Dual PPARα/γAgonism Normalizes Lipoprotein Profile of Renal Dyslipidemia

Abstract

Chronic kidney disease (CKD) is characterised by specific lipoprotein abnormalities and insulin resistance. Dual activation of the peroxisome proliferators-activated receptors (PPAR)αandγcan significantly improve insulin sensitivity. The aim of the study was to investigate the effects of a dual PPARα/γagonist on lipoprotein abnormalities in patients with CKD. One mg of the dual PPARα/γagonist 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 PPARα/γagonist has the potential to normalise most of the lipoprotein abnormalities in patients with CKD.