Limits...
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.

Show MeSH

Related in: MedlinePlus

Jackknife sensitivity analysis. Studies are ordered from top to bottom by their effect on heterogeneity when removed one at a time from the set of 22 studies. Removing any of the 10 studies at the top of the plot decreases heterogeneity, while removing any of the 12 studies at the bottom of the plot increases heterogeneity. The four studies that individually contributed the most to heterogeneity are shown as open circles. Circle size is proportional to the inverse variance.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2200657&req=5

Figure 4: Jackknife sensitivity analysis. Studies are ordered from top to bottom by their effect on heterogeneity when removed one at a time from the set of 22 studies. Removing any of the 10 studies at the top of the plot decreases heterogeneity, while removing any of the 12 studies at the bottom of the plot increases heterogeneity. The four studies that individually contributed the most to heterogeneity are shown as open circles. Circle size is proportional to the inverse variance.

Mentions: A jackknife-k sensitivity analysis [97] identified 10 studies that decreased heterogeneity when individually removed (right-hand side of Figure 4). Removal of any one of the remaining 12 studies increased heterogeneity (left-hand side of Figure 4). The four small studies [10,11,14,25] that individually contributed the most to heterogeneity are shown as open circles in Figure 4 (circle size is proportional to inverse variance). Removal of any single study or all possible two-study combinations failed to adequately resolve heterogeneity. In contrast, the removal of multiple three-study combinations (combinations [11,14,25][10,11,14][11,14,21] and [11,14,17]) reached our pre-defined target for homogeneity (after the removal of any one of the three-study groups above, I2 ≤ 9.5% and p ≥ 0.34). These four three-study groups represent only 7.9%, 9.4%, 12.0% and 13.7% of the entire study population, respectively.


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)

Jackknife sensitivity analysis. Studies are ordered from top to bottom by their effect on heterogeneity when removed one at a time from the set of 22 studies. Removing any of the 10 studies at the top of the plot decreases heterogeneity, while removing any of the 12 studies at the bottom of the plot increases heterogeneity. The four studies that individually contributed the most to heterogeneity are shown as open circles. Circle size is proportional to the inverse variance.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Jackknife sensitivity analysis. Studies are ordered from top to bottom by their effect on heterogeneity when removed one at a time from the set of 22 studies. Removing any of the 10 studies at the top of the plot decreases heterogeneity, while removing any of the 12 studies at the bottom of the plot increases heterogeneity. The four studies that individually contributed the most to heterogeneity are shown as open circles. Circle size is proportional to the inverse variance.
Mentions: A jackknife-k sensitivity analysis [97] identified 10 studies that decreased heterogeneity when individually removed (right-hand side of Figure 4). Removal of any one of the remaining 12 studies increased heterogeneity (left-hand side of Figure 4). The four small studies [10,11,14,25] that individually contributed the most to heterogeneity are shown as open circles in Figure 4 (circle size is proportional to inverse variance). Removal of any single study or all possible two-study combinations failed to adequately resolve heterogeneity. In contrast, the removal of multiple three-study combinations (combinations [11,14,25][10,11,14][11,14,21] and [11,14,17]) reached our pre-defined target for homogeneity (after the removal of any one of the three-study groups above, I2 ≤ 9.5% and p ≥ 0.34). These four three-study groups represent only 7.9%, 9.4%, 12.0% and 13.7% of the entire study population, respectively.

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