PURPOSE: Contrast-induced nephropathy (CIN) is an important cause of iatrogenic declines in kidney function and is related to greater morbidity, mortality and health care costs. Adenosine has been proposed to contribute to the pathophysiology of CIN. We performed a systematic review and meta-analysis to assess whether theophylline, an adenosine antagonist, is efficacious for the prevention of CIN.

METHODS: We searched for randomized controlled trials comparing prophylactic theophylline versus control in patients receiving radiocontrast media for angiography or computed tomography. Studies were identified in all languages by search of MEDLINE, EMBASE, Cochrane Controlled Clinical Trials Register and selected conference proceedings. Our primary outcome measures were the risk of CIN, the difference in serum creatinine between theophylline and control groups at 48 hours and need for dialysis.

RESULTS: Nine randomized controlled trials involving 585 patients were identified and included for analysis. Theophylline protocols and definitions of CIN were variable across studies. In general, there was considerable inconsistency of results across trials; therefore, pooled values may require cautious interpretation due to this heterogeneity (Q=9.77, p=0.08). Likewise, trial quality scores were uniformly low. The overall pooled odds ratio (OR) for development of CIN using a random-effects model was 0.40 (95% CI, 0.14 to 1.16, p=0.09) indicating a trend toward reduction in the incidence of CIN with theophylline, but this was not statistically significant. The pooled estimate for the difference in 48-hour serum creatinine between the theophylline and control groups was –15.2 µmol/L (95% CI, –24.6 to –5.7, p=0.002) indicating that theophylline may be protective in CIN. The incidence of CIN requiring dialysis was uncommon and reported in only one case. Adverse effects of theophylline were infrequently reported. There was no significant evidence of publication bias (p=0.85, Begg’s test). Meta-regression suggested that the heterogeneity in results across trials may be partially explained by year of study publication and overall trial quality. Furthermore, meta-regression suggested trends for larger benefit for theophylline in patients receiving ionic contrast media and no pre-specified hydration protocol. The heterogeneity in results across trials does not appear to be related to differences in age, diabetes mellitus, baseline serum creatinine levels, and volume of contrast media.

CONCLUSION: These findings indicate that published studies of theophylline for prevention of CIN yield conflicting results. Although promising, a large well-designed multi-centre trial that incorporates the evaluation of clinically relevant outcomes is required to more adequately assess the efficacy of theophylline for CIN prevention.

DNC

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