Abstract: FR-PO1157
Associations of Blood Mitochondrial DNA Quality and Quantity with Risk of CKD
Session Information
- CKD: Screening, Diagnosis, Serum and Urine Biomarkers, and Scoring Indices
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Eswarappa, Meghana, University of California San Francisco, San Francisco, California, United States
- Katz, Ronit, University of Washington, Seattle, Washington, United States
- Arking, Dan, Johns Hopkins Medicine McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, United States
- Shi, Wen, Johns Hopkins Medicine McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, United States
- Newcomb, Charles, Johns Hopkins Medicine McKusick-Nathans Institute of Genetic Medicine, Baltimore, Maryland, United States
- Tranah, Gregory J., California Pacific Medical Center Research Institute, San Francisco, California, United States
- Ix, Joachim H., University of California San Diego, La Jolla, California, United States
- Parikh, Chirag R., The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Cummings, Steven, California Pacific Medical Center Research Institute, San Francisco, California, United States
- Waikar, Sushrut S., Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, United States
- Parikh, Samir M., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States
- Shlipak, Michael, University of California San Francisco, San Francisco, California, United States
- Jotwani, Vasantha, University of California San Francisco, San Francisco, California, United States
Background
We evaluated the concurrent effects of the age-associated accumulation of somatic mutations in mitochondrial DNA (mtDNA), termed heteroplasmy, and mtDNA copy number, a marker of systemic mitochondria quantity, on chronic kidney disease (CKD) incidence.
Methods
We conducted a case-cohort study among community-living participants of the Health, Aging, and Body Composition study (Health ABC). A random sub-cohort of 502 participants was selected at baseline. We identified 157 cases of incident CKD, defined as a 40% or greater decline in eGFR to less than 60 ml/min/1.73m2 over 10 years of follow-up, including 30 cases from within the sub-cohort. MtDNA heteroplasmy and copy number were quantified from peripheral blood buffy coat specimens at baseline. Modified Cox regression evaluated the associations between three mtDNA exposure variables (a weighted heteroplasmy measure termed modified mitochondrial local constraint score sum [mMSS]; total heteroplasmy count; and copy number) and incident CKD.
Results
Among 480 participants in the random sub-cohort with quality-controlled mtDNA measures, the mean age was 74±3, 49% were female, and the mean baseline eGFR was 73±18 mL/min/1.73m2. In analyses adjusted for baseline eGFR, urine albumin-to-creatinine ratio, and CKD risk factors, each standard deviation (SD) higher mMSS was associated with a 1.23-fold (95%CI 1.02, 1.49) hazard of incident CKD, and a mMSS score >0.5 compared to 0 was associated with a 2.47-fold (95%CI 1.12, 5.48) hazard of incident CKD. There were no significant associations between mtDNA heteroplasmy count (HR 1.10 (95% CI 0.95, 1.27) per SD higher) or copy number (HR 0.93 (95% CI 0.75, 1.15) per SD higher) with incident CKD.
Conclusion
In an older community-dwelling cohort, a weighted measure of mtDNA heteroplasmy was associated with a higher risk of incident CKD.
Associations of mtDNA mMSS with Incident CKD in Health ABC
| mtDNA mMSS | No. at Risk | No. Events | Unadjusted HR (95% CI) | Adjusted HR (95% CI) |
| Continuous (per SD) | 496 | 153 | 1.26 (1.05, 1.53) | 1.23 (1.02, 1.49) |
| Groups | ||||
| =0 | 376 | 106 | 1.00 (ref) | 1.00 (ref) |
| 0 < mMSS ≤ 0.5 | 87 | 34 | 1.26 (0.76, 2.08) | 1.28 (0.75, 2.21) |
| > 0.5 | 33 | 13 | 2.65 (1.19, 5.90) | 2.47 (1.12, 5.48) |
| Incident CKD was defined by eGFR <60 ml/min/1.73m2 & 40% eGFR decline in persons with baseline eGFR >60 ml/min/1.73m2. The model was adjusted for age, sex, race, smoking, baseline eGFR, urine albumin-to-creatinine ratio, hypertension, diabetes, cardiovascular disease, systolic blood pressure, and body mass index. Abbreviations: mtDNA = mitochondrial DNA; mMSS = modified mitochondrial local constraint score sum; CKD = chronic kidney disease; Health ABC = Health, Aging, and Body Composition Study; SD = standard deviation | ||||
Funding
- Other NIH Support