Abstract: FR-PO1013
Endoplasmic Reticulum (ER) and Mitochondrial Stress Markers of Heavy Metals Exposure in the CRIC Study
Session Information
- CKD Mechanisms: From Mendel to Mars
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Baca, Justin T., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
- Taylor, Robert M., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
- Pankratz, V. Shane, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
- Yang, Wei, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Wang, Xue, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Unruh, Mark L., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
- Shah, Vallabh O., University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
Background
Chronic kidney disease (CKD) is a progressive disease that affects ~13% of the population. Heavy metal (HM) exposure contributes to the rapid progression of kidney disease due to persistent stress stimuli that lead to dysregulation of inflammatory and oxidative stress pathways. Our hypothesis is that cumulative exposure to metals increases progression of CKD via inflammation and oxidative stress.
Methods
We obtained matching nail samples (n=40) from 20 participants of the Chronic Renal Insufficiency Cohort (CRIC) at baseline (n=20) and 24-month follow-up (n=20). An equal number of subjects had fast progressing disease (n=10) and stable disease (n=10). Samples were a random pick of all available samples and were sent anonymized prior to analysis. We quantified twenty-five metalloids in the nail samples using Inductively Coupled Plasma Mass Spectrometry (ICP/MS). Mercury was measured on a Flow Injector Mercury System (FIMS), and boron with ICP/Optical Emission Spectroscopy (ICP/OES). Biochemical markers were measured at the CRIC Scientific and Data Coordinating Center (SDCC) using commercial kits.
Results
Marker concentrations at baseline and follow-up are shown for the fast progressing and stable progression cohorts.
Conclusion
Although not significant, in the fast-progressing disease cohort, ATF, VAR6, and PERK were all increased while GRP78, Caspase 12, and mitofilin were all decreased at follow-up. In the stable cohort, all markers were increased at follow-up with the exceptions of mitofilin (decreased) and PERK (unchanged). Increased ER and mitochondrial stress markers showed a trend towards higher metal burden.
Funding
- NIDDK Support