title: An Updated Study to Determine Association between Gadolinium-Based Contrast Agents and Nephrogenic Systemic Fibrosis.
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.
authors.affiliation: Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China; Graduate College, Southern Medical University, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China; Graduate College, Southern Medical University, Guangzhou, China.
authors.forename: Long
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Radiology, Guangdong Academy of Medical Sciences/Guangdong General Hospital, Guangzhou, Guangdong Province, China.
authors.forename: Shuixing
authors.initials: S
authors.lastname: Zhang
mesh_terms: D003287:Contrast Media / Q000009:adverse effects*; D005682:Gadolinium / Q000009:adverse effects*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications* / Q000628:therapy; D015201:Meta-Analysis as Topic; D054989:Nephrogenic Fibrosing Dermopathy / Q000139:chemically induced*; D012307:Risk Factors
chemical_list: D003287:Contrast Media; D005682:Gadolinium