Detection of Drug-Induced Acute Kidney Injury in Humans Using Urinary KIM-1, miR-21,-200c, and-423


Pavkovic, Mira, Robinson-Cohen, Cassianne, Chua, Alicia S, Nicoara, Oana, Cardenas-Gonzalez, Mariana, Bijol, Vanesa, Ramachandran, Krithika, Hampson, Lucy, Pirmohamed, Munir ORCID: 0000-0002-7534-7266, Antoine, Daniel J et al (show 4 more authors) (2016) Detection of Drug-Induced Acute Kidney Injury in Humans Using Urinary KIM-1, miR-21,-200c, and-423. TOXICOLOGICAL SCIENCES, 152 (1). pp. 205-213.

This is the latest version of this item.

[img] Text
Pavkovic et al ToxSci accepted version.pdf - Unspecified
Download (1MB)
[img] Text
Pavkovic et al ToxSci accepted version.pdf - Author Accepted Manuscript
Download (1MB)

Abstract

Drug-induced acute kidney injury (AKI) is often encountered in hospitalized patients. Although serum creatinine (SCr) is still routinely used for assessing AKI, it is known to be insensitive and nonspecific. Therefore, our objective was to evaluate kidney injury molecule 1 (KIM-1) in conjunction with microRNA (miR)-21, -200c, and -423 as urinary biomarkers for drug-induced AKI in humans. In a cross-sectional cohort of patients (n = 135) with acetaminophen (APAP) overdose, all 4 biomarkers were significantly (P < .004) higher not only in APAP-overdosed (OD) patients with AKI (based on SCr increase) but also in APAP-OD patients without clinical diagnosis of AKI compared with healthy volunteers. In a longitudinal cohort of patients with malignant mesothelioma receiving intraoperative cisplatin (Cp) therapy (n = 108) the 4 biomarkers increased significantly (P < .0014) over time after Cp administration, but could not be used to distinguish patients with or without AKI. Evidence for human proximal tubular epithelial cells (HPTECs) being the source of miRNAs in urine was obtained first, by in situ hybridization based confirmation of increase in miR-21 expression in the kidney sections of AKI patients and second, by increased levels of miR-21, -200c, and -423 in the medium of cultured HPTECs treated with Cp and 4-aminophenol (APAP degradation product). Target prediction analysis revealed 1102 mRNA targets of miR-21, -200c, and -423 that are associated with pathways perturbed in diverse pathological kidney conditions. In summary, we report noninvasive detection of AKI in humans by combining the sensitivity of KIM-1 along with mechanistic potentials of miR-21, -200c, and -423.

Item Type: Article
Uncontrolled Keywords: nephrotoxicity in patients, biomarker, acute kidney injury, microRNAs, KIM-1
Depositing User: Symplectic Admin
Date Deposited: 29 Aug 2018 06:16
Last Modified: 19 Jan 2023 01:26
DOI: 10.1093/toxsci/kfw077
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3025644

Available Versions of this Item

Dimensions
Altmetric
CORE (COnnecting REpositories)