Taking the "unknown" out of CKDu-optimizing approaches to uncover the cause(s) of epidemic-level kidney disease in low- and middle-income settings: a report from the ISN's International Consortium of CKDu Collaborators (ISN i3C).

Abstract

Chronic kidney disease of undetermined etiology (CKDu) is a major cause of mortality that affects communities, health systems, and national economies. Despite 2 decades of descriptive and analytical research, the causes of CKDu epidemics remain unclear. In February 2025, at the World Congress of Nephrology, the International Society of Nephrology's International Consortium of CKDu Collaborators met to discuss the obstacles to determining the cause(s) of the epidemics. Several key themes were identified: First, differences in CKDu burden between regions are poorly described, and this is complicated by inconsistent terminology. Second, some proposed primary causes of CKDu are also progression factors in chronic kidney disease of all causes. It is unclear whether such factors can explain CKDu epidemics, partly because of the challenges around distinguishing disease onset from progression. Lastly, there is a need for alternatives to self-report in capturing exposures. This report outlines the current state of the field, describes these themes in more detail, and offers suggestions to optimize future research efforts.