1) We developed an automated method for quantitating interstitial fibrosis during chronic kidney disease, where we can sample the entire kidney section, rather than selected high power fields of view, and our digital masking of vessel-associated collagen enabled us to remove this quantitative artifact. 2) In a study with mouse sepsis, we found that serum Cystatin C had a faster increase and reached peak levels more rapidly than serum creatinine. Serum creatinine had better performance than Cystatin C at later time points. We were able to develop a composite serum creatinine and serum Cystatin C score that performed well at all time points. Similar to our previous work, we found that cystatin C production was reduced in sepsis. Both serum Cystatin C and serum creatinine outperformed BUN at early prediction of sepsis-induced mortality. 3) We are continuing our work on exosomes as a source of biomarkers, including proteins and miRNA. We are exploring proper normalizing techniques for these biomarkers, including counting exosomes by Nanosight Tracking Analysis and measuring TSG101 by western blot. 4) We are continuing a public-private consortium with the HESI Genomics microRNA Focus Group to compare standard protocol vs site-specific protocols from multiple sites; variations will identify which preanalytical steps affect microRNA detection and quantification in biofluids in drug-induced injury models. The initial model is a cardiotoxin that stimulates release of miRNAs into the circulation, which will shed light on renal handling of miRNA. Urinary miRNA from non-renal sources is expected to be non-exosomal.

Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2015
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
Zip Code
Wolfinger, Russell D; Beedanagari, Sudheer; Boitier, Eric et al. (2018) Two approaches for estimating the lower limit of quantitation (LLOQ) of microRNA levels assayed as exploratory biomarkers by RT-qPCR. BMC Biotechnol 18:6
Cai, Yan; Xu, Ming-Jiang; Koritzinsky, Erik H et al. (2017) Mitochondrial DNA-enriched microparticles promote acute-on-chronic alcoholic neutrophilia and hepatotoxicity. JCI Insight 2:
Street, J M; Koritzinsky, E H; Glispie, D M et al. (2017) Urine Exosomes: An Emerging Trove of Biomarkers. Adv Clin Chem 78:103-122
Koritzinsky, Erik H; Street, Jonathan M; Star, Robert A et al. (2017) Quantification of Exosomes. J Cell Physiol 232:1587-1590
Street, Jonathan M; Koritzinsky, Erik H; Glispie, Deonna M et al. (2017) Urine Exosome Isolation and Characterization. Methods Mol Biol 1641:413-423
Koritzinsky, Erik H; Street, Jonathan M; Star, Robert A et al. (2017) Cover Image, Volume 232, Number 7, July 2017. J Cell Physiol 232:i
Bavendam, Tamara G; Norton, Jenna M; Kirkali, Ziya et al. (2016) Advancing a Comprehensive Approach to the Study of Lower Urinary Tract Symptoms. J Urol 196:1342-1349
Askenazi, David J; Morgan, Catherine; Goldstein, Stuart L et al. (2016) Strategies to improve the understanding of long-term renal consequences after neonatal acute kidney injury. Pediatr Res 79:502-8
Souza, Ana Carolina P; Bocharov, Alexander V; Baranova, Irina N et al. (2016) Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation. Kidney Int 89:809-22
Thompson, Karol L; Boitier, Eric; Chen, Tao et al. (2016) Absolute Measurement of Cardiac Injury-Induced microRNAs in Biofluids across Multiple Test Sites. Toxicol Sci 154:115-125

Showing the most recent 10 out of 26 publications