A new form of chronic tubulointerstitial kidney disease (CKD) not related to diabetes or hypertension appeared during the past four decades in several peri-equatorial and predominantly agricultural countries. Commonalities include underground stagnation of drinking water with prolonged contact with rocks, harsh climatic conditions with protracted dry seasons, and rampant poverty and malnutrition. In general, the cause is unknown, and the disease is therefore named CKD of unknown aetiology (CKDu). Since it is likely caused by a combination of factors, a better term would be CKD of multifactorial origin (CKDmfo). Middle-aged malnourished men with more than 10 years of exposure to environmental hazards are the most vulnerable. Over 30 factors have been proposed as causative, including agrochemicals and heavy metals, but none has been properly tested nor proven as causative, and unlikely to be the cause of CKDmfo/CKDu. Conditions such as, having favourable climatic patterns, adequate hydration, and less poverty and malnutrition seem to prevent the disease. With the right in vivo conditions, chemical species such as calcium, phosphate, oxalate, and fluoride form intra-renal nanomineral particles initiating the CKDmfo. This article examines the key potential chemical components causing CKDmfo together with the risk factors and vulnerabilities predisposing individuals to this disease. Research findings suggest that in addition to drinking water from stagnant sources that contain high ionic components, more than 10 years of exposure to environmental nephrotoxins and micronutrient malnutrition are needed to contract this fatal disease.
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