Chronic kidney disease (CKD) affects approximately 10% of the global population, and leads to five to ten million deaths annually. Growing in importance is a distinctive form with unknown/uncertain etiology (CKDu), the cause of which remains unknown and is not linked to factors normally associated with CKD. Symptoms of CKDu manifest late and are similar to late-stage CKD, complicating differential and early diagnosis and treatment. CKDu is prevalent in Nicaragua, El Salvador, India, Egypt, Sri Lanka and in several Balkan countries, with reported cases recently emerging in other countries in Asia and Africa.