Dietary effects on blood pressure control in primary aldosteronism using a cardiorenal model

Abstract

Primary aldosteronism (PA) is associated with hypertension (HTN), and these patients have significant lowering of blood pressure (BP) and improved hypokalemia when moving to a DASH dietary intervention (≤65 mEq/day Na+ and ≥120 mEq/day K+). However, current guidelines for PA treatment briefly recommend lowering Na+ intake and make no specific mention of supplementing K+ intake or using DASH in PA. Additionally, high levels of aldosterone increase the risk of developing cardiovascular and chronic kidney disease. However, the impact of DASH diet on hyperkalemia risk and the extent of BP reduction in PA patients with renal dysfunction are unknown. Because continuous monitoring of cardiovascular, neural, and hormonal changes during PA and its treatment cannot be achieved experimentally, we used the mathematical model of human physiology, HumMod, to test the responses to a DASH diet during PA. We hypothesized that both low Na+ and high K+ (DASH) have additive benefits on natriuresis and BP control during PA. We added known renal physiological effects of K+ in HumMod using data from David Young’s work in dogs and further validated the model’s response to changes in Na+ intake based off of chronic salt sensitivity experiments in PA patients. Starting from baseline conditions with normal Na+/K+ intake (150 and 40 mmol/day, respectively), we simulated an aldosterone secreting tumor to gradually increase plasma aldosterone to 20 ng/dL over 3 years. Baseline PA was associated with hypertension (149/85 mmHg), very low endogenous renin and aldosterone secretion, hypokalemia (2.6 mmol/L K+), and tumor aldosterone secretion of 360 μg/day. We simulated a chronic change in dietary intake: 1) Low Na+ diet- Na+ intake fixed at 65 mmol/day with normal K+ intake, 2) High K+ diet - 120 mmol/day K+ intake with normal Na+ intake, or 3) DASH diet- Low Na+ intake and high K+ intake. Lowering Na+ intake without or with high K+ intake (DASH) were associated with lower systolic BP over the first 4 weeks and persisted for 2 years despite continued activation of the renin-angiotensin system and increasing tumor aldosterone secretion. Simulating mineralocorticoid blockade (MCB) was associated with reductions in systolic BP (-17 mmHg), decrease in left ventricular mass, and correction of hypokalemia (~4.0 mmol/L), but BP still remained uncontrolled (134/81 mmHg), partly due to the compensatory increase in renin secretion. Adding DASH to MCB therapy completely normalized BP without inducing hyperkalemia (4.8 mmol/L). Simulating chronic kidney disease by reducing nephron number in the model amplified BP sensitivity to changes in both Na+ and K+ but increased plasma K+ near the hyperkalemic range. These current simulations may help better understand the sequence of physiological events in PA and yield new insights into its diagnosis and management in patients with different baseline renal function. The physiological effects of the DASH diet desperately need to be tested in patients with PA with various baseline renal function as our simulations suggest beneficial effects beyond current treatment guidelines. Supported by the National Institute on Minority Health and Health Disparities (R00 MD014738). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.