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PPAR Research
Volume 2014, Article ID 818530, 7 pages
http://dx.doi.org/10.1155/2014/818530
Review Article

New Insights into the PPARγ Agonists for the Treatment of Diabetic Nephropathy

1Department of Nephrology, Nanjing Children’s Hospital, Nanjing Medical University, Nanjing 210008, China
2Institute of Pediatrics, Nanjing Medical University, Nanjing, China
3Key Pediatric Laboratory of Nanjing City, Nanjing 210008, China
4Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA
5Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA

Received 18 November 2013; Accepted 16 December 2013; Published 29 January 2014

Academic Editor: Lihong Chen

Copyright © 2014 Zhanjun Jia et al. 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.

Abstract

Diabetic nephropathy (DN) is a severe complication of diabetes and serves as the leading cause of chronic renal failure. In the past decades, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) based first-line therapy can slow but cannot stop the progression of DN, which urgently requests the innovation of therapeutic strategies. Thiazolidinediones (TZDs), the synthetic exogenous ligands of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ), had been thought to be a promising candidate for strengthening the therapy of DN. However, the severe adverse effects including fluid retention, cardiovascular complications, and bone loss greatly limited their use in clinic. Recently, numerous novel PPARγ agonists involving the endogenous PPARγ ligands and selective PPARγ modulators (SPPARMs) are emerging as the promising candidates of the next generation of antidiabetic drugs instead of TZDs. Due to the higher selectivity of these novel PPARγ agonists on the regulation of the antidiabetes-associated genes than that of the side effect-associated genes, they present fewer adverse effects than TZDs. The present review was undertaken to address the advancements and the therapeutic potential of these newly developed PPARγ agonists in dealing with diabetic kidney disease. At the same time, the new insights into the therapeutic strategies of DN based on the PPARγ agonists were fully addressed.