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Theophylline for prevention of contrast-induced nephropathy: a systematic review and meta-analysis
Sean M Bagshaw1, William A Ghali
1Department of Critical Care Medicine, Calgary Health Region, and Departments of Internal Medicine, University of Calgary, Calgary, Alberta, Canada.
Insights
Theophylline may reduce contrast-induced nephropathy (CIN) risk, showing a trend toward lower incidence and significant reduction in serum creatinine levels. Further large-scale trials are needed to confirm its role in CIN prevention.
Area of Science:
- Nephrology
- Pharmacology
Background:
- Contrast-induced nephropathy (CIN) is a significant cause of kidney function decline, associated with increased morbidity and mortality.
- Adenosine is implicated in the pathophysiology of CIN.
- Theophylline, an adenosine antagonist, has been investigated for CIN prevention.
Purpose of the Study:
- To systematically review and meta-analyze randomized controlled trials on theophylline for preventing CIN.
- To assess the efficacy of theophylline in reducing CIN incidence and serum creatinine levels.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials.
- Searched MEDLINE, EMBASE, and Cochrane Controlled Clinical Trials Register.
- Included 9 trials with 585 patients comparing theophylline versus control in patients receiving radiocontrast media.
Main Results:
- A trend towards reduced CIN incidence with theophylline use was observed (OR = 0.40, P = .09).
- Theophylline significantly reduced 48-hour serum creatinine levels compared to control (mean difference = -0.17 mg/dL, P = .002).
- Heterogeneity across studies necessitates cautious interpretation of pooled results.
Conclusions:
- Theophylline may offer protective effects against CIN, potentially comparable to N-acetylcysteine.
- Findings are inconsistent across studies, highlighting the need for further research.
- A large, well-designed trial is required to definitively establish the role of theophylline in CIN prevention.
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.
Data Sources:
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.
Study Selection:
We searched for randomized controlled trials comparing theophylline vs control in patients receiving radiocontrast media for angiography or computed tomography.
Data Extraction:
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.
Data Synthesis:
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.
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