Diagnosis of Primary Aldosteronism: Comparison of Post Captopril Active Renin Concentration and Plasma Renin Activity

Background: The most common pharmacologic test for diagnosis of primary aldosteronism (PA) is administration of captopril to examine whether abnormal aldosterone to plasma rennin activity (PRA)(ARR) persists, although active rennin concentration (ARC) in contrast to PRA may offers advantages with regard to processing and standardization.

Objective: To assess whether post captopril ARC offer any additional advantage in screening primary aldosteronism (PA) than PRA and establish thresholds for the diagnosis using ARC.

Study Overview

• Status: Unknown
• Conditions: Primary Aldosteronism
• Intervention / Treatment: Drug: captopril test

Detailed Description

Primary aldosteronism (PA), characterized by an inappropriate production of aldosterone, affects 5-13% of patients with hypertension(1, 2). The use of aldosterone-renin ratio (ARR) as screening test contributes to the increased diagnostic rate of this disease(2), but it is not standardized among laboratories. As the incidence of PA has increased since ARR has been used as a screening test (3, 4), the difficulty in establishing a diagnosis of PA may be encountered because of atypical manifestations. Administration of captopril to differentiate the normal renin-angiotensin- aldosterone axis from autonomous secretion of aldosterone has been proved to be a safe and effective test in confirmation of the diagnosis (5-8). Several studies have demonstrated that the ARR after a single dose of captopril is diagnostic (5-8) and as sensitive as the saline loading test for the identification of aldosterone- producing adenoma (APA)(8).

Active rennin concentration (ARC) is considerably easier to perform; being a single immunoradiometric assay as opposed to the initial generation of angiotensin I generated from angiotensinogen followed by radioimmunoassay of PRA(9). It was demonstrated as a reliable and convenient screening tool for ambulatory conditions, independent of body posture (10). Decreased angiotensinogen level is noted in pathological status ( e.g. liver cirrhosis, sever cardiac failure) (11, 12) that results in dissociate of PRA measurement. PAC when used in conjunction with aldosterone to produce an ARRARC , has been reported to classify aldosteronism correctly(13). Although PRA is highly sensitive, the measurement is time-consuming and measured values can vary considerably between laboratories(14). In aldosteronism with suppressed renin, the ratio of ARR is clearly dependent on the variants lower detection limit(15). Though determination of ARC in contrast to PRA offers advantage with regard to processing and standardization, knowing the postcaptopril sensitivity and specificity as well as the optimum cut off value of ARC is paramount (16) help to the diagnosis PA (15, 17, 18) and might serve better performance than ARRPRA.

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: VinCent Wu, MD; Phone Number: +886937223278

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients were referred to the hypertension clinics for suspicious of aldosteronism after an initial evaluation, and recorded in the Taiwan Primary Aldosteronism Investigation (TAIPAI). The initial evaluation included (1) age at onset younger than 35 years, (2) hypertension that is difficult to control after initiating therapy, (3) clinical occurrence of a hypertensive crisis, (4) the presence of hypokaliemia or metabolic alkalosis, or a random aldosterone-renin ration (ARR) >30, and (5) evidence of adrenal incidentaloma and hypertension or hypokalemia. All patients with intention to confirm and received captopril test were recruited and data were prospectively collected.

Description

Inclusion Criteria:

1. age at onset younger than 35 years,
2. hypertension that is difficult to control after initiating therapy,
3. clinical occurrence of a hypertensive crisis,
4. the presence of hypokaliemia or metabolic alkalosis, or a random aldosterone-renin ration (ARR) >30, and
5. evidence of adrenal incidentaloma and hypertension or hypokalemia.

Exclusion Criteria:

1. chronic kidney disease with elevated estimated glomerular filtration rate (< 60, mL/min/1.73 m2)
2. liver disease with elevated GPT (> 35)
3. heart failure
4. classified as more than NYHA II,
5. hyperthyroidism
6. malignancy with metastasis

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
aldosteronism, hypertension	Drug: captopril test; The blood samplings were obtained one hour after the administration of 50 mg of captopril.The testing is performed in the morning on a seated ambulatory patient
hypertension	Drug: captopril test; The blood samplings were obtained one hour after the administration of 50 mg of captopril.The testing is performed in the morning on a seated ambulatory patient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determination of ARC in contrast to PRA offers advantage with regard to processing and standardization, knowing the postcaptopril sensitivity and specificity	1 day

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Novartis

Publications and helpful links

General Publications

• Wu VC, Kuo CC, Chang HW, Tsai CT, Lin CY, Lin LY, Lin YH, Wang SM, Huang KH, Fang CC, Ho YL, Liu KL, Chang CC, Chueh SC, Lin SL, Yen RF, Wu KD; TAIPAI study group. Diagnosis of primary aldosteronism: comparison of post-captopril active renin concentration and plasma renin activity. Clin Chim Acta. 2010 May 2;411(9-10):657-63. doi: 10.1016/j.cca.2010.01.027. Epub 2010 Feb 1.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Anticipated): January 1, 2009
• Study Completion (Anticipated): May 1, 2009

Study Registration Dates

• First Submitted: June 8, 2009
• First Submitted That Met QC Criteria: June 9, 2009
• First Posted (Estimate): June 10, 2009

Study Record Updates

• Last Update Posted (Estimate): June 10, 2009
• Last Update Submitted That Met QC Criteria: June 9, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: primary aldosteronism; PRA; ARC; captopril test; aldosterone-renin ratio; Primary aldosteronism (PA) than PRA and establish thresholds for the diagnosis using ARC.
• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Hyperaldosteronism; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Captopril
• Other Study ID Numbers: 200904076R