广州市糖尿病、高血压患者尿液6种金属暴露水平与肾功能下降的相关性研究

doi:10.12183/j.scjpm.2025.0395

摘要/Abstract

摘要： 目的探究广州市糖尿病、高血压患者尿液铝、钛、铜、锌、钼和镉等6种金属暴露水平与肾功能下降的相关性。方法于2023年选取广州市辖区糖尿病和（或）高血压患者为研究对象,根据患病情况进行分组（糖尿病组、高血压组、糖尿病合并高血压组）。测定尿铝、钛、铜、锌、钼和镉的水平;以血清肌酐（Cr）值估算肾小球滤过率（GFR）。采用logistic回归和加权分位数和（WQS）回归模型探讨尿液金属水平与肾功能下降（二分类变量结局）之间的关系。结果本研究调查广州市糖尿病、高血压患者1 414例,患者平均（63.7±9.6）岁,其中,男性558例（39.5%）,女性856例（60.53%）;检出肾功能下降者91例,阳性率为6.9%。尿液6种金属水平中位数分别为铝：31.47 μg/L、钛：103.25 μg/L、铜：9.23 μg/L、锌：306.12 μg/L、钼：48.44 μg/L、镉：1.50 μg/L。单金属logistic回归结果显示,在所有研究对象中,与肾功能下降显著相关的金属为铜（OR=1.98）、锌（OR=1.45）和钼（OR=1.41）;分组后进行单金属logistic回归分析,仅铜与肾功能下降呈正相关（P<0.05）。WQS回归分析结果显示,6种金属的联合效应与肾功能下降呈正相关（OR=1.39）,其中铜的权重最大（61.0%）。RCS模型显示估计肾小球滤过率与钛水平呈“V”型,与铜水平呈负相关（P_non-linear<0.05）。结论糖尿病、高血压患者尿液中铜离子水平与肾功能下降关系密切,且铜离子对糖尿病患者的肾脏损害比高血压或糖尿病合并高血压患者要严重。

关键词: 糖尿病, 高血压, 铝, 钛, 铜, 锌, 钼, 镉, 估计肾小球滤过率

Abstract: Objective To investigate the association between urinary levels of six metals (aluminum, titanium, copper, zinc, molybdenum, and cadmium) and renal function decline in patients with diabetes and/or hypertension in Guangzhou, China. Methods In 2023, participants with diabetes, hypertension, or both were enrolled and grouped accordingly to their medical conditions (diabetes group, hypertension group, diabetes with hypertension group). Urinary metal concentrations were measured, and renal function was assessed using estimated glomerular filtration rate (GFR) derived from serum creatinine (Cr). Logistic regression and Weighted Quantile Sum (WQS) regression models were employed to evaluate associations between urinary metal levels and renal function decline (binary outcome). Results A total of 1 414 patients with diabetes and/or hypertension were surveyed in Guangzhou, with an average age of (63.7 ± 9.6) years. Among them, 558 were male (39.5%) and 856 were female (60.53%). Renal function decline was observed in 91 participants (6.9%). Median urinary metal concentrations were: aluminum (31.47 μg/L), titanium (103.25 μg/L), copper (9.23 μg/L), zinc (306.12 μg/L), molybdenum (48.44 μg/L), and cadmium (1.50 μg/L). Univariate logistic regression revealed significant associations between renal function decline and copper (OR=1.98), zinc (OR=1.45), and molybdenum (OR=1.41). After stratification, only copper was significantly correlated with decreased renal function (P<0.05). The WQS regression indicated a positive combined effect of the six metals on renal function decline (OR=1.39), with copper contributing the highest weight (61.0%). The RCS model demonstrated a V-shape between titanium levels and eGFR, and a negative correlation between copper levels and eGFR (P_non-linear<0.05). Conclusions This study revealed a close relationship between urinary copper levels and declining renal function in patients with diabetes and hypertension. Moreover, copper ions appear to cause more severe kidney damage in patients with diabetes than in those with hypertension or diabetes combined with hypertension.

Key words: Diabetes, Hypertension, Aluminum, Titanium, Copper, Zinc, Molybdenum, Cadmium, Estimated glomerular filtration Rate (eGFR)

中图分类号:

R113

陈锦贤, 周洪伟, 张纸麟, 朱丽, 朱惠扬, 朱伟. 广州市糖尿病、高血压患者尿液6种金属暴露水平与肾功能下降的相关性研究[J]. 华南预防医学, 2025, 51(4): 395-401.

CHEN Jinxian, ZHOU Hongwei, ZHANG Zhilin, ZHU Li, ZHU Huiyang, ZHU Wei. Association between urinary exposure levels of six metals and renal function decline in patients with diabetes and hypertension in Guangzhou[J]. South China Journal of Preventive Medicine, 2025, 51(4): 395-401.

参考文献

[1] Bello AK, Nwankwo E, El Nahas AM.Prevention of chronic kidney disease: A global challenge[J].Kidney Int, 2005, 68(98): S11-S17.
[2] Ammirati AL.Chronic kidney disease[J]. Rev Assoc Med Bras, 2020, 66: 3-9.
[3] Madrigal JM, Ricardo AC, Persky V, et al.Associations between blood cadmium concentration and kidney function in the U. S. population: Impact of sex, diabetes and hypertension[J]. Environ Res, 2019, 169: 180-188.
[4] Yu Y, Meng W, Kuang H, et al.Association of urinary exposure to multiple metal(loid)s with kidney function from a national cross-sectional study[J]. Sci Total Environ, 2023, 882: 163100.
[5] Jha V, Garcia-Garcia G, Iseki K, et al.Chronic kidney disease: Global dimension and perspectives[J]. Lancet, 2013, 382(9888): 260-272.
[6] Yang F, Yi X, Guo J, et al.Association of plasma and urine metals levels with kidney function: A population-based cross-sectional study in China[J]. Chemosphere, 2019, 226: 321-328.
[7] Ferraro PM, Costanzi S, Naticchia A, et al.Low level exposure to cadmium increases the risk of chronic kidney disease: Analysis of the NHANES1999-2006[J]. BMC Public Health, 2010, 10: 304.
[8] Sanders AP, Mazzella MJ, Malin AJ, et al.Combined exposure to lead, cadmium, mercury, and arsenic and kidney health in adolescents age12-19 in NHANES2009-2014[J]. Environ Int, 2019, 131: 104993.
[9] Tsai C, Wu C, Kor C, et al.Prospective associations between environmental heavy metal exposure and renal outcomes in adults with chronic kidney disease[J]. Nephrology, 2018, 23(9): 830-836.
[10] San Martín SP, Bauçà JM, Martinez-Morillo E.Determination of aluminum concentrations in biological specimens: application in the clinical laboratory[J]. Adv Lab Med, 2022, 3(2): 153-166.
[11] Satarug S, Garrett SH, Sens MA, et al.Cadmium, environmental exposure and health outcomes[J]. Environ Health Perspect, 2010, 118(2): 182-190.
[12] Pan Y, Lin Y, Jiang L, et al.Removal of dental alloys and titanium attenuates trace metals and biological effects on liver and kidney[J]. Chemosphere, 2020, 243: 25205.
[13] Wang T, Lv Z, Fu X, et al.Associations between plasma metal levels and mild renal impairment in the general population of Southern China[J]. Ecotoxicol Environ Saf, 2022, 247: 114209.
[14] Tian X, Shan X, Ma L, et al.Mixed heavy metals exposure affects the renal function mediated by 8-OHG: A cross-sectional study in rural residents of China[J]. Environ Pollut, 2023, 317: 120727.
[15] Livingstone C.Zinc: physiology, deficiency, and parenteral nutrition[J]. Nutr Clin Pract Off Publ Am Soc Parenter Enter Nutr, 2015, 30(3): 371-382.
[16] EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, et al. Scientific opinion on the tolerable upper intake level for selenium[J]. EFSA J, 2023, 21(1): e07704.
[17] Stevens LA, Coresh J, Greene T, et al.Assessing kidney function-measured and estimated glomerular filtration rate[J]. N Engl J Med, 2006, 354(23): 2473-2483.
[18] Zhou TT, Hu B, Meng XL, et al.The associations between urinary metals and metal mixtures and kidney function in Chinese community-dwelling older adults with diabetes mellitus[J]. Ecotoxicol Environ Saf, 2021, 226: 112829.
[19] Park Y, Lee SJ.Association of blood heavy metal levels and renal function in Korean adults[J]. Int J Environ Res Public Health, 2022, 19(11): 6646.
[20] Carrico C, Gennings C, Wheeler DC, et al.Characterization of weighted quantile sum regression for highly correlated data in a risk analysis setting[J]. J Agric Biol Environ Stat, 2015, 20(1): 100-120.
[21] Kumar V, Kalita J, Misra UK, et al.A study of dose response and organ susceptibility of copper toxicity in arat model[J]. J Trace Elem Med Biol, 2015, 29: 269-274.
[22] Kumar V, Kalita J, Bora HK, et al.Relationship of antioxidant and oxidative stress markers in different organs following copper toxicity in arat model[J]. Toxicol Appl Pharm, 2016, 93: 37-43.
[23] Lei R, Wu C, Yang B, et al.Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: A rapid in vivo screening method for nanotoxicity[J]. Toxicol Appl Pharm, 2008, 232(2): 292-301.
[24] Grau-Perez M, Domingo-Relloso A, Garcia-Barrera T, et al.Association of single and joint metals with albuminuria and estimated glomerular filtration longitudinal change in middle-aged adults from Spain: The Aragon workers health study[J]. Environ Pollut, 2023, 318: 120851.
[25] Martinez VO, Nunes LS, Viana GS, et al.Biomarkers of cadmiumexposure and renal function in estuarine adult villagers[J]. Int Arch Occup Environ Health, 2022, 95(5): 981-992.
[26] Li Z, Kuang H, Li L, et al.What adverse health effects will environmental heavy metal co-exposure bring us: Based on a biological monitoring study of sanitation workers[J]. Environ Sci Pollut Res, 2022, 30(13): 35769-35780.