Environmental Geochemistry and Health

, Volume 38, Issue 1, pp 157–168 | Cite as

Drinking water quality and chronic kidney disease of unknown etiology (CKDu): synergic effects of fluoride, cadmium and hardness of water

  • Hewa M. S. Wasana
  • Dharshani Aluthpatabendi
  • W. M. T. D. Kularatne
  • Pushpa Wijekoon
  • Rohan Weerasooriya
  • Jayasundera Bandara
Original Paper


High prevalence of chronic kidney disease of unknown etiology (CKDu) in some regions of the world is suspected mainly due to a toxin-mediated renal failure. We examined the incidence of CKDu and potable chemical water quality in a CKDu-affected region. This region has been identified as a high-risk zone for CKDu (location: latitude: 8.3500°–9.0000°, longitude: 80.3833°–81.3000°, North Central Province, NCP, Sri Lanka) by the World Health Organization (WHO). However, within this macro-region, small pockets of CKDu non-prevalence zones do exist; notably, the residents in those pockets consume spring water. Therefore, the drinking water quality of four areas, namely high-CKDu-prevalence areas (zone I), low-CKDu-prevalence area (zone II), the CKDu-free isolated pockets (zone III) and control areas (controls) were examined for F, Al, Cd, and As, and hardness and the statistical analysis were carried out to probe possible correlations among these parameters. The fluoride and hardness concentrations of water in zone III and control areas are much lower compared to zones I and II, and the water hardness is ~61 mg/L CaCO3. In zones I and II, the harness of drinking water is ~121–180 mg/L CaCO3; however, Al, Cd and As concentrations are almost comparable and below WHO recommendations. In most of the locations in zones I and II, the F concentration in drinking water is higher than the WHO recommendations. The peculiar distribution patterns of CKDu point to a synergic effect of trace elements in water for etiology of the disease.


Chronic kidney disease Fluoride toxicity AlFx complex Metal toxicity CKDu Synergistic effect 



Support from A. Jegenathan, K. Wejerathne, D. Perera, U.W. Pradeep and P. Chandrasekera to collect samples is highly appreciated.

Supplementary material

10653_2015_9699_MOESM1_ESM.doc (7.3 mb)
Supplementary material 1 (DOC 7451 kb)


  1. Abeysekara, D. T. D. J., (2006). Clinical presentation of patients. In Proceedings of mini-symposium on chronic kidney disease of uncertain aetiology in Sri Lanka, (pp. 10–11). Erlangen: Germany.Google Scholar
  2. Adachi, K., Dote, T., Dote, E., Mitsui, G., & Kono, K. (2007). Strong acute toxicity, severe hepatic damage, renal injury and abnormal serum electrolytes after intravenous administration of cadmium fluoride in rats. Journal of Occupational Health-English Edition, 49, 235–241.CrossRefGoogle Scholar
  3. Aturaliya, T. N. C., Abeysekera, D. T. D. J., Amerasinghe, P. H., Kumarasiri, P. V. R., & Dissanayake, V. (2009). Prevalence of chronic kidney disease in two tertiary care hospitals: High proportion of cases with uncertain aetiology. Ceylon Journal of Medical Science, 54(1), 23–25.Google Scholar
  4. Bandara, J. M. R. S., Wijewardena, H. V. P., Liyanege, J., Upul, M. A., & Bandara, J. M. U. A. (2010). Chronic renal failure in Sri Lanka caused by elevated dietary cadmium: Trojan horse of the green revolution. Toxicology Letters, 198(1), 33–39.CrossRefGoogle Scholar
  5. Barbier, O., Jacquillet, G., Tauc, M., Cougnon, M., & Poujeol, P. (2005). Effect of heavy metals on, and handling by, the kidney. Nephron Physiology, 99(4), 105–110.CrossRefGoogle Scholar
  6. Cerdas, M. (2005). Chronic kidney disease in Costa Rica. Kidney International, 97, S31–S33.CrossRefGoogle Scholar
  7. Chandrajith, R., Dissanayake, C. B., Ariyarathna, T., Herath, H. M. J. M. K., & 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.CrossRefGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. Codreanu, I., Perico, N., Sharma, S. K., Schieppati, A., & Remuzzi, G. (2006). Prevention programmes of progressive renal disease in developing nations. Nephrology, 11(4), 321–328.CrossRefGoogle Scholar
  10. Dalrymple, L. S., Katz, R., Kestenbaum, B., Shlipak, M. G., Sarnak, M. J., Stehman-Breen, C., et al. (2011). Chronic kidney disease and the risk of end-stage renal disease versus death. Journal of General Internal Medicine, 26(4), 379–385.CrossRefGoogle Scholar
  11. Debelle, F. D., Vanherweghem, J. L., & Nortier, J. L. (2008). Aristolochic, acid nephropathy: A worldwide problem. Kidney International, 74(2), 158–169.CrossRefGoogle Scholar
  12. Dissanayake, C. B. (2005). Water quality in the dry zone of Sri Lanka—some interesting health aspect. Journal of the National Science Foundation of Sri Lanka, 33(3), 161–168.Google Scholar
  13. 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.CrossRefGoogle Scholar
  14. Dissanayake, D. M., Jayasekera, J. M. K. B., Ratnayake, P., Wickramasinghe, W., & Radella, Y. A. (2011). The short term effect cyanobacterial toxin extracts on mice kidney, In Proceedings of the Peradeniya University Research Sessions, Sri Lanka, Vol 16.Google Scholar
  15. Dissanayake, D. M., Jayasekera, J. M. K. B., Ratnayake, P., Wickramasinghe, W., Radella, Y. A., & Palugaswewa, W. B. (2012). Effect of concentrated water from reservoirs of high prevalence area for chronic kidney disease of unknown origin in Sri Lanka on mice. In Symposium proceedings, international symposium on water quality and human health: Challenges ahead, 22–23 March 2012, PGIS, Peradeniya, Sri Lanka proceedings. 12. Accessed at December 2012. Postgraduate Institute of Science, Sri Lanka, 2012.
  16. El Nahas, A. M., & Belle, A. K. (2005). Chronic kidney disease: The global challenge. Lancet, 365(9456), 331–340.CrossRefGoogle Scholar
  17. Ferraro, P. M., Costanzi, S., Naticchia, A., Sturniolo, A., & Gambaro, G. (2010). Low level exposure to cadmium increases the risk of chronic kidney disease: Analysis of the NHANES 1999–2006. BMC Public Health, 10, 304. doi: 10.1186/1471-2458-10-304.CrossRefGoogle Scholar
  18. Gamvroula, D., Alexakia, D., & Stamatis, G. (2013). Diagnosis of groundwater quality and assessment Megara basin (Attica. Greece). Arabian Journal of Geosciences, 6(7), 2367–2381.CrossRefGoogle Scholar
  19. Gooneratne, I. K., Ranaweera, A. K. P., Liyanarachchi, N. P., Gunawardane, N., & Lanerolle, R. D. (2008). Epidemiology of chronic kidney disease in a Sri Lankan population. International Journal of Diabetes in Developing Countries, 28(2), 60–64.CrossRefGoogle Scholar
  20. Greenberg, A. E., Clesceri, L. S., & Eaton, A. D. (2005). Standard methods for the examination of water and wastewater (18th ed.). Washington, DC: American Public Health Association, American Water Works Association and Water Environment Federation.Google Scholar
  21. Hassen, W., Abid, S., Achour, A., Creppy, E., & Bacha, H. (2004). Ochratoxin A and beta2-microglobulinuria in healthy individuals and in chronic interstitial nephropathy patients in the centre of Tunisia: A hot spot of ochratoxin a exposure. Toxicology, 199(2–3), 185–193.CrossRefGoogle Scholar
  22. Ileperuma, O. A., Dharmagunawardhane, H. A., & Herath, K. P. R. 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.CrossRefGoogle Scholar
  23. Inkielewicz, I., & Krechniaka, J. (2003). Fluoride content in soft tissues and urine of rats exposed to sodium fluoride in drinking water. Fluoride, 36(4), 263–266.Google Scholar
  24. Järup, L., Hellström, L., Alfvén, T., Carlsson, M. D., Grubb, A., Persson, B., et al. (2000). Low level exposure to cadmium and early kidney damage: The OSCAR study. Occupational and Environmental Medicine, 57(10), 668–672.CrossRefGoogle Scholar
  25. Jayasumana, M.A.C.S., Paranagama, P.A., Amarasinghe, M., Fonseka, S. I., & Wijekoon, D. V. K. Presence of arsenic in pesticides used in Sri Lanka.
  26. 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, 2013(14), 180. doi: 10.1186/1471-2369-14-180.CrossRefGoogle Scholar
  27. Jin, X., Qian, Z., Lu, B., Yang, W., & Bi, S. (2011). Density functional theory study on aqueous aluminum − fluoride complexes: Exploration of the intrinsic relationship between water-exchange rate constants and structural parameters for monomer aluminum complexes. Environmental Science and Technology, 45(1), 288–293.CrossRefGoogle Scholar
  28. Johnson, S, Misra, S. S., Sahu, R., & Saxena, P (2012). Environmental contamination and its association with Chronic Kidney Disease of Unknown Etiology in North Central Region of Sri Lanka, Centre for Science and Environment Report. CSE/PML/PR‐42/2012.
  29. Lubkowska, A., Zyluk, B., Chlubek, D., & Poland, S. (2002). Interactions between fluorine and aluminium. Fluoride, 35(2), 73–77.Google Scholar
  30. Nanayakkara, S., Senevirathna, S., Abeysekera, T., Chandrajith, R., Ratnatunga, N., Gunarathne, E., et al. (2013). 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
  31. Soderland, P., Lovekar, S., Weiner, D. E., Brooks, D. R., & Kaufman, J. S. (2010). Chronic kidney disease associated with environmental toxins and exposures. Advances in Chronic Kidney Disease, 17(3), 254–264.CrossRefGoogle Scholar
  32. Stamatis, G., Alexakia, D., Gamvroula, D., & Migiros, G. (2011). Groundwater quality assessment in Oropos–Kalamos basin. Environmental Earth Sciences, 64(4), 973–988.CrossRefGoogle Scholar
  33. Thijssen, S., Maringwa, J., Faes, C., Lambrichts, I., & Van Kerkhove, E. (2007). Chronic exposure of mice to environmentally relevant, low doses of cadmium leads to early renal damage, not predicted by blood or urine cadmium levels. Toxicology, 229(1–2), 145–156.CrossRefGoogle Scholar
  34. Varner, J. A., Jensen, K. F., Horvath, W., & Isaacson, R. L. (1998). Chronic administration of aluminum–fluoride or sodium–fluoride to rats in drinking water: Alterations in neuronal and cerebrovascular integrity. Brain Research, 784, 284–298.CrossRefGoogle Scholar
  35. Wanigasuriya, K. P., Peiris-John, R. J., & Wickremasinghe, R. (2011). Chronic kidney disease of unknown etiology in Sri Lanka: Is cadmium a likely cause? BMC Nephrology, 12, 32. doi: 10.1186/1471-2369-12-32.CrossRefGoogle Scholar
  36. Warnakulasuriya, K. A. A. S., Balasuriya, S., Perera, P. A. J., & Peiris, L. C. L. (1992). Determining optimal levels of fluoride in drinking water hot dry climates-A case study in Sri Lanka. Community Dental Oral Epidermiology, 20(6), 364–367.CrossRefGoogle Scholar
  37. Wasana, H.M.S., Aluthpatabendi, A., & Bandara, J. (2012). Drinking water quality assessment towards “Chronic Kidney Disease of unknown etiology in North Central Province of Sri Lanka. In Symposium proceedings, international symposium on water quality and human health: Challenges ahead, 22–23 March 2012, PGIS, Peradeniya, Sri Lanka proceedings. 12. Accessed at, December 2012. Postgraduate Institute of Science, Sri Lanka, 2012.
  38. Wasana, H. M. S., Perera, G. D. R. K., Gunawardena, P. S. De., & Bandara, J. (2015).  The impact of aluminum, fluoride, and aluminum–fluoride complexes in drinking water on chronic kidney disease. Environmental Science and Pollution Research. doi: 10.1007/s11356-015-4324-y.
  39. WHO. (1994). World Health Organization expert Committee on oral health status and fluoride use: Fluorides and oral health, WHO Technical Report series No 846. Geneva: World Health Organization.Google Scholar
  40. World Health Organization. (2012) Country office for Sri Lanka, WHO Sri Lanka home page.
  41. www report 2. Accessed 17 August 2014.
  42. Xiong, X., Liu, J., He, W., Xia, T., He, P., Chen, X., et al. (2007). Dose-effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children. Environmental Research, 3(1), 112–116.CrossRefGoogle Scholar
  43. Zhu, Y. N., Zhang, X. H., Xie, Q. L., Wang, D. Q., & Cheng, G. W. (2006). Solubility and stability of calcium arsenates at 25 °C. Water, Air, and Soil pollution, 169(1–4), 221–238.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Hewa M. S. Wasana
    • 1
  • Dharshani Aluthpatabendi
    • 1
  • W. M. T. D. Kularatne
    • 2
  • Pushpa Wijekoon
    • 2
  • Rohan Weerasooriya
    • 3
  • Jayasundera Bandara
    • 1
  1. 1.Institute of Fundamental StudiesKandySri Lanka
  2. 2.Department of Statistics and Computer Science, Faculty of ScienceUniversity of PeradeniyaPeradeniyaSri Lanka
  3. 3.Department of Soil Science, Faculty of AgricultureUniversity of PeradeniyaPeradeniyaSri Lanka

Personalised recommendations