Skip to main content

Advertisement

SpringerLink
Log in

Serum and urine fluoride levels in populations of high environmental fluoride exposure with endemic CKDu: a case–control study from Sri Lanka

  • Original Paper
  • Published:
Environmental Geochemistry and Health Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

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.

    CAS  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.

    Article  CAS  Google 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.

    Article  Google 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.

    Article  CAS  Google 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.

    Chapter  Google 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.

    Chapter  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google 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.

    Article  CAS  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.

    Article  Google 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.

    Article  Google Scholar 

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

    Article  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    CAS  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.

    Article  Google 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.

    Article  Google 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.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google 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.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    CAS  Google Scholar 

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

    Article  CAS  Google 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.

    Article  Google 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.

    Article  CAS  Google 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.

    CAS  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.

    Article  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.

    Article  Google 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.

    Article  CAS  Google 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.

    Article  Google Scholar 

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

    Article  CAS  Google 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.

    Article  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google 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.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the National Research Council (NRC) Target Orient research grant (TO 14-05).

Author information

Authors and Affiliations

  1. Centre for Education, Research and Training on Kidney Diseases (CERTKiD), Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka

    W. B. N. T. Fernando

  2. Transplant and Dialysis Unit, Teaching Hospital, Kandy, Sri Lanka

    Nishantha Nanayakkara

  3. Base Hospital, Girandurukotte, Sri Lanka

    Lishanthe Gunarathne

  4. Department of Geology, Faculty of Science, University of Peradeniya, Peradeniya, Sri Lanka

    Rohana Chandrajith

Authors
  1. W. B. N. T. Fernando
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nishantha Nanayakkara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lishanthe Gunarathne
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rohana Chandrajith
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rohana Chandrajith.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical statements

The study was carried out with the approval of the Ethical Review Board of the Faculty of Medicine, University of Peradeniya, Sri Lanka. Written consents were obtained from all subjects before collecting samples.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fernando, W.B.N.T., Nanayakkara, N., Gunarathne, L. et al. Serum and urine fluoride levels in populations of high environmental fluoride exposure with endemic CKDu: a case–control study from Sri Lanka. Environ Geochem Health 42, 1497–1504 (2020). https://doi.org/10.1007/s10653-019-00444-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10653-019-00444-x

Keywords

Search

Navigation