Nephrogenic Systemic Fibrosis: Risk Factors and Incidence Estimation

Purpose: To retrospectively review data in 13 patients with biopsy-confirmed nephrogenic systemic fibrosis (NSF), assess the associated risk factors, and report the incidence of NSF at the authors' institution.

Materials and Methods: This HIPAA-compliant study had institutional review board approval; informed consent was waived. Statistical analysis was performed for all available clinical and laboratory data in patients with biopsy-confirmed NSF. The data from the patients with NSF were compared with data from a control population of patients with renal insufficiency but who did not develop NSF.

Results: There were eight male and five female patients, aged 17–69 years, with a diagnosis of NSF. Within 6 months of diagnosis, all 13 patients had been exposed to gadodiamide and one had been exposed to gadobenate dimeglumine in addition to gadodiamide. At the time of contrast material–enhanced magnetic resonance (MR) imaging, all 13 patients had renal insufficiency (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) and were hospitalized for a proinflammatory event (major surgery, infection, or vascular event). The group with NSF had significantly decreased eGFR (P = .01), more proinflammatory events (P < .001), and more contrast-enhanced MR examinations per patient (P = .002) than did the control group.

Conclusion: A combination of factors, including altered kidney function, inflammatory burden, and exposure to gadolinium-based contrast agents may all play a role in development of NSF. Alternative imaging should be considered in patients with these factors. If use of a gadolinium-based agent is clinically indicated, the referring physician and patient should be informed of the potential risk of developing NSF.

© RSNA, 2007


  • 1 Cowper SE. Nephrogenic systemic fibrosis: the nosological and conceptual evolution of nephrogenic fibrosing dermopathy. Am J Kidney Dis 2005; 46(4): 763–765. Crossref, MedlineGoogle Scholar
  • 2 Galan A, Cowper SE, Bucala R. Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy). Curr Opin Rheumatol 2006;18(6):614–617. Crossref, MedlineGoogle Scholar
  • 3 Cowper SE. Nephrogenic fibrosing dermopathy. The International Center for Nephrogenic Fibrosing Dermopathy Research (ICNFDR). Published 2001. Updated January 13, 2007. Accessed December 7, 2006. Google Scholar
  • 4 Gibson SE, Farver CF, Prayson RA. Multiorgan involvement in nephrogenic fibrosing dermopathy: an autopsy case and review of the literature. Arch Pathol Lab Med 2006;130(2):209–212. Crossref, MedlineGoogle Scholar
  • 5 Cowper SE. Nephrogenic fibrosing dermopathy: the first 6 years. Curr Opin Rheumatol 2003;15(6):785–790. Crossref, MedlineGoogle Scholar
  • 6 Grobner T. Gadolinium: a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 2006;21(4):1104–1108. Crossref, MedlineGoogle Scholar
  • 7 Mendoza FA, Artlett CM, Sandorfi N, Latinis K, Piera-Velazquez S, Jimenez SA. Description of 12 cases of nephrogenic fibrosing dermopathy and review of the literature. Semin Arthritis Rheum 2006;35(4):238–249. Crossref, MedlineGoogle Scholar
  • 8 Swaminathan S, Leung N. Nephrogenic fibrosing dermopathy: lessons from the past. Int J Dermatol 2006;45(6):639–641. Crossref, MedlineGoogle Scholar
  • 9 Marckmann P, Skov L, Rossen K, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 2006;17(9):2359–2362. Crossref, MedlineGoogle Scholar
  • 10 Thomsen HS, Morcos SK, Dawson P. Is there a causal relation between the administration of gadolinium based contrast media and the development of nephrogenic systemic fibrosis (NSF)? Clin Radiol 2006;61:905–906. Crossref, MedlineGoogle Scholar
  • 11 High WA, Ayers RA, Chandler J, Zito G, Cowper SE. Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol 2007;56:21–26. Crossref, MedlineGoogle Scholar
  • 12 Boyd AS, Zic JA, Abraham JL. Gadolinium deposition in nephrogenic fibrosing dermopathy. J Am Acad Dermatol 2007;56:27–30. Crossref, MedlineGoogle Scholar
  • 13 Public health advisory: gadolinium-containing contrast agents for magnetic resonance imaging (MRI)—Omniscan, OptiMARK, Magnevist, ProHance, and MultiHance. U.S. Food and Drug Administration. Published June 8, 2006. Updated December 22, 2006. Accessed December 7, 2006. Google Scholar
  • 14 Thomsen HS. Nephrogenic systemic fibrosis: a serious late adverse reaction to gadodiamide. Eur Radiol 2006;16(12):2619–2621. Crossref, MedlineGoogle Scholar
  • 15 Thomsen HS. European Society of Urogenital Radiology guidelines on contrast media application. Curr Opin Urol 2007;17(1):70–76. Crossref, MedlineGoogle Scholar
  • 16 National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 suppl 1):S1–S266. Crossref, MedlineGoogle Scholar
  • 17 Maloo M, Abt P, Kashyap R, et al. Nephrogenic systemic fibrosis among liver transplant recipients: a single institution experience and topic update. Am J Transplant 2006;6(9):2212–2217. Crossref, MedlineGoogle Scholar
  • 18 Mackay-Wiggan JM, Cohen DJ, Hardy MA, Knobler EH, Grossman ME. Nephrogenic fibrosing dermopathy (scleromyxedema-like illness of renal disease). J Am Acad Dermatol 2003;48(1):55–60. Crossref, MedlineGoogle Scholar
  • 19 Hubbard V, Davenport A, Jarmulowicz M, Rustin M. Scleromyxoedema-like change in four renal dialysis patients. Br J Dermatol 2003;148(3):563–568. Crossref, MedlineGoogle Scholar
  • 20 Levine JM, Taylor RA, Elman LB, et al. Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy). Muscle Nerve 2004;30(5):569–577. Crossref, MedlineGoogle Scholar
  • 21 Obermoser G, Emberger M, Wieser M, Zelger B. Nephrogenic fibrosing dermopathy in two patients with systemic lupus erythematosus. Lupus 2004;13(8):609–612. Crossref, MedlineGoogle Scholar
  • 22 Jimenez SA, Artlett CM, Sandorfi N, et al. Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin. Arthritis Rheum 2004;50(8):2660–2666. Crossref, MedlineGoogle Scholar
  • 23 Caravan P, Ellison JJ, McMurry TJ, Lauffer RB. Gadolinium (III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev 1999;99:2293–2352. Crossref, MedlineGoogle Scholar
  • 24 Rocklage SM, Worah D, Kim SH. Metal ion release from paramagnetic chelates: what is tolerable? Magn Reson Med 1991;22(2):216–221; discussion 229–232. Crossref, MedlineGoogle Scholar
  • 25 Sekido T, Sagami F, Tirone P, Morisetti A, Bussi S, Master RE. General toxicity study of gadobenate dimeglumine formulation (E7155)(2): single-dose intravenous toxicity study in dogs [in Japanese]. J Toxicol Sci 1999;24(suppl 1):7–18. Crossref, MedlineGoogle Scholar
  • 26 Oksendal AN, Hals PA. Biodistribution and toxicity of MR imaging contrast media. J Magn Reson Imaging 1993;3(1):157–165. Crossref, MedlineGoogle Scholar
  • 27 Jackson GE, Wynchank S, Woudenberg M. Gadolinium(III) complex equilibria: the implications for Gd(III) MRI contrast agents. Magn Reson Med 1990;16(1):57–66. Crossref, MedlineGoogle Scholar
  • 28 Kuo PH, Kanal E, Abu-Alfa AK, Cowper SE. Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis. Radiology 2007;242(3):647–649. LinkGoogle Scholar
  • 29 Broome DR, Girguis MS, Baron PW, Cottrell AC, Kjellin I, Kirk GA. Gadodiamide-associated nephrogenic system fibrosis: why radiologists should be concerned. AJR Am J Roentgenol. Published December 8, 2006. Accessed December 8, 2006. Google Scholar

Article History

Published in print: 2007