Urinary Mitochondrial DNA Level as a Biomarker of Acute Kidney Injury Severity

Abstract

Background: Mitochondrial dysfunction contributes to the pathogenesis of acute kidney injury (AKI). The urinary mitochondrial DNA (mtDNA) level was previously shown to predict renal function recovery in AKI following cardiac surgery. Herein, we determine whether urinary mtDNA is a marker of severity and predictor of recovery in AKI due to other etiologies. Methods: We recruited 107 AKI patients. The urinary mtDNA level was measured, the severity of AKI was quantified, and patients were followed for 90 days. Results: The urinary mtDNA level had modest but statistically significant correlations with the peak serum creatinine level (Spearman's r = -0.248, p = 0.010) and the duration of hospital stay (r = -0.217, p = 0.025). Patients who required temporary dialysis also tended to have higher urinary mtDNA levels than those without dialysis (22.6 ± 4.5 vs. 24.9 ± 5.7 cycles, p = 0.06). There was no definite relation between the urinary mtDNA level and renal function recovery. Conclusion: The urinary mtDNA level is a marker of AKI severity, as reflected by its significant correlation with the peak serum creatinine level, duration of hospital stay, and probably the need for temporary dialysis. Our result suggests that urinary mtDNA has the potential to serve as a biomarker of AKI.

Mitochondria in Sepsis-Induced AKI

“…106 Therefore, recent studies evaluated the efficiency of urinary mtDNA (UmtDNA) as a marker of kidney injury in patients with AKI with various causes. [107][108][109][110] Currently, because of diverse patient cohorts, and small sample sizes with type 2 statistical error, the utility of UmtDNA is unclear. Hu et al 110 reported that UmtDNA identified renal dysfunction and mitochondrial damage in sepsis-induced AKI.…”

Serbest Mitokondriyal Dna nın Sistemik Dolaşımdaki Rolü Ve Hastalıkların Patogenezine Etkisi

“…Normal fizyolojik koşullarda mitokondri matriksinde bulunan mtDNA'nın, bazı durumlarda organelden sitoplazmaya ve buradan da hücre dışı matrise sızarak kan, idrar, tükürük, eklem sıvısı, beyin-omurilik sıvısı gibi çeşitli vücut sıvılarına katıldığı daha önce yapılmış olan çeşitli çalışmalarda ifade edilmiştir (7,(23)(24)(25)(26). Vücut sıvılarında bulunan organel DNA'sı, serbest mtDNA (circulating cell-free mtDNA/ccf-mtDNA) olarak adlandırılmaktadır.…”

Mitochondrial mechanisms and therapeutics in ischaemia reperfusion injury

“…Increased plasma mtDNA levels can be found in murine models of AKI and have been shown to be linked to an elevated innate immune response via activation of the TLR9 pathway [ 68 ]. In addition to its detection in the circulation, mtDNA can also be detected in the urine and levels have been shown to be significantly increased in the urine of patients after AKI [ 69 – 72 ]. The recognition that the kidney has a role in the clearance of DAMPs from plasma and the efficacy of dialysis in decreasing the amount of circulating mtDNA in patients may have future implications for our understanding of the pathogenesis of IR injury in AKI and the role of dialysis in managing IR injury [ 73 – 75 ].…”