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Original Investigation
December 9, 2019

Risk of Nephrogenic Systemic Fibrosis in Patients With Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Radiology, University of Michigan, Ann Arbor
  • 2Michigan Radiology Quality Collaborative, University of Michigan, Ann Arbor
  • 3Department of Orthopaedic Surgery, University of Michigan, Ann Arbor
  • 4Department of Epidemiology, University of Michigan, Ann Arbor
  • 5Taubman Health Sciences Library, University of Michigan, Ann Arbor
  • 6Dana-Farber Cancer Institute, Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, Massachusetts
  • 7Department of Urology, Michigan Medicine, Ann Arbor
JAMA Intern Med. Published online December 9, 2019. doi:10.1001/jamainternmed.2019.5284
Key Points

Question  What is the risk of nephrogenic systemic fibrosis in patients with stage 4 or 5 chronic kidney disease receiving a group II gadolinium-based contrast agent?

Findings  In this systematic review and meta-analysis of 16 unique studies and 4931 patients, the pooled incidence of nephrogenic systemic fibrosis after administration of a group II gadolinium-based contrast agent in patients with stage 4 or 5 chronic kidney disease was 0%; the upper bound of the 95% CI was 0.07%.

Meaning  Findings suggest that the risk of nephrogenic systemic fibrosis from group II gadolinium-based contrast agent administration in stage 4 or 5 chronic kidney disease is likely less than 0.07%; potential diagnostic harms of withholding group II gadolinium-based contrast agents for indicated examinations may outweigh the risk of nephrogenic systemic fibrosis in this population.

Abstract

Importance  Risk of nephrogenic systemic fibrosis (NSF) to individual patients with stage 4 or 5 chronic kidney disease (CKD; defined as estimated glomerular filtration rate of <30 mL/min/1.73 m2) who receive a group II gadolinium-based contrast agent (GBCA) is not well understood or summarized in the literature.

Objective  To assess the pooled risk of NSF in patients with stage 4 or 5 CKD receiving a group II GBCA.

Data Sources  A health sciences informationist searched the Ovid (MEDLINE and MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citation, and Daily and Versions), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Open Grey databases from inception to January 29, 2019, yielding 2700 citations.

Study Selection  Citations were screened for inclusion in a multistep process. Agreement for final cohort inclusion was determined by 2 blinded screeners using Cohen κ. Inclusion criteria consisted of stage 4 or 5 CKD with or without dialysis, administration of an unconfounded American College of Radiology classification group II GBCA (gadobenate dimeglumine, gadobutrol, gadoterate meglumine, or gadoteridol), and incident NSF as an outcome. Conference abstracts, retracted manuscripts, narrative reviews, editorials, case reports, and manuscripts not reporting total group II GBCA administrations were excluded.

Data Extraction and Synthesis  Data extraction was performed for all studies by a single investigator, including publication details, study design and time frame, patient characteristics, group II GBCA(s) administered, total exposures for patients with stage 4 or stage 5 CKD, total cases of unconfounded NSF, reason for GBCA administration, follow-up duration, loss to follow-up, basis for NSF screening, and diagnosis.

Main Outcomes and Measures  Pooled incidence of NSF and the associated upper bound of a 2-sided 95% CI (risk estimate) for the pooled data and each of the 4 group II GBCAs.

Results  Sixteen unique studies with 4931 patients were included (κ = 0.68) in this systematic review and meta-analysis. The pooled incidence of NSF was 0 of 4931 (0%; upper bound of 95% CI, 0.07%). The upper bound varied owing to different sample sizes for gadobenate dimeglumine (0 of 3167; upper bound of 95% CI, 0.12%), gadoterate meglumine (0 of 1204; upper bound of 95% CI, 0.31%), gadobutrol (0 of 330; upper bound of 95% CI, 1.11%), and gadoteridol (0 of 230; upper bound of 95% CI, 1.59%).

Conclusions and Relevance  This study’s findings suggest that the risk of NSF from group II GBCA administration in stage 4 or 5 CKD is likely less than 0.07%. The potential diagnostic harms of withholding group II GBCA for indicated examinations may outweigh the risk of NSF in this population.

Trial Registration  PROSPERO identifier: CRD42019123284

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