Abstract: SA-PO649
Urinary Exosomes Identify Inflammatory Pathways in Vancomycin Induced AKI
Session Information
- Pharmacology
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Le, Amy, UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences , La Jolla, California, United States
- Amato, Jordan, UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences , La Jolla, California, United States
- Jani, Vidhyut G., UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences , La Jolla, California, United States
- Mills, Robert, UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences , La Jolla, California, United States
- Gonzalez, David J., UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences , La Jolla, California, United States
- Tolwani, Ashita J., University of Alabama at Birmingham, Birmingham, Alabama, United States
- Acharya, Anjali, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
- Cerda, Jorge, Capital District Renal Physicians, Albany, New York, United States
- Joy, Melanie S., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Vaingankar, Sucheta M., University of California San Diego School of Medicine, San Diego, California, United States
- Ramachandrarao, Satish P., University of California San Diego School of Medicine, San Diego, California, United States
- Mehta, Ravindra L., University of California San Diego School of Medicine, San Diego, California, United States
- Awdishu, Linda, UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences , La Jolla, California, United States
Background
Vancomycin is used as a first line empiric therapy for gram positive organisms such as resistant Staphylococcus species. Vancomycin-induced acute kidney injury (VAN-AKI) has been reported in up to 43% of patients, especially in those targeting higher trough concentrations. The mechanism of injury in humans remains not well understood with recent evidence pointing to cast nephropathy. In this study, we investigate the protein contents of urinary exosomes in patients with VAN-AKI to further elucidate mechanisms of injury.
Methods
Urine samples from 10 patients with VAN-AKI who were enrolled in the DIRECT study and 12 healthy control urine samples from the UAB-UCSD O’Brien Center Biorepository were included in the analysis. Exosomes were extracted using solvent exclusion principle and polyethylene glycol induced precipitation. Protein quantification was analyzed by high throughput liquid chromatography/mass spectrometry. Significant proteins were determined by Pi score >1, which accounts for both fold change and t-test significance. Western blotting is currently being conducted as validation of proteomic findings.
Results
Subjects were male with a mean age of 40.8±18.3 years, BMI of 26.6±7.0, and a distribution of comorbidities. The mean peak serum creatinine was 3.7±1.4 mg/dL and time to kidney injury was 4.0±3.0 days. At discharge, 90% of patients demonstrated none or partial recovery; 33% experienced full recovery by day 28. Twelve samples were included in the final proteomic analysis and revealed 2009 proteins in all samples and 251 proteins significantly associated with VAN-AKI (Pi score >1). The top discriminatory proteins were fibrinogen, complement C3, complement C4, galectin-3-binding protein, alpha-2 macroglobulin, immunoglobulin heavy constant mu and serotransferrin. Galectin-3 binding protein binds glycoproteins such as serotransferrin and alpha 2 macroglobulin and up-regulation has been previously correlated with inflammation, fibrosis and rapid kidney function decline. Fibrinogen upregulation and complement activation have been demonstrated after ischemia reperfusion injury.
Conclusion
Urinary exosomes reveal up-regulation of inflammatory proteins after nephrotoxic injury in VAN-AKI.
Funding
- NIDDK Support