BACKGROUND Primary aldosteronism (PA), the most common curable salt-dependent form of arterial hypertension, features renal K+ loss and enhanced Na+ reabsorption. We investigated whether the electrolyte, water, and TonEBP (tonicity-responsive enhancer binding protein)/NFAT5 (nuclear factor of activated T cells 5) content is altered in the skin of patients with PA and corrected by surgical cure. METHODS We obtained skin biopsies from 80 subjects: 49 consecutive patients with PA, optimally treated with a mineralocorticoid receptor antagonist; 6 essential hypertensives; and 25 normotensive controls. We measured Na+, K+, water content with atomic absorption spectroscopy after ashing, and NFAT5 mRNA with digital droplet polymerase chain reaction. The patients with PA were retested after adrenalectomy. RESULTS We discovered a higher dry weight of the skin biopsy specimen at surgery than at follow-up (P<0.001) and a direct correlation with electrolyte and water content (all P<0.01), indicating the need for dry weight adjustment of electrolyte and water data. Surgical cure of PA markedly increased skin dry weight-adjusted K+ (from 1.14±0.1 to 2.81±0.27 µg/mg; P<0.001) and water content (from 2.92±1.4 to 3.85±0.23 mg/mg; P<0.001), but left dry weight-adjusted skin Na+ content unaffected. In patients with PA at baseline, NFAT5 mRNA was higher (P=0.031) than in normotensive controls and decreased after surgery (P=0.035). CONCLUSIONS Despite mineralocorticoid receptor antagonist treatment ensuring normokalemia, the patients with PA had a skin cell K+ depletion that was corrected by adrenalectomy. The activated NFAT5/TonEBP pathway during mineralocorticoid receptor antagonist administration suggests enhanced skin Na+ lymphatic drainage and can explain the lack of overt skin Na+ accumulation in patients with PA. Its deactivation after surgical cure can account for the lack of skin Na+ decrease postadrenalectomy. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT06090617.

中文翻译：

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原发性醛固酮增多症中皮肤高血压 （WHYSKI） 中的水和电解质含量。


背景 原发性醛固酮增多症 （PA） 是最常见的可治愈的盐依赖性动脉高血压形式，其特征是肾脏 K+ 丢失和 Na+ 重吸收增强。我们研究了 PA 患者皮肤中的电解质、水和 TonEBP （张力反应增强子结合蛋白）/NFAT5 （活化 T 细胞的核因子 5） 含量是否发生改变并通过手术治愈进行纠正。方法 我们从 80 名受试者那里获得了皮肤活检： 49 例连续的 PA 患者，用盐皮质激素受体拮抗剂进行最佳治疗;6 种基本高血压药;和 25 个正常血压对照。灰化后用原子吸收光谱法测量 Na + 、 K + 、水分含量，以及用数字液滴聚合酶链反应测量 NFAT5 mRNA。PA 患者在肾上腺切除术后重新检查。结果 我们发现手术时皮肤活检标本的干重高于随访时 （P<0.001），并且与电解质和水分含量直接相关 （均 P<0.01），表明需要调整电解质和水数据的干重。PA 的手术治愈显着增加了皮肤干重调整后的 K+（从 1.14±0.1 增加到 2.81±0.27 μg/mg;P<0.001）和水分含量（从 2.92±1.4 到 3.85±0.23 mg/mg;P<0.001），但干燥体重调整后的皮肤 Na + 含量不受影响。基线时 PA 患者的 NFAT5 mRNA 高于正常血压对照组 （P=0.031），术后降低 （P=0.035）。结论 尽管盐皮质激素受体拮抗剂治疗可确保正常血糖，但 PA 患者的皮肤细胞 K+ 耗竭通过肾上腺切除术得到纠正。 盐皮质激素受体拮抗剂给药期间激活的 NFAT5/TonEBP 通路表明皮肤 Na + 淋巴引流增强，可以解释 PA 患者缺乏明显的皮肤 Na + 积累。手术治愈后其失活可以解释肾上腺切除术后皮肤 Na+ 减少的缺乏。注册网址：https://www.clinicaltrials.gov;唯一标识符：NCT06090617。