Elsevier

The American Journal of Medicine

Volume 122, Issue 9, September 2009, Pages 874.e9-874.e15
The American Journal of Medicine

AJM online
Clinical research study
High-dose N-acetylcysteine for the Prevention of Contrast-induced Nephropathy

https://doi.org/10.1016/j.amjmed.2009.01.035Get rights and content

Abstract

Background

Whether N-acetylcysteine is beneficial for the prevention of contrast-induced nephropathy is uncertain.

Methods

We conducted a meta-analysis to evaluate the efficacy of high-dose N-acetylcysteine for the prevention of contrast-induced nephropathy. Our prespecified inclusion criteria were as follows: adult subjects; English language literature; administration of high-dose N-acetylcysteine a priori defined as a daily dose greater than 1200 mg or a single periprocedural dose (within 4 hours of contrast exposure) greater than 600 mg; prospective trials of individuals randomized to N-acetylcysteine, administered orally or intravenously, versus a control group; and trials that included the end point of the incidence of contrast-induced nephropathy. Trials that compared N-acetylcysteine with another active treatment were excluded.

Results

Sixteen comparisons of patients randomized to high-dose N-acetylcysteine versus controls met our prespecified inclusion criteria with a total sample size of 1677 subjects (842 assigned to high-dose N-acetylcysteine and 835 assigned to the control arm). The average population age was 68 years, 38.7% were diabetic, and the majority was male (67.8% of reported instances). The weighted mean baseline creatinine of the overall population was 1.58 mg/dL. No significant heterogeneity was detected (P = .09; I2 = 34%). The overall effect size assuming a common odds ratio revealed an odds ratio of 0.46 (95% confidence interval [CI], 0.33-0.63) for the occurrence of contrast-induced nephropathy with the use of high-dose N-acetylcysteine. The results of the more conservative random effects approach were similar (odds ratio = 0.52; 95% CI, 0.34-0.78). There was no evidence of publication bias (P = .34).

Conclusion

Our results suggest that high-dose N-acetylcysteine decreases the incidence of contrast-induced nephropathy.

Section snippets

Materials and Methods

Our prespecified inclusion criteria were as follows: adult subjects; English language literature; administration of high-dose N-acetylcysteine a priori defined as a daily dose greater than 1200 mg or a single periprocedural dose greater than 600 mg, periprocedural being described as immediately or within 4 hours of the planned contrast exposure (although the inherent arbitrariness of the high-dose definition is recognized, it was considered that a higher dose either as an individual or a

Results

Sixteen comparisons of patients randomized to high-dose N-acetylcysteine versus controls met our prespecified inclusion criteria with a total sample size of 1677 subjects (842 assigned to high-dose N-acetylcysteine and 835 assigned to the control arm).8, 9, 10, 11, 13, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 The results of the literature search are shown in Figure 1.27

The subject population was derived from 11 countries, and the majority of patients had some degree of renal insufficiency. The

Discussion

The role of N-acetylcysteine in the prevention of contrast-induced nephropathy has been controversial. After the original positive report, there have been several studies showing lack of benefit. Several large meta-analyses consistently found significant heterogeneity (variation of effect across studies greater than can be expected by chance) and thus could not reconcile the issue. Our analysis of the effect of a prespecified high-dose N-acetylcysteine did not find significant heterogeneity and

Conclusions

The present analysis suggests that N-acetylcysteine at individual periprocedural doses exceeding 600 mg or daily doses exceeding 1200 mg decreases the incidence of contrast-induced nephropathy. Further studies need to investigate whether these doses lead to improvement in other outcomes associated with post-contrast acute kidney injury, such as mortality.

Acknowledgments

We thank Dr Khalili for providing clarification regarding timing of N-acetylcysteine administration that resulted in inclusion of their study in the analysis. We also thank Drs Allaqaband and Poletti for providing additional unpublished information and Dr Miner for providing clarification regarding their respective studies.

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    Funding: None.

    Conflict of Interest: None.

    Authorship: All authors had access to the data and played a role in writing this manuscript.

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