Urinary Metabolomics From a Dose-Fractionated Polymyxin B Rat Model of Acute Kidney Injury.
Acute kidney injury
Animal model
Metabolomics
Polymyxin B
Polymyxins
Urinary biomarker
Journal
International journal of antimicrobial agents
ISSN: 1872-7913
Titre abrégé: Int J Antimicrob Agents
Pays: Netherlands
ID NLM: 9111860
Informations de publication
Date de publication:
Jul 2022
Jul 2022
Historique:
received:
22
10
2021
revised:
18
02
2022
accepted:
11
04
2022
pubmed:
24
4
2022
medline:
24
6
2022
entrez:
23
4
2022
Statut:
ppublish
Résumé
Polymyxin B treatment is limited by kidney injury. This study sought to identify Polymyxin B-related urinary metabolomic profile modifications for early detection of polymyxin-associated nephrotoxicity. Samples were obtained from a previously conducted study. Male Sprague-Dawley rats received dose-fractionated polymyxin B (12 mg/kg/day) once daily (QD), twice daily (BID), and thrice daily (TID) for three days, with urinary biomarkers and kidney histopathology scores determined. Daily urine was analysed for metabolites via 1H nuclear magnetic resonance (NMR). Principal components analyses identified spectral data trends with orthogonal partial least square discriminant analysis applied to classify metabolic differences. Metabolomes were compared across groups (i.e., those receiving QD, BID, TID, and control) using a mixed-effects models. Spearman correlation was performed for injury biomarkers and the metabolome. A total of 25 rats were treated with Polymyxin B, and n = 2 received saline, contributing 77 urinary samples. Pre-dosing samples clustered well, characterised by higher amounts of citrate, 2-oxoglutarate, and hippurate. Day 1 samples showed higher taurine; day 3 samples had higher lactate, acetate and creatine. Taurine was the only metabolite that significantly increased in both BID and TID compared with the QD group. Day 1 taurine correlated with increasing histopathology scores (rho = 0.4167, P = 0.038) and kidney injury molecule-1 (KIM-1) (rho = 0.4052, P = 0.036), whereas KIM-1 on day 1 and day 3 did not reach significance with histopathology (rho = 0.3248, P = 0.11 and rho = 0.3739, P = 0.066). Polymyxin B causes increased amounts of urinary taurine on day 1, which then normalizes to baseline concentrations. Taurine may provide one of the earlier signals of acute kidney damage caused by polymyxin B.
Sections du résumé
BACKGROUND
BACKGROUND
Polymyxin B treatment is limited by kidney injury. This study sought to identify Polymyxin B-related urinary metabolomic profile modifications for early detection of polymyxin-associated nephrotoxicity.
METHODS
METHODS
Samples were obtained from a previously conducted study. Male Sprague-Dawley rats received dose-fractionated polymyxin B (12 mg/kg/day) once daily (QD), twice daily (BID), and thrice daily (TID) for three days, with urinary biomarkers and kidney histopathology scores determined. Daily urine was analysed for metabolites via 1H nuclear magnetic resonance (NMR). Principal components analyses identified spectral data trends with orthogonal partial least square discriminant analysis applied to classify metabolic differences. Metabolomes were compared across groups (i.e., those receiving QD, BID, TID, and control) using a mixed-effects models. Spearman correlation was performed for injury biomarkers and the metabolome.
RESULTS
RESULTS
A total of 25 rats were treated with Polymyxin B, and n = 2 received saline, contributing 77 urinary samples. Pre-dosing samples clustered well, characterised by higher amounts of citrate, 2-oxoglutarate, and hippurate. Day 1 samples showed higher taurine; day 3 samples had higher lactate, acetate and creatine. Taurine was the only metabolite that significantly increased in both BID and TID compared with the QD group. Day 1 taurine correlated with increasing histopathology scores (rho = 0.4167, P = 0.038) and kidney injury molecule-1 (KIM-1) (rho = 0.4052, P = 0.036), whereas KIM-1 on day 1 and day 3 did not reach significance with histopathology (rho = 0.3248, P = 0.11 and rho = 0.3739, P = 0.066).
CONCLUSIONS
CONCLUSIONS
Polymyxin B causes increased amounts of urinary taurine on day 1, which then normalizes to baseline concentrations. Taurine may provide one of the earlier signals of acute kidney damage caused by polymyxin B.
Identifiants
pubmed: 35460851
pii: S0924-8579(22)00097-8
doi: 10.1016/j.ijantimicag.2022.106593
pii:
doi:
Substances chimiques
Biomarkers
0
Taurine
1EQV5MLY3D
Polymyxin B
J2VZ07J96K
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106593Informations de copyright
Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.