Abstract

BackgroundAcute kidney injury (AKI) is a syndrome characterized by the rapid loss of the kidney excretory function and is strongly associated with increased early and long-term patient morbidity and mortality. Early diagnosis of AKI is challenging; therefore we profiled plasma microRNA in an effort to identify potential diagnostic circulating markers of renal failure. The goal of the present study was to investigate the dynamic relationship of circulating and renal microRNA profiles within the first 24 hours after bilateral ischemia-reperfusion kidney injury in mice.Methodology/Principal FindingsBilateral renal ischemia was induced in C57Bl/6 mice (n = 10 per group) by clamping the renal pedicle for 27 min. Ischemia-reperfusion caused highly reproducible, progressive, concordant elevation of miR-714, miR-1188, miR-1897-3p, miR-877*, and miR-1224 in plasma and kidneys at 3, 6 and 24 hours after acute kidney injury compared to the sham-operated mice (n = 5). These dynamics correlated with histologic findings of kidney injury and with a conventional plasma marker of renal dysfunction (creatinine). Pathway analysis revealed close association between miR-1897-3p and Nucks1 gene expression, which putative downstream targets include genes linked to renal injury, inflammation and apoptosis.Conclusions/SignificanceSystematic profiling of renal and plasma microRNAs in the early stages of experimental AKI provides the first step in advancing circulating microRNAs to the level of promising novel biomarkers.

Highlights

  • Acute kidney injury (AKI) is a syndrome characterized by the rapid loss of the kidney excretory function [1]

  • MicroRNAs are recognized as crucial regulators of gene expression

  • These dynamics correlated with histologic findings of kidney injury and with an established plasma marker of renal dysfunction

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Summary

Introduction

Acute kidney injury (AKI) is a syndrome characterized by the rapid loss of the kidney excretory function [1] It is strongly associated with increased early and long-term patient morbidity and mortality, as well as subsequent development of chronic kidney disease [2]. AKI is typically diagnosed by the accumulation of end products of nitrogen metabolism (urea or creatinine) and/or decreased urine output [1]. These traditional markers are reliable, they lack the sensitivity and specificity that are necessary for early diagnosis. Acute kidney injury (AKI) is a syndrome characterized by the rapid loss of the kidney excretory function and is strongly associated with increased early and long-term patient morbidity and mortality. The goal of the present study was to investigate the dynamic relationship of circulating and renal microRNA profiles within the first 24 hours after bilateral ischemia-reperfusion kidney injury in mice

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