Journal Article

Rosiglitazone does not improve vascular function in subjects with chronic kidney disease

Doris T. Chan, Gerald F. Watts, Ashley B. Irish and Gursharan K. Dogra

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 26, issue 11, pages 3543-3549
Published in print November 2011 | ISSN: 0931-0509
Published online March 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr049
Rosiglitazone does not improve vascular function in subjects with chronic kidney disease

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Background. Thiazolidinediones such as rosiglitazone (RSG) are insulin-sensitizing agents, which may improve inflammation and vascular function, and thus potentially lower cardiovascular risk in patients with chronic kidney disease (CKD). However, there is growing concern about the adverse cardiovascular effects of RSG in diabetic patients without CKD, and the data in patients with CKD remain conflicting. This study examines the effect of RSG on vascular function in patients with CKD.

Methods. A randomized, double-blind placebo-controlled study comparing RSG 4 mg daily (n = 35) with placebo (n = 35) for 8 weeks was performed in CKD subjects. Primary outcome measures were flow-mediated dilatation (FMD), systemic arterial compliance (SAC) and augmentation index (AIx). Secondary outcomes included glyceryl trinitrate-mediated dilatation (GTN-MD), pulse-wave velocity (PWV), lipids, blood pressure, homoeostasis model assessment (HOMA), adiponectin, high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity interleukin 6 (hs-IL-6) and in vivo marker of endothelial function [von Willebrand Factor (vWF)].

Results. RSG lowered HOMA score [RSG geometric mean 1.7 (95% confidence interval 1.3–2.3); placebo 1.9 (1.4–2.5), P = 0.04], hs-CRP [RSG 1.2 (0.9–1.7) mg/L; placebo 1.6 (1.2–2.3), P = 0.04] and vWF [RSG mean 126.1 ± SD 45.7%; placebo 132.7 ± 41.7, P = 0.01] but not hs-IL-6. RSG did not significantly change arterial function (FMD, GTN-MD, SAC), arterial stiffness (AIx, PWV) or blood pressure. RSG increased triglyceride concentration [RSG 1.8 (1.3–1.9) mmol/L; placebo 1.5 (1.3–1.9), P = 0.01] without affecting other lipid and lipoprotein concentrations.

Conclusion. Short-term RSG therapy reduced insulin resistance, in vivo markers of inflammation and abnormal endothelial function but had no effect on arterial function and stiffness in patients with CKD.

Keywords: chronic kidney disease; inflammation; insulin resistance; thiazolidinediones; vascular function

Journal Article.  4269 words.  Illustrated.

Subjects: Nephrology

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