NGAL or lipocalin-2 is an inflammatory marker which can stabilize MMP-9, a proteinase known to be altered in diabetic kidney disease. Elevated circulating NGAL levels correlate with chronic kidney diseases, for example with IgA-mediated nephropathy. However, little is known about NGAL expression and its relationship with development of diabetic kidney disease. In this study we investigated kidney NGAL and its association with early diabetic nephropathy in a diabetic rodent model.
Diabetes was induced using STZ (65mg/kg) in male Sprague-Dawley rats (n=31). One week later when diabetes presence was confirmed some rats (n=17) were treated with insulin (10IU/day). Age-matched non-diabetic rodents (n=17) acted as control. After six weeks, the animals were terminated the kidneys harvested and plasma and urine collected. The one kidney was dissected to cortical and medullary fractions for measurement of gene expression by RT-qPCR. Histological studies were performed for analysis of kidney morphology.
Diabetes increased blood glucose and urinary albumin levels, which were normalized by insulin treatment. The expression of NGAL was found to be principally confined to the medulla-enriched fraction. In this fraction compared with control, diabetes decreased and insulin treatment increased NGAL gene expression. Histological analysis showed kidney basement membrane thickening in diabetic animals.
BW (g) BGL(mmol/L) UAlb:Cr Ratio NGAL mRNA Fold Diff. (/18S)
CON (n=17) 487±43 4.5±0.5 0.093±0.065 2.10±1.93
DM (n=14) 339±51* 21.1±6.4* 0.379±0.329* 0.07±0.05*
DM+INS (n=17) 399±55*# 3.0±1.3*# 0.127±0.078# 6.43±4.20*#
* p<0.05 significantly different from control group; # p<0.05 significantly different from diabetic group
These data suggest that diabetes can affect kidney NGAL mRNA in association with the development of complications. How these changes are related to circulating and urinary NGAL remain to be determined. NGAL is secreted mainly from tubular cells, and may have the potential to be a useful marker of tubular damage.