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• Original Article •
The change of association between nephrogenic systemic fibrosis and gadolinium-based contrast agents: an updated meta-analysis applying Hill’s criteria
ZHANG Bin  LIANG Long  CHEN Wen-bo  LI Xin-yun  ZHENG Jun-hui  LIANG Chang-hong  ZHANG Shui-xing 

DOI:10.3969/j.issn.1674-8034.2015.04.012.


[Abstract] Objective: To examine whether a causal link exists between gadolinium-based contrast agents (GBCAs) and nephrogenic systemic fibrosis (NSF) and if the link changes over time.Materials and Methods: Studies for analysis were identified by searching the PubMed, the Wiley Online Library, and the Cochrane Central Register of Controlled Trials up to December 18, 2014. Pooled odds ratios (OR) with 95% confidence intervals (CI) was calculated by using the fixed-effects model. Statistical heterogeneity was assessed by Cochrane’s Q test and I2 statistics. Publication bias was evaluated using peters test, funnel plots and fail-safe N. Quality assessment of included studies using Newcastle-Ottawa Scale (NOS). Influence analysis and cumulative meta-analysis were also conducted in this study. All statistical analyses were performed by R software (R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL http://www.R-project.org, 2014). Hill’s criteria was used to evaluate evidence in support of a potential causal link between GBCAs and NSF.Results: A total of 14 studies including 6398 patients met the inclusion criteria, but 3 was excluded since they reported no NSF events. Meta-analysis of controlled trials indicated the GBCAs exposure may significantly increase the risk of NSF (OR=16. 50, 95%CI: 7.46-36.53, P<0.01) and gadodiamide exposure may also increase the risk of NSF (OR=20.04, 95%CI: 3.72-107.78, P<0.01). No heterogeneity (P=0. 819, I2=0%; P=0. 873, I2=0%, respectively) was observed across studies. Hill’s criteria suggested a potential causal link between GBCAs and NSF. In addition, the cumulative analysis demonstrated that the pooled ORs for GBCAs and NSF decreased post-2007 compared to pre-2007 (OR=26.71; 95%CI: 10.27-69.44).Conclusions: Although this meta-analysis suggests a strong association and potentially causal relation between GBCAs exposure and the incidence of NSF in patients with renal insufficiency, the relation decreased after 2007. More studies are warranted to examine the potential association between GBCAs other than gadodiamide and NSF.
[Keywords] Nephrogenic systemic fibrosis；Renal insufficiency；Gadolinium；Meta-analysis；Magnetic resonance imaging

ZHANG Bin Graduate College, Southern Medical University, Guangzhou 510515, China; Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou 510080, China

LIANG Long Graduate College, Southern Medical University, Guangzhou 510515, China; Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou 510080, China

CHEN Wen-bo Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou 510080, China

LI Xin-yun Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou 510080, China

ZHENG Jun-hui Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou 510080, China

LIANG Chang-hong Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou 510080, China

ZHANG Shui-xing* Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou 510080, China

*Correspondence to: Zhang SX, E-mail: shui7515@hotmail.com

Conflicts of interest   None.

Received  2015-01-11
Accepted  2015-02-11
DOI: 10.3969/j.issn.1674-8034.2015.04.012
DOI:10.3969/j.issn.1674-8034.2015.04.012.

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