An update on the epidemiology of chronic kidney disease of uncertain etiology

PURPOSE OF REVIEW: Chronic kidney disease of uncertain etiology (CKDu) has devastating impacts on individuals and communities in affected regions, but it remains an ill-defined diagnosis of exclusion despite decades of environmental and epidemiologic research. The purpose of this review is to synthesize recent literature describing the global burden of disease and potential causal factors. RECENT FINDINGS: A large, international prevalence study quantitatively identified Uddanam, India, Northwest Nicaragua, and Anuradhapura, Sri Lanka as prominent CKDu hotspots. Stronger evidence for the role of heat stress in exacerbating kidney function decline among individuals with CKDu now includes validated measurements of core body temperature. Additionally, recent studies use urine metabolomics to support environmental exposure evaluation and generate hypotheses for future pathway analysis. While longitudinal studies remain infrequent, three key longitudinal studies provide greater insight into trajectories of kidney function decline in CKDu. SUMMARY: The cause(s) of CKDu remain uncertain, but greater integration of genetic, translational, biopsy, and longitudinal epidemiologic data hold promise for elucidating mechanistic pathways. Increased standardization of kidney biopsy protocols, epidemiologic definitions, and population surveillance methodologies would strengthen ongoing efforts to identify, treat, and prevent CKDu.