Renal PPARγ mRNA expression increases with impairment of renal function in patients with chronic kidney disease

Abstract

Aim: Peroxisome proliferator-activated receptor gamma (PPARγ) is generally accepted as renoprotective factor in type 2 diabetes mellitus, and PPARγ agonists have been reported to reduce albuminuria. However, little is known about renal PPARγ expression in chronic kidney disease, and especially human data are scarce. We hypothesized that renal PPARγ expression is associated with extent of proteinuria, kidney function, histological diagnosis and inflammatory mediators. Therefore, we investigated PPARγ mRNA expression in human kidney biopsies.

Methods: We quantified PPARγ mRNA as well as the expression of macrophage chemoattractant protein-1, transforming growth factor beta-1 and interleukin-6 in 64 human kidney biopsies from patients with chronic kidney disease and mild-to-marked proteinuria of diverse aetiology. We measured renal function, and macrophage invasion was quantified by CD68 and vascularization by CD34 immunostaining.

Results: PPARγ mRNA expression correlated inversely with renal function. Higher blood pressure levels were associated with higher PPARγ expression levels. PPARγ mRNA expression correlated significantly (P<0.001) with macrophage chemoattractant protein-1 mRNA expression and showed a negative trend with transforming growth factor beta-1 mRNA expression. No differences in PPARγ expression were detected with regard to extent of proteinuria, histological diagnosis, macrophage invasion, interleukin-6 expression, and age or body mass index.

Conclusions: PPARγ expression increases with loss of renal function and may be an important factor in maintaining normal renal function serving as a key protective mechanism to renal injury.