基于NHANES数据库中年人群血清同型半胱氨酸水平与肾功能下降的阈值效应分析

doi:10.20223/j.cnki.1000-8535.2025.08.007

广州医药 ›› 2025, Vol. 56 ›› Issue (8): 1061-1068.DOI: 10.20223/j.cnki.1000-8535.2025.08.007

基于NHANES数据库中年人群血清同型半胱氨酸水平与肾功能下降的阈值效应分析

何婷, 彭晓辉, 黄玉宇, 王衍慧, 连兴基, 张兵

华南理工大学附属第二医院（广州市第一人民医院）老年肾内科（广东广州 510180）

收稿日期:2025-03-11 出版日期:2025-08-20 发布日期:2025-09-17
通讯作者: 彭晓辉,E-mail：eypengxiaohui@scut.edu.cn
基金资助:
广州市科技市校（院）联合资助项目基础与应用基础研究项目（202201020512; 202102010017）; 广州市卫生健康科技一般引导项目（20221A011004）

Threshold effect of serum homocysteine level on kidney function decline among middle-aged adults in America based on NHANES database

HE Ting, PENG Xiaohui, HUANG Yuyu, WANG Yanhui, LIAN Xingji, ZHANG Bing

Department of Geriatrics,Guangzhou First People's Hospital,The Second Affiliated Hospital,School of Medicine,South China University of Technology,Guangzhou 510180,China

Received:2025-03-11 Online:2025-08-20 Published:2025-09-17

摘要/Abstract

摘要： 目的血清同型半胱氨酸（Hcy）水平与慢性肾脏病（CKD）的进展相关,但中年人群的非线性关联研究较少,本研究旨在寻找慢性肾脏病危险因素。方法本研究基于NHANES 1996—2006年数据,纳入5 361例45~65岁参与者,以估算肾小球滤过率（eGFR）<60 mL/（min·1.73 m²）和尿白蛋白/肌酐比值（uACR）≥30 mg/g评估肾功能下降。结果通过逻辑回归及平滑曲线拟合分析发现,Hcy每升高1 µmol/L,eGFR降低的风险增加8%（OR=1.08,95%CI：1.06~1.10）,uACR升高的风险增加2%（OR=1.02,95%CI：1.00~1.04）。非线性分析显示,Hcy对eGFR的阈值效应拐点为13.4 µmol/L（拐点左侧OR=1.59,95%CI：1.49~1.70;右侧无显著关联）。亚组分析表明,性别、高血压、糖尿病等协变量无交互作用,然而,在敏感性分析中,糖尿病患者中Hcy与eGFR降低的关联更强（交互P=0.015 8）。结论本研究提示,控制Hcy水平或可延缓美国中年人群（尤其是糖尿病患者）的肾功能衰退。

关键词: 血清同型半胱氨酸, 肾功能下降, 阈值效应, NHANES

Abstract: Objective Elevated serum homocysteine（Hcy）levels are linked to chronic kidney disease（CKD）progression,yet the nonlinear relationship in middle-aged populations remains underexplored．Methods This study analyzed data from 5 361 participants aged 45-65 years in the NHANES 1996-2006 cohort．Renal dysfunction was defined as an estimated glomerular filtration rate（eGFR）<60 mL/min/1.73 m² and urinary albumin-to-creatinine ratio（uACR）≥30 mg/g．Results Logistic regression and smoothed curve fitting revealed that each 1 µmol/L increase in Hcy elevated the risk of reduced eGFR by 8%（OR=1.08,95% CI：1.06-1.10）and uACR by 2%（OR=1.02,95% CI：1.00-1.04）．A nonlinear threshold effect was identified at 13.4 µmol/L,with a stronger association below this threshold（OR=1.59,95% CI：1.49-1.70）and no significant effect above it．Subgroup analyses showed no interactions with gender or hypertension,but a stronger Hcy-eGFR association was observed in diabetics（interaction P=0.0158）．Conclusions These findings suggest that controlling Hcy levels may mitigate renal decline,particularly in diabetic populations,warranting further causal investigations．

Key words: homocysteine, renal function decline, threshold effect, NHANES

何婷, 彭晓辉, 黄玉宇, 王衍慧, 连兴基, 张兵. 基于NHANES数据库中年人群血清同型半胱氨酸水平与肾功能下降的阈值效应分析[J]. 广州医药, 2025, 56(8): 1061-1068.

HE Ting, PENG Xiaohui, HUANG Yuyu, WANG Yanhui, LIAN Xingji, ZHANG Bing. Threshold effect of serum homocysteine level on kidney function decline among middle-aged adults in America based on NHANES database[J]. Guangzhou Medical Journal, 2025, 56(8): 1061-1068.

参考文献

[1] MILLS K T,XU Y,ZHANG W,et al.A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010[J].Kidney Int,2015,88(5):950-957.
[2] MADERO M,LEVIN A,AHMED S B,et al.Evaluation and management of chronic kidney disease:Synopsis of the kidney disease:Improving global outcomes 2024 clinical practice guideline[J].Ann Intern Med,2025,178(5):705-713.
[3] LU H,LUO Y,WANG C,et al.The urine albumin-to-creatinine ratio is a reliable indicator for evaluating complications of chronic kidney disease and progression in IgA nephropathy in China[J].Clinics(Sao Paulo),2016,71(5):243-250.
[4] LIU S,NIU J,WU S,et al.Urinary albumin-to-creatinine ratio levels are associated with subclinical atherosclerosis and predict CVD events and all-cause deaths:A prospective analysis[J].BMJ Open,2021,11(3):e040890.
[5] PERNA A F,INGROSSO D.Homocysteine and chronic kidney disease:An ongoing narrative[J].J Nephrol,2019,32(5):673-675.
[6] CLARKE R,COLLINS R.Can dietary supplements with folic acid or vitamin B6 reduce cardiovascular risk Design of clinical trials to test the homocysteine hypothesis of vascular disease[J].J Cardiovasc Risk,1998,5(4):249-255.
[7] XU X,QIN X,LI Y,et al.Efficacy of folic acid therapy on the progression of chronic kidney disease:The renal substudy of the China stroke primary prevention trial[J].JAMA Intern Med,2016,176(10):1443-1450.
[8] LI Y,DAVID SPENCE J,WANG X,et al.Effect of vitamin B₁₂ levels on the association between folic acid treatment and CKD progression:A post hoc analysis of a folic acid interventional trial[J].Am J Kidney Dis,2020,75(3):325-332.
[9] SHANKAR A,WANG J J,CHUA B,et al.Positive association between plasma homocysteine level and chronic kidney disease[J].Kidney Blood Press Res,2008,31(1):55-62.
[10] SHEN Z,ZHANG Z,ZHAO W.Relationship between plasma homocysteine and chronic kidney disease in US patients with type 2 diabetes mellitus:A cross-sectional study[J].BMC Nephrol,2022,23(1):419.
[11] 魏锦坤,林锡民,黄南和.冠心病患者血清HCY、HO-1水平及其与冠状动脉Gensini积分的相关性研究[J].广州医药,2022,53(5):72-75.
[12] LEVEY A S,STEVENS L A,SCHMID C H,et al.A new equation to estimate glomerular filtration rate[J].Ann Intern Med,2009,150(9):604-612.
[13] MORRIS M S.The role of B vitamins in preventing and treating cognitive impairment and decline[J].Adv Nutr,2012,3(6):801-812.
[14] RASZEWSKI G,LOROCH M,OWOC A,et al.Homocysteine and cognitive disorders of postmenopausal women measured by a battery of computer tests:Central nervous system vital signs[J].Arch Womens Ment Health,2015,18(4):623-630.
[15] KONG X,MA X,ZHANG C,et al.Hyperhomoc-ysteinemia increases the risk of chronic kidney disease in a Chinese middle-aged and elderly population-based cohort[J].Int Urol Nephrol,2017,49(4):661-667.
[16] FRANCIS M E,EGGERS P W,HOSTETTER T H,et al.Association between serum homocysteine and markers of impaired kidney function in adults in the United States[J].Kidney Int,2004,66(1):303-312.
[17] COHEN E,MARGALIT I,SHOCHAT T,et al.The relationship between the concentration of plasma homocysteine and chronic kidney disease:A cross sectional study of a large cohort[J].J Nephrol,2019,32(5):783-789.
[18] HUANG T,REN J,HUANG J,et al.Association of homocysteine with type 2 diabetes:A meta-analysis implementing mendelian randomization approach[J].BMC Genomics,2013(14):867.
[19] KUMAR J,INGELSSON E,LIND L,et al.No evidence of a causal relationship between plasma homocysteine and type 2 diabetes:A mendelian randomization study[J].Front Cardiovasc Med,2015(2):11.
[20] OSTRAKHOVITCH E A,TABIBZADEH S.Homocysteine in chronic kidney disease[J].Adv Clin Chem,2015(72):77-106.
[21] XIAO W,YE P,WANG F,et al.Plasma homocysteine is a predictive factor for accelerated renal function decline and chronic kidney disease in a community-dwelling population[J].Kidney Blood Press Res,2021,46(5):541-549.
[22] ZHANG C,XIA M,BOINI K M,et al.Epithelial-to-mesenchymal transition in podocytes mediated by activation of NADPH oxidase in hyperhomocysteinemia[J].Pflugers Arch,2011,462(3):455-467.
[23] CAI C,XIAO R,van HALM-LUTTERODT N,et al.Association of MTHFR,SLC19A1 genetic polymorphism,serum folate,vitamin B₁₂ and hcy status with cognitive functions in Chinese adults[J].Nutrients,2016,8(10):665.
[24] WANG L,CHEN J,LI J,et al.Threshold effect of plasma total homocysteine levels on cognitive function among hypertensive patients in China:A cross-sectional study[J].Front Neurol,2022(13):890499.

基于NHANES数据库中年人群血清同型半胱氨酸水平与肾功能下降的阈值效应分析

Threshold effect of serum homocysteine level on kidney function decline among middle-aged adults in America based on NHANES database

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 0

编辑推荐

Metrics

本文评价