The Influence of Aldosterone and Dietary Sodium on Calcium and Parathyroid Hormone Homeostasis

Presentation Number: SUN 504
Date of Presentation: April 2nd, 2017

Sarah Zaheer*1, Kiara Taquechel2, Jenifer Michelle Brown3, Jonathan S Williams4 and Anand Vaidya1
1Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 2Northeastern University, Boston, MA, 3Brigham and Women's Hospital, Harvard Medical School, MA, 4Brigham & Women's Hospital, Harvard Medical School, Boston, MA

Abstract

CONTEXT: Excess mineralocorticoid receptor (MR) activation in primary aldosteronism (PA) results in intravascular volume expansion. PA is also associated with higher urinary calcium excretion and parathyroid hormone (PTH) levels; effects that have often been ascribed to hyperaldosteronism.

OBJECTIVE: To investigate whether the influence of aldosterone on calcium and PTH regulation is mediated via modulation of intravascular volume homeostasis and/or other interactions with the MR.

METHODS: Eighteen subjects with type 2 diabetes and normal kidney function were evaluated in a clinical research center after completing 1 week of a sodium restricted diet (<50 mmol/d) (RES) to induce contraction of intravascular volume and stimulation of aldosterone, followed by 1 week of a liberalized sodium diet (>150 mmol/d) (LIB) to induce expansion of intravascular volume and suppression of aldosterone. Subjects also received an infusion of angiotensin II (AngII) (1 ng/kg/min for 45 mins) during the LIB intervention. Serum and ionized calcium, PTH, vitamin D metabolites, plasma renin activity (PRA), serum aldosterone, and urinary calcium and aldosterone excretion were measured before and after each intervention. Paired t-tests were used to analyze differences in means.

RESULTS: As expected, LIB resulted in higher urinary sodium excretion (295 vs. 20 mmol, P<0.0001) and a trend towards higher systolic blood pressure (128.78 vs. 123.31, P=0.11) compared to RES. Plasma renin activity (PRA) and serum aldosterone were suppressed on LIB and stimulated on RES (PRA=0.3 vs. 3.1 ng/mL*h, P<0.0001; aldosterone=3.7 vs. 24.9 ng/dL; P<0.0001). In conjunction with these changes, serum calcium concentrations were significantly lower during LIB compared to RES (8.9 vs. 9.8 mg/dL, P<0.0001), and 24h urinary calcium excretion was significantly higher during LIB when compared to RES (231.2 vs. 112.9 mg/24hr, P=0.0002). Despite lower serum calcium and higher urinary calcium excretion on LIB, PTH did not increase when compared to RES (35.2 vs. 40.6 pg/mL, P=0.26). When participants received an infusion of AngII, PTH and serum aldosterone levels acutely increased (PTH∆: +6.3 pg/mL, P=0.04; aldosterone∆: +7.4 ng/dL, P<0.0001); however, ionized calcium did not change (iCa∆: -0.01 mmol/L, P=0.22).

CONCLUSION: Herein, we disentangled intravascular volume status from aldosterone activity using dietary sodium interventions. We observed that volume expansion increased calciuria and decreased serum calcium, in a manner that was independent of aldosterone and PTH. Further, acutely increasing aldosterone with an infusion of AngII increased PTH in a calcium-independent manner. These physiologic observations suggest that the hypercalciuria seen in PA may be a manifestation of volume expansion and hyperfiltration alone, whereas high PTH levels in PA appear to be independent of calcium and volume homeostasis.

 

Nothing to Disclose: SZ, KT, JMB, JSW, AV