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

被引：17

作者：

Shihana, Fathima ^{[1
,2
,3
]}

Wong, Wilson K. M. ^{[4
]}

Joglekar, Mugdha, V ^{[4
]}

Mohamed, Fahim ^{[1
,2
,5
,6
,7
]}

Gawarammana, Indika B. ^{[2
]}

Isbister, Geoffrey K. ^{[8
]}

Hardikar, Anandwardhan A. ^{[4
,9
]}

Seth, Devanshi ^{[3
,10
,11
]}

Buckley, Nicholas A. ^{[1
,2
,11
]}

机构：

[1] Univ Sydney, Fac Med & Hlth, Clin Pharmacol & Toxicol Res Grp, Biomed Informat & Digital Hlth, Sydney, NSW, Australia

[2] Univ Peradeniya, Fac Med, South Asian Clin Toxicol Res Collaborat, Peradeniya, Sri Lanka

[3] Univ Sydney, Centenary Inst Canc Med & Cell Biol, Sydney, NSW, Australia

[4] Western Sydney Univ, Sch Med, Diabet & Islet Biol Grp, Campbelltown, NSW, Australia

[5] Univ Peradeniya, Dept Pharm, Allied Hlth Sci, Peradeniya, Sri Lanka

[6] Univ New South Wales, Australian Kidney Biomarker Reference Lab, Dept Nephrol, Prince Wales Hosp, Sydney, NSW, Australia

[7] Univ New South Wales, Clin Sch, Sydney, NSW, Australia

[8] Univ Newcastle, Clin Toxicol Res Grp, Newcastle, NSW, Australia

[9] Roskilde Univ, Dept Sci & Environm, Roskilde, Denmark

[10] Univ Sydney, Fac Med & Hlth, Discipline Clin Med & Addict Med, Sydney, NSW, Australia

[11] Royal Prince Alfred Hosp, Drug Hlth Serv, Sydney, NSW, Australia

来源：

SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期

基金：

英国医学研究理事会;

关键词：

TUBULAR INJURY; IDENTIFICATION; NEPHROTOXICITY; MECHANISMS; EXPRESSION; PROFILES; MIR-204; SERUM;

D O I：

10.1038/s41598-021-87918-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 38 条

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