PPARγ and chronic kidney disease

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists, exemplified by the thiazolidinediones (TZDs), have been used extensively for their beneficial effects to improve insulin sensitivity and lipid metabolism in type 2 diabetic patients. PPAR gamma receptors are part of the steroid hormone nuclear receptor family and, when activated by agonist binding, can affect numerous target genes expressing PPAR response elements. Results from experimental studies and a limited number of studies in humans suggest that PPAR gamma agonists have manifold effects beyond those on dysmetabolic syndrome. These potentially beneficial actions are mediated via renal parenchymal and infiltrating cells and modulate fibrotic, inflammatory, immune, proliferative, reactive oxygen and mitochondrial injury pathways. Thus, the potential benefits of TZDs in chronic kidney disease impact numerous pathogenic pathways. This review will focus on evidence of the effects of TZDs in nondiabetic chronic kidney disease in experimental and human disease settings.