Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) Agonist in Diabetic End-Stage Renal Disease Patients

Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) Agonist in Diabetic End-Stage Renal Disease Patients

A Randomized Placebo-Controlled Study to Evaluate the Efficacy of Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) Agonist in Inducing Carotid Atherosclerotic Plaque Regression in Diabetic End-Stage Renal Disease Patients

To test the hypothesis that PPAR-gamma agonist, rosiglitazone, induces carotid plaque regression in diabetic ESRD patients on maintenance PD via its anti-inflammatory property.

End-stage renal disease (ESRD) patients are at an increased risk of accelerated atherosclerosis and cardiovascular morbidity and mortality. Non-traditional risk factors such as inflammation and insulin resistance have important contributions to accelerated atherosclerosis in ESRD patients receiving long-term peritoneal dialysis (PD). The peroxisome proliferator-activated receptor-g (PPAR-g) is a member of the nuclear receptor family of ligand-dependent transcription factors. Activation of the PPAR-g has been shown in both clinical and experimental studies to have anti-inflammatory and anti-atherosclerotic properties other than insulin-sensitizing effects. Recent study also showed that PPAR-g agonists reduce plaque inflammation by inhibiting the activation of proinflammatory genes responsible for plaque development and growth. Hence, this study aims to examine the effects of PPAR-g activation on the progression of carotid plaque in diabetic ESRD patients receiving long-term PD using high-resolution magnetic resonance imaging (MRI).

Pioglitazone drug 15mg daily for 3 months then 30mg for 9 months (Peroxisome Proliferator-Activated Receptor-gamma agonist)

Change in inflammatory markers include C-reactive protein, interleukin-6, adiponectin, metalloproteinases

Inclusion Criteria: Diabetic ESRD patients receiving long-term PD treatment, with carotid plaque (defined as focal intima-media thickening >1mm) present on screening ultrasonography Patients who provide informed consent for the study Exclusion Criteria: Patients with systemic inflammatory disease such as systemic lupus erythematosus Patients with chronic liver disease or cirrhosis Patients with current active malignancy Patients with chronic rheumatic heart disease or congenital heart disease Patients with poor general condition Patients with plan for living related kidney transplant within coming 1 year Patients with pre-existing class III/IV heart failure, Patients with recurrent hypoglycemia Patients already on glitazone treatment Female patients with pregnancy Patients with contraindications for MRI examination including those with pacemaker or metallic implant.