Original Investigation
Dialysis
Gadolinium-Containing Magnetic Resonance Imaging Contrast and Nephrogenic Systemic Fibrosis: A Case-Control Study

https://doi.org/10.1053/j.ajkd.2007.12.036Get rights and content

Background

Nephrogenic systemic fibrosis (NSF) is a newly described disorder occurring in persons with renal failure. Gadolinium-based contrast used in magnetic resonance imaging (MRI) has been suggested as a cause. A cluster of patients with NSF was investigated to identify risk factors. Limited preliminary findings from this investigation were presented in the Morbidity and Mortality Weekly Report.

Study Design

Matched case-control.

Setting & Participants

Dialysis patients with and without a diagnosis of NSF treated at an academic medical center.

Predictor

Exposure to gadolinium-based contrast.

Outcomes & Measurements

Laboratory and clinical characteristics of NSF.

Results

19 of 28 cases identified at the hospital from December 2002 to August 2006 met inclusion criteria and were matched to 57 controls. In univariate analysis, receipt of gadolinium-containing MRI contrast in the preceding year (odds ratio [OR], 7.99; 95% confidence interval, 2.22 to 28.8) was associated with NSF; the measure of association increased as cumulative dose increased. Gadodiamide exposure (OR, 9.83; 95% confidence interval, 2.09 to 46.2) was associated more strongly with NSF than gadoversetamide (OR, 1.82; 95% confidence interval, 0.33 to 10.2). Although not statistically significant, cases were more likely than controls to have undergone primarily peritoneal dialysis in the preceding 6 months. There was no significant difference in receipt of high-dose recombinant erythropoietin between cases and controls. In multivariable analysis, gadolinium contrast exposure (OR, 8.97; 95% confidence interval, 1.28 to 63.0) remained significantly associated with NSF.

Limitations

Retrospective design, small sample size, inability to completely evaluate erythropoietin.

Conclusions

Receipt of gadolinium-containing MRI contrast is associated with NSF in a dose-dependent manner. The risk associated with gadolinium may differ by contrast agent and dialysis modality. Use of gadolinium-based contrast agents should be avoided when possible in patients with renal failure.

Section snippets

Case Definitions and Case Finding

A confirmed case was defined as clinical evidence (ie, skin thickening or hardening) and skin biopsy results consistent with NSF in a patient with renal failure in St Louis from January 1, 2000, to August 1, 2006. Suspected cases met clinical or biopsy criteria, but not both. Hospital staff searched a logbook of dermatology biopsies to identify cases. The hospital pathology database also was searched for diagnoses consistent with NSF since 2000. To identify additional cases, 8 pathology

Case Finding and Characteristics

Twenty-eight cases were identified at the hospital between December 2002 and August 2006, including 25 confirmed and 3 suspected cases.14 Expanded case finding in St Louis identified 5 additional patients with a diagnosis of NSF outside the hospital during the study period; however, additional information was unavailable for these patients. Six of the 25 confirmed cases from the hospital had insufficient health care encounters in the hospital system and therefore were excluded. Limited

Discussion

In 2006, the link between gadolinium contrast and NSF was first suggested in the literature.12 Also in that year, the Danish Medicines Agency reported 25 patients in whom NSF was diagnosed after gadolinium contrast exposure.3 Since that time, several studies have attempted to further define the role of gadolinium in NSF development and identify potential cofactors.13, 15, 16, 17, 18, 19 In this investigation, gadolinium-containing contrast was the factor most strongly associated with a

Acknowledgements

The authors acknowledge the assistance of Shawn Cowper, MD, Yale University School of Medicine and Richard Wang, DO, Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention.

This report was presented in part as a poster at the 2007 National Kidney Foundation Spring Clinical Meetings, Orlando, FL, April 11, 2007. Limited preliminary findings from this investigation were presented in the Morbidity and Mortality Weekly Report.14 The

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    Originally published online as doi:10.1053/j.ajkd.2007.12.036 on March 27, 2008.

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