The "Known Unknowns" of CKD of Undetermined Etiology In 2026: A Review

In 2025, the World Health Organization specifically called for action to address the epidemics of chronic kidney disease of undetermined etiology (CKDu) occurring in low-income agricultural settings as part of a wider resolution aimed at promoting kidney health to reduce the global burden of noncommunicable disease. Despite this high-level recognition of the problem and 2 decades of research efforts, there continues to be much debate surrounding the primary etiology of the disease. Furthermore, there remain other unknowns in the CKDu field, including the spectrum of kidney conditions that this term includes and the geographical extent of disease. This review details these areas of uncertainty to clarify what is known about the extent of CKDu burden, discusses the challenges around interpretation of existing studies, and describes recent published data that provide evidence for and against the cause(s) of the disease, specifically with respect to heat exposure. Finally, we address what we can do with what we know now and what we might do in the future to reduce the unknowns in CKDu.