LAUSR

BACKGROUND The risk for nephrogenic systemic fibrosis (NSF) after exposure to newer versus older gadolinium-based contrast agents (GBCAs) remains unclear. PURPOSE To synthesize evidence about NSF risk with newer versus older GBCAs across the spectrum of kidney function. DATA SOURCES MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science for English-language references from inception to 5 March 2020. STUDY SELECTION Randomized controlled trials, cohort studies, and case-control studies that assessed NSF occurrence after GBCA exposure. DATA EXTRACTION Data were abstracted by 1 investigator and verified by a second. Investigator pairs assessed risk of bias by using validated tools. DATA SYNTHESIS Of 32 included studies, 20 allowed for assessment of NSF risk after exposure to newer GBCAs and 12 (11 cohort studies and 1 case-control study) allowed for comparison of NSF risk between newer and older GBCAs. Among 83 291 patients exposed to newer GBCAs, no NSF cases developed (exact 95% CI, 0.0001 to 0.0258 case). Among the 12 studies (n = 118 844) that allowed risk comparison between newer and older GBCAs, 37 NSF cases developed after exposure to older GBCAs (exact CI, 0.0001 to 0.0523 case) and 4 occurred (3 confounded) after exposure to newer GBCAs (exact CI, 0.0018 to 0.0204 case). Data were scant for patients with acute kidney injury or those at risk for chronic kidney disease. LIMITATIONS Study heterogeneity prevented meta-analysis. Risk of bias was high in most studies because of inadequate exposure and outcome ascertainment. CONCLUSION Although NSF occurrence after exposure to newer GBCAs is very rare, the relatively scarce data among patients with acute kidney injury and those with risk factors for chronic kidney disease limit conclusions about safety in these populations. PRIMARY FUNDING SOURCE U.S. Department of Veterans Affairs. (PROSPERO: CRD42019135783).