Background

Obesity is one of the common cause of chronic kidney disease (CKD), independent of glycemic control. Recent studies suggest that body mass index is associated with incidence of CKD. Furthermore, insulin resistance observed in obesity has been associated with cardiovascular disease. These results suggest that obesity-induced abnormal metabolites may accelerate developing CKD, but the precise mechanism involved is unclear.

Aim
To clear the development of CKD in obesity and insulin resistant state, this study characterized the mechanism of albuminuria caused by inflammation and oxidative stress in the glomeruli of obesity and insulin-resistant rats.

Method
We used age-matched male Zucker fatty (ZF) and lean (ZL) rats. To determine nuclear factor κB (NF-κB) activation in the glomeruli, we used NF-κB-dependent enhanced green fluorescent protein (GFP) transgenic mice (cis-NF-κBEGFP). Obesity and insulin-resistant state in 8-week-cis-NF-kBEGFP mice were induced by feeding with a high-fat diet or with a normal diet for 2 months. Albuminuria was measured by Nephrat from 24hr urine collection housed in individual metabolic cages. IL-6 mRNA expressions in the glomeruli were evaluated by SYBR green procedure.Tissue for light microscopy was fixed in 4% paraformaldehyde phosphate buffer. Kidney sections were stained with periodic acid Schiff (PAS). Glomeruli were digitally photographed and the images were imported into Image-J software and analyzed morphometrically. Dissected glomeruli from obese and control cis-NF-κBEGFP were fixed in acetone and observed by digital fluorescence microscopy.

Results
Body weight and albuminuria were significantly increased in ZF rats when compared to ZL rats. Expression of inflammatory marker, IL-6 mRNA was significantly increased in the glomeruli of ZF rats. However, TNF-α mRNA was not increased. Analysis of renal pathology did not show mesangial matrix expansion. NF-κB activation was increased in the glomerulus from cis-NF-κBEGFP mice feeding with a high-fat diet.

Discussion
These results suggest only 2 months of obesity and insulin-resistant duration can cause albuminuria due to increase of inflammation or oxidative stress. However, 2 months of disease duration may not be long enough to develop renal pathological changes.

Obesity-associated glomerular inflammation increases albuminuria without renal histological changes