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


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


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


METHODS
Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers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).


CONCLUSIONS
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.
Division of Nephrology, St Michael's Hospital, University of Toronto, ON, Toronto, Canada M5B 1W8. harelz@smh.ca
Ziv
Z
Harel
Cameron
C
Gilbert
Ron
R
Wald
Chaim
C
Bell
Jeff
J
Perl
David
D
Juurlink
Joseph
J
Beyene
Prakesh S
PS
Shah
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000577:Amides / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D000959:Antihypertensive Agents / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005650:Fumarates / Q000009:adverse effects*; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced*; D016032:Randomized Controlled Trials as Topic
D000577:Amides; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D005650:Fumarates; C446481:aliskiren