A review of molecular mechanisms linked to potential renal injury agents in tropical rural farming communities

Upamalika, Samarawickrama Wanni Arachchige Madushani; Wannige, C.T.; Vidanagamachchi, S. M.; Gunasekara, T. D. K. S. C.; Kolli, Ramya Tulasi; Silva, P. Mangala C.S. De; Kulasiri, Don; Jayasundara, Nishad

doi:10.1016/j.etap.2022.103850

Cited by 6 publications

(5 citation statements)

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“…Data from Taiwan show that co-exposure of arsenic and glyphosate worsen kidney function in 3b and later stages of CKD [39]. Heavy metals can be reabsorbed and concentrated by the kidney inducing ROS and kidney injury [6]. Mice administered environmental levels of glyphosate alone and in Roundup with and without hard water develop proximal tubular cell injury, which is most severe in the combined group, suggesting a synergistic effect [40 ▪ ].…”

Section: Pathogenesismentioning

confidence: 99%

“…Proposed mechanisms for dehydration/heat stress-induced CKD include volume depletion-induced hyperosmolarity activating the proximal tubular aldose–reductase pathway leading to conversion of glucose to fructose with upregulation of fructokinase resulting in oxidative stress [7 ▪ ]. Dehydration augments proximal tubular fluid reabsorption, potentially amplifying uptake and intratubular concentration of nephrotoxins, including agrochemicals and heavy metals [6]. Hyperuricemia because of dehydration can cause intratubular uric acid deposition and kidney injury [47].…”

Section: Pathogenesismentioning

confidence: 99%

“…Coastal sugarcane communities had a 15% CKD prevalence in one study [5]. In Asia, Sri Lanka, one of the first countries to identify CKDu, has a CKD rate of up to 84% in endemic areas, most of which is thought to be CKDu [6]. The rate of CKD in Sri Lanka more than tripled from 2003–2008 to 2013–2017 in a highly endemic area [6] In India, CKDu is second only to diabetic nephropathy as a cause of CKD, with a 10–53.6% prevalence depending on the region and active involvement in farming [7 ▪ ].…”

Section: Chronic Kidney Disease With Unknown Cause Prevalencementioning

confidence: 99%

“…In Asia, Sri Lanka, one of the first countries to identify CKDu, has a CKD rate of up to 84% in endemic areas, most of which is thought to be CKDu [6]. The rate of CKD in Sri Lanka more than tripled from 2003–2008 to 2013–2017 in a highly endemic area [6] In India, CKDu is second only to diabetic nephropathy as a cause of CKD, with a 10–53.6% prevalence depending on the region and active involvement in farming [7 ▪ ]. CKDu in farm workers was reported in 18.6% in areas of Indonesia, 12% in Pakistan, and 2.7% of those age 15–60 years in Taiwan, a 63% increment compared with other occupations [8,9].…”

Section: Chronic Kidney Disease With Unknown Cause Prevalencementioning

confidence: 99%

“…Heavy metals and/or trace elements can contaminate agrochemicals resulting in simultaneous nephrotoxin exposures [14]. High fluoride levels have been found in black tea and groundwater in CKDu hot spots [6,7 ▪ ]. Groundwater in endemic vs. nonendemic areas contains higher concentrations of silica (21.0 vs. 30.1 mg/l, P < 0.05) and fluoride (0.45 vs. 0.80 mg/l, P < 0.05), with 25% of fluoride concentrations above the Sri Lanka-recommended level [34].…”

Section: Pathogenesismentioning

confidence: 99%

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Chronic kidney disease with unknown cause across the global spectrum

Nast

2023

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewIn the 1990s, a type of chronic kidney disease with unknown cause (CKDu) was identified in Central America and Sri Lanka. Patients lacked hypertension, diabetes, glomerulonephritis, or other usual causes of kidney failure. Affected patients are predominantly male agricultural workers aged 20--60 years, living in economically disadvantaged areas with poor access to medical care. Patients typically present late and progress to end-stage kidney disease within 5 years, resulting in social and economic hardship for families, regions, and countries. This review covers the current state of knowledge for this disease. Recent findingsThe prevalence of CKDu is increasing in known endemic regions and across the globe, reaching epidemic proportions. There is primary tubulointerstitial injury with secondary glomerular and vascular sclerosis. No definitive etiologic factors have been identified, and these may vary or overlap in different geographic locations. The leading hypotheses include exposure to agrochemicals, heavy metals and trace elements, and kidney injury from dehydration/heat stress. Infections and lifestyle factors may play a role, but are likely not key. Genetic and epigenetic factors are beginning to be explored. SummaryCKDu is a leading cause of premature death in young-to-middle-aged adults in endemic regions and has become a public health crisis. Studies are underway to investigate clinical, exposome, and omics factors, and hopefully will provide insights into pathogenetic mechanisms resulting in biomarker discovery, preventive measures, and therapeutics.

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Section: Pathogenesismentioning

confidence: 99%