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

Journal Article (Review;Journal Article)

The chronic kidney disease of unknown etiology (CKDu) is a global health concern primarily impacting tropical farming communities. Although the precise etiology is debated, CKDu is associated with environmental exposures including heat stress and chemical contaminants such as fluoride, heavy metals, and herbicide glyphosate. However, a comprehensive synthesis is lacking on molecular networks underpinning renal damage induced by these factors. Addressing this gap, here we present key molecular events associated with heat and chemical exposures. We identified that caspase activation and lipid peroxidation are common endpoints of glyphosate exposure, while vasopressin and polyol pathways are associated with heat stress and dehydration. Heavy metal exposure is shown to induce lipid peroxidation and endoplasmic reticulum stress from ROS activated MAPK, NFĸB, and caspase. Collectively, we identify that environmental exposure induced increased cellular oxidative stress as a common mechanism mediating renal cell inflammation, apoptosis, and necrosis, likely contributing to CKDu initiation and progression.

Full Text

Duke Authors

Cited Authors

  • Upamalika, SWAM; Wannige, CT; Vidanagamachchi, SM; Gunasekara, SC; Kolli, RT; De Silva, PMCS; Kulasiri, D; Jayasundara, N

Published Date

  • May 2022

Published In

Volume / Issue

  • 92 /

Start / End Page

  • 103850 -

PubMed ID

  • 35301132

Electronic International Standard Serial Number (EISSN)

  • 1872-7077

International Standard Serial Number (ISSN)

  • 1382-6689

Digital Object Identifier (DOI)

  • 10.1016/j.etap.2022.103850


  • eng