Inhibition of the RAAS (renin–angiotensin–aldosterone system) plays a pivotal role in the prevention and treatment of diabetic nephropathy and a spectrum of other proteinuric kidney diseases. Despite documented beneficial effects of RAAS inhibitors in diabetic patients with nephropathy, reversal of the progressive course of this disorder or at least long-term stabilization of renal function are often difficult to achieve, and many patients still progress to end-stage renal disease. Incomplete inhibition of the RAAS has been postulated as one of reasons for unsatisfactory therapeutic responses to RAAS inhibition in some patients. Inhibition of renin, a rate-limiting step in the RAAS activation cascade, could overcome at least some of the abovementioned problems associated with the treatment with traditional RAAS inhibitors. The present review focuses on experimental and clinical studies evaluating the two principal approaches to renin inhibition, namely direct renin inhibition with aliskiren and inhibition of the (pro)renin receptor. Moreover, the possibilities of renin inhibition and nephroprotection by interventions primarily aiming at non-RAAS targets, such as vitamin D, urocortins or inhibition of the succinate receptor GPR91 and cyclo-oxygenase-2, are also discussed.
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Review Article|
January 21 2013
Renin inhibition in the treatment of diabetic kidney disease
Radko Komers
1Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, OR 97239-2940, U.S.A.
Correspondence: Dr Radko Komers (email [email protected]).
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Publisher: Portland Press Ltd
Received:
September 03 2012
Revision Received:
October 26 2012
Accepted:
November 05 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2013 Biochemical Society
2013
Clin Sci (Lond) (2013) 124 (9): 553–566.
Article history
Received:
September 03 2012
Revision Received:
October 26 2012
Accepted:
November 05 2012
Citation
Radko Komers; Renin inhibition in the treatment of diabetic kidney disease. Clin Sci (Lond) 1 May 2013; 124 (9): 553–566. doi: https://doi.org/10.1042/CS20120468
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