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Abstract: TH-OR03

Associations of Blood Mitochondrial DNA Copy Number With Risk of AKI After Cardiac Surgery

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology‚ Risk Factors‚ and Prevention

Authors

  • Jotwani, Vasantha, University of California San Francisco, San Francisco, California, United States
  • Thiessen Philbrook, Heather, Johns Hopkins University, Baltimore, Maryland, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • Arking, Dan, Johns Hopkins University, Baltimore, Maryland, United States
  • Ix, Joachim H., University of California San Diego, La Jolla, California, United States
  • Tranah, Gregory J., California Pacific Medical Center, San Francisco, California, United States
  • Waikar, Sushrut S., Boston University, Boston, Massachusetts, United States
  • Parikh, Samir M., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Sarnak, Mark J., Tufts University, Medford, Massachusetts, United States
  • Shlipak, Michael, University of California San Francisco, San Francisco, California, United States
  • Parikh, Chirag R., Johns Hopkins University, Baltimore, Maryland, United States
Background

Mitochondria are necessary for recovery from ischemia-reperfusion injury due to their critical roles in oxidative phosphorylation. Mitochondrial DNA copy number (mtDNA-CN) is an indirect marker of mitochondrial abundance that has been used to quantify the number of mitochondrial genomes per cell. Prior epidemiologic studies have associated higher blood mtDNA-CN with reduced risks of chronic kidney disease and mortality, but to our knowledge no study has examined risk of acute kidney injury (AKI).

Methods

Among 628 adults undergoing cardiac surgery, mtDNA-CN was quantified in pre-operative blood buffy coat specimens using multiplexed SYBR Green-based qPCR. AKI was defined as >50% increase in serum creatinine or need for dialysis following surgery. Subclinical AKI was defined by the highest quintiles of urine interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), and chitinase-3-like-protein-1 (YKL-40) on the first post-operative day among those without clinical AKI. Multivariable logistic regression models were used to evaluate associations of mtDNA-CN with clinical and subclinical AKI.

Results

The mean age was 73±9 years and mean pre-operative eGFR was 72±18 ml/min/1.73m2. Each SD higher mtDNA-CN was associated with about a 38% lower risk of AKI (Table) in both unadjusted and multivariable adjusted models. There were no significant associations of mtDNA-CN with subclinical AKI, as defined by urinary levels of IL-18, KIM-1, MCP-1, or YKL-40.

Conclusion

Among adults undergoing cardiac surgery, higher pre-operative mtDNA-CN was associated with reduced risk of AKI but not with urinary biomarkers of tubular injury. MtDNA-CN may reflect kidney energetic reserve that promotes defense against acute ischemic stress.

Funding

  • NIDDK Support