KCNJ5 Somatic Mutations Are Associated With Better Long-term Outcomes in Patients With Unilateral Primary Aldosteronism

CONTEXT: The association between KCNJ5 somatic mutations and long-term outcomes in patients with operated unilateral primary aldosteronism (uPA) is unclear. OBJECTIVE: To evaluate associations among KCNJ5 somatic mutations, clinical characteristics, incident long-term cardiovascular events, and all-cause mortality in patients with uPA after adrenalectomy in a large longitudinal population study. METHODS: We enrolled patients with uPA from the Taiwan Primary Aldosteronism Investigation database who had undergone adrenalectomy between 2013 and 2017 and followed them until 2020. The outcomes were achieving complete clinical success at 1 year after adrenalectomy, long-term major adverse cardiac and cerebrovascular events (MACCEs), and mortality. RESULTS: Of the 358 enrolled patients (46.7% men; mean age, 51.3 years), 188 (52.5%) harbored KCNJ5 somatic mutations. The baseline characteristics of younger age (odds ratio OR = 2.44; P = .001), lower body mass index (OR = 2.04; P = .005), lower potassium (OR = 6.55; P < .001), and larger tumor size (OR = 2.05; P = .023) were potential predictors of KCNJ5 somatic mutations. The patients with uPA who were operated on and harboring KCNJ5 somatic mutations were associated with a higher likelihood of complete clinical success at 1 year after adrenalectomy (OR = 1.98; P = .016). KCNJ5 somatic mutation carriers (hazard ratio HR = 0.46; P = .044), those with a shorter duration of hypertension (HR = 1.05; P = .008), and those who achieved complete clinical success (HR = 0.49; P = .036) had a lower risk of MACCEs and mortality. CONCLUSION: Patients with uPA harboring KCNJ5 somatic mutations had a lower risk of long-term MACCEs and mortality following adrenalectomy. These patients were more likely to achieve complete clinical success, which contributed to improved outcomes. However, the benefits were influenced by factors such as baseline potassium levels, hypertension duration, BMI, eGFR, and residual hypertension, highlighting the interplay of genetic and clinical factors in determining prognosis.