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The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis

BMJ 2012; 344 doi: (Published 09 January 2012) Cite this as: BMJ 2012;344:e42
  1. Ziv Harel, research fellow12,
  2. Cameron Gilbert, student1,
  3. Ron Wald, associate professor13,
  4. Chaim Bell, associate professor235,
  5. Jeff Perl, assistant professor1,
  6. David Juurlink, associate professor2456,
  7. Joseph Beyene, associate professor2,
  8. Prakesh S Shah, associate professor267
  1. 1Division of Nephrology, St Michael’s Hospital, University of Toronto, ON, Toronto, Canada M5B 1W8
  2. 2Department of Health Policy, Management and Evaluation, University of Toronto
  3. 3Department of Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute of St Michael’s Hospital, University of Toronto
  4. 4Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto
  5. 5Institute for Clinical Evaluative Sciences, Toronto
  6. 6Department of Paediatrics, University of Toronto
  7. 7Department of Paediatrics, Mount Sinai Hospital, Toronto
  1. Correspondence to: Z Harel harelz{at}
  • Accepted 29 December 2011


Objective To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system.

Design Systematic review and meta-analysis of randomised controlled trials.

Data sources Medline, Embase, the Cochrane Library, and two trial registries, published up to 7 May 2011.

Study selection Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers with monotherapy using these agents for at least four weeks and that provided numerical data on the adverse event outcomes of hyperkalaemia and acute kidney injury. A random effects model was used to calculate pooled risk ratios and 95% confidence intervals for these outcomes.

Results 10 randomised controlled studies (4814 participants) were included in the analysis. Combination therapy with aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers significantly increased the risk of hyperkalaemia compared with monotherapy using angiotensin converting enzymes or angiotensin receptor blockers (relative risk 1.58, 95% confidence interval 1.24 to 2.02) or aliskiren alone (1.67, 1.01 to 2.79). The risk of acute kidney injury did not differ significantly between the combined therapy and monotherapy groups (1.14, 0.68 to 1.89).

Conclusion Use of aliskerin in combination with angiotensin converting enzyme inhibitors or angiotensin receptor blockers is associated with an increased risk for hyperkalaemia. The combined use of these agents warrants careful monitoring of serum potassium levels.


  • We thank Elizabeth Uleryk (librarian) for her help with the search strategy.

  • Contributors: ZH, RW, CB, JB, and PSS conceived and designed the study. ZH, CG, JB, and PSS analysed and interpreted the data. ZH and PSS drafted the manuscript. All authors critically revised the manuscript for important intellectual content. ZH had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding: None received.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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