Sodium and potassium renal balance in chronic aldosteronism.

Introduction 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). The pathophysiology of Primary Aldosteronism (PA), the most common cause of secondary hypertension, is known to imply retention of sodium and loss of potassium, but at “steady-state” their excretion should still match the intake. Aim We set out to test the hypothesis that chronic aldosteronism disrupts this balance, by exploring UNa/K and the renal handling of its determinants in the reversible model offered by PA, before and after its cure. Materials and methods We recruited 20 consecutive patients with unilateral PA, who had comprehensive blood and 24h urinary biochemical data available at diagnosis, 1 month and 6 months after adrenalectomy. Confounding medications were discontinued prior to testing and KCl supplements were provided as needed to correct hypokalaemia, without any additional dietary instruction. ANOVA/mixed effect analysis, with adequate post-hoc tests, 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. An independent cohort, including consecutive patients with a conclusive diagnosis of PA or primary (essential) hypertension (n=76 and 766, respectively), served for validation and exploration of relevant clinical covariates. Results All 20 PA patients (ARR: 89.6 [52.4-133.6] ng/mIU; UNa/K: 1.48 [1.21-1.98]) experienced biochemical cure after surgery (ARR: 7.9 [5.8-16.0] and 7.0 [3.1-12.2] ng/mIU at 1 and 6 months, respectively). Despite similar Na+ intake, as estimated by its 24h excretion (p=0.307), UNa/K increased after cure (p<0.001; 2.25 [1.79-2.79] and 2.50 [2.17-2.88] at 1 and 6 months, p=0.002 and <0.001 vs diagnosis, respectively), due to a decrease in K+ fractional and total excretion (p<0.001 for both). The change in total K+ excretion at 6 months correlated with mEq of KCl supplementation at diagnosis (ρ=0.708; p < 0.001), but the latter failed to predict the change in UNa/K (β = 0.007, p = 0.082), while (log2) aldosterone at diagnosis did (β = 1.932, p = 0.002; adjusted R2 = 0.379) at uni- and multivariable regression analysis. A sensitivity analysis limited to patients who didn’t receive KCl supplementation (n=9) confirmed the findings (UNa/K increase at 6 months, p=0.038; decrease in K+ fractional excretion with cure: p = 0.031). In the larger validation cohort of hypertensive patients, aldosterone independently predicted UNa/K (β=-0.142, p<0.001), along with age, sex and BMI (R2 = 0.107 for the whole model); results were consistent when the analysis was limited to patients who did not receive KCl supplementation or only to patients with essential hypertension. Discussion Excess aldosterone, in hypertensive patients with either PA or essential hypertension, independently lowers UNa/K. This may affect the interpretation of UNa/K for prediction of cardiovascular and renal outcomes, and highlight a chronic K+-wasting state, in all forms of CKMd that feature absolute or relative aldosteronism.