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PPAR Research
Volume 2008, Article ID 943614, 8 pages
Review Article

Renal and Vascular Mechanisms of Thiazolidinedione-Induced Fluid Retention

Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, UT 84132-2412, USA

Received 25 February 2008; Accepted 4 June 2008

Academic Editor: Jane Pinaire

Copyright © 2008 Tianxin Yang and Sunhapas Soodvilai. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor subtype (PPAR ) activators that are clinically used as an insulin sensitizer for glycemic control in patients with type 2 diabetes. Additionally, TZDs exhibit novel anti-inflammatory, antioxidant, and antiproliferative properties, indicating therapeutic potential for a wide variety of diseases associated with diabetes and other conditions. The clinical applications of TZDs are limited by the common major side effect of fluid retention. A better understanding of the molecular mechanism of TZD-induced fluid retention is essential for the development of novel therapies with improved safety profiles. An important breakthrough in the field is the finding that the renal collecting duct is a major site for increased fluid reabsorption in response to rosiglitazone or pioglitazone. New evidence also indicates that increased vascular permeability in adipose tissues may contribute to edema formation and body weight gain. Future research should therefore be directed at achieving a better understanding of the detailed mechanisms of TZD-induced increases in renal sodium transport and in vascular permeability.