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NDT Advance Access published online on September 21, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm584
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Nephrogenic systemic fibrosis after exposure to gadolinium in patients with renal failure

Othersen B. Jennifer1,2, John C. Maize2,3, Robert F. Woolson1,2 and Milos N. Budisavljevic1,2

1Department of Biostatistics, Bioinformatics and Epidemiology, Division of Nephrology, 2Department of Dermatology, Medical University of South Carolina, Charleston and 3Maize Center for Dermatopathology, Mt Pleasant, SC, USA

Correspondence and offprint requests to: Milos N. Budisavljevic, MD, Nephrology Division, Department of Medicine, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC, USA. Email: budisamn{at}musc.edu



  Abstract

Background. Nephrogenic systemic fibrosis is a debilitating disease occurring exclusively in patients with renal failure. The aetiology of nephrogenic systemic fibrosis is unclear, but recent reports suggest that exposure to gadolinium for enhancement of magnetic resonance imaging may play a role. In the present study, we assessed the association of exposure to gadolinium with the development of nephrogenic systemic fibrosis in patients with various stages of chronic kidney disease.

Methods. We analysed the exposure to gadolinium and development of nephrogenic systemic fibrosis in 849 patients on renal replacement therapy over 5 years. We also performed inquiry of development of the nephrogenic systemic fibrosis in 592 patients exposed to gadolinium and estimated to be in stages 3 and 4 of chronic kidney disease.

Results. In 849 patients undergoing chronic dialysis from 2001 through 2006 time period, four of the 261 who had received gadolinium (1.5%) and none of the 588 not exposed to gadolinium developed clinically apparent disease. The odds ratio for developing nephrogenic systemic fibrosis was 6.671 [95% confidence interval (CI) 1.537–53.97] in patients with a single gadolinium exposure compared to patients without gadolinium exposure. This ratio increased to 44.5 (95% CI 2.362–2913) in patients with multiple gadolinium exposures compared to patients not receiving gadolinium. None of the 592 patients estimated to be in stage 3 or 4 of chronic kidney disease developed nephrogenic systemic fibrosis after exposure to gadolinium.

Conclusion. Gadolinium exposure is associated with nephrogenic systemic fibrosis in patients on chronic renal replacement therapy at a low rate. This association appears to increase with repeated exposure to gadolinium. Since nephrogenic systemic fibrosis may be clinically occult, its prevalence may be higher than reported. Despite this association, it is unclear if gadolinium is the sole or most important factor in the pathogenesis of the disease.

Keywords: chronic kidney disease; end stage renal disease; gadolinium; magnetic resonance imaging; metabotropic glutamate receptors; nephrogenic systemic fibrosis

Received for publication: 28. 5.07
Accepted in revised form: 31. 7.07


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