Association of Blood Mitochondrial DNA Copy Number With Risk of Acute Kidney Injury After Cardiac Surgery

Acute kidney injury (AKI) is a common complication of cardiac surgery and its occurrence is associated with increased risk of all-cause mortality, adverse cardiovascular outcomes, and chronic kidney disease (CKD). 1 Coca S.G. Yusuf B. Shlipak M.G. Garg A.X. Parikh C.R. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2009; 53: 961-973https://doi.org/10.1053/j.ajkd.2008.11.034 Abstract Full Text Full Text PDF PubMed Scopus (895) Google Scholar Mitochondria are essential for healthy function of the kidneys due to their roles in oxidative phosphorylation, reactive oxygen species generation, and programmed cell death. 2 Che R. Yuan Y. Huang S. Zhang A. Mitochondrial dysfunction in the pathophysiology of renal diseases. American journal of physiology Renal physiology. Feb 15 2014; 306: F367-F378https://doi.org/10.1152/ajprenal.00571.2013 Crossref PubMed Scopus (303) Google Scholar Experimental evidence suggests that mitochondrial dysfunction is a key contributor to the pathophysiology of acute kidney injury (AKI) and that replenishment of mitochondrial stores is necessary for recovery from AKI, 3 Emma F. Montini G. Parikh S.M. Salviati L. Mitochondrial dysfunction in inherited renal disease and acute kidney injury. Nat Rev Nephrol. May 2016; 12: 267-280https://doi.org/10.1038/nrneph.2015.214 Crossref PubMed Scopus (263) Google Scholar , 4 Tran M. Tam D. Bardia A. et al. PGC-1alpha promotes recovery after acute kidney injury during systemic inflammation in mice. The Journal of clinical investigation. Oct 2011; 121: 4003-4014https://doi.org/10.1172/JCI58662 Crossref PubMed Scopus (384) Google Scholar , 5 Tran M.T. Zsengeller Z.K. Berg A.H. et al. PGC1alpha drives NAD biosynthesis linking oxidative metabolism to renal protection. Nature. Mar 24 2016; 531: 528-532https://doi.org/10.1038/nature17184 Crossref PubMed Scopus (370) Google Scholar but limited data exist in humans. Mitochondrial DNA copy number (mtDNA-CN) is an indirect marker of mitochondrial abundance that quantifies the number of mitochondrial genomes per cell. Recent studies have reported that higher blood mtDNA-CN is associated with reduced risks of chronic kidney disease (CKD), cardiovascular disease (CVD), and mortality, 6 Tin A. Grams M.E. Ashar F.N. et al. Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study. Journal of the American Society of Nephrology : JASN. Aug 2016; 27: 2467-2473https://doi.org/10.1681/ASN.2015060661 Crossref PubMed Scopus (94) Google Scholar , 7 Ashar F.N. Moes A. Moore A.Z. et al. Association of mitochondrial DNA levels with frailty and all-cause mortality. J Mol Med (Berl). Feb 2015; 93: 177-186https://doi.org/10.1007/s00109-014-1233-3 Crossref PubMed Scopus (155) Google Scholar , 8 Ashar F.N. Zhang Y. Longchamps R.J. et al. Association of Mitochondrial DNA Copy Number With Cardiovascular Disease. JAMA Cardiol. Nov 1 2017; 2: 1247-1255https://doi.org/10.1001/jamacardio.2017.3683 Crossref PubMed Scopus (176) Google Scholar , 9 He W.J. Li C. Huang Z. et al. Association of Mitochondrial DNA Copy Number with Risk of Progression of Kidney Disease. Clinical journal of the American Society of Nephrology : CJASN. Jul 2022; 17: 966-975https://doi.org/10.2215/CJN.15551121 Crossref PubMed Scopus (12) Google Scholar but no prior study has investigated associations with AKI. We hypothesized that mitochondrial quantity, assessed by mtDNA-CN, might indicate resilience from acute ischemic stress.