Kidney Week

Abstract: TH-OR089

Specific Mitochondrial Genetic Variants Are Associated with Kidney Dysfunction and Injury in Older Adults

Session Information

• Novel Risk Factors for CKD
  October 25, 2018 | Location: 6E, San Diego Convention Center
  Abstract Time: 06:06 PM - 06:18 PM

Category: CKD (Non-Dialysis)

• 1901 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

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

Vasantha Jotwani, MD

• 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, 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,

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

Gregory J. Tranah,

Background

Mitochondrial dysfunction is an important contributor to acute and chronic kidney damage, due to the critical roles of mitochondria for oxidative phosphorylation. Mitochondrial genetic variation has been associated with age-related cardiovascular and functional impairments, but little is known regarding the impact of common inherited mitochondrial DNA (mtDNA) variants on kidney health.

Methods

In this study of 2,728 ambulatory older adults enrolled in the Health, Aging, and Body Composition Study, we evaluated associations of 10 common inherited mtDNA haplotypes and 137 single nucleotide polymorphisms (SNPs) with estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and urine concentrations of kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18). DNA was extracted from blood buffy coat specimens and mtDNA genotype was determined using the Illumuna 1M chip. A total of 60 SNPs with minor allele frequency >=1% were examined for associations with kidney outcomes. All analyses stratified participants by European and African ancestry and adjusted for age, sex, and mitochondrial genetic ancestry.

Results

Among persons of European ancestry (n=1,660), m.10589G>A was associated with lower eGFR (57 vs 71 ml/min/1.73m²; p=0.009) and m.6776T>C was associated with higher ACR (98 vs 29 mg/g; p<0.0001), whereas haplogroup V (1721 vs 1172 pg/ml, p=0.0066) and m.3916G>A (2599 vs 1207 pg/ml, p<0.0001) were each associated with higher urine KIM-1. Among persons of African ancestry (n=1,137), m.15758A>G was associated with higher urine KIM-1 (3476 vs 1074 pg/ml, p<0.0001). There were no statistically significant associations of mtDNA variants with urine IL-18.

Conclusion

Specific inherited mtDNA variants are associated with kidney dysfunction and injury in older adults, suggesting that mitochondrial genetic variability may contribute to risk of kidney disease.

Funding

• NIDDK Support