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Variability, Clearance, and Concentration of Multiple Metals and Risk of Kidney Function Abnormality: A New Integrative Metal Exposure Assessment Approach

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Abstract

Metal exposure contributes significantly to the pathogenesis of kidney dysfunction. However, most studies have focused on metal concentration in a single matrix (i.e., blood or urine), and few have explored the associations of metal clearance and visit-to-visit variability with renal function. We conducted a three-wave repeated-measures study of 201 older adults. Metal clearance and visit-to-visit variability were calculated to reflect, respectively, the body burden and homeostasis of meals. Renal function was measured as the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Linear mixed-effects and Bayesian Kernel Machine Regression models were used to evaluate the effects of single metals and metal mixtures. The blood metal mixture was negatively associated with eGFR, and urinary Cu was positively associated with UACR (β = 0.417). The metal clearance ratios of Cu, Ni, and Sr were significantly and negatively associated with eGFR, and Cu had the largest effect estimate. The variability independent of the mean of urinary Cs was negatively associated with eGFR after adjustments for the individual metal mean concentration (IMM) of urinary Cs. Furthermore, the visit-to-visit variability of blood Sr was significantly and positively associated with UACR and independent of IMM. Among eight meals in blood and urine, urinary Cu contributed the most to the increase in UACR. We firstly proposed metal clearance and visit-to-visit variability, and found the new indicators are associated with kidney dysfunction. This study revealed real-world metal exposure from the perspective of metal mixtures and improved the understanding of the pathophysiology of metal exposure-induced kidney dysfunction.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Consent to Publish

The manuscript did not contain any individual person’s data in any form (including any individual details, images or videos).

Abbreviations

Al:

Aluminum

ARV:

Average real variability

BKMR:

Bayesian Kernel Machine Regression

BMI:

Body mass index

BUN:

Blood urea nitrogen

CaSR:

Calcium-sensing receptor

CI:

Confidence interval

CKD:

Chronic kidney disease

Ce:

Cesium

Cu:

Copper

CV:

Coefficients of variation

eGFR:

Estimated glomerular filtration rate

EPI equation:

Chronic Kidney Disease Epidemiology Collaboration equation

FDR:

False discovery rate

HbA1c:

Hemoglobin A1c

ICC:

Intraclass correlation coefficients

ICP-MS:

Inductively coupled plasma mass spectrometer

ID:

Identification

IMM:

Individual metal mean

IQR:

Interquartile range

LOD:

Limits of detection

MDRD equation:

Modification of Diet in Renal Disease equation

Mn:

Manganese

NHANES:

National Health and Nutrition Examination Survey

Ni:

Nickel

OR:

Odds ratio

Pb:

Lead

ROS:

Reactive oxygen species

SCr:

Serum creatinine

SD:

Standard deviation

Se:

Selenium

Sr:

Strontium

UACR:

Urinary albumin-to-creatinine ratios

UCr:

Urinary creatinine

VIM:

Variability independent of the mean

References

  • Aelion CM, Davis HT, Lawson AB, Cai B, McDermott S (2012) Associations of estimated residential soil arsenic and lead concentrations and community-level environmental measures with mother–child health conditions in South Carolina. Health Place 18:774–781

    Article  Google Scholar 

  • Al-Bairuty GA, Shaw BJ, Handy RD, Henry TB (2013) Histopathological effects of waterborne copper nanoparticles and copper sulphate on the organs of rainbow trout (Oncorhynchus mykiss). Aquat Toxicol 126:104–115

    Article  CAS  Google Scholar 

  • Alloway BJJS (2013) Heavy metals in soils: trace metals and metalloids in soils and their bioavailability. Springer, Dordrecht

    Book  Google Scholar 

  • Angel BM, Simpson SL, Granger E, Goodwyn K, Jolley DF (2017) Time-averaged concentrations are effective for predicting chronic toxicity of varying copper pulse exposures for two freshwater green algae species. Environ Pollut 230:787–797

    Article  CAS  Google Scholar 

  • Araki S, Aono H, Yokoyama K, Murata K (1986) Filterable plasma concentration, glomerular filtration, tubular balance, and renal clearance of heavy metals and organic substances in metal workers. Arch Environ Health 41:216–221

    Article  CAS  Google Scholar 

  • Barceloux DG (1999) Copper. J Toxicol Clin Toxicol 37:217–230

    Article  CAS  Google Scholar 

  • Bates CJ, Prentice A, Birch MC, Delves HT (2007) Dependence of blood indices of selenium and mercury on estimated fish intake in a national survey of British adults. Public Health Nutr 10:508–517

    Article  Google Scholar 

  • Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 57(1):289–300

    Google Scholar 

  • Bijlsma N, Cohen MM (2016) Environmental chemical assessment in clinical practice: unveiling the elephant in the room. Int J Environ Res Public Health 13:181

    Article  Google Scholar 

  • Bikbov B, Purcell C, Levey A et al (2020) Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 395:709–733

    Article  Google Scholar 

  • Bjornstad P, Cherney DZ, Snell-Bergeon JK, Pyle L, Rewers M, Johnson RJ, Maahs DM (2015) Rapid GFR decline is associated with renal hyperfiltration and impaired GFR in adults with Type 1 diabetes. Nephrol Dial Transplant 30:1706–1711

    Article  Google Scholar 

  • Bobb JF, Valeri L, Claus Henn B, Christiani DC, Wright RO, Mazumdar M, Godleski JJ, Coull BA (2015) Bayesian kernel machine regression for estimating the health effects of multi-pollutant mixtures. Biostatistics 16:493–508

    Article  Google Scholar 

  • Bonate PL, Reith K, Weir S (1998) Drug interactions at the renal level. Implications for drug development. Clin Pharmacokinet 34:375–404

    Article  CAS  Google Scholar 

  • Boncler M, Luzak B, Watala C (2006) Role of C-reactive protein in atherogenesis. Postepy Hig Med Dosw (Online) 60:538–546

    Google Scholar 

  • Bosch AC, O’Neill B, Sigge GO, Kerwath SE, Hoffman LC (2016) Heavy metals in marine fish meat and consumer health: a review. J Sci Food Agric 96:32–48

    Article  CAS  Google Scholar 

  • Bulka CM, Mabila SL, Lash JP, Turyk ME, Argos M (2017) Arsenic and obesity: a comparison of urine dilution adjustment methods. Environ Health Perspect 125:087020

    Article  Google Scholar 

  • Carville S, Wonderling D, Stevens P (2014) Early identification and management of chronic kidney disease in adults: summary of updated NICE guidance. BMJ 349:g4507

    Article  Google Scholar 

  • CDC (2019) National Health and Nutrition Examination Survey. 2013–2014 Data documentation, codebook and frequencies. Urine flow rate (UCFLOW_H). CDC

  • Ceriello A, Ihnat MA (2010) ‘Glycaemic variability’: a new therapeutic challenge in diabetes and the critical care setting. Diabet Med 27:862–867

    Article  CAS  Google Scholar 

  • Ceriello A, Kilpatrick ES (2013) Glycemic variability: both sides of the story. Diabetes Care 36(Suppl 2):S272-275

    Article  Google Scholar 

  • Chen C, Qu L, Li B, Xing L, Jia G, Wang T, Gao Y, Zhang P, Li M, Chen W, Chai Z (2005) Increased oxidative DNA damage, as assessed by urinary 8-hydroxy-2′-deoxyguanosine concentrations, and serum redox status in persons exposed to mercury. Clin Chem 51:759–767

    Article  CAS  Google Scholar 

  • Crinnion WJ (2010) The CDC fourth national report on human exposure to environmental chemicals: what it tells us about our toxic burden and how it assist environmental medicine physicians. Altern Med Rev 15:101–109

    Google Scholar 

  • Daniel J, Ziaee H, Pradhan C, Pynsent PB, McMinn DJ (2010) Renal clearance of cobalt in relation to the use of metal-on-metal bearings in hip arthroplasty. J Bone Jt Surg Am 92:840–845

    Article  Google Scholar 

  • Diamond GL, Thayer WC, Brown JS, Burgess M, Follansbee MH, Gaines LGT, Klotzbach JM (2019a) Estimates of urinary blood lead clearance and its relationship to glomerular filtration rate based on a large population survey. J Toxicol Environ Health A 82:379–382

    Article  CAS  Google Scholar 

  • Diamond GL, Thayer WC, Klotzbach JM, Ingerman LD (2019b) Urinary cadmium clearance, its relationship to glomerular filtration rate and implications for cadmium epidemiology. J Toxicol Environ Health A 82:1187–1198

    Article  CAS  Google Scholar 

  • Domingo-Relloso A, Grau-Perez M, Briongos-Figuero L, Gomez-Ariza JL, Garcia-Barrera T, Dueñas-Laita A, Bobb JF, Chaves FJ, Kioumourtzoglou MA, Navas-Acien A, Redon-Mas J, Martin-Escudero JC, Tellez-Plaza M (2019) The association of urine metals and metal mixtures with cardiovascular incidence in an adult population from Spain: the Hortega Follow-Up Study. Int J Epidemiol 48:1839–1849

    Article  Google Scholar 

  • Duc HN, Oh H, Kim MS (2021) Effects of antioxidant vitamins, curry consumption, and heavy metal levels on metabolic syndrome with comorbidities: a Korean community-based cross-sectional study. Antioxidants (Basel) 10(5):808

    Article  CAS  Google Scholar 

  • Eadon MT, Hack BK, Alexander JJ, Xu C, Dolan ME, Cunningham PN (2013) Cell cycle arrest in a model of colistin nephrotoxicity. Physiol Genomics 45:877–888

    Article  CAS  Google Scholar 

  • El-Missiry MA, Shabana S, Ghazala SJ, Othman AI, Amer ME (2021) Melatonin exerts a neuroprotective effect against γ-radiation-induced brain injury in the rat through the modulation of neurotransmitters, inflammatory cytokines, oxidative stress, and apoptosis. Environ Sci Pollut Res Int 28:31108–31121

    Article  CAS  Google Scholar 

  • Exley C, Burgess E, Philip J, Day EHJ, Melethil S, Yokel RA (1996) Aluminum toxicokinetics. J Toxicol Environ Health 48:569–584

    Article  CAS  Google Scholar 

  • Fik-Jaskółka MA, Mkrtchyan AF, Saghyan AS, Palumbo R, Belter A, Hayriyan LA, Simonyan H, Roviello V, Roviello GN (2020) Biological macromolecule binding and anticancer activity of synthetic alkyne-containing l-phenylalanine derivatives. Amino Acids 52:755–769

    Article  Google Scholar 

  • Gawlik D, Behne D, Kraft D, Offermann G (1989) The influence of renal insufficiency on caesium metabolism in man and rat (with a note on the Cs content of some biological standard materials). J Trace Elem Electrolytes Health Dis 3:43–50

    CAS  Google Scholar 

  • Geoffroy V, Chappard D, Marty C, Libouban H, Ostertag A, Lalande A, de Vernejoul MC (2011) Strontium ranelate decreases the incidence of new caudal vertebral fractures in a growing mouse model with spontaneous fractures by improving bone microarchitecture. Osteoporos Int 22:289–297

    Article  CAS  Google Scholar 

  • Goix S, Uzu G, Oliva P, Barraza F, Calas A, Castet S, Point D, Masbou J, Duprey JL, Huayta C, Chincheros J, Gardon J (2016) Metal concentration and bioaccessibility in different particle sizes of dust and aerosols to refine metal exposure assessment. J Hazard Mater 317:552–562

    Article  CAS  Google Scholar 

  • Gora RH, Kerketta P, Baxla SL, Toppo R, Prasad R, Patra PH, Roy BK (2014) Ameliorative effect of Tephrosia purpurea in arsenic-induced nephrotoxicity in rats. Toxicol Int 21:78–83

    Article  Google Scholar 

  • Green CB, Takahashi JS, Bass J (2008) The meter of metabolism. Cell 134:728–742

    Article  CAS  Google Scholar 

  • Guo H, Cui H, Peng X, Fang J, Zuo Z, Deng J, Wang X, Wu B, Chen K, Deng J (2015) Modulation of the PI3K/Akt pathway and Bcl-2 family proteins involved in chicken’s tubular apoptosis induced by nickel chloride (NiCl2). Int J Mol Sci 16:22989–23011

    Article  CAS  Google Scholar 

  • Guo ZN, Qu Y, Reziya H, Liu J, Yan XL, Zhang P, Zhang PD, Qi S, Yang Y (2020) Which parameters of beat-to-beat blood pressure best predict poor in-hospital outcome in spontaneous intracerebral hemorrhage? Front Aging Neurosci 12:603340

    Article  Google Scholar 

  • Haroun MK, Jaar BG, Hoffman SC, Comstock GW, Klag MJ, Coresh J (2003) Risk factors for chronic kidney disease: a prospective study of 23,534 men and women in Washington County, Maryland. J Am Soc Nephrol 14:2934–2941

    Article  Google Scholar 

  • Heacox HN, Gillman PL, Zwart SR, Smith SM (2017) Excretion of zinc and copper increases in men during 3 weeks of bed rest, with or without artificial gravity. J Nutr 147:1113–1120

    Article  CAS  Google Scholar 

  • Helal I, Fick-Brosnahan GM, Reed-Gitomer B, Schrier RW (2012) Glomerular hyperfiltration: definitions, mechanisms and clinical implications. Nat Rev Nephrol 8:293–300

    Article  CAS  Google Scholar 

  • Höllriegl V, Li WB, Oeh U (2006) Human biokinetics of strontium—Part II: final data evaluation of intestinal absorption and urinary excretion of strontium in human subjects after stable tracer administration. Radiat Environ Biophys 45:179–185

    Article  Google Scholar 

  • Hrubá F, Strömberg U, Černá M, Chen C, Harari F, Harari R, Horvat M, Koppová K, Kos A, Krsková A, Krsnik M, Laamech J, Li YF, Löfmark L, Lundh T, Lundström NG, Lyoussi B, Mazej D, Osredkar J, Pawlas K, Pawlas N, Prokopowicz A, Rentschler G, Spěváčková V, Spiric Z, Tratnik J, Skerfving S, Bergdahl IA (2012) Blood cadmium, mercury, and lead in children: an international comparison of cities in six European countries, and China, Ecuador, and Morocco. Environ Int 41:29–34

    Article  Google Scholar 

  • Ishida S, Lee J, Thiele DJ, Herskowitz I (2002) Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals. Proc Natl Acad Sci USA 99:14298–14302

    Article  CAS  Google Scholar 

  • Jalili C, Kazemi M, Cheng H, Mohammadi H, Babaei A, Taheri E, Moradi S (2021) Associations between exposure to heavy metals and the risk of chronic kidney disease: a systematic review and meta-analysis. Crit Rev Toxicol 51:165–182

    Article  CAS  Google Scholar 

  • Jin R, Zhu X, Shrubsole MJ, Yu C, Xia Z, Dai Q (2018) Associations of renal function with urinary excretion of metals: evidence from NHANES 2003–2012. Environ Int 121:1355–1362

    Article  CAS  Google Scholar 

  • Kirkley KS, Popichak KA, Afzali MF, Legare ME, Tjalkens RB (2017) Microglia amplify inflammatory activation of astrocytes in manganese neurotoxicity. J Neuroinflamm 14:99

    Article  Google Scholar 

  • Kohsaka A, Bass J (2007) A sense of time: how molecular clocks organize metabolism. Trends Endocrinol Metab 18:4–11

    Article  CAS  Google Scholar 

  • Kosiba AA, Wang Y, Chen D, Wong CKC, Gu J, Shi H (2020) The roles of calcium-sensing receptor (CaSR) in heavy metals-induced nephrotoxicity. Life Sci 242:117183

    Article  CAS  Google Scholar 

  • Kumar V, Kalita J, Misra UK, Bora HK (2015) A study of dose response and organ susceptibility of copper toxicity in a rat model. J Trace Elem Med Biol 29:269–274

    Article  CAS  Google Scholar 

  • Lentini P, Zanoli L, Granata A, Signorelli SS, Castellino P, Dell’Aquila R (2017) Kidney and heavy metals—the role of environmental exposure (Review). Mol Med Rep 15:3413–3419

    Article  CAS  Google Scholar 

  • Lestaevel P, Grandcolas L, Paquet F, Voisin P, Aigueperse J, Gourmelon P (2008) Neuro-inflammatory response in rats chronically exposed to (137)cesium. Neurotoxicology 29:343–348

    Article  CAS  Google Scholar 

  • Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F (2006) Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145:247–254

    Article  CAS  Google Scholar 

  • Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF III, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612

    Article  Google Scholar 

  • Li A, Pei L, Zhao M, Xu J, Mei Y, Li R, Xu Q (2019) Investigating potential associations between O3 exposure and lipid profiles: a longitudinal study of older adults in Beijing. Environ Int 133:105135

    Article  CAS  Google Scholar 

  • Li A, Mei Y, Zhao M, Xu J, Li R, Zhao J, Zhou Q, Ge X, Xu Q (2021a) Associations between air pollutant exposure and renal function: a prospective study of older adults without chronic kidney disease. Environ Pollut 277:116750

    Article  CAS  Google Scholar 

  • Li A, Mei Y, Zhao M, Xu J, Seery S, Li R, Zhao J, Zhou Q, Ge X, Xu Q (2021b) The effect of ambient ozone on glucose-homoeostasis: a prospective study of non-diabetic older adults in Beijing. Sci Total Environ 761:143308

    Article  CAS  Google Scholar 

  • Liao M, Liu H (2012) Gene expression profiling of nephrotoxicity from copper nanoparticles in rats after repeated oral administration. Environ Toxicol Pharmacol 34:67–80

    Article  CAS  Google Scholar 

  • Lin G, Zhou C, Lin M, Xu A, He F (2019) Strontium-incorporated titanium implant surface treated by hydrothermal reactions promotes early bone osseointegration in osteoporotic rabbits. Clin Oral Implants Res 30:777–790

    Article  Google Scholar 

  • Linder MC (2020) Copper homeostasis in mammals, with emphasis on secretion and excretion. A review. Int J Mol Sci 21(14):4932

    Article  CAS  Google Scholar 

  • Liu X, Wu S, Song Q, Wang X (2020a) Visit-to-visit variability of lipid measurements and the risk of myocardial infarction and all-cause mortality: a prospective cohort study. Atherosclerosis 312:110–116

    Article  CAS  Google Scholar 

  • Liu Y, Yuan Y, Xiao Y, Li Y, Yu Y, Mo T, Jiang H, Li X, Yang H, Xu C, He M, Guo H, Pan A, Wu T (2020b) Associations of plasma metal concentrations with the decline in kidney function: a longitudinal study of Chinese adults. Ecotoxicol Environ Saf 189:110006

    Article  CAS  Google Scholar 

  • Liu M, Chen X, Zhang S, Lin Y, Xiong Z, Zhong X, Guo Y, Sun X, Zhou H, Xu X, Wang L, Liao X, Zhuang X (2021a) Long-term visit-to-visit mean arterial pressure variability and the risk of heart failure and all-cause mortality. Front Cardiovasc Med 8:665117

    Article  CAS  Google Scholar 

  • Liu X, Logan J, Kwon Y, Lobo JM, Kang H, Sohn MW (2021b) Visit-to-visit blood pressure variability and sleep architecture. J Clin Hypertens (Greenwich) 23:323–330

    Article  Google Scholar 

  • Liu L, Li A, Xu Q, Wang Q, Han F, Xu C, Liu Z, Xu D, Xu D (2022) The association between urine elements and fasting glucose levels in a community-based elderly people in Beijing. Environ Sci Pollut Res Int 29(20):30102–30113

    Article  Google Scholar 

  • Lu S, Ren L, Fang J, Ji J, Liu G, Zhang J, Zhang H, Luo R, Lin K, Fan R (2016) Trace elements are associated with urinary 8-hydroxy-2′-deoxyguanosine level: a case study of college students in Guangzhou, China. Environ Sci Pollut Res Int 23:8484–8491

    Article  CAS  Google Scholar 

  • Luo J, Hendryx M (2020) Metal mixtures and kidney function: an application of machine learning to NHANES data. Environ Res 191:110126

    Article  CAS  Google Scholar 

  • Ma YC, Zuo L, Chen JH, Luo Q, Yu XQ, Li Y, Xu JS, Huang SM, Wang LN, Huang W, Wang M, Xu GB, Wang HY (2006) Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol 17:2937–2944

    Article  Google Scholar 

  • Mao L, Xia L, Chang J, Liu J, Jiang L, Wu C, Fang B (2017) The synergistic effects of Sr and Si bioactive ions on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration. Acta Biomater 61:217–232

    Article  CAS  Google Scholar 

  • Matsushita K, Mahmoodi BK, Woodward M, Emberson JR, Jafar TH, Jee SH, Polkinghorne KR, Shankar A, Smith DH, Tonelli M, Warnock DG, Wen CP, Coresh J, Gansevoort RT, Hemmelgarn BR, Levey AS (2012) Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. JAMA 307:1941–1951

    Article  CAS  Google Scholar 

  • Mohod CV, Dhote J (2013) Review of heavy metals in drinking water and their effect on human health. Int J Innov Res Sci Eng Technol 2:2992–2996

  • Nguyen HD, Kim MS (2021) Effects of heavy metal, vitamin, and curry consumption on metabolic syndrome during menopause: a Korean community-based cross-sectional study. Menopause 28:949–959

    Article  Google Scholar 

  • Nguyen HD, Oh H, Hoang NHM, Kim MS (2021) Association between heavy metals, high-sensitivity C-reaction protein and 10-year risk of cardiovascular diseases among adult Korean population. Sci Rep 11:14664

    Article  CAS  Google Scholar 

  • Nwabuo CC, Yano Y, Moreira HT, Appiah D, Vasconcellos HD, Aghaji QN, Viera A, Rana JS, Shah RV, Murthy VL, Allen NB, Schreiner PJ, Lloyd-Jones DM, Lima JAC (2020) Association between visit-to-visit blood pressure variability in early adulthood and myocardial structure and function in later life. JAMA Cardiol 5:795–801

    Article  Google Scholar 

  • O’Brien KM, Upson K, Cook NR, Weinberg CR (2016) Environmental chemicals in urine and blood: improving methods for creatinine and lipid adjustment. Environ Health Perspect 124:220–227

    Article  CAS  Google Scholar 

  • Öhrvik H, Aaseth J, Horn N (2017) Orchestration of dynamic copper navigation—new and missing pieces. Metallomics 9:1204–1229

    Article  Google Scholar 

  • Othman MS, Fareid MA, Abdel Hameed RS, Abdel Moneim AE (2020) The protective effects of melatonin on aluminum-induced hepatotoxicity and nephrotoxicity in rats. Oxid Med Cell Longev 2020:7375136

    Article  Google Scholar 

  • Pabla N, Ma Z, McIlhatton MA, Fishel R, Dong Z (2011) hMSH2 recruits ATR to DNA damage sites for activation during DNA damage-induced apoptosis. J Biol Chem 286:10411–10418

    Article  CAS  Google Scholar 

  • Pacyna JM, Pacyna EG (2001) An assessment of global and regional emissions of trace metals to the atmosphere from anthropogenic sources worldwide. Environ Rev 9:269–298

    Article  CAS  Google Scholar 

  • Park J, Kim Y (2021) Associations of blood heavy metals with uric acid in the Korean general population: analysis of data from the 2016–2017 Korean National Health and Nutrition Examination Survey. Biol Trace Elem Res 199:102–112

    Article  CAS  Google Scholar 

  • Peng DJ, Zhang YW, Li ZC, Li SJ, Cai M, Qin WX, Ou SY, Huang XW, Yuan ZX, Jiang YM (2019) Preventive impacts of PAS-Na on the slow growth and activated inflammatory responses in Mn-exposed rats. J Trace Elem Med Biol 54:134–141

    Article  CAS  Google Scholar 

  • Qaseem A, Hopkins RH Jr, Sweet DE, Starkey M, Shekelle P (2013) Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: a clinical practice guideline from the American College of Physicians. Ann Intern Med 159:835–847

    Article  Google Scholar 

  • Rosner B, Kugushw A, Burgner J (2000) Fundamental of biostatistics. Brooks/Cole, Boston

    Google Scholar 

  • Roy A, Manna P, Sil PC (2009) Prophylactic role of taurine on arsenic mediated oxidative renal dysfunction via MAPKs/NF-kappaB and mitochondria dependent pathways. Free Radic Res 43:995–1007

    Article  CAS  Google Scholar 

  • Sanders AP, Mazzella MJ, Malin AJ, Hair GM, Busgang SA, Saland JM, Curtin P (2019) Combined exposure to lead, cadmium, mercury, and arsenic and kidney health in adolescents age 12–19 in NHANES 2009–2014. Environ Int 131:104993

    Article  CAS  Google Scholar 

  • Schroeder MA (1990) Diagnosing and dealing with multicollinearity. West J Nurs Res 12:175–184

    Article  Google Scholar 

  • Sheng CS, Tian J, Miao Y, Cheng Y, Yang Y, Reaven PD, Bloomgarden ZT, Ning G (2020) Prognostic significance of long-term HbA(1c) variability for all-cause mortality in the ACCORD Trial. Diabetes Care 43:1185–1190

    Article  CAS  Google Scholar 

  • Shvachiy L, Geraldes V, Amaro-Leal Â, Rocha I (2018) Intermittent low-level lead exposure provokes anxiety, hypertension, autonomic dysfunction and neuroinflammation. Neurotoxicology 69:307–319

    Article  CAS  Google Scholar 

  • Sinha M, Manna P, Sil PC (2008) Arjunolic acid attenuates arsenic-induced nephrotoxicity. Pathophysiology 15:147–156

    Article  CAS  Google Scholar 

  • Smolders R, Koch HM, Moos RK, Cocker J, Jones K, Warren N, Levy L, Bevan R, Hays SM, Aylward LL (2014) Inter- and intra-individual variation in urinary biomarker concentrations over a 6-day sampling period. Part 1: metals. Toxicol Lett 231:249–260

    Article  CAS  Google Scholar 

  • Soderland P, Lovekar S, Weiner DE, Brooks DR, Kaufman JS (2010) Chronic kidney disease associated with environmental toxins and exposures. Adv Chronic Kidney Dis 17:254–264

    Article  Google Scholar 

  • Song N, Yang M, Zhang H, Yang SK (2021) Intracellular calcium homeostasis and kidney disease. Curr Med Chem 28:3647–3665

    Article  CAS  Google Scholar 

  • Stenvinkel P, Chertow GM, Devarajan P, Levin A, Andreoli SP, Bangalore S, Warady BA (2021) Chronic inflammation in chronic kidney disease progression: role of Nrf2. Kidney Int Rep 6:1775–1787

    Article  Google Scholar 

  • Stevens PE, Levin A (2013) Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 158:825–830

    Article  Google Scholar 

  • Stone S, McKnight K, Legendre L, Koppel DJ, Binet MT, Simpson SL, Jolley DF (2021) The effects of pulse exposures of metal toxicants on different life stages of the tropical copepod Acartia sinjiensis. Environ Pollut 285:117212

    Article  CAS  Google Scholar 

  • Tett SE, Kirkpatrick CM, Gross AS, McLachlan AJ (2003) Principles and clinical application of assessing alterations in renal elimination pathways. Clin Pharmacokinet 42:1193–1211

    Article  Google Scholar 

  • Tjalkens RB, Popichak KA, Kirkley KA (2017) Inflammatory activation of microglia and astrocytes in manganese neurotoxicity. Adv Neurobiol 18:159–181

    Article  Google Scholar 

  • Tsai HJ, Hung CH, Wang CW, Tu HP, Li CH, Tsai CC, Lin WY, Chen SC, Kuo CH (2021) Associations among heavy metals and proteinuria and chronic kidney disease. Diagnostics (Basel) 11(2):282

    Article  CAS  Google Scholar 

  • Vervaet BA, D’Haese PC, Verhulst A (2017) Environmental toxin-induced acute kidney injury. Clin Kidney J 10:747–758

    Article  CAS  Google Scholar 

  • Wang Y (2018) China food composition tables. Peking University Medical Press, Beijing

    Google Scholar 

  • Wang Y, Jarad G, Tripathi P, Pan M, Cunningham J, Martin DR, Liapis H, Miner JH, Chen F (2010) Activation of NFAT signaling in podocytes causes glomerulosclerosis. J Am Soc Nephrol 21:1657–1666

    Article  CAS  Google Scholar 

  • Wang YX, Sun Y, Feng W, Wang P, Yang P, Li J, Huang Z, Chen YJ, Liu C, Sun L, Yue J, Gu LJ, Zeng Q, Lu WQ (2016) Association of urinary metal levels with human semen quality: a cross-sectional study in China. Environ Int 91:51–59

    Article  CAS  Google Scholar 

  • Wang YX, Pan A, Feng W, Liu C, Huang LL, Ai SH, Zeng Q, Lu WQ (2019) Variability and exposure classification of urinary levels of non-essential metals aluminum, antimony, barium, thallium, tungsten and uranium in healthy adult men. J Expo Sci Environ Epidemiol 29:424–434

    Article  CAS  Google Scholar 

  • Wang A, Li H, Yuan J, Zuo Y, Zhang Y, Chen S, Wu S, Wang Y (2020) Visit-to-visit variability of lipids measurements and the risk of stroke and stroke types: a prospective cohort study. J Stroke 22:119–129

    Article  Google Scholar 

  • Weaver VM, Kotchmar DJ, Fadrowski JJ, Silbergeld EK (2016) Challenges for environmental epidemiology research: are biomarker concentrations altered by kidney function or urine concentration adjustment? J Expo Sci Environ Epidemiol 26:1–8

    Article  CAS  Google Scholar 

  • Webster AC, Nagler EV, Morton RL, Masson P (2017) Chronic kidney disease. Lancet 389:1238–1252

    Article  Google Scholar 

  • Webster L, Larive B, Gassman J, Bullen A, Weisbord SD, Palevsky PM, Fried LF, Raphael K, Isakova T, Ix JH (2020) A simple equation to estimate urinary flow rate using urine creatinine. Am J Nephrol 51:395–400

    Article  CAS  Google Scholar 

  • Woo KT, Choong HL, Wong KS, Tan HB, Chan CM (2012) The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney Int 81:1044–1045

    Article  Google Scholar 

  • Wu X, Cobbina SJ, Mao G, Xu H, Zhang Z, Yang L (2016) A review of toxicity and mechanisms of individual and mixtures of heavy metals in the environment. Environ Sci Pollut Res Int 23:8244–8259

    Article  CAS  Google Scholar 

  • Wu CY, Wong CS, Chung CJ, Wu MY, Huang YL, Ao PL, Lin YF, Lin YC, Shiue HS, Su CT, Chen HH, Hsueh YM (2019) The association between plasma selenium and chronic kidney disease related to lead, cadmium and arsenic exposure in a Taiwanese population. J Hazard Mater 375:224–232

    Article  CAS  Google Scholar 

  • Xia Y, Liu X, Wu D, Xiong H, Ren L, Xu L, Wu W, Zhang H (2017) Influence of beat-to-beat blood pressure variability on vascular elasticity in hypertensive population. Sci Rep 7:8394

    Article  Google Scholar 

  • Xie Y, Bowe B, Mokdad AH, Xian H, Yan Y, Li T, Maddukuri G, Tsai CY, Floyd T, Al-Aly Z (2018) Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016. Kidney Int 94:567–581

    Article  Google Scholar 

  • Xing M, Jiang Y, Bi W, Gao L, Zhou YL, Rao SL, Ma LL, Zhang ZW, Yang HT, Chang J (2021) Strontium ions protect hearts against myocardial ischemia/reperfusion injury. Sci Adv. https://doi.org/10.1126/sciadv.abe0726

    Article  Google Scholar 

  • Xu X, Nie S, Ding H, Hou FF (2018) Environmental pollution and kidney diseases. Nat Rev Nephrol 14:313–324

    Article  CAS  Google Scholar 

  • Xu J, Zhao M, Pei L, Liu X, Wei L, Li A, Mei Y, Xu Q (2020) Effects of heavy metal mixture exposure on hematological and biomedical parameters mediated by oxidative stress. Sci Total Environ 705:134865

    Article  CAS  Google Scholar 

  • Yan M, Tang C, Ma Z, Huang S, Dong Z (2016) DNA damage response in nephrotoxic and ischemic kidney injury. Toxicol Appl Pharmacol 313:104–108

    Article  CAS  Google Scholar 

  • Yang F, Yi X, Guo J, Xu S, Xiao Y, Huang X, Duan Y, Luo D, Xiao S, Huang Z, Yuan H, He M, Shen M, Chen X (2019) Association of plasma and urine metals levels with kidney function: a population-based cross-sectional study in China. Chemosphere 226:321–328

    Article  CAS  Google Scholar 

  • Yang J, Yang A, Cheng N, Huang W, Huang P, Liu N, Bai Y (2020) Sex-specific associations of blood and urinary manganese levels with glucose levels, insulin resistance and kidney function in US adults: National Health and Nutrition Examination Survey 2011–2016. Chemosphere 258:126940

    Article  CAS  Google Scholar 

  • Yano Y, Fujimoto S, Kramer H, Sato Y, Konta T, Iseki K, Iseki C, Moriyama T, Yamagata K, Tsuruya K, Narita I, Kondo M, Kimura K, Asahi K, Kurahashi I, Ohashi Y, Watanabe T (2015) Long-term blood pressure variability, new-onset diabetes mellitus, and new-onset chronic kidney disease in the Japanese general population. Hypertension 66:30–36

    Article  CAS  Google Scholar 

  • Yu ZB, Zhu Y, Li D, Wu MY, Tang ML, Wang JB, Chen K (2020) Association between visit-to-visit variability of HbA(1c) and cognitive decline: a pooled analysis of two prospective population-based cohorts. Diabetologia 63:85–94

    Article  CAS  Google Scholar 

  • Yuan Y, Xiao Y, Feng W, Liu Y, Yu Y, Zhou L, Qiu G, Wang H, Liu B, Liu K, Yang H, Li X, Min X, Zhang C, Xu C, Zhang X, He M, Hu FB, Pan A, Wu T (2017) Plasma metal concentrations and incident coronary heart disease in Chinese adults: the Dongfeng-Tongji Cohort. Environ Health Perspect 125:107007

    Article  Google Scholar 

  • Zappitelli M, Juarez M, Castillo L, Coss-Bu J, Goldstein SL (2009) Continuous renal replacement therapy amino acid, trace metal and folate clearance in critically ill children. Intensive Care Med 35:698–706

    Article  CAS  Google Scholar 

  • Zhao H, Wang Y, Fei D, Guo M, Yang X, Mu M, Yu H, Xing M (2019) Destruction of redox and mitochondrial dynamics co-contributes to programmed cell death in chicken kidney under arsenite or/and copper(II) exposure. Ecotoxicol Environ Saf 179:167–174

    Article  CAS  Google Scholar 

  • Zhao M, Xu J, Li A, Mei Y, Ge X, Liu X, Wei L, Xu Q (2020) Multiple exposure pathways and urinary chromium in residents exposed to chromium. Environ Int 141:105753

    Article  CAS  Google Scholar 

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Funding

This study was supported by the China Medical Board (Grant No. 15-230); China Prospective Cohort Study of Air Pollution and Health Effects in Typical Areas (C-PAT) (Grant No. MEE-EH-20190802); the Fundamental Research Funds for the Central Universities (Grant No. 3332019147); Peking Union Medical College Graduate Innovation Fund (No. 2019-1004-02); the Chinese Academy of Medical Science Innovation Fund for Medical Sciences (Grant No. 2017-I2M-1-009). These funders did not participate in the organization of study design, data collection, analysis, and writing, and did not impose any restrictions regarding the publication of the report.

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Author notes

  1. Ang Li and Jiaxin Zhao contributed equally, therefore they are joint first-coauthors.

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China

    Ang Li, Jiaxin Zhao, Yayuan Mei, Quan Zhou, Meiduo Zhao, Jing Xu, Xiaoyu Ge & Qun Xu

  2. Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China

    Ang Li, Jiaxin Zhao, Yayuan Mei, Quan Zhou, Meiduo Zhao, Jing Xu, Xiaoyu Ge & Qun Xu

Authors
  1. Ang Li
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  2. Jiaxin Zhao
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  3. Yayuan Mei
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  4. Quan Zhou
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  5. Meiduo Zhao
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  7. Xiaoyu Ge
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Contributions

All authors contributed to the resources, organization, and completion of filed research work. Conceptualization, investigation, methodology, data analysis, and original draft preparation were performed by AL and JZ. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Qun Xu.

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The study was approved by the Institutional Ethics Committees of Institute of Basic Medicine, Chinese Academy of Medical Sciences.

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Li, A., Zhao, J., Mei, Y. et al. Variability, Clearance, and Concentration of Multiple Metals and Risk of Kidney Function Abnormality: A New Integrative Metal Exposure Assessment Approach. Expo Health 15, 161–184 (2023). https://doi.org/10.1007/s12403-022-00484-2

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