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


METHODS
Studies were identified in all languages by search of MEDLINE (1966 through November 2003), EMBASE (1980 through week 44 [November] of 2003), and the Cochrane Controlled Clinical Trials Register (1996 through November 2003) databases and selected conference proceedings.


METHODS
We searched for randomized controlled trials comparing theophylline vs control in patients receiving radiocontrast media for angiography or computed tomography.


METHODS
Our primary outcome measures were the risk of CIN, the difference in serum creatinine levels 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 varied across studies. There was evidence of heterogeneity of results across trials (Q = 9.77; P = .08); therefore, pooled values require cautious interpretation. The overall pooled odds ratio (OR) using a conservative random-effects model was 0.40 (95% confidence interval [CI], 0.14 to 1.16; P = .09) indicating a trend toward reduction in the incidence of CIN with theophylline use. The pooled estimate for the difference in 48-hour serum creatinine levels between the theophylline and control groups was -0.17 mg/dL (95% CI, -0.28 to -0.06 mg/dL) (-15.2 micromol/L [95% CI, -24.6 to -5.7 micromol/L]) (P = .002), indicating that theophylline may be protective in CIN. The incidence of CIN requiring dialysis was uncommon and reported in only 1 case.


CONCLUSIONS
Theophylline may reduce the incidence of CIN with an efficacy that is perhaps comparable to that reported in studies of N-acetylcysteine. However, findings are inconsistent across studies. A large, well-designed trial that incorporates the evaluation of clinically relevant outcomes is required to more adequately assess the role for theophylline in CIN prevention.
Bagshaw
Sean M
SM
Department of Critical Care Medicine, Calgary Health Region, and Departments of Internal Medicine, University of Calgary, Calgary, Alberta, Canada.
Ghali
William A
WA
D000792:Angiography / Q000379:methods; D003287:Contrast Media / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D013806:Theophylline / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed / Q000379:methods; D014665:Vasodilator Agents / Q000627:therapeutic use*
D003287:Contrast Media; D014665:Vasodilator Agents; D013806:Theophylline