D J Kelly1, Y Zhang, G Moe, G Naik, R E Gilbert. 1. Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC 3065, Australia. dkelly@medstv.unimelb.edu.au
Abstract
AIMS/HYPOTHESIS: 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/ INTERPRETATION: 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.
AIMS/HYPOTHESIS: 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/ INTERPRETATION: 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.
Authors: Darren J Kelly; Richard E Gilbert; Alison J Cox; Tina Soulis; George Jerums; Mark E Cooper Journal: J Am Soc Nephrol Date: 2001-10 Impact factor: 10.121
Authors: Sally A Mifsud; Sandford L Skinner; Mark E Cooper; Darren J Kelly; Jennifer L Wilkinson-Berka Journal: J Am Soc Nephrol Date: 2002-03 Impact factor: 10.121
Authors: J L Wilkinson-Berka; G Tan; K J Binger; L Sutton; K McMaster; D Deliyanti; G Perera; D J Campbell; A G Miller Journal: Diabetologia Date: 2011-07-14 Impact factor: 10.122
Authors: Adam Whaley-Connell; Ravi Nistala; Javad Habibi; Melvin R Hayden; Rebecca I Schneider; Megan S Johnson; Roger Tilmon; Nathan Rehmer; Carlos M Ferrario; James R Sowers Journal: Am J Physiol Renal Physiol Date: 2009-12-09