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

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 (CaPO4) crystal formation in renal tissues. Our recent histological and preliminary electron microscopic data reveal deposition of CaPO4 crystals and nano-tubes in kidneys. While CaPO4 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.

Comment on “Glyphosate and Fluoride in High-Hardness Drinking Water Are Positively Associated with Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka”

“…The levels of glyphosate in the water reported in this and all other published articles in Sri Lanka are far too low to cause any human health concerns, which makes glyphosate an improbable contributory agent of CKDu, as has been reported by others, as well. − The finding that 44% of tested well water samples in CKDu areas had ultralow but detectable amounts of glyphosate (due to the instrument’s high sensitivity) does not support the view that glyphosate is a causative agent or even associated with CKDu. As reported here, the detection of glyphosate (and AMPA) in human urine and blood cannot be interpreted as exposure capable of causing chronic toxic effects. , …”

“…As with other researchers, 312,14,15 this article suggests that "multiple" factors (i.e., hardness, alkaline water, and increased fluoride level) contribute to this complex problem; hence, previously, it termed CKD of muti-factorial origin. 4,5,14 Nevertheless, the article's title does not tally with the data presented, 1 and the evidence does not justify the conclusion that glyphosate is associated with or a causative agent of CKDu.…”

“…Glyphosate does not cause chronic kidney disease of unknown etiology (CKDu), appropriately known as CKD of crystal-tubular nephropathy (CTN). 4 Nimal Chandrasena orcid.org/0000-0002-3661-6857 Sunil J. Wimalawansa orcid.org/0000-0003-1096-8595…”

“…There is convincing evidence that the combined effect of multiple factors in well water (such as water hardness, increased Ca 2+ and fluoride levels, among others), ,,, including natural geochemical contamination of groundwater − (not agrochemicals or heavy metals), is more closely linked with CKDu than glyphosate or heavy metals. An overenthusiastic title and conclusions without supporting data would mislead the public and falsely perpetuate blame on glyphosate and other pesticides for causing CKDu.…”

“…We are concerned that such a misinterpretation could stigmatize and harm affected communities by diverting funds from providing basic support, agricultural needs, and essential potable drinking water that reduces the incidence of CKDu. Glyphosate does not cause chronic kidney disease of unknown etiology (CKDu), appropriately known as CKD of crystal-tubular nephropathy (CTN) …”