Pioglitazone Attenuates Dysmetabolism in Peritoneal Dialysis (PD) Patients
Pioglitazone Attenuates Dysmetabolism in Peritoneal Dialysis (PD) Patients
1. Background:Cardiovascular disease (CVD) is the major cause of mortality in peritoneal
 dialysis (PD) patients, in whom it is partly attributable to a higher prevalence of
 dysmetabolism. Currently, few treatments are available with a proven effect on
 dyslipidemia, insulin resistance and inflammation in this patient group.

 2. Study design: Randomized, cross-over trial.

 3. Settings and Participants: Prevalent PD patients (>20 years old, s-triglycerides >1.8
 mmol/L) who had never received glitazones were enrolled.

 4. Interventions: Participants were randomized to receive either oral pioglitazone (PIO; 15
 mg once daily) and no pioglitazone, both for 12 weeks and in random order, with a
 four-week wash out in between.

 5. Outcomes and measurements: The primary endpoint was change of serum triglyceride (TG)
 level during the PIO as compared to no PIO. Secondary endpoints included changes in
 other lipid levels, HOMA-IR, adipocytokines and CRP. Outcome effects were assessed using
 a GLM.
Cardiovascular disease (CVD) is the major cause of mortality in chronic kidney disease,
 including peritoneal dialysis (PD) patients. While survival has not been shown to differ
 between peritoneal and hemodialysis, because of glucose uptake from the dialysate PD patients
 are more prone to dyslipidemia, insulin resistance (IR) and obesity. These metabolic
 disorders are substantially linked to the development of CVD and mortality in this patient
 population.

 Hypertriglyceridemia, reported to be present in 70% of PD patients, is linked to both glucose
 uptake from the peritoneum and IRand promote vascular damage. Inflammation has been proposed
 to be a fundamental promoter of atherosclerosis and demonstrated a dose-response relationship
 between C-reactive protein (CRP) and mortality . Adipocytokines, such as adiponectin，leptin
 and resistin, also play important roles in the development of dyslipidemia, IR,
 atherosclerosis, inflammation and CVD in PD patients. Therefore, therapies targeted at
 metabolic disorder are an important component of treatment for PD patients. Fibrates,
 peroxisome proliferator-activated receptors (PPAR)-α agonist, can lower serum TG, however,
 its use in PD patients is limited by its limited efficacy and often-appeared adverse effects
 such as rhabdomyolysis and hepatic impairment. Nowadays, PPAR-γ agonist, thiazolidinediones
 (TZDs), represented by pioglitazone and rosiglitazone, exert their hypoglycemic properties
 through reduction of insulin resistance. For more than ten years, they have been used to
 control blood glucose in type 2 diabetes mellitus (T2DM). In addition, TZDs have also been
 noted to have beneficial effects on lipid metabolism and inflammation apart from their
 effects on glycogenic control. However, the study about TZDs in the treatment of metabolic
 disorder in PD patients, especially in nondiabetic subjects is very scarce and limited.

 We, therefore set out to investigate the effect of TZDs, pioglitazone on hyperlipidemia,
 insulin resistance, inflammation and adipokine dysmetabolism of PD patients, especially in
 nondiabetic patients.
Inclusion Criteria:

 All patients received more than one month regular continuous ambulatory peritoneal
 dialysis(CAPD) or intermittent peritoneal dialysis(IPD). The causes of chronic renal
 failure were diabetes and non-diabetes.-

 Exclusion Criteria:

 history of allergy to thiazolidinediones and fenofibrate; history of any sever adverse
 event for fibrate that can't be tolerated by the patients; patient can not be follow-up
 regularly; history of myocardial infarction(MI) or coronary artery bypass graft (CABG)
 surgery within the past 1 month, history of cerebral vascular accident (CVA) or
 percutaneous transluminal coronary angioplasty(PTCA) within the past 6 months; chronic use
 of non-steroidal anti-inflammatory drugs(NSAIDs), steroids or immunosuppressives; patient
 with the acute infection; patient with malignant tumor; have the evidence of severe hepatic
 injury (ALT/AST>100u/L).-