Next Article in Journal
Medically Important Alterations in Transport Function and Trafficking of ABCG2
Previous Article in Journal
Crosstalk among Calcium ATPases: PMCA, SERCA and SPCA in Mental Diseases
Previous Article in Special Issue
Suppressed Hepatic Production of Indoxyl Sulfate Attenuates Cisplatin-Induced Acute Kidney Injury in Sulfotransferase 1a1-Deficient Mice
Article

Urinary Exosomes Identify Inflammatory Pathways in Vancomycin Associated Acute Kidney Injury

1
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA
2
School of Medicine, University of California, San Diego, CA 92093, USA
3
School of Medicine, University of Alabama, Birmingham, AL 35233, USA
4
Albert Einstein College of Medicine, The Bronx, NY 10461, USA
5
Albany Medical College, Albany, NY 12208, USA
6
Division of Renal Diseases and Hypertension, Skaggs School of Pharmacy and Pharmaceutical, Aurora, CO 80045, USA
7
School of Medicine, University of Colorado, Aurora, CO 80045, USA
8
Mount Sinai School of Medicine, New York, NY 10029, USA
9
Department of Cellular and Molecular Medicine, University of Michigan Medical System, Ann Arbor, MI 48109, USA
*
Author to whom correspondence should be addressed.
Membership of the Direct Investigators is provided in the Acknowledgments.
Academic Editor: Satohiro Masuda
Int. J. Mol. Sci. 2021, 22(6), 2784; https://doi.org/10.3390/ijms22062784
Received: 29 December 2020 / Revised: 23 February 2021 / Accepted: 25 February 2021 / Published: 10 March 2021
(This article belongs to the Special Issue Molecular Mechanisms and Biomarkers in Drug-Induced Organ Injury)
Background: Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant Staphylococcusaureus. Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those with higher targeted trough concentrations. The precise mechanism of injury in humans remains elusive, with recent evidence directed towards proximal tubule cell apoptosis. In this study, we investigated the protein contents of urinary exosomes in patients with V-AKI to further elucidate biomarkers of mechanisms of injury and potential responses. Methods: Urine samples from patients with V-AKI who were enrolled in the DIRECT study and matched healthy controls 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 identity and quantification was determined by label-free liquid chromatography mass spectrometry (LC/MS). 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 partial recovery; 33% experienced full recovery by day 28. Proteomic analyses on five V-AKI and 7 control samples revealed 2009 proteins in all samples and 251 proteins significantly associated with V-AKI (Pi-score > 1). The top discriminatory proteins were complement C3, complement C4, galectin-3-binding protein, fibrinogen, alpha-2 macroglobulin, immunoglobulin heavy constant mu and serotransferrin. Conclusion: Urinary exosomes reveal up-regulation of inflammatory proteins after nephrotoxic injury in V-AKI. Further studies are necessary in a large patient sample to confirm these findings for elucidation of pathophysiologic mechanisms and validation of potential injury biomarkers. View Full-Text
Keywords: vancomycin; AKI; nephrotoxicity; exosomes; inflammation; complement; immune pathways vancomycin; AKI; nephrotoxicity; exosomes; inflammation; complement; immune pathways
Show Figures

Figure 1

MDPI and ACS Style

Awdishu, L.; Le, A.; Amato, J.; Jani, V.; Bal, S.; Mills, R.H.; Carrillo-Terrazas, M.; Gonzalez, D.J.; Tolwani, A.; Acharya, A.; Cerda, J.; Joy, M.S.; Nicoletti, P.; Macedo, E.; Vaingankar, S.; Mehta, R.; RamachandraRao, S.P.; on behalf of the Direct Investigators. Urinary Exosomes Identify Inflammatory Pathways in Vancomycin Associated Acute Kidney Injury. Int. J. Mol. Sci. 2021, 22, 2784. https://doi.org/10.3390/ijms22062784

AMA Style

Awdishu L, Le A, Amato J, Jani V, Bal S, Mills RH, Carrillo-Terrazas M, Gonzalez DJ, Tolwani A, Acharya A, Cerda J, Joy MS, Nicoletti P, Macedo E, Vaingankar S, Mehta R, RamachandraRao SP, on behalf of the Direct Investigators. Urinary Exosomes Identify Inflammatory Pathways in Vancomycin Associated Acute Kidney Injury. International Journal of Molecular Sciences. 2021; 22(6):2784. https://doi.org/10.3390/ijms22062784

Chicago/Turabian Style

Awdishu, Linda, Amy Le, Jordan Amato, Vidhyut Jani, Soma Bal, Robert H. Mills, Marvic Carrillo-Terrazas, David J. Gonzalez, Ashita Tolwani, Anjali Acharya, Jorge Cerda, Melanie S. Joy, Paola Nicoletti, Etienne Macedo, Sucheta Vaingankar, Ravindra Mehta, Satish P. RamachandraRao, and on behalf of the Direct Investigators. 2021. "Urinary Exosomes Identify Inflammatory Pathways in Vancomycin Associated Acute Kidney Injury" International Journal of Molecular Sciences 22, no. 6: 2784. https://doi.org/10.3390/ijms22062784

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop