Research Paper Volume 12, Issue 16 pp 16357—16367
Association between Nrf2 and CDKN2A expression in patients with end-stage renal disease: a pilot study
- 1 Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
- 2 Institute for Health Outcomes and Policy, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA
- 3 Nephrology Section, Memphis VA Medical Center, Memphis, TN 38104, USA
Received: May 13, 2020 Accepted: June 29, 2020 Published: July 13, 2020https://doi.org/10.18632/aging.103685
How to Cite
Copyright © 2020 Sumida et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Patients with end-stage renal disease (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. 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, using Spearman’s rank correlation and multivariable linear regression models with adjustment for potential confounders. There was a significant negative correlation between Nrf2 and CDKN2A expression (rho=-0.51, P=0.002); 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=-1.51, P=0.01), independent of chronological age, gender, race, and diabetes status. These findings suggest a potential contribution of Nrf2 dysfunction to the development of premature biological aging and its related morbidities in ESRD patients.