Urinary mitochondrial DNA is a biomarker of mitochondrial disruption and renal dysfunction in acute kidney injury.
Recent studies show the importance of mitochondrial dysfunction in the initiation and progression of acute kidney injury (AKI). However, no biomarkers exist linking renal injury to mitochondrial function and integrity. To this end, we evaluated urinary mitochondrial DNA (UmtDNA) as a biomarker of renal injury and function in humans with AKI following cardiac surgery. mtDNA was isolated from the urine of patients following cardiac surgery and quantified by quantitative PCR. Patients were stratified into no AKI, stable AKI, and progressive AKI groups based on Acute Kidney Injury Network (AKIN) staging. UmtDNA was elevated in progressive AKI patients and was associated with progression of patients with AKI at collection to higher AKIN stages. To evaluate the relationship of UmtDNA to measures of renal mitochondrial integrity in AKI, mice were subjected to sham surgery or varying degrees of ischemia followed by 24 h of reperfusion. UmtDNA increased in mice after 10-15 min of ischemia and positively correlated with ischemia time. Furthermore, UmtDNA was predictive of AKI in the mouse model. Finally, UmtDNA levels were negatively correlated with renal cortical mtDNA and mitochondrial gene expression. These translational studies demonstrate that UmtDNA is associated with recovery from AKI following cardiac surgery by serving as an indicator of mitochondrial integrity. Thus UmtDNA may serve as valuable biomarker for the development of mitochondrial-targeted therapies in AKI.
Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Ryan M
RM
Whitaker
Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
L Jay
LJ
Stallons
Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Joshua E
JE
Kneff
Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
Joseph L
JL
Alge
Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Jennifer L
JL
Harmon
Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Jennifer J
JJ
Rahn
Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.|Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina, USA.
John M
JM
Arthur
Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Craig C
CC
Beeson
Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Sherine L
SL
Chan
Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.|Ralph H. Johnson Veterans Administration Medical Center, Charleston, South Carolina, USA.
Rick G
RG
Schnellmann