Novel chemiluminescent immunoassay to measure plasma aldosterone and plasma active renin concentrations for the diagnosis of primary aldosteronism

AbstractDetermination of plasma aldosterone concentrations (PAC) and plasma active renin concentrations (ARC) is essential for the diagnosis of primary aldosteronism (PA). In Japan, although PAC and ARC are measured by radioimmunoassay and immunoradiometric assay, respectively, non-radioisotopic methods with better detection sensitivity, measurement accuracy, and technical simplicity are needed. We developed two-site sandwich chemiluminescent enzyme immunoassays (CLEIAs) to measure both PAC and ARC using monoclonal antibodies immobilized onto ferrite particles. The results of both assays are obtained simultaneously from a single plasma sample within 30 min using a fully automated system. The novel CLEIAs were validated using plasma samples from patients with PA (n = 52) and essential hypertension (n = 23). The PAC determined by the CLEIA was significantly correlated with that measured by liquid chromatography/mass spectrometry or conventional radioimmunoassay. The ARC determined by the CLEIA was significantly correlated with that measured by immunoradiometric assay. The limits of detection of the CLEIAs for PAC and ARC were 0.1 ng/dl and 0.04 pg/ml, respectively, which were better than those of conventional methods (PAC: 2.5 ng/dl; ARC: 5 pg/ml). The PAC and PAC/ARC ratio (ARR) were significantly higher, and the ARC significantly lower, in patients with PA than in those with essential hypertension. An ARR cut-off of 1.31 ng/dl per pg/ml showed a sensitivity of 96.2% and specificity of 78.3% for PA screening. The newly developed CLEIAs for measuring PAC and ARC could provide a clinically powerful alternative to conventional methods used for hypertension screening in clinical practice.

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Dopamine reduces aldosterone and 18-hydroxycorticosterone response to angiotensin II in patients with essential low-renin hypertension and idiopathic hyperaldosteronism

Clinical Science ◽

10.1042/cs0680291 ◽

1985 ◽

Vol 68 (3) ◽

pp. 291-299 ◽

Cited By ~ 11

Author(s):

Helmut Witzgall ◽

Reinhard Lorenz ◽

Klaus Von Werder ◽

Peter C. Weber

Keyword(s):

Essential Hypertension ◽

Angiotensin Ii ◽

Primary Aldosteronism ◽

Plasma Levels ◽

Plasma Aldosterone ◽

Induced Response ◽

Maximal Increase ◽

Low Renin Hypertension ◽

Normotensive Subjects ◽

Idiopathic Hyperaldosteronism

1. Plasma aldosterone, 18-hydroxycorticosterone (18-OH-B), 18-hydroxydeoxycorticosterone (18-OH-DOC), corticosterone, cortisol and prolactin levels were determined during an angiotensin II infusion at increasing rates both with and without a simultaneous infusion of dopamine in seven normotensive subjects, in ten patients with essential hypertension, and in ten patients with primary aldosteronism. In a second set of experiments, maximum increases of these plasma levels were determined after metoclopramide (10 mg intravenously) in all subgroups. 2. As compared with the other groups, an exaggerated angiotensin II-induced response of plasma aldosterone and 18-OH-B levels was observed in the five patients with low-renin essential hypertension (LREH) and in five patients with idiopathic hyperaldosteronism (IHA). 3. Dopamine reduced the maximal increase of aldosterone and of 18-OH-B after angiotensin II to 259 ± 48 (sem) pg/ml and 511 ± 152 pg/ml repectively in LREH (without dopamine: 515 ± 74 and 908 ± 201 respectively; P<0.05), and to 466 ± 197 and 741 ± 212 in IHA (without dopamine: 766 ± 193 and 1264 ± 337 respectively; P<0.05). 4. The maximal increases of plasma aldosterone, 18-OH-B, and prolactin after metoclopramide (10 mg intravenously) were higher (P<0.01) in patients with LREH and in patients with primary aldosteronism. Plasma levels of 18-OH-DOC, corticosterone and cortisol were not affected by the stimuli applied. 5. The exaggerated response to metoclopramide as well as to angiotensin II and its reversion only by pharmacological doses of dopamine are consistent with an increased but ineffective dopamine inhibition of aldosterone and 18-OH-B in LREH and IHA.

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Screening for Primary Aldosteronism in Essential Hypertension: Diagnostic Accuracy of the Ratio of Plasma Aldosterone Concentration to Plasma Renin Activity

Yearbook of Surgery ◽

10.1016/s0090-3671(08)70424-5 ◽

2006 ◽

Vol 2006 ◽

pp. 161

Author(s):

T.J. Fahey

Keyword(s):

Essential Hypertension ◽

Plasma Renin Activity ◽

Diagnostic Accuracy ◽

Primary Aldosteronism ◽

Plasma Renin ◽

Plasma Aldosterone ◽

Renin Activity ◽

Plasma Aldosterone Concentration

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Screening for Primary Aldosteronism in Essential Hypertension: Diagnostic Accuracy of the Ratio of Plasma Aldosterone Concentration to Plasma Renin Activity

Yearbook of Cardiology ◽

10.1016/s0145-4145(07)70028-x ◽

2006 ◽

Vol 2006 ◽

pp. 48-49

Author(s):

W.J. Elliott

Keyword(s):

Essential Hypertension ◽

Plasma Renin Activity ◽

Diagnostic Accuracy ◽

Primary Aldosteronism ◽

Plasma Renin ◽

Plasma Aldosterone ◽

Renin Activity ◽

Plasma Aldosterone Concentration

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Impaired Renin Stimulation in Pre-Eclampsia

Clinical Science ◽

10.1042/cs0860575 ◽

1994 ◽

Vol 86 (5) ◽

pp. 575-581 ◽

Cited By ~ 18

Author(s):

Mark A. Brown ◽

Loretta Reiter ◽

Alison Rodger ◽

Judith A. Whitworth

Keyword(s):

Pregnant Women ◽

Sodium Excretion ◽

Plasma Aldosterone ◽

Urinary Sodium ◽

Creatinine Ratio ◽

Angiotensin I ◽

Plasma Aldosterone Concentration ◽

Active Renin ◽

Fractional Sodium Excretion ◽

Plasma Active Renin

1. Pre-eclampsia is characterized by reduced plasma active renin concentration and renal prostacyclin production. The aim of this study was to determine whether the plasma active renin concentration could be stimulated in women with pre-eclampsia by intravenous frusemide, which stimulates renin acutely through a prostacyclin-mediated mechanism. 2. Plasma active renin concentration, plasma aldosterone concentration, haematocrit and urinary sodium, creatinine and 6-keto-prostaglandin F1α were measured before (0) and 15, 30 and 60 min after intravenous frusemide in 10 non-pregnant women, 10 normal pregnant women and nine women with pre-eclampsia. Six normal pregnant and six non-pregnant women underwent the same measurements after injection of 2ml of saline to control for effects of time and posture. 3. Baseline plasma active renin concentration (but not plasma aldosterone concentration) was lower in pre-eclamptic women [4.0 (1.7–6.2) pmol of angiotensin I h−1 ml−1; median (interquartile range)] than in normal pregnant women [6.7 (5.3–12.2) pmol of angiotensin I h−1 ml−1] (P < 0.05). Baseline urinary 6-keto-prostaglandin F1α/creatinine ratio, urinary sodium excretion and fractional sodium excretion did not differ between normal pregnant and pre-eclamptic women. 4. After frusemide, plasma active renin concentration rose significantly in non-pregnant (P = 0.002) and normal pregnant (P = 0.008) women, but not in women with pre-eclampsia. Individual results showed stimulation in all non-pregnant and normal pregnant women but in only six out of nine pre-eclamptic women, significantly fewer than in normal pregnancy (P < 0.05). The overall magnitude of the response of plasma active renin concentration to frusemide was blunted significantly in pre-eclamptic compared with normal pregnant women (P = 0.022). 5. Absolute and fractional sodium excretion and haematocrit rose significantly in all groups and the magnitude of change did not differ among groups for any of these parameters. The urinary 6-keto-prostaglandin F1α/creatinine ratio increased significantly only in non-pregnant women (P = 0.01), with variable individual responses in normal and hypertensive pregnant women. 6. This study shows that normal pregnant women exhibit natriuresis and stimulation of plasma renin after frusemide similar to that of non-pregnant women. However, pre-eclamptic women, as a group, have impaired renin stimulation after frusemide but a similar natriuresis to that of normal pregnant women. The mechanisms of these changes are unclear but are consistent with the notion of ‘exhausted’ renal renin in some women with pre-eclampsia.

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EXPLORATION OF THE SEATED SALINE SUPPRESSION TEST FOR THE DIAGNOSIS OF PRIMARY ALDOSTERONISM IN THE CHINESE POPULATION

Endocrine Practice ◽

10.4158/ep-2020-0064 ◽

2020 ◽

Vol 26 (8) ◽

pp. 891-899 ◽

Cited By ~ 1

Author(s):

Dan Zhang ◽

Tao Chen ◽

Haoming Tian ◽

Yuanmei Li ◽

Dan Mo ◽

...

Keyword(s):

Essential Hypertension ◽

Receiver Operating Characteristic ◽

Primary Aldosteronism ◽

Operating Characteristic ◽

Plasma Aldosterone ◽

Youden Index ◽

Plasma Aldosterone Concentration ◽

Suppression Test ◽

Aldosterone Producing Adenoma ◽

Idiopathic Hyperaldosteronism

Objective: We prospectively investigated the accuracy of the seated saline suppression test (SSST) in 113 patients with hypertension (including 93 primary aldosteronism [PA] and 20 essential hypertension patients) in the Department of Endocrinology and Metabolism. Methods: Each patient underwent a recumbent saline suppression test (RSST) and SSST. The accuracy of the SSST for a confirmative PA diagnosis and subtype classification was evaluated and compared with the RSST. Results: The area under the receiver operating characteristic (ROC) curve of plasma aldosterone concentration (PAC) for the SSST was significantly greater than that for the RSST (0.945 ± 0.0199 vs. 0.828 ± 0.0404; P<.05). The ROC analysis showed that the optimal PAC cut-off values were 12.94 ng/dL for the SSST (sensitivity 86.02%, specificity 95%; Youden index [YI] 0.810) and 12.04 ng/dL for the RSST (sensitivity 83.15%, specificity 57%; YI 0.401). The optimal PAC cut-off value for classifying aldosterone-producing adenoma and idiopathic hyperaldosteronism was 18.12 ng/dL for the SSST (sensitivity 73.5%, specificity 79.5%). No patients experienced adverse events during the SSST. Conclusion: The SSST is safe and convenient for PA diagnosis. The accuracy of the SSST for a confirmatory diagnosis of PA was better than that of the RSST. The SSST is a reliable alternative for PA confirmation in Chinese individuals. Abbreviations: APA = aldosterone-producing adenoma; ARR = aldosterone to renin ratio; AVS = adrenal vein sampling; CT = computed tomography; EH = essential hypertension; IHA = idiopathic hyperaldosteronism; MRI = magnetic resonance imaging; PA = primary aldosteronism; PAC = plasma aldosterone concentration; PRA = plasma renin activity; ROC = receiver operating characteristic; RSST = recumbent saline suppression test; SSST = seated saline suppression test; YI = Youden index

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Age-Related Cutoffs of Plasma Aldosterone/Renin Concentration for Primary Aldosteronism Screening

International Journal of Endocrinology ◽

10.1155/2018/8647026 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Linqiang Ma ◽

Ying Song ◽

Mei Mei ◽

Wenwen He ◽

Jinbo Hu ◽

...

Keyword(s):

Essential Hypertension ◽

Retrospective Study ◽

Primary Aldosteronism ◽

Age Groups ◽

Plasma Renin ◽

Final Analysis ◽

Plasma Aldosterone ◽

Plasma Aldosterone Concentration ◽

Hypertensive Patients ◽

Age Related

Aim. This retrospective study is aimed at investigating whether aldosterone-renin ratio (ARR) cutoffs calculated by the plasma aldosterone concentration (PAC)/plasma renin concentration (PRC) should be set differently in patients of different ages. Methods. 521 hypertensive patients were screened for primary aldosteronism (PA) by the PAC/PRC. 174 patients diagnosed with PA and 311 patients with essential hypertension (EH) were included in the final analysis. Subjects were subdivided into four age groups: <40, 40–49, 50–59, and ≥60 years old. Results. The accuracy of the ARR varied greatly among the different age groups. An ARR of 3.7 (ng/dl)/(μIU/ml) had a sensitivity of 100% and a specificity of 80% in patients ≥ 60 years old. With this cutoff, the sensitivities in patients < 40, 40–49, and 50–59 years old were 74%, 82%, and 87%, respectively, and the specificities were 94%, 95%, and 94%, respectively. To achieve a sensitivity higher than 90%, the ARR cutoff needed to be lowered to 2.0 (ng/dl)/(μIU/ml) for patients 40–49 and 50–59 years old, resulting in sensitivities of 90% and 95%, respectively, and specificities of 80% and 84%, respectively. To achieve a sensitivity higher than 90%, the ARR cutoff needed to be lowered to 1.0 (ng/dl)/(μIU/ml) for patients < 40 years old, resulting in a sensitivity of 90% and a specificity of 82%. Conclusions. An ARR of 3.7 (ng/dl)/(μIU/ml) is optimal for patients ≥ 60 years; for patients 40–59 years, the optimal ARR cutoff is 2.0; for those younger than 40 years, an ARR of 1.0 may be more reasonable.

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