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
Pediatric Nephrology
Published in: Pediatric Nephrology 12/2008

01-12-2008 | Review

Nephrogenic systemic fibrosis and the use of gadolinium-based contrast agents

Author: Jeffrey G. Penfield

Published in: Pediatric Nephrology | Issue 12/2008

Login to get access

Abstract

Nephrogenic systemic fibrosis (NSF) is a disease seen exclusively in patients with decreased renal function. The use of gadolinium-based contrast agents (GBCAs) has a strong association with NSF. Linear non-ionic GBCAs that are more prone to release free gadolinium are the more likely to cause NSF. The number of reported cases has increased recently, and there are currently nine pediatric cases, the patients ranging in age from 8 years to 19 years, and the oldest adult patient is 87 years of age. The most successful treatment is improvement of renal function with renal transplantation or with recovery of acute kidney injury. NSF can be severely debilitating and even fatal. Avoidance of a GBCA in patients at risk, or limitation of the dose in the patients who need gadolinium enhancement, is recommended.
Literature
1.
Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE (2000) Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 356:1000–1001PubMed
2.
Daram SR, Cortese CM, Bastani B (2005) Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis: report of a new case with literature review. Am J Kidney Dis 46:754–759PubMed
3.
Auron A, Shao L, Warady BA (2006) Nephrogenic fibrosing dermopathy in children. Pediatr Nephrol 21:1307–1311PubMed
4.
Jain SM, Wesson S, Hassanein A, Canova E, Hoy M, Fennell RS, Dharnidharka VR (2004) Nephrogenic fibrosing dermopathy in pediatric patients. Pediatr Nephrol 19:467–470PubMed
5.
Jan F, Segal JM, Dyer J, LeBoit P, Siegfried E, Frieden IJ (2003) Nephrogenic fibrosing dermopathy: two pediatric cases. J Pediatr 143:678–681PubMed
6.
Cowper SE (2003) Nephrogenic fibrosing dermopathy: the first 6 years. Curr Opin Rheumatol 15:785–790PubMed
7.
Mendoza FA, Artlett CM, Sandorfi N, Latinis K, Piera-Velazquez S, Jimenez SA (2006) Description of 12 cases of nephrogenic fibrosing dermopathy and review of the literature. Semin Arthritis Rheum 35:238–249PubMedPubMedCentral
8.
Streams BN, Liu V, Liegeois N, Moschella SM (2003) Clinical and pathologic features of nephrogenic fibrosing dermopathy: a report of two cases. J Am Acad Dermatol 48:42–47PubMed
9.
Cowper SE, Bucala R (2003) Nephrogenic fibrosing dermopathy: suspect identified, motive unclear. Am J Dermatopathol 25:358PubMed
10.
Jimenez SA, Artlett CM, Sandorfi N, Derk C, Latinis K, Sawaya H, Haddad R, Shanahan JC (2004) Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin. Arthritis Rheum 50:2660–2666PubMed
11.
Parsons AC, Yosipovitch G, Sheehan DJ, Sangüeza OP, Greenberg CS, Sane DC (2007) Transglutaminases: the missing link in nephrogenic systemic fibrosis. Am J Dermatopathol 29:433–436PubMed
12.
Cowper SE, Su LD, Bhawan J, Robin HS, LeBoit PE (2001) Nephrogenic fibrosing dermopathy. Am J Dermatopathol 23:383–393PubMed
13.
Levine JM, Taylor RA, Elman LB, Bird SJ, Lavi E, Stolzenberg ED, McGarvey ML, Asbury AK, Jimenez SA (2004) Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy). Muscle Nerve 30:569–577PubMed
14.
Keyrouz S, Rudnicki SA (2007) Neuromuscular involvement in nephrogenic systemic fibrosis. J Clin Neuromuscul Dis 9:297–302PubMed
15.
Krous H, Breisch E, Chadwick A, Pinckney L, Malicki DM, Benador N (2007) Nephrogenic systemic fibrosis with multiorgan involvement in a teenage male after lymphoma, Ewing sarcoma, end stage renal disease, and hemodialysis. Pediatr Dev Pathol 10:395–402PubMed
16.
Kucher C, Steere J, Elenitsas R, Siegel DL, Xu X (2006) Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis with diaphragmatic involvement in a patient with respiratory failure. J Am Acad Dermatol 54:S31–34PubMed
17.
Centers for Disease Control and Prevention (CDC) (2007) Nephrogenic fibrosing dermopathy associated with exposure to gadolinium-containing contrast agents—St Louis, Missouri, 2002–2006. MMWR Morb Mortal Wkly Rep 56:137–141
18.
Collidge TA, Thomson PC, Mark PB, Traynor JP, Jardine AG, Morris ST, Simpson K, Roditi GH (2007) Gadolinium-enhanced MR imaging and nephrogenic systemic fibrosis: retrospective study of a renal replacement therapy cohort. Radiology 245:168–175PubMed
19.
Richmond H, Zwerner J, Kim Y, Fiorentino D (2007) Nephrogenic systemic fibrosis: relationship to gadolinium and response to photopheresis. Arch Dermatol 143:1025–1030PubMed
20.
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 56:3433–3441PubMed
21.
Wahba IM, Simpson EL, White K (2007) Gadolinium is not the only trigger for nephrogenic systemic fibrosis: insights from two cases and review of the recent literature. Am J Transplant 7:2425–2432PubMed
22.
Weiss AS, Lucia MS, Teitelbaum I (2007) A case of nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis. Nat Clin Pract Nephrol 3:111–115PubMed
23.
Kucher C, Xu X, Pasha T, Elenitsas R (2005) Histopathologic comparison of nephrogenic fibrosing dermopathy and scleromyxedema. J Cutan Pathol 32:484–490PubMed
24.
Gelpi E, de la Paz MP, Terracini B, Abaitua I, de la Cámara AG, Kilbourne EM, Lahoz C, Nemery B, Philen RM, Soldevilla L, Tarkowski S, WHO/CISAT Scientific Committee for the Toxic Oil Syndrome. Centro de Investigación para el Síndrome del Aceite Tóxico (2002) The Spanish toxic oil syndrome 20 years after its onset: a multidisciplinary review of scientific knowledge. Environ Health Perspect 110:457–464PubMedPubMedCentral
25.
Silver RM, Heyes MP, Maize JC, Quearry B, Vionnet-Fuasset M, Sternberg EM (1990) Scleroderma, fasciitis, and eosinophilia associated with the ingestion of tryptophan. N Engl J Med 322:874–881PubMed
26.
Grobner T (2006) Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 21:1104–1108PubMed
27.
28.
Penfield JG, Reilly RF Jr (2007) What nephrologists need to know about gadolinium. Nat Clin Pract Nephrol 3:654–668PubMed
29.
Broome DR, Girguis MS, Baron PW, Cottrell AC, Kjellin I, Kirk GA (2007) Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. AJR Am J Roentgenol 188:586–592PubMed
30.
Deo A, Fogel M, Cowper SE (2007) Nephrogenic systemic fibrosis: a population study examining the relationship of disease development to gadolinium exposure. Clin J Am Soc Nephrol 2:264–267PubMed
31.
Othersen JB, Maize JC, Woolson RF, Budisavljevic MN (2007) Nephrogenic systemic fibrosis after exposure to gadolinium in patients with renal failure. Nephrol Dial Transplant 22:3179–3185PubMed
32.
Reilly RF (2008) Risk for nephrogenic systemic fibrosis with gadoteridol (ProHance) in patients who are on long-term hemodialysis. Clin J Am Soc Nephrol 3:747–751PubMedPubMedCentral
33.
Gibby WA, Gibby KA, Gibby WA (2004) Comparison of Gd DTPA-BMA (Omniscan) versus Gd HP-DO3A (ProHance) retention in human bone tissue by inductively coupled plasma atomic emission spectroscopy. Invest Radiol 39:138–142PubMed
34.
High WA, Ayers RA, Chandler J, Zito G, Cowper SE (2007) Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol 56:21–26PubMed
35.
Thakral C, Abraham JL (2007) Automated scanning electron microscopy and x-ray microanalysis for in situ quantification of gadolinium deposits in skin. J Electron Microsc 56:181–187
36.
Abraham JL, Thakral C, Skov L, Rossen K, Marckmann P (2007) Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis. Br J Dermatol 158:273–280PubMed
37.
High WA, Ayers RA, Cowper SE (2007) Gadolinium is quantifiable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol 56:710–712PubMed
38.
Saussereau E, Lacroix C, Cattaneo A, Mahieu L, Goulle JP (2008) Hair and fingernail gadolinium ICP-MS contents in an overdose case associated with nephrogenic systemic fibrosis. Forensic Sci 176:54–57
39.
Morcos SK (2007) Nephrogenic systemic fibrosis following the administration of extracellular gadolinium based contrast agents: is the stability of the contrast agent molecule an important factor in the pathogenesis of this condition? Br J Radiol 80:73–76PubMed
40.
Thomsen HS, Marckmann P, Logager VB (2007) Nephrogenic systemic fibrosis (NSF): a late adverse reaction to some of the gadolinium based contrast agents. Cancer Imaging 7:130–137PubMedPubMedCentral
41.
Wedeking P, Kumar K, Tweedle MF (1992) Dissociation of gadolinium chelates in mice: relationship to chemical characteristics. Magn Reson Imaging 10:641–648PubMed
42.
Idee JM, Port M, Raynal I, Schaefer M, Le Greneur S, Corot C (2006) Clinical and biological consequences of transmetallation induced by contrast agents for magnetic resonance imaging: a review. Fundam Clin Pharmacol 20:563–576PubMed
43.
Joffe P, Thomsen HS, Meusel M (1998) Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Acad Radiol 5:491–502PubMed
44.
45.
Sadowski EA, Bennett LK, Chan MR, Wentland AL, Garrett AL, Garrett RW, Djamali A (2007) Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology 243:148–157PubMed
46.
Saab G, Abu-Alfa A (2007) Are patients with moderate renal failure at risk for developing nephrogenic systemic fibrosis? Radiology 244:930–931; author reply 931–932PubMed
47.
48.
Grobner T, Prischl FC (2007) Gadolinium and nephrogenic systemic fibrosis. Kidney Int 72:260–264PubMed
49.
Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, Thomsen HS (2006) Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 17:2359–2362PubMed
50.
Hubbard V, Davenport A, Jarmulowicz M, Rustin M (2003) Scleromyxoedema-like changes in four renal dialysis patients. Br J Dermatol 148:563–568PubMed
51.
Mackay-Wiggan JM, Cohen DJ, Hardy MA, Knobler EH, Grossman ME (2003) Nephrogenic fibrosing dermopathy (scleromyxedema-like illness of renal disease). J Am Acad Dermatol 48:55–60PubMed
52.
Swartz RD, Crofford LJ, Phan SH, Ike RW, Su LD (2003) Nephrogenic fibrosing dermopathy: a novel cutaneous fibrosing disorder in patients with renal failure. Am J Med 114:563–572PubMed
53.
Goveia M, Chan BP, Patel PR (2007) Evaluating the role of recombinant erythropoietin in nephrogenic systemic fibrosis. J Am Acad Dermatol 57:725–727PubMed
54.
Perazella MA, Ishibe S, Perazella MA, Reilly RF (2003) Nephrogenic fibrosing dermopathy: an unusual skin condition associated with kidney disease. Semin Dial 16:276–280PubMed
55.
Pieringer H, Schmekal B, Janko O, Biesenbach G (2007) Treatment with corticosteroids does not seem to benefit nephrogenic systemic fibrosis. Nephrol Dial Transplant 22:3094PubMed
56.
Gilliet M, Cozzio A, Burg G, Nestle FO (2005) Successful treatment of three cases of nephrogenic fibrosing dermopathy with extracorporeal photopheresis. Br J Dermatol 152:531–536PubMed
57.
Kintossou R, D’Incan M, Chauveau D, Bens G, Franck F, Dauplat MM, Viraben R, Déchelotte P, Souteyrand P (2007) Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis: role of gadolinium? Ann Dermatol Venereol 134:667–671PubMed
58.
Lauchli S, Zortea-Caflisch C, Nestle FO, Burg G, Kempf W (2004) Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis. Dermatology 208:278–280PubMed
59.
60.
Thomsen HS, Almen T, Morcos SK (2002) Gadolinium-containing contrast media for radiographic examinations: a position paper. Eur Radiol 12:2600–2605PubMed
61.
Morcos SK, Thomsen HS, Webb JA (1999) Contrast-media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR). Eur Radiol 9:1602–1613PubMed
62.
63.
Staatz G, Nolte-Ernsting CC, Haage P, Tacke J, Rohrmann D, Stollbrink C, Günther RW (2001) Gadolinium-enhanced T(1)-weighted MR urography versus T(2)-weighted (HASTE) MR urography in children. Rofo 173:991–996PubMed
64.
Saitoh T, Hayasaka K, Tanaka Y, Kuno T, Nagura Y (2006) Dialyzability of gadodiamide in hemodialysis patients. Radiat Med 24:445–451PubMed
65.
Broome DR, Cottrell AC, Kanal E (2007) Response to “Will dialysis prevent the development of nephrogenic systemic fibrosis after gadolinium-based contrast administration?”. AJR Am J Roentgenol 189:W234–W235PubMed
66.
67.
Dharnidharka VR, Wesson SK, Fennell RS (2006) Gadolinium and nephrogenic fibrosing dermopathy in pediatric patients. Pediatr Nephrol 22:1395PubMed
68.
DiCarlo JB, Gupta EA, Solomon AR (2007) A pediatric case of nephrogenic fibrosing dermopathy: improvement after combination therapy. J Am Acad Dermatol 54:914–916
69.
Sanchez-Ross M, Snyder R, Colome-Grimmer MI, Blumberg M, Huttenbach Y, Raimer S (2007) Nephrogenic fibrosing dermopathy in a patient with systemic lupus erythematosus and acute lupus nephritis. Pediatr Dermatol 24:E36–39PubMed
70.
Gibson SE, Farver CF, Prayson RA (2006) Multiorgan involvement in nephrogenic fibrosing dermopathy: an autopsy case and review of the literature. Arch Pathol Lab Med 130:209–212PubMed
71.
Ting WW, Stone MS, Madison KC, Kurtz K (2003) Nephrogenic fibrosing dermopathy with systemic involvement. Arch Dermatol 139:903–906PubMed
72.
Morcos SK (2007) Erratum of Nephrogenic systemic fibrosis following the administration of extracellular gadolinium based contrast agents: is the stability of the contrast agent molecule an important factor in the pathogenesis of this condition? Br J Radiol 80:586
73.
Kafi R, Fisher GJ, Quan T, Shao Y, Wang R, Voorhees JJ, Kang S (2004) UV-A1 phototherapy improves nephrogenic fibrosing dermopathy. Arch Dermatol 140:1322–1324PubMed
74.
Wahba IM, White K, Meyer M, Simpson EL (2007) The case for ultraviolet light therapy in nephrogenic fibrosing dermopathy—report of two cases and review of the literature. Nephrol Dial Transplant 22:631–636PubMed
75.
Baron PW, Cantos K, Hillebrand DJ, Hu KQ, Ojogho ON, Nehlsen-Cannarella S, Concepcion W (2003) Nephrogenic fibrosing dermopathy after liver transplantation successfully treated with plasmapheresis. Am J Dermatopathol 25:204–209PubMed
76.
Yerram P, Saab G, Karuparthi PR, Hayden MR, Khanna R (2007) Nephrogenic systemic fibrosis: a mysterious disease in patients with renal failure—role of gadolinium-based contrast media in causation and the beneficial effect of intravenous sodium thiosulfate. Clin J Am Soc Nephrol 2:258–263PubMed
77.
Chung HJ, Chung KY (2004) Nephrogenic fibrosing dermopathy: response to high-dose intravenous immunoglobulin. Br J Dermatol 150:596–597PubMed
Metadata
Title
Nephrogenic systemic fibrosis and the use of gadolinium-based contrast agents
Author
Jeffrey G. Penfield
Publication date
01-12-2008
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 12/2008
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-008-0862-6

Other articles of this Issue 12/2008

Pediatric Nephrology 12/2008 Go to the issue

Letter to the Editors

Ambulatory blood pressure in children with diabetes 1

Review

The kidney in leptospirosis

Original Article

Simvastatin ameliorates glomerulosclerosis in Adriamycin-induced-nephropathy rats

Original Article

Peritoneal membrane recruitment in rats: a micro-computerized tomography (μCT) study

Original Article

Hyponatremia in pediatric community-acquired pneumonia

Educational Feature

Nephrotoxicity as a cause of acute kidney injury in children