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.
Similar content being viewed by others
References
Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE (2000) Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 356:1000–1001
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 46:754–759
Auron A, Shao L, Warady BA (2006) Nephrogenic fibrosing dermopathy in children. Pediatr Nephrol 21:1307–1311
Jain SM, Wesson S, Hassanein A, Canova E, Hoy M, Fennell RS, Dharnidharka VR (2004) Nephrogenic fibrosing dermopathy in pediatric patients. Pediatr Nephrol 19:467–470
Jan F, Segal JM, Dyer J, LeBoit P, Siegfried E, Frieden IJ (2003) Nephrogenic fibrosing dermopathy: two pediatric cases. J Pediatr 143:678–681
Cowper SE (2003) Nephrogenic fibrosing dermopathy: the first 6 years. Curr Opin Rheumatol 15:785–790
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 35:238–249
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 48:42–47
Cowper SE, Bucala R (2003) Nephrogenic fibrosing dermopathy: suspect identified, motive unclear. Am J Dermatopathol 25:358
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 50:2660–2666
Parsons AC, Yosipovitch G, Sheehan DJ, Sangüeza OP, Greenberg CS, Sane DC (2007) Transglutaminases: the missing link in nephrogenic systemic fibrosis. Am J Dermatopathol 29:433–436
Cowper SE, Su LD, Bhawan J, Robin HS, LeBoit PE (2001) Nephrogenic fibrosing dermopathy. Am J Dermatopathol 23:383–393
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 30:569–577
Keyrouz S, Rudnicki SA (2007) Neuromuscular involvement in nephrogenic systemic fibrosis. J Clin Neuromuscul Dis 9:297–302
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 10:395–402
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:S31–34
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
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 245:168–175
Richmond H, Zwerner J, Kim Y, Fiorentino D (2007) Nephrogenic systemic fibrosis: relationship to gadolinium and response to photopheresis. Arch Dermatol 143:1025–1030
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 56:3433–3441
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 7:2425–2432
Weiss AS, Lucia MS, Teitelbaum I (2007) A case of nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis. Nat Clin Pract Nephrol 3:111–115
Kucher C, Xu X, Pasha T, Elenitsas R (2005) Histopathologic comparison of nephrogenic fibrosing dermopathy and scleromyxedema. J Cutan Pathol 32:484–490
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 110:457–464
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 322:874–881
Grobner T (2006) Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 21:1104–1108
Danish Medicines Agency (online 29 May 2006) Investigation of the safety of MRI contrast medium Omniscan [press release] [https://doi.org/www.dkma.dk/1024/visUKLSArtikel.asp?artikelID=8931]
Penfield JG, Reilly RF Jr (2007) What nephrologists need to know about gadolinium. Nat Clin Pract Nephrol 3:654–668
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 188:586–592
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 2:264–267
Othersen JB, Maize JC, Woolson RF, Budisavljevic MN (2007) Nephrogenic systemic fibrosis after exposure to gadolinium in patients with renal failure. Nephrol Dial Transplant 22:3179–3185
Reilly RF (2008) Risk for nephrogenic systemic fibrosis with gadoteridol (ProHance) in patients who are on long-term hemodialysis. Clin J Am Soc Nephrol 3:747–751
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 39:138–142
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 56:21–26
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
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 158:273–280
High WA, Ayers RA, Cowper SE (2007) Gadolinium is quantifiable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol 56:710–712
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
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 80:73–76
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 7:130–137
Wedeking P, Kumar K, Tweedle MF (1992) Dissociation of gadolinium chelates in mice: relationship to chemical characteristics. Magn Reson Imaging 10:641–648
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 20:563–576
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 5:491–502
European Medicines Agency: EPARs for Authorised Medicinal Products for Human Use. Available at https://doi.org/www.emea.europa.eu/humandocs/Humans/EPAR/optimark/optimark.htm, accessed 29 November 2007
Sadowski EA, Bennett LK, Chan MR, Wentland AL, Garrett AL, Garrett RW, Djamali A (2007) Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology 243:148–157
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 931–932
US Food and Drug Administration: Information on Gadolinium-Containing Contrast Agents. Available at https://doi.org/www.fda.gov/cder/drug/infopage/gcca/default.htm
Grobner T, Prischl FC (2007) Gadolinium and nephrogenic systemic fibrosis. Kidney Int 72:260–264
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 17:2359–2362
Hubbard V, Davenport A, Jarmulowicz M, Rustin M (2003) Scleromyxoedema-like changes in four renal dialysis patients. Br J Dermatol 148:563–568
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 48:55–60
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 114:563–572
Goveia M, Chan BP, Patel PR (2007) Evaluating the role of recombinant erythropoietin in nephrogenic systemic fibrosis. J Am Acad Dermatol 57:725–727
Perazella MA, Ishibe S, Perazella MA, Reilly RF (2003) Nephrogenic fibrosing dermopathy: an unusual skin condition associated with kidney disease. Semin Dial 16:276–280
Pieringer H, Schmekal B, Janko O, Biesenbach G (2007) Treatment with corticosteroids does not seem to benefit nephrogenic systemic fibrosis. Nephrol Dial Transplant 22:3094
Gilliet M, Cozzio A, Burg G, Nestle FO (2005) Successful treatment of three cases of nephrogenic fibrosing dermopathy with extracorporeal photopheresis. Br J Dermatol 152:531–536
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 134:667–671
Lauchli S, Zortea-Caflisch C, Nestle FO, Burg G, Kempf W (2004) Nephrogenic fibrosing dermopathy treated with extracorporeal photopheresis. Dermatology 208:278–280
Steen H, Schwenger V (2007) Good MRI images: to Gad or not to Gad? Pediatr Nephrol 22:1239–1242
Thomsen HS, Almen T, Morcos SK (2002) Gadolinium-containing contrast media for radiographic examinations: a position paper. Eur Radiol 12:2600–2605
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 9:1602–1613
Blondin D, Koester A, Andersen K, Kurz KD, Moedder U, Cohnen M (2007) Renal transplant failure due to urologic complications: comparison of static fluid with contrast-enhanced magnetic resonance urography. Eur J Radiol DOI https://doi.org/10.1016/j.ejrad.2007.10.026
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 173:991–996
Saitoh T, Hayasaka K, Tanaka Y, Kuno T, Nagura Y (2006) Dialyzability of gadodiamide in hemodialysis patients. Radiat Med 24:445–451
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–W235
Pharmacovigilance Working Party (PhVWP) of the Committee for Medicinal Products for Human Use (CHMP). Available at https://doi.org/www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con2030232.pdf
Dharnidharka VR, Wesson SK, Fennell RS (2006) Gadolinium and nephrogenic fibrosing dermopathy in pediatric patients. Pediatr Nephrol 22:1395
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
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:E36–39
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 130:209–212
Ting WW, Stone MS, Madison KC, Kurtz K (2003) Nephrogenic fibrosing dermopathy with systemic involvement. Arch Dermatol 139:903–906
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
Kafi R, Fisher GJ, Quan T, Shao Y, Wang R, Voorhees JJ, Kang S (2004) UV-A1 phototherapy improves nephrogenic fibrosing dermopathy. Arch Dermatol 140:1322–1324
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 22:631–636
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 25:204–209
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 2:258–263
Chung HJ, Chung KY (2004) Nephrogenic fibrosing dermopathy: response to high-dose intravenous immunoglobulin. Br J Dermatol 150:596–597
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Penfield, J.G. Nephrogenic systemic fibrosis and the use of gadolinium-based contrast agents. Pediatr Nephrol 23, 2121–2129 (2008). https://doi.org/10.1007/s00467-008-0862-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-008-0862-6