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NDT Advance Access originally published online on July 31, 2006
Nephrology Dialysis Transplantation 2006 21(10):2696-2702; doi:10.1093/ndt/gfl448
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Are peroxisome proliferator-activated receptors new therapeutic targets in diabetic and non-diabetic nephropathies?

Henri Boulanger1,, Rafik Mansouri1, Jean François Gautier2 and Denis Glotz1

1Department of Nephrology and Transplantation and 2Department of Diabetes and Endocrinology, Saint-Louis Hospital, Paris, France

Correspondence and offprint requests to: Henri Boulanger, Department of Nephrology and Transplantation, Saint-Louis Hospital, 1, avenue Claude-Vellefaux, 75475 Paris Cedex 10, France. Email: henri.boulanger@sls.aphp.fr

Keywords: diabetic and non-diabetic nephropathies; peroxisome proliferator-activated receptors (PPAR) {alpha}, {gamma} and ß/{delta} agonists; renal protection

The first 150 words of the full text of this article appear below.



   Introduction
 
Peroxisome proliferator-activated receptors (PPAR), members of the nuclear hormone-receptor superfamily of ligand-binding-transcription factors, are involved in the pathophysiology of the metabolic syndrome. Agonist activation of PPAR provides a new pharmacological pathway to the treatment of the metabolic syndrome and its complications. Since one of the major complications of this syndrome is nephropathy, the potential benefit of PPAR{alpha}, -{gamma} and –ß/{delta} agonists on kidney merits examination. Moreover, numerous studies have demonstrated that, in addition to their hypolipidaemic and anti-diabetic effects, these drugs possess anti-inflammatory, anti-fibrotic and anti-proliferative properties. These data strongly suggest a potential benefit of PPAR agonists on diabetic and non-diabetic nephropathies. Herein, we describe the currently known effects of PPAR{alpha}, -{gamma} and -ß/{delta} agonists on diabetic and non-diabetic nephropathies, and more precisely, focus on their potential positive impact on kidneys.



   Renal effects of PPAR{alpha} agonists
 
PPAR{alpha} agonists are involved in lipid-metabolism regulation primarily by increasing fatty acid ß oxidation. PPAR{alpha} are predominantly . . . [Full Text of this Article]



   Importance of the PPAR{alpha}-induced ß-oxidation pathway for maintaining adequate renal proximal tubule function
 


   PPAR{alpha} activation prevents excess renal lipid accumulation and renal function deterioration in diabetic and non-diabetic animal models
 


   Anti-inflammatory properties of PPAR{alpha} agonists
 


   PPAR{alpha}–cytochrome P-450 activation pathway and pressure natriuresis regulation
 


   Evidence of renal protection by PPAR{alpha} agonists in humans
 


   Renal effects of PPAR{gamma} agonists
 


   PPAR{gamma} agonist-induced fluid retention and lower blood pressure
 
Mechanism of PPAR{gamma} agonist-induced fluid retention
PPAR{gamma} agonist-induced mechanisms lowering blood pressure


   Anti-inflammatory, anti-proliferative and anti-fibrotic properties of PPAR{gamma} agonists
 
In vitro effects on mesangial cells
In vitro effects on renal tubule cells
Diabetic animal models with nephropathy
Non-diabetic animal models with nephropathy


   Evidence of renal protection by PPAR{gamma} agonists in humans
 
PPAR{gamma} agonists decrease UAE
Nephroprotective effect of the PPAR{gamma}2 polymorphism Pro12Ala among T2D patients


   Renal effects of PPARß/{delta} agonists
 
PPARß/{delta} agonists provide strong renal protection in the model of ischaemic acute renal failure


   Conclusion and therapeutic perspectives
 

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H. Boulanger, R. Mansouri, J. F. Gautier, and D. Glotz
Reply--PPAR agonists in diabetic nephropathy
Nephrol. Dial. Transplant., July 1, 2007; 22(7): 2095 - 2096.
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