Biochemical and renal-metabolic profiles distinguishing primary aldosteronism from essential hypertension: a systematic review and meta-analysis with implications for endocrine hypertension screening

Abstract

Introduction To characterize electrolyte and renal-metabolic profiles in primary aldosteronism (PA) compared with essential hypertension (EH), and to examine differences between unilateral/lateralizing and bilateral PA. Methods PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception through 13 July 2026. Random-effects meta-analyses pooled standardized mean differences (SMD; Hedges' g), supplemented by clinical-unit mean-difference analyses, subgroup analyses, sensitivity analyses, and study-level meta-regression. Results A total of 74 observational studies involving 26,143 participants were included. Compared with hypertensive controls, PA was associated with lower serum potassium (SMD = −1.15, 95% CI −1.27 to −1.02), higher serum sodium (SMD = 0.51, 95% CI 0.38 to 0.63), and lower uric acid (SMD = −0.23, 95% CI −0.35 to −0.12), whereas creatinine, estimated glomerular filtration rate (eGFR), and blood urea nitrogen (BUN) did not differ significantly. Corresponding PA-minus-control mean differences were −0.49 mmol/L for potassium, +1.20 mmol/L for sodium, and −20.7 μmol/L for uric acid. Potassium was lower in unilateral/lateralizing than in bilateral PA (SMD = −0.85). The potassium difference versus controls was greater in studies with high plasma aldosterone concentration (PAC) than in those with low PAC (SMD −1.44 vs. −1.03; p for subgroup difference = 0.010), although continuous PAC meta-regression was not significant. UACR/ACR and urinary albumin excretion were higher in PA (SMD = 0.49 and 0.73). Discussion PA shows a persistent electrolyte phenotype and higher albuminuria despite similar cross-sectional filtration markers. These findings support renal assessment with UACR alongside routine filtration measures and reinforce that PA screening should not depend on overt hypokalemia alone. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261286832.