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Article(id=1240972417972105664, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240972413354176744, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202312035, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1701532800000, receivedDateStr=2023-12-03, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773800480596, onlineDateStr=2026-03-18, pubDate=1715270400000, pubDateStr=2024-05-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773800480596, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773800480596, creator=13701087609, updateTime=1773800480596, updator=13701087609, issue=Issue{id=1240972413354176744, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='9', pageStart='1537', pageEnd='1728', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773800479495, creator=13701087609, updateTime=1773800596829, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1240972905568334240, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240972413354176744, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1240972905568334241, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240972413354176744, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1555, endPage=1561, ext={EN=ArticleExt(id=1240972418236346846, articleId=1240972417972105664, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Analysis of the correlation between serum 25-hydroxyvitamin D and all-cause death and cardiovascular disease in patients with chronic kidney disease based on NHANES, columnId=1240413921954295836, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods, runingTitle=null, highlight=null, articleAbstract=
Objective

The 25(OH)D deficiency is a prevalent issue among patients with chronic kidney disease (CKD). The aim of our study is to investigate whether low levels of 25(OH)D are associated with increased all-cause and cardiovascular mortality in patients with CKD.

Methods

This retrospective cohort study utilized the National Health and Nutrition Examination Survey (NHANES) and the National Death Index (NDI) 2007—2018 database to investigate the association between 25(OH)D levels and all-cause mortality as well as cardiovascular mortality. A total of 2 668 eligible subjects were included in this study, with follow-up conducted until December 31, 2019. Cox proportional hazards regression, restricted cubic spline, Kaplan-Meier survival curves, and competing risk survival analysis were performed to evaluate the associations. Furthermore, subgroup and sensitivity analyses were performed.

Results

During a median follow-up of 6 years in a weighted population of 11 715 452 eligible participants, there were 665 deaths from any cause, including 196 cardiovascular-related deaths. After adjusting for covariates, lower levels of 25(OH)D were significantly associated with increased risks for both all-cause (HR=0.85, 95%CI: 0.77-0.94) and cardiovascular mortality (SHR=0.80, 95%CI: 0.67-0.94). Consistent results were also observed when analyzing 25(OH)D as a categorical variable (quartile) (both P<0.05). Weighted restricted cubic splines revealed an inverse J-shaped association between levels of 25 (OH) D and all-cause mortality (Pnonliner> 0.05). Subgroup analysis (Pinteraction>0.05) and sensitivity analysis (HR=0.85, 95%CI: 0.77-0.93) yielded similar findings.

Conclusion

Lower 25(OH)D levels, both as a continuous and categorical variable, are significantly associated with an increased risk of all-cause mortality and cardiovascular disease-related mortality.The 25(OH)D has a negative j-shaped association with all-cause and cardiovascular mortality.

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目的

25(OH)D缺乏在慢性肾脏病(chronic renal disease, CKD)患者中很常见。我们的目的是验证低25（OH）D水平是否会增加CKD患者发生全因死亡及心血管死亡的风险。

方法

本研究为回顾性队列研究，基于美国国家健康与营养调查(NHANES)和美国国家死亡指数(NDI) 2007—2018年数据库。共纳入2 668例符合条件的受试者，并随访至2019年12月31日。采用Kaplan-Meier生存曲线、Cox回归和限制性立方样条分析评估25（OH）D和全因死亡率、心血管疾病死亡之间的关系。

结果

在11 715 452例符合纳入标准的加权人群中，中位随访6年期间，发生了665例全因死亡，其中196例死于心血管原因。在校正协变量后，较低的25（OH）D水平与CKD患者的全因死亡（HR=0.85，95%CI：0.77～0.94）及心血管疾病死亡（SHR=0.80，95%CI：0.67～0.94）风险升高显著相关。当25（OH）D作为分类变量(四分位数)进行分析时，也观察到一致的结果（P均<0.05）。加权的限制立方样条曲线显示25（OH）D水平与全因死亡率呈反“J”型相关系(PNonliner>0.05)，亚组分析（交互作用的P>0.05）和敏感性分析（HR=0.85，95%CI：0.77～0.93）也显示出相似的结果。

结论

无论是作为一个连续变量还是分类变量，低25(OH)D水平都与CKD全因死亡和心血管疾病死亡风险增加显著相关，而且25(OH)D与全因死亡和心血管死亡呈反“J”型相关。

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蒋红樱，E-mail:
, copyrightStatement=本刊刊出的所有文章不代表中华预防医学会和本刊编委会的观点，除非特别声明。, copyrightOwner=中华预防医学会和四川大学华西公共卫生学院, extLink=null, articleAbsUrl=null, sourceXml=OlgDoKBVZWo4Vw7TGTPwAg==, magXml=pDDClj6OvhLWzbquw1Qu3A==, pdfUrl=null, pdf=mecop6je0avnZk+G003mjA==, pdfFileSize=1421406, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=Gf87AeLGWaMUBEsOhQE7qw==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=179AMTeKJNHDEkhNm7RteA==, mapNumber=null, authorCompany=null, fund=null, authors=

李洛华（1990—），男，主治医师，研究方向：慢性肾脏病的研究

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李洛华（1990—），男，主治医师，研究方向：慢性肾脏病的研究

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APOL1 risk variants and cardiovascular disease: results from the AASK (African American study of kidney disease and hypertension)[J].Arteriosclerosis, Thrombosis, and Vascular Biology, 2017, 37(9):1765-1769., articleTitle=APOL1 risk variants and cardiovascular disease: results from the AASK (African American study of kidney disease and hypertension), refAbstract=null)], funds=[Fund(id=1240986262585267114, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, awardId=YNWR-MY-2019-075, language=CN, fundingSource=云南省万人计划“名医”专项资金项目(YNWR-MY-2019-075), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1240986254309905063, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, xref=1., ext=[AuthorCompanyExt(id=1240986254322487976, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, companyId=1240986254309905063, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=The First People’s Hospital of Jiujiang, Jiujiang, Jiangxi 332000, China), AuthorCompanyExt(id=1240986254330876585, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, companyId=1240986254309905063, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.九江市第一人民医院肾内科，江西 九江 332000)]), AuthorCompany(id=1240986254431539885, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, xref=2., ext=[AuthorCompanyExt(id=1240986254439928494, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, companyId=1240986254431539885, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.昆明医科大学第二附属医院肾内科，云南 昆明 650000)])], figs=[ArticleFig(id=1240986257828926201, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=EN, label=Figure 1, caption=Flow chart of patients enrollment, figureFileSmall=Pb+1L321Z1ykQpYfjXE3og==, figureFileBig=WLbmBe+y0DFtFBowLF5MdQ==, tableContent=null), ArticleFig(id=1240986258072195837, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=CN, label=图1, caption=入组患者流程图, figureFileSmall=Pb+1L321Z1ykQpYfjXE3og==, figureFileBig=WLbmBe+y0DFtFBowLF5MdQ==, tableContent=null), ArticleFig(id=1240986258193830661, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=EN, label=Figure 2, caption=Kaplan-Meier analysis of all-cause death based on 25(OH)D quartiles, figureFileSmall=TGAAbZa8EIe66SNo992ptg==, figureFileBig=2acsVu/JvnpJwn/rAUACNQ==, tableContent=null), ArticleFig(id=1240986258386768650, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=CN, label=图2, caption=Kaplan-Meier分析25(OH)D四分位数分组全因死亡率, figureFileSmall=TGAAbZa8EIe66SNo992ptg==, figureFileBig=2acsVu/JvnpJwn/rAUACNQ==, tableContent=null), ArticleFig(id=1240986258684564242, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=EN, label=Figure 3, caption=Cumulative incidence of CVD deaths based on the competing risks analysis, figureFileSmall=eKHDi6x+g5JRMpHseq1Grw==, figureFileBig=9oZksPUgE8sVJXPNAhokkg==, tableContent=null), ArticleFig(id=1240986258835559194, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=CN, label=图3, caption=CVD死亡累积发生率的竞争风险分析, figureFileSmall=eKHDi6x+g5JRMpHseq1Grw==, figureFileBig=9oZksPUgE8sVJXPNAhokkg==, tableContent=null), ArticleFig(id=1240986258986554144, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=EN, label=Figure 4, caption=Restricted cubic spline model for the associations between 25(OH)D and all-cause mortality, figureFileSmall=Kce8RhxOssUQlKaaHfv05Q==, figureFileBig=trBJKPUhZe5b2KtSi2Y2kw==, tableContent=null), ArticleFig(id=1240986259095606055, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=CN, label=图4, caption=25(OH)D与全因死亡率的限制立方样条图

注：对性别、年龄、种族、BMI、吸烟、CVD、高血压、糖尿病、血红蛋白、ALT、AST、Tb、ALP、白蛋白、肌酐、尿酸、尿素、磷、钙、HDL-c、LDL-c、eGFR、UACR、膳食维生素D、CRP校正后的加权限制性立方样条模型。

, figureFileSmall=Kce8RhxOssUQlKaaHfv05Q==, figureFileBig=trBJKPUhZe5b2KtSi2Y2kw==, tableContent=null), ArticleFig(id=1240986259766694701, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=EN, label=Figure 5, caption=Forest plot for subgroup analysis of association between 25(OH)D and all-cause mortality, figureFileSmall=FZ6HTXss7+BK5aovN2EIwQ==, figureFileBig=KJIgYwPsC45faPq7wkDVGQ==, tableContent=null), ArticleFig(id=1240986260144182070, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=CN, label=图5, caption=亚组分析25(OH)D与全因死亡率之间的关系, figureFileSmall=FZ6HTXss7+BK5aovN2EIwQ==, figureFileBig=KJIgYwPsC45faPq7wkDVGQ==, tableContent=null), ArticleFig(id=1240986260542640961, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=EN, label=Table 1, caption=

Baseline characteristics of patients with CKD grouped according to 25(OH)D quartile in NHANES, 2007—2018［（），n（%），M（P25，P75）］

, figureFileSmall=null, figureFileBig=null, tableContent=
25(OH)D (nmol/L)总数
(n=2 668)		Q1
(0～45.90)
(n=670)		Q2
(>45.90～58.50)
(n=667)		Q3
(>58.50～78.60)
(n=670)		Q4
(>78.60）
(n=661)		F/H/χ2值P值
加权11 715 4522 616 2642 943 8142 999 3573 156 017
年龄（岁）55.24±0.4654.93±0.9054.05±0.7755.08±0.9156.76±0.8021.348<0.001
性别24.352<0.001
女1 394(54.69)384(59.97)364(58.48)352(55.47)294(45.84)
男1 274(45.31)286(40.03)303(41.52)318(44.53)367(54.16)
种族161.595<0.001
墨西哥裔美国人496(13.17)118(13.86)136(14.27)130(13.58)112(11.27)
非西班牙裔的黑人830(20.61)299(35.29)241(23.95)160(14.63)130(11.18)
非西班牙裔白人823(51.83)137(37.76)173(48.71)226(54.16)286(63.89)
其他拉美裔266( 6.57)64(6.22)53(5.08)86(8.94)63(6.01)
其他种族253( 7.82)52(6.87)64(7.99)68(8.69)70(7.64)
公民身份2.4860.220
非美国公民377(11.11)74( 8.96)103(12.36)104(12.63)96(10.45)
美籍公民2 283(88.64)594(91.04)562(87.64)562(87.37)564(89.55)
婚姻9.6750.020
离婚340(12.95)87(13.01)85(12.32)81(13.71)87(14.13)
与伴侣同住163( 6.80)43(6.20)35(6.98)47(9.04)38(5.70)
已婚1 185(47.59)251(42.47)303(48.33)298(47.90)332(55.31)
未婚351(13.83)125(19.35)88(14.73)82(12.70)56(10.94)
分居120( 3.46)42(5.71)29(3.53)27(3.17)22(2.17)
丧偶417(12.77)95(13.27)107(14.11)110(13.49)105(11.75)
高血压8.8050.010
否856(36.35)189(29.55)211(34.83)239(40.25)217(39.85)
是1 812(63.65)480(70.45)456(65.17)431(59.75)444(60.15)
糖尿病4.6870.080
否1 482(58.99)351(54.17)367(56.94)378(60.80)385(62.96)
是1 186(41.01)318(45.83)300(43.06)292(39.20)276(37.04)
CVD史2.6670.180
否1 925(75.19)467(72.80)492(78.74)491(79.27)475(77.69)
是653(22.25)176(27.20)156(21.26)156(20.73)164(22.31)
教育程度10.4270.040
高中以下444(11.02)93( 8.98)107(10.81)128(12.21)116(11.88)
高中512(16.33)155(21.21)127(15.96)111(15.41)119(13.70)
高中以上1 707(72.51)421(69.81)430(73.23)430(72.38)425(74.42)
BMI (kg/m2)31.55±0.2432.37±0.4031.92±0.5231.60±0.5430.50±0.4211.6500.010
随访时间（月)72.75±1.2773.28±2.4072.50±2.4674.01±1.8171.70±2.532.4000.740
白细胞 (109/L)7.73±0.107.53±0.108.05±0.327.62±0.107.70±0.1111.777<0.001
血红蛋白 (g/dl)13.81±0.0513.42±0.1013.82±0.0913.82±0.0614.13±0.1012.814<0.001
ALT (U/L)25.66±0.7927.78±3.1226.50±1.3324.61±0.8124.17±0.588.446<0.001
AST (U/L)26.70±0.6130.16±2.4127.33±1.1525.14±0.5324.78±0.4510.232<0.001
Tb (μmol/L)11.24±0.1311.52±0.3211.17±0.2710.77±0.2311.55±0.277.165<0.001
ALP (mmol/L)76.54±0.7679.21±1.3676.91±1.4478.48±2.2272.17±1.0645.016<0.001
白蛋白(g/L)41.17±0.1040.12±0.2041.25±0.2041.37±0.1641.93±0.178.696<0.001
肌酐(μmol/L)95.55±2.3696.96±3.2096.83±5.0492.39±2.8395.90±4.498.433<0.001
尿酸(μmol/L)350.54±2.71357.45±4.42347.67±6.10346.19±4.74351.86±5.1614.431<0.001
尿素(mmol/L)5.81±0.085.77±0.195.72±0.175.68±0.136.01±0.169.465<0.001
磷(mmol/L)1.21±0.011.20±0.011.22±0.011.20±0.011.19±0.0125.402<0.001
钙(mmol/L)2.34±0.002.32±0.012.34±0.012.34±0.012.35±0.007.550<0.001
HDL-c (mmol/L)1.29±0.011.36±0.031.28±0.021.27±0.021.27±0.027.021<0.001
LDL-c (mmol/L)2.83±0.032.87±0.072.76±0.072.92±0.072.79±0.0611.3460.008
eGFR [ml/（min·1.73 m2）]82.98±0.9283.60±1.7385.00±1.6483.09±1.7280.75±1.6115.903<0.001
UACR (mg/g)268.95±25.59415.36±78.13294.51±51.41223.74±32.35171.50±22.9011.7770.004
膳食维生素D(mcg)8.50±0.286.43±0.348.26±0.519.07±0.579.67±0.5713.330<0.001
CRP（mg/L）0.28(0.12,0.67)0.37(0.13,0.75)0.29(0.14,0.66)0.23(0.12,0.57)0.27(0.13,0.64)1.0600.210
), ArticleFig(id=1240986261012403022, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=CN, label=表1, caption=

NHANES 2007—2018年25(OH)D四分位数分组的CKD患者基线特征［（），n（%），M（P25，P75）］

, figureFileSmall=null, figureFileBig=null, tableContent=
25(OH)D (nmol/L)总数
(n=2 668)		Q1
(0～45.90)
(n=670)		Q2
(>45.90～58.50)
(n=667)		Q3
(>58.50～78.60)
(n=670)		Q4
(>78.60）
(n=661)		F/H/χ2值P值
加权11 715 4522 616 2642 943 8142 999 3573 156 017
年龄（岁）55.24±0.4654.93±0.9054.05±0.7755.08±0.9156.76±0.8021.348<0.001
性别24.352<0.001
女1 394(54.69)384(59.97)364(58.48)352(55.47)294(45.84)
男1 274(45.31)286(40.03)303(41.52)318(44.53)367(54.16)
种族161.595<0.001
墨西哥裔美国人496(13.17)118(13.86)136(14.27)130(13.58)112(11.27)
非西班牙裔的黑人830(20.61)299(35.29)241(23.95)160(14.63)130(11.18)
非西班牙裔白人823(51.83)137(37.76)173(48.71)226(54.16)286(63.89)
其他拉美裔266( 6.57)64(6.22)53(5.08)86(8.94)63(6.01)
其他种族253( 7.82)52(6.87)64(7.99)68(8.69)70(7.64)
公民身份2.4860.220
非美国公民377(11.11)74( 8.96)103(12.36)104(12.63)96(10.45)
美籍公民2 283(88.64)594(91.04)562(87.64)562(87.37)564(89.55)
婚姻9.6750.020
离婚340(12.95)87(13.01)85(12.32)81(13.71)87(14.13)
与伴侣同住163( 6.80)43(6.20)35(6.98)47(9.04)38(5.70)
已婚1 185(47.59)251(42.47)303(48.33)298(47.90)332(55.31)
未婚351(13.83)125(19.35)88(14.73)82(12.70)56(10.94)
分居120( 3.46)42(5.71)29(3.53)27(3.17)22(2.17)
丧偶417(12.77)95(13.27)107(14.11)110(13.49)105(11.75)
高血压8.8050.010
否856(36.35)189(29.55)211(34.83)239(40.25)217(39.85)
是1 812(63.65)480(70.45)456(65.17)431(59.75)444(60.15)
糖尿病4.6870.080
否1 482(58.99)351(54.17)367(56.94)378(60.80)385(62.96)
是1 186(41.01)318(45.83)300(43.06)292(39.20)276(37.04)
CVD史2.6670.180
否1 925(75.19)467(72.80)492(78.74)491(79.27)475(77.69)
是653(22.25)176(27.20)156(21.26)156(20.73)164(22.31)
教育程度10.4270.040
高中以下444(11.02)93( 8.98)107(10.81)128(12.21)116(11.88)
高中512(16.33)155(21.21)127(15.96)111(15.41)119(13.70)
高中以上1 707(72.51)421(69.81)430(73.23)430(72.38)425(74.42)
BMI (kg/m2)31.55±0.2432.37±0.4031.92±0.5231.60±0.5430.50±0.4211.6500.010
随访时间（月)72.75±1.2773.28±2.4072.50±2.4674.01±1.8171.70±2.532.4000.740
白细胞 (109/L)7.73±0.107.53±0.108.05±0.327.62±0.107.70±0.1111.777<0.001
血红蛋白 (g/dl)13.81±0.0513.42±0.1013.82±0.0913.82±0.0614.13±0.1012.814<0.001
ALT (U/L)25.66±0.7927.78±3.1226.50±1.3324.61±0.8124.17±0.588.446<0.001
AST (U/L)26.70±0.6130.16±2.4127.33±1.1525.14±0.5324.78±0.4510.232<0.001
Tb (μmol/L)11.24±0.1311.52±0.3211.17±0.2710.77±0.2311.55±0.277.165<0.001
ALP (mmol/L)76.54±0.7679.21±1.3676.91±1.4478.48±2.2272.17±1.0645.016<0.001
白蛋白(g/L)41.17±0.1040.12±0.2041.25±0.2041.37±0.1641.93±0.178.696<0.001
肌酐(μmol/L)95.55±2.3696.96±3.2096.83±5.0492.39±2.8395.90±4.498.433<0.001
尿酸(μmol/L)350.54±2.71357.45±4.42347.67±6.10346.19±4.74351.86±5.1614.431<0.001
尿素(mmol/L)5.81±0.085.77±0.195.72±0.175.68±0.136.01±0.169.465<0.001
磷(mmol/L)1.21±0.011.20±0.011.22±0.011.20±0.011.19±0.0125.402<0.001
钙(mmol/L)2.34±0.002.32±0.012.34±0.012.34±0.012.35±0.007.550<0.001
HDL-c (mmol/L)1.29±0.011.36±0.031.28±0.021.27±0.021.27±0.027.021<0.001
LDL-c (mmol/L)2.83±0.032.87±0.072.76±0.072.92±0.072.79±0.0611.3460.008
eGFR [ml/（min·1.73 m2）]82.98±0.9283.60±1.7385.00±1.6483.09±1.7280.75±1.6115.903<0.001
UACR (mg/g)268.95±25.59415.36±78.13294.51±51.41223.74±32.35171.50±22.9011.7770.004
膳食维生素D(mcg)8.50±0.286.43±0.348.26±0.519.07±0.579.67±0.5713.330<0.001
CRP（mg/L）0.28(0.12,0.67)0.37(0.13,0.75)0.29(0.14,0.66)0.23(0.12,0.57)0.27(0.13,0.64)1.0600.210
), ArticleFig(id=1240986261142426458, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=EN, label=Table 2, caption=

Association of 25(OH)D with all-cause mortality (Cox regression model) (n=2 668)

, figureFileSmall=null, figureFileBig=null, tableContent=
25(OH)DHR未校正模型模型1模型2
HR(95%CI)P值HR(95%CI)P值HR(95%CI)P值
每增加一个标准差0.92 (0.85～0.99)0.0220.82 (0.76～0.89)<0.0010.85 (0.77～0.94)0.001
分类
Q1参照参照参照
Q20.83 (0.68～1.02)0.0840.84 (0.68～1.04)0.1160.9 (0.7～1.16)0.423
Q30.73 (0.59～0.9)0.0040.63 (0.5～0.79)<0.0010.71 (0.54～0.93)0.013
Q40.83 (0.67～1.02)0.0800.64 (0.51～0.79)<0.0010.72 (0.55～0.94)0.014
趋势性P值0.036<0.0010.006
), ArticleFig(id=1240986261335364447, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=CN, label=表2, caption=

25(OH)D与全因死亡率的相关性(Cox回归模型)(n=2 668)

, figureFileSmall=null, figureFileBig=null, tableContent=
25(OH)DHR未校正模型模型1模型2
HR(95%CI)P值HR(95%CI)P值HR(95%CI)P值
每增加一个标准差0.92 (0.85～0.99)0.0220.82 (0.76～0.89)<0.0010.85 (0.77～0.94)0.001
分类
Q1参照参照参照
Q20.83 (0.68～1.02)0.0840.84 (0.68～1.04)0.1160.9 (0.7～1.16)0.423
Q30.73 (0.59～0.9)0.0040.63 (0.5～0.79)<0.0010.71 (0.54～0.93)0.013
Q40.83 (0.67～1.02)0.0800.64 (0.51～0.79)<0.0010.72 (0.55～0.94)0.014
趋势性P值0.036<0.0010.006
), ArticleFig(id=1240986261670908776, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=EN, label=Table 3, caption=

Association of 25(OH)D with CVD mortality (competing-risk model)

, figureFileSmall=null, figureFileBig=null, tableContent=
25(OH)D未校正模型模型1模型2
SHR(95%CI)P值SHR(95%CI)P值SHR(95%CI)P值
每增加一个标准差0.79 (0.68～0.92)0.0030.80 (0.69～0.92)0.0020.80 (0.67～0.94)0.005
分类
Q1参照参照参照
Q20.68 (0.45～1.02)0.0600.69 (0.47～1.01)0.0570.67 (0.33～1.35)0.260
Q30.66 (0.44～1)0.0510.65 (0.44～0.96)0.0290.52 (0.25～1.07)0.076
Q40.52 (0.34～0.79)0.0020.55 (0.37～0.82)0.0030.470 (0.22～0.98)0.044
趋势性P值0.0030.0040.055
), ArticleFig(id=1240986261813515124, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=CN, label=表3, caption=

25(OH)D与CVD死亡率的关系(竞争风险模型)

, figureFileSmall=null, figureFileBig=null, tableContent=
25(OH)D未校正模型模型1模型2
SHR(95%CI)P值SHR(95%CI)P值SHR(95%CI)P值
每增加一个标准差0.79 (0.68～0.92)0.0030.80 (0.69～0.92)0.0020.80 (0.67～0.94)0.005
分类
Q1参照参照参照
Q20.68 (0.45～1.02)0.0600.69 (0.47～1.01)0.0570.67 (0.33～1.35)0.260
Q30.66 (0.44～1)0.0510.65 (0.44～0.96)0.0290.52 (0.25～1.07)0.076
Q40.52 (0.34～0.79)0.0020.55 (0.37～0.82)0.0030.470 (0.22～0.98)0.044
趋势性P值0.0030.0040.055
), ArticleFig(id=1240986262014841730, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=EN, label=Table 4, caption=

Association between 25(OH)D and all-cause mortality after exclusion of CKD patients who underwent dialysis in the past 12 months (n=2 621)

, figureFileSmall=null, figureFileBig=null, tableContent=
25(OH)D未校正模型模型1模型2
HR(95%CI)P值HR(95%CI)P值HR(95%CI)P值
每增加一个标准差0.91 (0.84～0.98)0.0120.80 (0.74～0.87)<0.0010.85 (0.77～0.93)0.001
分类
Q1参照参照参照
Q20.82 (0.66～1.01)0.0660.79 (0.63～0.98)0.0350.9 (0.7～1.16)0.414
Q30.81 (0.66～1.01)0.0570.61 (0.48～0.76)<0.0010.71 (0.54～0.93)0.014
Q40.71 (0.57～0.89)0.0020.59 (0.47～0.74)<0.0010.7 (0.54～0.91)0.008
趋势性P值0.024<0.0010.003
), ArticleFig(id=1240986262165836683, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240972417972105664, language=CN, label=表4, caption=

排除过去12个月内接受透析的CKD患者后25(OH)D与全因死亡率的关系(n=2 621)

, figureFileSmall=null, figureFileBig=null, tableContent=
25(OH)D未校正模型模型1模型2
HR(95%CI)P值HR(95%CI)P值HR(95%CI)P值
每增加一个标准差0.91 (0.84～0.98)0.0120.80 (0.74～0.87)<0.0010.85 (0.77～0.93)0.001
分类
Q1参照参照参照
Q20.82 (0.66～1.01)0.0660.79 (0.63～0.98)0.0350.9 (0.7～1.16)0.414
Q30.81 (0.66～1.01)0.0570.61 (0.48～0.76)<0.0010.71 (0.54～0.93)0.014
Q40.71 (0.57～0.89)0.0020.59 (0.47～0.74)<0.0010.7 (0.54～0.91)0.008
趋势性P值0.024<0.0010.003
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基于NHANES调查分析慢性肾脏病患者血清25(OH)D与全因死亡和心血管疾病死亡的相关性
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李洛华 1 , 蒋红樱 2
现代预防医学 | 流行病与统计方法 2024,51(9): 1555-1561
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现代预防医学 | 流行病与统计方法 2024, 51(9): 1555-1561
基于NHANES调查分析慢性肾脏病患者血清25(OH)D与全因死亡和心血管疾病死亡的相关性
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李洛华1, 蒋红樱2
作者信息
  • 1.九江市第一人民医院肾内科，江西 九江 332000
  • 2.昆明医科大学第二附属医院肾内科，云南 昆明 650000

    • 李洛华（1990—），男，主治医师，研究方向：慢性肾脏病的研究

通讯作者:

蒋红樱，E-mail:
Analysis of the correlation between serum 25-hydroxyvitamin D and all-cause death and cardiovascular disease in patients with chronic kidney disease based on NHANES
Luo-hua LI1, Hong-ying JIANG2
Affiliations
  • The First People’s Hospital of Jiujiang, Jiujiang, Jiangxi 332000, China
出版时间: 2024-05-10 doi: 10.20043/j.cnki.MPM.202312035
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摘要
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目的

25(OH)D缺乏在慢性肾脏病(chronic renal disease, CKD)患者中很常见。我们的目的是验证低25（OH）D水平是否会增加CKD患者发生全因死亡及心血管死亡的风险。

方法

本研究为回顾性队列研究，基于美国国家健康与营养调查(NHANES)和美国国家死亡指数(NDI) 2007—2018年数据库。共纳入2 668例符合条件的受试者，并随访至2019年12月31日。采用Kaplan-Meier生存曲线、Cox回归和限制性立方样条分析评估25（OH）D和全因死亡率、心血管疾病死亡之间的关系。

结果

在11 715 452例符合纳入标准的加权人群中，中位随访6年期间，发生了665例全因死亡，其中196例死于心血管原因。在校正协变量后，较低的25（OH）D水平与CKD患者的全因死亡（HR=0.85，95%CI：0.77～0.94）及心血管疾病死亡（SHR=0.80，95%CI：0.67～0.94）风险升高显著相关。当25（OH）D作为分类变量(四分位数)进行分析时，也观察到一致的结果（P均<0.05）。加权的限制立方样条曲线显示25（OH）D水平与全因死亡率呈反“J”型相关系(PNonliner>0.05)，亚组分析（交互作用的P>0.05）和敏感性分析（HR=0.85，95%CI：0.77～0.93）也显示出相似的结果。

结论

无论是作为一个连续变量还是分类变量，低25(OH)D水平都与CKD全因死亡和心血管疾病死亡风险增加显著相关，而且25(OH)D与全因死亡和心血管死亡呈反“J”型相关。

25 (OH) D  /  心血管疾病  /  全因死亡率  /  NHANES  /  CKD
Objective

The 25(OH)D deficiency is a prevalent issue among patients with chronic kidney disease (CKD). The aim of our study is to investigate whether low levels of 25(OH)D are associated with increased all-cause and cardiovascular mortality in patients with CKD.

Methods

This retrospective cohort study utilized the National Health and Nutrition Examination Survey (NHANES) and the National Death Index (NDI) 2007—2018 database to investigate the association between 25(OH)D levels and all-cause mortality as well as cardiovascular mortality. A total of 2 668 eligible subjects were included in this study, with follow-up conducted until December 31, 2019. Cox proportional hazards regression, restricted cubic spline, Kaplan-Meier survival curves, and competing risk survival analysis were performed to evaluate the associations. Furthermore, subgroup and sensitivity analyses were performed.

Results

During a median follow-up of 6 years in a weighted population of 11 715 452 eligible participants, there were 665 deaths from any cause, including 196 cardiovascular-related deaths. After adjusting for covariates, lower levels of 25(OH)D were significantly associated with increased risks for both all-cause (HR=0.85, 95%CI: 0.77-0.94) and cardiovascular mortality (SHR=0.80, 95%CI: 0.67-0.94). Consistent results were also observed when analyzing 25(OH)D as a categorical variable (quartile) (both P<0.05). Weighted restricted cubic splines revealed an inverse J-shaped association between levels of 25 (OH) D and all-cause mortality (Pnonliner> 0.05). Subgroup analysis (Pinteraction>0.05) and sensitivity analysis (HR=0.85, 95%CI: 0.77-0.93) yielded similar findings.

Conclusion

Lower 25(OH)D levels, both as a continuous and categorical variable, are significantly associated with an increased risk of all-cause mortality and cardiovascular disease-related mortality.The 25(OH)D has a negative j-shaped association with all-cause and cardiovascular mortality.

25(OH)D  /  Cardiovascular diseases  /  All-cause mortality  /  NHANES  /  CKD
李洛华, 蒋红樱. 基于NHANES调查分析慢性肾脏病患者血清25(OH)D与全因死亡和心血管疾病死亡的相关性. 现代预防医学, 2024 , 51 (9) : 1555 -1561 . DOI: 10.20043/j.cnki.MPM.202312035
Luo-hua LI, Hong-ying JIANG. Analysis of the correlation between serum 25-hydroxyvitamin D and all-cause death and cardiovascular disease in patients with chronic kidney disease based on NHANES[J]. Modern Preventive Medicine, 2024 , 51 (9) : 1555 -1561 . DOI: 10.20043/j.cnki.MPM.202312035
正文
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慢性肾脏疾病(chronic renal disease, CKD)是一个重要的全球性公共卫生问题。由于高血压、代谢性疾病、衰老等因素，CKD的发病率明显增加。它影响到世界约8%～16%的人口，是第16大死亡原因[1]。25-羟维生素D[25-hydroxyvitamin D, 25(OH)D]在人体中发挥着重要作用，它在肾脏中转化为其活性形式，并帮助维持矿物质代谢平衡和调节免疫系统。维生素D代谢紊乱在CKD患者中常见，并在该人群中进行常规评估和治疗。然而，一些研究表明，较低的维生素D浓度与CKD患者死亡和心血管并发症风险增加相关[2-4]。在最近的一项队列研究中，研究人员通过多因素回归分析发现，基线25(OH)D水平与CKD结局之间没有显著关联[5]。由此可见，CKD患者维生素D缺乏与预后的关系尚存争议。此外，对于CKD患者25-羟基维生素D的最佳血清阈值尚无共识。鉴于越来越多的证据表明25(OH)D在CKD发展中的重要性，研究基线25(OH)D水平是否可以作为CKD患者死亡率的预测因子是至关重要的。本研究使用2007—2018年全国健康与营养调查(NHANES)的数据，探讨美国成人CKD患者全因死亡和心血管疾病(cardiovascular disease, CVD)死亡率与25(OH)D水平之间的关系。
1　资料与方法
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1.1　研究对象
本研究纳入了2007—2018年NHANES中2 668名符合条件的参与者，涵盖了所有年龄≥18岁的个体，排除了孕妇和数据资料不完整者，见图1。生存数据的时间范围从访谈日期至死亡或截至2019年12月31日，死亡率随访数据不合格的个体排除在外。本研究使用的数据来自公开数据库(https://www.cdc.gov/nchs/nhanes/index.htm，于2023年8月11日访问)[6]。
根据《改善全球肾脏病预后组织（KDIGO）指南》，CKD的分期是根据估计的肾小球滤过率(estimated glomerular filtration rate, eGFR)和/或肾脏损害的证据来确定的[7]。NHANES研究是由疾病预防控制中心进行的，国家卫生统计中心(NCHS)伦理审查委员会批准了这项研究。所有参与者均提供知情同意[8]。
1.2　研究资料
研究的变量包括性别、年龄、种族、体重指数(body mass index, BMI)、CVD、高血压、糖尿病、教育程度(高中以下、高中或同等学历、高中以上)。通过标准化访谈收集血红蛋白、丙氨酸转氨酶(alanine transaminase, ALT)、天冬氨酸转氨酶(aspartate aminotransferase, AST)、总胆红素(total bilirubin,Tb)、碱性磷酸酶(alkaline phosphatase, ALP)、白蛋白、肌酐、尿酸、血尿素氮磷、钙、高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-c)、低密度脂蛋白胆固醇(low density lipoprotein cholesterin, LDL-c)、eGFR、UACR、膳食中维生素D摄入量、C反应蛋白(C-reactive protein, CRP)等实验室数据。由经过培训的医务人员进行体格检查、实验室检查和问卷调查。
1.3　死亡结局的确定
全因死亡的定义为截至2019年12月31日的美国国家死亡索引(National Death Index)记录，随访期间的所有原因导致的死亡。CVD死亡根据《国际疾病分类》第10版的编码I00-I09、I11、I13、I20-I51、I60-I69来确定[9-10]。
1.4　统计分析
考虑到NHANES调查的复杂、多阶段、概率抽样设计，对某些平民、非制度化美国亚组人群的代表性参与者进行了过抽样。为了确保结果的可靠性，因此，我们整合了在NHANES分析中创建的样本权重，新合并的样本权重即为原始2年基础权重除以6得到的权重。采用描述性统计分析人群特征和分布[6]。符合正态分布连续变量表示为（均数±标准差），偏态分布以［M（P25，P75）］表示。分类变量以频率和百分比表示。25(OH)D按四分位数进行分类，并确定趋势性P值。使用Kaplan-Meier生存分析和竞争风险模型对生存率估计值和累积事件发生率进行了比较。经Schoenfeld残差法检验25（OH）D对生存风险的影响满足PH等比例风险假定后，采用Cox回归比例风险模型分析25(OH)D与全因死亡和CVD死亡的关系。此外，本研究还排除了过去12个月内接受过透析的参与者后进行了敏感性分析，从而以减少潜在的反向因果偏倚。根据年龄(0～60岁、>60岁)、性别(男性、女性)、BMI(0～25 kg/m2、>25～30 kg/m2、>30 kg/m2)、种族、高血压史(是或否)、糖尿病史(是或否)、CVD史进行分层，探讨25(OH)D与全因死亡的相关性。研究25(OH)D与不同分层因素之间的潜在交互作用。使用R软件(4.3.1版)进行了所有统计学分析。检验水准α=0.05。
2　结果
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2.1　基线人口与临床特征
共有2 668名参与者(NHANES 2007—2018年)符合纳入标准，基于新合并的样本权重加权后共有11 715 452名具有全国代表性的参与者。在16 551人/年的随访期间，共记录了665例死亡，其中196例死于心血管原因。死亡病例中女性占54.69%，平均年龄(55.24±0.46)岁。中位随访期为72月。25(OH)D的加权后基线数值为（60.7±0.8）nmol/L。根据25(OH)D四分位分组的基线特征见表1。年轻、女性和非西班牙裔白种人的25(OH)D水平更低，同时他们高血压、糖尿病或CVD史的患病率也更高
2.2　25(OH)D与CKD预后的关系
Kaplan-Meier生存分析和竞争风险模型显示，与25(OH)D水平较高的患者相比，25(OH)D水平较低的患者的全因死亡和CVD死亡风险显著增加，见图2、3。加权后多变量Cox回归分析显示，在校正年龄、性别、种族、BMI、种族、慢性病史和实验室指标后，低25（OH）D水平与全因死亡率和CVD死亡率的增加显著相关。如表2所示，从最低到最高25（OH）D类别（0～45.9、&gt；45.9～58.5、&gt；58.5～78.6和&gt；78.6），多变量调整的全因死亡风险成逐渐下降趋势（趋势性P值&lt；0.05）。表3结果显示，CVD死亡风险同样呈下降趋势（趋势性P值<0.05）。此外，25(OH)D水平每增加一个标准差，CKD患者的全因死亡风险就会降低15%，CVD死亡风险就会降低20%。
2.3　25(OH)D与CKD死亡率之间的剂量反应关系
如图4所示，加权后的限制性立方样条曲线显示，在对几个潜在混杂因素进行校正后，25(OH)D与全因死亡率之间的非线性关联无统计学意义(PNonliner>0.05)。此外，25(OH)D水平与全因死亡率呈负相关。
2.4　亚组及敏感性分析
如图5所示，我们进行了亚组分析，以调查人口统计学特征和合并症是否可以影响25(OH)D和全因死亡率之间的相关性。结果显示不同年龄(0～60岁、>60岁)、性别(男性、女性)、BMI (0～25 kg/m2, >25～30 kg/m2，>30 kg/m2)、种族、高血压史(是或否)、糖尿病史(是或否)和CVD史（有或无）的亚组中保持一致，与25(OH)D无明显的交互作用(交互作用的P值均为>0.05)。值得注意的是，25(OH)D与全因死亡率之间的相关性在BMI为0～25 kg/m2、其他种族及无高血压的患者中均无统计学意义(P>0.05)。排除过去12月曾透析的参与者后，敏感性分析仍得到了与之相似的结果，这更增加了我们研究结果的稳健性，见表4。
3　讨论
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在这项具有全国代表性的横断面研究中，本研究观察到25(OH)D水平与全因死亡和CVD死亡显著相关。这些结果在各种分层和敏感性分析中保持一致。限制性立方样条分析显示，25(OH)D水平与全因死亡风险呈线性关系，较低的25(OH)D水平与较高的全因死亡风险相关。值得注意的是，关于25(OH)D与CKD患者死亡率之间关系的纵向数据很少。然而，一项纳入168例CKD患者的小型观察性研究表明，25(OH)D可预测死亡和肾脏病进展[11]。观察性研究表明，较低的25(OH)D水平与肾脏疾病进展显著相关[12-13]，维生素D缺乏被认为是CKD进展和死亡的预后因素。少量的队列研究表明，透析前CKD患者循环中25(OH)D水平降低提示全因死亡风险增加[14-15]。这些发现与本研究中观察到的结果基本一致。
维生素D缺乏在CKD患者中很常见，甚至在早期阶段，而且比一般人群更明显。这可能是由于几个因素，包括由于肾单位减少和肾小管功能障碍导致的1α-羟化酶活性降低[16-17]。关于25(OH)D缺乏与CKD患者预后相关的机制有多种，包括调节细胞增殖[17]、分化、免疫调节、骨代谢、通过肾素调节控制血压[18]，以及改变与动脉粥样硬化相关的炎症反应[19]。在肾脏中，维生素D信号与足细胞形态相关，通过保护足细胞减少肾脏疾病的进展。此外，维生素D及其类似物还通过免疫调节、抗炎和抑制RAS等机制改善肾小球硬化和间质纤维化[20]。
本研究发现，25(OH)D缺乏同样增加CVD死亡率。可能的机制如下：25(OH)D缺乏可能与成纤维细胞生长因子23 (fibroblast growth factor 23,FGF23)有关，FGF23的血清水平随着肾功能损害显著升高，FGF23的上调直接导致1-α-羟化酶活性降低，促使肾小管对磷的再吸收减少，并抑制1,25-二羟基维生素D的产生。高浓度的FGF23与CKD患者的左心室肥厚、CVD死亡和肾病进展相关[21]。
此外，本研究显示低25(OH)D水平与蛋白尿之间存在关联，这也可能是导致25(OH)D下降的原因之一[22]。正如有研究显示蛋白尿是CKD患者发生CVD和死亡的独立危险因素[23]。观察性研究报道，维生素D缺乏与蛋白尿、肾小球滤过率降低和CKD的快速进展有关[24]。在本研究中，Q1组的UACR明显高于其他组，这更支持维生素D缺乏与更高的蛋白尿发生率相关的观点。此外，动物研究表明，维生素D对多种肾病模型的蛋白尿、肾小球结构维持和体液调节有有益作用[25]。
尽管本研究结果表明低25(OH)D是CKD患者死亡的危险因素，但关于25(OH)D在CKD中的作用及其最佳阈值仍缺乏文献共识。维持较高的血清25(OH)D水平对CKD患者预防骨质疏松和CVD以及保护免疫系统功能至关重要。多项研究表明，维生素D治疗不仅可以改善而且可以逆转足细胞损伤，尤其是在1,25-(OH) d3缺乏的动物模型中[26]。肾功能受损可导致维生素D代谢和活化受损，使血清25(OH)D水平进一步降低。因此，维持充足的血清25(OH)D对CKD患者的预后至关重要[27]。
本研究还发现非裔美国人/黑人总体上比其他种族患维生素D缺乏症的比例更高，这与已有的研究不谋而合[28-29]。这也可以解释许多心脏代谢疾病在非裔美国人中也不成比例的高发病率也与维生素D的水平较低有关[28]。值得注意的是，维生素D代谢物的种族差异得到了充分的证明[22]。黑皮肤的25(OH)D水平较低，因为富含黑色素的皮肤减少了对合成维生素D所需的紫外线B的吸收，但我们没有注意到25(OH)D的种族与研究结果之间的显著交互作用。此外，与欧裔美国人相比，非裔美国人的全因死亡和与CKD相关的CVD风险更高[30]。这是一种独立的效应，与维生素D氧化应激/炎症相互作用有关，还是由于其他原因，目前尚不清楚。
本研究存在一些优势和局限性。本研究使用具有全国代表性的大型样本进行了分析，并针对人口统计学、检查和实验室协变量以及膳食中维生素D摄入量进行了校正，这使我们能够可靠地评估25(OH)D水平与研究结果之间的关系。敏感性和亚组分析进一步证实了我们结果的稳健性，获得了相似的结果。当然本研究也存在某些局限性。首先，观察性研究设计无法建立真正的因果关系，但我们在敏感性分析中排除了过去12月内透析的参与者。其次，本研究仅校正了维生素D饮食摄入量，没有校正关于营养维生素D补充剂、活性维生素D类似物的使用信息。另外，由于信息是患者自我报告的，无法避免可能的测量误差。而且我们无法评估全因死亡及CVD死亡访视期间25（OH）D变化的影响，因为25（OH）D在本研究中只测量了一次，NHANES 2007—2018仅收集基线时的25（OH）D信息，这可能低估了两者之间的联系。最后，虽然本研究已经调整了大范围的混杂因素，但仍可能存在残余或未测量的混杂因素。此外，未来的研究希望能进一步探索最佳的维生素D阈值水平以及探讨有效的治疗策略，以更加全面的改善CKD患者的预后。
总之，本研究发现25(OH)D与全因死亡率和CVD死亡率呈反“J”型关系，较低的25（OH）D与全因死亡和CVD死亡风险升高呈线性相关。这些结果支持25（OH）D对CKD死亡的独立预后价值。建议在当前对包括ESRD之内的所有CKD患者常规检测25（OH）D，用于识别CKD死亡的高危人群，以帮助从预防性治疗中获益的高危个体。
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  • 云南省万人计划“名医”专项资金项目(YNWR-MY-2019-075)
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参考文献 引证文献
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2024年第51卷第9期
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doi: 10.20043/j.cnki.MPM.202312035
  • 接收时间：2023-12-03
  • 首发时间：2026-03-18
  • 出版时间：2024-05-10
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  • 收稿日期：2023-12-03
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云南省万人计划“名医”专项资金项目(YNWR-MY-2019-075)
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    1.九江市第一人民医院肾内科，江西 九江 332000
    2.昆明医科大学第二附属医院肾内科，云南 昆明 650000

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蒋红樱，E-mail:
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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