Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
European Radiology
Published in: European Radiology 2/2013

01-02-2013 | Contrast Media

Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR Contrast Medium Safety Committee guidelines

Published in: European Radiology | Issue 2/2013

Login to get access

Abstract

Purpose

To update the guidelines of the Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) on nephrogenic systemic fibrosis and gadolinium-based contrast media.

Areas covered

Topics reviewed include the history, clinical features and prevalence of nephrogenic systemic fibrosis and the current understanding of its pathophysiology. The risk factors for NSF are discussed and prophylactic measures are recommended. The stability of the different gadolinium-based contrast media and the potential long-term effects of gadolinium in the body have also been reviewed.

Key Points

• Clinical features, risk factors and prevention of nephrogenic systemic fibrosis are reviewed
• Patients with GFR below 30 ml/min/1.73 m 2 have increased risk of developing NSF
• Low stability gadolinium contrast media show the strongest association with NSF
• Following guidelines regarding gadolinium contrast agents minimises the risk of NSF
• Potential long-term harm from gadolinium accumulation in the body is discussed
Literature
1.
Thomsen HS (2007) ESUR guideline: gadolinium-based contrast media and nephrogenic systemic fibrosis. Eur Radiol 17:2692–2696PubMedCrossRef
2.
Stacul F, van der Molen AJ, Reimer P, Webb JAW, Thomsen HS, Morcos SK, Almén T, Aspelin P, Bellin M-F, Clement O, Heinz-Peer G; Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) (2011) Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines. Eur Radiol 21:2527–2541PubMedCrossRef
3.
Prince MR, Arnoldus C, Frisoli JK (1996) Nephrotoxicity of high-dose gadolinium compared with iodinated contrast. JMRI 1:162–166CrossRef
4.
Thomsen HS, Almén T, Morcos SK; Contrast Media Safety Committee of the European Society of Urogenital Radiology (2002) Gadolinium-containing contrast media for radiographic examinations: a position paper. Eur Radiol 12:2600–2605PubMed
5.
Gemmette JJ, Forauer AR, Kazanijan S, Dasika N, Williams DM, Cho K (2001) Safety of large volume gadolinium angiography. J Vasc Interv Radiol 12(Part 2):S28
6.
Cowper SE, Robin HS, Steinberg SM et al (2000) Scleromyxoedema-like cutaneous disease in renal dialysis patients. Lancet 356:1000–1001PubMedCrossRef
7.
Grobner T (2006) Gadolinium: a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis. Nephrol Dial Transplant 21:1104–1108PubMedCrossRef
8.
Marckmann P, Skov L, Rossen K et al (2006) Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 17:2359–2362PubMedCrossRef
9.
Thomsen HS, Marckmann P (2008) Extracellular Gd-CM: Differences in prevalence of NSF. Eur J Radiol 66:180–183PubMedCrossRef
10.
Thomsen HS (2009) Delayed reactions: nephrogenic systemic fibrosis. In: Thomsen HS, Webb JAW (eds) Contrast media: safety issues and ESUR guidelines, 2nd edn. Springer, Heidelberg, pp 187–196
11.
Thomsen HS (2009) Nephrogenic systemic fibrosis: history and epidemiology. Radiol Clin N Am 47:827–831PubMedCrossRef
12.
Broome DR (2008) Nephrogenic systemic fibrosis associated with gadolinium based contrast agents: a summary of the medical literature reporting. Eur J Radiol 66:230–234PubMedCrossRef
13.
Idée J-M, Port M, Dencausse A, Lancelot E, Corot C (2009) Involvement of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: an update. Radiol Clin N Am 47:855–869PubMedCrossRef
14.
Evans CH (1990) The occurrence and metabolism of lanthanides. In: Biochemistry of the lanthanides. Plenum Press, New York, pp 285–337
15.
Palasz A, Czekaj P (2000) Toxicological and cytophysiological aspects of lanthanides action. Acta Biochim Pol 47:1107–1114PubMed
16.
Adding LC, Bannenberg GL, Gustafsson LE (2001) Basic experimental studies and clinical aspects of gadolinium salts and chelates. Cardiovasc Drug Rev 19:41–56PubMedCrossRef
17.
Korolenko TA, Dergunova MA, Alekseenko TV et al (2006) Intralysosomal accumulation of gadolinium and lysosomal damage during selective depression of liver macrophages in vivo. Bull Exp Biol Med 142:391–394PubMedCrossRef
18.
Spencer AJ, Wilson SA, Batchelor J et al (1997) Gadolinium chloride toxicity in the rat. Toxicol Pathol 25:245–255PubMedCrossRef
19.
De Haën C (2001) Conception of the first magnetic resonance imaging contrast agents; a brief history. Top Magn Reson Imaging 12:221–2230PubMedCrossRef
20.
Thomsen HS, Dawson P, Tweedle MF (2012) MR and CT contrast agents for perfusion imaging and regulatory issues. In: Bammer R (ed) MR & CT perfusion imaging: clinical applications and theoretical principles. Lippincott Williams & Wilkins, Philadelphia (in press)
21.
Morcos SK (2009) Chelates and stability. In Thomsen HS, Webb JAW (eds) Contrast media: safety issues and ESUR guidelines, 2nd edn. Springer, Heidelberg, pp 155-160
22.
Tweedle MF, Wedeking P, Kumar K (1995) Biodistribution of radiolabeled formulated gadopentetate, gadoteridol, gadoterate and gadodiamide in mice and rats. Invest Radiol 30:372–380PubMedCrossRef
23.
Pietsch H, Lengsfeld P, Jost G, Frenzel T, Hütter J, Sieber MA (2009) Long-term retention of gadolinium in the skin of rodents following the administration of gadolinium-based contrast agents. Eur Radiol 19:1417–1424PubMedCrossRef
24.
Evans CH, Drouven BJ (1983) The promotion of collagen polymerization by lanthanide and calcium ions. Biochem J 213:751–758PubMed
25.
Brouven BJ, Evans CK (1986) Collagen fibrillogenesis in the presence of lanthanides. J Biol Chim 261:11792–11797
26.
Brady T, Gore J (1991) Discussion. Presented at SMRM Workshop on Contrast Enhanced Magnetic Resonance, Napa, CA, May 23-25, 1991. Magn Reson Med 22:229–232CrossRef
27.
Müller N, Günzel P, Schöbel C (1992) Ionic and non-ionic gadolinium-containing magnetic resonance contrast media. Comparison of effects and their reversibility in repeated dose toxicity studies in rats. Adv MRI Contrast 1(Suppl 1):15–28
28.
Edward M, Quinn JA, Mukherjee S et al (2008) Gadodiamide contrast agent ‘activates’ fibroblasts: a possible cause of nephrogenic systemic fibrosis. J Pathol 214:584–593PubMedCrossRef
29.
Morcos SK (2011) Experimental studies investigating the pathophysiology of nephrogenic systemic fibrosis; what did we learn so far? Eur Radiol 21:496–500PubMedCrossRef
30.
Abu-Alfa AK (2011) Nephrogenic systemic fibrosis and gadolinium-based contrast agents. Adv Chronic Kidney Dis 18:188–198PubMedCrossRef
31.
Thomsen HS (2010) Contrast-enhanced MRI in patients with impaired renal function: recent recommendations to minimize the risk of nephrogenic systemic fibrosis. Solutions Contrast Imaging 1:2–7
32.
Marckmann P, Skov L (2009) Nephrogenic systemic fibrosis: clinical picture and treatment. Radiol Clin N Am 47:833–840PubMedCrossRef
33.
Marckmann P, Skov L, Rossen K et al (2008) Clinical manifestations of gadodiamide-related nephrogenic systemic fibrosis. Clin Nephrol 69:161–168PubMed
34.
Giradi M, Kay J, Elston DM, LeBoit PE, Abu-Alfa A, Cowper SE (2011) Nephrogenic systemic fibrosis: clinicopathological definition and workup recommendations. J Am Acad Dermatol 65:1095–1106CrossRef
35.
Todd DJ, Kagan A, Chibnik LB, Kay J (2007) Cutaneous changes of nephrogenic systemic fibrosis. Predictor of early mortality and association with gadolinium exposure. Arthritis Rheum 56:3433–3441PubMedCrossRef
36.
Qureshi ZP, Bennett CL, Sator OA, Norris LB, Xirasagar A, Thomsen HS (2012) Gadolinium induced nephrogenic systemic fibrosis, the rise and fall of an iatrogenic disease. Clin Kidney J 5:82–88
37.
Rydahl C, Thomsen HS, Marckman P (2008) High prevalence of nephrogenic systemic fibrosis in chronic renal failure patients exposed to gadodiamide, a Gadolinium(Gd)-containing magnetic resonance contrast agent. Invest Radiol 43:141–144PubMedCrossRef
38.
COMMISSION DECISION of 1.7.2010 concerning, in the framework of Article 31 of Directive 2001/83/EC of the European Parliament and of the Council, the marketing authorisations for Gadolinium-containing contrast agents for human use which contain one or more of the active substances “gadodiamide, gadopentetic acid, gadobenic acid, gadoxetic acid, gadoteridol, gadobutrol and gadoteric acid”. http://​ec.​europa.​eu/​health/​documents/​community-register/​html/​refh_​others.​htm. Accessed December 2011
39.
40.
Wertman R, Altun E, Martin DR et al (2008) Risk of nephrogenic systemic fibrosis: evaluation of gadolinium chelate contrast agents at four American universities. Radiology 248:799–806PubMedCrossRef
41.
Elmholdt TR, Pedersen M, Jorgensen B et al (2011) Nephrogenic systemic fibrosis is found only among gadolinium-exposed patients with renal insufficiency: a case–control study from Denmark. Br J Dermatol 165:828–836PubMedCrossRef
42.
Tsushima Y, Kanal E, Thomsen HS (2010) Nephrogenic systemic fibrosis: risk factors suggested from Japanese published cases. Brit J Radiol 83:590–595PubMedCrossRef
43.
Marckmann P, Skov L, Rossen K, Heaf JG, Thomsen HS (2007) Case–control study of gadodiamide-related nephrogenic systemic fibrosis. Nephrol Dial Transplant 22:3174–3178PubMedCrossRef
44.
National Institute for Health and Clinical Excellence (2008) Early identification and management of Chronic kidney disease in adults in primaty and secondary care. www.​nice.​org.​uk/​CG073. Assessed June 17th 2012
45.
Sena BF, Stern JP, Pandharipande PV et al (2010) Screening patients to assess renal function before administering gadolinium chelates: assessment of the Choyke questionnaire. AJR Am J Roentgenol 195:424–428PubMedCrossRef
46.
Maloo M, Abt P, Kashyap R et al (2006) Nephrogenic systemic fibrosis among liver transplant recipients: a single institution experience and topic update. Am J Transplant 6:2212–2217PubMedCrossRef
47.
Chow DS, Bahrami S, Raman SS et al (2011) Risk of nephrogenic systemic fibrosis in liver transplantation patients. AJR Am J Roentgenol 197:658–662PubMedCrossRef
48.
KDOQI Clinical Practice Guidelines for chronic kidney disease (2002) Evaluation, classification and stratification. Am J Kidney Dis 39:S1–S266CrossRef
49.
Grebe SO, Borrmann M, Altenburg A, Wesselman U, Hein D, Haage P (2008) Chronic inflammation and accelerated atherosclerosis as important cofactors in nephrogenic systemic fibrosis following intravenous gadolinium exposure. Clin Exp Nephrol 12:403–406PubMedCrossRef
50.
Heinz-Peer G, Neruda A, Watschinger B et al (2010) Prevalence of NSF following intravenous gadolinium-contrast media administration in dialysis patients with endstage renal disease. Eur J Radiol 76:12–34CrossRef
51.
Abraham JL, Thakral C, Skov L et al (2008) Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis. Brit J Dermatol 158:273–280CrossRef
52.
Sieber MA, Lengsfeld P, Frenzel T et al (2008) Preclinical investigation to compare different gadolinium-based contrast agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions. Eur Radiol 18:2164–2173PubMedCrossRef
53.
Wadas TJ, Sherman CD, Miner JH et al (2010) The biodistribution of [153Gd]Gd-labeled magnetic resonance contrast agents in a transgenic mouse model of renal failure differs greatly from control mice. Magn Reson Med 64:1274–1280PubMedCrossRef
54.
White GW, Gibby WA, Tweedle MF (2006) Comparison of Gd (DTPA-BMA) (Omniscan) versus Gd(HP-DO3A) (ProHance) relative to gadolinium retention in human bone tissue by inductively coupled plasma mass spectroscopy. Invest Radiol 41:272–278PubMedCrossRef
55.
Webb JAW (2009) Pregnancy and lactation. In: Thomsen HS, Webb JAW (eds) Contrast media: safety issues and ESUR Guidelines, 2nd edn. Springer, Heidelberg, pp 95–102
56.
57.
Morcos SK, Thomsen HS, Webb JAW; Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) (2007) Dialysis and contrast media. Eur Radiol 12:3026–3030
58.
Thomsen HS (2008) Is NSF only the tip of the “gadolinium toxicity” iceberg? J Magn Reson Imaging 28:284–286PubMedCrossRef
59.
Lind Ramskov K, Thomsen HS (2009) Nephrogenic systemic fibrosis and contrast medium-induced nephropathy: a choice between the devil and the deep blue sea for patients with reduced renal function? Acta Radiol 50:965–967PubMedCrossRef
60.
Martin DR, Semelka RC, Chapman A et al (2009) Nephrogenic systemic fibrosis versus contrast-induced nephropathy: risks and benefits of contrast-enhanced MR and CT renally impaired patients. J Magn Reson Imaging 30:1350–1356PubMedCrossRef
Metadata
Title
Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR Contrast Medium Safety Committee guidelines
Publication date
01-02-2013
Published in
European Radiology / Issue 2/2013
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-012-2597-9

Other articles of this Issue 2/2013

European Radiology 2/2013 Go to the issue

Musculoskeletal

Bone mineral density measurements of the proximal femur from routine contrast-enhanced MDCT data sets correlate with dual-energy X-ray absorptiometry

Head and Neck

Diffusion-weighted MR imaging including bi-exponential fitting for the detection of recurrent or residual tumour after (chemo)radiotherapy for laryngeal and hypopharyngeal cancers

Vascular-Interventional

In vitro stent lumen visualisation of various common and newly developed femoral artery stents using MR angiography at 1.5 and 3 tesla

Molecular Imaging

The high angiogenic activity in very early breast cancer enables reliable imaging with VEGFR2-targeted microbubbles (BR55)

Computed Tomography

Changes in measured size of atherosclerotic plaque calcifications in dual-energy CT of ex vivo carotid endarterectomy specimens: effect of monochromatic keV image reconstructions

Computed Tomography

Computed tomography of the chest with model-based iterative reconstruction using a radiation exposure similar to chest X-ray examination: preliminary observations