Arterial stiffness and blood pressure improvement in aldosterone-producing adenoma harboring <i>KCNJ5</i> mutations after adrenalectomy

Chang, Chia Hui; Hu, Ya Hui; Tsai, Yao Chou; Wu, Che Hsiung; Wang, Shuo-Meng; Lin, Lian Yu; Lin, Yu Hung; Satoh, Fumitoshi; Wu, Kwan Dun; Wu, Vin Cent

doi:10.18632/oncotarget.16269

Cited by 17 publications

(15 citation statements)

References 48 publications

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“…Receiver operating characteristic (ROC) curve was used to evaluate the cut-off value of screening ARR in PA patients with or without DM. In order to display the implications of ARR for individual patients, a generalized additive model (GAM) (with spline) incorporating the subject-specific (longitudinal) random effects were plotted and adjusted for other clinical parameters to predict the possibility of PA [ 27 , 28 ]. Simple and multiple generalised additive models (GAMs) were fitted to detect nonlinear effects of continuous covariates and identify the appropriate cut-off point(s) for discretising continuous covariates, if necessary, during the stepwise variable selection procedure.…”

Section: Methodsmentioning

confidence: 99%

Higher Screening Aldosterone to Renin Ratio in Primary Aldosteronism Patients with Diabetes Mellitus

Chang

Huang

et al. 2018

JCM

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Accumulated evidence has shown that low renin hypertension is common in patients with diabetic nephropathy. However, the performance of aldosterone to renin ratio (ARR) in primary aldosteronism (PA) patients with diabetes has not been well validated. Here, we report the performance of screening ARR in PA patients with diabetes. The study enrolled consecutive patients and they underwent ARR testing at screening. Then the diagnosis of PA was confirmed from the Taiwan Primary Aldosteronism Investigation registration dataset. Generalized additive model smoothing plot was used to validate the performance of screening ARR in PA patients with or without diabetes. During this study period, 844 PA patients were confirmed and 136 (16.0%) among them had diabetes. Other 816 patients were diagnosed with essential hypertension and used as the control group and 89 (10.9%) among them had diabetes. PA patients with diabetes were older and had a longer duration of hypertensive latency, higher systolic blood pressure and lower glomerular filtration rate than those PA patients without diabetes. The cut-off value of ARR in the generalized additive model predicting PA was 65 ng/dL per ng/mL/h in diabetic patients, while 45 ng/dL per ng/mL/h in non-diabetic patients. There was a considerable prevalence of diabetes among PA patients, which might be capable of interfering with the conventional screening test. The best cut-off value of ARR, more than 65 ng/dL per ng/mL/h in PA patients with diabetes, was higher than those without diabetes.

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Section: Methodsmentioning

confidence: 99%

Higher Screening Aldosterone to Renin Ratio in Primary Aldosteronism Patients with Diabetes Mellitus

Chang

Huang

et al. 2018

JCM

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“…In our analysis, the long-term solid outcome of ESRD rate decreased after surgical intervention compared with MRA treatment alone in patients with EH or PA, although decreased short-term kidney function was found in patients with APA after adrenalectomy [4]. Improvements in renal function include microalbuminuria due to the resolution of glomerular hyperfiltration in PA after adrenalectomy [9, 41]. Our results suggest that patients with APA who respond to adrenalectomy demonstrate better outcomes in 10-year probability of incident ESRD than those receiving MRA alone (Fig.…”

Section: Discussionmentioning

confidence: 99%

Adrenalectomy Improves the Long-Term Risk of End-Stage Renal Disease and Mortality of Primary Aldosteronism

Chen

Lin

Huang

et al. 2019

Journal of the Endocrine Society

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Objective Primary aldosteronism (PA) is a common cause of secondary hypertension, and the long-term effect of excess aldosterone on kidney function is unknown. Patients and Methods We used a longitudinal population database from the Taiwan National Health Insurance system and applied a validated algorithm to identify patients with PA diagnosed between 1997 and 2009. Results There were 2699 patients with PA recruited, of whom 761 patients with an aldosterone-producing adenoma (APA) were identified. The incidence rate of end-stage renal disease (ESRD) was 3% in patients with PA after targeted treatments and 5.2 years of follow-up, which was comparable to the rate in controls with essential hypertension (EH). However, after taking mortality as a competing risk, we found a significantly lower incidence of ESRD when comparing patients with PA vs EH [subdistribution hazard ratio (sHR), 0.38; P = 0.007] and patients with APA vs EH (sHR 0.55; P = 0.021) after adrenalectomy; however, we did not see similar results in groups with mineralocorticoid receptor antagonist (MRA)‒treated PA vs EH. There was also a significantly lower incidence of mortality in groups with PA and APA who underwent adrenalectomy than among EH controls ( P < 0.001). Conclusion Regarding incident ESRD, patients with PA were comparable to their EH counterparts after treatment. After adrenalectomy, patients with APA had better long-term outcomes regarding progression to ESRD and mortality than hypertensive controls, but MRA treatments did not significantly affect outcome.

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“…APA patients with KCNJ5 mutation are younger and have higher aldosterone levels and more severe hypokalemia compared with non-mutant carriers [179]. Although APA patients with KCNJ5 mutation had better hypertension recovery after adrenalectomy, we observed no difference in PWV improvement after adrenalectomy regardless of whether or not the patient had the KCNJ5 mutation [172].…”

Section: Clinical Data and Treatment Among Pa And Endothelial Dysfmentioning

confidence: 90%

Endothelial Dysfunction in Primary Aldosteronism

Chen

Tsai

Pan

et al. 2019

IJMS

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Primary aldosteronism (PA) is characterized by excess production of aldosterone from the adrenal glands and is the most common and treatable cause of secondary hypertension. Aldosterone is a mineralocorticoid hormone that participates in the regulation of electrolyte balance, blood pressure, and tissue remodeling. The excess of aldosterone caused by PA results in an increase in cardiovascular and cerebrovascular complications, including coronary artery disease, myocardial infarction, stroke, transient ischemic attack, and even arrhythmia and heart failure. Endothelial dysfunction is a well-established fundamental cause of cardiovascular diseases and also a predictor of worse clinical outcomes. Accumulating evidence indicates that aldosterone plays an important role in the initiation and progression of endothelial dysfunction. Several mechanisms have been shown to contribute to aldosterone-induced endothelial dysfunction, including aldosterone-mediated vascular tone dysfunction, aldosterone- and endothelium-mediated vascular inflammation, aldosterone-related atherosclerosis, and vascular remodeling. These mechanisms are activated by aldosterone through genomic and nongenomic pathways in mineralocorticoid receptor-dependent and independent manners. In addition, other cells have also been shown to participate in these mechanisms. The complex interactions among endothelium, inflammatory cells, vascular smooth muscle cells and fibroblasts are crucial for aldosterone-mediated endothelial dysregulation. In this review, we discuss the association between aldosterone and endothelial function and the complex mechanisms from a molecular aspect. Furthermore, we also review current clinical research of endothelial dysfunction in patients with PA.

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Arterial stiffness and blood pressure improvement in aldosterone-producing adenoma harboring KCNJ5 mutations after adrenalectomy

Cited by 17 publications

References 48 publications

Higher Screening Aldosterone to Renin Ratio in Primary Aldosteronism Patients with Diabetes Mellitus

Higher Screening Aldosterone to Renin Ratio in Primary Aldosteronism Patients with Diabetes Mellitus

Adrenalectomy Improves the Long-Term Risk of End-Stage Renal Disease and Mortality of Primary Aldosteronism

Endothelial Dysfunction in Primary Aldosteronism

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