Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Environmental metal exposures and kidney function of Guatemalan sugarcane workers

Journal of Exposure Science & Environmental Epidemiology volume 32, pages 461–471 (2022)Cite this article

Abstract

Background

Exposure to environmental metals can cause nephrotoxicity. There is an international epidemic of chronic kidney disease of unknown cause (CKDu). Whether metal exposures contribute to kidney dysfunction in populations at risk for CKDu remains unresolved.

Objective

Urinary metals (arsenic, cadmium, nickel, and uranium) were examined in 222 sugarcane cutters in Guatemala at three time points over 1 year.

Methods

We explored the relationships between metal concentrations and markers of kidney function using multivariable linear mixed-effect models.

Results

Arsenic, cadmium, and nickel were detected in the majority of the 340 urine samples and were generally within limits previously considered to be nonnephrotoxic. Nevertheless, higher urine cadmium was inversely associated with estimated glomerular filtration rate (eGFR) (β: −4.23, 95% confidence interval [CI]: −6.92, −1.54) and positively associated with neutrophil gelatinase-associated lipocalin (NGAL) (β: 2.92, 95% CI: 1.20, 4.64). Higher urine arsenic was also inversely associated with eGFR (β: −4.36, 95% CI: −7.07, −1.64).

Significance

Our findings suggest that exposures to metals, including cadmium and arsenic, might contribute to kidney toxicity seen in workers at risk for CKDu. These findings are consistent with the potential for metal nephrotoxicity at lower than expected levels in the setting of manual work in a very hot environment.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Study timeline and design.

References

  1. Johnson RJ, Wesseling C, Newman LS. Chronic kidney disease of unknown cause in agricultural communities. N Engl J Med. 2019;380:1843–52.

    Article  PubMed  Google Scholar 

  2. Jayasumana C, Paranagama P, Agampodi S, Wijewardane C, Gunatilake S, Siribaddana S. Drinking well water and occupational exposure to Herbicides is associated with chronic kidney disease, in Padavi-Sripura, Sri Lanka. Environ Health. 2015;14:6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Wesseling C, Crowe J, Hogstedt C, Jakobsson K, Lucas R, Wegman DH, et al. Resolving the enigma of the Mesoamerican nephropathy: a research workshop summary. Am J Kidney Dis. 2014;63:396–404.

    Article  PubMed  Google Scholar 

  4. Vervaet BA, D’Haese PC, Verhulst A. Environmental toxin-induced acute kidney injury. Clin Kidney J. 2017;10:747–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fowler BA. Mechanisms of kidney cell injury from metals. Environ Health Perspect. 1993;100:57–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy metal toxicity and the environment. Exp Suppl. 2012;2012:133–64.

    Google Scholar 

  7. Pearce N, Caplin B. Let’s take the heat out of the CKDu debate: more evidence is needed. Occup Environ Med. 2019;76:357–9.

    Article  PubMed  Google Scholar 

  8. Rango T, Jeuland M, Manthrithilake H, McCornick P. Nephrotoxic contaminants in drinking water and urine, and chronic kidney disease in rural Sri Lanka. Sci Total Environ. 2015;518:574–85.

    Article  PubMed  CAS  Google Scholar 

  9. Jayasumana C, Gunatilake S, Senanayake P. Glyphosate, hard water and nephrotoxic metals: are they the culprits behind the epidemic of chronic kidney disease of unknown etiology in Sri Lanka? Int J Environ Res Public Health. 2014;11:2125–47.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kulathunga M, Wijayawardena MAA, Naidu R, Wijeratne AW. Chronic kidney disease of unknown aetiology in Sri Lanka and the exposure to environmental chemicals: a review of literature. Environ Geochem Health. 2019;41:2329–38.

    Article  CAS  PubMed  Google Scholar 

  11. Bandara JMRS, Senevirathna DMAN, Dasanayake DMRSB, Herath V, Bandara JMRP, Abeysekara T, et al. Chronic renal failure among farm families in cascade irrigation systems in Sri Lanka associated with elevated dietary cadmium levels in rice and freshwater fish (Tilapia). Environ Geochem Health. 2008;30:465–78.

    Article  CAS  PubMed  Google Scholar 

  12. Herath HMAS, Kawakami T, Nagasawa S, Serikawa Y, Motoyama A, Chaminda GGT, et al. Arsenic, cadmium, lead, and chromium in well water, rice, and human urine in Sri Lanka in relation to chronic kidney disease of unknown etiology. J Water Health. 2018;16:212–22.

    Article  Google Scholar 

  13. Jayasumana C, Gunatilake S, Siribaddana S. Simultaneous exposure to multiple heavy metals and glyphosate may contribute to Sri Lankan agricultural nephropathy. BMC Nephrol. 2015;16:103.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Bustamante-Montes LP, Flores-Polanco JA, Isaac-Olive K, Hernandez-Tellez M, Campuzano-Gonzalez ME, Ramirez-Duran N. Exploratory study on the association of heavy metals and the nephropathy of unknown etiology in the western state of mexico. Rev Internacional De Contaminacion Ambiental. 2018;34:555–64.

    Article  Google Scholar 

  15. McClean M, Laws R, Kaufman JS, Weiner DE, Rodrıguez JMS, Ramirez-Rubio O, et al. Biological sampling report: investigating biomarkers of kidney injury and chronic kidney disease among workers in Western Nicaragua. Boston University; Boston University School of Public Health 715 Albany St - Boston, MA; 2012.

  16. Smpokou ET, Gonzalez-Quiroz M, Martins C, Alvito P, Le Blond J, Glaser J, et al. Environmental exposures in young adults with declining kidney function in a population at risk of Mesoamerican nephropathy. Occup Environ Med. 2019;76:920–6.

    Article  PubMed  Google Scholar 

  17. Fischer RSB, Unrine J, Vangala C, Sanderson WT, Mandayam S, Murray KO. Evidence of nickel and other trace elements and their relationship to clinical findings in acute Mesoamerican nephropathy: a case-control analysis. PLoS ONE. 2020;15(11):e0240988.

  18. Wijkstrom J, Gonzalez-Quiroz M, Hernandez M, Trujillo Z, Hultenby K, Ring A, et al. Renal morphology, clinical findings, and progression rate in Mesoamerican nephropathy. Am J Kidney Dis. 2017;69:626–36.

    Article  PubMed  Google Scholar 

  19. Butler-Dawson J, Krisher L, Asensio C, Cruz A, Tenney L, Weitzenkamp D, et al. Risk factors for declines in kidney function in sugarcane workers in Guatemala. J Occup Environ Med. 2018;60:548–58.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Butler-Dawson J, Krisher L, Yoder H, Dally M, Sorensen C, Johnson RJ, et al. Evaluation of heat stress and cumulative incidence of acute kidney injury in sugarcane workers in Guatemala. Int Arch Occup Environ Health. 2019;92(7):977–90.

  21. Pruszkowski E, Neubauer K, Thomas R. An overview of clinical applications by inductively coupled plasma mass spectrometry. At Spectrosc. 1998;19:111–5.

    CAS  Google Scholar 

  22. Nixon DE, Moyer TP. Routine clinical determination of lead, arsenic, cadmium, and thallium in urine and whole blood by inductively coupled plasma mass spectrometry. Spectrochimica Acta Part B: Atomic Spectroscopy. 1996;51:13–25.

    Article  Google Scholar 

  23. Jarrett JM, Cadwell KL, Jones RL. Urine multi-element ICP-DRC-MS: antimony, arsenic, barium, beryllium, cadmium, cesium, cobalt, lead, manganese, molybdenum, platinum, strontium, thallium, tin, tungsten, and uranium. CDC-Division of Laboratory Sciences, Laboratory Protocol. Centers for Disease Control and Prevention, Adopted October 01, 1994, updated September 15, 2014.

  24. Fiseha T, Tamir Z. Urinary markers of tubular injury in early diabetic nephropathy. Int J Nephrol. 2016;2016:4647685.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Devarajan P. Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury. Biomark Med. 2010;4:265–80.

    Article  CAS  PubMed  Google Scholar 

  26. Vaidya VS, Waikar SS, Ferguson MA, Collings FB, Sunderland K, Gioules C, et al. Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci. 2008;1:200–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Levey AS, Stevens LA, Schmid CH, Zhang YP, Castro AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Caruso RV, O’Connor RJ, Stephens WE, Cummings KM, Fong GT. Toxic metal concentrations in cigarettes obtained from U.S. smokers in 2009: results from the International Tobacco Control (ITC) United States survey cohort. Int J Environ Res Public Health. 2013;11:202–17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Hornung R, Reed L. Estimation of average concentration in the presence of nondetectable values. Appl Occup Environ Hyg. 1990;5:46–51.

    Article  CAS  Google Scholar 

  30. Barr DB, Wilder LC, Caudill SP, Gonzalez AJ, Needham LL, Pirkle JL. Urinary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements. Environ Health Perspect. 2005;113:192–200.

    Article  CAS  PubMed  Google Scholar 

  31. World Health Organization. Office of Occupational H. Biological monitoring of chemical exposure in the workplace: guidelines. Geneva: World Health Organization;1996.

  32. Weaver VM, Kim N-S, Jaar BG, Schwartz BS, Parsons PJ, Steuerwald AJ, et al. Associations of low-level urine cadmium with kidney function in lead workers. Occup Environ Med. 2011;68:250–6.

    Article  CAS  PubMed  Google Scholar 

  33. Akesson A, Lundh T, Vahter M, Bjellerup P, Lidfeldt J, Nerbrand C, et al. Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure. Environ Health Perspect. 2005;113:1627–31.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Hellstrom L, Elinder CG, Dahlberg B, Lundberg M, Jarup L, Persson B, et al. Cadmium exposure and end-stage renal disease. Am J Kidney Dis. 2001;38:1001–8.

    Article  CAS  PubMed  Google Scholar 

  35. Adams RG, Harrison JF, Scott P. The development of cadmium-induced proteinuria, impaired renal function, and osteomalacia in alkaline battery workers. Q J Med. 1969;38:425–43.

    CAS  PubMed  Google Scholar 

  36. Navarro-Moreno LG, Quintanar-Escorza MF, Gonzalez S, Mondragon R, Cerbon-Solorzano J, Valdes J, et al. Effects of lead intoxication on intercellular junctions and biochemical alterations of the renal proximal tubule cells. Toxicol Vitro. 2009;23:1298–304.

    Article  CAS  Google Scholar 

  37. Gerhardt RE, Hudson JB, Raghunatha RN, Sobel RE. Chronic renal insufficiency from cortical necrosis induced by arsenic poisoning. Arch Intern Med. 1978;138:1267–9.

    Article  CAS  PubMed  Google Scholar 

  38. Hambach R, Lison D, D’Haese P, Weyler J, Francois G, De Schryver A, et al. Adverse effects of low occupational cadmium exposure on renal and oxidative stress biomarkers in solderers. Occup Environ Med. 2013;70:108–13.

    Article  CAS  PubMed  Google Scholar 

  39. Zheng LY, Umans JG, Tellez-Plaza M, Yeh F, Francesconi KA, Goessler W, et al. Urine arsenic and prevalent albuminuria: evidence from a population-based study. Am J Kidney Dis. 2013;61:385–94.

    Article  CAS  PubMed  Google Scholar 

  40. Sorensen CJ, Butler-Dawson J, Dally M, Krisher L, Griffin BR, Johnson RJ, et al. Risk factors and mechanisms underlying cross-shift decline in kidney function in Guatemalan sugarcane workers. J Occup Environ Med. 2019;61:239–50.

    Article  CAS  PubMed  Google Scholar 

  41. Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR, et al. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol. 2009;4:337–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chuang KJ, Pan CH, Su CL, Lai CH, Lin WY, Ma CM, et al. Urinary neutrophil gelatinase-associated lipocalin is associated with heavy metal exposure in welding workers. Sci Rep. 2015;5:18048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Nordberg GF, Fowler BA, Nordberg M. Handbook on the toxicology of metals. 3rd ed. Academic Press; Academic Press/Elsevier, USA; 2007.

  44. CDC. Fourth report on human exposure to environmental chemicals, updated tables, (January 2019). Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2019.

  45. Roncal-Jimenez C, Lanaspa MA, Jensen T, Sanchez-Lozada LG, Johnson RJ. Mechanisms by which dehydration may lead to chronic kidney disease. Ann Nutr Metab. 2015;66:10–3.

    Article  CAS  PubMed  Google Scholar 

  46. Correa-Rotter R, Wesseling C, Johnson RJ. CKD of unknown origin in Central America: the case for a Mesoamerican nephropathy. Am J Kidney Dis. 2014;63:506–20.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Chaumont A, Nickmilder M, Dumont X, Lundh T, Skerfving S, Bernard A. Associations between proteins and heavy metals in urine at low environmental exposures: evidence of reverse causality. Toxicol Lett. 2012;210:345–52.

    Article  CAS  PubMed  Google Scholar 

  48. Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function—measured and estimated glomerular filtration rate. N Engl J Med. 2006;354:2473–83.

    Article  CAS  PubMed  Google Scholar 

  49. National Research Council. Arsenic in drinking water: 2001 update. Washington, DC: The National Academies Press; 2001.

  50. Krisher L, Butler-Dawson J, Asensio C, Yoder H, Cruz A, Pilloni D, et al. A total worker health approach to assessing kidney health in sugarcane workers in Guatemala: an opportunity for nutrition intervention. Poster presented at the Third International Workshop on Chronic Kidney Diseases of Uncertain/Non-Traditional Etiology in Mesoamerica and Other Regions, Costa Rica, 2019.

Download references

Acknowledgements

The authors would like to thank all their collaborators including Hillary Yoder, MS, Stephen Brindley, MS, Nicholas Smith, and all the workers who have made this work possible. The authors would also like to acknowledge Trace Metals Core Facility at the Mailman School of Public Health, Columbia University, for the analysis of the urine samples.

Funding

This study was supported by Centers for Disease Control and Prevention (U19 OH011227) and National Institutes of Health (NIH) (R21 ES028826), and in part by Pantaleon and the Chancellor, University of Colorado, CU Anschutz Campus. Metal laboratory analysis was supported by NIH grants P30 ES009089 and P42 ES010349. Funders had no role in data analysis, interpretation of data, writing the manuscript, or the decision to submit the findings for publication.

Author information

Authors and Affiliations

  1. Center for Health, Work & Environment, Colorado School of Public Health, University of Colorado, Aurora, CO, USA

    Jaime Butler-Dawson, Katherine A. James, Lyndsay Krisher, Diana Jaramillo, Miranda Dally, John Adgate & Lee S. Newman

  2. Department of Environmental and Occupational Health, Colorado School of Public Health, University of Colorado, Aurora, CO, USA

    Jaime Butler-Dawson, Katherine A. James, Lyndsay Krisher, Miranda Dally, John Adgate & Lee S. Newman

  3. Colorado Consortium on Climate Change and Human Health, University of Colorado, Aurora, CO, USA

    Jaime Butler-Dawson, Katherine A. James, Lyndsay Krisher, Diana Jaramillo, Miranda Dally, Richard J. Johnson & Lee S. Newman

  4. Rocky Mountain Poison and Drug Safety, Denver Health and Hospital Authority, Denver, CO, USA

    Natalie Neumann

  5. Department of Emergency Medicine, Yale School of Medicine, New Haven, CT, USA

    Natalie Neumann

  6. Pantaleon, Guatemala City, Guatemala

    Daniel Pilloni, Alex Cruz & Claudia Asensio

  7. Division of Renal Diseases and Hypertension, Department of Medicine, School of Medicine, University of Colorado, Aurora, CO, USA

    Richard J. Johnson

  8. Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, School of Medicine, University of Colorado, Aurora, CO, USA

    Lee S. Newman

  9. Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, CO, USA

    Lee S. Newman

Authors
  1. Jaime Butler-Dawson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katherine A. James
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lyndsay Krisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Diana Jaramillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Miranda Dally
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Natalie Neumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daniel Pilloni
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alex Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Claudia Asensio
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Richard J. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. John Adgate
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Lee S. Newman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jaime Butler-Dawson.

Ethics declarations

Conflict of interest

The University of Colorado has a memorandum of agreement with Pantaleon, a Guatemala-based agribusiness. Pantaleon provides partial financial support for research through a contract with the university and has provided access to the employees who volunteered to participate in this research project. The University of Colorado employed appropriate research methods in keeping with academic freedom, based conclusions on critical analysis of the evidence, and reported findings fully and objectively. The terms of this arrangement have been reviewed and approved by the University of Colorado in accordance with its conflict of interest policies.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Butler-Dawson, J., James, K.A., Krisher, L. et al. Environmental metal exposures and kidney function of Guatemalan sugarcane workers. J Expo Sci Environ Epidemiol 32, 461–471 (2022). https://doi.org/10.1038/s41370-021-00292-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41370-021-00292-x

Keywords

  • Metal exposure
  • Kidney function
  • Agricultural workers

This article is cited by

Search

Advanced search

Quick links