Chronic kidney disease with unknown cause across the global spectrum.

Purpose Of Review: In the 1990s, a type of chronic kidney disease with unknown cause (CKDu) was identified in Central America and Sri Lanka. Patients lacked hypertension, diabetes, glomerulonephritis, or other usual causes of kidney failure. Affected patients are predominantly male agricultural workers aged 20-60 years, living in economically disadvantaged areas with poor access to medical care. Patients typically present late and progress to end-stage kidney disease within 5 years, resulting in social and economic hardship for families, regions, and countries. This review covers the current state of knowledge for this disease.

Recent Findings: The prevalence of CKDu is increasing in known endemic regions and across the globe, reaching epidemic proportions. There is primary tubulointerstitial injury with secondary glomerular and vascular sclerosis. No definitive etiologic factors have been identified, and these may vary or overlap in different geographic locations. The leading hypotheses include exposure to agrochemicals, heavy metals and trace elements, and kidney injury from dehydration/heat stress. Infections and lifestyle factors may play a role, but are likely not key. Genetic and epigenetic factors are beginning to be explored.

Summary: CKDu is a leading cause of premature death in young-to-middle-aged adults in endemic regions and has become a public health crisis. Studies are underway to investigate clinical, exposome, and omics factors, and hopefully will provide insights into pathogenetic mechanisms resulting in biomarker discovery, preventive measures, and therapeutics.