Kidney Week

Abstract: TH-PO1023

Associations of Epigenetic Age Acceleration and Kidney Function in the Bogalusa Heart Study

Session Information

• CKD: Epidemiology, Risk Factors, and Prevention - 1
  October 24, 2024 | 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

• Kirkpatrick, Brenna J., University of Illinois Chicago College of Medicine, Chicago, Illinois, United States

Brenna J. Kirkpatrick

• Kelly, Tanika, University of Illinois Chicago College of Medicine, Chicago, Illinois, United States

Tanika Kelly, PhD, MPH

• Li, Changwei, Tulane University, New Orleans, Louisiana, United States

Changwei Li, MD, PhD, MPH

• Lash, James P., University of Illinois Chicago College of Medicine, Chicago, Illinois, United States

James P. Lash, MD, FASN

Background

Chronic kidney disease (CKD) is an age-related condition associated with significant morbidity and mortality that affects approximately 14% of the US population. As the average age in the US increases, it is critical to identify factors that may predispose individuals to heightened risk of kidney dysfunction. Epigenetic age acceleration (EAA), defined as the difference between chronological age and a composite DNA methylation-derived age, has emerged as a robust predictor of numerous health conditions. Multiple EAA measures have been validated, each with its own physiologic implications. We hypothesized that accelerated epigenetic aging is associated with baseline kidney function and its prospective decline in the Bogalusa Heart Study (BHS).

Methods

We examined associations between four EAA measures (intrinsic EAA [IEAA], extrinsic EAA [EEAA], PhenoAA, and GrimAA) and kidney function in BHS, a longitudinal, prospective study aimed at characterizing cardiometabolic risk factors across the lifespan. Kidney function was assessed as estimated glomerular filtration rate (eGFR), calculated using the race-free CKD-EPI creatinine-based equation. Multiple logistic regression was used to examine cross-sectional associations of EAA with the discrete reduced kidney function outcome (eGFR < 60 mL/min/1.73 m²) at the most recent study visit (N=1,249). For participants with repeated kidney function measurements, multiple logistic mixed effects models were used to assess associations of baseline EAA and progression to the reduced kidney function outcome (N=965). Cross-lagged panel models were constructed to examine directionality of associations between EAA and kidney function at two time points (N=676).

Results

At baseline, each standard deviation increase in EEAA, GrimAA, and PhenoAA conferred significant 1.73, 1.55, and 1.46 increased odds of reduced kidney function, respectively (P=2.11 X 10-3, 0.04, 0.03, respectively). Likewise baseline EEAA and GrimAA were prospectively associated with 2.03 and 3.50 increased odds of incident kidney function decline (P=0.02 and 2.88 X 10-3, respectively). Path coefficients from baseline EEAA and GrimAA to follow-up eGFR were statistically significant.

Conclusion

Our findings implicate accelerated epigenetic aging as a novel predictor of kidney function decline.

Funding

• Other NIH Support