Abstract:
BACKGROUND:Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Renin-angiotensin-aldosterone system (RAAS) plays a critical role in the development of DKD with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) being the mainstay of treatment. Systemic RAAS activity has been implicated in the pathogenesis of DKD, but lately interest has shifted to intrarenal RAAS effect. With the discovery of the (pro)renin receptor and ACE independent pathways of angiotensin II production, our understanding of role of renin in end organ damage has improved significantly. SUMMARY:We summarize our current understanding of ACE dependent and independent pathways in the development of DKD and the preclinical models demonstrating renal effects of direct renin inhibitors (DRIs). We then review clinical studies and trials performed so far evaluating the efficacy of aliskiren on renal outcomes and safety in DKD. KEY MESSAGE:At present, there is little evidence for renal benefit of aliskiren in DKD beyond that offered by ACEIs or ARBs. Combining aliskiren with ACEI or ARB in DKD did not significantly improve renal outcomes in comparison with ACEI or ARB monotherapy in clinical trials. Slightly more adverse events including hyperkalemia, acute kidney injury and hypotension were observed in the combination therapy as compared to the monotherapy. Thus, current evidence suggests that aliskiren, because of its antihypertensive and antiproteinuric effects, maybe used as monotherapy in DKD and considered an equivalent alternative to ACEIs or ARBs. Careful monitoring for renal adverse effects would allow safe clinical use of DRI.
journal_name
Ren Failjournal_title
Renal failureauthors
Dhakarwal P,Agrawal V,Kumar A,Goli KM,Agrawal Vdoi
10.3109/0886022X.2014.900425subject
Has Abstractpub_date
2014-07-01 00:00:00pages
963-9issue
6eissn
0886-022Xissn
1525-6049journal_volume
36pub_type
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