Sodium-Endothelial Function-CKD Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00141622
Recruitment Status : Completed
First Posted : September 1, 2005
Last Update Posted : May 15, 2007
British Heart Foundation
St. George's Hospital Charitable Foundation
Information provided by:
St George's, University of London

Brief Summary:
Heart disease and stroke, known as cardiovascular disease, are major causes of death in people with chronic kidney disease. Abnormalities of a metabolic pathway called the “L-arginine-nitric oxide” pathway are thought to be particularly important in these people, and previous research in animals has suggested that sodium (salt) affects part of this metabolic pathway. The purpose of our research is to study the effects of sodium intake on the “L-arginine-nitric oxide” pathway, and on blood vessel function, in patients with kidney disease.

Condition or disease Intervention/treatment Phase
Kidney Failure, Chronic Drug: Slow sodium Not Applicable

Detailed Description:

Chronic kidney disease (CKD) is associated with abnormalities of endothelial function (EF) and nitric oxide (NO) synthesis, and it is proposed that the endogenous NO synthase inhibitor asymmetrical dimethylarginine (ADMA) plays a central role. In man ADMA is largely metabolized by dimethylarginine dimethylaminohydrolase (DDAH), with some renal excretion occurring. Sodium inhibits DDAH expression in experimental animals and, given that CKD is frequently characterized by sodium retention, it would be interesting to study the effects of sodium loading on DDAH activity/expression, ADMA levels and EF in CKD patients.

To answer these questions, we have designed a double-blind cross-over study employing Slow Sodium (150 mmol/day) and placebo for seven days in individuals with mild-to-moderate CKD. Changes in the ratio of urinary ADMA to dimethylamine (DMA, an ADMA metabolite) will be used as an marker of DDAH activity/expression. ADMA will be measured by ELISA, DMA by high performance liquid chromatography, and EF by venous occlusion plethysmography.

We propose to test the following hypothesis; that in subjects with mild-to-moderate CKD under conditions of high sodium intake, as compared to low-normal sodium intake:

(i) The ratio [ADMA]urine:[DMA]urine is increased (ii) [ADMA]plasma is increased (iii) Endothelium-dependent vasodilatation is reduced

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Primary Purpose: Prevention
Official Title: Does Sodium Affect Endothelial Function in Individuals With Chronic Kidney Disease?
Study Start Date : April 2005
Study Completion Date : October 2006

Primary Outcome Measures :
  1. Under conditions of high (vs. low sodium intake) ...
  2. (i) The ratio [ADMA]urine:[DMA]urine is increased
  3. (ii) [ADMA]plasma is increased
  4. (iii) Endothelium-dependent vasodilatation is reduced

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • CKD Stages 2 and 3 [= calculated creatinine clearance of 30 to 89 ml/min/1.73m2 by Cockcroft-Gault formula]
  • 18 to 75 years old

Exclusion Criteria:

  • >3 g/24 hours of proteinuria
  • Uncontrolled hypertension (systolic BP >160 mmHg, diastolic BP >100 mmHg on/off anti-hypertensive medication)
  • Diabetes mellitus
  • Tobacco smoking
  • Total fasting cholesterol >6 mmol/L
  • Uncontrolled heart failure or active IHD
  • Chronic liver failure
  • Active malignancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00141622

United Kingdom
Blood Pressure Unit, Department of Cardiac & Vascular Sciences, SGUL
London, United Kingdom, SW17 0RE
Sponsors and Collaborators
St George's, University of London
British Heart Foundation
St. George's Hospital Charitable Foundation
Principal Investigator: Timothy WR Doulton, BSc MRCP SGUL Identifier: NCT00141622     History of Changes
Other Study ID Numbers: LREC 04/Q0803/181
First Posted: September 1, 2005    Key Record Dates
Last Update Posted: May 15, 2007
Last Verified: August 2005

Keywords provided by St George's, University of London:
Endothelial dysfunction

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Failure, Chronic
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic