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纳米晶体诱导的热带国家慢性肾小管肾病:诊断、缓解和消除。

Nanocrystal-induced chronic tubular-nephropathy in tropical countries: diagnosis, mitigation, and eradication.

机构信息

Cardiometabolic & Endocrine Institute, Department of Medicine, Endocrinology, Nutrition, (formerly UMDNJ/Rutgers University), New Brunswick, NJ, 08902, USA.

, Moratuwa, Sri Lanka.

出版信息

Eur J Med Res. 2023 Jul 5;28(1):221. doi: 10.1186/s40001-023-01162-y.

DOI:10.1186/s40001-023-01162-y
PMID:37408060
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10320992/
Abstract

In tropical countries, a mysterious tubulo-interstitial chronic renal disease (CKD), unrelated to diabetes, hypertension, and immunological causes, manifested four decades ago. Approximately 25,000 primarily middle-aged male farmers succumb annually to this crystal-tubular nephropathy (CTN). Without any known causative factors, it was identified as CKD of unknown aetiology (CKDu). Because multiple factors contribute to causing it later, was changed to CKD of multi-factorial (CKDmfo). Despite no evidence, it was hypothesised to cause by agrochemicals or heavy metals in food or drinking contaminated water. However, current data suggest that the CKD-CTN is due to natural geogenic water contamination. Consumption of concentrated stagnant groundwater from deep-dug wells and tube wells containing hard water and fluoride, overdecades is necessary for its clinical manifestations. In all affected countries have prolonged annual dry seasons that led to the evopo-concentration of ions and minerals in groundwater, making hard water even more unpalatable, thus, peasants consume lesser amounts of water. They develop chronic dehydration from daily exposure to hot climatic conditions aggravated by regular alcohol intake. These conditions provide a highly conducive environment-a perfect storm for calcium phosphate (CaPO) crystal formation in renal tissues. Our recent histological and preliminary electron microscopic data reveal deposition of CaPO crystals and nano-tubes in kidneys. While CaPO nano-minerals are unstable, the presence of fluoride ions stabilises and allows their growth. This new concept paves the path for highly cost-effective, straightforward local solutions to protect farm workers and eliminate the disease, without embarking on expensive medications, interventions, or building hospitals. Chronic dehydration-associated CKD-CTN is preventable by increased consumption of potable water. Increasing clean water consumption reduces CKD-CTN incidence, and associated morbidities and premature deaths. However, the damage becomes irreversible when the disease advances beyond CKD stage IIIB. The incidence of this deadly renal failure can be prevented by its education, lifestyle changes, and increased water consumption, not by treating the renal disease or expanding dialysis centres/hospitals, or transplantation services. Eradication of CKD-CTN cost significantly less than the current approach of treating affected persons and unnecessarily expanding health infrastructure. Since the manifestation of CKD-CTN is due to consuming naturally contaminated drinking water (with calcium containing hard water and fluoride), it is not difficult to remove these to prevent CKD-CTN: thus, international assistance is unwarranted for its eradication. The straightforward approaches described here will prevent CKD-CTN and save thousands of lives in affected farming communities.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad9e/10320992/67b06f4ec686/40001_2023_1162_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad9e/10320992/5aff355ce2e6/40001_2023_1162_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad9e/10320992/e5df354a8db6/40001_2023_1162_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad9e/10320992/67b06f4ec686/40001_2023_1162_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad9e/10320992/5aff355ce2e6/40001_2023_1162_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad9e/10320992/684ccb1ceb1e/40001_2023_1162_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad9e/10320992/e5df354a8db6/40001_2023_1162_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad9e/10320992/67b06f4ec686/40001_2023_1162_Fig4_HTML.jpg
摘要

在热带国家,一种与糖尿病、高血压和免疫原因无关的神秘的肾小管间质性慢性肾病(CKD)在四十年前出现。每年约有 25000 名主要是中年男性农民死于这种晶体管状肾病(CTN)。由于没有任何已知的致病因素,它被确定为病因不明的 CKD(CKDu)。由于后来有多种因素导致这种疾病,因此更改为多因素的 CKD(CKDmfo)。尽管没有证据表明它是由食物中的农用化学品或重金属或受污染的饮用水引起的,但还是提出了这种假设。然而,目前的数据表明,CKD-CTN 是由于天然地质源性水的污染。饮用深钻井和管井中含有硬水和氟化物的浓缩停滞地下水,数十年后会出现临床症状。在所有受影响的国家,都有长期的旱季,导致地下水中的离子和矿物质浓缩,使硬水更加难喝,因此农民的用水量减少。他们因日常暴露在炎热的气候条件下而慢性脱水,加上经常饮酒,情况恶化。这些条件提供了一个高度有利的环境——钙磷酸盐(CaPO)晶体在肾组织中形成的完美风暴。我们最近的组织学和初步电子显微镜数据显示,肾脏中存在 CaPO 晶体和纳米管的沉积。虽然 CaPO 纳米矿物质不稳定,但氟离子的存在会使其稳定并允许其生长。这一新概念为保护农场工人和消除疾病铺平了道路,无需采用昂贵的药物、干预措施或建造医院,而是提供了高性价比的、直接的本地解决方案。增加饮用水的摄入量可预防与慢性脱水相关的 CKD-CTN。增加清洁水的摄入量可降低 CKD-CTN 的发病率以及相关的发病率和过早死亡。然而,当疾病进展到 CKD 第三阶段 B 以外时,损害将变得不可逆转。通过教育、生活方式的改变和增加水的摄入量,而不是通过治疗肾脏疾病或扩大透析中心/医院或移植服务,可以预防这种致命的肾衰竭的发生。消除 CKD-CTN 的成本明显低于目前治疗受影响者和不必要地扩大卫生基础设施的方法。由于 CKD-CTN 的表现是由于饮用受自然污染的饮用水(含有钙的硬水和氟化物)所致,因此去除这些物质以预防 CKD-CTN 并不困难:因此,消除 CKD-CTN 不需要国际援助。这里描述的简单方法将预防 CKD-CTN,并挽救受影响的农业社区中的数千人的生命。

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