Chronic kidney disease (CKD) is characterised by specific lipoprotein abnormalities and insulin resistance. Dual activation of the peroxisome proliferators-activated receptors (PPAR) α and γ can significantly improve insulin sensitivity. The aim of the study was to investigate the effects of a dual PPAR α/γ agonist on lipoprotein abnormalities in patients with CKD. One mg of the dual PPAR α/γ agonist tesaglitazar was given once daily during six weeks to CKD patients, and to healthy subjects. Plasma lipids, apolipoproteins (apo) and discrete lipoprotein subclasses were measured at baseline and end of treatment. In the CKD patients apoA-I increased significantly by 9%, and apoB decreased by 18%. There was an increase of apoC-III in HDL by 30%, and a parallel decrease of apoC-III in VLDL + LDL by 13%. Both the apoB-containing cholesterol-rich and the triglyceride-rich subclasses decreased significantly. With the exception of ApoC-III,all plasma lipids apolipoproteins and lipoprotein subclasses were reduced by treatment down to similar levels as the baseline levels of a healthy group of reference subjects. This study suggests that by improving insulin sensitivity a dual PPAR α/γ agonist has the potential to normalise most of the lipoprotein abnormalities in patients with CKD. 1. Introduction Chronic renal insufficiency is characterized by specific lipoprotein abnormalities [1–3], insulin resistance, and accelerated cardiovascular disease (CVD) [4–6]. The renal dyslipidemia shares many features with the alterations of the lipoprotein metabolism found in patients with insulin resistance [7]. Hence, reduction of insulin resistance in chronic renal insufficiency could theoretically have positive effects on renal dyslipidemia and, consequently, also positive effects on CVD morbidity in patients with chronic kidney disease (CKD). It is well documented that patients with chronic renal insufficiency as well as patients with diabetes mellitus are at high cardiovascular risk and that the characteristic lipoprotein abnormalities play an important role in atherogenesis [8, 9]. In a post-hoc analysis of the VA-HIT study the peroxisome proliferators-activated receptor (PPAR) α agonist gemfibrozil was shown to reduce cardiovascular morbidity in coronary patients with mild to moderate renal insufficiency [10]. Furthermore, in a post-hoc analysis of the PROactive trial the PPAR γ-agonist pioglitazone significantly reduced cardiovascular morbidity in type 2 diabetic patients with reduced renal function and documented macrovascular disease [11]. Tesaglitazar is a dual PPAR
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