Urinary Exosomes Identify Inflammatory Pathways in Vancomycin Associated Acute Kidney Injury.
AKI
complement
exosomes
immune pathways
inflammation
nephrotoxicity
vancomycin
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
10 Mar 2021
10 Mar 2021
Historique:
received:
29
12
2020
revised:
23
02
2021
accepted:
25
02
2021
entrez:
3
4
2021
pubmed:
4
4
2021
medline:
4
5
2021
Statut:
epublish
Résumé
Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant
METHODS
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
CONCLUSIONS
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.
Identifiants
pubmed: 33801801
pii: ijms22062784
doi: 10.3390/ijms22062784
pmc: PMC7999309
pii:
doi:
Substances chimiques
Biomarkers
0
Vancomycin
6Q205EH1VU
Creatinine
AYI8EX34EU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK079337
Pays : United States
Organisme : International Serious Adverse Events Consortium
ID : 12-1325
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