Urinary Mitochondrial DNA Levels Identify Acute Kidney Injury in Surgical Critical Illness Patients.

Abstract

Recent studies showed that mitochondrial injury and mitochondrial DNA (mtDNA) damage are associated with the initiation and progression of acute kidney injury (AKI). However, practical limitations of existing assays of mitochondrial function have limited our ability to study the link between mitochondrial dysfunction and renal injury. Therefore, we evaluated urinary mtDNA (UmtDNA) as a biomarker of AKI in critical illness patients. DNA was isolated from urine samples in surgical intensive care unit (SICU) patients and quantified by quantitative polymerase chain reaction (PCR). Correlation analyses showed the relationships between the UmtDNA and several biomarkers of renal dysfunction. Moreover, we evaluated the predictive and diagnostic values of UmtDNA in newly developed AKI, renal replacement therapy (RRT), and hospital mortality using receiver operating characteristics curves. MtDNA were expressed as PCR threshold cycle (Tc) number. Lower Tc indicated increased urinary mtDNA concentration. The baseline UmtDNA levels were elevated in SICU patients especially in AKI patients, compared with that in healthy controls. UmtDNA Tc number inversely correlated with serum creatine and urinary neutrophil gelatinase-associated lipocalin and directly with estimated glomerular filtration rate. Furthermore, baseline UmtDNA levels had high effectiveness in predicting development of AKI, initiation of RRT, and hospital mortality. Elevated UmtDNA levels could identify newly developed AKI and predict RRT or hospital mortality in SICU patients. UmtDNA Tc number correlated with markers of renal injury and dysfunction, suggesting the involvement of mitochondrial injury in kidney damage among surgical critical illness patients.