Abstract
Epidemiological evidence for the relationship between cadmium exposure and mortality in specific chronic kidney disease (CKD) populations remains scarce. We aimed to explore the relationships between cadmium concentrations in urine and blood and all-cause mortality among CKD patients in the USA. This cohort study was composed of 1825 CKD participants from the National Health and Nutrition Examination Survey (NHANES) (1999–2014) who were followed up to December 31, 2015. All-cause mortality was ascertained by matching the National Death Index (NDI) records. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in relation to urinary and blood cadmium concentrations by Cox regression models. During an average follow-up period of 82 months, 576 CKD participants died. Compared with the lowest quartiles, HRs (95% CIs) for all-cause mortality associated with the fourth weighted quartiles of urinary and blood cadmium concentrations were 1.75 (1.28 to 2.39) and 1.59 (1.17 to 2.15), respectively. Furthermore, the HRs (95% CIs) for all-cause mortality per ln-transformed IQR increment in cadmium concentrations in urine (1.15 μg/g UCr) and blood (0.95 μg/L) were 1.40 (1.21 to 1.63) and 1.22 (1.07 to 1.40), respectively. Linear concentration–response relationships between urinary and blood cadmium concentrations and all-cause mortality were also found. Our findings suggested that increased cadmium concentrations in both urine and blood significantly contributed to enhanced mortality risk in CKD patients, thus highlighting that efforts to reduce cadmium exposure may reduce mortality risk in high-risk populations with CKD.
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Data availability
All data relevant to the study are publicly available on the NHANES website (https://www.cdc.gov/nchs/nhanes/).
References
Åkesson A, Barregard L, Bergdahl IA, Nordberg GF, Nordberg M, Skerfving S (2014) Non-renal effects and the risk assessment of environmental cadmium exposure. Environ Health Perspect 122:431–438. https://doi.org/10.1289/ehp.1307110
Barregard L, Sallsten G, Fagerberg B, Borné Y, Persson M, Hedblad B, Engström G (2016) Blood cadmium levels and incident cardiovascular events during follow-up in a population-based cohort of Swedish adults: the Malmö diet and cancer study. Environ Health Perspect 124:594–600. https://doi.org/10.1289/ehp.1509735
Borné Y, Fagerberg B, Persson M, Sallsten G, Forsgard N, Hedblad B, Barregard L, Engström G (2014) Cadmium exposure and incidence of diabetes mellitus--results from the Malmö diet and cancer study. PLoS One 9:e112277. https://doi.org/10.1371/journal.pone.0112277
CDC (2022a) Centers for Disease Control and Prevention: National Health and Nutrition Examination Survey [article online]. Available from https://www.cdc.gov/nchs/nhanes/. Accessed April 16, 2022.
CDC (2022b) Centers for Disease Control and Prevention: National Health and Nutrition Examination Survey 1999-2000 data documentation, codebook, and frequencies: standard biochemistry profile & hormones (LAB18) [article online]. Available from https://wwwn.cdc.gov/Nchs/Nhanes/1999-2000/LAB18.htm. Accessed April 20, 2022.
CDC (2022c) Centers for Disease Control and Prevention: National Health and Nutrition Examination Survey 2005-2006 data documentation, codebook, and frequencies: standard biochemistry profile (BIOPRO_D) [article online]. Available from https://wwwn.cdc.gov/Nchs/Nhanes/2005-2006/BIOPRO_D.htmAccessed April 20, 2022.
CDC (2022d) Centers for Disease Control and Prevention: National Health and Nutrition Examination Survey 2007-2008 data documentation, codebook, and frequencies: albumin & creatinine - urine (ALB_CR_E) [article online]. Available from https://wwwn.cdc.gov/Nchs/Nhanes/2007-2008/ALB_CR_E.htm. Accessed April 20, 2022.
CDC (2022e) Centers for Disease Control and Prevention: National Center for Health Statistics Public-Use Linked Mortality File (updated March 2020) [article online]. Available from https://www.cdc.gov/nchs/data-linkage/mortality-public.htm Accessed April 22, 2022.
CDC (2022f) Centers for Disease Control and Prevention: National Health and Nutrition Examination Survey 1999-2000 data documentation, codebook, and frequencies: demographic variables & sample weights (DEMO) [article online]. Available from https://wwwn.cdc.gov/Nchs/Nhanes/1999-2000/DEMO.htm. Accessed April 16, 2022.
CDC (2022g) Centers for Disease Control and Prevention: National Health and Nutrition Examination Survey 1999-2000 data documentation, codebook, and frequencies: cadmium, lead, mercury, cotinine & nutritional biochemistries (LAB06) [article online]. Available from https://wwwn.cdc.gov/Nchs/Nhanes/1999-2000/LAB06.htm. Accessed April 20, 2022.
CDC (2022h) Centers for Disease Control and Prevention: accessed April 20, 2022 National Health and Nutrition Examination Survey: NHANES survey methods and analytic guidelines [article online]. Available from https://wwwn.cdc.gov/nchs/nhanes/analyticguidelines.aspx#analytic-guidelines. Accessed April 25, 2022.
Chan TC, Zhang Z, Lin BC, Lin C, Deng HB, Chuang YC, Chan JWM, Jiang WK, Tam T, Chang LY, Hoek G, Lau AKH, Lao XQ (2018) Long-term exposure to ambient fine particulate matter and chronic kidney disease: a cohort study. Environ Health Perspect 126:107002. https://doi.org/10.1289/ehp3304
Chen C, Xun P, Tsinovoi C, McClure LA, Brockman J, MacDonald L, Cushman M, Cai J, Kamendulis L, Mackey J, He K (2018) Urinary cadmium concentration and the risk of ischemic stroke. Neurology 91:e382–e391. https://doi.org/10.1212/wnl.0000000000005856
Chen TK, Knicely DH, Grams ME (2019) Chronic kidney disease diagnosis and management: a review. JAMA 322:1294–1304. https://doi.org/10.1001/jama.2019.14745
Chowdhury R, Ramond A, O'Keeffe LM, Shahzad S, Kunutsor SK, Muka T, Gregson J, Willeit P, Warnakula S, Khan H, Chowdhury S, Gobin R, Franco OH, Di Angelantonio E (2018) Environmental toxic metal contaminants and risk of cardiovascular disease: systematic review and meta-analysis. BMJ 362:k3310. https://doi.org/10.1136/bmj.k3310
Couser WG, Remuzzi G, Mendis S, Tonelli M (2011) The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney Int 80:1258–1270. https://doi.org/10.1038/ki.2011.368
Deering KE, Callan AC, Prince RL, Lim WH, Thompson PL, Lewis JR, Hinwood AL, Devine A (2018) Low-level cadmium exposure and cardiovascular outcomes in elderly Australian women: a cohort study. Int J Hyg Environ Health 221:347–354. https://doi.org/10.1016/j.ijheh.2017.12.007
Duan W, Xu C, Liu Q, Xu J, Weng Z, Zhang X, Basnet TB, Dahal M, Gu A (2020) Levels of a mixture of heavy metals in blood and urine and all-cause, cardiovascular disease and cancer mortality: a population-based cohort study. Environ Pollut 263:114630. https://doi.org/10.1016/j.envpol.2020.114630
GBD (2020) Chronic kidney disease collaboration: 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. https://doi.org/10.1016/s0140-6736(20)30045-3
Guo J, Su L, Zhao X, Xu Z, Chen G (2016) Relationships between urinary antimony levels and both mortalities and prevalence of cancers and heart diseases in general US population, NHANES 1999-2010. Sci Total Environ 571:452–460. https://doi.org/10.1016/j.scitotenv.2016.07.011
Guo X, Su W, Li N, Song Q, Wang H, Liang Q, Li Y, Lowe S, Bentley R, Zhou Z, Song EJ, Cheng C, Zhou Q, Sun C (2022) Association of urinary or blood heavy metals and mortality from all causes, cardiovascular disease, and cancer in the general population: a systematic review and meta-analysis of cohort studies. Environ Sci Pollut Res Int 29:67483–67503. https://doi.org/10.1007/s11356-022-22353-w
Hsu CW, Yen TH, Chen KH, Lin-Tan DT, Lin JL, Weng CH, Huang WH (2015) Effect of blood cadmium level on mortality in patients undergoing maintenance hemodialysis. Medicine (Baltimore) 94:e1755. https://doi.org/10.1097/md.0000000000001755
Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, Saran R, Wang AY, Yang CW (2013) Chronic kidney disease: global dimension and perspectives. Lancet 382:260–272. https://doi.org/10.1016/s0140-6736(13)60687-x
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. https://doi.org/10.1016/j.envint.2018.11.002
Kataranovski M, Mirkov I, Belij S, Nikolic M, Zolotarevski L, Ciric D, Kataranovski D (2009) Lungs: remote inflammatory target of systemic cadmium administration in rats. Environ Toxicol Pharmacol 28:225–231. https://doi.org/10.1016/j.etap.2009.04.008
Kim K, Melough MM, Sakaki JR, Ha K, Marmash D, Noh H, Chun OK (2019) Association between urinary cadmium to zinc intake ratio with adult mortality in a follow-up study of NHANES 1988-1994 and 1999-2004. Nutrients 12:56. https://doi.org/10.3390/nu12010056
Lanphear BP, Rauch S, Auinger P, Allen RW, Hornung RW (2018) Low-level lead exposure and mortality in US adults: a population-based cohort study. Lancet Public Health 3:e177–e184. https://doi.org/10.1016/s2468-2667(18)30025-2
Lee CC, Weng CH, Huang WH, Yen TH, Lin JL, Lin-Tan DT, Chen KH, Hsu CW (2016) Association between blood cadmium levels and mortality in peritoneal dialysis. Medicine (Baltimore) 95:e3717. https://doi.org/10.1097/md.0000000000003717
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, 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. https://doi.org/10.7326/0003-4819-150-9-200905050-00006
Li Q, Nishijo M, Nakagawa H, Morikawa Y, Sakurai M, Nakamura K, Kido T, Nogawa K, Dai M (2011) Relationship between urinary cadmium and mortality in habitants of a cadmium-polluted area: a 22-year follow-up study in Japan. Chin Med J (Engl) 124:3504–3509
Li Z, Fan Y, Tao C, Yan W, Huang Y, Qian H, Xu Q, Wan T, Chen Y, Qin Y, Lu C (2022) Association between exposure to cadmium and risk of all-cause and cause-specific mortality in the general US adults: a prospective cohort study. Chemosphere 307:136060. https://doi.org/10.1016/j.chemosphere.2022.136060
Lin HC, Chou SH, Fan PC, Zhu Z, Pan J, Li J, Chang CH, Wu VC, Chen SW, Chu PH (2022) The association between day-1 urine cadmium excretion and 30-day mortality in patients with acute myocardial infarction: a multi-institutional cohort study. Int J Cardiol 22:01321–01323. https://doi.org/10.1016/j.ijcard.2022.09.011
Liu Y, Geng T, Wan Z, Lu Q, Zhang X, Qiu Z, Li L, Zhu K, Liu L, Pan A, Liu G (2022) Associations of serum folate and vitamin B12 levels with cardiovascular disease mortality among patients with type 2 diabetes. JAMA Netw Open 5:e2146124. https://doi.org/10.1001/jamanetworkopen.2021.46124
Matović V, Buha A, Ðukić-Ćosić D, Bulat Z (2015) Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys. Food Chem Toxicol 78:130–140. https://doi.org/10.1016/j.fct.2015.02.011
Matsushita K, Coresh J, Sang Y, Chalmers J, Fox C, Guallar E, Jafar T, Jassal SK, Landman GW, Muntner P, Roderick P, Sairenchi T, Schöttker B, Shankar A, Shlipak M, Tonelli M, Townend J, van Zuilen A, Yamagishi K et al (2015) Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol 3:514–525. https://doi.org/10.1016/s2213-8587(15)00040-6
Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT (2010) Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 375:2073–2081. https://doi.org/10.1016/s0140-6736(10)60674-5
Orr SE, Bridges CC (2017) Chronic kidney disease and exposure to nephrotoxic metals. Int J Mol Sci 18:1039. https://doi.org/10.3390/ijms18051039
Ran J, Sun S, Han L, Zhao S, Chen D, Guo F, Li J, Qiu H, Lei Y, Tian L (2020) Fine particulate matter and cause-specific mortality in the Hong Kong elder patients with chronic kidney disease. Chemosphere 247:125913. https://doi.org/10.1016/j.chemosphere.2020.125913
Sakurai M, Suwazono Y, Nishijo M, Nogawa K, Watanabe Y, Yoneda K, Ishizaki M, Morikawa Y, Kido T, Nakagawa H (2021) The relationship between the urinary cadmium concentration and cause-specific mortality in subjects without severe renal damage: a 35-year follow-up study in a cadmium-polluted area of Japan. Int J Environ Res Public Health 18:7747. https://doi.org/10.3390/ijerph18157747
Sherrer SM, Penland E, Modrich P (2018) The mutagen and carcinogen cadmium is a high-affinity inhibitor of the zinc-dependent MutLα endonuclease. Proc Natl Acad Sci U S A 115:7314–7319. https://doi.org/10.1073/pnas.1807319115
Shi L, Yuan Y, Xiao Y, Long P, Li W, Yu Y, Liu Y, Liu K, Wang H, Zhou L, Yang H, Li X, He M, Wu T (2021) Associations of plasma metal concentrations with the risks of all-cause and cardiovascular disease mortality in Chinese adults. Environ Int 157:106808. https://doi.org/10.1016/j.envint.2021.106808
Suwazono Y, Nogawa K, Morikawa Y, Nishijo M, Kobayashi E, Kido T, Nakagawa H, Nogawa K (2015) All-cause mortality increased by environmental cadmium exposure in the Japanese general population in cadmium non-polluted areas. J Appl Toxicol 35:817–823. https://doi.org/10.1002/jat.3077
Tägt J, Helte E, Donat-Vargas C, Larsson SC, Michaëlsson K, Wolk A, Vahter M, Kippler M, Åkesson A (2022) Long-term cadmium exposure and fractures, cardiovascular disease, and mortality in a prospective cohort of women. Environ Int 161:107114. https://doi.org/10.1016/j.envint.2022.107114
Tellez-Plaza M, Guallar E, Howard BV, Umans JG, Francesconi KA, Goessler W, Silbergeld EK, Devereux RB, Navas-Acien A (2013) Cadmium exposure and incident cardiovascular disease. Epidemiology 24:421–429. https://doi.org/10.1097/EDE.0b013e31828b0631
Tellez-Plaza M, Navas-Acien A, Menke A, Crainiceanu CM, Pastor-Barriuso R, Guallar E (2012) Cadmium exposure and all-cause and cardiovascular mortality in the U.S. general population. Environ Health Perspect 120:1017–1022. https://doi.org/10.1289/ehp.1104352
Tyson CC, Luciano A, Modliszewski JL, Corcoran DL, Bain JR, Muehlbauer M, Ilkayeva O, Pourafshar S, Allen J, Bowman C, Gung J, Asplin JR, Pendergast J, Svetkey LP, Lin PH, Scialla JJ (2021) Effect of bicarbonate on net acid excretion, blood pressure, and metabolism in patients with and without CKD: the acid base compensation in CKD study. Am J Kidney Dis 78:38–47. https://doi.org/10.1053/j.ajkd.2020.10.015
Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M (2007) Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Med 4:e297. https://doi.org/10.1371/journal.pmed.0040297
Watanabe Y, Nogawa K, Nishijo M, Sakurai M, Ishizaki M, Morikawa Y, Kido T, Nakagawa H, Suwazono Y (2020) Relationship between cancer mortality and environmental cadmium exposure in the general Japanese population in cadmium non-polluted areas. Int J Hyg Environ Health 223:65–70. https://doi.org/10.1016/j.ijheh.2019.10.005
Wen Y, Huang S, Zhang Y, Zhang H, Zhou L, Li D, Xie C, Lv Z, Guo Y, Ke Y, Wu T, Cheng J (2019) Associations of multiple plasma metals with the risk of ischemic stroke: a case-control study. Environ Int 125:125–134. https://doi.org/10.1016/j.envint.2018.12.037
Yang J, Lo K, Yang A (2022) Trends in urinary and blood cadmium levels in U.S. adults with or without comorbidities, 1999-2018. Nutrients 14:802. https://doi.org/10.3390/nu14040802
Zhang NH, Luo R, Cheng YC, Ge SW, Xu G (2020) Leisure-time physical activity and mortality in CKD: a 1999-2012 NHANES analysis. Am J Nephrol 51:919–929. https://doi.org/10.1159/000511685
Zhang YB, Chen C, Pan XF, Guo J, Li Y, Franco OH, Liu G, Pan A (2021) Associations of healthy lifestyle and socioeconomic status with mortality and incident cardiovascular disease: two prospective cohort studies. BMJ 373:n604. https://doi.org/10.1136/bmj.n604
Zhong Q, Wu HB, Niu QS, Jia PP, Qin QR, Wang XD, He JL, Yang WJ, Huang F (2021) Exposure to multiple metals and the risk of hypertension in adults: a prospective cohort study in a local area on the Yangtze River, China. Environ Int 153:106538. https://doi.org/10.1016/j.envint.2021.106538
Zhu K, Zhang Y, Lu Q, Geng T, Li R, Wan Z, Zhang X, Liu Y, Li L, Qiu Z, He M, Liu L, Pan A, Liu G (2022) Associations of exposure to lead and cadmium with risk of all-cause and cardiovascular disease mortality among patients with type 2 diabetes. Environ Sci Pollut Res Int 29:76805–76815. https://doi.org/10.1007/s11356-022-21273-z
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The authors are very grateful to all of the NHANES staff and participants for their hard work and selfless sharing of data.
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JZ, XW, and XH contributed to the study conception and design. Material preparation, data extraction, and analysis were performed by JZ and XW. The first draft of the manuscript was written by JZ. ZM, YD, YY, SC, CO, XS, JP, and XH critically reviewed and edited the article. All authors read and approved the final manuscript.
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Zhang, J., Wang, X., Ma, Z. et al. Associations of urinary and blood cadmium concentrations with all-cause mortality in US adults with chronic kidney disease: a prospective cohort study. Environ Sci Pollut Res 30, 61659–61671 (2023). https://doi.org/10.1007/s11356-023-26451-1
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DOI: https://doi.org/10.1007/s11356-023-26451-1