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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Transl+Res
2015 ; 7
(5
): 825-40
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Efficacy of aliskiren, compared with angiotensin II blockade, in slowing the
progression of diabetic nephropathy in db/db mice: should the combination therapy
be a focus?
#MMPMID26175845
Zhou G
; Liu X
; Cheung AK
; Huang Y
Am J Transl Res
2015[]; 7
(5
): 825-40
PMID26175845
show ga
Although the intensive use of angiotensin II blockade (ACEI or ARB), progression
of diabetic nephropathy is common. A feedback increase in renin production often
accompanies angiotensin II blockade. We therefore examined whether aliskiren, a
direct renin inhibitor, confers better renoprotection than angiotensin II
blockade and whether the addition of aliskiren to an ACEI or ARB would enhance
the efficacy in slowing the progression of glomerulosclerosis in diabetes.
Untreated db/db mice developed progressive mesangial matrix expansion and
albuminuria between weeks 18 and 22, associated with reduction of WT-1
immunopositive podocytes and nephrin and podocin production and induction of
desmin and B7-1 generation and renal expression of TGFß1, PAI-1, fibronectin and
type IV collagen. Treatment with aliskiren at 30 mg/kg/d inhibited the increases
in albuminuria and markers of renal fibrosis and the changes that are indicative
of podocyte injury seen in the db/db mice. Notably, the therapeutic effect of
aliskiren was similar to that of either enalapril or valsartan given alone at
maximally effective doses. Combined therapy caused the loss of 10% ~ 16.6% of
db/db mice, yielded no further reduction in renal fibrosis and podocyte injury
but further reduced albuminuria and renal production of TNF?, Nox2 and p47phox
and urine MCP-1 and malondialdehyde levels, the markers of renal inflammation and
oxidative stress. These results suggest that aliskiren, enalapril and valsartan
are equally effective in slowing the progression of diabetic nephropathy. The use
of combination therapy with aliskiren and ACEI/ARB may not be strongly supported.