的1.94倍(OR=1.94,95%CI:1.46~2.61)。当NHHR作为连续变量时,NHHR每升高一个单位,肾功能快速下降风险增加1.21倍(OR=1.21,95%CI:1.08~1.36)。限制性立方样条结果显示,NHHR与肾功能快速下降呈现近似对数曲线的饱和效应关系(Pnonlinearity<0.05),拐点分析显示NHHR≤3.52时,随着NHHR升高,肾功能快速下降风险增加。当NHHR>3.52,肾功能快速下降风险趋于饱和。可见在中老年人中,较高的NHHR与纵向肾功能快速下降相关且存在非线性关系。

肾功能快速下降  /  非高密度脂蛋白胆固醇  /  高密度脂蛋白胆固醇  /  队列研究  /  CHARLS

In order to explore the relationship between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) and the risk of rapid decline in kidney function, data from the China health and retirement longitudinal study (CHARLS) conducted in 2011 and 2015 was utilized. It includes 4 055 participants aged 40 and above with a baseline estimated glomerular filtration rate (eGFR) of at least 60 mL/(min·1.73m2), calculated using serum creatinine and cystatin C levels. Rapid kidney function decline is defined as a decrease in eGFR of 3 mL/(min·1.73m2·a). A multivariable logistic regression model was used to investigate the association between NHHR and the risk of rapid kidney function decline. Additionally, restricted cubic spline and threshold effect analyses were used to evaluate the dose-response relationship. The results show that over the 4-year follow-up, 447 participants (11.02%) experienced rapid decline in kidney function. In the fully adjusted multivariable logistic regression model, those in the highest NHHR group (T3) faced a 1.94-fold increased risk of rapid kidney function decline compared to the lowest NHHR group (T1) (OR=1.94,95%CI:1.46~2.61). As a continuous variable, each unit increase in NHHR is associated with a 1.21-fold increase in risk (OR=1.21, 95%CI:1.08~1.36). The restricted cubic spline analysis demonstrates a near logarithmic curve saturation effect between NHHR and rapid kidney function decline (Pnonlinearity<0.05). It is concluded that with NHHR ≤3.52, the risk increases as NHHR rises, while NHHR >3.52 marks a saturation point. In conclusion, among middle-aged and elderly individuals, a higher NHHR is linked to a greater risk of rapid decline in kidney function, displaying a nonlinear relationship.

rapid decline in kidney function  /  Non-HDL-C  /  HDL-C  /  cohort studies  /  CHARLS
郑航, 王茂泓, 李雪, 张珍珍. 非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值和肾功能快速下降之间的关系: 基于中国健康与养老追踪调查的纵向队列数据. 科学技术与工程, 2025 , 25 (13) : 5377 -5383 . DOI: 10.12404/j.issn.1671-1815.2404785
Hang ZHENG, Mao-hong WANG, Xue LI, Zhen-zhen ZHANG. Association between Non-HDL-C to HDL-C ratio and Rapid Decline in Renal Function: A Longitudinal Cohort Study Based on CHARLS[J]. Science Technology and Engineering, 2025 , 25 (13) : 5377 -5383 . DOI: 10.12404/j.issn.1671-1815.2404785
正文
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慢性肾脏疾病(chronic kidney disease, CKD)作为进行性肾衰竭的主要危险因素,全球患病率约为14.3%,已成为全球卫生事业的巨大挑战[1]。中国CKD患病率约为10.8%,患者人数超1.32亿人,且仍呈上升趋势。但因CKD发病过程隐匿,患者通常发现时已是中晚期阶段[2]。CKD患者一旦进入终末期肾脏病阶段,只能通过肾移植、血液透析、腹膜透析等肾脏替代治疗维持生命[3]。昂贵的治疗费用和长期的治疗过程不仅给患者身体和精神带来巨大压力,也给家庭和社会带来巨大的经济负担[4-6]。
近年来,血脂异常和慢性肾脏疾病之间的关系成为研究热点[7]。多项研究表明,血清中脂蛋白水平及比例变化与慢性肾脏疾病的发生和发展密切相关。章如山等[8]对安庆市农村高血压患者的研究发现,高血压患者的LDL-C与肾功能轻度下降呈现正相关,这在舒张压升高的患者中更加明显。邝邕军等[9]研究发现,甘油三酯(triglyceride, TG)/高密度脂蛋白胆固醇比值水平使2型糖尿病患者的肾损伤风险明显增加。传统脂质参数,仅能从单方面反映血清脂质水平变化,难以综合判断血清血脂整体水平。非高密度脂蛋白胆固醇(non-high density lipoprotein cholesterol, Non-HDL-C)与高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-C)比值NHHR作为结合TG、LDL-C、HDL-C等的综合指标,不仅在胰岛素抵抗、代谢综合征等疾病中有优越的诊断效果,更作为慢性肾脏疾病的潜在预测指标,引起学术界广泛关注。Hao等[10]的一项横断面研究发现,NHHR与糖尿病肾病的发病风险增加显著相关。虽然目前很多研究结果表明脂蛋白与CKD密切相关,但NHHR与CKD的联系尚未确定。现基于中国健康与养老追踪调查(China health and retirement longitudinal study, CHARLS)数据库,首次通过纵向大队列研究,探讨中国中老年人群中NHHR与CKD的潜在联系。
1 研究对象与方法
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1.1 研究设计
获取了CHARLS数据库2011年和2015年的数据,共纳入了4 055名参与者。CHARLS是全国性的纵向调查,采用多阶段分层概率比例抽样策略,从农村和城市地区招募参与者,覆盖了全国28个省份的150个县和450个社区,研究设计和队列概况的细节先前已被描述[11]。研究按照赫尔辛基宣言的原则进行,并得到北京大学机构审查委员会的批准(IRB00001052-11015)。所有参与者在参与CHARLS研究前都提供了书面知情同意书。2011年共有17 705名参与者参与了基线调查,排除40岁以下性别、婚姻等基本信息和身高、体重、血压等体格检查信息缺失者4 377人,排除肌酐、总胆固醇(serum total cholesterol, TC)、HDL-C等生化指标缺失者6 126人,排除基线eGFR低于60 mL/(min·1.73 m2)和服用降脂药物以及患有恶性肿瘤的参与者1 007人,排除2015年肾功能指标缺失的参与者2 140人,最终纳入参与者共4 055人,如图1所示。
1.2 研究变量
1.2.1 数据收集和标本
中国疾病预防控制中心医务人员根据标准方案采集空腹静脉血样本,随后在中心实验室进行检测。采用酶比色法测定血清葡萄糖和血脂,采用Jaffe反应速率法测定血清肌酐,采用颗粒增强比浊法测定血清胱抑素C。使用欧姆龙HEM-7200型血压计连续测量3次参与者血压,每次间隔45 s。使用立式身高计测量参与者身高,要求参与者按标准姿势测量。使用体重秤测量参与者体重,要求参与者脱下鞋子站在体重秤上。通过问卷调查年龄、性别、受教育程度、婚姻状况、居住地等基线人工统计学特征和吸烟、饮酒、病史等生活健康状况。
1.2.2 NHHR评估
非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值(NNHR)计算公式为
NNHR=wTC-wHDL-C
式(1)中:NNHR为非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值;wTC为总胆固醇浓度,mmol/L;wHDL-C为高密度脂蛋白胆固醇浓度,mmol/L。
将纳入的参与者根据NHHR的三分位数分为3组:T1组(低比值组)、T2组(中比值组)、T3组(高比值组)。使用三组的组内中位数生成趋势检验数据。
1.2.3 肾脏功能评估
采用慢性肾脏疾病流行病学协作组的肌酐-胱抑素C方程计算肾小球滤过率eGFR,公式如下。
eGRF=135min C r k , 1 αmax C r k , 1 - 0.601×min C y s C 0.8 , 1 - 0.375max C y s C 0.8 , 1 - 0.711×0.995×0.969
式(2)中:Cr为血清肌酐,mg/dl;CysC为血清胱抑素C,mg/L;在女性评估中,k=0.7,α=-0.248,在男性评估中,k=0.9,α=-0.207。
通过eGFR评估肾功能变化,2011年和2015年参与者的eGFR分别作为基线和终点肾功能指标。结局指标eGFR的快速下降定义为:eGFR下降≥3 mL/(min·1.73m2·a),以前的研究中已多次使用该截止值。
1.2.4 协变量评估
将过往研究中和肾功能下降相关的混杂因素确定为协变量,包括人口统计数据、生活习惯和健康状况。人口统计数据包括年龄、性别、婚姻状态、受教育程度。生活方式包括吸烟、饮酒状况。健康状况包括基线eGFR水平、尿酸、空腹血糖、收缩压、舒张压、体重指数(body mass index, BMI)、中风、心血管疾病、肺部疾病等。婚姻状况分为两种:从未结过婚和从前结过婚但现在单身的归于现在单身者,仍在婚姻关系之中的归于已婚。吸烟状况分为两种:吸烟超过100支并正在吸烟的人被认为吸烟者,从未吸烟或超过100支但已戒烟者被认为不吸烟者。饮酒行为被分为三类:从不饮酒者,每月饮酒少于1次者,每月饮酒1次以上者。中风、心血管疾病及肺部疾患的定义根据自我报告的医学诊断和是否使用相关治疗分为患相关疾病者和无相关疾病者。
1.3 统计分析
描述性统计对分类变量用数字(百分比)报告,对连续性变量用均数±标准差报告。采用适当的统计检验,包括单因素方差分析、Kruskal-Walis H检验、卡方检验,比较肾功能快速下降参与者的基线特征。使用多变量logistic回归模型来描述NHHR与肾脏预后之间的关系。模型1未对任何协变量进行调整;模型2对年龄、性别、受教育程度、居住地和婚姻状态进行调整;模型3进一步调整吸烟、饮酒状况、BMI、收缩压、舒张压、基线eGFR、尿酸、空腹血糖、中风、心血管疾病、肺部疾病等。所用统计分析均使用软件R 4.3.0完成。检验水准α=0.05。
2 结果
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2.1 参与者特征
参与者基于eGFR是否快速下降的基线特征如表1所示。在分析的4 055名参与者中,447人出现eGFR快速下降,3 608人未出现eGFR快速下降。获得以下基线值,参与者平均年龄为(59±9.0)岁,女性占比54.1%,平均基线eGFR为(88.3±14.5) mL/(min·1.73m2)。与无eGFR快速下降组相比,eGFR快速下降组的参与者倾向于有更高的收缩压和舒张压,低体重和超重/肥胖,基础肾小球滤过率水平更高,差异具有统计学意义(P<0.05)。
2.2 基线NNHR与eGFR快速下降的关联分析
在4年的随访期后,447名(11.02%)参与者的eGFR快速下降。模型1未调整混杂因素,模型2对年龄、性别、受教育程度、居住地及婚姻状况进行调整,模型3进一步调整饮酒、吸烟、基线eGFR、尿酸、血糖、收缩压、舒张压、BMI、中风、心血管疾病、肺部疾病。在3种回归模型中,基线NNHR升高均可导致eGFR快速下降的风险增高。在模型3中,基线NNHR作为连续性变量时,结果显示基线NNHR每增加一个单位,eGFR快速下降风险增加1.21倍(OR=2.89,95%CI:1.08~1.36),其中OR(odds ratio)表示比值比,OR(95%CI)表示OR的95%置信区间(CI),是指对OR估计值的可靠性进行评估的一个统计区间。将基线NNHR按照三分位数分为3组,基线NHHR最高组(T3)引发eGFR快速下降风险是基线NHHR最低组(T1)的1.94倍(OR=1.94,95%CI:1.46~2.61)。如表2所示。
2.3 基线NHHR与eGFR快速下降的剂量-反应关系
在限制性立方样条分析中,调整年龄、性别、受教育程度、居住地、婚姻状况、吸烟、饮酒、尿酸、基线eGFR、空腹血糖、血压、BMI、中风、心血管疾病、肺部疾病后,发现基线NHHR与eGFR快速下降的风险之间存在非线性关系,呈近似对数函数(log)曲线,并呈饱和效应关系(P=0.024),如图2所示。
拐点分析结果显示,当基线NHHR<3.520时,随着NHHR的升高,eGFR快速下降的风险迅速增加。当基线NHHR≥3.520时,随着NHHR的升高,eGFR快速下降的风险趋于平缓。如表3所示。
2.4 亚组分析
以基线NHHR三分位数分组,调整混杂因素后,纳入年龄、性别、吸烟、尿酸、收缩压、血糖、基线eGFR进行亚组分析,结果表明,NHHR的T3组在各组中均有统计学意义,均不存在明显交互作用,结果稳定。NHHR的T2组在60岁以上的男性参与者中,以及在吸烟、高尿酸、高收缩压、血糖及eGFR正常的参与者中,有统计学意义(P<0.05),且不存在明显交互作用。如图3所示。
3 讨论
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选取2011年与2015年的CHARLS数据,探讨了基线NHHR与eGFR快速下降发生风险的关系。将基线NHHR三分位数分组进行多因素logistic回归模型分析。结果显示,基线NHHR最高组(T3组)引起eGFR快速下降风险是基线NHHR最低组(T1组)的1.94倍。采用限制行立方样条函数和阈值效应探讨了基线NHHR与eGFR快速下降风险的剂量-反应关系,二者呈近似对数函数(log)曲线关系,呈现饱和效应。当基线NHHR<3.520时,基线NHHR与eGFR快速下降风险呈正相关;当基线NHHR≥3.520时,eGFR快速下降风险趋于饱和。
既往研究表明,血脂代谢异常通过多种途径导致肾功能损伤[12]。一项UUO小鼠模型的研究表明,通过增强游离脂肪酸氧化,可减少肾脏脂质积累并减轻肾脏纤维化[13]。而在高脂肪饮食小鼠中,甾醇调节元件结合蛋白(sterol-regulatory element-binding protein, SREBP)表达增加,并且与肾脏脂质和肾损伤相关[14]。在阿霉素诱导的局灶节段性肾小球硬化(focal segmental glomerulosclerosis, FSGS)小鼠模型中,肾皮质脂质积累增加了CKD进展的易感性[15]。多项临床研究也证明了血脂代谢紊乱对肾功能的影响。家族性高脂血症患者有更高的CKD风险,表明脂质升高是肾功能损伤的危险因素[16]。一项他汀类药物对CKD预后疗效的荟萃分析证明,通过减低血清LDL-C和TG水平,可减缓CKD患者肾小球滤过率下降[17]。
Non-HDL-C由LDL-C、极低密度脂蛋白(very low density lipoprotein cholesterol, VLDL-C)、中密度脂蛋白(intermediate density lipoprotein, IDL-C)、乳糜微粒及其富含TG的脂蛋白残余物组成[18]。LDL-C体内代谢而成的氧化低密度脂蛋白(oxidized low density lipoprotein, Ox-LDL-C),可诱导氧化应激和炎症反应,促进肾小球和肾间质细胞纤维化,导致肾组织损伤[19-20]。VLDL-C及其代谢产物可激活免疫反应,并可直接损伤肾小球内皮细胞,导致肾脏功能损伤[21-22]。IDL-C与肾小球系膜细胞相互作用,导致细胞增殖和基质生成,从而导致肾小球硬化[23]。乳糜颗粒和富含TG的脂蛋白残余物导致肾损伤机制尚不十分清楚,但相关证据表明,其可通过脂质沉积、炎症反应和细胞凋亡等机制加速肾脏疾病进展[24-25]。Non-HDL-C与肾功能损伤关系密切,美国国家脂质协会已将Non-HDL-C确定为主要治疗靶点[26]。
HDL-C对肾脏的保护作用已经成为共识。既往的研究证明,HDL-C可以通过降低细胞黏附分子的表达和减少白细胞浸润来减轻肾脏的炎症损伤[27]。HDL-C也可以通过清除自由基和减少脂质过氧化物生成来减少肾细胞氧化损伤[28]。HDL-C还可以通过改善脂质代谢,减少胆固醇积累,减轻肾小球和肾小管损伤[29]。
NHHR由Non-HDL-C和HDL-C组成,是评估血清脂质水平的综合指标。NHHR既可以用于评估动脉粥样硬化程度,又与胰岛素抵抗密切相关,并且评估效果均优于传统的脂质参数,具有更高的准确性[30-32]。动脉粥样硬化和胰岛素抵抗均与CKD发展关系密切[33]。NHHR通过综合Non-HDL-C中多种组成成分的肾损伤作用和HDL-C的保护作用,可以从更完整的程度上评估血清脂质成分改变对肾功能的影响,具有十分巨大的临床应用前景。
4 结论
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本文是第一个基于中国大队列研究NHHR与纵向肾功能下降关系的研究。通过采用限制性立方样条分析、多元Logistic回归、阈值效应分析、亚组分析等相结合的方法,对NHHR与eGFR快速下降之间的关系进行全面评估,并细致地纳入多个协变量。这些方法有助于提高研究结果的可信度。
研究存在以下局限性。首先,CHARLS队列中缺少尿蛋白的相关信息,无法分析NHHR与蛋白尿的关系。其次,受缺失数据的限制,调整后模型中的eGFR快速下降人数在分层后样本量偏小,需要在更大规模的人群中验证。第三,排除血清血脂和肌酐水平数据缺失的参与者可能导致潜在偏倚。如果能够做进一步的调查并提供更高等级的因果关系,则具有更大的临床价值。
基金
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  • 国家自然科学基金地区基金(82160879)
文献
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2025年第25卷第13期
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doi: 10.12404/j.issn.1671-1815.2404785
  • 接收时间：2024-06-26
  • 首发时间：2025-07-09
  • 出版时间：2025-05-08
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  • 收稿日期：2024-06-26
  • 修回日期：2025-02-06
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国家自然科学基金地区基金(82160879)
作者信息
    1 江西中医药大学临床医学院, 南昌 330004
    2 江西中医药大学附属医院, 南昌 330006

通讯作者:

* 王茂泓(1970—),男,汉族,江西南昌人,博士,主任中医师,博士研究生导师。研究方向:中西医结合防治肾系疾病。E-mail:。
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species		 占总种数比例
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total species (%)		 属
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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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