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⁻³₄ 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 (Ca²⁺, PO⁻³₄ , F⁻, and Mg²⁺), 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.

在过去的四十年中，在某些经济较差的赤道周边农业国家中，慢性多因素起源的肾脏疾病（CKDmfo）也被称为未知来源的CKD。CKDmfo是一种环境诱导的职业介导的慢性肾小管间质疾病。长时间暴露于环境肾毒性剂和减轻病情是其表现的前提。假定有30多种致病因素，但没有一个经过适当科学检验以能够包含或排除。近年来，氟化物已被认为是CKDmfo的致病因素。因此，本综述探讨了该理论的利弊，以及氟化物导致CKDmfo的潜在可能性。^-3 ₄ 磷灰石和氟磷灰石晶体以及在肾小管中浓缩的管状滤液和管状细胞内的纳米管形成。所提供的信息基于过去二十年来在斯里兰卡收集的已发表工作和数据。但是，证据和概念适用于所有受CKDmfo影响的国家。因此，介绍的内容可能有助于科学家将病因范围缩小到少数几个，政府部门也可以实施有效的预防该病的计划。这一发现表明，在除环境地球化学组件，疾病表现需要元件之间（A）长时间暴露于环境肾毒素和因素，（B）相互作用（钙²⁺，PO ^-3 ₄ ，F ^-，以及Mg ²⁺），以及（C）人的脆弱性，例如慢性脱水以及抗氧化剂和微量营养素缺乏症。纳米矿物质在肾小管组织中的体内沉淀是几年来引起的，引起肾小管间质疾病-CKDmfo。固有的脆弱性和条件以及纳米矿物质沉淀会触发肾小管细胞氧化应激，炎症和纤维化，并最终导致肾小管间质性慢性肾衰竭-CKDmfo。