Cardiovascular and metabolic characters of KCNJ5 somatic mutations in primary aldosteronism

Abstract

BackgroundPrimary aldosteronism (PA) is the leading cause of curable endocrine hypertension, which is associated with a higher risk of cardiovascular and metabolic insults compared to essential hypertension. Aldosterone-producing adenoma (APA) is a major cause of PA, which can be treated with adrenalectomy. Somatic mutations are the main pathogenesis of aldosterone overproduction in APA, of which KCNJ5 somatic mutations are most common, especially in Asian countries. This article aimed to review the literature on the impacts of KCNJ5 somatic mutations on systemic organ damage.Evidence acquisitionPubMed literature research using keywords combination, including “aldosterone-producing adenoma,” “somatic mutations,” “KCNJ5,” “organ damage,” “cardiovascular,” “diastolic function,” “metabolic syndrome,” “autonomous cortisol secretion,” etc.ResultsAPA patients with KCNJ5 somatic mutations are generally younger, female, have higher aldosterone levels, lower potassium levels, larger tumor size, and higher hypertension cure rate after adrenalectomy. This review focuses on the cardiovascular and metabolic aspects of KCNJ5 somatic mutations in APA patients, including left ventricular remodeling and diastolic function, abdominal aortic thickness and calcification, arterial stiffness, metabolic syndrome, abdominal adipose tissue, and correlation with autonomous cortisol secretion. Furthermore, we discuss modalities to differentiate the types of mutations before surgery.ConclusionKCNJ5 somatic mutations in patients with APA had higher left ventricular mass (LVM), more impaired diastolic function, thicker aortic wall, lower incidence of metabolic syndrome, and possibly a lower incidence of concurrent autonomous cortisol secretion, but better improvement in LVM, diastolic function, arterial stiffness, and aortic wall thickness after adrenalectomy compared to patients without KCNJ5 mutations.

The mitochondrial energy metabolism pathway-related signature predicts prognosis and indicates immune microenvironment infiltration in osteosarcoma

“…KCNJ5 is a Potassium Inwardly Rectifying Channel Subfamily J Member 5, which encodes a G-protein-activated inward rectifier potassium channel. [17] This potassium channel mediates the outward current of potassium ions to maintain hyperpolarization and stabilize the resting membrane potential. [18] To date, most studies have focused on the relationship between the KCNJ5 mutation and aldosteronism caused by adrenal adenoma, [19] and it has been found that overexpression of KCNJ5 can inhibit the growth of tumor cells.…”

Conn’s syndrome - role as a secondary cause of arterial hypertension

“…2 The authors stressed the primary aldosteronism in a transient hypertension of pregnancy. Chang YY et al reviewed clinical data and genetic mutations among patients with PA. 3 They cited PA as now considered the most common modifiable secondary hypertension (up to 15%), and up to 30% of the resistant and refractory cases; while aldosteronoma (30%-35%) and bilateral adrenal hyperplasia (60%-65%) are the major causes of PA. 3 Besides, the patients with KCNJ5 somatic mutations can have higher left ventricle mass (LVM), inappropriately excessive LVM, and better improvement after adrenalectomy. 3 Jia M et al reported 3 patients with biochemically confirmed PA, and the diagnoses were delayed by aldosterone-to-renin ratio (ARR) initial analysis with non-suppressed renin.…”

“…Chang YY et al reviewed clinical data and genetic mutations among patients with PA. 3 They cited PA as now considered the most common modifiable secondary hypertension (up to 15%), and up to 30% of the resistant and refractory cases; while aldosteronoma (30%-35%) and bilateral adrenal hyperplasia (60%-65%) are the major causes of PA. 3 Besides, the patients with KCNJ5 somatic mutations can have higher left ventricle mass (LVM), inappropriately excessive LVM, and better improvement after adrenalectomy. 3 Jia M et al reported 3 patients with biochemically confirmed PA, and the diagnoses were delayed by aldosterone-to-renin ratio (ARR) initial analysis with non-suppressed renin. 4 The reevaluated ARR was close to cutoff still with normal renin after strict and extended drug washout, and a further workup for PA showed a unilateral aldosterone producing adenoma that was surgically removed, with subsequent complete biochemical remission.…”

Comparison of different medical treatments for primary hyperaldosteronism: a systematic review and network meta-analysis

“…Over the past two decades, numerous studies have explored primary hyperaldosteronism, 21 with recent advancements in genetic research, 22 , 23 diagnostic testings, 24 – 26 and prognostic factor evaluations, 11 , 22 which have deepened our understanding of the disease. However, despite these advancements, there remained a notable gap in the literature regarding the comparative efficacy of different medical treatments.…”