Metabolic Effects of Thiazolidinediones in Chronic Kidney Disease
Status:
Terminated
Trial end date:
2007-09-01
Target enrollment:
Participant gender:
Summary
The substantially increased cardiovascular morbidity and mortality rates in chronic kidney
disease (CKD) patients cannot be sufficiently explained by traditional coronary risk factors.
It is apparent that inflammation of the vessel wall plays an essential role in the
pathophysiology of atherosclerosis, and the strong association between elevated inflammatory
biomarkers and cardiovascular death further supports this mechanism. Approximately 50% of the
mortality in this population of patients is attributable to cardiovascular disease. Insulin
resistance is also a common problem in uremic patients. It has been shown that insulin
resistance may contribute to atherosclerotic cardiovascular disease. An intriguing
observation in CKD patients with advanced uremia is that the metabolic profile of these
patients is characterized by persistent low-grade inflammation, a state of insulin
resistance, and significantly increased prevalence of atherosclerosis. It is possible that
these metabolic derangements can be the inciting factors for development and progression of
uremic atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a
ligand-activated nuclear transcription factor found in cells of the immune system and the
vasculature, where it exerts an overall protective effect on the development of
atherosclerosis, in part through modulation of inflammation. The agonists for PPAR-gamma
improve not only the insulin resistance, but also have profound beneficial effects on
inflammation, oxidative stress, endothelium, and lipid metabolism. In this proposal, the
investigators hypothesize that short-term administration of a PPAR-gamma agonist
(pioglitazone) will improve the inflammatory state, insulin resistance, and endothelial
dysfunction in chronic kidney disease patients with advanced uremia.
Phase:
Phase 2
Details
Lead Sponsor:
Vanderbilt University Vanderbilt University Medical Center