Kallikrein-kinin (KKS) and Renin-angiotensin-aldosterone System (RAAS) in Primary Aldosteronism

December 15, 2014 updated by: National Taiwan University Hospital

The tissue kallikrein-kinin (KKS) and renin-angiotension-aldosterone system (RAAS) had been implicated in regulating blood pressure and electrolyte homeostasis. Both of the KKS and RAAS may work coordinately to regulate salt metabolism, local blood flow. Thus, we conducted this study to elucidate, first, whether some alterations in components of the kallikrein-kinin system could do effect on aldosterone secretion.

Previous study has shown the post captopril plasma aldosterone concentration (PAC)/ plasma rennin activity (PRA) ration (ARR) was a reliable method for diagnosis of primary aldosteronism (PA). The ARR change by angiotensin II receptor blockade was reported to be significantly higher than that by ACE inhibitor. This study assessed whether angiotensin II receptor blockade offers any additional advantage in the diagnosis of PA. Clinically we evaluated the sensitivity and specificity of captopril (angiotensin-converting enzyme inhibition) and losartan (angiotensin II type 1 receptor blocker) test in PA patient. This interaction mechanism, in term, could further explain the interaction of KKS and RAAS.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hypertension affects 20% to 25% of adult population. Most patients are diagnosed as having essential or primary hypertension. Up to 10% to 15 % have an identifiable cause and many of those have an adrenal basis [Miroslava H. et al., 2002]. The tissue kallikrein-kinin (KKS) and renin-angiotension-aldosterone system (RAAS) had been implicated in regulating blood pressure and electrolyte homeostasis. Recent studies in humans indicate that the vasodilator tissue KKS, the counterpart of the tissue RAAS, is also expressed in the adrenal gland. The adrenal gland regulates sodium and water excretion and reabsorption through the release of aldosterone and corticosterone. Previous study reveals an anatomical linkage between the tissue KKS and sodium and water metabolism. Both of the KKS and RAAS may work coordinately to regulate salt metabolism, local blood flow. In contrast, although many investigators have supported the notion that Ang II and BK physiologically antagonize each other's effects on blood pressure, there are many instances where the two peptides exert common actions. For example, the Bradykinin also stimulates aldosterone release from adrenocortical cells through B2 receptors. Furthermore, the AT1 receptor and the bradykinin (B2) receptor form stable heterodimers, the two major signaling proteins triggered by AT1. In vitro studies (Margolius 1995) have shown that kallikrein acts as a prorenin-activating enzyme, and that tissue kallikrein can generate angiotensin II.

However, the interactions between both systems are complex and not always simply antagonistic. The interactions of the two systems on aldosterone secretion are not examined Thus, we conducted this study to elucidate, first, whether some alterations in components of the kallikrein-kinin system could do effect on aldosterone secretion.

Our study provides evidence that bradykinin contributes substantially to the aldosterone secretion with or without the effects of angiotensin. The data also could confirm whether ATR2-Bradykinin-B2-aldosterone really works. We want to realize the expression of angiotensin and bradykinin in the adrenal gland and hypertension related to these systems.

Previous study has showed the post captopril plasma aldosterone concentration (PAC)/ plasma rennin activity (PRA) ration (ARR) was a reliable method for diagnosis of primary aldosteronism (PA). The ARR change by angiotensin II receptor blockade was reported to be significantly higher than that by ACE inhibitor. This study assessed whether angiotensin II receptor blockade offers any additional advantage in the diagnosis of PA. Clinically we evaluated the sensitivity and specificity of captopril (angiotensin-converting enzyme inhibition) and losartan (angiotensin II type 1 receptor blocker) test in PA patient. This interaction mechanism, in term, could further explain the interaction of KKS and RAAS.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taipei, Taiwan
        • National Taiwan University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients with hypertension admitted for the diagnosis of primary aldosteronism

Exclusion Criteria:

Pregnant or lactating women. (Pre-menopause women, capable of bearing children will undergo pregnancy test), hypertension without discontinuous b-blocker, ACEI or ARB for more than 10 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Diagnosis of primary aldosteronism

Secondary Outcome Measures

Outcome Measure
Subgroup analysis of primary aldosteronism

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Investigators

  • Study Chair: Kwan-Dun Wu, MD, PhD, National Taiwan University Hospital
  • Study Director: Vin-Cent Wu, MD, National Taiwan University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2002

Primary Completion (Actual)

December 1, 2005

Study Completion (Actual)

December 1, 2005

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Estimate)

December 17, 2014

Last Update Submitted That Met QC Criteria

December 15, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9361700632

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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