Diagnostic Properties of Aldosterone-Renin Ratio in Primary Aldosteronism Among Hypertensives.

Aldosterone-Renin Ratio to Diagnose Primary Aldosteronism in a Population of Patients With Therapy-Resistant Hypertension: Test Characteristics, Diagnostic Value and Predictive Value for Antihypertensive Treatment. The Dutch ARRAT Study.

This study aims to evaluate the diagnostic value of the Aldosterone-Renin Ratio (ARR)as a screening test for primary aldosteronism among hypertensives. The test characteristics will be studied. Furthermore, the effect of eplerenone, a selective aldosterone-receptor antagonist will be studied.

Study Overview

• Status: Unknown
• Conditions: Hypertension; Hyperaldosteronism
• Intervention / Treatment: Drug: eplerenone

Detailed Description

Although primary aldosteronism (PA) was formerly seen as a rare cause of hypertension, this condition is now thought to be the commonest cause of secondary hypertension, with the prevalence ranging up to 10-15 % of all hypertensives. Identification of patients with PA allows for specific treatment, for instance unilateral adrenalectomy in case of an aldosterone-producing adenoma or the administration of an aldosterone-receptor antagonist in case of bilateral adrenal hyperplasia.

Since the introduction of the aldosterone-renin ratio (ARR) as a screening tool for PA in 1981, there has been considerable debate about the diagnostic value. The values for aldosterone and renin are highly dependent on many factors, including posture, time of day and medication. Also, the cut-off values for the identification of PA remain controversial.

This study aims to evaluate the test characteristics of the ARR in a population of patients with therapy-resistant hypertension, the dependence of the ARR on medication type and the predictive value on the response on eplerenone, a selective aldosterone-receptor antagonist.

• Study Type: Observational
• Enrollment: 500

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Not yet recruiting
    • VU Medical Center
  • Amsterdam, Netherlands
    • Not yet recruiting
    • Academical Medical Center
  • Capelle aan de IJssel, Netherlands
    • Not yet recruiting
    • Ijsselland Hospital
  • Gorinchem, Netherlands
    • Not yet recruiting
    • Beatrix Hospital
  • Nijmegen, Netherlands
    • Not yet recruiting
    • University Medical Center St. Radboud
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus Medical Center
  • Rotterdam, Netherlands
    • Recruiting
    • Ikazia Hospital
  • Rotterdam, Netherlands
    • Not yet recruiting
    • MCRZ, lokation Zuider/Clara
  • Rotterdam, Netherlands
    • Not yet recruiting
    • Oogziekenhuis
  • Rotterdam, Netherlands
    • Not yet recruiting
    • Sint Franciscus Gasthuis
  • Schiedam, Netherlands
    • Not yet recruiting
    • Vlietland Hospital
  • Spijkenisse, Netherlands
    • Not yet recruiting
    • Ruwaard van Putten Hospital
  • Waalwijk, Netherlands
    • Not yet recruiting
    • Twee Steden Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 18-65 years
• blood pressure above 140 mmHg systolic and above 90 mmHg diastolic
• use of at least 2 antihypertensive drugs

Exclusion Criteria:

• known cause of hypertension, including white-coat hypertension
• severe renal failure (kreat > 200 umol/l)
• BMI above 32 kg/m2
• poorly regulated diabetes mellitus (HbA1C > 8.0 %)
• heart failure
• stroke or myocardial infarction within 6 months before inclusion
• angina pectoris
• pregnancy
• neoplastic disease, within 5 years before inclusion
• alcohol abuse

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Pfizer; Dutch Kidney Foundation
• Investigators: Principal Investigator: A.H. van den Meiracker, MD, PhD, Erasmus Medical Center

Publications and helpful links

General Publications

• Hiramatsu K, Yamada T, Yukimura Y, Komiya I, Ichikawa K, Ishihara M, Nagata H, Izumiyama T. A screening test to identify aldosterone-producing adenoma by measuring plasma renin activity. Results in hypertensive patients. Arch Intern Med. 1981 Nov;141(12):1589-93.
• Gordon RD, Klemm SA, Stowasser M, Tunny TJ, Storie WJ, Rutherford JC. How common is primary aldosteronism? Is it the most frequent cause of curable hypertension? J Hypertens Suppl. 1993 Dec;11(5):S310-1. No abstract available.
• Strauch B, Zelinka T, Hampf M, Bernhardt R, Widimsky J Jr. Prevalence of primary hyperaldosteronism in moderate to severe hypertension in the Central Europe region. J Hum Hypertens. 2003 May;17(5):349-52. doi: 10.1038/sj.jhh.1001554.
• Stowasser M, Gordon RD, Gunasekera TG, Cowley DC, Ward G, Archibald C, Smithers BM. High rate of detection of primary aldosteronism, including surgically treatable forms, after 'non-selective' screening of hypertensive patients. J Hypertens. 2003 Nov;21(11):2149-57. doi: 10.1097/00004872-200311000-00025.
• Schwartz GL, Turner ST. Screening for primary aldosteronism in essential hypertension: diagnostic accuracy of the ratio of plasma aldosterone concentration to plasma renin activity. Clin Chem. 2005 Feb;51(2):386-94. doi: 10.1373/clinchem.2004.041780.
• Giacchetti G, Ronconi V, Lucarelli G, Boscaro M, Mantero F. Analysis of screening and confirmatory tests in the diagnosis of primary aldosteronism: need for a standardized protocol. J Hypertens. 2006 Apr;24(4):737-45. doi: 10.1097/01.hjh.0000217857.20241.0f.
• Kaplan NM. The current epidemic of primary aldosteronism: causes and consequences. J Hypertens. 2004 May;22(5):863-9. doi: 10.1097/00004872-200405000-00001.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Study Completion: November 1, 2009

Study Registration Dates

• First Submitted: December 4, 2006
• First Submitted That Met QC Criteria: December 4, 2006
• First Posted (ESTIMATE): December 5, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): March 7, 2007
• Last Update Submitted That Met QC Criteria: March 6, 2007
• Last Verified: March 1, 2007

More Information

Terms related to this study

• Keywords: hypertension; screening; primary aldosteronism; eplerenone; aldosteron-renin ratio; aldosteron-receptor antagonist
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Endocrine System Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Hypertension; Hyperaldosteronism; Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: MEC-2006-103; C05.2151; EudraCT nr: 2006-006618-13