Considering the amount of novel knowledge generated in the last five years, a team of experienced hypertensionlogists was assembled to furnish updated clinical practice guidelines for the management of primary aldosteronism. To identify the most relevant studies, the authors utilized a systematic literature review in international databases by applying the PICO strategy, and then they were required to make use of only those meeting predefined quality criteria. For studies of diagnostic tests, only those that fulfilled the Standards for Reporting of Diagnostic Accuracy recommendations were considered. Each section was jointly prepared by at least two co-authors, who provided Class of Recommendation and Level of Evidence following the American Heart Association methodology. The guidelines were sponsored by the Italian Society of Arterial Hypertension and underwent two rounds of revision, eventually reexamined by an External Committee. They were presented and thoroughly discussed in two face-to-face meetings with all co-authors and then presented on occasion of the 36th Italian Society of Arterial Hypertension meeting in order to gather further feedbacks by all members. The text amended according to these feedbacks was subjected to a further peer review. After this process, substantial updated information was generated, which could simplify the diagnosis of primary aldosteronism and assist practicing physicians in optimizing treatment and follow-up of patients with one of the most common curable causes of arterial hypertension.

A blood pressure (BP)-independent metabolic shift towards a catabolic state upon high sodium (Na⁺) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. We sought to investigate the real-life impact of high Na⁺ intake on measures of renal Na⁺/water handling and metabolic signatures, as surrogates for cardiovascular risk, in hypertensive patients. We analysed clinical and biochemical data from 766 consecutive patients with essential hypertension, collected at the time of screening for secondary causes. The systematic screening protocol included 24 h urine (24 h-u-) collection on usual diet and avoidance of renin–angiotensin–aldosterone system-confounding medications. Urinary 24 h-Na⁺ excretion, used to define classes of Na⁺ intake (low ≤2.3 g/day; medium 2.3–5 g/day; high >5 g/day), was an independent predictor of glomerular filtration rate after correction for age, sex, BP, BMI, aldosterone, and potassium excretion [P = 0.001; low: 94.1 (69.9–118.8) vs. high: 127.5 (108.3–147.8) mL/min/1.73 m²]. Renal Na⁺ and water handling diverged, with higher fractional excretion of Na⁺ and lower fractional excretion of water in those with evidence of high Na⁺ intake [FE_Na: low 0.39% (0.30–0.47) vs. high 0.81% (0.73–0.98), P < 0.001; FE_water: low 1.13% (0.73–1.72) vs. high 0.89% (0.69–1.12), P = 0.015]. Despite higher FE_Na, these patients showed higher absolute 24 h Na⁺ reabsorption and higher associated tubular energy expenditure, estimated by tubular Na⁺/ATP stoichiometry, accordingly [Δhigh–low = 18 (12–24) kcal/day, P < 0.001]. At non-targeted liquid chromatography/mass spectrometry plasma metabolomics in an unselected subcohort (n = 67), metabolites which were more abundant in high versus low Na⁺ intake (P < 0.05) mostly entailed intermediates or end products of protein catabolism/urea cycle. When exposed to high Na⁺ intake, kidneys dissociate Na⁺ and water handling. In hypertensive patients, this comes at the cost of higher glomerular filtration rate, increased tubular energy expenditure, and protein catabolism from endogenous (muscle) or excess exogenous (dietary) sources. Glomerular hyperfiltration and the metabolic shift may have broad implications on global cardiovascular risk independent of BP.