Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria
Condition: Proteinuria; Diabetic Nephropathy; Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Diabetic Nephropathies; Proteinuria
Study type: Interventional
Phase: Phase 4

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.
    

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.
    

Intervention name(s): ramipril
Intervention type(s): Drug
Intervention MeSH terms: Ramipril
Intervention model: Single Group Assignment
Masking: Single
Primary purpose: Treatment
Keywords: CD95; ADMA; proteinuria; diabetic nephropathy; CD95 and ADMA levels