Urinary microRNAs as non-invasive biomarkers for toxic acute kidney injury in humans

Fathima Shihana*, Wilson K.M. Wong, Mugdha V. Joglekar, Fahim Mohamed, Indika B. Gawarammana, Geoffrey K. Isbister, Anandwardhan A. Hardikar, Devanshi Seth, Nicholas A. Buckley

*Corresponding author

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

Abstract

MicroRNAs in biofluids are potential biomarkers for detecting kidney and other organ injuries. We profiled microRNAs in urine samples from patients with Russell’s viper envenoming or acute self-poisoning following paraquat, glyphosate, or oxalic acid [with and without acute kidney injury (AKI)] and on healthy controls. Discovery analysis profiled for 754 microRNAs using TaqMan OpenArray qPCR with three patients per group (12 samples in each toxic agent). From these, 53 microRNAs were selected and validated in a larger cohort of patients (Russell’s viper envenoming = 53, paraquat = 51, glyphosate = 51, oxalic acid = 40) and 27 healthy controls. Urinary microRNAs had significantly higher expression in patients poisoned/envenomed by different nephrotoxic agents in both discovery and validation cohorts. Seven microRNAs discriminated severe AKI patients from no AKI for all four nephrotoxic agents. Four microRNAs (miR-30a-3p, miR-30a-5p, miR-92a, and miR-204) had > 17 fold change (p < 0.0001) and receiver operator characteristics area-under-curve (ROC-AUC) > 0.72. Pathway analysis of target mRNAs of these differentially expressed microRNAs showed association with the regulation of different nephrotoxic signaling pathways. In conclusion, human urinary microRNAs could identify toxic AKI early after acute injury. These urinary microRNAs have potential clinical application as early non-invasive diagnostic AKI biomarkers.

OriginalsprogEngelsk
Artikelnummer9165
TidsskriftScientific Reports
Vol/bind11
Udgave nummer1
ISSN2045-2322
DOI
StatusUdgivet - dec. 2021

Citer dette