title: Renin-Angiotensin System Blockade and Long-term Clinical Outcomes in Kidney Transplant Recipients: A Meta-analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  Renin-angiotensin system [RAS] blockade has been established as the cornerstone of therapy in the general population, and especially in chronic kidney disease. However, its efficacy in the kidney transplant population remains unknown.
  
  
  METHODS
  We conducted a systematic review and meta-analysis using MEDLINE (1966 to November 2015), Embase (1980 to November 2015), and the Cochrane Library (third quarter 2015), as well as a PubMed search for recent nonindexed citations.
  
  
  METHODS
  Adult kidney transplant recipients.
  
  
  METHODS
  Randomized controlled trials, with follow-up of 1 year or longer and reporting clinical outcomes of interest.
  
  
  METHODS
  RAS blockade (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) versus placebo, active comparator, or standard of care.
  
  
  RESULTS
  All-cause mortality, all-cause transplant failure, and doubling of serum creatinine level.
  
  
  RESULTS
  8 trials (1,502 participants) were included in the systematic review. RAS blockade did not significantly alter all-cause mortality (risk ratio [RR], 0.96; 95% CI, 0.62-1.51), transplant failure (RR, 0.76; 95% CI, 0.49-1.18), or creatinine level doubling (RR, 0.84; 95% CI, 0.51-1.39) compared to the control group. This result was robust across the subgroups of interest (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker intervention, follow up ≥ 1 year, and baseline proteinuria as an inclusion criterion). There was significantly higher risk for hyperkalemia with RAS blockade (RR, 2.44; 95% CI, 1.53-3.90). There was no statistical heterogeneity in any of these pooled analyses.
  
  
  CONCLUSIONS
  Relatively smaller number of events (overall, 71 deaths and 72 transplant failures among 8 trials) and relatively short follow-up (only 2 trials > 5 years).
  
  
  CONCLUSIONS
  This analysis neither supports nor refutes the hypothesis that RAS blockade improves clinical outcomes in kidney transplant recipients. A trial with more than 10,000 patients would be needed to definitively answer whether RAS blockade reduces transplant loss in this population. In the meantime, clinicians should weigh the risks and benefits of using these medications with their patients on a case-by-case basis.
authors.affiliation: Centre for Practice Changing Research, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada; Faculty of Medicine, University of Ottawa, Ottawa, Canada; Division of Nephrology, Department of Medicine, The Ottawa Hospital, Ottawa, Canada.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Hiremath
authors.affiliation: Centre for Practice Changing Research, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Fergusson
authors.affiliation: Centre for Practice Changing Research, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Fergusson
authors.affiliation: Centre for Practice Changing Research, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.
authors.forename: Alexandria
authors.initials: A
authors.lastname: Bennett
authors.affiliation: Centre for Practice Changing Research, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada; Faculty of Medicine, University of Ottawa, Ottawa, Canada; Division of Nephrology, Department of Medicine, The Ottawa Hospital, Ottawa, Canada. Electronic address: gknoll@toh.ca.
authors.forename: Greg A
authors.initials: GA
authors.lastname: Knoll
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D016030:Kidney Transplantation; D011183:Postoperative Complications / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: Kidney transplant; RAS blockade; all-cause graft failure; all-cause mortality; angiotensin receptor blocker (ARB); angiotensin-converting enzyme (ACE) inhibitor; hyperkalemia; meta-analysis; renal transplant recipient; renin-angiotensin system (RAS); serum creatinine doubling; systematic review