Kidney Week

Abstract: PO2435

Characterization of Nano-Sized Silica in Sugarcane Ash and Its Potential Role in the Pathogenesis of CKD of an Unknown Etiology

Session Information

• CKD: Inflammation, Endothelial Dysfunction, and Signaling
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2103 CKD (Non-Dialysis): Mechanisms

Authors

• Rogers, Keegan L., University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, United States

Keegan L. Rogers

• Roncal-jimenez, Carlos Alberto, University of Colorado Anschutz Medical Campus, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States

Carlos Alberto Roncal-jimenez,

• Johnson, Richard J., University of Colorado Anschutz Medical Campus, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States

Richard J. Johnson,

• Brown, Jared Michael, University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, United States

Jared Michael Brown,

Background

Sugarcane burning by farmers in developing countries is hypothesized to contribute to an endemic kidney pathology called chronic kidney disease of an unknown etiology (CKDu). Further, elemental analysis of the sugarcane stalks was shown to have a high percentage of amorphous silica (SiO₂). We hypothesized that burning of sugarcane generates nano-sized particles that are easily inhaled and translocated to the kidney thereby contributing to CKDu in sugarcane workers.

Methods

To determine if nano-sized particles are present in sugarcane ash, we utilized single particle inductively coupled plasma mass spectrometry (ICP-MS) and dynamic light scattering (DLS). To determine the effects of SiNPs on the kidney, we used a human proximal convoluted tubule cell line (HK-2) to recapitulate the nephron’s exposure to sugarcane ash, desilicated ash, sugarcane ash derived SiNPs, and pristine 200 nm SiNPs at 0.25, 2.5, and 25 μg/mL.

Results

Using single particle ICP-MS, we identified silica nanoparticles (SiNPs) within digested sugarcane ash which ranged in size from 190-212 nm. DLS analysis of digested ash confirmed the presence of nanoparticles with a hydrodynamic diameter of ~180 nm and Despite not being directly cytotoxic to HK-2 cells at 6 hours at any dose, SiNPs are taken up leading to significant production of reactive oxygen species and mitochondrial superoxide within the first hour of exposure at all doses.

Conclusion

This indicates that the presence of silica nanoparticles from sugarcane ash in the kidney may lead to NLRP3 inflammasome activation and epithelial mesenchymal transition occurring which will lead to a CKDu phenotype and disease pathogenesis.

Funding

• NIDDK Support