Chronic kidney disease of unknown etiology (CKDu) is a global epidemic. Sri Lanka has experienced a doubling of the disease every 4 or 5 years since it was first identified in the North Central province in the mid-1990s. The disease primarily affects people in agricultural regions who are missing the commonly known risk factors for CKD. Sri Lanka is not alone: health workers have reported prevalence of CKDu in Mexico, Nicaragua, El Salvador, and the state of Andhra Pradesh in India. A global search for the cause of CKDu has not identified a single factor, but rather many factors that may contribute to the etiology of the disease. Some of these factors include heat stroke leading to dehydration, toxic metals such as cadmium and arsenic, fluoride, low selenium, toxigenic cyanobacteria, nutritionally deficient diet and mycotoxins from mold exposure. Furthermore, exposure to agrichemicals, particularly glyphosate and paraquat, are likely compounding factors, and may be the primary factors. Here, we argue that glyphosate in particular is working synergistically with most of the other factors to increase toxic effects. We propose, further, that glyphosate causes insidious harm through its action as an amino acid analogue of glycine, and that this interferes with natural protective mechanisms against other exposures. Glyphosate’s synergistic health effects in combination with exposure to other pollutants, in particular paraquat, and physical labor in the ubiquitous high temperatures of lowland tropical regions, could result in renal damage consistent with CKDu in Sri Lanka.

There has been an epidemic of Chronic Kidney Disease of Unknown Etiology (CKDu) affecting the agricultural communities in Sri Lanka, spanning three decades. The main pathological finding has been chronic interstitial nephritis. This narrative review focuses on the efficacy of Reverse Osmosis (RO) technology in purifying water and its impact in reducing CKDu. PubMed, Cochrane and Google Scholar were used to search for peer-reviewed articles from 2000 to 2023. The themes that emerged from the literature review were validated through the opinions of key informants and subject matter experts.There were anecdotal, as well as some research evidence to indicate that RO-treated water is efficacious in preventing and slowing down the progression of CKDu. This relationship needs further investigation with well-designed prospective studies. The literature review also revealed many social, technical and environmental issues related to the use of RO machines. Despite the potential benefits of RO machines, these issues must be resolved in order to prevent serious problems in the future.In conclusion, this review underscores the need for further research, interventions and regulatory measures related to the use of RO machines to reshape the CKDu trajectory in Sri Lanka.