Kidney Week

Abstract: TH-PO865

Mitochondrial DNA Haplotypes and Risk of CKD and AKI

Session Information

• CKD: Epidemiology, Risk Factors, Prevention - I
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2201 CKD (Non-Dialysis): Epidemiology‚ Risk Factors‚ and Prevention

Authors

• Jotwani, Vasantha, University of California San Francisco, San Francisco, California, United States

Vasantha Jotwani,

• Sarnak, Mark J., Tufts University, Medford, Massachusetts, United States

Mark J. Sarnak,

• Thiessen Philbrook, Heather, Johns Hopkins University, Baltimore, Maryland, United States

Heather Thiessen Philbrook,

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

Ronit Katz,

• Ix, Joachim H., University of California San Diego, La Jolla, California, United States

Joachim H. Ix,

• Waikar, Sushrut S., Boston University, Boston, Massachusetts, United States

Sushrut S. Waikar,

• Parikh, Chirag R., Johns Hopkins University, Baltimore, Maryland, United States

Chirag R. Parikh,

• Tranah, Gregory J., California Pacific Medical Center, San Francisco, California, United States

Gregory J. Tranah,

• Parikh, Samir M., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Samir M. Parikh,

• Shlipak, Michael, University of California San Francisco, San Francisco, California, United States

Michael Shlipak,

• Arking, Dan, Johns Hopkins University, Baltimore, Maryland, United States

Dan Arking,

Background

Experimental models suggest an important role for mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD) and acute kidney injury (AKI), but little is known regarding the impact of mitochondrial genetic variation on kidney health. We evaluated associations of inherited mitochondrial DNA (mtDNA) haplotypes with risk of CKD and AKI in a large population-based cohort.

Methods

Among UK Biobank participants who self-identified as white, we tested eight distinct mtDNA haplotypes (N=379,432) with minor allele frequency >0.5% that were previously identified based on associations with traits associated with mtDNA copy number. Individuals with prevalent end-stage kidney disease were excluded. We used linear and logistic regression models to evaluate associations of these mtDNA haplotypes with estimated glomerular filtration rate by serum creatinine and cystatin C (eGFR, N=362,802), AKI defined by diagnostic codes (N=14,170 cases), and urine albumin/creatinine ratio (ACR, N=114,662).

Results

The mean age was 57±8 years and the mean eGFR was 90±14 ml/min/1.73m². MtDNA haplotype was significantly associated with eGFR (p= 2.84E-12), but not with risk of AKI (p=0.256) or urine ACR (p=0.538). The association of mtDNA haplotype with eGFR remained significant after adjustment for diabetes mellitus and hypertension (p=1.20E-10). When compared to the reference haplotype, mtDNA haplotypes I, IV, and V were each associated with higher eGFR (Table).

Conclusion

Among self-identified white UK Biobank participants, mtDNA haplotype was associated with eGFR, but not with AKI risk or albuminuria.

Funding

• NIDDK Support