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Effect of theophylline on prevention of contrast-induced acute kidney injury: a meta-analysis of randomized controlled trials.

BACKGROUND
Whether treatment with adenosine receptor antagonists such as theophylline can prevent contrast-induced acute kidney injury (AKI) remains controversial.


STUDY DESIGN
We conducted a meta-analysis of randomized controlled trials using MEDLINE (1966 to July 2011), EMBASE (1980 to July 2011), Web of Science (1986 to July 2011), and the Cochrane Central Register of Controlled Trials (1996 to July 2011), without language restriction.


SETTING & POPULATION
Patients undergoing contrast procedures.


SELECTION CRITERIA FOR STUDIES
Randomized controlled trials assessing adenosine antagonists versus control for prevention of contrast-induced AKI.


INTERVENTION
Adenosine antagonists with or without N-acetylcysteine versus control with or without N-acetylcysteine.


OUTCOMES
Contrast-induced AKI, change in serum creatinine level, requirement of dialysis, and in-hospital mortality.


RESULTS
16 trials (1,412 participants) were included. Theophylline significantly decreased the risk of contrast-induced AKI (13 trials, 1,222 patients; risk ratio, 0.48; 95% CI, 0.26-0.89; P = 0.02; I(2) = 45%) and had a protective effect on the absolute change in serum creatinine concentration (13 trials, 1,170 patients; standardized mean difference, -0.31 mg/dL; 95% CI, -0.50 to -0.11; P = 0.002; I(2) = 60%). Meta-regression showed a significant relation between the relative risk of contrast nephropathy and baseline serum creatinine level or Jadad score. No clear effects of treatment on risk of dialysis and in-hospital mortality were identified.


LIMITATIONS
Power to assess clinical end points was limited.


CONCLUSIONS
Theophylline treatment significantly reduced the incidence of contrast-induced AKI and had a modest improvement on kidney function after contrast exposure in the general population. However, beneficial effects of theophylline were not observed in patients with high baseline creatinine values (serum creatinine ≥1.5 mg/dL). In addition, the long-term effect of this agent on more clinically important outcomes was not established. Future large-scale high-quality multicenter trials in participants with different underlying risks of contrast-induced AKI and that incorporate the evaluation of clinically relevant outcomes are required.