Abstract Body: Introduction: Primary aldosteronism (PA), the most common curable salt-dependent form of arterial hypertension, features renal K⁺ loss and enhanced Na⁺ reabsorption.
Hypothesis: We assessed the hypothesis that alterations of electrolyte, water, and Tonicity-responsive Enhancer Binding Protein/NFAT5 mRNA content occur in the skin of PA patients and are corrected by surgical cure.
Methods: We obtained skin biopsies in 80 subjects: 49 consecutive consenting PA patients, optimally treated with a mineralocorticoid receptor antagonist (MRA) before adrenalectomy; 6 patients with essential hypertension, and 25 normotensive controls. We measured Na⁺, K⁺ and water content with atomic absorption spectrometry after ashing and NFAT5 mRNA with digital droplet PCR. The PA patients were retested after adrenalectomy.
Results: We discovered that the skin biopsy specimen dry weight (DW) was higher at surgery than follow-up (p<0.001) and correlated directly with electrolyte and water content (all p<0.01), indicating the need for adjusting electrolyte and water data for DW. Surgical cure of PA markedly increased skin DW-adjusted K⁺ (from 1.14±0.1 µg/mg to 2.81±0.27 µg/mg, p<0.001) and water content (from 2.92±1.4 mg/mg to 3.85±0.23 mg/mg, p<0.001), but left DW-adjusted skin Na⁺ content unaffected. In the PA patients NFAT5 mRNA copy number was higher (p=0.03) than in the normotensive controls and decreased after surgery (p=0.03).
Conclusions: In conclusion, surgical cure, but not optimal MRA treatment corrected the prominent skin cell K⁺ depletion that occurred despite normal serum K⁺ levels. The lack of overt skin Na⁺ accumulation in PA patients during MRA treatment could be explained by enhanced skin Na⁺ lymphatic drainage due to the documented activation of the skin NFAT5/TonEBP pathway.