Disentangling the relationships between the renin-angiotensin-aldosterone system, calcium physiology, and risk for kidney stones

Abstract

Context: Complex relationships between aldosterone and calcium homeostasis have beenproposed.Objective: To disentangle the influence of aldosterone and intravascular volume on calciumphysiology.Design: Patient-oriented and epidemiology studies.Setting: Clinical research center and nationwide cohorts.Participants/Interventions: Patient-oriented study (n = 18): Participants were evaluatedafter completing a sodium-restricted (RES) diet to contract intravascular volume and after aliberalized-sodium (LIB) diet to expand intravascular volume. Cross-sectional studies (n = 3755):the association between 24h urinary sodium and calcium excretion and risk for kidney stoneswas assessed.Results: Patient-oriented study: compared to a RES-diet, a LIB-diet suppressed renin activity(LIB: 0.3 [0.1, 0.4] vs. RES: 3.1 [1.7, 5.3] ng/mL/h; P < 0.001) and plasma aldosterone (LIB: 2.0[2.0, 2.7] vs. RES: 20.0 [16.1, 31.0] vs. ng/dL; P < 0.001), but increased calciuria (LIB: 238.4 ± 112.3vs. RES: 112.9 ± 60.8 mg/24hr; P < 0.0001) and decreased serum calcium (LIB: 8.9 ± 0.3 vs. RES:9.8 ± 0.4 mg/dL; P < 0.0001). Epidemiology study: mean urinary calcium excretion was higher withgreater urinary sodium excretion. Compared to a urinary sodium excretion of < 120 mEq/day, aurinary sodium excretion of =220 mEq/day was associated with a higher risk for having kidneystones in women (risk ratio = 1.79 [95% confidence interval 1.05, 3.04]) and men (risk ratio = 2.06[95% confidence interval 1.27, 3.32]).Conclusions: High dietary sodium intake suppresses aldosterone, decreases serum calcium, andincreases calciuria and the risk for developing kidney stones. Our findings help disentanglethe influences of volume from aldosterone on calcium homeostasis and provide support forthe recommendation to restrict dietary sodium for kidney stone prevention.