Bilateral renal
denervation (BRD) has been shown to reduce
hypertension and improve renal function in both human and experimental studies. We hypothesized that chronic intervention with BRD may also attenuate renal injury and
fibrosis in
diabetic nephropathy. This hypothesis was examined in a female
streptozotocin-induced diabetic (mRen-2)27 rat (TGR) shown to capture the cardinal features of human
diabetic nephropathy. Following diabetic induction, BRD/
sham surgeries were conducted repeatedly (at the week 3, 6, and 9 following induction) in both diabetic and normoglycemic animals. Renal
denervation resulted in a progressive decrease in systolic blood pressure from first
denervation to termination (at 12 wk post-diabetic induction) in both normoglycemic and diabetic rats. Renal
norepinephrine content was significantly raised following diabetic induction and ablated in denervated normoglycemic and diabetic groups. A significant increase in glomerular basement membrane thickening and mesangial expansion was seen in the diabetic kidneys; this morphological appearance was markedly reduced by BRD. Immunohistochemistry and
protein densitometric analysis of diabetic innervated kidneys confirmed the presence of significantly increased levels of
collagens I and IV, α-smooth muscle actin, the ANG II type 1 receptor, and
transforming growth factor-β. Renal
denervation significantly reduced
protein expression of these fibrotic markers. Furthermore, BRD attenuated
albuminuria and prevented the loss of glomerular
podocin expression in these diabetic animals. In conclusion, BRD decreases systolic blood pressure and reduces the development of renal
fibrosis, glomerulosclerosis, and
albuminuria in this model of
diabetic nephropathy. The evidence presented strongly suggests that renal
denervation may serve as a therapeutic intervention to attenuate the progression of renal injury in
diabetic nephropathy.