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. 2015 Jun 15;10(6):e0129720.
doi: 10.1371/journal.pone.0129720. eCollection 2015.

An Updated Study to Determine Association between Gadolinium-Based Contrast Agents and Nephrogenic Systemic Fibrosis

Bin Zhang  1 , Long Liang  1 , Wenbo Chen  2 , Changhong Liang  2 , Shuixing Zhang  2
Affiliations

An Updated Study to Determine Association between Gadolinium-Based Contrast Agents and Nephrogenic Systemic Fibrosis

Bin Zhang et al. PLoS One. .

Abstract

Background: Nephrogenic systemic fibrosis (NSF) is a rare but serious disorder disease affecting patients with advanced renal disease. Although multiple studies have indicated an association between gadolinium-based contrast agents (GBCAs) and NSF, some studies published after 2007 found no association. We therefore performed a meta-analysis to evaluate the association and analyze related (co)factors.

Methods: Studies for analysis were identified by searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials through December 2014. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using the fixed-effects model. Statistical heterogeneity was assessed by Q statistics and the I2 test. Publication bias was evaluated using Begg's test, Egger's test, funnel plot, and classic fail-safe N. Study quality was assessed using the Newcastle-Ottawa Scale. We also conducted sensitivity analyses, subgroup analyses and a cumulative meta-analysis. All statistical analyses were performed using Comprehensive Meta-Analysis 2.0.

Results: A total of 14 studies (6,398 patients) met the inclusion criteria, but 3 were excluded since they reported no NSF events. Meta-analysis of controlled trials indicated a significant association between GBCAs and NSF development (OR = 16.504; 95% CI: 7.455-36.533; P < 0.001) and between gadodiamide and NSF (OR = 20.037; 95% CI: 3.725-107.784; P < 0.001). No statistical heterogeneity was observed across studies (P = 0.819, I2 = 0%; P = 0.874, I2 = 0%, respectively). Cumulative analysis demonstrated that the pooled ORs for association between GBCAs and NSF decreased post-2007 compared to pre-2007 (OR = 26.708; 95% CI: 10.273-69.436; P<0.001).

Conclusions: Although this updated meta-analysis found a significant association between GBCAs and the incidence of NSF in patients with advanced renal disease, the association decreased after 2007. More studies, especially randomized controlled trials, are warranted to examine the potential association between GBCAs other than gadodiamide and NSF.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow diagram of included studies.
Fig 2
Fig 2. Forest plot of association between GBCAs and the development of NSF.
Fig 3
Fig 3. Cumulative meta-analysis plot of GBCAs group vs Control group.
We added one study at a time chronologically until all studies were included.
Fig 4
Fig 4. Funnel plot for publication bias.
Fig 5
Fig 5. Sensitivity analysis plot of GBCAs group vs Control group.
To assess the influence of single study on pooled estimate, we omitted one study at a time.
Fig 6
Fig 6. Forest plot of association between Gadodiamide exposure and the development of NSF.
Fig 7
Fig 7. Sensitivity analysis plot of gadodiamide group vs. control group.
To assess the influence of single study on pooled estimate, we omitted one study at a time.
See this image and copyright information in PMC

References

    1. Chao CC, Yang CC, Hsiao CH, Pan MK, Lin CH, et al. (2008) Nephrogenic systemic fibrosis associated with gadolinium use. J Formos Med Assoc 107: 270–274. 10.1016/S0929-6646(08)60147-3 - DOI - PubMed
    1. Broome DR (2008) Nephrogenic systemic fibrosis associated with gadolinium based contrast agents: a summary of the medical literature reporting. Eur J Radiol 66: 230–234. 10.1016/j.ejrad.2008.02.011 - DOI - PubMed
    1. Todd DJ, Kagan A, Chibnik LB, Kay J (2007) Cutaneous changes of nephrogenic systemic fibrosis: predictor of early mortality and association with gadolinium exposure. Arthritis Rheum 56: 3433–3441. - PubMed
    1. Introcaso CE, Hivnor C, Cowper S, Werth VP (2007) Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis: a case series of nine patients and review of the literature. Int J Dermatol 46: 447–452. - PubMed
    1. Reiter T, Ritter O, Prince MR, Nordbeck P, Wanner C, et al. (2012) Minimizing risk of nephrogenic systemic fibrosis in cardiovascular magnetic resonance. J Cardiovasc Magn Reson 14: 31 10.1186/1532-429X-14-31 - DOI - PMC - PubMed

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