title: Update on role of direct renin inhibitor in diabetic kidney disease.
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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology, Lehigh Valley Health Network , Allentown, PA , USA .
authors.forename: Pradeep
authors.initials: P
authors.lastname: Dhakarwal
authors.forename: Vibha
authors.initials: V
authors.lastname: Agrawal
authors.forename: Anshul
authors.initials: A
authors.lastname: Kumar
authors.forename: Kiran M
authors.initials: KM
authors.lastname: Goli
authors.forename: Varun
authors.initials: V
authors.lastname: Agrawal
mesh_terms: D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren
keywords: Aliskiren; angiotensin converting enzyme inhibitor; angiotensin receptor blocker; chronic kidney disease; diabetic nephropathy; direct renin inhibitor