Kidney Week

Abstract: SA-PO823

A Pilot Study to Explore Relationships of Mitochondrial DNA Copy Number in Blood and Kidney Tissue and Their Associations with Kidney Health

Session Information

• Molecular Mechanisms of CKD - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1903 CKD (Non-Dialysis): Mechanisms

Authors

• Jotwani, Vasantha, UCSF, San Francisco, California, United States

Vasantha Jotwani,

• Tranah, Gregory J., Sutter Health, San Francisco, California, United States

Gregory J. Tranah,

• Katz, Ronit, University of Washington, Seattle, Washington, United States

Ronit Katz,

• Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States

Mark J. Sarnak,

• Parikh, Chirag R., Yale University and VAMC, New Haven, Connecticut, United States

Chirag R. Parikh,

• Cummings, Steven, San Francisco Coordinating Center, Mill Valley, California, United States

Steven Cummings,

• Ix, Joachim H., UCSD, San Diego, California, United States

Joachim H. Ix,

• Parikh, Samir M., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States

Samir M. Parikh,

• Tin, Adrienne, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Adrienne Tin,

• Arking, Dan, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Dan Arking,

• Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States

Michael Shlipak,

• Waikar, Sushrut S., Harvard Medical School, Boston, Massachusetts, United States

Sushrut S. Waikar,

Background

Despite several animal studies linking mitochondrial damage to the development of acute and chronic kidney injury, human studies have been sparse due to our limited methods for assessment of mitochondrial health by stored specimens. A key question is whether peripheral mitochondrial measures adequately reflect mitochondrial health in kidney tissue. We conducted a pilot study to compare mitochondrial DNA (mtDNA) copy number in blood and kidney tissue and to evaluate their associations with renal function and pathology.

Methods

We measured mtDNA copy number in blood buffy coat and kidney specimens of 9 participants of the Brigham and Women’s Hospital Nephrectomy Cohort who were selected to represent a broad range of age and kidney function. MtDNA copy number was determined by a real-time quantitative PCR assay that measures the ratio of the mtDNA-encoded ND1 gene to the single-copy nuclear β2-Microglobulin gene. Kidney specimens were assessed by a pathologist using a standardized scoring protocol.

Results

The mean age was 64 ± 12 years and mean eGFR was 46 ± 21 ml/min/1.73m². Blood mtDNA copy number (r=0.739, p=0.023) and kidney mtDNA copy number (r=0.883, p=0.002; Figure) correlated strongly with eGFR and with each other (r=0.756, p=0.019). Compared to participants with severe tubulointerstitial fibrosis, participants with mild fibrosis had higher blood and kidney mtDNA copy numbers (p=0.03).

Conclusion

Higher mtDNA copy number, measured in blood or kidney, correlated positively with eGFR and negatively with tubulointerstitial fibrosis, suggesting that mitochondrial abundance is important for kidney health. Strong correlations between mtDNA copy number in blood and kidney tissue support the use of peripheral mitochondrial measures in future studies.

Funding

• NIDDK Support