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

BackgroundNephrogenic 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.MethodsStudies 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.ResultsA 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 P 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; PConclusionsAlthough 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.