Analytical and clinical validation of rapid chemiluminescence enzyme immunoassay for urinary thioredoxin, an oxidative stress-dependent early biomarker of acute kidney injury.
Acute kidney injury
Chemiluminescence enzyme immunoassay
Early diagnosis
Oxidative stress
Rapid biomarker
Thioredoxin
Journal
Clinica chimica acta; international journal of clinical chemistry
ISSN: 1873-3492
Titre abrégé: Clin Chim Acta
Pays: Netherlands
ID NLM: 1302422
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
11
03
2020
revised:
22
04
2020
accepted:
22
04
2020
pubmed:
30
4
2020
medline:
14
1
2021
entrez:
30
4
2020
Statut:
ppublish
Résumé
Oxidative stress is now recognized to be an important therapeutic target in kidney diseases. However, there are currently no biomarkers that can be used clinically to diagnose renal oxidative stress. A rapid assay system for urinary thioredoxin 1, an oxidative stress-dependent biomarker of acute kidney injury (AKI), was developed as a chemiluminescence enzyme immunoassay and validated analytically and clinically. Analytic evaluation revealed that hemolytic hemoglobin caused measurements to be abnormally high, above the detectable range. However, urine sediment containing red blood cells did not affect the measurements. Assays using our proposed chemiluminescence enzyme immunoassay were completed within as little as 6 min, whereas a conventional ELISA > 4 h. Aciduria <pH 6.0 led to a significant underestimation of thioredoxin 1 concentrations. However, the effects of aciduria were completely reversible with use of a buffer developed for pH adjustment. Urinary thioredoxin 1 was increased in patients with AKI, but was unaffected by extrarenal oxidative stress diseases, including hypoxemia and myocardial infarction, or by chronic kidney disease in which serum creatinine concentrations were comparable. These results suggest that the chemiluminescent enzyme immunoassay system for urinary thioredoxin 1 enables rapid and specific diagnosis of AKI associated with oxidative stress.
Sections du résumé
BACKGROUND
BACKGROUND
Oxidative stress is now recognized to be an important therapeutic target in kidney diseases. However, there are currently no biomarkers that can be used clinically to diagnose renal oxidative stress.
METHODS
METHODS
A rapid assay system for urinary thioredoxin 1, an oxidative stress-dependent biomarker of acute kidney injury (AKI), was developed as a chemiluminescence enzyme immunoassay and validated analytically and clinically.
RESULTS
RESULTS
Analytic evaluation revealed that hemolytic hemoglobin caused measurements to be abnormally high, above the detectable range. However, urine sediment containing red blood cells did not affect the measurements. Assays using our proposed chemiluminescence enzyme immunoassay were completed within as little as 6 min, whereas a conventional ELISA > 4 h. Aciduria <pH 6.0 led to a significant underestimation of thioredoxin 1 concentrations. However, the effects of aciduria were completely reversible with use of a buffer developed for pH adjustment. Urinary thioredoxin 1 was increased in patients with AKI, but was unaffected by extrarenal oxidative stress diseases, including hypoxemia and myocardial infarction, or by chronic kidney disease in which serum creatinine concentrations were comparable.
CONCLUSIONS
CONCLUSIONS
These results suggest that the chemiluminescent enzyme immunoassay system for urinary thioredoxin 1 enables rapid and specific diagnosis of AKI associated with oxidative stress.
Identifiants
pubmed: 32348784
pii: S0009-8981(20)30180-7
doi: 10.1016/j.cca.2020.04.025
pii:
doi:
Substances chimiques
Biomarkers
0
TXN protein, human
0
Thioredoxins
52500-60-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
271-279Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.