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A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity.

Gonzales DA, Norsworthy KJ, Kern SJ, Banks S, Sieving PC, Star RA, Natanson C, Danner RL - BMC Med (2007)

Bottom Line: Benefit in cluster 2 was unexpectedly associated with NAC-induced decreases in creatinine from baseline (p = 0.07).Dialysis use across all studies (five control, eight treatment; p = 0.42) did not suggest that NAC is beneficial.This meta-analysis does not support the efficacy of NAC to prevent CIN.

View Article: PubMed Central - HTML - PubMed

Affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA. dgonzales@cc.nih.gov

ABSTRACT

Background: Meta-analyses of N-acetylcysteine (NAC) for preventing contrast-induced nephrotoxicity (CIN) have led to disparate conclusions. Here we examine and attempt to resolve the heterogeneity evident among these trials.

Methods: Two reviewers independently extracted and graded the data. Limiting studies to randomized, controlled trials with adequate outcome data yielded 22 reports with 2746 patients.

Results: Significant heterogeneity was detected among these trials (I2 = 37%; p = 0.04). Meta-regression analysis failed to identify significant sources of heterogeneity. A modified L'Abbé plot that substituted groupwise changes in serum creatinine for nephrotoxicity rates, followed by model-based, unsupervised clustering resolved trials into two distinct, significantly different (p < 0.0001) and homogeneous populations (I2 = 0 and p > 0.5, for both). Cluster 1 studies (n = 18; 2445 patients) showed no benefit (relative risk (RR) = 0.87; 95% confidence interval (CI) 0.68-1.12, p = 0.28), while cluster 2 studies (n = 4; 301 patients) indicated that NAC was highly beneficial (RR = 0.15; 95% CI 0.07-0.33, p < 0.0001). Benefit in cluster 2 was unexpectedly associated with NAC-induced decreases in creatinine from baseline (p = 0.07). Cluster 2 studies were relatively early, small and of lower quality compared with cluster 1 studies (p = 0.01 for the three factors combined). Dialysis use across all studies (five control, eight treatment; p = 0.42) did not suggest that NAC is beneficial.

Conclusion: This meta-analysis does not support the efficacy of NAC to prevent CIN.

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Related in: MedlinePlus

Funnel plot of precision versus log RR. Log RR of developing CIN is plotted versus precision for each of the 22 studies in this meta-analysis. Four studies later identified as contributing most to heterogeneity are noted with open circles and are seen to produce asymmetry in the plot. The summary log RR for all 22 studies is denoted by the open diamond.
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Figure 3: Funnel plot of precision versus log RR. Log RR of developing CIN is plotted versus precision for each of the 22 studies in this meta-analysis. Four studies later identified as contributing most to heterogeneity are noted with open circles and are seen to produce asymmetry in the plot. The summary log RR for all 22 studies is denoted by the open diamond.

Mentions: Although non-significant (p ≤ 0.11, but p > 0.05 when applying any one of the three methods used for analysis), a visual inspection of a funnel plot suggested publication bias with four studies [10,11,14,25] contributing most to the apparent asymmetry (shown with open circles on the left-hand side of Figure 3). An extensive meta-regression analysis of patient and study characteristics found no study-specific characteristic (publication date, size, quality as measured by Jadad score or total NAC dose) or patient-related characteristic (age, diabetes, gender, contrast volume, baseline creatinine or CIN event rate in the control group) that significantly co-varied with NAC efficacy (Table 2).


A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity.

Gonzales DA, Norsworthy KJ, Kern SJ, Banks S, Sieving PC, Star RA, Natanson C, Danner RL - BMC Med (2007)

Funnel plot of precision versus log RR. Log RR of developing CIN is plotted versus precision for each of the 22 studies in this meta-analysis. Four studies later identified as contributing most to heterogeneity are noted with open circles and are seen to produce asymmetry in the plot. The summary log RR for all 22 studies is denoted by the open diamond.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2200657&req=5

Figure 3: Funnel plot of precision versus log RR. Log RR of developing CIN is plotted versus precision for each of the 22 studies in this meta-analysis. Four studies later identified as contributing most to heterogeneity are noted with open circles and are seen to produce asymmetry in the plot. The summary log RR for all 22 studies is denoted by the open diamond.
Mentions: Although non-significant (p ≤ 0.11, but p > 0.05 when applying any one of the three methods used for analysis), a visual inspection of a funnel plot suggested publication bias with four studies [10,11,14,25] contributing most to the apparent asymmetry (shown with open circles on the left-hand side of Figure 3). An extensive meta-regression analysis of patient and study characteristics found no study-specific characteristic (publication date, size, quality as measured by Jadad score or total NAC dose) or patient-related characteristic (age, diabetes, gender, contrast volume, baseline creatinine or CIN event rate in the control group) that significantly co-varied with NAC efficacy (Table 2).

Bottom Line: Benefit in cluster 2 was unexpectedly associated with NAC-induced decreases in creatinine from baseline (p = 0.07).Dialysis use across all studies (five control, eight treatment; p = 0.42) did not suggest that NAC is beneficial.This meta-analysis does not support the efficacy of NAC to prevent CIN.

View Article: PubMed Central - HTML - PubMed

Affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA. dgonzales@cc.nih.gov

ABSTRACT

Background: Meta-analyses of N-acetylcysteine (NAC) for preventing contrast-induced nephrotoxicity (CIN) have led to disparate conclusions. Here we examine and attempt to resolve the heterogeneity evident among these trials.

Methods: Two reviewers independently extracted and graded the data. Limiting studies to randomized, controlled trials with adequate outcome data yielded 22 reports with 2746 patients.

Results: Significant heterogeneity was detected among these trials (I2 = 37%; p = 0.04). Meta-regression analysis failed to identify significant sources of heterogeneity. A modified L'Abbé plot that substituted groupwise changes in serum creatinine for nephrotoxicity rates, followed by model-based, unsupervised clustering resolved trials into two distinct, significantly different (p < 0.0001) and homogeneous populations (I2 = 0 and p > 0.5, for both). Cluster 1 studies (n = 18; 2445 patients) showed no benefit (relative risk (RR) = 0.87; 95% confidence interval (CI) 0.68-1.12, p = 0.28), while cluster 2 studies (n = 4; 301 patients) indicated that NAC was highly beneficial (RR = 0.15; 95% CI 0.07-0.33, p < 0.0001). Benefit in cluster 2 was unexpectedly associated with NAC-induced decreases in creatinine from baseline (p = 0.07). Cluster 2 studies were relatively early, small and of lower quality compared with cluster 1 studies (p = 0.01 for the three factors combined). Dialysis use across all studies (five control, eight treatment; p = 0.42) did not suggest that NAC is beneficial.

Conclusion: This meta-analysis does not support the efficacy of NAC to prevent CIN.

Show MeSH
Related in: MedlinePlus