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Does fluoride cause the mysterious chronic kidney disease of multifactorial origin?

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Abstract

A chronic kidney disease of multifactorial origin (CKDmfo), also known as CKD of unknown origin, started to manifest during the past four decades in certain economically poor, peri-equatorial agricultural countries. CKDmfo is an environmentally induced, occupationally-mediated, chronic tubulointerstitial disease. Prolonged exposure to environmental nephrotoxic agents and extenuating conditions are prerequisites for its manifestation. More than 30 causative factors have been postulated, but none one has been properly scientifically tested, to be able to include or exclude. In recent years, fluoride has come to be considered a key contender as a causative agent of CKDmfo. Therefore, this review examines the pros and cons of that theory and the potential plausibility that fluoride causes CKDmfo. It also examines the potential interactions and additive or synergistic effects of certain geogenic factors, especially, the plausibility of CaPO−34 apatite and fluorapatite crystals and nanotube formation in concentrated tubular filtrate and within tubular cells, in renal tubules. The information presented is based on published work and data collected over the past two decades in Sri Lanka. However, the evidence and concepts are applicable to all CKDmfo-affected countries. Thus, the presented content might facilitate scientists to narrowed down causative factors to just a few and government departments to implement effective programs for preventing this disease. The findings suggest that in addition to the geogenic components, disease manifestation requires (A) prolonged exposure to environmental nephrotoxins and factors, (B) interactions among elements (Ca2+, PO−34 , F−, and Mg2+), and (C) vulnerability of the person, such as chronic dehydration, and antioxidant and micronutrient deficiencies. In vivo precipitation of nanominerals in renal tubular tissues that arising over several years causes tubulointerstitial disease—CKDmfo. Inherent vulnerabilities and conditions, together with nanomineral precipitation, trigger renal tubular cell oxidative stresses, inflammation, and fibrosis, and eventually causing tubulointerstitial chronic renal failure—CKDmfo.

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Fig. 1
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These figures were modified from previously published data sets (Wimalawansa 2014, 2016a; Dissanayake and Chandrajith 2007; Dharmagunawardhane 1993; Dissanayake 2005b; Weeraratne and Wimalawansa 2015; Chandrajith et al. 2005; Wimalawansa and Wimalawansa 2015b)

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References

  • Abdulkader, R., Burdmann, E. A., Lebrao, M. L., Duarte, Y. A. O., & Zanetta, D. M. T. (2017). Aging and decreased glomerular filtration rate: An elderly population-based study. PLoS ONE, 12(12), e0189935.

    Google Scholar 

  • Agalakova, A. A., & Gusev, G. P. (2012). Molecular mechanisms of cytotoxicity and apoptosis induced by inorganic fluoride. ISRN Cell Biology, 2012, 1–16.

    Google Scholar 

  • Ahn, J. S. (2012). Geochemical occurrences of arsenic and fluoride in bedrock groundwater: A case study in Geumsan County, Korea. Environmental Geochemistry and Health, 34(Suppl 1), 43–54.

    CAS  Google Scholar 

  • Alarcon-Herrera, M. T., Bundschuh, J., Nath, B., Nicolli, H. B., Gutierrez, M., Reyes-Gomez, V. M., et al. (2013). Co-occurrence of arsenic and fluoride in groundwater of semi-arid regions in Latin America: Genesis, mobility and remediation. Journal of Hazardous Materials, 262, 960–969.

    CAS  Google Scholar 

  • Aravinna, P., Priyantha, N., Pitawala, A., & Yatigammana, S. K. (2017). Use pattern of pesticides and their predicted mobility into shallow groundwater and surface water bodies of paddy lands in Mahaweli river basin in Sri Lanka. Journal of Environmental Science and Health. Part B: Pesticides, Food Contaminants, and Agricultural Wastes, 52(1), 37–47.

    CAS  Google Scholar 

  • Athapattu, B. C. L., Thalgaspitiya, T., Yasaratne, U. L. S., & Vithanage, M. (2017). Biochar-based constructed wetlands to treat reverse osmosis rejected concentrates in chronic kidney disease endemic areas in Sri Lanka. Environmental Geochemistry and Health, 39(6), 1397–1407.

    CAS  Google Scholar 

  • Bandara, J. M., Senevirathna, D. M., Dasanayake, D. M., Herath, V., Bandara, J. M., Abeysekara, T., et al. (2008). 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). Environmental Geochemistry and Health, 30(5), 465–478.

    CAS  Google Scholar 

  • Barbier, O., Arreola-Mendoza, L., & Del Razo, L. M. (2010). Molecular mechanisms of fluoride toxicity. Chemico-Biological Interactions, 188(2), 319–333.

    CAS  Google Scholar 

  • Barnett, L. M. A., & Cummings, B. S. (2018). Nephrotoxicity and renal pathophysiology: A contemporary perspective. Toxicological Sciences, 164(2), 379–390.

    CAS  Google Scholar 

  • Battaleb-Looie, S., Moore, F., Jacks, G., & Ketabdari, M. R. (2012). Geological sources of fluoride and acceptable intake of fluoride in an endemic fluorosis area, southern Iran. Environmental Geochemistry and Health, 34(5), 641–650.

    CAS  Google Scholar 

  • Berbasova, T., Nallur, S., Sells, T., Smith, K. D., Gordon, P. B., Tausta, S. L., et al. (2017). Fluoride export (FEX) proteins from fungi, plants and animals are ‘single barreled’ channels containing one functional and one vestigial ion pore. PLoS ONE, 12(5), e0177096.

    Google Scholar 

  • Boyde, C. D., & Cerklewski, F. L. (1987). Influence of type and level of dietary protein on fluoride bioavailability in the rat. Journal of Nutrition, 117(12), 2086–2090.

    CAS  Google Scholar 

  • Brindha, K., & Elango, L. (2011). Fluoride in groundwater: Causes, implications and mitigation measures. In: S. D. E. Monroy (Ed.), Fluoride properties, applications and environmental management (pp. 111–136). Nova publishers. https://www.novapublishers.com/catalog/product_info.php?products_id=15895.

  • Brouwer, I. D., Dirks, O. B., De Bruin, A., & Hautvast, J. G. (1988). Unsuitability of World Health Organisation guidelines for fluoride concentrations in drinking water in Senegal. Lancet, 1(8579), 223–225.

    CAS  Google Scholar 

  • Cao, J., Zhao, Y., & Liu, J. (1997). Brick tea consumption as the cause of dental fluorosis among children from Mongol, Kazak and Yugu populations in China. Food and Chemical Toxicology, 35(8), 827–833.

    CAS  Google Scholar 

  • Caverzasio, J., Palmer, G., & Bonjour, J. P. (1998). Fluoride: mode of action. Bone, 22(6), 585–589.

    CAS  Google Scholar 

  • Chan, L. M. A., Saikat, S., & Lynch, P. (2013). Human exposure of fluoride from tea (Camellia sinensis L.): A UK based issue. Food Research International, 1–2, 564–570.

    Google Scholar 

  • Chandrajith, R., Dissanayake, C. B., Ariyarathna, T., Herath, H. M., & Padmasiri, J. P. (2011a). Dose-dependent Na and Ca in fluoride-rich drinking water—another major cause of chronic renal failure in tropical arid regions. Science of the Total Environment, 409(4), 671–675.

    CAS  Google Scholar 

  • Chandrajith, R., Dissanayake, C. B., & Tobschall, H. J. (2005). The abundances of rarer trace elements in paddy (rice) soils of Sri Lanka. Chemosphere, 58(10), 1415–1420.

    CAS  Google Scholar 

  • Chandrajith, R., Nanayakkara, S., Itai, K., Aturaliya, T. N., Dissanayake, C. B., Abeysekera, T., et al. (2011b). Chronic kidney diseases of uncertain etiology (CKDue) in Sri Lanka: Geographic distribution and environmental implications. Environmental Geochemistry and Health, 33(3), 267–278.

    CAS  Google Scholar 

  • Chattopadhyay, A., Podder, S., Agarwal, S., & Bhattacharya, S. (2011). Fluoride-induced histopathology and synthesis of stress protein in liver and kidney of mice. Archives of Toxicology, 85(4), 327–335.

    CAS  Google Scholar 

  • Chiang, C. K., Tanaka, T., & Nangaku, M. (2012). Dysregulated oxygen metabolism of the kidney by uremic toxins: Review. Journal of Renal Nutrition, 22(1), 77–80.

    CAS  Google Scholar 

  • Dharmagunawardhane, H. A. D. (1993). CB Fluoride problems in Sri Lanka. Environmental Management and Health, 4(2), 9–16.

    Google Scholar 

  • Dharmaratne, R. W. (2015). Fluoride in drinking water and diet: The causative factor of chronic kidney diseases in the North Central Province of Sri Lanka. Environmental Health and Preventive Medicine, 20(4), 237–242.

    CAS  Google Scholar 

  • Diouf, A., Sy, F. O., Niane, B., Ba, D., & Ciss, M. (1994). Dietary intake of fluorine through of tea prepared by the traditional method in Senegal. Dakar Medical, 39(2), 227–230.

    CAS  Google Scholar 

  • Dissanayake, C. B. (1996). Water quality and dental health in the Dry Zone of Sri Lanka. Geological Society, London, Special Publications, 113(1), 131–140.

    CAS  Google Scholar 

  • Dissanayake, C. B. (2005a). Global voices of science. Of stones and health: Medical geology in Sri Lanka. Science, 309(5736), 883–885.

    CAS  Google Scholar 

  • Dissanayake, C. (2005b). Water quality in the dry Zone of Sri Lanka—Some interesting health aspects. Journal of the National Science Foundation of Sri Lanka, 33(3), 161–168.

    Google Scholar 

  • Dissanayake, C. B., & Chandrajith, R. (2007). Medical geology in tropical countries with special reference to Sri Lanka. Environmental Geochemistry and Health, 29(2), 155–162.

    CAS  Google Scholar 

  • Dissanayake, C. B., & Chandrajith, R. (2019). Fluoride and hardness in groundwater of tropical regions—Review of recent evidence indicating tissue calcification and calcium phosphate nanoparticle formation in kidney tubules. Ceylon Journal of Science, 48(3), 197–207.

    Google Scholar 

  • Diyabalanage, S., Abekoon, S., Watanabe, I., Watai, C., Ono, Y., Wijesekara, S., et al. (2016a). Has irrigated water from Mahaweli River contributed to the kidney disease of uncertain etiology in the dry zone of Sri Lanka? Environmental Geochemistry and Health, 38(3), 679–690.

    CAS  Google Scholar 

  • Diyabalanage, S., Navarathna, T., Abeysundara, H. T., Rajapakse, S., & Chandrajith, R. (2016b). Trace elements in native and improved paddy rice from different climatic regions of Sri Lanka: Implications for public health. Springerplus, 5(1), 1864.

    Google Scholar 

  • Dreher, R., Buttgereit, F., Demary, W., Gortz, B., Hein, G., Kern, P., et al. (2006). Insufficiency fractures in rheumatology. Case report and overview. Zeitschrift für Rheumatologie, 65(5), 417–423.

    CAS  Google Scholar 

  • Dunuweera, R., Shimomura, R. M., Priyankarage, M., Jayasingha, P., & Wimalawansa, S. J. (2017). Chronic kidney disease of multifunctional origin (CKDmfo) prevailing in Sri Lanka: Re-evaluated. World Journal of Pharmaceutical Research, 6(16), 33–66.

    CAS  Google Scholar 

  • Edirisinghe, E., Manthrithilake, H., Pitawala, H., Dharmagunawardhane, H. A., & Wijayawardane, R. L. (2018). Geochemical and isotopic evidences from groundwater and surface water for understanding of natural contamination in chronic kidney disease of unknown etiology (CKDu) endemic zones in Sri Lanka. Isotopes in Environmental and Health Studies, 54(3), 244–261.

    CAS  Google Scholar 

  • Fawell, J., Bailey, K., Chilton, J., Dahi, E., Fewtrell, L. et al. (2006). https://apps.who.int/iris/handle/10665/43514. Geneva: World Health Organization. Accessed 6 Sept 2019.

  • Faye, M., Lemrabott, A. T., Cisse, M. M., Fall, K., Keita, Y., Ngaide, A. A., et al. (2017). Prevalence and risk factors of chronic kidney disease in an african semi-urban area: Results from a cross-sectional survey in Gueoul, Senegal. Saudi Journal of Kidney Diseases and Transplantation, 28(6), 1389–1396.

    Google Scholar 

  • Forbes, W. F., Hayward, L. M., & Agwani, N. (1991). Dementia, aluminium, and fluoride. Lancet, 338(8782–8783), 1592–1593.

    CAS  Google Scholar 

  • Futrakul, N., & Futrakul, P. (2012). Urgent call for reconsideration of chronic kidney disease. World Journal of Nephrology, 1(6), 155–159.

    Google Scholar 

  • Garcon, G., Leleu, B., Marez, T., Zerimech, F., Haguenoer, J. M., Furon, D., et al. (2007). Biomonitoring of the adverse effects induced by the chronic exposure to lead and cadmium on kidney function: Usefulness of alpha-glutathione S-transferase. Science of the Total Environment, 377(2–3), 165–172.

    CAS  Google Scholar 

  • Gbadebo, A. M. (2012). Groundwater fluoride and dental fluorosis in southwestern Nigeria. Environmental Geochemistry and Health, 34(5), 597–604.

    CAS  Google Scholar 

  • Glaser, J., Weiss, I., & La Isla, F. (2014). CKDu: Strategies for saving lives now. MEDICC Review, 16(2), 81–82.

    Google Scholar 

  • Grollman, A. P., & Jelakovic, B. (2007). Role of environmental toxins in endemic (Balkan) nephropathy. Journal of the American Society of Nephrology, 18(11), 2817–2823.

    CAS  Google Scholar 

  • Gupta, S. K., Gupta, R. C., Seth, A. K., & Gupta, A. (1996). Reversal of fluorosis in children. Acta Paediatrica Japonica, 38(5), 513–519.

    CAS  Google Scholar 

  • Horowitz, H. S. (1999). Proper use of fluoride products in fluoridated communities. Lancet, 353(9163), 1462.

    CAS  Google Scholar 

  • Idini, A., Dore, E., Fancello, D., & Frau, F. (2019). Defluoridation of water through the transformation of octacalcium phosphate into fluorapatite. Heliyon, 5(8), e02288.

    Google Scholar 

  • Ileperuma, O. A., Dharmagunawardhane, H. A., & Herath, K. P. (2009). Dissolution of aluminium from sub-standard utensils under high fluoride stress: A possible risk factor for chronic renal failure in the North-Central Province. Journal of the National Science Foundation of Sri Lanka, 37(3), 219–222.

    CAS  Google Scholar 

  • Inam, M. A., Khan, R., Akram, M., Khan, S., Park, D. R., & Yeom, I. T. (2019). Interaction of arsenic species with organic ligands: Competitive removal from water by coagulation-flocculation-sedimentation (C/F/S). Molecules, 24(8), 1619.

    CAS  Google Scholar 

  • Jayasekara, J. M., Dissanayake, D. M., Adhikari, S. B., & Bandara, P. (2013). Geographical distribution of chronic kidney disease of unknown origin in North Central Region of Sri Lanka. Ceylon Medical Journal, 58(1), 6–10.

    CAS  Google Scholar 

  • Jayasekera, J., Dissnayake, D. M., Ratnayake, P., Wikramasinghe, W., Radella, Y. A., & Palugaswewa, W. B. (2012). Accessed at Sri Lanka Medical Association Annual Scientific Sessions, Colombo, Sri Lanka. http://issuu.com/slmanews/docs/ckdu_abstract_book.

  • Jayatilake, N., Mendis, S., Maheepala, P., & Mehta, F. R. (2013). Chronic kidney disease of uncertain aetiology: Prevalence and causative factors in a developing country. BMC Nephrology, 14(1), 180.

    Google Scholar 

  • Jha, S. K., Mishra, V. K., Sharma, D. K., & Damodaran, T. (2011). Fluoride in the environment and its metabolism in humans. Reviews of Environmental Contamination and Toxicology, 211, 121–142.

    CAS  Google Scholar 

  • Jia, H., Qian, H., Qu, W., Zheng, L., Feng, W., & Ren, W. (2019). Fluoride occurrence and human health risk in drinking water wells from southern edge of chinese loess plateau. International Journal of Environmental Research and Public Health, 16(10), 1683.

    CAS  Google Scholar 

  • Jia, Y., Xi, B., Jiang, Y., Guo, H., Yang, Y., Lian, X., et al. (2018). Distribution, formation and human-induced evolution of geogenic contaminated groundwater in China: A review. Science of the Total Environment, 643, 967–993.

    CAS  Google Scholar 

  • Khandare, A. L. R. G. (2006). Uptake of fluoride, aluminum and molybdenum by some vegetables from irrigation water. Journal of Human Ecology, 19(4), 283–288.

    Google Scholar 

  • Lasantha, P. A. P., Gonawala, J. M. L., & Wijekoon, D. (2008). Groundwater quality in Anuradhapura district with special reference to fluoride. Groundwater in Sri Lanka-most precious but highly threatened resource. Colombo, Sri Lanka: National Academy of Sciences of Sri Lanka (pp 48–64).

  • Levine, K. E., Redmon, J. H., Elledge, M. F., Wanigasuriya, K. P., Smith, K., Munoz, B., et al. (2015). Quest to identify geochemical risk factors associated with chronic kidney disease of unknown etiology (CKDu) in an endemic region of Sri Lanka—A multimedia laboratory analysis of biological, food, and environmental samples. Environmental Monitoring and Assessment, 188(10), 548.

    Google Scholar 

  • Li, L. (2003). The biochemistry and physiology of metallic fluoride: Action, mechanism, and implications. Critical Reviews in Oral Biology and Medicine, 14(2), 100–114.

    Google Scholar 

  • Li, S., Smith, K. D., Davis, J. H., Gordon, P. B., Breaker, R. R., & Strobel, S. A. (2013). Eukaryotic resistance to fluoride toxicity mediated by a widespread family of fluoride export proteins. Proceedings of the National Academy of Sciences of the United States of America, 110(47), 19018–19023.

    CAS  Google Scholar 

  • Lung, S. C., Cheng, H. W., & Fu, C. B. (2008). Potential exposure and risk of fluoride intakes from tea drinks produced in Taiwan. Journal of Exposure Science and Environmental Epidemiology, 18(2), 158–166.

    CAS  Google Scholar 

  • Luo, Q., Cui, H., Deng, H., Kuang, P., Liu, H., Lu, Y., et al. (2017). Sodium fluoride induces renal inflammatory responses by activating NF-κB signaling pathway and reducing anti-inflammatory cytokine expression in mice. Oncotarget, 8(46), 80192–80207.

    Google Scholar 

  • Malde, M. K., Greiner-Simonsen, R., Julshamn, K., & Bjorvatn, K. (2006). Tealeaves may release or absorb fluoride, depending on the fluoride content of water. Science of the Total Environment, 366(2–3), 915–917.

    Google Scholar 

  • Marumo, F. L., & Li, J. P. (1996). Renal disease and trace elements. Nihon Rinsho, 54(1), 93–98.

    CAS  Google Scholar 

  • Mebratu, Y., & Tesfaigzi, Y. (2009). How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? Cell Cycle, 8(8), 1168–1175.

    CAS  Google Scholar 

  • Mohamed, N. E. (2016). The role of calcium in ameliorating the oxidative stress of fluoride in rats. Biological Trace Element Research, 170(1), 128–144.

    CAS  Google Scholar 

  • Mondal, D., Dutta, G., & Gupta, S. (2016). Inferring the fluoride hydrogeochemistry and effect of consuming fluoride-contaminated drinking water on human health in some endemic areas of Birbhum district, West Bengal. Environmental Geochemistry and Health, 38(2), 557–576.

    CAS  Google Scholar 

  • Mondal, D., Gupta, S., Reddy, D. V., & Dutta, G. (2017). Fluoride enrichment in an alluvial aquifer with its subsequent effect on human health in Birbhum district, West Bengal, India. Chemosphere, 168, 817–824.

    CAS  Google Scholar 

  • Mukherjee, I., & Singh, U. K. (2018). Groundwater fluoride contamination, probable release, and containment mechanisms: A review on Indian context. Environmental Geochemistry and Health, 40(6), 2259–2301.

    CAS  Google Scholar 

  • Mukherjee, I., Singh, U. K., & Patra, P. K. (2019). Exploring a multi-exposure-pathway approach to assess human health risk associated with groundwater fluoride exposure in the semi-arid region of east India. Chemosphere, 233, 164–173.

    CAS  Google Scholar 

  • Nanayakkara, S., Komiya, T., Ratnatunga, N., Senevirathna, S. T., Harada, K. H., Hitomi, T., et al. (2012a). Tubulointerstitial damage as the major pathological lesion in endemic chronic kidney disease among farmers in North Central Province of Sri Lanka. Environmental Health and Preventive Medicine, 17(3), 213–221.

    Google Scholar 

  • Nanayakkara, S., Senevirathna, S., Harada, K. H., Chandrajith, R., Hitomi, T., Abeysekera, T., et al. (2019). Systematic evaluation of exposure to trace elements and minerals in patients with chronic kidney disease of uncertain etiology (CKDu) in Sri Lanka. Journal of Trace Elements in Medicine and Biology, 54, 206–213.

    CAS  Google Scholar 

  • Nanayakkara, S., Senevirathna, S. T., Abeysekera, T., Chandrajith, R., Ratnatunga, N., Gunarathne, E. D., et al. (2014). An integrative study of the genetic, social and environmental determinants of chronic kidney disease characterized by tubulointerstitial damages in the North Central Region of Sri Lanka. Journal of Occupational Health, 56(1), 28–38.

    CAS  Google Scholar 

  • Nanayakkara, S., Senevirathna, S. T., Karunaratne, U., Chandrajith, R., Harada, K. H., Hitomi, T., et al. (2012b). Evidence of tubular damage in the very early stage of chronic kidney disease of uncertain etiology in the North Central Province of Sri Lanka: A cross-sectional study. Environmental Health and Preventive Medicine, 17(2), 109–117.

    Google Scholar 

  • Nixon, J. M., & Carpenter, R. G. (1974). Mortality in areas containing natural fluoride in their water supplies, taking account of socioenvironmental factors and water hardness. Lancet, 2(7888), 1068–1071.

    CAS  Google Scholar 

  • O’Mullane, D. M., Baez, R. J., Jones, S., Lennon, M. A., Petersen, P. E., Rugg-Gunn, A. J., et al. (2016). Fluoride and oral health. Community Dental Health, 33(2), 69–99.

    Google Scholar 

  • Onyango, M. S., Kojima, Y., Aoyi, O., Bernardo, E. C., & Matsuda, H. (2004). Adsorption equilibrium modeling and solution chemistry dependence of fluoride removal from water by trivalent-cation-exchanged zeolite F-9. Journal of Colloid and Interface Science, 279(2), 341–350.

    CAS  Google Scholar 

  • Pal, K. C. M. N., Bhaumik, R., Banerjee, A., & Datta, J. K. (2012). Incorporation of fluoride in vegetation and associated biochemical changes due to fluoride contamination in water and soil: A comparative field. Annals of Environmental Science, 6, 23–39.

    Google Scholar 

  • Pehrsson, P. R. P. K., & Perry, C. R. (2011). The fluoride content of select brewed and microwave-brewed black teas in the United States. Journal of Food Composition and Analysis, 24(7), 971–979.

    CAS  Google Scholar 

  • Phuc, H. D., Kido, T., Oanh, N. T. P., Manh, H. D., Anh, L. T., Oyama, Y., et al. (2017). Effects of aging on cadmium concentrations and renal dysfunction in inhabitants in cadmium-polluted regions in Japan. Journal of Applied Toxicology, 37(9), 1046–1052.

    CAS  Google Scholar 

  • Rahim, Z. H., Bakri, M. M., Zakir, H. M., Ahmed, I. A., & Zulkifli, N. A. (2014). High fluoride and low pH level have been detected in popular flavoured beverages in Malaysia. Pakistan Journal of Medical Sciences, 30(2), 404–408.

    Google Scholar 

  • Rango, T., Jeuland, M., Manthrithilake, H., & McCornick, P. (2015). Nephrotoxic contaminants in drinking water and urine, and chronic kidney disease in rural Sri Lanka. Science of the Total Environment, 518–519, 574–585.

    Google Scholar 

  • Reddy, D. V., Nagabhushanam, P., Sukhija, B. S., Reddy, A. G. S., & Smedley, P. L. (2010). Fluoride dynamics in the granitic aquifer of the Wailapally watershed, Nalgonda District India. Chemical Geology, 269, 278–289.

    CAS  Google Scholar 

  • Ribeiro, D. A., Cardoso, C. M., Yujra, V. Q., Viana, M. D. B., Aguiar, O., Jr., Pisani, L. P., et al. (2017). Fluoride induces apoptosis in mammalian cells: In vitro and in vivo studies. Anticancer Research, 37(9), 4767–4777.

    CAS  Google Scholar 

  • Roncal Jimenez, C. A., Ishimoto, T., Lanaspa, M. A., Rivard, C. J., Nakagawa, T., Ejaz, A. A., et al. (2014). Fructokinase activity mediates dehydration-induced renal injury. Kidney International, 86(2), 294–302.

    CAS  Google Scholar 

  • Ryu, S., Chang, Y., Woo, H. Y., Lee, K. B., Kim, S. G., Kim, D. I., et al. (2009). Time-dependent association between metabolic syndrome and risk of CKD in Korean men without hypertension or diabetes. American Journal of Kidney Diseases, 53(1), 59–69.

    CAS  Google Scholar 

  • Saxena, V., & Ahmed, S. (2003). Inferring the chemical parameters for the dissolution of fluoride in groundwater.Environmental Geology, 43(6), 731–736.

    CAS  Google Scholar 

  • Senevirathna, L., Abeysekera, T., Nanayakkara, S., Chandrajith, R., Ratnatunga, N., Harada, K. H., et al. (2012). Risk factors associated with disease progression and mortality in chronic kidney disease of uncertain etiology: A cohort study in Medawachchiya, Sri Lanka. Environmental Health and Preventive Medicine, 17(3), 191–198.

    Google Scholar 

  • Sharma, R., Tsuchiya, M., Skobe, Z., Tannous, B. A., & Bartlett, J. D. (2010). The acid test of fluoride: How pH modulates toxicity. PLoS ONE, 5(5), e10895.

    Google Scholar 

  • Silva, F. G. (2004). Chemical-induced nephropathy: A review of the renal tubulointerstitial lesions in humans. Toxicologic Pathology, 32(Suppl 2), 71–84.

    CAS  Google Scholar 

  • Smedley, P. L., Nicolli, H. B., Macdonald, D. M. J., Barros, A. J., & Tullio, J. O. (2002). Hydrogeochemistry of arsenic and other inorganic constituents in groundwaters from La Pampa, Argentina. Applied Geochemistry, 17, 259–284.

    CAS  Google Scholar 

  • Smith, G. E. (1986). Fluoride, the environment, and human health. Perspectives in Biology and Medicine, 29(4), 560–572.

    CAS  Google Scholar 

  • Song, C., Fu, B., Zhang, J., Zhao, J., Yuan, M., Peng, W., et al. (2017). Sodium fluoride induces nephrotoxicity via oxidative stress-regulated mitochondrial SIRT3 signaling pathway. Scientific Reports, 7(1), 672.

    Google Scholar 

  • Song, G. H., Gao, J. P., Wang, C. F., Chen, C. Y., Yan, X. Y., Guo, M., et al. (2014). Sodium fluoride induces apoptosis in the kidney of rats through caspase-mediated pathways and DNA damage. Journal of Physiology and Biochemistry, 70(3), 857–868.

    CAS  Google Scholar 

  • Stauffer, R. E. (1980). Molybdenum blue applied to arsenic and phosphorus determinations in fluoride- and silica-rich geothermal waters. Environmental Science and Technology, 14(12), 1475–1481.

    CAS  Google Scholar 

  • Steiner, M., Helfenstein, U., & Menghini, G. (2004). Effect of 1000 ppm relative to 250 ppm fluoride toothpaste. A meta-analysis. American Journal of Dentistry, 17(2), 85–88.

    Google Scholar 

  • Susheela, A. K., & Bhatnagar, M. (2002). Reversal of fluoride induced cell injury through elimination of fluoride and consumption of diet rich in essential nutrients and anti. Molecular and Cellular Biochemistry, 234, 335–340.

    Google Scholar 

  • Ulinski, T., Sellier-Leclerc, A. L., Tudorache, E., Bensman, A., & Aoun, B. (2012). Acute tubulointerstitial nephritis. Pediatric Nephrology (Berlin, Germany), 27(7), 1051–1057.

    Google Scholar 

  • UNICEF. (2014). Accessed at WHO. http://apps.who.int/iris/bitstream/10665/112727/1/9789241507240_eng.pdf.

  • Vazquez Mejia, G., Martinez-Miranda, V., Fall, C., Linares-Hernandez, I., & Solache-Rios, M. (2016). Comparison of Fe–Al-modified natural materials by an electrochemical method and chemical precipitation for the adsorption of F- and As(V). Environmental Technology, 37(5), 558–568.

    CAS  Google Scholar 

  • Vesey, D. A. (2010). Transport pathways for cadmium in the intestine and kidney proximal tubule: Focus on the interaction with essential metals. Toxicology Letters, 198(1), 13–19.

    CAS  Google Scholar 

  • Wanigasuriya, K. (2014). Update on uncertain etiology of chronic kidney disease in Sri Lanka’s north-central dry zone. MEDICC Review, 16(2), 61–65.

    Google Scholar 

  • Wasana, H. M., Aluthpatabendi, D., Kularatne, W. M., Wijekoon, P., Weerasooriya, R., & Bandara, J. (2016). Drinking water quality and chronic kidney disease of unknown etiology (CKDu): Synergic effects of fluoride, cadmium and hardness of water. Environmental Geochemistry and Health, 38(1), 157–168.

    CAS  Google Scholar 

  • Wasana, H. M., Perera, G. D., De Gunawardena, P. S., & Bandara, J. (2015). The impact of aluminum, fluoride, and aluminum–fluoride complexes in drinking water on chronic kidney disease. Environmental Science and Pollution Research International, 22(14), 11001–11009.

    CAS  Google Scholar 

  • Wasana, H. M., Perera, G. D., Gunawardena, P. S., Fernando, P. S., & Bandara, J. (2017). WHO water quality standards Vs Synergic effect(s) of fluoride, heavy metals and hardness in drinking water on kidney tissues. Scientific Reports, 7, 42516.

    CAS  Google Scholar 

  • Weeraratne, S., & Wimalawansa, S. J. A. (2015). Major irrigation project (Accelerated Mahaweli Programme) and the chronic kidney disease of multifactorial origin in Sri Lanka. International Journal of Environmental and Agriculture Research, 1(6), 16–27.

    Google Scholar 

  • WHO. (2011). World Health Organization guidelines for drinking-water quality. Geneva: World Health Organization.

    Google Scholar 

  • WHO. (2016). International expert consultation on chronic kidney disease of unknown etiology (CKDu) in Sri Lanka. Colombo: WHO Country Office. ISBN 978-955-0261-15-4.

    Google Scholar 

  • WHO. (2017). Guidelines for drinking-water quality, 4th edition, incorporating the 1st addendum. https://www.who.int/water_sanitation_health/publications/drinking-water-quality-guidelines-4-including-1st-addendum/en/. Water Sanitation Hygiene, Geneva. ISBN 978-92-4-154995-0.

  • WHO. (2018). Developing drinking-water quality regulations and standards. https://www.who.int/water_sanitation_health/publications/developing-dwq-regulations/en/. Geneva: WHO. ISBN 978-92-4-151394-4.

  • Wickramarathna, S., Balasooriya, S., Diyabalanage, S., & Chandrajith, R. (2017). Tracing environmental aetiological factors of chronic kidney diseases in the dry zone of Sri Lanka—A hydrogeochemical and isotope approach. Journal of Trace Elements in Medicine and Biology, 44, 298–306.

    Google Scholar 

  • Wickremasinghe, A. R., Peiris-John, R. J., & Wanigasuriya, K. P. (2011). Chronic kidney disease of unknown aetiology in the North Central Province of Sri Lanka: Trying to unravel the mystery. Ceylon Medical Journal, 56(4), 143–146.

    CAS  Google Scholar 

  • Wimalawansa, S. J. (2013). Chronic kidney disease in Rajarata, worse than tsunami. http://www.sundayobserver.lk/2013/11/24/fea06.asp. Sunday Observer. Colombo.

  • Wimalawansa, S. J. (2013b). Purification of contaminated water with reverse osmosis: Effective solution of providing clean water for human needs in developing countries. Journal of Emerging Technology and Advanced Engineering., 3(12), 75–89.

    Google Scholar 

  • Wimalawansa, S. J. (2014). Escalating chronic kidney diseases in Sri Lanka: Causes, solutions and recommendations. Environmental Health and Preventive Medicine, 19(6), 375–394.

    Google Scholar 

  • Wimalawansa, S. J. (2015a). Escalating chronic kidney diseases in Sri Lanka: Causes, solutions and recommendations—Update and responses. Environmental Health and Preventive Medicine, 20, 152–157.

    Google Scholar 

  • Wimalawansa, S. J. (2015b). Agrochemicals and chronic kidney disease of multifactorial origin: Environmentally induced occupational exposure disease. International Journal of Nephrology and Kidney Failure, 1(2), 1–9.

    Google Scholar 

  • Wimalawansa, S. J. (2015c). The role of ions, heavy metals, fluoride, and agrochemicals: Critical evaluation of potential aetiological factors of chronic kidney disease of multifactorial origin (CKDmfo/CKDu) and recommendations for its eradication. Environmental Geochemistry and Health. https://doi.org/10.1007/s10653-015-9739-3.

    Article  Google Scholar 

  • Wimalawansa, S. J. (2016a). The role of ions, heavy metals, fluoride, and agrochemicals: Critical evaluation of potential aetiological factors of chronic kidney disease of multifactorial origin (CKDmfo/CKDu) and recommendations for its eradication. Environmental Geochemistry and Health, 38(3), 639–678.

    CAS  Google Scholar 

  • Wimalawansa, S. J. (2016b). Effect of water hardness on non-communicable diseases including chronic kidney disease of multifactorial origin (CKDmfo/CKDuo). Journal of Environmental Health Science and Engineering, 2(1), 1–11.

    Google Scholar 

  • Wimalawansa, S. J. (2017) Epidemic of chronic kidney disease of unknown origin in Sri Lanka: What really causing it? Guidance for eradication. In World Water Day symposium 2017. Organization of Professional Association, Colombo Sri Lanka.

  • Wimalawansa, S. J. (2019). Molecular and cellular toxicity of fluoride in mystery, tubulointerstitial chronic kidney disease: A systematic review. Reviews in Environmental Science and Bio/Technology. https://doi.org/10.1007/s11157-019-09521-0.

    Article  Google Scholar 

  • Wimalawansa, S. J., & Dissanayake, C. B. (2020). Factors affecting the environmentally induced, chronic kidney disease of unknown aetiology in dry zonal regions in tropical countries—Novel findings. Environments, 7(2), 1–26.

    Google Scholar 

  • Wimalawansa, S., Ileperuma, O., & Weeraratne, S. (2018). Attempts to change the globally accepted term, CKDu, to KDUCAL, NUCAL, or CINAC are inappropriate. American Journal of Kidney Diseases, 71(6), 914.

    Google Scholar 

  • Wimalawansa, S. A., & Wimalawansa, S. J. (2014). Agrochemical-related environmental pollution: Effects on human health. Global Journal of Biology, Agriculture and Health Sciences, 3(3), 72–83.

    Google Scholar 

  • Wimalawansa, S. J., & Wimalawansa, S. A. (2015a). Chronic kidney disease of multifactorial origin (CKDmfo) in Sri Lanka: Escalating incidence and long-term survival estimates. Journal of Nephrology and Urology Research, 22(4), 1–17.

    Google Scholar 

  • Wimalawansa, S. A., & Wimalawansa, S. J. (2015b). Clean water, healthy environment, and preservation of watersheds: Correct, enforceable policies are essential. Jacobs Journal of Hydrology, 1(1), 3–15.

    Google Scholar 

  • Wimalawansa, S. A., & Wimalawansa, S. J. (2016). Environmentally induced, occupational diseases with emphasis on chronic kidney disease of multifactorial origin affecting tropical countries. Annals of Occupational and Environmental Medicine, 28, 33.

    Google Scholar 

  • Wong, M. H., Fung, K. F., & Carr, H. P. (2003). Aluminium and fluoride contents of tea, with emphasis on brick tea and their health implications. Toxicology Letters, 137(1–2), 111–120.

    CAS  Google Scholar 

  • World-Health-Organization. (1983). WHO, Guidelines for drinking water quantity. Geneva: World Health Organization.

    Google Scholar 

  • Yadav, K. K., Kumar, V., Gupta, N., Kumar, S., Rezania, S., & Singh, N. (2019). Human health risk assessment: Study of a population exposed to fluoride through groundwater of Agra city, India. Regulatory Toxicology and Pharmacology, 106, 68–80.

    CAS  Google Scholar 

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    Sunil J. Wimalawansa

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Wimalawansa, S.J. Does fluoride cause the mysterious chronic kidney disease of multifactorial origin?. Environ Geochem Health 42, 3035–3057 (2020). https://doi.org/10.1007/s10653-019-00503-3

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