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Abstract: PO1134

Association Between Nrf2 and CDKN2A Expression in Patients with ESRD: A Pilot Study

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Sumida, Keiichi, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Han, Zhongji, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Dashputre, Ankur A., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Potukuchi, Praveen Kumar, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Chiu, Chi-Yang, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Kovesdy, Csaba P., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
Background

Patients with ESRD display phenotypic features of premature biological aging, characterized by disproportionately high morbidity and mortality at a younger age. Nuclear factor erythroid 2-related factor 2 (Nrf2) activity, a master regulator of antioxidative responses, declines with age and is implicated in the pathogenesis of age-related disorders; however, little is known about the association between Nrf2 and premature biological aging in ESRD patients.

Methods

In a cross-sectional pilot cohort of 34 ESRD patients receiving maintenance hemodialysis, we measured the expression of Nrf2 and cyclin-dependent kinase inhibitor 2A (CDKN2A, or p16INK4a, a biomarker of biological aging) genes in whole blood and examined the association of Nrf2 with CDKN2A expression and with chronological age, using Spearman’s rank correlation and multivariable linear regression models with adjustment for chronological age, gender, race, and diabetes status.

Results

The mean (SD) age was 62.6 (9.8) years old; 52.9% of patients were male; 70.6% were African American; and 70.6% were diabetic. There was a significant negative correlation between Nrf2 and CDKN2A expression (rho=-0.51, P=0.002; Figure); while no significant correlation was found between Nrf2 expression and chronological age (rho=-0.02, P=0.91). After multivariable adjustment, Nrf2 expression remained significantly and negatively associated with CDKN2A expression (β coefficient=-0.0151, P=0.01).

Conclusion

Lower Nrf2 expression levels were significantly and negatively associated with higher CDKN2A expression levels in whole blood of patients with ESRD, independent of chronological age. Our findings suggest a potential contribution of Nrf2 dysfunction to the development of premature biological aging and its related morbidities in ESRD patients.