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Endemic occurrence of chronic kidney disease with unknown etiology is reported in certain parts of the north central dry zone of Sri Lanka and has become a new and emerging health issue. The disease exclusively occurs in settlements where groundwater is the main source of drinking water and is more common among low socio-economic groups, particularly among the farming community. Due to its remarkable geographic distribution and histopathological evidence, the disease is believed to be an environmentally induced problem. This paper describes a detailed hydrogeochemical study that has been carried out covering endemic and non-endemic regions. Higher fluoride levels are common in drinking water from both affected and non-affected regions, whereas Ca-bicarbonate type water is more common in the affected regions. In terms of the geochemical composition of drinking water, affected households were rather similar to control regions, but there is a large variation in the Na/Ca ratio within each of the two groups. Fluoride as shown in this study causes renal tubular damage. However it does not act alone and in certain instances it is even cytoprotective. The fine dividing line between cytotoxicity and cytoprotectivity of fluoride appears to be the effect of Ca2+ and Na+ of the ingested water on the F- metabolism. This study illustrates a third major cause (the other two being hypertension and diabetes) of chronic kidney diseases notably in tropical arid regions such as the dry zone of Sri Lanka. (C) 2010 Elsevier B.V. All rights reserved.