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. 2020 Jul 21;173(2):110-119.
doi: 10.7326/M20-0299. Epub 2020 Jun 23.

Risk for Nephrogenic Systemic Fibrosis After Exposure to Newer Gadolinium Agents: A Systematic Review

Joseph Lunyera  1 , Dinushika Mohottige  2 , Anastasia-Stefania Alexopoulos  3 , Hilary Campbell  4 , C Blake Cameron  1 , Nicole Sagalla  5 , Timothy J Amrhein  3 , Matthew J Crowley  3 , Jessica R Dietch  6 , Adelaide M Gordon  7 , Andrzej S Kosinski  8 , Sarah Cantrell  9 , John W Williams Jr  10 , Jennifer M Gierisch  11 , Belinda Ear  7 , Karen M Goldstein  10
Affiliations

Risk for Nephrogenic Systemic Fibrosis After Exposure to Newer Gadolinium Agents: A Systematic Review

Joseph Lunyera et al. Ann Intern Med. .

Abstract

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).

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Conflict of interest statement

Disclosures: Dr. Campbell reports that a grant from the U.S. Department of Veterans Affairs funded this study. Dr. Dietch reports grants from the National Institutes of Health–National Institute of Allergy and Infectious Diseases and the U.S. Department of Defense outside the submitted work. Drs. Kosinski and Williams report grants from the U.S. Department of Veterans Affairs during the conduct of the study. Dr. Goldstein reports other support from the VA Office of Research and Development during the conduct of the study (VA Evidence Synthesis Program receives funding from VA HSR&D to support center activities related to conducting systematic reviews [such as staff salary support]). Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-0299.

Figures

Figure 1.
Figure 1.
Evidence search and selection. ACR = American College of Radiology; GBCA = gadolinium-based contrast agent; KQ = key question; NSF = nephrogenic systemic fibrosis. * Occurrence of NSF per index exposure to ACR group II and III GBCAs. † Occurrence of NSF per index exposure to ACR group II and III GBCAs compared with ACR Group I GBCAs.
Figure 2.
Figure 2.
Occurrence of NSF after index exposure to GBCAs. ACR = American College of Radiology; CKD = chronic kidney disease; GBCA = gadolinium-based contrast agent; NSF = nephrogenic systemic fibrosis; ROB = risk of bias. Top. Index exposures to ACR group II and III agents. Bottom. Index exposures to ACR group II and III agents compared with exposures to ACR group I agents. * Prospective cohort study. † The study by Soulez and colleagues (50) has 2 rows depicted, one for each GBCA. ‡ The study by Amet and colleagues (55) has only 1 row depicted, because the group I exposures were fewer than 26.
See this image and copyright information in PMC

References

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