Does fluoride cause the mysterious chronic kidney disease of multifactorial origin?

A chronic kidney disease of multifactorial origin (CKDmfo), also known as CKD of unknown origin, started to manifest during the past four decades in certain economically poor, peri-equatorial agricultural countries. CKDmfo is an environmentally induced, occupationally-mediated, chronic tubulointerstitial disease. Prolonged exposure to environmental nephrotoxic agents and extenuating conditions are prerequisites for its manifestation. More than 30 causative factors have been postulated, but none one has been properly scientifically tested, to be able to include or exclude. In recent years, fluoride has come to be considered a key contender as a causative agent of CKDmfo. Therefore, this review examines the pros and cons of that theory and the potential plausibility that fluoride causes CKDmfo. It also examines the potential interactions and additive or synergistic effects of certain geogenic factors, especially, the plausibility of CaPO apatite and fluorapatite crystals and nanotube formation in concentrated tubular filtrate and within tubular cells, in renal tubules. The information presented is based on published work and data collected over the past two decades in Sri Lanka. However, the evidence and concepts are applicable to all CKDmfo-affected countries. Thus, the presented content might facilitate scientists to narrowed down causative factors to just a few and government departments to implement effective programs for preventing this disease. The findings suggest that in addition to the geogenic components, disease manifestation requires (A) prolonged exposure to environmental nephrotoxins and factors, (B) interactions among elements (Ca, PO , F, and Mg), and (C) vulnerability of the person, such as chronic dehydration, and antioxidant and micronutrient deficiencies. In vivo precipitation of nanominerals in renal tubular tissues that arising over several years causes tubulointerstitial disease-CKDmfo. Inherent vulnerabilities and conditions, together with nanomineral precipitation, trigger renal tubular cell oxidative stresses, inflammation, and fibrosis, and eventually causing tubulointerstitial chronic renal failure-CKDmfo.