Concordant changes of plasma and kidney microRNA in the early stages of acute kidney injury: time course in a mouse model of bilateral renal ischemia-reperfusion.
BACKGROUND
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. 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.


RESULTS
Bilateral 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
Systematic 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.
Cardiometabolic Diseases and Diabetic Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
Melissa A
MA
Bellinger
Cardiometabolic Diseases and Diabetic Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
James S
JS
Bean
Cardiometabolic Diseases and Diabetic Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
Melissa A
MA
Rader
Investigational Pathology, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
Kathleen M
KM
Heinz-Taheny
Covance Laboratories, Greenfield, Indiana, United States of America.
Jairo S
JS
Nunes
Statistics-Discovery/Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
Joseph V
JV
Haas
Cardiometabolic Diseases and Diabetic Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
Laura F
LF
Michael
Cardiometabolic Diseases and Diabetic Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, United States of America.
Mark D
MD
Rekhter
D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010949:Plasma / Q000378:metabolism*; D015424:Reperfusion / Q000379:methods; D015427:Reperfusion Injury / Q000378:metabolism*
D015415:Biomarkers; D003404:Creatinine; D035683:MicroRNAs; D009687:Nuclear Proteins; D010750:Phosphoproteins; C000591522:Nucks1 protein, mouse