Aliskiren, a novel renin inhibitor, is renoprotective in a model of advanced diabetic nephropathy in rats.
OBJECTIVE
Blockade of the renin-angiotensin system (RAS) with either ACE inhibitors or angiotensin receptor blocker is a key therapeutic strategy in slowing progression of diabetic nephropathy. Interruption of the RAS may also be achieved by blocking the activity of renin, the rate-limiting step in angiotensin II biosynthesis. However, it is not known whether drugs in this class also reduce the structural and functional manifestations of diabetic nephropathy.


METHODS
Using diabetic transgenic (mRen-2)27 rats, a rodent model of advanced diabetic nephropathy, we compared the efficacy of the renin inhibitor, aliskiren (10 mg kg(-1) day(-1) by osmotic mini-pump), with the ACE inhibitor, perindopril (0.2 mg kg(-1) day(-1) in drinking water), over a 16 week period.


RESULTS
Both perindopril and aliskiren reduced blood pressure, albuminuria and structural injury in experimental diabetic nephropathy, although not to the same extent. Aliskiren, at the dose used, did not reduce systemic blood pressure as much as perindopril, but both compounds were equally effective in reducing albuminuria and glomerulosclerosis in diabetic animals. The magnitude of interstitial fibrosis was attenuated to a greater degree by aliskiren than by perindopril.


CONCLUSIONS
These findings suggest that therapies aimed at different targets within the RAS may not have identical effects in attenuating structural injury in experimental diabetic nephropathy.
Kelly
D J
DJ
Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia. dkelly@medstv.unimelb.edu.au
Zhang
Y
Y
Moe
G
G
Naik
G
G
Gilbert
R E
RE
D000450:Aldosterone / Q000032:analysis; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D005650:Fumarates / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D000092502:Renin Inhibitors