KCNJ5 mutation as a predictor for resolution of hypertension after surgical treatment of aldosterone-producing adenoma

Objective: To investigate the effect of KCNJ5 mutations on the cure of hypertension in patients with aldosterone-producing adenoma (APA) after unilateral adrenalectomy. Methods: Our study included 142 patients with APA, who were detected with an endocrinological abnormality and diagnosed with hypertension, as confirmed by pathological analysis. We sequenced KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1 from APA tissue samples, and performed a retrospective analysis to determine correlations between wild-type or mutated KCNJ5 and patient clinical characteristics. Results: Somatic KCNJ5 mutations were identified in 106 of 142 patients with APA, 136 of whom had resolution of hyporeninemic-hyperaldosteronemia 1 year after surgery. Of the 136 patients, 81 patients had resolution of hypertension ('Cured group' vs. 'Improved group'). We found increased prevalence of KCNJ5 mutations in the Cured group compared to the Improved group (85.2% vs. 60.0%, respectively; P = 0.002), which was associated with younger age, shorter duration of hypertension, fewer antihypertensive medications, lower BMI, higher aldosterone level, higher estimated glomerular filtration rate, and milder vascular complications. In both groups we found that harbouring a KCNJ5 mutation, taking fewer antihypertensive medications, and the duration of hypertension were independently associated with resolution of hypertension by unilateral adrenalectomy. In patients with KCNJ5-mutated APA, left ventricular hypertrophy was significantly decreased by surgical treatment in patients from either Cured or Improved groups, although those patients with wild-type KCNJ5 showed no change. Conclusions: Testing for KCNJ5 mutations in young patients with APA may provide a prognostic indication for resolution of hypertension and severity of vascular complications.