Age-Related Autonomous Aldosterone Production

Presentation Number: OR10-1
Date of Presentation: April 3rd, 2017

Kazutaka Nanba*1, Anand Vaidya2, Gordon H Williams2, Isabel Zheng1, Tobias Else1 and William E. Rainey3
1University of Michigan, Ann Arbor, MI, 2Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 3The University of Michigan, Ann Arbor, MI

Abstract

Background:Both aging and inappropriate secretion of aldosterone increase the risk for developing cardiovascular disease; however, the influence of aging on aldosterone secretion and physiology is not well understood.

Objective: To investigate the hypothesis that aging is associated with autonomous renin-independent aldosterone production by evaluating patterns of adrenal aldosterone synthase (CYP11B2) expression, and circulating renin and aldosterone physiology, over a wide range of age.

Methods: The relationship between age and adrenal CYP11B2 expression was evaluated in 112 normal adrenals from kidney donors (age 0-68y). Following immunohistochemistry, CYP11B2 expressing area and area of abnormal foci of CYP11B2 expressing cells called aldosterone-producing cell clusters (APCC) were analyzed using ImageJ software. In a separate clinical study of 677 participants without primary aldosteronism, who were studied on both high and restricted sodium diets (age 18-71y), we used multivariable linear regression to assess the independent associations between age and renin-angiotensin-aldosterone system physiology.

Results:In adrenal tissue, continuous CYP11B2 expression in zona glomerulosa was more frequently observed in young adrenals than that seen in older adrenals, and many older adrenals showed discontinuous or no zona glomerulosa CYP11B2 expression. CYP11B2 expressing area normalized to adrenal cortex was negatively correlated with age (r=−0.454, P<0.0001), whereas the area of APCC normalized to adrenal cortex was positively correlated with age (r=0.367, P<0.0001). The ratio of APCC to normal CYP11B2 expressing area was also positively correlated with age (r=0.584, P<0.0001). When human participants were studied on a high sodium balance, older age was independently associated with a higher aldosterone-to-renin ratio (adjusted β=+0.554 units per 10 years, P<0.001), a finding that was determined by the lack of aldosterone suppression with aging, even though renin activity progressively declined. In contrast, when the same participants were sodium restricted, physiologic stimulation of aldosterone was blunted with older age (β=−4.6 ng/dL per 10 years, P<0.0001).

Conclusion: Aging is associated with a pattern of decreased zona glomerulosa CYP11B2 expression and increased APCC expression. This histopathologic finding parallels the age-related renin-independent aldosteronism and abnormal aldosterone physiology observed in this study and provides one potential explanation for age-related cardiovascular risk.

 

Nothing to Disclose: KN, AV, GHW, IZ, TE, WER