Growing evidence suggests that active
vitamin D slows the progression of
chronic kidney diseases. Here we compared the individual renal protective efficacy of
paricalcitol and
trandolapril (an
angiotensin-converting enzyme inhibitor) in obstructive nephropathy, and examined any potential additive effects of their combination on attenuating renal
fibrosis and
inflammation. Mice underwent unilateral
ureteral obstruction and were treated individually with
paricalcitol or
trandolapril or their combination. Compared to vehicle-treated controls, monotherapy with
paricalcitol or
trandolapril inhibited the expression and accumulation of
fibronectin and type I and
type III collagen, suppressed alpha-smooth muscle actin,
vimentin, and Snail1 expression, and reduced total
collagen content in the obstructed kidney. Combination
therapy led to a more profound inhibition of all parameters. Monotherapy also suppressed renal
RANTES (regulated on activation, normal T cell expressed and secreted) and
tumor necrosis factor (
TNF)-alpha expression and inhibited renal infiltration of T cells and macrophages, whereas the combination had additive effects.
Renin expression was induced in the fibrotic kidney and was augmented by
trandolapril.
Paricalcitol blocked
renin induction in the absence or presence of
trandolapril. Our study indicates that
paricalcitol has renal protective effects, comparable to that of
trandolapril, in reducing interstitial
fibrosis and
inflammation. Combination
therapy had additive efficacy in retarding renal
scar formation during obstructive nephropathy.