Chronic kidney disease of unknown etiology (CKDu) has become an alarming health issue in Sri Lanka. The disease is more notable among farming communities and people who consume groundwater as their main source of drinking water. To assess the possible links between drinking water chemistry and expansion of CKDu, the study was compared with hydrogeochemical data of drinking water sources in a CKDu prevalent area (Girandurukotte GND, Badulla District) and a reference area (Dambethalawa GND, Ampara District) in Sri Lanka. Based on the results, nephrotoxic heavy metal (Cd, Cr, Pb, and As) concentrations were significantly higher in the CKDu prevalent site than the reference area, compromised the harmful consequences to the people in the CKDu hotspot. Results of the inverse distance weighted (IDW) interpolation tool indicated the nephrotoxic heavy metals contents including Cd, Pb, As, and Cr in CKDu hotspot were changed in the ranges of 9.78–187.25 μg/L, 0.08–0.66 μg/L, 20.76–103.30 μg/L, and 0.03–0.34 μg/L. The random distribution patterns were shown by the result in Moran’s index values. Noteworthy, the results have emphasized a strong association between fluoride and water hardness. The frequency of occurrence above the threshold limit of fluoride was 28% in non-CKDu water samples, while 81% in CKDu prevalent sites. The hardness values in the CKDu prevalent site indicated “moderately hard water,” while the non-CKDu area indicated the “soft water.” Furthermore, this paper quantified overall water quality and heavy metal contamination and assessed the human health risks associated with drinking water. According to the results of the water quality index, 90% of the samples in the CKDu prevalent area were classified as “poor water” and “very poor water” for drinking purposes, while 73.33% of the samples in the non-CKDu area were “good” and “excellent” for drinking usage. Calculated chronic daily intake (CDIoral) and hazard quotient (HQoral) of nephrotoxicants were higher in CKDu hotspot than the non-CKDu site. Besides, the hazard index (HI) values obtained for the CKDu prevalent area exceeding the acceptable limit (HI = 1) indicated potential health risks to the people in those areas. This study suggests that long-term exposure to nephrotoxic heavy metals, water hardness, and fluoride present in drinking water may threaten human health and affect kidney functions. Therefore, regular monitoring and better management of water supplies in CKDu prevalent areas are essential to determine the contamination load and reduce the health impacts due to excessive and long-term exposure to the nephrotoxicants.
