THE IMPACT OF CHRONIC ALDOSTERONISM ON URINARY SODIUM-TO-POTASSIUM RATIO

Objective: Urinary sodium-to-potassium ratio (UNa/K), as a measure of their respective intake, is a recognized predictor of incident hypertension and overt cardiovascular-kidney-metabolic disease (CKMd). Primary Aldosteronism (PA), the most common cause of secondary hypertension, is characterized by retention of sodium and loss of potassium. We hypothesized that cure of PA would lead to an increase in UNaK, even at steady-state. Design and method: We recruited consecutive patients with post-surgical confirmation of unilateral PA, with complete blood and 24 h urinary biochemical data available at diagnosis, 1 month and 6 months after curative adrenalectomy. More than 6 weeks prior to testing, all confounding medications were discontinued and KCl supplements were provided as needed, in case of hypokalemia at diagnosis. ANOVA (mixed effect analysis), with post-hoc Dunnett test, was used to compare values of UNa/K and its determinants at different timepoints; uni- and multivariable regression analysis identified predictors of changes in UNa/K. Results: All 22 patients (s-Aldosterone: 23.6 [16.4-36.0] pmol/L; ARR: 86.0 [48.2-130.7] ng/mIU; sK+: 3.5±0.3 mmol/L, 24h-urinary Na+ and K+ excretion: 170±47 mmol/d and 108±41, respectively; UNa/K: 1.48 [1.16-2.20]) showed complete biochemical response after adrenalectomy (ARR: 6.7 [5.6-13.2] and 6.5 [2.0-9.9] ng/mIU at 1 and 6 months, respectively). Despite similar Na+ intake, as estimated by its 24 h excretion (p=0.971), UNa/K increased after cure (p<0.001; 2.25[1.79-2.79] and 2.61[2.11-2.89] at 1 and 6 months, p=0.027 and p=0.004 vs diagnosis, respectively), driven by a decrease in K+ fractional and total excretion (p<0.001 for both). The change in K+ excretion at 6 months correlated with mEq of KCL supplementation (rho=0.48; p=0.036), but the latter failed to predict the change in UNa/K (beta=0.005, p=0.194), while (log2) aldosterone at diagnosis did (beta=0.62, p=0.005; R2=0.395). A sensitivity analysis limited to patients who didn’t receive KCL supplementation (n=8) confirmed the findings (UNa/K increase at 6 months, p=0.033; decrease in K+ fractional excretion with cure: p=0.012). Conclusions: In patients with PA, excess aldosterone lowers UNa/K, which increases after cure independent of intake. This may affect the interpretation of UNa/K in all forms of CKMd that feature absolute or relative aldosterone excess.