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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Acetylcysteine for prevention of contrast-induced nephropathy after intravascular angiography: a systematic review and meta-analysis

SM Bagshaw and WA Ghali.

Review published: 2004.

CRD summary

This review assessed the effect of acetylcysteine on contrast-induced nephropathy and serum creatinine following the administration of contrast media. The authors concluded that the efficacy of acetylcysteine remains unproven and further research is required. In general, this was a well-conducted review, and the authors' conclusions appear appropriate.

Authors' objectives

To assess the effect of acetylcysteine on the incidence of contrast-induced nephropathy and serum creatinine levels following the administration of contrast media.


MEDLINE, EMBASE and the Cochrane CENTRAL Register were searched from inception to April 2003, and searches were updated in June 2004. The search terms were reported and no language restrictions were applied. The reference lists of identified articles and selected conference proceedings were reviewed manually and experts in the field were contacted.

Study selection

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) were eligible for inclusion.

Specific interventions included in the review

Studies comparing acetylcysteine plus hydration with hydration alone were eligible for inclusion. The included studies used acetycysteine at a variety of doses and schedules. All patients were administered a hydration protocol and all received low or iso-osmolar non-ionic contrast media. In the majority of studies angiography was elective, rather than an emergency procedure.

Participants included in the review

Studies of patients undergoing intravascular angiography were eligible for inclusion. The proportion of diabetic patients in the included studies ranged from 13 to 64%.

Outcomes assessed in the review

The primary outcomes of interest were the incidence of contrast-induced nephropathy and change in serum creatinine levels. The studies were required to have an explicit definition of contrast-induced nephropathy to be eligible for inclusion. The definitions were variable across the included studies, although in most cases the time for ascertaining contrast-induced nephropathy was 48 hours after exposure to the contrast media. The secondary outcome measure was the requirement for renal replacement.

How were decisions on the relevance of primary studies made?

Two reviewers independently evaluated identified articles for eligibility for the review.

Assessment of study quality

The studies were assessed and scored using the Jadad quality criteria, which assess randomisation, blinding, use of a placebo, the reporting of losses to follow-up, and baseline comparability of the treatment groups. Two reviewers independently assessed the methodological quality of all included studies, with any disagreements resolved by consensus.

Data extraction

Two reviewers independently extracted the data from all included studies. Any discrepancies in the data extraction were resolved by consensus. The study authors were contacted for additional information if required.

Methods of synthesis

How were the studies combined?

Data from the studies were combined, using a random-effects model, to estimate the pooled odds ratios (ORs) with 95% confidence intervals (CIs) for each dichotomous outcome. The pooled differences, with 95% CI, between treatment groups were also calculated using a random-effects model. The presence of publication bias was assessed using Begg's test for asymmetry and Egger's test.

How were differences between studies investigated?

Statistical heterogeneity was assessed using the chi-squared test. A meta-regression was also performed to assess whether there were any clinical or study quality factors that were influencing the results. A priori consideration for factors contributing to heterogeneity included the following: baseline serum creatinine levels, volume of contrast media, volume of hydration, age, diabetes mellitus, and elective or emergency procedure.

Results of the review

Fourteen RCTs (n=1,261) were included.

There was a statistically significant reduction in contrast-induced nephropathy with acetylcysteine compared with control, with an overall OR of 0.54 (95% CI: 0.32, 0.91, P=0.022). However, significant statistical heterogeneity was identified across the studies (P=0.032). There was no statistically significant difference in serum creatinine levels between treatment groups, with an overall difference between groups of -7.2 micromol/L (95% CI: -19.7, 5.3, P=0.26). However, significant statistical heterogeneity was identified (P<0.0005).

The investigation by meta-regression suggested that the heterogeneity could be partially explained by whether the angiographs were elective or emergency procedures. The ORs were found to be lower in those studies with elective angiographs than in those including emergency procedures (P=0.06). According to the meta-regression, patient age, baseline serum creatinine levels, volume of contrast media, diabetes mellitus, or any of the study quality criteria did not account for the heterogeneity observed. The Jadad quality scores assigned to the individual studies ranged from 1 to 5, with 9 studies scoring 4 or 5. The authors stated that the result of the Begg's test (P=0.03) and Egger's test (P=0.09) suggested possible publication bias.

Authors' conclusions

The efficacy of acetylcysteine for the prevention of contrast-induced nephropathy remains unproven; further research is required.

CRD commentary

This review addressed a clear research question using well-defined inclusion criteria. Relevant electronic databases were searched for studies and details of the search strategy were reported. Language restrictions were not applied and attempts were made to locate unpublished studies. However, the possibility of publication bias was identified. Adequate methods were used to minimise the possibility of reviewer bias and error in the study selection and data extraction processes. The quality of the included studies was assessed using established criteria, and was used in the investigation of heterogeneity. Some relevant details of the primary studies were reported. Standard meta-analytic techniques were used and the present heterogeneity was investigated; it appears to have been considered a priori. In general, this was a well-conducted review and, given the heterogeneity and publication bias, the authors' cautious conclusions appear appropriate.

Implications of the review for practice and research

Practice: The authors stated that it is now perhaps reasonable to use acetylcysteine in routine care because of its relative ease of use and safety.

Research: The authors stated that the true efficacy of acetylcysteine must be clarified in a well-designed, multicentre trial. The authors stated that such a trial should address clinically relevant end points such as renal insufficiency, rather than surrogate markers, and consider stratification on hypothesised important subgroups, such as those with a low ejection fraction.

Bibliographic details

Bagshaw S M, Ghali W A. Acetylcysteine for prevention of contrast-induced nephropathy after intravascular angiography: a systematic review and meta-analysis. BMC Medicine 2004; 2:38. [PMC free article: PMC526263] [PubMed: 15500690]

Indexing Status

Subject indexing assigned by NLM


Acetylcysteine /therapeutic use; Angiography /adverse effects; Contrast Media /adverse effects; Humans; Kidney Diseases /chemically induced /prevention & control



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 15500690

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