Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria

• ClinicalTrials.gov Identifier: NCT00893425
• Recruitment Status: Completed
• First Posted: May 6, 2009
• Last Update Posted: June 3, 2009
• Sponsor: Gulhane School of Medicine
• Information provided by: Gulhane School of Medicine

Study Description

Brief Summary:

In recent years, diabetic nephropathy, which may lead to dialysis treatment, is the most prevalent underlying disease of people in developed countries. A wide range of studies have been carried out, from various points of view, to understand the progress of renal dysfunction in diabetic nephropathy. The endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) is elevated in patients with chronic kidney disease (CKD) and may have a role in the cardiovascular mortality and morbidity of these patients. In diabetic nephropathy, high ADMA levels were related to progression of diabetic nephropathy. The Fas (CD95) antigen is a cell surface polypeptide belonging to the tumor necrosis factor receptor (TNF-R) family (type I membrane protein) that transduces a death signal after interaction with its ligand. Apoptotic cells are then recognized and removed by phagocytes. Recent studies suggest that, in uremic patients, peripheral blood mononuclear cells undergo accelerated apoptosis and this correlates with Fas levels. There is no data about the effects of Renin angiotensin system blockage (RAS) on CD95 and ADMA levels in diabetic patients with proteinuria. The aim of this study was to find out whether the beneficial effects of RAS blockage in diabetic proteinuria has any relation with the alteration of ADMA and CD95levels. The investigators searched for the effects of ACE inhibitor ramipril on the clinical and laboratory parameters of diabetic patients with proteinuria.

Condition or disease	Intervention/treatment	Phase
Proteinuria; Diabetic Nephropathy; Chronic Kidney Disease	Drug: ramipril	Phase 4

Detailed Description:

The patients who were non-obese (BMI < 30 kg/m2), non dyslipidemic (total cholesterol < 200 mg/dl, Triglyceride<150mg/dl), and free of cardiovascular events (negative medical history, negative ECG findings) were investigated for enrollment. CKD stage 1 patients older than 18 years of age and willing to participate to the study were screened. From the 231 patients with established type 2 diabetes mellitus, 126 had proteinuria and/or hypertension (24 h protein excretion 1-2 g/day, systolic blood pressures ≥ 140 mmHg and/or diastolic blood pressures ≥ 90 mmHg, respectively). All cases were first referrals and at the time of the study all were off treatment. Patients with history of coronary artery disease, smokers and those taking statins or renin-angiotensin blockers were excluded because of the effect of these factors on endothelial dysfunction. Of 126 screened patients 78 met the study criteria and were included in this study. The duration of proteinuria and diabetic nephropathy after initial diagnosis was not known.

The exclusion criteria were as follows: A)Nephrotic syndrome, B)coronary heart disease (patients with ischemic ST-T alterations and voltage criteria for LVH on electrocardiogram, and with history of revascularization or myocardial infarction), C) elevated liver enzymes (AST or ALT levels ≥ 40 U/L) and D) renal failure (serum creatinine levels > 1.3 mg/dl). In order to evaluate the effect of RAS blockade on plasma PTX3 concentrations, patients with proteinuria were given an ACE inhibitor (ramipril 10 mg/day) for 12 weeks. The effect of RAS blockade on insulin sensitivity and proteinuria was also investigated.

After the intervention period, blood samples were obtained for assay of plasma PTX3 concentrations, HbA1c , and insulin resistance scores (HOMA-IR).

Urine samples were also collected over a 24-hour period to determine the degree of proteinuria.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 78 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: Single
• Primary Purpose: Treatment
• Official Title: Effect of Renin Angiotensin System Blockade on CD95 and ADMA Levels in Type-2 Diabetic Patients With Proteinuria
• Study Start Date: January 2008
• Actual Primary Completion Date: March 2009
• Actual Study Completion Date: April 2009

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Flow mediated dilatation

Secondary Outcome Measures :

1. ADMA CD95

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• CKD stage 1 patients
• Older than 18 years of age
• Type 2 Diabetic patients
• Proteinuria

Exclusion Criteria:

• History of coronary artery disease
• Smokers
• Taking statins or renin-angiotensin blockers

Contacts and Locations

Locations

Turkey

Gulhane School of Medicine

Ankara, Turkey, 06108

Sponsors and Collaborators

Gulhane School of Medicine

Investigators

• Principal Investigator: Mahmut I Yilmaz, MD; Gulhane School of Medicine

More Information

• ClinicalTrials.gov Identifier: NCT00893425
• Other Study ID Numbers: GATARAMCD9509
• First Posted: May 6, 2009
• Last Update Posted: June 3, 2009
• Last Verified: June 2009

Keywords provided by Gulhane School of Medicine:

CD95; ADMA; proteinuria; diabetic nephropathy; CD95 and ADMA levels

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Diabetic Nephropathies; Proteinuria; Urologic Diseases; Renal Insufficiency; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Urination Disorders; Urological Manifestations; Ramipril; Angiotensin-Converting Enzyme Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents