Fluoride Action Network



High water hardness associated with high water fluoride and the geographical distribution of Chronic Kidney Disease of unknown etiology (CKDu) in Sri Lanka are well correlated. We undertook this study to observe the effects of high water hardness with high fluoride on kidney and liver in rats and efficacy of distilled water in reducing the effects.


Test water sample with high water hardness and high fluoride was collected from Mihinthale region and normal water samples were collected from Kandy region. Twenty-four rats were randomly divided into 8 groups and water samples were introduced as follows as daily water supply. Four groups received normal water for 60 (N1) and 90 (N2) days and test water for 60 (T1) and 90 (T2) days. Other four groups received normal (N3) and test (T3) water for 60 days and followed by distilled water for additional 60 days and normal (N4) and test (T4) water for 90?days followed by distilled water for another 90 days. The rats were sacrificed following treatment. Serum samples were subjected to biochemical tests; serum creatinine, urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and elemental analysis. Histopathological examinations were carried out using kidney and liver samples.


Test water treated groups were associated with acute tubular injury with loss of brush border and test water followed with distilled water treated groups maintained a better morphology with minimal loss of brush border. Serum creatinine levels in T1 and T2 groups and urea level in T2 group were significantly (p < 0.05) increased compared to control groups. After administration of distilled water, both parameters were significantly reduced in T4 group (p <0.05) compared to T2. Serum AST activity was increased in T4 group (p <0.05) compared to control group with no histopathological changes in liver tissues. The serum sodium levels were found to be much higher compared to the other electrolytes in test groups.


Hard water with high fluoride content resulted in acute tubular injury with a significant increase in serum levels of creatinine, urea and AST activity. These alterations were minimized by administering distilled water.

Excerpt & References


Chronic kidney disease (CKD) is viewed as part of the rising worldwide non-communicable disease burden. Hypertension and diabetes mellitus are the important risk factors for this disease in all developed and many developing countries [1]. In early nineties, there has been a rising incidence and prevalence of chronic renal failures that has emerged in the North Central region (NCR) of Sri Lanka where the disease is not associated with any known risk factors [2]. Due to the elusive nature of the disease, it has been named “Chronic Kidney Disease of unknown etiology” (CKDu). Because of its slow progressive loss of kidney function, CKDu often gets worst slowly and remain undiagnosed over a long period of time [3].

Ground water source is considered as a causative factor for CKDu [4, 5]. The elevated levels of fluoride, which is defined as above 0.5?mg/L by the World Health Organization in groundwater sources is observed in CKDu endemic regions [6]. Therefore, fluoride has received increased attention as a risk factor in the etiology of CKDu [7, 8]. Jayasumana et al (2014) and other groups reported that water hardness could contribute to the etiology of CKDu due to exceeding the levels of ideal water hardness of between 150 and 250?mg/L CaCO3 [9,10,11]. Moreover, the hydrogeochemical investigations in CKDu endemic areas revealed that both fluoride and hardness is elevated in all CKDu endemic regions [12].

Previous studies revealed that high concentrations of groundwater fluoride distributed in the dry zone, whereas minimal fluoride levels were reported in the wet zone (Fig. 1a). Further, Chandrajith et al. (2011), reported high fluoride levels from 1.3–5.3?ppm in CKDu endemic areas such as Girandurukotte, Nikawewa, Madawachchiya and Padaviya in Sri Lanka [8]. These findings were further confirmed by the occurrence of clinically diagnosed dental and skeletal fluorosis in these areas [13, 14]. In contrast, CKDu occurrence was less even in the areas with high concentrations of groundwater fluoride such as Huruluwewa and Wellawaya [8].

Fig. 1

Geographical distribution of water hardness, ground water fluoride and CKDu patients in Sri Lanka. a Distribution of fluoride in ground water in Sri Lanka (Source: Chandrajith et al.; 2012) b Ground water hardness variation over Sri Lanka (Source: National water supply and drainage board, Sri Lanka; www.waterboard.lk) c Distribution and prevalence of CKDu in Sri Lanka (Source: Jayasumana et al.; 2014)

The hardness of drinking water is mainly dependent on the concentration of dissolved cations namely, calcium and magnesium predominantly in combination with the anions, bicarbonate, sulphate and chloride [15]. Other cations such as Al, Zn, Ba, Fe, Sr, and Mn have minor contribution for the total hardness of water [16, 17]. Increased total water hardness is common in northern and northern central parts of Sri Lanka (Fig. 1b). Jayasumana et al (2014), reported high water hardness (up to 820?mg/L) in CKDu endemic areas which showed a correlation with the prevalence of CKDu [3, 18]. But, unexpected low occurrence of CKDu was found in Jaffna and Puttalam districts even with reported higher water hardness (approximately 1500?mg/L) [19, 20].

When we overlapped the high fluoride areas with high water hardness areas surprisingly, the same areas were overlapped with the reported high occurrences of CKDu namely Medawachchiya, Girandurukotte, Kabithigollawa, Padaviya, Medirigiriya, Dehiattakandiya and Nikawewa regions in the dry zone of Sri Lanka (Fig. 1c) [21].

Therefore, we hypothesized that both high fluoride and high water hardness together contributes to the pathogenesis of CKDu. In our previous study, the effect of fluoride alone on kidney and liver were investigated and proved that there is a possibility of inducing renal damage by elevated serum creatinine levels with exposure to extremely high fluoride levels (20ppmF) for longer period but not with low concentrations [22]. In this study, we performed a comparative study of the effect of both high fluoride and high water hardness on kidney and liver in rats by treating orally a water sample collected from CKDu endemic area. And also, we examined whether the distilled water could reverse the damage created by these factors…

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*Original article online at https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-020-01763-3