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Combination therapy with paricalcitol and trandolapril reduces renal fibrosis in
obstructive nephropathy
#MMPMID19759524
Tan X
; He W
; Liu Y
Kidney Int
2009[Dec]; 76
(12
): 1248-57
PMID19759524
show ga
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.
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