63 A Case for Amorphous Silica Nanoparticle Exposure in the Development of Chronic Kidney Disease of Unknown Etiology

Abstract

Abstract We have hypothesized that sugarcane burning in developing countries contributes to an endemic kidney pathology in agricultural workers called chronic kidney disease of an unknown etiology (CKDu).  Elemental analysis shows that sugarcane stalks contain a high percentage of amorphous silica (SiO2). Therefore, we hypothesized that burning of sugarcane generates silica nanoparticles (SiNPs) that present an inhalation hazard to these agricultural workers. To determine if SiNPs are present in sugarcane ash and kidney biopsies from agricultural workers, we utilized single particle inductively coupled plasma mass spectrometry and found SiNPs, which ranged in size from 190-212 nm, in sugarcane ash. In a small cohort of CKDu patients from El Salvador and Mexico, we found a significant increase in the number of SiNPs in their kidney biopsies within a similar size range as observed in sugarcane ash. Additionally, Wistar rats exposed to sugarcane ash intranasally for 24 weeks developed focal injury in the tubulointerstitium and glomeruli with deposition of SiNPs in the kidney.  To further determine the cellular effects of SiNPs, we exposed human proximal convoluted tubule (PCT) cells to sugarcane ash, de-silicated ash, or sugarcane ash derived SiNPs. Despite not being directly cytotoxic to PCT cells at 24 hrs, SiNPs were taken up and generated reactive oxygen species. Vimentin staining confirmed PCT cells underwent epithelial-mesenchymal transition (EMT) following treatment with ash or SiNPs but not with de-silicated ash. These findings suggest SiNPs present in sugarcane ash are capable of driving EMT in PCT cells potentially contributing to a CKDu phenotype.