Fluoride Action Network

Abstract

Chronic kidney disease of uncertain etiology (CKDu) is a common health issue among farming communities in the dry zone of Sri Lanka where groundwater fluoride is known to be higher than recommended levels. Excessive environmental ingestion of fluoride is widely considered as a possible factor for the onset of CKDu. This study was carried out to evaluate the serum and urine fluoride levels in biopsy-proven, non-dialysis CKDu patients. Control subjects were selected from the same area without any deteriorated kidney functions. Serum and urine fluoride levels were determined by ion-selective electrode method. Higher content of serum and urine fluoride levels were observed in patients with chronic renal failures. In CKDu cases, the serum fluoride concentrations ranged between 0.47 and 9.58 mg/L (mean 1.39 ± 1.1 mg/L), while urine levels were varied between 0.45 and 6.92 mg/L (mean 1.53 ± 0.8 mg/L). In patients, urine fluoride levels showed a significant difference with the CKDu stage; however, no difference was obtained between genders and age. In endemic controls, serum and urine fluoride levels ranged between 0.51 and 1.92 mg/L (mean = 1.07 ± 0.3 mg/L) and 0.36 and 3.80 mg/L (mean = 1.26 ± 0.6 mg/L), respectively. Significantly higher fluoride in serum and urine was noted in CKDu patients compared to endemic control groups. Higher fluoride exposure via drinking water is possibly the reason for higher fluoride in serum, while excessive urinary excretion would be due to deterioration of the kidney, suggesting a possible nephrotoxic role of environmental fluoride exposure.

*Original abstract online at https://link.springer.com/article/10.1007%2Fs10653-019-00444-x

References

Abdennebi, E. H., Fandi, R., & Lamnaouer, D. (1995). Human fluorosis in Morocco: Analytical and clinical investigations. Veterinary and Human Toxicology, 37(5), 465–468.Google Scholar

Al-Wakeel, J. S., Mitwalli, A. H., Huraib, S., Al-Mohaya, S., Abu-Aisha, H., Chaudhary, A. R., et al. (1997). Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients. Nephrology, Dialysis, Transplantation, 12(7), 1420–1424.CrossRefGoogle Scholar

Anand, S., Montez-Rath, M. E., Adasooriya, D., Ratnatunga, N., Kambham, N., Wazil, A., et al. (2019). prospective biopsy-based study of CKD of unknown etiology in Sri Lanka. Clinical Journal of the American Society of Nephrology, 14(2), 224–232.CrossRefGoogle Scholar

Bandara, J. M. R. S., Senevirathna, D. M. A. N., Dasanayake, D. M. R. S. B., Herath, V., Bandara, J. M. R. P., 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.CrossRefGoogle Scholar

Buzalaf, M. A. R., & Levy, S. M. (2011). Fluoride intake of children: Considerations for dental caries and dental fluorosis. In M. A. R. Buzalaf (Ed.), Fluoride and the oral environment (pp. 1–19). Basel: Karger AG Publishers.CrossRefGoogle Scholar

Buzalaf, M. A. R., & Whitford, G. M. (2011). Fluoride metabolism. In M. A. R. Buzalaf (Ed.), Fluoride and the oral environment (pp. 20–36). Basel: Karger AG Publishers.CrossRefGoogle Scholar

Cerdas, M. (2005). Chronic kidney disease in Costa Rica. Kidney International, 68, S31–S33.CrossRefGoogle Scholar

Cerklewski, F. L. (1997). Fluoride bioavailability—Nutritional and clinical aspects. Nutrition Research, 17(5), 907–929.CrossRefGoogle Scholar

Chandrajith, R., Abeypala, U., Dissanayake, C. B., & Tobschall, H. J. (2007). Fluoride in Ceylon tea and its implications to dental health. Environmental Geochemistry and Health, 29(5), 429–434.CrossRefGoogle Scholar

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

Chandrajith, R., Padmasiri, J. P., Dissanayake, C. B., & Prematilaka, K. M. (2012). Spatial distribution of fluoride in groundwater of Sri Lanka. Journal of the National Science Foundation of Sri Lanka, 40(4), 303–309.CrossRefGoogle Scholar

Cowell, D. C., & Taylor, W. H. (1981). Ionic fluoride: A study of its physiological variation in man. Annals of Clinical Biochemistry, 18(2), 76–83.CrossRefGoogle Scholar

Dharma-wardana, M. W. C., Amarasiri, S. L., Dharmawardene, N., & Panabokke, C. R. (2015). Chronic kidney disease of unknown aetiology and ground-water ionicity: Study based on Sri Lanka. Environmental Geochemistry and Health, 37(2), 221–231.CrossRefGoogle Scholar

Dissanayake, C. B., & Chandrajith, R. (1999). Medical geochemistry of tropical environments. Earth Science Reviews, 47(3), 219–258.CrossRefGoogle Scholar

El Minshawy, O. (2011). End-stage renal disease in the El-Minia Governorate, upper Egypt: An epidemiological study. Saudi Journal of Kidney Diseases and Transplantation, 22(5), 1048–1054.Google Scholar

Husdan, H., Vogl, R., Oreopoulos, D., Gryfe, C., & Rapoport, A. (1976). Serum ionic fluoride: Normal range and relationship to age and sex. Clinical Chemistry, 22(11), 1884–1888.Google Scholar

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.CrossRefGoogle Scholar

Jha, V., Garcia-Garcia, G., Iseki, K., Li, Z., Naicker, S., Plattner, B., et al. (2013). Chronic kidney disease: Global dimension and perspectives. The Lancet, 382(9888), 260–272.CrossRefGoogle Scholar

Kanduti, D., Sterbenk, P., & Artnik, B. (2016). Fluoride: A review of use and effects on health. Materia Socio-Medica, 28(2), 133–137.CrossRefGoogle Scholar

Kumar, S., Lata, S., Yadav, J., & Yadav, J. P. (2017). Relationship between water, urine and serum fluoride and fluorosis in school children of Jhajjar District, Haryana, India. Applied Water Science, 7(6), 3377–3384.CrossRefGoogle Scholar

Levine, K. E., Redmon, J. H., Elledge, M. F., Wanigasuriya, K. P., Smith, K., Munoz, B., et al. (2016). 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, 548.CrossRefGoogle Scholar

Liu, J.-L., Xia, T., Yu, Y.-Y., Sun, X.-Z., Zhu, Q., He, W., et al. (2005). The dose-effect relationship of water fluoride levels and renal damage in children. Journal of Hygiene Research, 34(3), 287–288.Google Scholar

Luke, J. (2001). Fluoride deposition in the aged human pineal gland. Caries Research, 35(2), 125–128.CrossRefGoogle Scholar

Nanayakkara, S., Senevirathna, S. T. M. L. D., Abeysekera, T., Chandrajith, R., Ratnatunga, N., Gunarathne, E. D. L., 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, 28–38.CrossRefGoogle Scholar

O’Neill, E., Awale, G., Daneshmandi, L., Umerah, O., & Lo, K. W.-H. (2018). The roles of ions on bone regeneration. Drug Discovery Today, 23(4), 879–890.CrossRefGoogle Scholar

Parkins, F. M., Tinanoff, N., Moutinho, M., Anstey, M. B., & Waziri, M. H. (1974). Relationships of human plasma fluoride and bone fluoride to age. Calcified Tissue Research, 16(1), 335–338.CrossRefGoogle Scholar

Rafique, T., Ahmed, I., Soomro, F., Khan, M. H., & Shirin, K. (2015). Fluoride levels in urine, blood plasma and serum of people living in an endemic fluorosis area in the Thar desert, Pakistan. Journal of the Chemical Society of Pakistan, 37(6), 1212–1219.Google Scholar

Rajapurkar, M. M., John, G. T., Kirpalani, A. L., Abraham, G., Agarwal, S. K., Almeida, A. F., et al. (2012). What do we know about chronic kidney disease in India: First report of the Indian CKD registry. BMC Nephrology, 13(1), 10.CrossRefGoogle Scholar

Ranasinghe, N., Kruger, E., Chandrajith, R., & Tennant, M. (2019). The heterogeneous nature of water well fluoride levels in Sri Lanka: An opportunity to mitigate the dental fluorosis. Community Dentistry and Oral Epidemiology, 47, 236–242.CrossRefGoogle Scholar

Reddy, D. V., & Gunasekar, A. (2013). Chronic kidney disease in two coastal districts of Andhra Pradesh, India: Role of drinking water. Environmental Geochemistry and Health, 35(4), 439–454.CrossRefGoogle Scholar

Schiffl, H. H., & Binswanger, U. (1980). Human urinary fluoride excretion as influenced by renal functional impairment. Nephron, 26(2), 69–72.CrossRefGoogle Scholar

Shimonovitz, S., Patz, D., Ever-Hadani, P., Singer, L., Zacut, D., Kidroni, G., et al. (1995). Umbilical cord fluoride serum levels may not reflect fetal fluoride status. Journal of Perinatal Medicine, 23(4), 279–282.CrossRefGoogle Scholar

Singer, L., & Ophaug, R. (1979). Concentrations of ionic, total, and bound fluoride in plasma. Clinical Chemistry, 25(4), 523–525.Google Scholar

Spak, C.-J., Berg, U., & Ekstrand, J. (1985). Renal clearance of fluoride in children and adolescents. Pediatrics, 75(3), 575–579.Google Scholar

Torra, M., Rodamilans, M., & Corbella, J. (1998). Serum and urine ionic fluoride. Biological Trace Element Research, 63(1), 67–71.CrossRefGoogle Scholar

Torres, C., Aragón, A., González, M., Jakobsson, K., Elinder, C. G., Lundberg, I., et al. (2010). Decreased kidney function of unknown cause in Nicaragua: A community-based survey. American Journal of Kidney Diseases, 55(3), 485–496.CrossRefGoogle Scholar

Ugran, V., Desai, N. N., Chakraborti, D., Masali, K. A., Mantur, P., Kulkarni, S., et al. (2017). Groundwater fluoride contamination and its possible health implications in Indi taluk of Vijayapura District (Karnataka State), India. Environmental Geochemistry and Health, 39(5), 1017–1029.CrossRefGoogle Scholar

Usuda, K., Kono, K., Dote, T., Watanabe, M., Shimizu, H., Tanimoto, Y., et al. (2009). Fluoride analysis and fluoride related health problems in clinical, experimental, occupational and environmental aspects: A narrative review. Biomedical Research on Trace Elements, 20(4), 274–283.Google Scholar

VanDervort, D. R., López, D. L., Orantes Navarro, C. M., & Rodríguez, D. S. (2014). Spatial distribution of unspecified chronic kidney disease in El Salvador by crop area cultivated and ambient temperature. MEDICC Review, 16(2), 31–38.Google Scholar

Vlahos, P., Schensul, S. L., Nanayakkara, N., Chandrajith, R., Haider, L., Anand, S., et al. (2019). Kidney progression project (KiPP): Protocol for a longitudinal cohort study of progression in chronic kidney disease of unknown etiology in Sri Lanka. Global Public Health, 14(2), 214–226.CrossRefGoogle Scholar

Warnakulasuriya, K. A. A. S., Balasuriya, S., Perera, P. A. J., & Peiris, L. C. L. (1992). Determining optimal levels of fluoride in drinking water for hot, dry climates—A case study in Sri Lanka. Community Dentistry and Oral Epidemiology, 20(6), 364–367.CrossRefGoogle Scholar

Wesseling, C., Crowe, J., Hogstedt, C., Jakobsson, K., Lucas, R., & Wegman, D. H. (2013). The epidemic of chronic kidney disease of unknown etiology in Mesoamerica: A call for interdisciplinary research and action. American Journal of Public Health, 103(11), 1927–1930.CrossRefGoogle Scholar

Whitford, G. M. (1999). Fluoride metabolism and excretion in children. Journal of Public Health Dentistry, 59(4), 224–228.CrossRefGoogle Scholar

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.CrossRefGoogle Scholar

Xiong, X. Z., Liu, J. L., He, W. H., Xia, T., He, P., Chen, X. M., et al. (2007). Dose–effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children. Environmental Research, 103(1), 112–116.CrossRefGoogle Scholar

Zohoori, F. V., Innerd, A., Azevedo, L. B., Whitford, G. M., & Maguire, A. (2015). Effect of exercise on fluoride metabolism in adult humans: A pilot study. Nature Scientific Reports, 5, 16905.CrossRefGoogle Scholar

Zuo, H., Chen, L., Kong, M., Qiu, L., Lü, P., Wu, P., et al. (2018). Toxic effects of fluoride on organisms. Life Sciences, 198, 18–24.CrossRefGoogle Scholar