The cause of Chronic Kidney Disease of unknown etiology (CKDu) in the rural dry zone of Sri Lanka remains unidentified, despite vast research efforts that brought about an extensive list of potential risk factors. Among these, the long-term exposure to various nephrotoxic elements through drinking groundwater was widely suspected owing to the unique geographical distribution of the disease. This review focuses on such well-known hypotheses suspecting the relations with fluoride, hardness, major ions, heavy metals, metalloids, organic matter, agrochemical residues, pathogens, and bacterial toxins in the groundwaters of the CKDu-endemic region. It was comprehensively discussed why each of these constituents was considered a risk factor of CKDu, how could they possibly trigger the pathogenesis of the disease, what was the evidence that supported or failed each hypothesis, and whether providing safe drinking water had been effective at mitigating the progression of the disease. Although plenty of circumstantial evidence supported an etiology related to groundwater for CKDu, it was impossible to elucidate the cause–effect relationships between drinking impaired groundwater and the occurrence of the disease. Future research should be effectively designed to clarify the role of groundwater in the onset of CKDu by taking into account the gaps in past research.

尽管进行了大量研究工作并产生了大量潜在风险因素，但斯里兰卡农村干燥地区的慢性肾脏病（CKDu）的病因仍未确定。其中，由于该病独特的地理分布，人们普遍怀疑通过饮用地下水长期暴露于各种肾毒性元素。本综述重点关注这些众所周知的假设，怀疑与 CKDu 流行地区地下水中的氟化物、硬度、主要离子、重金属、准金属、有机物、农药残留、病原体和细菌毒素之间的关系。全面讨论了为什么这些成分中的每一个都被认为是 CKDu 的危险因素，它们如何可能引发疾病的发病机制，支持或否定每个假设的证据是什么，提供安全饮用水是否能有效减缓疾病的进展。尽管大量间接证据支持 CKDu 与地下水有关的病因，但无法阐明饮用受损地下水与疾病发生之间的因果关系。未来的研究应该通过考虑过去研究的空白来有效地设计以阐明地下水在 CKDu 发病中的作用。无法阐明饮用受损地下水与疾病发生之间的因果关系。未来的研究应该通过考虑过去研究的空白来有效地设计以阐明地下水在 CKDu 发病中的作用。无法阐明饮用受损地下水与疾病发生之间的因果关系。未来的研究应该通过考虑过去研究的空白来有效地设计以阐明地下水在 CKDu 发病中的作用。