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Nephrogene systemische Fibrose (NSF) – Implikationen für die Radiologie

Nephrogenic systemic fibrosis (NSF) – implications for radiology

  • Leitthema: Kontrastmittelsichheit
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Zusammenfassung

Die nephrogene systemische Fibrose (NSF) ist eine 1997 erstmals beschriebene systemische Erkrankung mit einer 5%igen Mortalität, die bislang ausschließlich bei Patienten mit terminaler Niereninsuffizienz (glomeruläre Filtrationsrate [GFR] <30 ml/min/1,73 m2) aufgetreten ist und für die eine Assoziation mit der vorherigen Verabreichung verschiedener Gadolinium- (Gd-)haltiger MR-Kontrastmittel beobachtet wurde. Laut retrospektiver Fall-Kontroll-Studien war die Odds Ratio für die Entwicklung einer NSF bei Patienten mit stark eingeschränkter Nierenfunktion 22- bis 32-fach höher, wenn Gadodiamid verabreicht wurde. Weltweit sind zum aktuellen Zeitpunkt ca. 250 gesicherte Fälle einer NSF bekannt, von denen 177 mit der Gabe von Gadodiamid assoziiert sind, 78 mit der Gabe von Gadopentetat-Dimeglumine. Dieser Beitrag beleuchtet die Zusammenhänge von NSF und Gd-Chelaten und gibt eine Übersicht über die veröffentlichten Richtlinien internationaler Zulassungsbehörden und Fachgremien. Wenngleich der genaue Pathomechanismus der NSF-Entstehung bisher noch nicht bekannt ist, hat die europäische Pharmakovigilanz-Arbeitsgruppe dennoch entschieden, dass Gadodiamid und Gadopentetat-Dimeglumine bei bestimmten Risikopatienten nicht mehr eingesetzt werden dürfen. Für alle anderen Gd-haltigen Kontrastmittel ist eine strenge Indikationsstellung mit Minimierung der Gd-Dosis notwendig. In den USA hat die FDA für alle Gd-haltigen Kontrastmittel eine Anwendungswarnung („black box warning“) erlassen.

Abstract

Nephrogenic systemic fibrosis (NSF) is a systemic disease with a 5% mortality which was first described in 1997 and which only occurs in patients with severely impaired renal function (GFR <30 ml/min per 1.73 m2) and for which an association with previous administration of several Gd-chelates has been observed. According to retrospective case control studies the odds ratio for a patient with severely impaired renal function to develop NSF was increased by a factor of 22–32 when gadodiamide was administered. At this time there are approximately 250 confirmed cases of NSF of which 177 are associated with the administration of gadodiamide and 78 are associated with gadopentetate dimeglumine. This review article elucidates the postulated pathogenesis of NSF and provides an overview of the published statements and recommendations from international regulatory authorities and from international advisory boards. Even though the pathogenesis is not completely understood at this time, the European Pharmacovigilance Working Party has decided that gadodiamide and gadopentetate dimeglumine must not be used in high-risk patients. Other Gd-containing contrast agents should only be administered after thorough assessment of the indication and with minimized Gd dose. In the USA, the FDA has issued a black box warning for Gd-containing contrast agents.

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Literatur

  1. Cowper SE, Robin HS, Steinberg SM et al. (2000) Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 356: 1000–1001

    Article  PubMed  CAS  Google Scholar 

  2. Cowper SE (2003) Nephrogenic fibrosing dermopathy: the first 6 years. Curr Opin Rheumatol 15: 785–790

    Article  PubMed  Google Scholar 

  3. Sadowski EA, Bennett LK, Chan MR et al. (2007) Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology 243: 148–157

    PubMed  Google Scholar 

  4. 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: 2359–2362

    Article  PubMed  Google Scholar 

  5. Grobner T (2006) Gadolinium – a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 21(4): 1104–1108

    Article  PubMed  CAS  Google Scholar 

  6. GE-Healthcare (2007) http://www.amershamhealth-us.com/omniscan/GE%20Healthcare%20Paper%20On%20Nephrogenic%20Systemic%20Fibrosis.pdf

  7. Khurana A, Runge VM, Narayanan M et al. (2007) Nephrogenic systemic fibrosis: a review of 6 cases temporally related to gadodiamide injection (omniscan). Invest Radiol 42: 139–145

    Article  PubMed  Google Scholar 

  8. Broome DR, Girguis MS, Baron PW et al. (2007) Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. AJR Am J Roentgenol 188: 586–592

    Article  PubMed  Google Scholar 

  9. Bayer-Schering-Pharma (2007) http://www.berleximaging.com/html/magnevist/nsf_nfd.html

  10. Puttagunta NR, Gibby WA, Puttagunta VL (1996) Comparative transmetallation kinetics and thermodynamic stability of gadolinium-DTPA bis-glucosamide and other magnetic resonance imaging contrast media. Invest Radiol 31: 619–624

    Article  PubMed  CAS  Google Scholar 

  11. 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(950): 73–76

    Article  PubMed  CAS  Google Scholar 

  12. 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

    Article  PubMed  Google Scholar 

  13. Wible JH jr, Hynes MR (2004) Measurement of serum calcium concentration after administration of gadoversetamide in dogs. Radiology 233: 158–164

    Article  PubMed  Google Scholar 

  14. Doorenbos CJ, Ozyilmaz A, van Wijnen M (2003) Severe pseudohypocalcemia after gadolinium-enhanced magnetic resonance angiography. N Engl J Med 349: 817–818

    Article  PubMed  Google Scholar 

  15. Prince MR, Erel HE, Lent RW et al. (2003) Gadodiamide administration causes spurious hypocalcemia. Radiology 227: 639–646

    Article  PubMed  Google Scholar 

  16. Puttagunta NR, Gibby WA, Smith GT (1996) Human in vivo comparative study of zinc and copper transmetallation after administration of magnetic resonance imaging contrast agents. Invest Radiol 31: 739–742

    Article  PubMed  CAS  Google Scholar 

  17. Sieber M, Pietsch H, Walter J, Weinmann HJ (2007) Are gadolinium contrast agents a possible trigger for the development of nephrogenic fibrosing dermopathy? Eur Radiol 17(S): 158

    Google Scholar 

  18. Nael K, Michaely HJ, Kramer U et al. (2006) Pulmonary circulation: contrast-enhanced 3.0-T MR angiography – initial results. Radiology 240: 858–868

    Article  PubMed  Google Scholar 

  19. Ruehm SG, Nanz D, Baumann A et al. (2001) 3D contrast-enhanced MR angiography of the run-off vessels: value of image subtraction. J Magn Reson Imaging 13: 402–411

    Article  PubMed  CAS  Google Scholar 

  20. Wikstrom J, Holmberg A, Johansson L et al. (2000) Gadolinium-enhanced magnetic resonance angiography, digital subtraction angiography and duplex of the iliac arteries compared with intra-arterial pressure gradient measurements. Eur J Vasc Endovasc Surg 19: 516–523

    Article  PubMed  CAS  Google Scholar 

  21. Thurnher SA, Capelastegui A, Del Olmo FH et al. (2001) Safety and effectiveness of single- versus triple-dose gadodiamide injection-enhanced MR angiography of the abdomen: a phase III double-blind multicenter study. Radiology 219: 137–146

    PubMed  CAS  Google Scholar 

  22. Thomsen HS, Morcos SK, Dawson P (2006) Is there a causal relation between the administration of gadolinium based contrast media and the development of nephrogenic systemic fibrosis (NSF)? Clin Radiol 61: 905–906

    Article  PubMed  CAS  Google Scholar 

  23. Thomsen HS (2006) Nephrogenic systemic fibrosis: a serious late adverse reaction to gadodiamide. Eur Radiol 16: 2619–2621

    Article  PubMed  Google Scholar 

  24. High WA, Ayers RA, Chandler J et al. (2007) Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol 56: 21–26

    Article  PubMed  Google Scholar 

  25. Boyd AS, Zic JA, Abraham JL (2007) Gadolinium deposition in nephrogenic fibrosing dermopathy. J Am Acad Dermatol 56: 27–30

    Article  PubMed  Google Scholar 

  26. Mendoza FA, Artlett CM, Sandorfi N et al. (2006) Description of 12 cases of nephrogenic fibrosing dermopathy and review of the literature. Semin Arthritis Rheum 35: 238–249

    Article  PubMed  Google Scholar 

  27. MHRA-Homepage (2007) http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON2031545&RevisionSelectionMethod=LatestReleased

  28. Leiner T, Herborn CU, Goyen M (2007) Nephrogenic systemic fibrosis is not exclusively associated with gadodiamide. Eur Radiol: Epub ahead of print

    Google Scholar 

  29. Rodrigo E, Fernandez-Fresnedo G, Ruiz JC et al. (2003) Assessment of glomerular filtration rate in transplant recipients with severe renal insufficiency by Nankivell, modification of diet in renal disease (MDRD), and Cockroft-Gault equations. Transplant Proc 35: 1671–1672

    Article  PubMed  CAS  Google Scholar 

  30. Thomsen HS (2007) European Society of Urogenital Radiology guidelines on contrast media application. Curr Opin Urol 17: 70–76

    Article  PubMed  Google Scholar 

  31. Michaely H, Kramer H, Nael K et al. (2006) Intraindividual comparison of high-spatial resolution abdominal MRA at 1.5T and 3.0T. 573. Radiology 244(3), in press

  32. Michaely HJ, Kramer H, Lodemann KP et al. (2007) Renal MRA at 3.0T with 0.1 mmol/kg gadolinium – interindividual comparision to renal MRA at 1.5T with full dose of gadolinium. Abstract ISMRM 2007

  33. Galan A, Cowper SE, Bucala R (2006) Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy). Curr Opin Rheumatol 18: 614–617

    Article  PubMed  Google Scholar 

  34. McCullough PA, Adam A, Becker CR et al. (2006) Epidemiology and prognostic implications of contrast-induced nephropathy. Am J Cardiol 98: 5K–13K

    Article  PubMed  CAS  Google Scholar 

  35. Finn WF (2006) The clinical and renal consequences of contrast-induced nephropathy. Nephrol Dial Transplant 21: i2–i10

    Article  PubMed  Google Scholar 

  36. Miyazaki M, Takai H, Sugiura S et al. (2003) Peripheral MR angiography: separation of arteries from veins with flow-spoiled gradient pulses in electrocardiography-triggered three-dimensional half-Fourier fast spin-echo imaging. Radiology 227: 890–896

    Article  PubMed  Google Scholar 

  37. Li W, Tutton S, Vu AT et al. (2005) First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)-based blood pool agent. J Magn Reson Imaging 21: 46–52

    Article  PubMed  Google Scholar 

  38. Tombach B, Reimer P, Bremer C et al. (2004) First-pass and equilibrium-MRA of the aortoiliac region with a superparamagnetic iron oxide blood pool MR contrast agent (SH U 555 C): results of a human pilot study. NMR Biomed 17: 500–506

    Article  PubMed  Google Scholar 

  39. Rohrer M, Bauer H, Mintorovitch J et al. (2005) Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Invest Radiol 40: 715–724

    Article  PubMed  Google Scholar 

  40. Laurent S, Elst LV, Muller RN (2006) Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents. Contrast Media Mol Imaging 1: 128–137

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institut für Klinische Radiologie, Klinikum Mannheim der Universität Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Deutschland

    H.J. Michaely & S.O. Schoenberg

  2. Institut für Klinische Radiologie, Klinikum Großhadern der Ludwig-Maximilians-Universität München, München, Deutschland

    H.J. Michaely, M.F. Reiser & S.O. Schoenberg

  3. Hospital at Herlev, Copenhagen University, Kopenhagen, Dänemark

    H.S. Thomsen

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  1. H.J. Michaely
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  2. H.S. Thomsen
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  4. S.O. Schoenberg
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Correspondence to H.J. Michaely.

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Michaely, H., Thomsen, H., Reiser, M. et al. Nephrogene systemische Fibrose (NSF) – Implikationen für die Radiologie. Radiologe 47, 785–793 (2007). https://doi.org/10.1007/s00117-007-1537-1

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  • DOI: https://doi.org/10.1007/s00117-007-1537-1

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