Peroxisome Proliferator-Activated Receptor-Gamma Activation in Peritoneal Dialysis Patients (PPAR)

Primary Outcome Measures:

• Change in carotid intima-media thickness [ Time Frame: wk 48 ] [ Designated as safety issue: No ]
  

Secondary Outcome Measures:

• Change in endothelial function, carotid plaque, vascular calcium score, arterial stiffening, abdominal visceral fat, C-reactive protein, HOMA, residual renal function, insulin dosage, overall survival and cardiovascular event-free survival [ Time Frame: at wk 24, wk 48 and wk 96 ] [ Designated as safety issue: No ]
  
• carotid intima-media thickness [ Time Frame: Wk 24 and wk 96 ] [ Designated as safety issue: No ]
  

Other Outcome Measures:

• Circulating endothelial progenitor cells [ Time Frame: Week 0, 24, 48 and 96 ] [ Designated as safety issue: No ]
  

Peritoneal dialysis patients are at increased risk of cardiovascular morbidity and mortality and are related to the presence of accelerated atherosclerosis. Other than the traditional cardiovascular risk factors, there is increasing evidence that inflammation is associated with the development of atherosclerosis and cardiovascular events in both the general and dialysis population. C-reactive protein is predictive of higher all-cause mortality and cardiovascular mortality, independent of other cardiovascular risk factors and atherosclerotic vascular disease. As a considerable proportion of peritoneal dialysis patients showed elevated C-reactive protein, it raises an important question as to whether lowering C-reactive protein will have any cardiovascular and survival benefit in these patients. On the other hand, insulin resistance with associated hyperinsulinemia is frequently observed in chronic renal failure and dialysis patients. Although the exact mechanism of insulin resistance needs further evaluation, studies indicated that insulin resistance is an important cardiovascular risk factor and outcome predictor in the general and dialysis population. Moreover, recent evidence indicates an association between chronic inflammation and insulin resistance although the exact interrelationship remains unclear. The peroxisome proliferator-activated receptor-gamma (PPAR-g) is a member of the nuclear receptor family of ligand-dependent transcription factors. PPAR-g is highly expressed in adipose tissue and clinical study has confirmed efficacy of the specific ligands for PPAR-gamma, namely thiazolidinediones (TZD), in improving insulin sensitivity. Recent experimental and clinical studies demonstrated that TZD has anti-inflammatory and anti-atherosclerotic properties other than insulin sensitizing effect in type 2 diabetics. We hypothesize that modulation of the PPAR-g activity may be a novel therapeutic strategy for reducing inflammation and improving insulin sensitivity and may retard the progression of atherosclerosis and possibly reduce mortality of our peritoneal dialysis patients.