Progression of potential etiologies of the chronic kidney disease of unknown etiology in Sri Lanka

Chronic kidney disease of unknown etiology (CKDu) is a major health issue in agricultural areas in Sri Lanka. Despite many attempts to identifying causative factors of CKDu, the real cause/s remain/s elusive to date. Understanding the progression of potential etiologies may provide valuable insight into this quest. Literature relevant to CKDu addresses several etiologies, including quality of drinking water in the affected areas including hardness, fluoride, ionicity, agrochemical and heavy metal contaminations, consumption of contaminated food, and the genetic makeup of vulnerable populations. Progression of the etiologies revealed persistent interest in heavy metals of multiple origins: waterborne, foodborne, or soilborne. Secondary factors, such as water hardness, fluoride, and ionicity appear to act synergistically, aggravating the role of heavy metals on the onset, and the progression of CKDu. Demographical factors, such as male sex, over 50 years of age, agriculture-related occupation, and the consumption of contaminated water and food are intricately related with the disease progression while other minor risk factors such as smoking, alcohol consumption, etc. exasperate the disease condition. Since, none of these etiologies are examined adequately, conducting laboratory exposure studies under <i>in-vivo</i> and <i>in-vitro</i> settings to understand their role in CKDu is crucial.