Abstract
The ‘alarm clock’ for human beings in the era of climate medicine has rung. Original diseases have appeared, that could not be explained and attributed to common causes, which are suggested to be linked to global warming and environmental factors. Such an indolent disease is the chronic kidney disease of unknown cause (CKDu), introduced also as Mesoamerican or Uddanam nephropathy. Scientists equate the climate impact on kidneys with the canary in the coal mine; coal miners used to carry caged canaries with them, so that if poisonous gases, such as methane or carbon monoxide leaked into the mine-shaft, the gases would kill the canary before killing the miners; similarly, kidneys are injured before devastating and lethal complications occur in humans. In some regions of Central America, the deaths due to chronic kidney disease increased by 177% with a death toll being as high as over 20,000. It was first documented in animals that periodic heat and dehydration have a major role in causing chronic kidney disease. Based on that observation, it is advocated that young male agricultural workers in Central America and South Asia, develop renal disease by getting exposed to extreme heat repeatedly. The clinico-pathological characteristics of this type of kidney injury, do not belong to an existing classification, even though a form of tubulo-interstitial renal disease has been proposed. In this review, we will discuss about CKDu, its epidemiology and pathophysiological mechanisms, clinical presentation and diagnostic biomarkers and examine potential therapeutic options.
-
Research funding: None declared.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Not applicable.
-
Ethical approval: The local Institutional Review Board deemed the study exempt from review.
References
1. Cusumano, A, Garcia Garcia, G, Gonzalez Bedat, C. The Latin American dialysis and transplant registry: report 2006. Ethn Dis 2009;19(1 Suppl):S1-3–S1-6.Search in Google Scholar
2. Wanigasuriya, KP, Peiris-John, RJ, Wickremasinghe, R, Hittarage, A. Chronic renal failure in North Central Province of Sri Lanka: an environmentally induced disease. Trans R Soc Trop Med Hyg 2007;101:1013–7, https://doi.org/10.1016/j.trstmh.2007.05.006.Search in Google Scholar PubMed
3. Mani, MK. Chronic renal failure in India. Nephrol Dial Transplant 1993;8:684–9, https://doi.org/10.1093/ndt/8.8.684.Search in Google Scholar PubMed
4. Glaser, J, Lemery, J, Rajagopalan, B, Diaz, HF, García-Trabanino, R, Taduri, G, et al.. Climate change and the emergent epidemic of CKD from heat stress in rural communities: the case for heat stress nephropathy. Clin J Am Soc Nephrol 2016;11:1472–83, https://doi.org/10.2215/cjn.13841215.Search in Google Scholar PubMed PubMed Central
5. Sanderson, EW, Jaiteh, M, Levy, MA. The human footprint and the last of the wild. Bioscience 2002;52:891–904, https://doi.org/10.1641/0006-3568(2002)052[0891:thfatl]2.0.co;2.10.1641/0006-3568(2002)052[0891:THFATL]2.0.CO;2Search in Google Scholar
6. Dally, M, Butler-Dawson, J, Krisher, L, Monaghan, A, Weitzenkamp, D, Sorensen, C, et al.. The impact of heat and impaired kidney function on productivity of Guatemalan sugarcane workers. PLoS One 2018;13: e0205181, https://doi.org/10.1371/journal.pone.0205181.Search in Google Scholar
7. Borg, M, Nitschke, M, Williams, S, McDonald, S, Nairn, J, Bi, P. Using the excess heat factor to indicate heatwave-related urinary disease: a case study in Adelaide, South Australia. Int J Biometeorol 2019;63:435–47, https://doi.org/10.1007/s00484-019-01674-5.Search in Google Scholar
8. Borg, M, Bi, P, Nitschke, M, Williams, S, McDonald, S. The impact of daily temperature on renal disease incidence: an ecological study. Environ Health 2017;16:114, https://doi.org/10.1186/s12940-017-0331-4.Search in Google Scholar
9. Weiner, DE, McClean, MD, Kaufman, JS, Brooks, DR. The Central American epidemic of CKD. Clin J Am Soc Nephrol 2013;8:504–11, https://doi.org/10.2215/cjn.05050512.Search in Google Scholar
10. Raines, N, Gonzalez, M, Wyatt, C, Kurzrok, M, Pool, C, Lemma, T, et al.. Risk factors for reduced glomerular filtration rate in a Nicaraguan community affected by Mesoamerican nephropathy. MEDICC Rev 2014;16:16–22, https://doi.org/10.37757/MR2014.V16.N2.4.Search in Google Scholar
11. Ganguli, A. Uddanam nephropathy/regional nephropathy in India: preliminary findings and a plea for further research. Am J Kidney Dis 2016;68:344–8, https://doi.org/10.1053/j.ajkd.2016.04.012.Search in Google Scholar
12. Cuadra, SN, Jakobsson, K, Hogstedt, C, Wesseling, C. Chronic kidney disease: assessment of current knowledge and feasibility for regional research collaboration in Central America. In: Chronic Kidney Disease: Assessment of Current Knowledge and Feasibility for Regional Research Collaboration in Central America. Work & Health Series, No. 2. Heredia, Costa Rica: SALTRA, IRET-UNA; 2006.Search in Google Scholar
13. Ramirez-Rubio, O, McClean, MD, Amador, JJ, Brooks, DR. An epidemic of chronic kidney disease in Central America: an overview. J Epidemiol Community Health 2013;67:1–3, https://doi.org/10.1136/jech-2012-201141.Search in Google Scholar PubMed
14. Wijkström, J, Leiva, R, Elinder, CG, Leiva, S, Trujillo, Z, Trujillo, L, et al.. Clinical and pathological characterization of Mesoamerican Nephropathy: a new kidney disease in Central America. Am J Kidney Dis 2013;62:908–18, https://doi.org/10.1053/j.ajkd.2013.05.019.Search in Google Scholar PubMed
15. Athuraliya, NT, Abeysekera, TD, Amerasinghe, PH, Kumarasiri, R, Bandara, P, Karunaratne, U. Uncertain etiologies of proteinuric-chronic kidney disease in rural Sri Lanka. Kidney Int 2011;80:1212–21, https://doi.org/10.1038/ki.2011.258.Search in Google Scholar PubMed
16. Trabanino, RG, Aguilar, R, Silva, CR, Mercado, MO, Merino, RL. End-stage renal disease among patients in a referral hospital in El Salvador. Rev Panam Salud Publica 2002;12:202–6, https://doi.org/10.1590/s1020-49892002000900009.Search in Google Scholar PubMed
17. Costello, A, Abbas, M, Allen, A, Bellamy, R, Friel, S, Groce, N. Managing the health effects of climate change: Lancet and University College London institute for global health Commission. Lancet 2009;373:1693–733, https://doi.org/10.1016/s0140-6736(09)60935-1.Search in Google Scholar
18. Watts, N, Adger, WN, Agnolucci, P, Blackstock, J, Byass, P, Cai, W, et al.. Health and climate change: policy responses to protect public health. Lancet 2015;386:1861–914, https://doi.org/10.1016/s0140-6736(15)60854-6.Search in Google Scholar PubMed
19. Parikh, C, Berl, T. Disorders of water metabolism. In: Floege, J, Johnson, RJ, Feehally, J, editors Comprehensive Clinical Nephrology, 4th ed. ed. Philadelphia: Elsevier; 2010.10.1016/B978-0-323-05876-6.00008-3Search in Google Scholar
20. Cirillo, P, Gersch, MS, Mu, W, Scherer, PM, Kim, KM, Gesualdo, L, et al.. Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators in proximal tubular cells. J Am Soc Nephrol 2009;20:545–53, https://doi.org/10.1681/asn.2008060576.Search in Google Scholar
21. Clark, WF, Sontrop, JM, Macnab, JJ. Urine volume and change in estimated GFR in a community-based cohort study. J Am Soc Nephrol 2011;6:2634–41, https://doi.org/10.2215/cjn.01990211.Search in Google Scholar PubMed PubMed Central
22. Strippoli, GF, Craig, JC, Rochtchina, E, Flood, VM, Wang, JJ, Mitchell, P. Fluid and nutrient intake and risk of chronic kidney disease. Nephrology 2011;16:326–34, https://doi.org/10.1111/j.1440-1797.2010.01415.x.Search in Google Scholar PubMed
23. 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, https://doi.org/10.1097/jom.0000000000001529.Search in Google Scholar PubMed PubMed Central
24. Jayatilake, N, Mendis, S, Maheepala, P, Mehta, FR. Chronic kidney disease of uncertain aetiology: prevalence and causative factors in a developing country. BMC Nephrol 2013;14:180, https://doi.org/10.1186/1471-2369-14-180.Search in Google Scholar PubMed PubMed Central
25. Hranjec, T, Kovac, A, Kos, J, Mao, W, Chen, JJ, Grollman, AP, et al.. Endemic nephropathy: the case for chronic poisoning by Aristolochia. Croat Med J 2005;46:116–25.Search in Google Scholar
26. Vanherweghem, JL. [A new form of nephropathy secondary to the absorption of Chinese herbs]. Bull Mem Acad R Med Belg 1994;149:128–35.Search in Google Scholar
27. Debelle, FD, Vanherweghem, JL, Nortier, JL. Aristolochic acid nephropathy: a worldwide problem. Kidney Int 2008;74:158–69, https://doi.org/10.1038/ki.2008.129.Search in Google Scholar PubMed
28. Henderson, DA. A follow-up of cases of plumbism in children. Australas Ann Med 1954;3:219–24, https://doi.org/10.1111/imj.1954.3.3.219.Search in Google Scholar PubMed
29. Johnson, RJ, Wesseling, C, Newman, LS. Chronic kidney disease of unknown cause in agricultural communities. N Engl J Med 2019;19:1843–52, https://doi.org/10.1056/nejmra1813869.Search in Google Scholar
30. Fassett, RG, Venuthurupalli, SK, Gobe, GC, Coombes, JS, Cooper, MA, Hoy, WE. Biomarkers in chronic kidney disease: a review. Kidney Int 2011;80:806–21, https://doi.org/10.1038/ki.2011.198.Search in Google Scholar PubMed
31. Wasung, ME, Chawla, LS, Madero, M. Biomarkers of renal function, which and when? Clin Chim Acta 2015;438:350–7, https://doi.org/10.1016/j.cca.2014.08.039.Search in Google Scholar PubMed
32. Sayanthooran, S, Magana-Arachchi, DN, Gunerathne, L. Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study. BMC Nephrol 2018;18:31, https://doi.org/10.1186/s12882-017-0440-x.Search in Google Scholar PubMed PubMed Central
33. Adams, DR, Eng, CM. Next-generation sequencing to diagnose suspected genetic disorders. N Engl J Med 2018;379:353–62, https://doi.org/10.1056/NEJMra1711801.Search in Google Scholar PubMed
34. Peraza, S, Wesseling, C, Aragón, A, Leiva, R, Trabanino, R, Torres, C, et al.. Decreased kidney function among agricultural workers in El Salvador. Am J Kidney Dis 2012;59:531–40, https://doi.org/10.1053/j.ajkd.2011.11.039.Search in Google Scholar PubMed
35. Jha, V, Parameswaran, S. Community-acquired acute kidney injury in tropical countries. Nat Rev Nephrol 2013;9:278–90, https://doi.org/10.1038/nrneph.2013.36.Search in Google Scholar PubMed
36. Brikowski, TH, Lotan, Y, Pearle, MS. Climate-related increase in the prevalence of urolithiasis in the United States. Proc Natl Acad Sci USA 2008;105:9841–6, https://doi.org/10.1073/pnas.0709652105.Search in Google Scholar PubMed PubMed Central
37. Herrera, R, Orantes, CM, Almaguer, M. Clinical characteristics of chronic kidney disease of nontraditional causes in Salvadoran farming communities. MEDICC Rev 2014;16:39–48, https://doi.org/10.37757/MR2014.V16.N2.7.Search in Google Scholar PubMed
38. Wegman, DH, Apelqvist, J, Bottai, M, Ekström, U, García-Trabanino, R, Glaser, J, et al.. Work Health and Efficiency (WE) Program Working Group. Intervention to diminish dehydration and kidney damage among sugarcane workers. Scand J Work Environ Health 2018;44:16–24, https://doi.org/10.5271/sjweh.3659.Search in Google Scholar PubMed
39. Chandrajith, R, Nanayakkara, S, Itai, K, Aturaliya, TNC, Dissanayake, CB, Abeysekera, T. Chronic kidney diseases of uncertain etiology (CKDue) in Sri Lanka: geographic distribution and environmental implications. Environ Geochem Health 2011;33:267–78, https://doi.org/10.1007/s10653-010-9339-1.Search in Google Scholar PubMed
40. Abraham, G, Varughese, S, Thandavan, T, Iyengar, A, Fernando, E, Naqvi, SAJ. Chronic kidney disease hotspots in developing countries in South Asia. Clin Kidney J 2016;9:135–41, https://doi.org/10.1093/ckj/sfv109.Search in Google Scholar PubMed PubMed Central
41. Reddy, DV, Gunasekar, A. Chronic kidney disease in two coastal districts of Andhra Pradesh, India: role of drinking water. Environ Geochem Health 2013;35:439–54, https://doi.org/10.1007/s10653-012-9506-7.Search in Google Scholar PubMed
42. Barsoum, RS. Burden of chronic kidney disease: North Africa. Kidney Int 2013;3:164–6, https://doi.org/10.1038/kisup.2013.5.Search in Google Scholar PubMed PubMed Central
43. El Minshawy, O, Ghabrah, T, El Bassuoni, E. End-stage renal disease in Tabuk Area, Saudi Arabia: an epidemiological study. Saudi J Kidney Dis Transpl 2014;25:192–5, https://doi.org/10.4103/1319-2442.124574.Search in Google Scholar PubMed
44. Mix, J, Elon, L, Vi Thien Mac, V. Hydration status, kidney function, and kidney injury in Florida agricultural workers. J Occup Environ Med 2018;60:e253–e260, https://doi.org/10.1097/jom.0000000000001261.Search in Google Scholar PubMed
45. Moyce, S, Mitchell, D, Armitage, T, Tancredi, D, Joseph, J, Schenker, M. Heat strain, volume depletion and kidney function in California agricultural workers. Occup Environ Med 2017;74:402–9, https://doi.org/10.1136/oemed-2016-103848.Search in Google Scholar PubMed PubMed Central
46. Roncal-Jimenez, CA, Sato, Y, Milagres, T. Experimental heat stress nephropathy and liver injury are improved by allopurinol. Am J Physiol Renal Physiol 2018;315:F726–F733, https://doi.org/10.1152/ajprenal.00543.2017.Search in Google Scholar PubMed PubMed Central
© 2021 Walter de Gruyter GmbH, Berlin/Boston
