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Vedere T, Khalifa M. Primary Hyperaldosteronism: A Comprehensive Review of Pathophysiology, Diagnosis, and Treatment. Urol Clin North Am 2025; 52:205-216. [PMID: 40250888 DOI: 10.1016/j.ucl.2025.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2025]
Abstract
Primary hyperaldosteronism (PA) is the most common endocrine cause of hypertension, characterized by autonomous aldosterone hormone production from the adrenal glands. It encompasses a wide spectrum of renin-independent aldosterone production with diverse histopathological etiologies. A vast majority of PA is caused by bilateral disease, remains underdiagnosed and is linked to serious cardiometabolic risks. This review outlines our current understanding of the etiopathogenesis of PA, and provides a comprehensive overview of the diagnostic strategies and management of PA.
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Affiliation(s)
- Tarunya Vedere
- Division of Endocrinology, Diabetes and Metabolism, UConn Health, 263 Farmington Avenue, Farmington, CT 06030, USA; Division of Endocrine Neoplasia, Neag Comprehensive Cancer Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
| | - Maram Khalifa
- Division of Endocrinology, Diabetes and Metabolism, UConn Health, 263 Farmington Avenue, Farmington, CT 06030, USA
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Chang YC, Wu XM, Chen TY, Chen UL, Liao CW, Lai TS, Chang CC, Lee BC, Yang FY, Chen ZW, Chang YY, Chueh JS, Wu VC, Tsai CH, Hung CS, Lin YH. Evaluating the effects of adrenalectomy and mineralocorticoid receptor antagonist on cardiac remodeling and diastolic function in patients with aldosterone-producing adenoma. Hypertens Res 2025; 48:529-539. [PMID: 39448809 DOI: 10.1038/s41440-024-01946-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 09/26/2024] [Accepted: 09/28/2024] [Indexed: 10/26/2024]
Abstract
Cardiac remodeling and diastolic dysfunction in patients with aldosterone-producing adenomas (APA) can be improved after adrenalectomy. However, the effect of mineralocorticoid receptor antagonist (MRA) treatment remains unclear. The aim of this study is to evaluate the effect of MRA on cardiac remodeling and diastolic dysfunction in patients with PA. We prospectively enrolled patients with APA from 1993 to 2023, who either received medical treatment with MRAs or underwent adrenalectomy. Biochemical characteristics and echocardiographic findings were collected at baseline and one year after treatment. Propensity score matching was conducted based on baseline biochemical characteristics, left ventricular mass index (LVMI), and diastolic function. A total of 467 APA patients were enrolled in the study. After propensity score matching, 159 patients who underwent adrenalectomy were matched with 159 patients who received MRAs. After therapy, patients who received MRAs showed significant improvement in diastolic function after one year of treatment but not LVMI. Compared to the MRA group, the adrenalectomy group had greater improvement in systolic blood pressure, plasma aldosterone concentration, plasma renin activity, aldosterone-to-renin ratio, and LVMI. In multivariable regression analysis, pretreatment echocardiographic values were significantly associated with changes in both LVMI and E/e', while the treatment strategy showed a significant association with changes in LVMI. Thus, one year after therapy, both adrenalectomy and MRA are effective in improving diastolic function in patients with APA. However, adrenalectomy is more effective than MRA treatment in reversing cardiac remodeling in patients with APA.
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Affiliation(s)
- Yu-Ching Chang
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Xue-Ming Wu
- Department of Internal Medicine, Taoyuan General Hospital, Taoyuan, Taiwan
| | - Tsung-Yan Chen
- Division of Cardiology, Department of Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan
| | - Uei-Lin Chen
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Division of Cardiology, Department of Internal Medicine, Taoyuan Min Sheng General Hospital, Taoyuan, Taiwan
| | - Che-Wei Liao
- Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Tai-Shuan Lai
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chin-Chen Chang
- Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Bo-Ching Lee
- Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Fang-Yu Yang
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Zheng-Wei Chen
- Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan
| | - Yi-Yao Chang
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Cardiology Division of Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Jeff S Chueh
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
| | - Vin-Cent Wu
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Cheng-Hsuan Tsai
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
- Cardiovascular Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Chi-Sheng Hung
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
- Cardiovascular Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Yen-Hung Lin
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Cardiovascular Center, National Taiwan University Hospital, Taipei, Taiwan
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Passman J, Hwang J, Tang J, Fagen M, Epps M, Peifer M, Howell JT, Cohen JB, Delgado MK, Wachtel H, Herman DS. Active Choice Nudge to Increase Screening for Primary Aldosteronism in At-Risk Patients. J Am Coll Surg 2025; 240:46-59. [PMID: 39431610 PMCID: PMC11649442 DOI: 10.1097/xcs.0000000000001221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2024]
Abstract
BACKGROUND Primary aldosteronism (PA) is the most common cause of secondary hypertension, yet screening remains startlingly infrequent. We describe (1) PA screening practices in a large, diverse health system, (2) the development of a computable phenotype for PA screening, and (3) the design and pilot deployment of an electronic health record (EHR)-based active choice nudge to recommend PA screening. STUDY DESIGN A multidisciplinary team developed a multipronged intervention to improve PA screening informed by guidelines, expertise, and multivariable analyses of factors associated with screening. The intervention included EHR-based tools to automatically identify screen-eligible patients, an active choice nudge recommending screening for these patients, and screening result interpretation. The intervention was piloted across 2 primary care practices for 7 months. Screening frequencies were compared with clinics not receiving the intervention. RESULTS The baseline frequency of screening of eligible patients within 1 year was 1.4%. Higher mean systolic blood pressure (odds ratio [OR] 1.4; p < 0.001), more antihypertensive medications (OR 1.3; p = 0.002), lower minimum serum potassium (OR 2.0; p = 0.001), specialist care (OR 3.0; p < 0.001), and Black race (OR 1.5; p = 0.001) were associated with a higher likelihood of screening. The refined computable phenotype identified a subcohort with a higher frequency of positive screening (8.6% vs 4.1%; p = 0.03). In a pilot study of an active choice nudge, a greater proportion of eligible patients were screened in the intervention clinics (16.4%) than in the nonintervention clinics (1.8%; p < 0.001). CONCLUSIONS PA screening rates are low. This pilot study suggests an EHR-based nudge leveraging a precise computable phenotype can dramatically increase appropriate PA screening.
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Affiliation(s)
- Jesse Passman
- Department of Surgery, University of Pennsylvania Health System, Philadelphia, PA
- Leonard Davis Institute of Health Economics, University of Pennsylvania
| | - Jasmine Hwang
- Department of Surgery, University of Pennsylvania Health System, Philadelphia, PA
- Leonard Davis Institute of Health Economics, University of Pennsylvania
| | - Justin Tang
- Department of Pathology and Laboratory Medicine, University of Pennsylvania Health System, Philadelphia, PA
| | - Madeline Fagen
- Penn Medicine Nudge Unit, Center for Health Care Transformation & Innovation, University of Pennsylvania Health System, Philadelphia, PA
| | - Mika Epps
- Information Services, University of Pennsylvania Health System, Philadelphia, PA
| | - MaryAnne Peifer
- Leonard Davis Institute of Health Economics, University of Pennsylvania
- Department of Family Medicine, University of Pennsylvania Health System, Philadelphia, PA
| | - JT Howell
- Department of Family Medicine, University of Pennsylvania Health System, Philadelphia, PA
| | - Jordana B. Cohen
- Department of Medicine, Division of Renal Electrolyte and Hypertension, University of Pennsylvania Health System, Philadelphia, PA
| | - M. Kit Delgado
- Penn Medicine Nudge Unit, Center for Health Care Transformation & Innovation, University of Pennsylvania Health System, Philadelphia, PA
| | - Heather Wachtel
- Department of Surgery, University of Pennsylvania Health System, Philadelphia, PA
| | - Daniel S. Herman
- Leonard Davis Institute of Health Economics, University of Pennsylvania
- Department of Pathology and Laboratory Medicine, University of Pennsylvania Health System, Philadelphia, PA
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Wu M, Wang R, Zeng Q, Shuai W, Zhang H, Dong Y. Association Between Uric Acid to High-Density Lipoprotein Cholesterol Ratio and Kidney Function in Patients With Primary Aldosteronism: A Cross-Sectional Study. J Clin Hypertens (Greenwich) 2025; 27:e14960. [PMID: 39686832 PMCID: PMC11774081 DOI: 10.1111/jch.14960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 11/25/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024]
Abstract
The relationship between the uric acid to high-density lipoprotein cholesterol ratio (UHR) and kidney function in patients with primary aldosteronism (PA) is unclear. Therefore, this research explored the link between the UHR and kidney function in PAs. This research was conducted at the 2nd Affiliated Hospital of Nanchang University and involved PA individuals hospitalized between October 2017 and April 2022. A total of 653 eligible participants were included in the analysis for this research. The kidney function was assessed by the estimated glomerular filtration rate (eGFR), which is calculated using the modification of diet in renal disease (MDRD) equation. Chronic kidney disease (CKD) was defined as an eGFR <60 mL/min per 1.73 m2 or the ratio of urine microalbumin to creatinine (UACR) ≥30 mg/g. The study used multivariable-adjusted linear regression analyses to investigate the association between log-transformed UHR levels and, eGFR and CKD. After multivariable adjustments, the results indicated an inverse association between Lg-UHR and eGFR (per SD increment; β: -9.02; 95% CI: -11.59, -6.46). Compared to PA patients with the lowest level of Lg-UHR (T1), patients with the highest level of Lg-UHR (T3) had a lower eGFR (β: -20.14, 95% CI: -26.25, -14.04). Conversely, Lg-UHR and CKD showed a positive association cross-sectionally (per SD increment; OR: 1.67; 95% CI: 1.26, 2.23). Compared to PA patients in T1 level, patients in T3 level had a higher prevalence of CKD (OR: 2.52, 95% CI: 1.26, 5.05). In patients with PA, UHR is inversely associated with eGFR and positively associated with CKD.
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Affiliation(s)
- Meng‐Bo Wu
- Department of Cardiovascular Medicinethe 2nd Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchangJiangxiChina
| | - Rui Wang
- Department of Cardiovascular Medicinethe 2nd Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchangJiangxiChina
| | - Qing‐Tian Zeng
- Department of Cardiovascular Medicinethe 2nd Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchangJiangxiChina
| | - Wen‐Liang Shuai
- Department of Cardiovascular Medicinethe 2nd Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchangJiangxiChina
| | - Hang‐Cheng Zhang
- Department of Cardiovascular Medicinethe 2nd Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchangJiangxiChina
| | - Yi‐Fei Dong
- Department of Cardiovascular Medicinethe 2nd Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchangJiangxiChina
- Jiangxi Key Laboratory of Molecular MedicineNanchangJiangxiChina
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Widjaja J, Yang J, Harrison J. Improving diagnosis of primary aldosteronism through education: a modified Delphi study to identify key learning points. Ther Adv Chronic Dis 2024; 15:20406223241306952. [PMID: 39734384 PMCID: PMC11672389 DOI: 10.1177/20406223241306952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 11/18/2024] [Indexed: 12/31/2024] Open
Abstract
Background Primary aldosteronism (PA) is the most common endocrine cause of secondary hypertension and can be effectively managed, or even cured, with targeted treatment. Despite this, it remains largely undiagnosed leaving a significant patient population with resistant hypertension and modifiable cardiovascular risk. Objective To determine expert consensus on key information about PA that should ideally be taught to medical students as a step toward improving the detection of this common, underdiagnosed, and often easily treated condition. Design The study employed a modified Delphi method which consisted of three rounds, the first of which contained an open-ended question about key areas that experts believe to be most important for inclusion in medical teaching resources and then progressing to assessment of individual versus group rankings of consensus items. Experts included both clinician-educator-researchers and patients with lived experience. Results Nine critical knowledge areas in epidemiology, diagnostics, and pathophysiology were identified by the Delphi as consensus items, with the highest ranked being: "PA is common but often under-diagnosed - think about it with every hypertensive patient." Conclusion Experts reached a consensus, for the first time, on nine critical knowledge areas about PA that should be covered in medical education. Importantly, the consensus accounted for patients' values and decisions. The results of this study could be used to assess medical student knowledge and their learning resources to facilitate curriculum development and medical resource updates to ensure the timely and accurate diagnosis of PA in hypertensive patients.
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Affiliation(s)
- Jocelyn Widjaja
- Faculty of Medicine Nursing and Health Sciences, Monash University, Wellington Road, Clayton, VIC 3800, Australia
| | - Jun Yang
- Monash University, Clayton, VIC, Australia
- Hudson Institute of Medical Research, Clayton, VIC, Australia
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Jiang Y, Zhou L, Zhang C, Su T, Jiang L, Zhou W, Zhong X, Wu L, Wang W. Suppressed Renin Status Is a Risk Factor for Cardiocerebrovascular Events in Bilateral Primary Aldosteronism Treated With Mineralocorticoid Receptor Antagonists. Endocr Pract 2024; 30:1180-1187. [PMID: 39260773 DOI: 10.1016/j.eprac.2024.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/28/2024] [Accepted: 09/03/2024] [Indexed: 09/13/2024]
Abstract
OBJECTIVE Mineralocorticoid receptor antagonists are the recommended medical therapy for bilateral primary aldosteronism (BPA). Patients with BPA have higher risk of cardiocerebrovascular disease (CCVD) than those with essential hypertension. There is no consensus on the criteria to assess the effectiveness of medical therapy for BPA. This study aimed to investigate the incidence of and risk factors for CCVD after medical therapy of BPA. METHODS We conducted a retrospective cohort study including 240 patients with BPA treated with mineralocorticoid receptor antagonists. The posttreatment plasma renin activity (PRA) was defined as unsuppressed (PRA, ≥1 ng/mL/h); otherwise, it was defined as suppressed. We analyzed the association of posttreatment PRA status with CCVD outcomes. RESULTS Of patients with BPA, 7.1% (17/240) developed CCVD at a median follow-up of 5.0 (range, 2.96-7.66) years. Moreover, 57.1% of patients had a PRA of ≥1 ng/mL/h after treatment. Patients with a PRA of <1 ng/mL/h had a higher incidence of CCVD (12.6% vs 2.9%, P < .05) and were at higher risk than those with a PRA of ≥1 ng/mL/h (hazard ratio, 4.50 [95% CI, 1.47-13.83; P < .05]; adjusted hazard ratio, 3.98 [95% CI, 1.22-13.02; P < .05]). CONCLUSION Patients with BPA who receive pharmacologic treatment have a high incidence of CCVD. PRA may be an indicator that mineralocorticoids are being adequately antagonized.
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Affiliation(s)
- Yiran Jiang
- Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lihua Zhou
- Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Cui Zhang
- Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tingwei Su
- Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lei Jiang
- Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiwei Zhou
- Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xu Zhong
- Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Luming Wu
- Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiqing Wang
- Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Centre for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Laboratory for Endocrine and Metabolic diseases, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine, and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
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Ma Y, Tang X, Ge Q, Xu J, Gao P, Wang J, Zhu L. Chronological outcomes of renal function after adrenalectomy in patients with primary aldosteronism across age groups. Front Endocrinol (Lausanne) 2024; 15:1467742. [PMID: 39574955 PMCID: PMC11578701 DOI: 10.3389/fendo.2024.1467742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 10/22/2024] [Indexed: 11/24/2024] Open
Abstract
Background Patients with primary aldosteronism present with renal function decline after unilateral adrenalectomies. Our study aimed to assess the evolution of renal function after adrenalectomy in patients with primary aldosteronism across different age groups and to identify risk factors for postoperative renal function deterioration. Methods We included 210 patients with primary aldosteronism categorized into three age groups: <40, 40-60, and ≥60 years old. We followed up the patients for 1 month, 1 year, and 5 years after adrenalectomy to assess outcomes. Multivariate analyses were performed to identify predictors of renal function deterioration, and a univariate logistic regression analysis was used to assess the relationship between KCNJ5 mutation status and the decline in renal function. Results Patients aged <40 years had a shorter duration of hypertension, higher preoperative diastolic blood pressure, and higher preoperative estimated glomerular filtration rate (eGFR) than did those in the other age groups. This group also exhibited the highest rate of complete clinical success, although there were no significant differences in complete biochemical success among age groups. Renal function declined in all three groups after adrenalectomy. However, changes in blood pressure and eGFR in the short- or long-term after adrenalectomy showed no significant differences among the three groups. Hypertension duration, preoperative systolic blood pressure (SBP), and plasma aldosterone concentration (PAC) were predictors of postoperative renal function deterioration. KCNJ5 wild-type status was significantly correlated with the occurrence of chronic kidney disease after adrenalectomy. Conclusions Unilateral adrenalectomy demonstrates favorable biochemical and clinical outcomes in patients with primary aldosteronism, irrespective of age. Long-term eGFR decline is similar among the different age groups. KCNJ5 mutation exhibits a protective effect against the risk of chronic kidney disease after unilateral adrenalectomy.
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Affiliation(s)
- Yu Ma
- Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai, China
- Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaofeng Tang
- Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai, China
- Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qian Ge
- Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai, China
- Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianzhong Xu
- Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai, China
- Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Pingjin Gao
- Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai, China
- Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiguang Wang
- Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai, China
- Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Limin Zhu
- Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai, China
- Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Gupta G, Teo AED, Swee DS, Loh LM, Chuah M, Loh WJ, Saffari SE, Koh XH, Kek PC, Puar TH. Prolonged Hypokalemia and Delayed Diagnosis of Primary Aldosteronism: Clinical Course and Risk Factors. J Clin Endocrinol Metab 2024; 109:e1574-e1581. [PMID: 38134306 DOI: 10.1210/clinem/dgad752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 12/01/2023] [Accepted: 12/19/2023] [Indexed: 12/24/2023]
Abstract
CONTEXT Primary aldosteronism (PA) is a common cause of hypertension (HT). However, diagnosis is often delayed, leading to poorer clinical outcomes. Hypokalemia with HT is characteristic of PA, and is an indication for screening. OBJECTIVE We evaluated if patients with PA had prolonged hypokalemia before diagnosis, the subsequent biochemical/clinical control, and factors associated with delayed diagnosis. METHODS Our study included all PA patients with hypokalemia diagnosed between 2001 and 2022. Delayed diagnosis was defined as duration of hypokalemia of more than 1 year from first occurrence to first evaluation by a PA specialist. Patients were reassessed post adrenalectomy using the Primary Aldosteronism Surgery Outcomes criteria. We performed multivariable analysis to assess for factors associated with delayed diagnosis. RESULTS Among 240 patients with PA who presented with hypokalemia, 122 (51%) patients had delayed diagnosis, with prolonged hypokalemia of median duration 4.5 years (range, 2.4-7.5 years). Patients with delayed diagnosis were older, had longer duration of HT, higher pill burden, lower renal function, and more prevalent cardiovascular disease. Factors associated with delayed diagnosis included older age, presence of hyperlipidemia, and less severe hypokalemia (serum potassium >3.0 mmol/L). Compared to patients with early diagnosis, a lower proportion of those with delayed diagnosis underwent adrenal vein sampling (73% vs 58%) (P < .05). Sixty of 118 (50.8%) nondelayed, and 39 of 122 (32.0%) patients with delayed diagnosis, underwent surgery. CONCLUSION Despite manifestation of hypokalemia, many patients with PA fail to be promptly screened. Greater emphasis in HT guidelines, and efforts to improve awareness of PA among primary care physicians, are urgently needed.
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Affiliation(s)
- Gaytri Gupta
- Duke National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
| | - Ada E D Teo
- Department of Endocrinology, National University Health System, Singapore 119074, Singapore
| | - Du Soon Swee
- Department of Endocrinology, Singapore General Hospital, Singapore 169608, Singapore
| | - Lih Ming Loh
- Department of Endocrinology, Singapore General Hospital, Singapore 169608, Singapore
| | - Matthew Chuah
- Department of Endocrinology, Sengkang General Hospital, Singapore 554886, Singapore
| | - Wann Jia Loh
- Department of Endocrinology, Changi General Hospital, Singapore 529889, Singapore
| | - Seyed Ehsan Saffari
- Duke National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
- National Neuroscience Institute, Singapore 308433, Singapore
| | - Xuan Han Koh
- Health Science Research Department, Changi General Hospital, Singapore 529889, Singapore
| | - Peng Chin Kek
- Department of Endocrinology, Singapore General Hospital, Singapore 169608, Singapore
| | - Troy H Puar
- Duke National University of Singapore (NUS) Medical School, Singapore 169857, Singapore
- Department of Endocrinology, Changi General Hospital, Singapore 529889, Singapore
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Freeman MW, Halvorsen YD, Bond M, Murphy B, Isaacsohn J. Results from a Phase 1 Study Assessing the Pharmacokinetics of the Aldosterone Synthase Inhibitor Baxdrostat in Participants with Varying Degrees of Renal Function. Clin Pharmacol Drug Dev 2024; 13:410-418. [PMID: 38311833 DOI: 10.1002/cpdd.1371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 12/19/2023] [Indexed: 02/06/2024]
Abstract
Baxdrostat is a selective small-molecule aldosterone synthase inhibitor in development for treatment of hypertension and chronic kidney disease. This phase 1, open-label, parallel-group study assessed the safety and pharmacokinetics (PK) of baxdrostat in participants with varying degrees of renal function. Participants were enrolled into control (estimated glomerular filtration rate [eGFR] ≥60 mL/min), moderate to severe renal impairment (eGFR 15-59 mL/min), or kidney failure (eGFR <15 mL/min) groups and received a single 10-mg baxdrostat dose followed by 7 days of inpatient PK blood and urine sampling. Safety was assessed by adverse events, clinical laboratory evaluations, vital signs, physical examinations, and electrocardiograms (ECGs). Thirty-2 participants completed the study. There were no deaths and only 1 mild drug-related adverse event (diarrhea). No clinically meaningful changes in laboratory values, vital signs, physical examinations, or ECGs occurred. Plasma concentration-time curves of baxdrostat were similar among all groups. Urine PK parameters were similar (approximately 12% excreted) in the moderate to severe renal impairment and control groups. Inadequate urine production in the kidney failure group resulted in minimal urinary baxdrostat excretion. Renal impairment had no significant impact on systemic exposure or clearance of baxdrostat, suggesting that dose adjustment due to PK differences in patients with kidney disease is unnecessary.
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Affiliation(s)
- Mason W Freeman
- Center for Computational and Integrative Biology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- CinCor Pharma, Inc., Waltham, MA, USA
| | | | - Mary Bond
- CinRx Pharma, LLC, Cincinnati, OH, USA
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Lai ZQ, Fu Y, Liu JW, Zhang HJ, Zhang H, Liang NP, Dong YF. The impact of superselective adrenal artery embolization on renal function in patients with primary aldosteronism: a prospective cohort study. Hypertens Res 2024; 47:944-958. [PMID: 37957243 DOI: 10.1038/s41440-023-01503-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 10/13/2023] [Accepted: 10/13/2023] [Indexed: 11/15/2023]
Abstract
Superselective adrenal artery embolization (SAAE) is an effective treatment for patients with primary aldosteronism (PA). However, the impact of SAAE on renal function in the PA population remains uncertain. We investigated the estimated glomerular filtration rate (eGFR) and age, sex, body mass index, and diabetes-specific percentiles of eGFR residuals in 182 PA patients treated with SAAE in a prospective cohort from Nanchang SAAE in treating PA registry study. Data suggest that SAAE caused a significant decrease in eGFR from 91.9 ± 26.1 to 88.7 ± 24.1 ml/min/1.73 m2 (p < 0.05) after a median follow-up of 8 months in PA patients. Patients experienced a significant decrease in eGFR from 110.6 ± 18.9 to 103.8 ± 18.2 ml/min/1.73 m2 (p < 0.001) and a very slight increase from 71.1 ± 14.8 to 71.8 ± 17.8 ml/min/1.73 m2 (p = 0.770) with baseline eGFR ≥90 and <90 ml/min/1.73 m2, respectively. Patients with high eGFR residuals (glomerular hyperfiltration) experienced a significant decrease in their eGFR levels from 123.1 ± 22.6 to 105.0 ± 18.6 ml/min/1.73 m2 (p < 0.001). In contrast, there was no significant impact of SAAE on the eGFR of patients with normal or low eGFR residuals. The very early eGFR changes (24 h after SAAE) best predicted the effect of SAAE on eGFR changes after median of eight months in PA patients. On the whole, SAAE seems to have a beneficial impact on renal function in patients with PA, the results of which vary depending on the patient's baseline eGFR and glomerular hyperfiltration status.
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Affiliation(s)
- Ze-Qun Lai
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yang Fu
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jian-Wei Liu
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Hong-Jin Zhang
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Huang Zhang
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ning-Peng Liang
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yi-Fei Dong
- Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China.
- Jiangxi Key Laboratory of Molecular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, China.
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11
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Pan LH, Chen YY, Pan CT, Hsu CY, Tseng CS, Yen IW, Chan CK, Lin LY. Follow-up care and assessment of comorbidities and complications in patients with primary aldosteronism: The clinical practice guideline of the Taiwan Society of aldosteronism. J Formos Med Assoc 2024; 123 Suppl 2:S141-S152. [PMID: 37620221 DOI: 10.1016/j.jfma.2023.08.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 05/20/2023] [Accepted: 08/08/2023] [Indexed: 08/26/2023] Open
Abstract
Primary aldosteronism (PA) is the most common form of endocrine hypertension, characterized by excess aldosterone production that leads to an increased risk of cardiovascular events and target organ damage. Both adrenalectomy and medical treatment have shown efficacy in improving clinical outcomes and comorbidities associated with PA, including a specific subtype of PA with autonomous cortisol secretion (ACS). Understanding the comorbidities of PA and establishing appropriate follow-up protocols after treatment are crucial for physicians to enhance morbidity and mortality outcomes in patients with PA. Additionally, the screening for hypercortisolism prior to surgery is essential, as the prognosis of patients with coexisting PA and ACS differs from those with PA alone. In this review, we comprehensively summarize the comorbidities of PA, encompassing cardiovascular, renal, and metabolic complications. We also discuss various post-treatment outcomes and provide insights into the strategy for glucocorticoid replacement in patients with overt or subclinical hypercortisolism. This clinical practice guideline aims to equip medical professionals with up-to-date information on managing concurrent hypercortisolism, assessing treatment outcomes, and addressing comorbidities in patients with PA, thereby improving follow-up care.
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Affiliation(s)
- Li-Hsin Pan
- Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ying-Ying Chen
- Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chien-Ting Pan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Taiwan
| | - Chih-Yao Hsu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Taiwan
| | - Chi-Shin Tseng
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
| | - I-Weng Yen
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Taiwan
| | - Chieh-Kai Chan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Taiwan
| | - Liang-Yu Lin
- Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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12
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Ananda RA, Gwini SM, Long KM, Lai JH, Chen G, Russell GM, Stowasser M, Fuller PJ, Yang J. Diagnostic Delay and Disease Burden in Primary Aldosteronism: An International Patient Survey. Hypertension 2024; 81:348-360. [PMID: 38095087 DOI: 10.1161/hypertensionaha.123.21965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 11/14/2023] [Indexed: 01/19/2024]
Abstract
BACKGROUND Primary aldosteronism (PA) is a common but underdiagnosed cause of hypertension. Many patients experience preventable end-organ injury due to delayed or missed diagnosis but data on the experience of patients are limited. METHODS We evaluated the lived experience of PA and determines factors associated with diagnostic delay through an international anonymous online cross-sectional survey, codesigned by researchers and PA consumers. We distributed the survey through academic medical centers, Amazon Mechanical Turk, Twitter, PA patient advocacy groups, and hypertension support groups on Facebook between March 21 and June 5, 2022. RESULTS Of 684 eligible respondents, 66.5% were women. Diagnostic delay (defined as ≥5 years between the diagnosis of hypertension and PA) was reported in 35.6%. Delay was more likely in women than in men (odds ratio, 1.55 [95% CI, 1.10-2.20]) and respondents with ≥3 comorbidities versus none (odds ratio, 1.77 [95% CI, 1.05-3.02]), ≥10 symptoms versus none (odds ratio, 2.73 [95% CI, 1.74-4.44]), and on ≥4 antihypertensive medications versus none (odds ratio, 18.23 [95% CI, 6.24-77.72]). Three-quarters of patients (74.4%) experienced reduced symptom burden following targeted PA treatment. Quality of life improved in 62.3% of patients, and greater improvement was associated with being a woman (odds ratio, 1.42, [95% CI, 1.02-1.97]), receiving adrenalectomy (odds ratio, 2.36 [95% CI, 1.67-3.35]), and taking fewer antihypertensive medications following diagnosis (odds ratio, 5.28 [95% CI, 3.55-7.90]). CONCLUSIONS One-third of patients with PA experienced prolonged diagnostic delays. Targeted treatment led to reduced symptom burden and improved quality of life. Gender differences in diagnostic delay and symptom burden are prominent. These findings suggest that routine screening for PA at the onset of hypertension may reduce diagnostic delay and facilitate timely diagnosis.
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Affiliation(s)
- Roshan A Ananda
- Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, Australia (R.A.A., J.H.L., P.J.F., J.Y.)
- School of Public Health, Imperial College London, United Kingdom (R.A.A.)
| | - Stella May Gwini
- School of Public Health and Preventive Medicine Monash University, Melbourne, VIC, Australia (S.M.G.)
- Department of Biostatistics, University Hospital Geelong, Barwon Health, VIC, Australia (S.M.G.)
| | - Katrina M Long
- National Centre for Healthy Ageing, Frankston, VIC, Australia (K.M.L.)
| | - Jordan H Lai
- Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, Australia (R.A.A., J.H.L., P.J.F., J.Y.)
| | - Gang Chen
- School of Primary and Allied Health Care (K.M.L.), Centre for Health Economics, Monash Business School (G.C.), Monash University, Frankston, VIC, Australia
| | - Grant M Russell
- Department of General Practice (G.M.R.), Monash University, Frankston, VIC, Australia
| | - Michael Stowasser
- Endocrine Hypertension Research Centre, University of Queensland, Brisbane, QLD, Australia (M.S.)
| | - Peter J Fuller
- Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, Australia (R.A.A., J.H.L., P.J.F., J.Y.)
- Department of Endocrinology, Monash Health, Clayton, VIC, Australia (P.J.F., J.Y.)
| | - Jun Yang
- Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, Australia (R.A.A., J.H.L., P.J.F., J.Y.)
- Department of Endocrinology, Monash Health, Clayton, VIC, Australia (P.J.F., J.Y.)
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13
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Hundemer GL, Leung AA, Kline GA, Brown JM, Turcu AF, Vaidya A. Biomarkers to Guide Medical Therapy in Primary Aldosteronism. Endocr Rev 2024; 45:69-94. [PMID: 37439256 PMCID: PMC10765164 DOI: 10.1210/endrev/bnad024] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 06/23/2023] [Accepted: 07/11/2023] [Indexed: 07/14/2023]
Abstract
Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin-biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology. Even though the vast majority of patients with PA will ultimately be treated medically rather than surgically, there is a lack of guidance on how to optimize medical therapy and on key metrics of success. Herein, we review the evidence justifying approaches to medical management of PA and biomarkers that reflect endocrine principles of restoring normal physiology. We review the current arsenal of medical therapies, including dietary sodium restriction, steroidal and nonsteroidal mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, and aldosterone synthase inhibitors. It is crucial that clinicians recognize that multimodal medical treatment for PA can be highly effective at reducing the risk for adverse cardiovascular and kidney outcomes when titrated with intention. The key biomarkers reflective of optimized medical therapy are unsurprisingly similar to the physiologic expectations following surgical adrenalectomy: control of blood pressure with the fewest number of antihypertensive agents, normalization of serum potassium without supplementation, and a rise in renin. Pragmatic approaches to achieve these objectives while mitigating adverse effects are reviewed.
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Affiliation(s)
- Gregory L Hundemer
- Department of Medicine, Division of Nephrology, University of Ottawa, Ottawa, ON K1H 8L6, Canada
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
| | - Alexander A Leung
- Department of Medicine, Division of Endocrinology and Metabolism, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
- Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Gregory A Kline
- Department of Medicine, Division of Endocrinology and Metabolism, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Jenifer M Brown
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Adina F Turcu
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA
| | - Anand Vaidya
- Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
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14
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Lai CF, Lin YH, Huang KH, Chueh JS, Wu VC. Kidney function predicts new-onset cardiorenal events and mortality in primary aldosteronism: approach of the 2021 race-free eGFR equation. Hypertens Res 2024; 47:233-244. [PMID: 37714953 DOI: 10.1038/s41440-023-01400-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/23/2023] [Accepted: 07/31/2023] [Indexed: 09/17/2023]
Abstract
Individuals with primary aldosteronism (PA) exhibit glomerular hyperfiltration, which may conceal underlying kidney damage. This observational cohort study enrolled 760 coronary artery disease-naive patients diagnosed with PA between January 1, 2007 and December 31, 2018 (male, 45%; mean age, 52.3 ± 11.9 years). The baseline estimated glomerular filtration rate (eGFR) was calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which includes serum creatinine and cystatin C but omits the race variable. During a mean follow-up of 5.8 ± 3.2 years, new-onset composite cardiovascular events (total death, non-fatal myocardial infarction, and coronary revascularization procedure) occurred at a crude incidence rate of 10.9 per 1,000 person-years. Multivariable Cox proportional hazards analysis showed that baseline eGFR was independently associated with composite cardiovascular events (hazard ratio [HR], 0.98 [95% CI, 0.97-0.99]). Penalized splines smoothing in multivariable regression analysis demonstrated that the risk of composite cardiovascular events increased negatively and linearly when patients had a baseline eGFR less than 85 mL/min/1.73 m2. Patients with baseline eGFR <85 mL/min/1.73 m2 were independently associated with higher risks of composite cardiovascular events (HR, 2.39 [95% CI, 1.16-4.93]), all-cause mortality (HR, 4.63 [95% CI, 1.59-13.46]), and adverse kidney events (sub-distribution HR, 5.96 [95% CI, 3.69-9.62], with mortality as a competing risk). Our data support baseline eGFR as a predictor for new-onset adverse cardiorenal events and emphasizes the importance of the early detection of kidney function impairment in hypertensive patients with PA. We also firstly validate the 2021 race-free CKD-EPI eGFR equation in Asian patents with PA. Even with the glomerular hyperfiltration phenomenon, baseline eGFR in patients with primary aldosteronism is associated with subsequent cardiorenal outcomes. The results also firstly point to the validity of the 2021 race-free CKD-EPI eGFR equation in healthcare and clinical decision-making.
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Affiliation(s)
- Chun-Fu Lai
- Renal Division, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yen-Hung Lin
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Primary Aldosteronism Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Kuo-How Huang
- Department of Urology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jeff S Chueh
- Department of Urology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Vin-Cent Wu
- Renal Division, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
- Primary Aldosteronism Center, National Taiwan University Hospital, Taipei, Taiwan.
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15
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Gkaniatsa E, Zverkova Sandström T, Rosengren A, Trimpou P, Olsson DS, Lind M, Muth A, Johannsson G, Ragnarsson O. Mortality in Patients With Primary Aldosteronism: A Swedish Nationwide Study. Hypertension 2023; 80:2601-2610. [PMID: 37855142 DOI: 10.1161/hypertensionaha.123.21895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 10/10/2023] [Indexed: 10/20/2023]
Abstract
BACKGROUND Primary aldosteronism (PA) is associated with increased mortality. The extent to which this phenomenon is affected by sex, age, comorbidities at diagnosis, and different treatment modalities is largely unknown. The objective was to determine all-cause and cause-specific mortality in a population-based cohort of patients with PA and the impact of age at diagnosis, sex, comorbidities, and treatment modalities. METHODS We used national registers to identify patients diagnosed with PA between 1997 and 2019 (n=2419) and controls (n=24 187) from the general population, matched for sex, age, and county of residence. We obtained mortality data from the Cause-of-Death Register. We used Cox regression models, adjusted for socioeconomic factors and diabetes, to estimate adjusted hazard ratios (HRs [95% CI]). RESULTS Overall, 346 (14.3%) patients with PA and 2736 (11.3%) controls died during a median follow-up time of 8.1 years. PA was associated with increased risk from all-cause mortality (HR, 1.23 [95% CI, 1.10-1.38]), death from cardiovascular disease (HR, 1.57 [95% CI, 1.30-1.89]), and stroke (HR, 1.85 [95% CI, 1.16-2.93]). Patients with cardiovascular disease at diagnosis (HR, 1.53 [1.26-1.85]), age >56 years (HR, 1.28 [95% CI, 1.13-1.45]), patients treated with a low dose of a mineralocorticoid receptor antagonist (HR, 1.30 [95% CI, 1.02-1.66]), and untreated patients (HR, 2.51 [95% CI, 1.72-3.67]) had excess mortality. CONCLUSIONS Mortality, mainly due to cardiovascular disease, is increased in patients with PA compared with controls from the general population, particularly in patients aged >56 years, patients with preexisting cardiovascular comorbidities, and patients receiving low dose of a mineralocorticoid receptor antagonist.
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Affiliation(s)
- Eleftheria Gkaniatsa
- Department of Endocrinology (E.G., P.T., D.S.O., G.J., O.R.), Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Medicine, Geriatrics and Emergency Medicine (A.R.), Sahlgrenska University Hospital, Gothenburg, Sweden
| | | | - Annika Rosengren
- Department of Medicine, Geriatrics and Emergency Medicine (A.R.), Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine (A.R., M.L.), University of Gothenburg, Sweden
| | - Penelope Trimpou
- Department of Endocrinology (E.G., P.T., D.S.O., G.J., O.R.), Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Medicine, Geriatrics and Emergency Medicine (A.R.), Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Daniel S Olsson
- Department of Endocrinology (E.G., P.T., D.S.O., G.J., O.R.), Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine (E.G., P.T., D.S.O., G.J., O.R.), University of Gothenburg, Sweden
- Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden (D.S.O.)
| | - Marcus Lind
- Department of Molecular and Clinical Medicine, Institute of Medicine (A.R., M.L.), University of Gothenburg, Sweden
- Department of Medicine, NU Hospital Group, Uddevalla, Sweden (M.L.)
| | - Andreas Muth
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska University Hospital (A.M.), University of Gothenburg, Sweden
| | - Gudmundur Johannsson
- Department of Endocrinology (E.G., P.T., D.S.O., G.J., O.R.), Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine (E.G., P.T., D.S.O., G.J., O.R.), University of Gothenburg, Sweden
| | - Oskar Ragnarsson
- Department of Endocrinology (E.G., P.T., D.S.O., G.J., O.R.), Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine (E.G., P.T., D.S.O., G.J., O.R.), University of Gothenburg, Sweden
- Sahlgrenska Academy, Wallenberg Centre for Molecular and Translational Medicine, Institute of Medicine (O.R.), University of Gothenburg, Sweden
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16
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Li J, Yang N, Chou H, Shi L, Wei M, Li Y. Central diastolic blood pressure, plasma aldosterone and uric acid are associated with microalbuminuria in essential hypertension: a case-control study. BMC Cardiovasc Disord 2023; 23:511. [PMID: 37848834 PMCID: PMC10583460 DOI: 10.1186/s12872-023-03515-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 09/16/2023] [Indexed: 10/19/2023] Open
Abstract
OBJECTIVE To study the development of microalbuminuria (MAU) in essential hypertension (EHT), we investigated the association of MAU with central blood pressure (CBP), direct renin concentration (DRC), plasma aldosterone (PA), and uric acid (UA). METHOD We determined 24 h-urinary albumin excretion (24 h-UAE) in patients with EHT who were hospitalized at TEDA International Cardiovascular Hospital from June 2020 to May 2022. We defined MAU as 24 h-UAE in the range of 30 mg/24 h to 300 mg/24 h. Univariate and multivariate analyses were conducted to determine the associations of MAU with CBP, DRC, PA, and UA in EHT, considering demographic and clinical information. We also plotted receiver operating characteristic curves (ROCs) for predicting MAU using these results. RESULTS More than a quarter of patients (26.5%, 107/404, 95% CI: 22.2-31.1%) were diagnosed with MAU in EHT. A higher body mass index (BMI), longer duration of hypertension, and higher severity were associated with MAU. Also, nearly 10% more creatinine levels were recorded in the MAU group than in the control group (69.5 ± 18.7 µmol/L vs. 64.8 ± 12.5 µmol/L, P = 0.004). The increase was also observed for PA (15.5, 9.7-20.6 ng/dL vs. 12.3, 9.0-17.3 ng/dL, P = 0.024) and UA (419.8 ± 105.6 µmol/L vs. 375.1 ± 89.5 µmol/L, P < 0.001) in the MAU group compared to that in the control group. Several variables were associated with MAU, including central diastolic blood pressure (CDBP) (OR = 1.017, 95% CI: 1.002-1.032, P = 0.027), PA (OR = 1.043, 95% CI: 1.009-1.078, P = 0.012) and UA (OR = 1.005, 95% CI: 1.002-1.008, P < 0.001). For MAU prediction, the area under the curve (AUC) was 0.709 (95% CI: 0.662-0.753; P < 0.001) when CDBP, PA, and UA were used in combination, and the optimal probability of the cut-off value was 0.337. CONCLUSION We found that CDBP, PA, and UA, used for MAU prediction, might be associated with its development during EHT.
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Affiliation(s)
- Jinlong Li
- Department of Hypertension, Clinical School of Cardiovascular Disease, Tianjin Medical University, Tianjin, 300457, China
- Department of Hypertension, TEDA International Cardiovascular Hospital, Tianjin, 300457, China
| | - Ning Yang
- Department of Hypertension, TEDA International Cardiovascular Hospital, Tianjin, 300457, China
| | - Hongda Chou
- Department of Hypertension, TEDA International Cardiovascular Hospital, Tianjin, 300457, China
| | - Leilei Shi
- Department of Hypertension, TEDA International Cardiovascular Hospital, Tianjin, 300457, China
| | - Maoti Wei
- Center for Clinical Epidemiology, TEDA International Cardiovascular Hospital, Tianjin, 300457, China
| | - Yuming Li
- Department of Hypertension, TEDA International Cardiovascular Hospital, Tianjin, 300457, China.
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17
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Asakawa M, Takagi N, Hamada D, Yamasaki Y, Takaku Y, Kawada M, Murata T, Katsuta H. Usefulness of Alternative Therapy with Hydrocortisone in the Postoperative Management of Severe Primary Aldosteronism. Intern Med 2023; 62:2981-2988. [PMID: 36858518 PMCID: PMC10641202 DOI: 10.2169/internalmedicine.1279-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Accepted: 12/28/2022] [Indexed: 03/03/2023] Open
Abstract
Mineralocorticoid deficiency (MD) with hyperkalemia is an important complication of adrenalectomy in patients with primary aldosteronism (PA). We herein report a 52-year-old man with refractory hypertension, hypokalemia, and severe renal dysfunction due to PA caused by a right adrenal adenoma. His estimated glomerular filtration rate (eGFR) transiently increased immediately after adrenalectomy but then gradually declined, and he developed hyperkalemia. A postoperative endocrine examination revealed MD. Considering the patient's hypertension and severe renal dysfunction, we administered hydrocortisone instead of fludrocortisone, which improved the hyperkalemia and stopped the decline in the eGFR. Alternative therapy with hydrocortisone may be useful in such patients with MD.
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Affiliation(s)
- Masahiro Asakawa
- Department of Endocrinology and Metabolism, Tokyo Teishin Hospital, Japan
| | - Noriko Takagi
- Department of Endocrinology and Metabolism, Tokyo Teishin Hospital, Japan
| | - Daisuke Hamada
- Department of Endocrinology and Metabolism, Tokyo Teishin Hospital, Japan
| | - Yuko Yamasaki
- Department of Endocrinology and Metabolism, Tokyo Teishin Hospital, Japan
| | - Yutaro Takaku
- Department of Nephrology, Tokyo Teishin Hospital, Japan
| | | | - Taro Murata
- Department of Urology, Tokyo Teishin Hospital, Japan
| | - Hidenori Katsuta
- Department of Endocrinology and Metabolism, Tokyo Teishin Hospital, Japan
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18
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Araujo-Castro M, Pascual-Corrales E, Martín Rojas P, Parra Ramírez P. Primary aldosteronism: Practical recommendations for treatment and follow-up. HIPERTENSION Y RIESGO VASCULAR 2023; 40:215-221. [PMID: 37993292 DOI: 10.1016/j.hipert.2023.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 08/08/2023] [Accepted: 08/15/2023] [Indexed: 11/24/2023]
Abstract
Primary aldosteronism (PA) is the most common cause of secondary arterial hypertension. For unilateral cases, surgery offers the possibility of cure, with unilateral adrenalectomy being the treatment of choice, whereas bilateral forms of PA are treated mainly with mineralocorticoid receptor antagonists (MRA). The goals of treatment for PA due to either unilateral or bilateral adrenal disease include reversal of the adverse cardiovascular effects of hyperaldosteronism, normalization of serum potassium in patients with hypokalemia, and normalization of blood pressure. The Primary Aldosteronism Surgery Outcome group (PASO) published a study defining clinical and biochemical outcomes based on blood pressure and correction of hypokalemia and aldosterone to renin ratio (ARR) levels for patients undergoing total unilateral adrenalectomy for unilateral PA. In this review, we provide several practical recommendations for the medical and surgical management and follow-up of patients with PA.
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Affiliation(s)
- M Araujo-Castro
- Endocrinology & Nutrition Department, Hospital Universitario Ramón y Cajal, Madrid, Spain; Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Spain; University of Alcalá, Madrid, Spain.
| | - E Pascual-Corrales
- Endocrinology & Nutrition Department, Hospital Universitario Ramón y Cajal, Madrid, Spain; Instituto de Investigación Biomédica Ramón y Cajal (IRYCIS), Spain
| | - P Martín Rojas
- Endocrinology & Nutrition Department, Hospital Universitario La Paz Madrid, Spain
| | - P Parra Ramírez
- Endocrinology & Nutrition Department, Hospital Universitario La Paz Madrid, Spain
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19
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Rege J, Bandulik S, Nanba K, Kosmann C, Blinder AR, Plain A, Vats P, Kumar-Sinha C, Lerario AM, Else T, Yamazaki Y, Satoh F, Sasano H, Giordano TJ, Williams TA, Reincke M, Turcu AF, Udager AM, Warth R, Rainey WE. Somatic SLC30A1 mutations altering zinc transporter ZnT1 cause aldosterone-producing adenomas and primary aldosteronism. Nat Genet 2023; 55:1623-1631. [PMID: 37709865 PMCID: PMC12051258 DOI: 10.1038/s41588-023-01498-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 08/08/2023] [Indexed: 09/16/2023]
Abstract
Primary aldosteronism (PA) is the most common form of endocrine hypertension and is characterized by inappropriately elevated aldosterone production via a renin-independent mechanism. Driver somatic mutations for aldosterone excess have been found in approximately 90% of aldosterone-producing adenomas (APAs). Other causes of lateralized adrenal PA include aldosterone-producing nodules (APNs). Using next-generation sequencing, we identified recurrent in-frame deletions in SLC30A1 in four APAs and one APN (p.L51_A57del, n = 3; p.L49_L55del, n = 2). SLC30A1 encodes the ubiquitous zinc efflux transporter ZnT1 (zinc transporter 1). The identified SLC30A1 variants are situated close to the zinc-binding site (His43 and Asp47) in transmembrane domain II and probably cause abnormal ion transport. Cases of PA with SLC30A1 mutations showed male dominance and demonstrated increased aldosterone and 18-oxocortisol concentrations. Functional studies of the SLC30A151_57del variant in a doxycycline-inducible adrenal cell system revealed pathological Na+ influx. An aberrant Na+ current led to depolarization of the resting membrane potential and, thus, to the opening of voltage-gated calcium (Ca2+) channels. This resulted in an increase in cytosolic Ca2+ activity, which stimulated CYP11B2 mRNA expression and aldosterone production. Collectively, these data implicate zinc transporter alterations as a dominant driver of aldosterone excess in PA.
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Affiliation(s)
- Juilee Rege
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
| | - Sascha Bandulik
- Medical Cell Biology, University of Regensburg, Regensburg, Germany
| | - Kazutaka Nanba
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
- Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Carla Kosmann
- Medical Cell Biology, University of Regensburg, Regensburg, Germany
| | - Amy R Blinder
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
| | - Allein Plain
- Medical Cell Biology, University of Regensburg, Regensburg, Germany
| | - Pankaj Vats
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
- Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Chandan Kumar-Sinha
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
- Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Antonio M Lerario
- Division of Metabolism, Endocrine, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Tobias Else
- Division of Metabolism, Endocrine, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Yuto Yamazaki
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Fumitoshi Satoh
- Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | | | - Tracy Ann Williams
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig Maximilian University of Munich, Munich, Germany
- Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Martin Reincke
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig Maximilian University of Munich, Munich, Germany
| | - Adina F Turcu
- Division of Metabolism, Endocrine, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Aaron M Udager
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
- Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA
- Department of Pathology, University of Michigan, Ann Arbor, MI, USA
| | - Richard Warth
- Medical Cell Biology, University of Regensburg, Regensburg, Germany
| | - William E Rainey
- Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
- Division of Metabolism, Endocrine, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
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20
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Funes Hernandez M, Bhalla V. Underdiagnosis of Primary Aldosteronism: A Review of Screening and Detection. Am J Kidney Dis 2023; 82:333-346. [PMID: 36965825 DOI: 10.1053/j.ajkd.2023.01.447] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 01/08/2023] [Indexed: 03/27/2023]
Abstract
A clinical condition may be missed due to its higher-than-recognized prevalence or inadequate diagnostic screening. Both factors apply to primary aldosteronism, which is woefully underdiagnosed as a cause of hypertension and end-organ damage. Screening tests should be strongly considered for diseases that pose significant morbidity or mortality if left untreated, that have a high prevalence, and that have treatments that lead to improvement or cure. In this review we present the evidence for each of these points. We outline studies that estimate the prevalence of primary aldosteronism in different at-risk populations and how its recognition has changed over time. We also evaluate myriad studies of screening rates for primary aldosteronism and what factors do and do not influence current screening practices. We discuss the ideal conditions for screening, measuring the aldosterone to renin ratio in different populations that use plasma renin activity or direct renin concentration, and the steps for diagnostic workup of primary aldosteronism. Finally, we conclude with potential strategies to implement higher rates of screening and diagnosis of this common, consequential, and treatable disease.
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Affiliation(s)
- Mario Funes Hernandez
- Stanford Hypertension Center and Division of Nephrology, Department of Medicine, School of Medicine, Stanford University, Stanford, California
| | - Vivek Bhalla
- Stanford Hypertension Center and Division of Nephrology, Department of Medicine, School of Medicine, Stanford University, Stanford, California.
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21
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Sheu JY, Wang SM, Wu VC, Huang KH, Tseng CS, Lee YJ, Tsai YC, Lin YH, Chueh JS. Estimated glomerular filtration rate-dip after medical target therapy associated with increased mortality and cardiovascular events in patients with primary aldosteronism. J Hypertens 2023; 41:1401-1410. [PMID: 37334546 DOI: 10.1097/hjh.0000000000003479] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/20/2023]
Abstract
OBJECTIVES The correlation of the changes of estimated glomerular filtration rate (eGFR) with long-term cardiovascular complications in patients with primary aldosteronism (PA) following mineralocorticoid receptor antagonists (MRA) treatment remains ambiguous. This prospective study aims to determine factors associated with all-cause mortality and de novo cardiovascular events of PA patients against the eGFR-dip. METHODS A total of 208 newly diagnosed PA patients were enrolled from January 2017 to January 2019. MRA was administered with at least a 6-month follow-up. The 'eGFR-dip' was defined as the difference between eGFR at 6 months after MRA treatment and respective baseline eGFR divided by the baseline eGFR. RESULTS After a mean 5.7 years follow-up, an eGFR-dip more than 12%, which was detected in 99 (47.6%) of the 208 patients, was a significant independent risk factor predicting composite outcomes (all-cause mortality, de-novo three-point major adverse cardiovascular events, and/or congestive heart failure). Multivariable logistic regression showed that age [odds ratio (OR), 0.94; P = 0.003], pretreatment plasma aldosterone concentration (PAC; OR, 0.98; P = 0.004), and initial eGFR (OR, 0.97; P < 0.001) had a positive linkage with the eGFR-dip more than 12%. CONCLUSIONS Nearly half of PA patients had an eGFR-dip more than 12% after 6 months of MRA treatment. They had a higher incidence of all-cause mortality and de novo cardiovascular events. Elder age, higher pretreatment PAC, or higher initial eGFR could be associated with an elevated risk of an eGFR-dip more than 12%.
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Affiliation(s)
- Jia-Yuh Sheu
- Department of Medical Education, National Taiwan University Hospital
| | - Shuo-Meng Wang
- Department of Urology, National Taiwan University Hospital
- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group
- Primary Aldosteronism Center of National Taiwan University Hospital, Taipei, Taiwan
| | - Vin-Cent Wu
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine
- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group
- Primary Aldosteronism Center of National Taiwan University Hospital, Taipei, Taiwan
| | - Kuo-How Huang
- Department of Urology, National Taiwan University Hospital
- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group
- Primary Aldosteronism Center of National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Shin Tseng
- Department of Urology, National Taiwan University Hospital
| | - Yuan-Ju Lee
- Department of Urology, National Taiwan University Hospital
| | - Yao-Chou Tsai
- Division of Urology, Department of Surgery, Taipei Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei City
| | - Yen-Hung Lin
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine
- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group
- Primary Aldosteronism Center of National Taiwan University Hospital, Taipei, Taiwan
| | - Jeff S Chueh
- Department of Urology, National Taiwan University Hospital
- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group
- Primary Aldosteronism Center of National Taiwan University Hospital, Taipei, Taiwan
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22
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Mansour N, Mittermeier A, Walter R, Schachtner B, Rudolph J, Erber B, Schmidt VF, Heinrich D, Bruedgam D, Tschaidse L, Nowotny H, Bidlingmaier M, Kunz SL, Adolf C, Ricke J, Reincke M, Reisch N, Wildgruber M, Ingrisch M. Integration of clinical parameters and CT-based radiomics improves machine learning assisted subtyping of primary hyperaldosteronism. Front Endocrinol (Lausanne) 2023; 14:1244342. [PMID: 37693351 PMCID: PMC10484561 DOI: 10.3389/fendo.2023.1244342] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 08/08/2023] [Indexed: 09/12/2023] Open
Abstract
Objectives The aim of this study was to investigate an integrated diagnostics approach for prediction of the source of aldosterone overproduction in primary hyperaldosteronism (PA). Methods 269 patients from the prospective German Conn Registry with PA were included in this study. After segmentation of adrenal glands in native CT images, radiomic features were calculated. The study population consisted of a training (n = 215) and a validation (n = 54) cohort. The k = 25 best radiomic features, selected using maximum-relevance minimum-redundancy (MRMR) feature selection, were used to train a baseline random forest model to predict the result of AVS from imaging alone. In a second step, clinical parameters were integrated. Model performance was assessed via area under the receiver operating characteristic curve (ROC AUC). Permutation feature importance was used to assess the predictive value of selected features. Results Radiomics features alone allowed only for moderate discrimination of the location of aldosterone overproduction with a ROC AUC of 0.57 for unilateral left (UL), 0.61 for unilateral right (UR), and 0.50 for bilateral (BI) aldosterone overproduction (total 0.56, 95% CI: 0.45-0.65). Integration of clinical parameters into the model substantially improved ROC AUC values (0.61 UL, 0.68 UR, and 0.73 for BI, total 0.67, 95% CI: 0.57-0.77). According to permutation feature importance, lowest potassium value at baseline and saline infusion test (SIT) were the two most important features. Conclusion Integration of clinical parameters into a radiomics machine learning model improves prediction of the source of aldosterone overproduction and subtyping in patients with PA.
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Affiliation(s)
- Nabeel Mansour
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Andreas Mittermeier
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Roman Walter
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | | | - Jan Rudolph
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Bernd Erber
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Vanessa F. Schmidt
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Daniel Heinrich
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
| | - Denise Bruedgam
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
| | - Lea Tschaidse
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
| | - Hanna Nowotny
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
| | - Martin Bidlingmaier
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
| | - Sonja L. Kunz
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
| | - Christian Adolf
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
| | - Jens Ricke
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Martin Reincke
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
| | - Nicole Reisch
- Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany
| | - Moritz Wildgruber
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Michael Ingrisch
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
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23
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Charoensri S, Turcu AF. Primary Aldosteronism Prevalence - An Unfolding Story. Exp Clin Endocrinol Diabetes 2023; 131:394-401. [PMID: 36996879 DOI: 10.1055/a-2066-2696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/01/2023]
Abstract
Primary aldosteronism (PA) is characterized by dysregulated, renin-independent aldosterone excess. Long perceived as rare, PA has emerged as one of the most common causes of secondary hypertension. Failure to recognize and treat PA results in cardiovascular and renal complications, through processes mediated by both direct target tissue insults and indirectly, by hypertension. PA spans a continuum of dysregulated aldosterone secretion, which is typically recognized in late stages after treatment-resistant hypertension and cardiovascular and/or renal complications develop. Determining the precise disease burden remains challenging due to heterogeneity in testing, arbitrary thresholds, and populations studied. This review summarizes the reports on PA prevalence among the general population and in specific high-risk subgroups, highlighting the impact of rigid versus permissive criteria on PA prevalence perception.
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Affiliation(s)
- Suranut Charoensri
- Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, USA. Ann Arbor, Michigan
- Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Khon Kaen University, Thailand
| | - Adina F Turcu
- Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, USA. Ann Arbor, Michigan
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24
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Rocca A, Gkaniatsa E, Brunese MC, Hessman E, Muth A, Nwaru BI, Ragnarsson O, Bobbio E, Esposito D. Therapeutic outcomes with surgical and medical management for primary aldosteronism: protocol for a systematic review and meta-analysis. BMJ Open 2023; 13:e072585. [PMID: 37518075 PMCID: PMC10387625 DOI: 10.1136/bmjopen-2023-072585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 07/18/2023] [Indexed: 08/01/2023] Open
Abstract
INTRODUCTION Treatment strategies for primary aldosteronism (PA) include unilateral adrenalectomy and medical treatment with mineralocorticoid receptor (MR) antagonists. Whether these two different treatment strategies are comparable in mitigating the detrimental effect of PA on outcomes is still debated. OBJECTIVES The primary aim of this systematic review is to identify, appraise and synthesise existing literature comparing clinical outcomes after treatment in patients with PA. METHODS AND ANALYSIS A systematic and comprehensive search will be performed using PubMed, Web of Science and EMBASE, for studies published until December 2022. Observational and interventional studies will be eligible for inclusion. The quality of observational studies will be assessed using the Newcastle-Ottawa Scale, while interventional studies will be assessed using the Cochrane Effective Practice Organization of Care tool. The collected evidence will be narratively synthesised. We will perform meta-analysis to pool estimates from studies considered to be homogeneous. Reporting of the systematic review and meta-analysis will be in accordance with the Meta-analysis of Observational Studies in Epidemiology Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. ETHICS AND DISSEMINATION As this study is based solely on the published literature, no ethics approval is required. This review will aim to provide some estimates on outcomes, including survival, rates of clinical and biochemical control, cardiovascular and cerebrovascular events, as well as data on quality of life and renal function, in patients with PA treated surgically or with MR antagonists. The study findings will be presented at scientific meetings and will be published in an international peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER CRD42022362506.
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Affiliation(s)
- Aldo Rocca
- Department of Medicine and Health Science 'V Tiberio', University of Molise, Campobasso, Italy
| | - Eleftheria Gkaniatsa
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Maria Chiara Brunese
- Department of Medicine and Health Science 'V Tiberio', University of Molise, Campobasso, Italy
| | - Eva Hessman
- Biomedical Library, Gothenburg University Library, University of Gothenburg, Gothenburg, Sweden
| | - Andreas Muth
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Bright I Nwaru
- Krefting Research Centre, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Wallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Oskar Ragnarsson
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Emanuele Bobbio
- Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Daniela Esposito
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
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25
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Nakano Y, Murakami M, Hara K, Fukuda T, Horino M, Takeuchi A, Niitsu Y, Shiba K, Tsujimoto K, Komiya C, Yokoyama M, Ikeda K, Yoshimoto T, Fujii Y, Yamada T. Long-term effects of primary aldosteronism treatment on patients with primary aldosteronism and chronic kidney disease. Clin Endocrinol (Oxf) 2023; 98:323-331. [PMID: 36367014 DOI: 10.1111/cen.14849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 11/05/2022] [Accepted: 11/08/2022] [Indexed: 11/13/2022]
Abstract
OBJECTIVE Primary aldosteronism (PA) is a major cause of secondary hypertension and is associated with chronic renal injury. The glomerular filtration rate (GFR) in PA rapidly decreases after the removal of glomerular hyperfiltration due to aldosterone excess by adrenalectomy (ADX) or mineralocorticoid receptor antagonist (MRA) treatment and is stable in the long term. However, the effects of these treatments on the long-term renal function of PA patients with chronic kidney disease (CKD) is not well understood. DESIGN AND PATIENTS In this single-center, retrospective study, acute and chronic changes in the estimated GFR (eGFR) were examined in 107 patients with PA, including 49 patients with post-treatment CKD defined as eGFR < 60 ml/min/1.73 m2 . RESULTS The reduction in eGFR observed 1 month after ADX in the CKD group (N = 31) was -20.1 ± 8.2 ml/min/1.73 m2 . Multivariate analysis showed that pre-treatment eGFR and plasma aldosterone concentration were independent predictive factors of the acute reduction in eGFR after ADX. The reduction of eGFR observed 1 month after MRA administration in the post-treatment CKD group (N = 18) was -9.2 ± 5.9 ml/min/1.73 m2 . Multivariate analysis showed that the duration of hypertension and pre-treatment eGFR were independent predictive factors of the acute reduction in eGFR after ADX administration. In 20 patients with CKD (N = 12 ADX and N = 8 MRA) followed for more than 5 years post-treatment, there was no further significant decline in eGFR over a follow-up period of 7 (6, 8) years nor any difference between the two treatment modalities. CONCLUSIONS Our study suggests that treatment of PA in stage 3 CKD is safe and useful in preventing renal injury.
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Affiliation(s)
- Yujiro Nakano
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
- Department of Endocrinology and Metabolism, Kanazawa University, Takaramachi, Ishikawa, Japan
| | - Masanori Murakami
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Kazunari Hara
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Tatsuya Fukuda
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Masato Horino
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Akira Takeuchi
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Yoshihiro Niitsu
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Kumiko Shiba
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
- The Center for Personalized Medicine for Healthy Aging, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Kazutaka Tsujimoto
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Chikara Komiya
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Minato Yokoyama
- Department of Urology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Kenji Ikeda
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Takanobu Yoshimoto
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
- Department of Diabetes and Endocrinology, Tokyo Metropolitan Hiroo Hospital, Shibuya-ku, Tokyo, Japan
| | - Yasuhisa Fujii
- Department of Urology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
| | - Tetsuya Yamada
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
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26
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Fernandes-Rosa FL, Boulkroun S, Fedlaoui B, Hureaux M, Travers-Allard S, Drossart T, Favier J, Zennaro MC. New advances in endocrine hypertension: from genes to biomarkers. Kidney Int 2023; 103:485-500. [PMID: 36646167 DOI: 10.1016/j.kint.2022.12.021] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 12/16/2022] [Accepted: 12/19/2022] [Indexed: 01/15/2023]
Abstract
Hypertension (HT) is a major cardiovascular risk factor that affects 10% to 40% of the general population in an age-dependent manner. Detection of secondary forms of HT is particularly important because it allows the targeted management of the underlying disease. Among hypertensive patients, the prevalence of endocrine HT reaches up to 10%. Adrenal diseases are the most frequent cause of endocrine HT and are associated with excess production of mineralocorticoids (mainly primary aldosteronism), glucocorticoids (Cushing syndrome), and catecholamines (pheochromocytoma). In addition, a few rare diseases directly affecting the action of mineralocorticoids and glucocorticoids in the kidney also lead to endocrine HT. Over the past years, genomic and genetic studies have allowed improving our knowledge on the molecular mechanisms of endocrine HT. Those discoveries have opened new opportunities to transfer knowledge to clinical practice for better diagnosis and specific treatment of affected subjects. In this review, we describe the physiology of adrenal hormone biosynthesis and action, the clinical and biochemical characteristics of different forms of endocrine HT, and their underlying genetic defects. We discuss the impact of these discoveries on diagnosis and management of patients, as well as new perspectives related to the use of new biomarkers for improved patient care.
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Affiliation(s)
| | | | | | - Marguerite Hureaux
- Université Paris Cité, PARCC, Inserm, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France
| | - Simon Travers-Allard
- Université Paris Cité, PARCC, Inserm, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Physiologie, Paris, France
| | - Tom Drossart
- Université Paris Cité, PARCC, Inserm, Paris, France; Université de Paris Cité, PARCC, Inserm, Equipe Labellisée par la Ligue contre le Cancer, Paris, France
| | - Judith Favier
- Université Paris Cité, PARCC, Inserm, Paris, France; Université de Paris Cité, PARCC, Inserm, Equipe Labellisée par la Ligue contre le Cancer, Paris, France
| | - Maria-Christina Zennaro
- Université Paris Cité, PARCC, Inserm, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France.
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27
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Voss N, Mørup S, Clausen C, Feltoft CL, Jepsen JV, Hornum M, Andreassen M, Krogh J. Prognostic value of contralateral suppression on kidney function after surgery in patients with primary aldosteronism. Clin Endocrinol (Oxf) 2023; 98:306-314. [PMID: 36263597 DOI: 10.1111/cen.14836] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 10/12/2022] [Accepted: 10/13/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND OBJECTIVE Adrenalectomy for primary aldosteronism (PA) has been associated with decreased kidney function after surgery. It has been proposed that elimination of excess aldosterone unmasks an underlying failure of the kidney function. Contralateral suppression (CLS) is considered a marker of aldosterone excess and disease severity, and the purpose of this study was to assess the hypothesis that CLS would predict change in kidney function after adrenalectomy in patients with PA. DESIGN AND PATIENTS Patients with PA referred for adrenal venous sampling (AVS) between May 2011 and August 2021 and who were subsequently offered surgical or medical treatment were eligible for the current study. RESULTS A total of 138 patients were included and after AVS 85/138 (61.6%) underwent adrenalectomy while 53/138 (38.4%) were treated with MR-antagonists. In surgically treated patients the estimated glomerular filtration rate (eGFR) was reduced by 11.5 (SD: 18.5) compared to a reduction of 5.9 (SD: 11.5) in medically treated patients (p = .04). Among surgically treated patients, 59/85 (69.4%) were classified as having CLS. After adrenalectomy, patients with CLS had a mean reduction in eGFR of 17.5 (SD: 17.6) compared to an increase of 1.8 (SD: 12.8) in patients without CLS (p < .001). The association between CLS and change in kidney function remained unchanged in multivariate analysis. Post-surgery, 16/59 (27.1%) patients with CLS developed hyperkalemia compared to 2/26 (7.7%) in patients without CLS (p = .04). CONCLUSION This retrospective study found that CLS was a strong and independent predictor of a marked reduction of eGFR and an increased risk of hyperkalemia after adrenalectomy in patients with PA.
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Affiliation(s)
- Nathalie Voss
- Department of Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Sara Mørup
- Department of Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Caroline Clausen
- Department of Radiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Claus Larsen Feltoft
- Department of Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
| | - Jan Viberg Jepsen
- Department of Urology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
| | - Mads Hornum
- Department of Nephrology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen University, Copenhagen, Denmark
| | - Mikkel Andreassen
- Department of Nephrology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen University, Copenhagen, Denmark
| | - Jesper Krogh
- Department of Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen University, Copenhagen, Denmark
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Wu VC, Chan CK, Chueh JS, Chen YM, Lin YH, Chang CC, Lin PC, Chung SD. Markers of Kidney Tubular Function Deteriorate While Those of Kidney Tubule Health Improve in Primary Aldosteronism After Targeted Treatments. J Am Heart Assoc 2023; 12:e028146. [PMID: 36789834 PMCID: PMC10111488 DOI: 10.1161/jaha.122.028146] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
Background Targeted treatment with mineralocorticoid receptor antagonists (MRAs) or adrenalectomy in patients with primary aldosteronism (PA) causes a decline in estimated glomerular filtration rate; however, the associated simultaneous changes in biomarkers of kidney tubule health still remain unclear. Methods and Results We matched 104 patients with newly diagnosed unilateral PA who underwent adrenalectomy with 104 patients with unilateral PA who were treated with MRAs, 104 patients with bilateral PA treated with MRAs, and 104 patients with essential hypertension who served as controls. Functional biomarkers were measured before the targeted treatment and 1 year after treatment, including serum markers of kidney function (cystatin C, creatinine), urinary markers of proximal renal tubular damage (L-FABP [liver-type fatty-acid binding protein], KIM-1 [kidney injury molecule-1]), serum markers of kidney tubular reserve and mineral metabolism (intact parathyroid hormone), and proteinuria. Compared with the patients with essential hypertension, the patients with PA had higher pretreatment serum intact parathyroid hormone and urinary creatinine-corrected parameters, including L-FABP, KIM-1, and albumin. The patients with essential hypertension and with PA had similar cystatin C levels. After treatment with MRAs or adrenalectomy of unilateral PA and MRAs of bilateral PA, the patients with PA had increased serum cystatin C and decreased urinary L-FABP/creatinine, KIM-1/creatinine, creatinine-based estimated glomerular filtration rate, intact parathyroid hormone, and proteinuria (all P<0.05). In multivariable regression models, a higher urinary L-FABP/creatinine ratio and older age were significantly correlated with the occurrence of kidney failure (estimated glomerular filtration rate dip ≥30%) in the patients with PA after targeted treatment. Conclusions Compared with the matched patients with essential hypertension, the incident patients with PA at diagnosis had higher levels of several biomarkers, including markers of kidney damage, tubular reserve/mineral metabolism, and proteinuria. Functional kidney failure in the patients with PA after treatment could be predicted by a higher baseline urinary L-FABP/creatinine ratio and older age. After targeted treatments in the patients with bilateral or unilateral PA, these biomarkers of kidney tubule health were restored, but creatinine-based estimated glomerular filtration rate declined, which may therefore reflect hemodynamic changes rather than intrinsic damage to kidney tubular cells.
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Affiliation(s)
- Vin-Cent Wu
- Department of Internal Medicine National Taiwan University Hospital and College of Medicine, National Taiwan University Taipei Taiwan.,TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group Taipei Taiwan.,Primary Aldosteronism Center at National Taiwan University Hospital (NTUH-PAC) Taipei Taiwan
| | - Chieh-Kai Chan
- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group Taipei Taiwan.,Department of Internal Medicine National Taiwan University Hospital Hsin-Chu Branch Hsin-Chu County Taiwan
| | - Jeff S Chueh
- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group Taipei Taiwan.,Department of Urology National Taiwan University Hospital and College of Medicine, National Taiwan University Taipei Taiwan
| | - Yung-Ming Chen
- Department of Internal Medicine National Taiwan University Hospital and College of Medicine, National Taiwan University Taipei Taiwan
| | - Yen-Hung Lin
- Department of Internal Medicine National Taiwan University Hospital and College of Medicine, National Taiwan University Taipei Taiwan.,TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group Taipei Taiwan.,Primary Aldosteronism Center at National Taiwan University Hospital (NTUH-PAC) Taipei Taiwan
| | - Chin-Chen Chang
- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group Taipei Taiwan.,Department of Imaging Medicine National Taiwan University Hospital and College of Medicine, National Taiwan University Taipei Taiwan
| | - Po-Chih Lin
- Department of Internal Medicine National Taiwan University Hospital and College of Medicine, National Taiwan University Taipei Taiwan
| | - Shiu-Dong Chung
- Division of Urology, Department of Surgery Far Eastern Memorial Hospital New Taipei City Taiwan.,Department of Nursing College of Healthcare and Management, General Education Center, Asia Eastern University of Science and Technology New Taipei City Taiwan
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- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group Taipei Taiwan
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29
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Cohen JB, Bancos I, Brown JM, Sarathy H, Turcu AF, Cohen DL. Primary Aldosteronism and the Role of Mineralocorticoid Receptor Antagonists for the Heart and Kidneys. Annu Rev Med 2023; 74:217-230. [PMID: 36375469 PMCID: PMC9892285 DOI: 10.1146/annurev-med-042921-100438] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Primary aldosteronism (PA) is the most common cause of secondary hypertension but is frequently underrecognized and undertreated. Patients with PA are at a markedly increased risk for target organ damage to the heart and kidneys. While patients with unilateral PA can be treated surgically, many patients with PA are not eligible or willing to undergo surgery. Steroidal mineralocorticoid receptor antagonists (MRAs) are highly effective for treating PA and reducing the risk of target organ damage. However, steroidal MRAs are often underprescribed and can be poorly tolerated by some patients due to side effects. Nonsteroidal MRAs reduce adverse renal and cardiovascular outcomes among patients with diabetic kidney disease and are bettertolerated than steroidal MRAs. While their blood pressure-lowering effects remain unclear, these agents may have a potential role in reducing target organ damage in patients with PA.
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Affiliation(s)
- Jordana B Cohen
- Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; ,
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Irina Bancos
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA;
| | - Jenifer M Brown
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA;
| | - Harini Sarathy
- Division of Nephrology, Department of Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, California, USA;
| | - Adina F Turcu
- Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA;
| | - Debbie L Cohen
- Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; ,
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Yoshida Y, Fujiki R, Kinoshita M, Sada K, Miyamoto S, Ozeki Y, Mori Y, Matsuda N, Noguchi T, Nakama H, Okamoto M, Gotoh K, Masaki T, Shibata H. Importance of dietary salt restriction for patients with primary aldosteronism during treatment with mineralocorticoid receptor antagonists: The potential importance of post-treatment plasma renin levels. Hypertens Res 2023; 46:100-107. [PMID: 36229529 DOI: 10.1038/s41440-022-01045-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/07/2022] [Accepted: 09/09/2022] [Indexed: 02/03/2023]
Abstract
We measured dietary salt intake in 26 patients with primary aldosteronism treated with mineralocorticoid receptor antagonists and evaluated whether plasma renin levels were affected by dietary salt intake pre-treatment and post 6 months of mineralocorticoid receptor antagonist treatment. The dietary salt intake level was calculated using spot urine sodium and creatinine concentrations, body weight, height, and age. The clinical parameters pre- and post- treatment were compared. The systolic and diastolic blood pressure levels decreased, and the serum potassium and active renin concentration increased significantly. Although the dietary salt intake did not change after treatment, the differences in dietary salt intake and active renin concentration pre- and post- treatment were inversely correlated (r = -0.418, p = 0.03). The 26 patients were divided into two groups with active renin concentration levels ≥5 pg/mL (Group 1) and <5 pg/mL (Group 2) after treatment. The Group parameters did not differ pre- and post- treatment. Group 1 evidenced improvements in systolic and diastolic blood pressures, and the potassium level and active renin concentration over time; Group 2 did not. Group 1 evidenced no significant correlation between the differences in dietary salt intake and active renin concentration levels (r = -0.481, p = 0.11) but Group 2 showed a strong inverse correlation (r = -0.7599, p = 0.01). In conclusion, we found that an active renin concentration level <5 pg/mL post-mineralocorticoid receptor antagonist treatment may indicate that salt sensitivity has not adequately improved, emphasizing the importance of measuring plasma renin levels after such treatment.
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Affiliation(s)
- Yuichi Yoshida
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Rika Fujiki
- Faculty of Medicine, Oita University, Yufu, Japan
| | - Mizuki Kinoshita
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Kentaro Sada
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Shotaro Miyamoto
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yoshinori Ozeki
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Yumi Mori
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Naoki Matsuda
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Takaaki Noguchi
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Hiroshi Nakama
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Mitsuhiro Okamoto
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Koro Gotoh
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Takayuki Masaki
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan
| | - Hirotaka Shibata
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu, Japan.
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Vaidya A, Hundemer GL, Nanba K, Parksook WW, Brown JM. Primary Aldosteronism: State-of-the-Art Review. Am J Hypertens 2022; 35:967-988. [PMID: 35767459 PMCID: PMC9729786 DOI: 10.1093/ajh/hpac079] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/15/2022] [Accepted: 06/27/2022] [Indexed: 12/15/2022] Open
Abstract
We are witnessing a revolution in our understanding of primary aldosteronism (PA). In the past 2 decades, we have learned that PA is a highly prevalent syndrome that is largely attributable to pathogenic somatic mutations, that contributes to cardiovascular, metabolic, and kidney disease, and that when recognized, can be adequately treated with widely available mineralocorticoid receptor antagonists and/or surgical adrenalectomy. Unfortunately, PA is rarely diagnosed, or adequately treated, mainly because of a lack of awareness and education. Most clinicians still possess an outdated understanding of PA; from primary care physicians to hypertension specialists, there is an urgent need to redefine and reintroduce PA to clinicians with a modern and practical approach. In this state-of-the-art review, we provide readers with the most updated knowledge on the pathogenesis, prevalence, diagnosis, and treatment of PA. In particular, we underscore the public health importance of promptly recognizing and treating PA and provide pragmatic solutions to modify clinical practices to achieve this.
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Affiliation(s)
- Anand Vaidya
- Department of Medicine, Center for Adrenal Disorders, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Gregory L Hundemer
- Department of Medicine (Division of Nephrology) and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - Kazutaka Nanba
- Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
- Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA
| | - Wasita W Parksook
- Department of Medicine, Division of Endocrinology and Metabolism, and Division of General Internal Medicine, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Jenifer M Brown
- Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
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Chen SY, Chen JY, Huang WC, Puar THK, Chin Kek P, Chueh JS, Lin YH, Wu VC, Study Group T. Cardiovascular outcomes and all-cause mortality in primary aldosteronism after adrenalectomy or mineralocorticoid receptor antagonist treatment: a meta-analysis. Eur J Endocrinol 2022; 187:S47-S58. [PMID: 36315466 DOI: 10.1530/eje-22-0375] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 10/31/2022] [Indexed: 11/08/2022]
Abstract
BACKGROUND In patients with primary aldosteronism (PA), long-term cardiovascular and mortality outcomes after adrenalectomy vs mineralocorticoid receptor antagonist (MRA) have not been compared yet. We aim to compare the clinical outcomes of these patients after treatment. DESIGN AND METHODS A systematic review and meta-analysis was conducted by searching PubMed, Cochrane library, and Embase from no start date restriction to 18 December 2021. Our composite primary outcomes were long-term all-cause mortality and/or major adverse cardiovascular events (MACE), including coronary artery disease (CAD), stroke, arrhythmia, and congestive heart failure. We adopted the random-effects model and performed subgroup analyses, meta-regression, and trial sequential analysis (TSA). RESULTS A total of 9 studies with 8473 adult patients with PA (≥18 years) were enrolled. A lower incidence of composite primary outcomes was observed in the adrenalectomy group (odds ratio (OR): 0.46 (95% CI: 0.38-0.56), P < 0.001). We found a lower incidence of all-cause mortality (OR: 0.33 (95% CI: 0.15-0.73), P = 0.006) and MACE (OR: 0.55, (95% CI: 0.40-0.74), P = 0.0001) in the adrenalectomy group. The incidence of CAD (OR: 0.33 (95% CI: 0.15-0.75), P = 0.008), arrhythmias (OR: 0.46 (95% CI: 0.27-0.81), P = 0.007), and congestive heart failure (OR: 0.52 (95% CI: 0.33-0.81), P = 0.004) was also lower in adrenalectomy group. The metaregression showed patient's age may attenuate the benefits of adrenalectomy on composite primary outcomes (coefficient: 1.084 (95% CI: 1.005-1.169), P = 0.036). TSA demonstrated that the accrued sample size and effect size were sufficiently large to draw a solid conclusion, and the advantage of adrenalectomy over MRA was constant with the chronological sequence. CONCLUSIONS In conclusion, adrenalectomy could be preferred over MRA for patients with PA in reducing the risk of all-cause mortality and/or MACE and should be considered as the treatment of choice. That patients with PA could get less benefit from adrenalectomy as they age warrants further investigation.
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Affiliation(s)
- Sheng-Yin Chen
- School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jui-Yi Chen
- Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Wei-Chieh Huang
- Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Troy Hai Kiat Puar
- Department of Endocrinology, Changi General Hospital, SingHealth, Singapore
| | - Peng Chin Kek
- Department of Endocrinology, Singapore General Hospital, Singapore
| | - Jeff S Chueh
- Department of Urology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yen-Hung Lin
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group, Taiwan
| | - Vin-Cent Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group, Taiwan
| | - Taipai Study Group
- TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group, Taiwan
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Abstract
Primary aldosteronism is a common cause of hypertension and is a risk factor for cardiovascular and renal morbidity and mortality, via mechanisms mediated by both hypertension and direct insults to target organs. Despite its high prevalence and associated complications, primary aldosteronism remains largely under-recognized, with less than 2% of people in at-risk populations ever tested. Fundamental progress made over the past decade has transformed our understanding of the pathogenesis of primary aldosteronism and of its clinical phenotypes. The dichotomous paradigm of primary aldosteronism diagnosis and subtyping is being redefined into a multidimensional spectrum of disease, which spans subclinical stages to florid primary aldosteronism, and from single-focal or multifocal to diffuse aldosterone-producing areas, which can affect one or both adrenal glands. This Review discusses how redefining the primary aldosteronism syndrome as a multidimensional spectrum will affect the approach to the diagnosis and subtyping of primary aldosteronism.
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Affiliation(s)
- Adina F Turcu
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, USA.
| | - Jun Yang
- Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria, Australia
- Department of Medicine, Monash University, Clayton, Victoria, Australia
| | - Anand Vaidya
- Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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Arjani S, Bostonian TJ, Prasath V, Quinn PL, Chokshi RJ. Cost-effectiveness of adrenal vein sampling- vs computed tomography-guided adrenalectomy for unilateral adrenaloma in primary aldosteronism. J Endocrinol Invest 2022; 45:1899-1908. [PMID: 35612811 DOI: 10.1007/s40618-022-01821-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 05/05/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE Adrenalectomies performed for the treatment of primary aldosteronism due to unilateral adenoma are traditionally confirmed with, and guided by, results from adrenal vein sampling (AVS). However, the usefulness of AVS at the expense of cost and complications is debated, and many institutions have independent protocols that use AVS to varying degrees. METHODS Cost-effectiveness of AVS- vs computed tomography (CT)-based adrenalectomy was calculated using decision tree models. The tree was populated with values describing biochemical post-operative outcomes from the published literature; patients were placed into AVS- or CT-dependent treatment arms. Biochemical outcomes were defined based on patients' potassium levels and aldosterone-renin ratios. Patients underwent adrenalectomies and received medical management dosed based on surgical outcomes. Costs were represented by Medicare (FY2021) reimbursement rates (US$) and quality-adjusted life-years (QALYs) were calculated using published morbidity and survival data. A willingness-to-pay of $100,000 per QALY gained was set to determine the most cost-effective strategy. The primary outcome was the incremental cost-effectiveness ratio (ICER) associated with biochemical outcomes. RESULTS The base case analyses favored the use of AVS-guided care, which cost $307.65 more but yielded 0.78 more QALYs, resulting in an ICER of $392.57. These results were upheld by all one-way and two-way sensitivity analyses. In 100,000 random-sampling simulations, AVS-guided care was favored 100% of the time. CONCLUSIONS For patients with primary aldosteronism receiving adrenalectomies with curative intent, the more cost-effective method based on biochemical outcomes is AVS-based care. Recent literature suggests biochemical resolution should be favored over clinical resolution, due to long-term detriments of increased aldosterone independent of clinical symptoms.
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Affiliation(s)
- S Arjani
- Rutgers New Jersey Medical School, Newark, NJ, USA
| | | | - V Prasath
- Rutgers New Jersey Medical School, Newark, NJ, USA
| | - P L Quinn
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - R J Chokshi
- Department of Surgery, Division of Surgical Oncology, Rutgers New Jersey Medical School, 205 South Orange Ave, F1222, Newark, NJ, 07103, USA.
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Manosroi W, Tacharearnmuang N, Atthakomol P. Clinical and biochemical predictors and predictive model of primary aldosteronism. PLoS One 2022; 17:e0272049. [PMID: 35930535 PMCID: PMC9355203 DOI: 10.1371/journal.pone.0272049] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 07/12/2022] [Indexed: 11/18/2022] Open
Abstract
Background
Primary aldosteronism (PA) is the most common cause of secondary hypertension. The diagnosis of PA currently requires multiple complicated measures. The aims of this study were to identify easy-to-obtain clinical and biochemical predictors, and to create predictive model to facilitate the identification of a patient at high risk of having PA.
Materials and methods
This 2-year retrospective cohort study was conducted at a tertiary care medical center. A total of 305 patients who had been tested for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were identified. Patients with incomplete results of PAC and PRA and those who had an established diagnosis of Cushing’s syndrome or pheochromocytoma were excluded. Logistic regression analysis was used to identify significant predictors and to create predictive model of PA.
Results
PA was diagnosed in 128 of the patients (41.96%). Significant predictive factors for PA were age >60 years (OR 2.12, p = 0.045), female (OR 1.65, p<0.001), smoking (OR 2.79, p<0.001), coronary artery disease (OR 2.29, p<0.001), obstructive sleep apnea (OR 1.50, p = 0.017), systolic blood pressure >160 mmHg (OR 1.15, P<0.001), serum potassium <3 mEq/L (OR 3.72, p = 0.030), fasting blood glucose >126 mg/dL (OR 0.48, p = 0.001) and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 (OR 1.79, p = 0.001). Predictive model was created with a total score ranged from 0 to 42. A score above 7.5 indicated a higher probability of having PA with a sensitivity of 72% and a specificity of 70%. The diagnostic performance of the predictive model based on area under the curve was 71%.
Conclusions
The clinical and biochemical predictive factors including predictive model identified in this study can be employed as an additional tool to help identify patients at risk of having PA and could help reduce the number of screening and confirmation tests required for PA.
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Affiliation(s)
- Worapaka Manosroi
- Endocrine and Metabolism Unit, Internal Medicine Department, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai, Chiang Mai, Thailand
- * E-mail:
| | | | - Pichitchai Atthakomol
- Orthopedics Department, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai, Chiang Mai, Thailand
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Cardiovascular and Renal Outcomes with Finerenone, a Selective Mineralocorticoid Receptor Antagonist. Cardiol Ther 2022; 11:337-354. [PMID: 35737275 PMCID: PMC9381668 DOI: 10.1007/s40119-022-00269-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/07/2022] [Indexed: 12/13/2022] Open
Abstract
Overactivation of the renin-angiotensin-aldosterone system (RAAS) has been shown to be pathologic in heart failure and albuminuric chronic kidney disease (CKD), triggering pro-inflammatory and pro-fibrotic cellular pathways. The standard of care in these disease states includes treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers. Mineralocorticoid receptor antagonists (MRAs) are also a mainstay in the treatment of heart failure with reduced ejection fraction; however, therapy is often limited by treatment-related hyperkalemia. In albuminuric CKD, the risk of hyperkalemia, acute kidney injury (AKI), and hypotension also remains significant. Finerenone is a novel non-steroidal MRA that may obviate some of these concerns and have therapeutic potential in additional patient populations. Finerenone was developed using the chemical structure of a dihydropyridine channel blocker but optimized to create a bulky MRA without any activity at the L-type calcium channel. It has several novel cellular mechanisms that may account for its ability to reduce cardiac hypertrophy and proteinuria more efficiently than an equinatriuretic dose of a steroidal MRA, while retaining anti-inflammatory and anti-fibrotic properties. Finerenone also has a lower rate of treatment-related hyperkalemia and AKI than steroidal MRAs with a smaller effect on systolic blood pressure, greatly expanding its therapeutic utility. The recently published FIGARO-DKD and FIDELIO-DKD trials demonstrate that treatment with finerenone in patients with type II diabetes and albuminuric CKD results in improved cardiovascular outcomes and a lower risk of CKD progression. Patients enrolled in these studies were already on maximally tolerated ACE inhibitor or angiotensin receptor blocker therapy. Trials investigating finerenone's therapeutic effect in patients with heart failure with preserved ejection fraction (HFpEF) and non-diabetic CKD, as well sodium-glucose cotransporter 2 (SGLT2) and finerenone combination therapy in patients with diabetic nephropathy, are ongoing.
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Lu YC, Liu KL, Wu VC, Wang SM, Lin YH, Chueh SCJ, Wu KD, Huang KH. Factors associated with renal function change after unilateral adrenalectomy in patients with primary aldosteronism. Int J Urol 2022; 29:831-837. [PMID: 35474521 DOI: 10.1111/iju.14905] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 03/31/2022] [Indexed: 11/30/2022]
Abstract
OBJECTIVES Decreased glomerular filtration rate has been reported in patients with primary aldosteronism after unilateral adrenalectomy. Glomerular hyperfiltration has been assumed to mask the preoperative subtle renal impairment. In this study, we investigated predictors for decreased estimated glomerular filtration rate after adrenalectomy in patients with primary aldosteronism. METHODS From January 2006 through September 2018, 328 patients with confirmatory diagnoses of primary aldosteronism received unilateral laparoscopic adrenalectomy and subsequent follow-up for 12 months. We prospectively collected related parameters of the clinical outcomes and renal function to identify predictors of renal function impairment at 12 months after surgery. RESULTS Patients were stratified into three groups by preoperative estimated glomerular filtration rate level: 144 (43.9%) with estimated glomerular filtration rate ≥90, 130 (39.6%) with estimated glomerular filtration rate within 60-89.9, and 54 (16.5%) with estimated glomerular filtration rate <60 mL/min/1.73 m2 . The estimated glomerular filtration rate decreased significantly at the 6th month and remained stable at the 12th month, postoperatively. Patients with estimated glomerular filtration rate ≥90 had better clinical outcome with 59.6% success rate (P = 0.006) among three groups. Multivariate logistic regression analysis indicated that preoperative estimated glomerular filtration rate (odds ratio 1.012, P = 0.02) and hypokalemia (odds ratio 2.018, P = 0.024) were associated with renal impairment at 12th month after adrenalectomy. Multivariate linear regression analysis revealed high preoperative estimated glomerular filtration rate (β = 0.261, P < 0.001), high preoperative systolic blood pressure (β = 0.168, P = 0.003), high level of microalbuminuria (β = 0.024, P = 0.001), and low level of serum potassium (β = -4.883, P = 0.007) were associated with estimated glomerular filtration rate percentage decline at 12th month after adrenalectomy. CONCLUSIONS Estimated glomerular filtration rate declined significantly after adrenalectomy in patients with estimated glomerular filtration rate ≥90. The study provided important information to identify primary aldosteronism patients with higher risk of estimated glomerular filtration rate decline after adrenalectomy and might help to adopt early interventions to improve the outcomes.
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Affiliation(s)
- Yu-Cheng Lu
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
| | - Kao-Lang Liu
- Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan
| | - Vin-Cent Wu
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shuo-Meng Wang
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Hung Lin
- Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | | | - Kwan-Dun Wu
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Kuo-How Huang
- Department of Urology, National Taiwan University Hospital, Taipei, Taiwan
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Stavropoulos K, Imprialos KP, Patoulias D, Katsimardou A, Doumas M. Impact of Primary Aldosteronism in Resistant Hypertension. Curr Hypertens Rep 2022; 24:285-294. [PMID: 35445928 DOI: 10.1007/s11906-022-01190-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/29/2022] [Indexed: 11/03/2022]
Abstract
PURPOSE OF REVIEW In this narrative review, we aim to summarize the latest data on the association between primary aldosteronism and resistant hypertension, as well as to emphasize the necessity for screening for primary aldosteronism all patients with resistant hypertension. RECENT FINDINGS Epidemiological data suggests that up to one out of five patients with resistant hypertension suffer from primary aldosteronism. Patients with primary aldosteronism have increased incidence of renal disease, diabetes mellitus, atrial fibrillation, and obstructive sleep apnea, as well as they are characterized by an extended target organ damage and increased cardiovascular morbidity and mortality. Specific treatments for primary hyperaldosteronism (adrenalectomy and mineralocorticoid receptor antagonists) have significant impact on blood pressure, can reverse target organ damage, and mitigate cardiovascular risk. All patients with resistant hypertension should be evaluated for primary aldosteronism. Patients diagnosed with the disease may further undergo lateralization with adrenal vein sampling in order to receive the optimal therapeutic option which results in significant improvements in quality of life and cardiovascular profile.
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Affiliation(s)
| | | | - Dimitrios Patoulias
- 2nd Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Greece
| | - Alexandra Katsimardou
- 2nd Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Greece
| | - Michael Doumas
- 2nd Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Greece
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Chauhan K, Schachna E, Libianto R, Ryan J, Hutton H, Fuller PJ, Wilson S, Kerr PG, Yang J. Screening for primary aldosteronism is underutilised in patients with chronic kidney disease. J Nephrol 2022; 35:1667-1677. [PMID: 35195879 PMCID: PMC9300536 DOI: 10.1007/s40620-022-01267-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 02/01/2022] [Indexed: 12/25/2022]
Abstract
BACKGROUND Primary aldosteronism (PA) is the most common and potentially curable endocrine cause of secondary hypertension, and carries a worse prognosis than essential hypertension. Despite the high prevalence of hypertension in patients with chronic kidney disease (CKD), the screening rates for primary aldosteronism in CKD are unknown. METHODS In this study, we retrospectively reviewed medical records of 1627 adults who presented to the nephrology clinics of 2 tertiary hospitals in Melbourne, Australia, between 2014 and 2019. In addition to assessing the pattern of screening, we also evaluated patient-specific factors associated with the decision to test for primary aldosteronism. Patients were excluded from the final analysis if they did not have CKD, had an organ transplant, had end stage renal failure, or had insufficient data or follow-up. RESULTS Of the 600 patients included in the analysis, 234 (39%) had an indication for screening for primary aldosteronism based on recommendations made by the Endocrine Society. However, only 33 (14%) were tested. They were younger, had a higher mean systolic blood pressure, better renal function, and lower mean serum potassium than those who were indicated but not screened. Of the 33 screened patients, an elevated aldosterone-to-renin ratio was noted in 8 patients and a diagnosis of primary aldosteronism was made in 4 patients. CONCLUSIONS The screening rate for primary aldosteronism is low in a CKD population, especially in patients who are older, have a lower eGFR and normal serum potassium. The consequences of undiagnosed primary aldosteronism in this select population may be substantial due to the cardiovascular and renal sequelae associated with untreated disease.
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Affiliation(s)
| | - Eitan Schachna
- Central Clinical School, Monash University, Clayton, Australia
| | - Renata Libianto
- Department of Endocrinology, Monash Health, Clayton, Australia
- Endocrine Hypertension Group, Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Level 3, Block E, Monash Medical Centre, Clayton Road, Clayton, VIC, 3168, Australia
| | - Jessica Ryan
- School of Clinical Sciences, Monash University, Clayton, Australia
- Department of Nephrology, Monash Health, Clayton, Australia
| | - Holly Hutton
- Central Clinical School, Monash University, Clayton, Australia
- Department of Nephrology, Alfred Health, Melbourne, Australia
| | - Peter J Fuller
- Department of Endocrinology, Monash Health, Clayton, Australia
- Endocrine Hypertension Group, Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Level 3, Block E, Monash Medical Centre, Clayton Road, Clayton, VIC, 3168, Australia
| | - Scott Wilson
- Central Clinical School, Monash University, Clayton, Australia
- Department of Nephrology, Alfred Health, Melbourne, Australia
| | - Peter G Kerr
- School of Clinical Sciences, Monash University, Clayton, Australia
- Department of Nephrology, Monash Health, Clayton, Australia
| | - Jun Yang
- School of Clinical Sciences, Monash University, Clayton, Australia.
- Department of Endocrinology, Monash Health, Clayton, Australia.
- Endocrine Hypertension Group, Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Level 3, Block E, Monash Medical Centre, Clayton Road, Clayton, VIC, 3168, Australia.
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Sharma M, Singh V, Sharma R, Koul A, McCarthy ET, Savin VJ, Joshi T, Srivastava T. Glomerular Biomechanical Stress and Lipid Mediators during Cellular Changes Leading to Chronic Kidney Disease. Biomedicines 2022; 10:407. [PMID: 35203616 PMCID: PMC8962328 DOI: 10.3390/biomedicines10020407] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 01/31/2022] [Accepted: 02/04/2022] [Indexed: 02/04/2023] Open
Abstract
Hyperfiltration is an important underlying cause of glomerular dysfunction associated with several systemic and intrinsic glomerular conditions leading to chronic kidney disease (CKD). These include obesity, diabetes, hypertension, focal segmental glomerulosclerosis (FSGS), congenital abnormalities and reduced renal mass (low nephron number). Hyperfiltration-associated biomechanical forces directly impact the cell membrane, generating tensile and fluid flow shear stresses in multiple segments of the nephron. Ongoing research suggests these biomechanical forces as the initial mediators of hyperfiltration-induced deterioration of podocyte structure and function leading to their detachment and irreplaceable loss from the glomerular filtration barrier. Membrane lipid-derived polyunsaturated fatty acids (PUFA) and their metabolites are potent transducers of biomechanical stress from the cell surface to intracellular compartments. Omega-6 and ω-3 long-chain PUFA from membrane phospholipids generate many versatile and autacoid oxylipins that modulate pro-inflammatory as well as anti-inflammatory autocrine and paracrine signaling. We advance the idea that lipid signaling molecules, related enzymes, metabolites and receptors are not just mediators of cellular stress but also potential targets for developing novel interventions. With the growing emphasis on lifestyle changes for wellness, dietary fatty acids are potential adjunct-therapeutics to minimize/treat hyperfiltration-induced progressive glomerular damage and CKD.
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Affiliation(s)
- Mukut Sharma
- Research and Development Service, Kansas City VA Medical Center, Kansas City, MO 64128, USA;
- Midwest Veterans’ Biomedical Research Foundation, Kansas City, MO 64128, USA; (A.K.); (V.J.S.); (T.S.)
- Department of Internal Medicine, The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, MO 66160, USA;
| | - Vikas Singh
- Neurology, Kansas City VA Medical Center, Kansas City, MO 64128, USA;
| | - Ram Sharma
- Research and Development Service, Kansas City VA Medical Center, Kansas City, MO 64128, USA;
| | - Arnav Koul
- Midwest Veterans’ Biomedical Research Foundation, Kansas City, MO 64128, USA; (A.K.); (V.J.S.); (T.S.)
| | - Ellen T. McCarthy
- Department of Internal Medicine, The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, MO 66160, USA;
| | - Virginia J. Savin
- Midwest Veterans’ Biomedical Research Foundation, Kansas City, MO 64128, USA; (A.K.); (V.J.S.); (T.S.)
| | - Trupti Joshi
- Department of Health Management and Informatics, University of Missouri, Columbia, MO 65201, USA;
| | - Tarak Srivastava
- Midwest Veterans’ Biomedical Research Foundation, Kansas City, MO 64128, USA; (A.K.); (V.J.S.); (T.S.)
- Section of Nephrology, Children’s Mercy Hospital and University of Missouri, Kansas City, MO 64108, USA
- Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri, Kansas City, MO 64108, USA
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Lin X, Ullah MHE, Wu X, Xu F, Shan SK, Lei LM, Yuan LQ, Liu J. Cerebro-Cardiovascular Risk, Target Organ Damage, and Treatment Outcomes in Primary Aldosteronism. Front Cardiovasc Med 2022; 8:798364. [PMID: 35187110 PMCID: PMC8847442 DOI: 10.3389/fcvm.2021.798364] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 12/20/2021] [Indexed: 02/03/2023] Open
Abstract
Primary aldosteronism (PA) is the most common type of endocrine hypertension, and numerous experimental and clinical evidence have verified that prolonged exposure to excess aldosterone is responsible for an increased risk of cerebro-cardiovascular events and target organ damage (TOD) in patients with PA. Therefore, focusing on restoring the toxic effects of excess aldosterone on the target organs is very important to reduce cerebro-cardiovascular events. Current evidence convincingly demonstrates that both surgical and medical treatment strategies would benefit cerebro-cardiovascular outcomes and mortality in the long term. Understanding cerebro-cardiovascular risk in PA would help clinical doctors to achieve both early diagnosis and treatment. Therefore, in this review, we will summarize the cerebro-cardiovascular risk in PA, focusing on the TOD of aldosterone, including brain, heart, vascular system, renal, adipose tissues, diabetes, and obstructive sleep apnea (OSA). Furthermore, the various treatment outcomes of adrenalectomy and medical treatment for patients with PA will also be discussed. We hope this knowledge will help improve cerebro-cardiovascular prognosis and reduce the incidence and mortality of cerebro-cardiovascular events in patients with PA.
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Affiliation(s)
- Xiao Lin
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Muhammad Hasnain Ehsan Ullah
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiong Wu
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Feng Xu
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Su-Kang Shan
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Li-Min Lei
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Ling-Qing Yuan
- Department of Endocrinology and Metabolism, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital, Central South University, Changsha, China
- Ling-Qing Yuan
| | - Jun Liu
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Medical Imaging in Hunan Province, Changsha, China
- Department of Radiology Quality Control Center in Hunan Province, Changsha, China
- *Correspondence: Jun Liu
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Ahmed S, Hundemer GL. Benefits of Surgical Over Medical Treatment for Unilateral Primary Aldosteronism. Front Endocrinol (Lausanne) 2022; 13:861581. [PMID: 35557845 PMCID: PMC9086781 DOI: 10.3389/fendo.2022.861581] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 03/28/2022] [Indexed: 11/26/2022] Open
Abstract
Primary aldosteronism is the most common and modifiable form of secondary hypertension. Left untreated, primary aldosteronism leads high rates of cardiovascular, metabolic, and kidney disease. Therefore, early diagnosis and targeted therapy are crucial to improve long-term patient outcomes. In the case of unilateral primary aldosteronism, surgical adrenalectomy is the guideline-recommended treatment of choice as compared to alternative medical therapies such as mineralocorticoid receptor antagonist medications. Surgical adrenalectomy is not only highly successful in reversing the biochemical abnormalities inherent to primary aldosteronism, but also in mitigating the long-term risks associated with this disease. Indeed, as opposed to medical treatment alone, surgical adrenalectomy offers the potential for disease cure. Within this review article, we review the existing evidence highlighting the benefits of surgical over medical treatment for unilateral primary aldosteronism.
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Affiliation(s)
- Sumaiya Ahmed
- Department of Medicine, Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
| | - Gregory L. Hundemer
- Department of Medicine (Division of Nephrology) and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada
- *Correspondence: Gregory L. Hundemer,
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Parasiliti-Caprino M, Bioletto F, Ceccato F, Lopez C, Bollati M, Di Carlo MC, Voltan G, Rossato D, Giraudo G, Scaroni C, Ghigo E, Maccario M. The Accuracy of Simple and Adjusted Aldosterone Indices for Assessing Selectivity and Lateralization of Adrenal Vein Sampling in the Diagnosis of Primary Aldosteronism Subtypes. Front Endocrinol (Lausanne) 2022; 13:801529. [PMID: 35250861 PMCID: PMC8888437 DOI: 10.3389/fendo.2022.801529] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 01/19/2022] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE This study aimed to evaluate the reliability of simple and corrected aldosterone indices for assessing the selectivity and lateralization of adrenal vein sampling (AVS) in patients with primary aldosteronism. METHODS Data of all consecutive patients with primary aldosteronism who underwent AVS for subtype diagnosis, followed at two Italian referral centers, were analyzed retrospectively. RESULTS AVS achieved bilateral selectivity in 112/144 patients. Unilateral disease was diagnosed in 60 cases (53.6%) and idiopathic hyperaldosteronism in 52 individuals (46.4%). The aldosterone index (aldosterone ratio between an adrenal vein and the inferior vena cava) showed a high accuracy in predicting selectivity, compared to a cortisol selectivity index of 1.1, and a moderate accuracy, compared to cortisol cut-offs of 2 and 3. The simple aldosterone index showed a moderate accuracy in predicting ipsi/contralateral aldosterone hypersecretion, while lesion side- and hypokalemia-corrected aldosterone index revealed a significant improvement in predicting ipsi/contralateral disease. Moreover, the comparative aldosterone index (aldosterone ratio in the dominant vs the non-dominant adrenal vein) revealed a high accuracy in predicting unilateral primary aldosteronism. For an immediate clinical application of our results, the adjusted cut-offs were calculated, according to the Youden's criterion and to a pre-established specificity of 90%, for all possible combinations of lesion side at imaging and presence/absence of hypokalemia. CONCLUSIONS This study demonstrated the diagnostic accuracy of simple and clinical-/imaging-corrected aldosterone indices for adrenal vein sampling in subtype diagnosis of primary aldosteronism and suggests the potential application of these tools to select patients for adrenalectomy when standard indices cannot be performed.
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Affiliation(s)
- Mirko Parasiliti-Caprino
- Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, City of Health and Science University Hospital, University of Turin, Turin, Italy
- *Correspondence: Mirko Parasiliti-Caprino, ; orcid.org/0000-0002-6930-7073
| | - Fabio Bioletto
- Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, City of Health and Science University Hospital, University of Turin, Turin, Italy
| | - Filippo Ceccato
- Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padua, Padua, Italy
| | - Chiara Lopez
- Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, City of Health and Science University Hospital, University of Turin, Turin, Italy
| | - Martina Bollati
- Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, City of Health and Science University Hospital, University of Turin, Turin, Italy
| | - Maria Chiara Di Carlo
- Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, City of Health and Science University Hospital, University of Turin, Turin, Italy
| | - Giacomo Voltan
- Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padua, Padua, Italy
| | - Denis Rossato
- Radiology Unit, City of Health and Science University Hospital, University of Turin, Turin, Italy
| | - Giuseppe Giraudo
- Surgery, City of Health and Science University Hospital, University of Turin, Turin, Italy
| | - Carla Scaroni
- Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padua, Padua, Italy
| | - Ezio Ghigo
- Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, City of Health and Science University Hospital, University of Turin, Turin, Italy
| | - Mauro Maccario
- Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, City of Health and Science University Hospital, University of Turin, Turin, Italy
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Saiki A, Otsuki M, Tamada D, Kitamura T, Mukai K, Yamamoto K, Shimomura I. Increased Dosage of MRA Improves BP and Urinary Albumin Excretion in Primary Aldosteronism With Suppressed Plasma Renin. J Endocr Soc 2022; 6:bvab174. [PMID: 34909517 PMCID: PMC8664755 DOI: 10.1210/jendso/bvab174] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Indexed: 11/21/2022] Open
Abstract
Purpose Excessive aldosterone secretion causes a high risk of cardio-cerebrovascular events. Mineralocorticoid receptor antagonist (MRA) is 1 of the treatment strategies for primary aldosteronism (PA). However, current MRA treatment is insufficient because MRA-treated patients with suppressed plasma renin activity (PRA) < 1 ng/mL/h still had a higher risk of cardiovascular disease than those with unsuppressed PRA. This is a prospective interventional study to determine the effects of an increase in MRA dosage on blood pressure (BP) control and urinary albumin excretion (UAE) in MRA-treated PA patients. Methods Thirty-four PA patients were recruited, and 24 patients (6 male, 18 female) completed this study. Serum potassium concentration was assessed every two months to adjust the dosage of MRA safely for 6 months. The primary outcomes were the changes in BP and UAE between baseline and 6 months. Results Systolic BP (SBP) and log10UAE decreased significantly as the daily dose of MRA increased. Diastolic BP (DBP) tended to decrease. We divided the PA patients into two groups (baseline PRA < 1 ng/mL/h and baseline PRA ≥ 1 ng/mL/h) according to PRA. In the group with baseline PRA < 1 ng/mL/h but not that with baseline PRA ≥ 1 ng/mL/h, SBP, DBP and log10UAE after 6 months were significantly lower than those at baseline. Conclusions The increase in MRA dosage improved BP and UAE in PA patients with suppressed PRA.
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Affiliation(s)
- Aya Saiki
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Michio Otsuki
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Daisuke Tamada
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Tetsuhiro Kitamura
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Kosuke Mukai
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Koichi Yamamoto
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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Reincke M, Bancos I, Mulatero P, Scholl UI, Stowasser M, Williams TA. Diagnosis and treatment of primary aldosteronism. Lancet Diabetes Endocrinol 2021; 9:876-892. [PMID: 34798068 DOI: 10.1016/s2213-8587(21)00210-2] [Citation(s) in RCA: 159] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 07/21/2021] [Accepted: 07/26/2021] [Indexed: 02/07/2023]
Abstract
Primary aldosteronism is a common cause of secondary hypertension associated with excess cardiovascular morbidities. Primary aldosteronism is underdiagnosed because it does not have a specific, easily identifiable feature and clinicians can be poorly aware of the disease. The diagnostic investigation is a multistep process of screening, confirmatory testing, and subtype differentiation of unilateral from bilateral forms for therapeutic management. Adrenal venous sampling is key for reliable subtype identification, but can be bypassed in patients with specific characteristics. For unilateral disease, surgery offers the possibility of cure, with total laparoscopic unilateral adrenalectomy being the treatment of choice. Bilateral forms are treated mainly with mineralocorticoid receptor antagonists. The goals of treatment are to normalise both blood pressure and excessive aldosterone production, and the primary aims are to reduce associated comorbidities, improve quality of life, and reduce mortality. Prompt diagnosis of primary aldosteronism and the use of targeted treatment strategies mitigate aldosterone-specific target organ damage and with appropriate patient management outcomes can be excellent. Advances in molecular histopathology challenge the traditional concept of primary aldosteronism as a binary disease, caused by either a unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia. Somatic mutations drive autonomous aldosterone production in most adenomas. Many of these same mutations have been identified in nodular lesions adjacent to an aldosterone-producing adenoma and in patients with bilateral disease. In addition, germline mutations cause rare familial forms of aldosteronism (familial hyperaldosteronism types 1-4). Genetic testing for inherited forms in suspected cases of familial hyperaldosteronism avoids the burdensome diagnostic investigation in positive patients. In this Review, we discuss advances and future management approaches in the diagnosis of primary aldosteronism.
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Affiliation(s)
- Martin Reincke
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
| | - Irina Bancos
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Paolo Mulatero
- Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Ute I Scholl
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Functional Genomics, Berlin, Germany
| | - Michael Stowasser
- Endocrine Hypertension Research Centre, University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, QLD, Australia
| | - Tracy Ann Williams
- Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany; Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy
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Saito K, Kurihara I, Itoh H, Ichijo T, Katabami T, Tsuiki M, Wada N, Yoneda T, Sone M, Oki K, Yamada T, Kobayashi H, Tamura K, Ogawa Y, Kawashima J, Inagaki N, Yamamoto K, Yamada M, Kamemura K, Fujii Y, Suzuki T, Yasoda A, Tanabe A, Naruse M. Subtype-specific trends in the clinical picture of primary aldosteronism over a 13-year period. J Hypertens 2021; 39:2325-2332. [PMID: 34224538 DOI: 10.1097/hjh.0000000000002924] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Primary aldosteronism has two main clinically and biologically distinct subtypes: unilateral aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). We aimed to evaluate the changes of each subtype's clinical characteristics over a 13-year period. METHODS This retrospective study involved time-trend analyses to identify changes in the clinical features of APA and BAH at diagnosis (2006-2018). A nationwide database from 41 Japanese referral centers was searched, which identified 2804 primary aldosteronism patients with complete baseline information and adrenal venous sampling (AVS) data. RESULTS The proportion of patients with APA decreased from 51% in 2006-2009 to 22% in 2016-2018. Among the 1634 patients with BAH, trend analyses revealed decreases in hypertension duration (median 7--3 years; P < 0.01) and hypokalemia prevalence (18--11%; P < 0.01). However, among the 952 patients with APA, there were no significant changes in hypertension duration (median 8 years) and hypokalemia prevalence (overall 70%). Furthermore, the APA group had a trend towards increased use of multiple hypertensive drugs at diagnosis (30--43%; P < 0.01). When subtypes were reclassified according to the precosyntropin stimulation AVS data, APA patients tended to be diagnosed earlier and at milder forms, consistent with the trend in overall primary aldosteronism patients. CONCLUSION During 2006-2018, we identified marked subtype-specific trends in the clinical findings at the diagnosis of primary aldosteronism. Our results suggested that the emphasis on the implementing cosyntropin stimulation during AVS might lead to under-identification of APA, especially in patients with mild or early cases.
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Affiliation(s)
- Kohei Saito
- Department of Endocrinology, Metabolism and Nephrology, School of Medicine, Keio University, Tokyo
- Center for Diabetes, Endocrinology and Metabolism, Shizuoka General Hospital, Shizuoka
| | - Isao Kurihara
- Department of Endocrinology, Metabolism and Nephrology, School of Medicine, Keio University, Tokyo
- Department of Medical Education, National Defense Medical College, Tokorozawa
| | - Hiroshi Itoh
- Department of Endocrinology, Metabolism and Nephrology, School of Medicine, Keio University, Tokyo
| | - Takamasa Ichijo
- Department of Endocrinology and Metabolism, Saiseikai Yokohamashi Tobu Hospital, Yokohama
| | - Takuyuki Katabami
- Division of Metabolism and Endocrinology, Department of Internal Medicine, St Marianna University School of Medicine Yokohama City Seibu Hospital, Yokohama
| | - Mika Tsuiki
- Clinical Research Institute of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto
| | - Norio Wada
- Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo
| | - Takashi Yoneda
- Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa
| | - Masakatsu Sone
- Division of Metabolism and Endocrinology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki
| | - Kenji Oki
- Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima
| | - Tetsuya Yamada
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
| | - Hiroki Kobayashi
- Division of Nephrology, Hypertension, and Endocrinology, Nihon University School of Medicine, Tokyo
| | - Kouichi Tamura
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Kanagawa
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka
| | - Junji Kawashima
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto
| | - Nobuya Inagaki
- Department of Diabetes, Endocrinology, and Nutrition, Kyoto University, Kyoto
| | - Koichi Yamamoto
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka
| | - Masanobu Yamada
- Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma
| | | | - Yuichi Fujii
- Department of Cardiology, JR Hiroshima Hospital, Hiroshima
| | - Tomoko Suzuki
- Department of Public Health, International University of Health and Welfare School of Medicine, Chiba
| | - Akihiro Yasoda
- Clinical Research Institute of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto
| | - Akiyo Tanabe
- Division of Endocrinology, National Center for Global Health and Medicine, Tokyo
| | - Mitsuhide Naruse
- Clinical Research Institute of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto
- Endocrine Center, Ijinkai Takeda General Hospital, Kyoto, Japan
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47
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Tang F, Loh LM, Foo RS, Loh WJ, Lim DST, Zhang M, Tan PT, Swee DS, Khoo J, Tay D, Lee L, Tan SY, Zhu L, Soh SB, Tan E, Kek PC, Puar TH. Tolerability and Efficacy of Long-Term Medical Therapy in Primary Aldosteronism. J Endocr Soc 2021; 5:bvab144. [PMID: 34541440 PMCID: PMC8442943 DOI: 10.1210/jendso/bvab144] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Indexed: 12/02/2022] Open
Abstract
INTRODUCTION Patients with primary aldosteronism (PA) have increased cardiovascular risk, and there are concerns about the efficacy of medical therapy. OBJECTIVE We aimed to assess long-term tolerability and efficacy of medical therapy in PA patients. METHODS We conducted a retrospective study on 201 PA patients treated with medical therapy (spironolactone, eplerenone, or amiloride) from 2000 to 2020 at 2 tertiary centers. Clinical and biochemical control and side effects were assessed. RESULTS Among 155 patients on long-term medications, 57.4% achieved blood pressure (BP) <140/90 mmHg, 90.1% achieved normokalemia (48.0% potassium ≥4.3 mmol/L), and 63.2% achieved renin >1 ng/mL/h. Concordance of biochemical control using potassium and renin levels was 49.1%. Side effects were experienced by 52.3% of patients, with 10.3% switching, 22.6% decreasing dose, and 11.0% stopping medications. Risk factors for side effects were spironolactone use, dose ≥ 50 mg, treatment duration ≥1 year, male gender, and unilateral PA. Patients with unilateral PA used higher spironolactone doses vs bilateral (57 vs 50 mg, P < 0.001) and had more side effects (63.2% vs 41.8%, P = 0.008). Forty-six unilateral PA patients who underwent surgery after initial medical therapy experienced improved BP (systolic from 141 to 135 mmHg, P = 0.045; diastolic from 85 to 79 mmHg, P = 0.002). CONCLUSION Dose-dependent side effects limit efficacy of medical therapy in PA. Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy. For unilateral PA, surgery remains preferable, yielding better control with less long-term side effects.
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Affiliation(s)
- Fengjie Tang
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Lih M Loh
- Department of Endocrinology, Singapore General Hospital, SingHealth, Singapore 169608, Singapore
| | - Roger S Foo
- Cardiovascular Research Institute, Centre for Translational Medicine, MD6, National University Health System, Singapore 117599, Singapore
- Genome Institute of Singapore, Singapore 138672, Singapore
| | - Wann J Loh
- Department of Endocrinology, Changi General Hospital, SingHealth, Singapore 529889, Singapore
| | - Dawn S T Lim
- Department of Endocrinology, Singapore General Hospital, SingHealth, Singapore 169608, Singapore
| | - Meifen Zhang
- Department of Endocrinology, Changi General Hospital, SingHealth, Singapore 529889, Singapore
| | - Pei T Tan
- Department of Clinical Trial Research Unit, Changi General Hospital, SingHealth, Singapore 529889, Singapore
| | - Du S Swee
- Department of Endocrinology, Singapore General Hospital, SingHealth, Singapore 169608, Singapore
| | - Joan Khoo
- Department of Endocrinology, Changi General Hospital, SingHealth, Singapore 529889, Singapore
| | - Donovan Tay
- Department of Endocrinology, Sengkang General Hospital, SingHealth, Singapore 544886, Singapore
| | - Lynette Lee
- Department of Endocrinology, Singapore General Hospital, SingHealth, Singapore 169608, Singapore
- Department of Endocrinology, Changi General Hospital, SingHealth, Singapore 529889, Singapore
| | - Sarah Y Tan
- Department of Endocrinology, Singapore General Hospital, SingHealth, Singapore 169608, Singapore
- Department of Endocrinology, Changi General Hospital, SingHealth, Singapore 529889, Singapore
| | - Ling Zhu
- Department of Endocrinology, Singapore General Hospital, SingHealth, Singapore 169608, Singapore
| | - Shui B Soh
- Department of Endocrinology, Changi General Hospital, SingHealth, Singapore 529889, Singapore
| | - Eberta Tan
- Department of Endocrinology, Changi General Hospital, SingHealth, Singapore 529889, Singapore
| | - Peng C Kek
- Department of Endocrinology, Singapore General Hospital, SingHealth, Singapore 169608, Singapore
| | - Troy H Puar
- Department of Endocrinology, Changi General Hospital, SingHealth, Singapore 529889, Singapore
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48
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Association of achieved blood pressure after treatment for primary aldosteronism with long-term kidney function. J Hum Hypertens 2021; 36:904-910. [PMID: 34462544 DOI: 10.1038/s41371-021-00595-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 07/22/2021] [Accepted: 08/10/2021] [Indexed: 11/08/2022]
Abstract
Little is known regarding the association of blood pressure (BP) after treatment for primary aldosteronism (PA) (i.e., adrenalectomy and mineralocorticoid receptor antagonists) with long-term renal outcomes, and whether the association is independent of BP before treatment. Using a dataset from a nationwide registry of PA in Japan, we assessed whether achieved BP levels 6 months after treatment for PA are associated with annual changes in estimated glomerular filtration rate (eGFR), rapid eGFR decline, and incident chronic kidney disease (CKD) during the 5-year follow-up period. The cohort included 1266 PA patients. In multivariable linear regression including systolic BP (SBP) levels before treatment for PA, estimates (95% confidence interval [CI]) for annual changes in eGFR after month 6 associated with one-standard deviation (1-SD) higher SBP at month 6 were -0.08 (-0.15, -0.02) mL/min/1.73 m2/year. After multivariable adjustment, the estimate (95% CI) for annual changes in eGFR after month 6 was -0.12 (-0.21, -0.02) for SBP ≥ 130 mmHg vs. SBP < 130 mmHg at month 6. Among 537 participants without CKD at baseline, a 1-SD higher SBP was associated with a higher risk for incident CKD events (hazard ratio [95% CI]: 1.40 [1.00, 1.94]). Higher SBP after treatment for PA was associated with a higher risk for kidney dysfunction over time, independently of BP levels before treatment. Achieving SBP lower than 130 mmHg after treatment for PA may be linked to better kidney outcomes.
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49
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Yang YS, Lee SH, Kim JH, Yoo JH, Lee JH, Lee SY, Hong AR, Lee DH, Koh JM, Kim JH, Kim SW. Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism. Endocrinol Metab (Seoul) 2021; 36:875-884. [PMID: 34376041 PMCID: PMC8419620 DOI: 10.3803/enm.2021.1047] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 06/21/2021] [Accepted: 07/12/2021] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominant METHODS In this retrospective observational multi-center study, we analyzed PA patients who underwent both successful adrenocorticotropin hormone-stimulated AVS and unilateral adrenalectomy. Successful cannulation was defined as the selectivity index (cortisoladrenal/cortisolperipheral) ≥3. Clinical and biochemical outcomes after unilateral adrenalectomy were evaluated based on the international Primary Aldosteronism Surgical Outcome consensus. RESULTS Among 263 patients analyzed, 247 had CS (93.9%). Patients with CS had lower serum potassium levels, higher plasma aldosterone concentration, higher aldosterone-to-renin ratio (ARR), and larger adenoma size than those without CS. Those with CS showed significantly higher lateralization index than those without CS (P<0.001). Although postoperative blood pressure and ARR significantly decreased in those with CS, clinical and biochemical outcomes were comparable in both groups. When the cut-off value of age was determined using receiver operating characteristic (ROC) analysis, patients aged ≥50 years old with contralateral suppression index (CSI; the ratio between aldosterone/cortisolnondominant and aldosterone/cortisolperipheral) ≤0.26 had greater odds ratio (6.43; 95% confidence interval, 1.30 to 31.69) of incident chronic kidney disease than those aged <50 years with CSI >0.26 after adjusting for other factors. CONCLUSION CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.
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Affiliation(s)
- Ye Seul Yang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
- Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Seoul,
Korea
| | - Seung Hun Lee
- Division of Endocrinology and Metabolism, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Korea
| | - Jung Hee Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
| | - Jee Hee Yoo
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Jung Hyun Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
| | - Seo Young Lee
- Department of Internal Medicine, Mediplex Sejong Hospital, Incheon,
Korea
| | - A Ram Hong
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju,
Korea
| | - Dong-Hwa Lee
- Department of Internal Medicine, Chungbuk National University Hospital, Cheongju,
Korea
| | - Jung-Min Koh
- Division of Endocrinology and Metabolism, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Korea
| | - Jae Hyeon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Sang Wan Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
- Division of Endocrinology and Metabolism, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul,
Korea
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50
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Moon SJ, Jang HN, Kim JH, Moon MK. Lipid Profiles in Primary Aldosteronism Compared with Essential Hypertension: Propensity-Score Matching Study. Endocrinol Metab (Seoul) 2021; 36:885-894. [PMID: 34372626 PMCID: PMC8419600 DOI: 10.3803/enm.2021.1012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 06/07/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND There has been controversy regarding the association between primary aldosteronism (PA) and dyslipidemia and few studies considered the effects of diabetes and renal function on lipid metabolism. We analyzed lipid profiles of PA patients and compared them to propensity-score (PS)-matched essential hypertension (EH) patients adjusting for glycemic status and renal function. METHODS Patients who were diagnosed with PA using a saline-infusion test at Seoul National University Hospital from 2000 to 2018 were retrospectively analyzed. EH patients who had aldosterone-renin ratio (ARR) results were selected as controls. Covariates, including diabetes, were PS-matched for patients with PA, lateralized PA, non-lateralized PA, and high ARR to EH patients, respectively. RESULTS Among a total of 80 PA and 80 EH patients, total cholesterol (TC) and triglyceride (TG) levels were significantly lower in the PA patients than in the EH patients (least-squares mean±standard error: 185.5±4.4 mg/dL vs. 196.2±4.4 mg/dL, P=0.047, for TC; and 132.3±11.5 mg/dL vs. 157.4±11.4 mg/dL, P=0.035, for TG) in fully adjusted model (adjusting for multiple covariates, including diabetes status, glycosylated hemoglobin level, and estimated glomerular filtration rate). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol levels between the two groups. According to increments in aldosterone levels, an increasing tendency of HDL-C and decreasing tendencies of TG and non-HDL-C were observed. CONCLUSION PA patients had lower TC and TG levels than EH patients, independent of glycemic status and renal function.
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Affiliation(s)
- Sun Joon Moon
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Han Na Jang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul,
Korea
| | - Jung Hee Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul,
Korea
| | - Min Kyong Moon
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul,
Korea
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