Abstract: SA-PO107
Association of Altered Urinary miR-141 and miR-192 Expression with AKI Outcome
Session Information
- AKI: Mechanisms - Primary Injury and Repair - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Bowen, Timothy, Cardiff University, Cardiff, United Kingdom
- Newbury, Lucy Jade, Cardiff University, Cardiff, United Kingdom
- Khalid, Usman, Cardiff Transplant Unit, Cardiff, United Kingdom
- Simpson, Kate A., Cardiff University, Cardiff, United Kingdom
- Jenkins, Robert H., Cardiff University, Cardiff, United Kingdom
- Fraser, Donald, Cardiff University, Cardiff, United Kingdom
Background
Acute Kidney Injury (AKI) is characterised by a sudden decline in kidney function and affects over 20% of US hospitalisations, resulting in a greater than 4-fold increased mortality. The mechanisms underlying AKI recovery versus non-recovery remain poorly understood, and current biomarkers have limited capacity to predict outcome. These factors limit the development of new therapies. Here we evaluated the potential of urinary microRNAs (miRNAs) as biomarkers in patients with severe AKI.
Methods
Daily consecutive urine samples were collected from 30 patients with AKI stage III by KDIGO criteria. 377 miRNAs were profiled by RT-qPCR screening in pooled samples from recovery (n = 6) and non-recovery (n = 5) groups, with validation using individual assays. MiRNAs exhibiting altered expression in the urine of patients subsequently recovering vs. not recovering renal function were evaluated in in vivo (ischemia reperfusion injury (IRI) in the rat) and in vitro (proximal tubular epithelial cells (PTCs) exposed to hypoxia or oxidative stress) models by RNA sequencing and RT-qPCR. To identify miRNA targets, selected miRNAs were manipulated using transfection-based gain- and loss-of-function approaches in vitro.
Results
An extensive pattern of miRNA changes was observed, notably decreased miR-192 and increased miR-141 expression that predicted non-recovery. Alterations in miRNA expression were validated and linked to changes in our rat IRI model and in PTC miRNA expression in vitro. Network analysis of predicted miRNA targets converged on protein tyrosine phosphatase type G (PTPRG) and dysregulated PTPRG expression was confirmed.
Conclusion
These data identify quantifiable urinary miRNAs that predict outcome following AKI, and link these miRNAs to potential mechanisms of injury and recovery following AKI.