Unrecognized Autonomous Aldosterone Secretion Characterized By Stimulated Renin Phenotypes

Presentation Number: SUN 519
Date of Presentation: April 2nd, 2017

Gregory Hundemer*1, Rene Baudrand2, Jenifer Michelle Brown3, Gary Curhan4, Gordon H Williams1 and Anand Vaidya1
1Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 2Pontificia Universidad Catolica de Chile, Santiago, Chile, 3Brigham and Women's Hospital, Harvard Medical School, MA, 4Brigham and Women's Hospital, Harvard Medical School

Abstract

Context: Primary aldosteronism (PA) is characterized by renin-independent aldosteronism and excess mineralocorticoid receptor (MR) activation. Mild cases of autonomous aldosterone secretion may go unrecognized using current diagnostic criteria for PA. We previously reported that sodium restriction stimulates renin in mild cases of PA, whereas renin remains suppressed in severe cases of PA.

Objective: To investigate the hypothesis that the inability to stimulate renin serves as a biomarker for unrecognized autonomous aldosterone secretion and MR activation.

Methods: Cross-sectional study of 663 normotensive and stage I hypertensive participants, who were confirmed to not have PA and were on no antihypertensive medications. Participants had their maximally stimulated plasma renin activity (PRA) measured while standing upright after achieving a sodium balance of <40 mmol/d. Tertiles of maximally stimulated PRA were hypothesized to reflect the degree of MR activation: lowest PRA tertile= “Inappropriate/Excess MR Activity”; middle PRA tertile = “Intermediate MR Activity”; highest PRA tertile= “Physiologic MR Activity”. All participants underwent detailed biochemical and vascular characterizations under conditions of liberalized sodium intake (>150 mmol/d) and associations with stimulated renin phenotypes were performed.

Main Outcome Measures. Aldosterone-to-renin ratio (ARR), urinary aldosterone excretion, blood pressure (BP), renal plasma flow (RPF) measured by para-aminohippurate clearance, and potassium homeostasis.

Results. Participants in the lowest stimulated PRA tertile had the highest ARR (18.7 vs. 12.0 vs. 9.1 ng/dL per ng/mL/h, p < 0.0001), urinary aldosterone excretion rate (8.3 vs. 7.4 vs. 7.0 mcg/24h, p = 0.0009), systolic BP (141 vs. 132 vs. 129 mmHg, p < 0.0001), and the most suppressed PRA when sodium loaded (0.20 vs. 0.32 vs. 0.40 ng/mL/h, p < 0.0001). Further, participants with the lowest stimulated PRA had the highest renovascular dysfunction (RPF: 475 vs. 532 vs. 548 mL/min/1.73m2, p < 0.0001). A non-significant trend suggesting lower serum and higher urinary potassium in the lowest stimulated PRA tertile became significant after stratification by hypertensive status. Normotensives with the lowest stimulated PRA had the highest urinary potassium excretion (81.1 vs. 75.3 vs. 72.1 mmol/L, p = 0.02) and hypertensives with the lowest stimulated PRA had the lowest serum potassium (4.06 vs. 4.14 vs. 4.23 mmol/L, p = 0.0007).

Conclusions. In participants without overt PA, the inability to stimulate renin was associated with higher ARR, urinary aldosterone excretion, BP, and renovascular dysfunction. These observations, in addition to suggestive trends in potassium homeostasis, indicate an extensive spectrum of unrecognized autonomous aldosterone secretion and MR activation that may be identified using renin as a biomarker.

 

Nothing to Disclose: GH, RB, JMB, GC, GHW, AV