pubmed.ncbi.nlm.nih.gov

Association between Nrf2 and CDKN2A expression in patients with end-stage renal disease: a pilot study - PubMed

  • ️Wed Jan 01 2020

Association between Nrf2 and CDKN2A expression in patients with end-stage renal disease: a pilot study

Keiichi Sumida et al. Aging (Albany NY). 2020.

Abstract

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.

Keywords: CDKN2A; Nrf2; aging; end-stage renal disease; inflammation.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST: None of the authors have relevant conflicts of interest.

Figures

Figure 1
Figure 1

Correlation between Nrf2 and CDKN2A expression levels in 34 HD patients. Abbreviation: CDKN2A = cyclin dependent kinase inhibitor 2A, Nrf2 = nuclear factor erythroid 2 related factor 2, RQ = relative quantity.

Figure 2
Figure 2

Correlation between Nrf2 expression level and chronological age in 34 HD patients. Abbreviation: Nrf2 = nuclear factor erythroid 2 related factor 2, RQ = relative quantity.

Similar articles

Cited by

References

    1. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004; 351:1296–305. 10.1056/NEJMoa041031 - DOI - PubMed
    1. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998; 32:S112–19. 10.1053/ajkd.1998.v32.pm9820470 - DOI - PubMed
    1. Kooman JP, Kotanko P, Schols AM, Shiels PG, Stenvinkel P. Chronic kidney disease and premature ageing. Nat Rev Nephrol. 2014; 10:732–42. 10.1038/nrneph.2014.185 - DOI - PubMed
    1. Margolick JB, Ferrucci L. Accelerating aging research: how can we measure the rate of biologic aging? Exp Gerontol. 2015; 64:78–80. 10.1016/j.exger.2015.02.009 - DOI - PMC - PubMed
    1. Kooman JP, Dekker MJ, Usvyat LA, Kotanko P, van der Sande FM, Schalkwijk CG, Shiels PG, Stenvinkel P. Inflammation and premature aging in advanced chronic kidney disease. Am J Physiol Renal Physiol. 2017; 313:F938–50. 10.1152/ajprenal.00256.2017 - DOI - PubMed

MeSH terms

Substances