Renoprotection by Direct Renin Inhibition: A Systematic Review and Meta- Analysis

Curr Vasc Pharmacol. 2018 Jan 26;16(2):157-167. doi: 10.2174/1570161115666170502104809.


Even mild abnormalities of the renal structure or function can increase the risk of mortality and complications in other organs. Therefore, safe and effective treatments are necessary in order to influence the progression of renal disease. We used 2 methods to assess the renoprotective effects of aliskiren: 1) a statistical analysis of clinical trials that investigated aliskiren-induced renoprotection, in terms of changes in serum creatinine concentration (sCr) or estimated glomerular filtration rate (eGFR), and, 2) clinical trials that investigated the renoprotective effects of aliskiren with respect to changes in albuminuria or proteinuria. In the forest plot, the overall risk ratio (%) for renal impairment with respect to changes in sCr or eGFR was 0.97 (0.88-1.06; overall p=0.48). The tabulation of data from clinical trials included 10 entries for monotherapy with aliskiren and 6 entries for add-on aliskiren. All of the clinical trials, except one, showed a decrease in proteinuria or albuminuria following aliskiren treatment. In conclusion, inhibiting renin and prorenin with aliskiren is a more promising renoprotective treatment compared with blocking the renin/prorenin receptors (RPR). One of the main mechanisms by which aliskiren may confer renoprotection is by decreasing albuminuria and proteinuria. However, it does not seem to change sCr and eGFR in patients at risk of developing renal disease. Furthermore, co-administration of an angiotensinconverting- enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) and aliskiren was shown to decrease albuminuria and proteinuria to a greater extent compared with monotherapy with these agents.

Keywords: Aliskiren; albuminuria; estimated glomerular filtration rate; kidney disease; prorenin; proteinuria; renin; renoprotection; serum creatinine concentration.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Albuminuria / diagnosis
  • Albuminuria / drug therapy*
  • Albuminuria / metabolism
  • Albuminuria / physiopathology
  • Amides / adverse effects
  • Amides / therapeutic use*
  • Animals
  • Clinical Trials as Topic
  • Fumarates / adverse effects
  • Fumarates / therapeutic use*
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Kidney Diseases / diagnosis
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism
  • Kidney Diseases / physiopathology
  • Renal Agents / adverse effects
  • Renal Agents / therapeutic use*
  • Renin / antagonists & inhibitors*
  • Renin / metabolism
  • Renin-Angiotensin System / drug effects*
  • Treatment Outcome


  • Amides
  • Fumarates
  • Renal Agents
  • aliskiren
  • Renin