Abstract | BACKGROUND: METHODS: We isolated DNA from plasma and urine of patients. mtDNA levels were quantified by quantitative PCR. Sepsis patients were divided into no AKI, mild AKI, and severe AKI groups according to RIFLE criteria. Additionally, cecal ligation and puncture (CLP) was established in rats to evaluate the association between UmtDNA and mitochondrial function. RESULTS: A total of 52 (49.5%) developed AKI among enrolled sepsis patients. Increased systemic mtDNA did not correlate with systemic inflammation or acute renal dysfunction in sepsis patients, while AKI did not have an additional effect on circulating mtDNA levels. In contrast, UmtDNA was significantly enriched in severe AKI patients compared with that in the mild AKI or no AKI group, positively correlated with plasma creatinine, urinary neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1, and inversely with the estimated glomerular filtration rate. Additionally, UmtDNA increased in rats following CLP-induced sepsis. UmtDNA was predictive of AKI development and correlated with plasma creatinine and blood urea nitrogen in the rat sepsis model. Finally, the UmtDNA level was inversely correlated with the cortical mtDNA copy number and relative expression of mitochondrial gene in the kidney. CONCLUSION: An elevated UmtDNA level correlates with mitochondrial dysfunction and renal injury in sepsis patients, indicating renal mitochondrial injury induced by sepsis. Therefore, UmtDNA may be regarded as a valuable biomarker for the occurrence of AKI and the development of mitochondria-targeted therapies following sepsis-induced AKI.
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Authors | Qiongyuan Hu, Jianan Ren, Huajian Ren, Jie Wu, Xiuwen Wu, Song Liu, Gefei Wang, Guosheng Gu, Kun Guo, Jieshou Li |
Journal | Oxidative medicine and cellular longevity
(Oxid Med Cell Longev)
Vol. 2018
Pg. 8074936
( 2018)
ISSN: 1942-0994 [Electronic] United States |
PMID | 29682165
(Publication Type: Journal Article)
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Chemical References |
- DNA, Mitochondrial
- RNA, Messenger
- Adenosine Triphosphate
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Topics |
- Acute Kidney Injury
(urine)
- Adenosine Triphosphate
(metabolism)
- Adult
- Animals
- DNA, Mitochondrial
(urine)
- Female
- Glomerular Filtration Rate
(physiology)
- Humans
- Kidney
(metabolism, pathology)
- Male
- Middle Aged
- Pregnancy
- RNA, Messenger
(genetics)
- Rats
- Rats, Sprague-Dawley
- Sepsis
(complications, urine)
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