Multi-pronged research on endemic chronic kidney disease of unknown etiology in Sri Lanka: a systematic review

Increasing prevalence of endemic chronic kidney disease of unknown etiology (CKDu) in Sri Lanka is a major health problem since the 1990s. Despite numerous studies on CKDu, research groups have been unable to develop a comprehensive approach to mitigate the disorder, and thereby to identify research gaps. We conducted a systematic literature review of 119 publications on CKDu in Sri Lanka from Pubmed, Google Scholar, and Scopus, published until end September 2020. A higher CKDu prevalence in the working population of the North Central Province was reported with recent studies indicating patients from non-endemic regions as well. A majority were etiological studies that recorded conflicting and inconclusive evidence on CKDu etiology. Studies on clinico-pathological, diagnostic, biochemical, and molecular biological aspects of CKDu, studies analyzing CKDu symptom burden, anthropological, and behavioral impacts of CKDu, were reviewed as well. A dearth of research exists on nutritional, demographical, immunological, and microbial aspects of CKDu. The overview of the reviewed literature indicated the absence of a comprehensive plan of action to mitigate this situation. Hence, we propose the "One Health" approach with a systems dynamics model as a potential way forward to alleviate the CKDu epidemic in Sri Lanka. This enables the representation of multiple causative agents (and interactions thereof) among environmental, animal, and human systems, in concert with the "exposome" that provides the totality of exposure the individual has undergone since birth.