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Prevalence of nephrogenic systemic fibrosis in renal insufficiency patients: Results of the FINEST study
European Journal of Radiology 73 (2010) 357–359
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Prevalence of nephrogenic systemic fibrosis in renal insufficiency patients: Results of the FINEST study Nicolas Janus a,∗ , Vincent Launay-Vacher a , Svetlana Karie a , Olivier Clement b , Elena Ledneva a , Camille Frances c , Gabriel Choukroun d , Gilbert Deray a a
Department of Nephrology, Pitié-Salpêtrière Hospital, 83 boulevard de l’Hôpital, 75013 Paris, France Department of Radiology, Georges Pompidou European Hospital, Paris, France Department of Dermatology, Tenon Hospital, Paris, France d Department of Nephrology, Amiens University Hospital, Amiens, France b c
a r t i c l e
i n f o
Article history: Received 25 August 2008 Received in revised form 6 November 2008 Accepted 21 November 2008 Keywords: Nephrognic systemic fibrosis MRI examination Gadolinium chelate
a b s t r a c t Purpose: Nephrogenic systemic fibrosis (NSF) is characterized by widespread tissue fibrosis, mainly affecting the skin. Gadolinium chelates have been implicated in the onset of NSF in patients with renal impairment (RI). The FINEST study (FIbrose Néphrogénique SysTémique) was designed to determine the prevalence of NSF after magnetic resonance imaging (MRI) in French RI patients. Materials and methods: We studied all patients with RI who had at least one MRI examination during a one-year period, with or without gadolinium chelate administration. Data were collected retrospectively from 9 Nephrology Departments in France, and included sex, age, renal function, type of gadolinium administered, and subsequent cutaneous disorders. If a patient presented a cutaneous disorder, a skin biopsy was performed to confirm the diagnostic. Results: The 308 eligible patients had a mean age of 59.9 years, 59% were men, and 54% had stage 5 RI. 75% of those 308 patients received a Gadolinium chelate. Among those patients who received a gadolinium chelate, 76% received gadoterate, 20% gadopentetate, 3% gadodiamide and 1% gadobenate. No cutaneous disorders were recorded after MRI. Conclusion: These results confirm that NSF is a rare disease. Based on a reported frequency, ∼3.5% in patients with glomerular filtration rate <30 ml/min/1.73 m2 ), some cases should have been observed in our study which included 308 patients. Most patients received gadoterate, a macrocyclic gadolinium chelate for which no case of NSF has been observed worldwide. This suggests that more stable macrocyclic agents may be less likely to induce NSF. © 2008 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Materials and methods
First described in 2000, nephrogenic systemic fibrosis (NSF) is an emerging cutaneous and systemic disorder characterized by widespread tissue fibrosis [1]. About 190 biopsy-proven cases of NSF have now been published in the literature [2]. In 2006 it was suggested that gadolinium chelates might be responsible for NSF in patients with renal impairment (RI) [3,4]. There are no data on the prevalence of NSF in French RI patients. The FINEST study (FIbrose Néphrogénique SysTémique) was thus designed to determine the prevalence of NSF in French RI patients after magnetic resonance imaging (MRI), with or without gadolinium chelate administration.
FINEST was a French national retrospective study conducted in 9 Nephrology centers. Patients were eligible if they were at least 18 years old, had a reduced glomerular filtration rate (GFR), and had at least one MRI examination, with or without gadolinium chelate administration, between 1 July 2005 and 1 July 2006. The following data were collected, from the nephrological medical file of the patients, in each case: age, sex, renal function and type of gadolinium chelate used for the MRI examination. The study was intentionally performed retrospectively in order not to influence the choice of gadolinium chelate by the physician and this in order to give a clean picture of the actual practice in France. Patients were stratified according to their renal function, by using the K/DOQI–KDIGO (kidney disease outcomes quality initiative–kidney disease improving global outcomes) classification of chronic kidney disease (CKD) from the nephrological medical file of the patients [5]. The medical files were also examined for reports
∗ Corresponding author. Tel.: +33 1 42 17 72 86; fax: +33 1 42 17 72 12. E-mail address: [email protected] (N. Janus). 0720-048X/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2008.11.021
358
N. Janus et al. / European Journal of Radiology 73 (2010) 357–359
of cutaneous disorders occurring within 4 months following MRI, including swelling, thickening, hardening of the skin, hyperpigmented patches and plaques, and burning or itching of the skin of the extremities (arms and legs) and trunk. The follow-up period was fixed to 4 months after the MRI examination. Indeed, NSF most often occurred during the first 3 months after MRI, according to the literature [4]. Patients were routinely seen by nephrologist(s) during the follow-up period. In addition, the local physicians of the 9 centres were asked if they had detected any case of NSF among their patients. The doses and the cumulative doses were not collected. 3. Results A total of 308 patients were enrolled. Their mean age was 59.9 years (18–106), and 59% of patients (181/308) were men. All patients had CKD in the K/DOQI–KDIGO classification [5] (Table 1). Among the 165 patients with stage 5 CKD, 60% (99/165) were on regular dialysis (93 on hemodialysis and 6 on peritoneal dialysis). A gadolinium chelate was administered to 75% (232/308) of the patients. Four products were used, one macrocyclic and the other three linear (Table 2). Most patients (76%, 176/232) received gadoterate; 20% (46/232) of patients received gadopentetate, and only a minority received gadodiamide (3%, 7/232) or gadobenate (1%, 3/232). Fifty-five per cent (96/176) of patients who received gadoterate had stage 5 RI (Table 3). The medical records mentioned no cutaneous disorders occurring within 4 months after MRI. All these patients were alive after the follow-up and were seen by a physician during this period.
Table 1 Renal function of FINEST study patients according to the K/DOQI–KDIGO classification (n = 308). GFR (mL/min/1.73 m2 )
Number of patients
Percent of patients
60–90 30–60 15–30 <15 No data available
22 56 62 165 3
7.1% 18.2% 20.1% 53.6% 1%
K/DOQI: kidney disease outcomes quality initiative. KDIGO: kidney disease improving global outcomes. GFR: glomerular filtration rate.
Table 2 Use of gadolinium chelates in FINEST study patients (n = 232 patients with Gd-MRI). Trade name
Chemical compound
Number of patients
Percent of patients
Dotarem® (Guerbet, France) Magnevist® (Berlex, Inc., NJ, USA/Canada and Schering AG, Germany) Omniscan® (Nycomed, Princeton, NJ, USA and GE Healthcare SA) MultiHance® (Bracco Diagnostics, Pricenton, NJ, USA)
Gadoterate Gadopentetate
176 46
75.9% 19.8%
Gadodiamide
7
3%
Gadobenate
3
1.3%
Table 3 Renal function of patients receiving gadoterate, according to the K/DOQI–KDIGO classification (n = 176). GFR (mL/min/1.73 m2 )
Number of patients
Percent of patients
60–90 30–60 15–30 <15 No data available
10 29 39 96 2
5.7% 16.5% 22.2% 54.5% 1.1%
K/DOQI: kidney disease outcomes quality initiative. KDIGO: kidney disease improving global outcomes. GFR: glomerular filtration rate.
Furthermore, after the end of the data collection, when asking the nephrologists if any case of NSF had been detected in their patients, nephrologists from two centers detected two patients with NSF (diagnosed by skin biopsy). Both patients had MRI examinations outside of the inclusion criteria for time of examination (from July 2005 to July 2006) and were therefore not included. 4. Discussion In previous study, the prevalence/incidence of NSF in stage 5 CKD patients was about 18% after gadodiamide exposure (with biopsy confirmation) [6] and about 30% after gadopentetate exposures (without biopsy confirmation) [7]. In our study, most patients received a macrocyclic gadolinium chelate (gadoterate) for which no case of NSF has been observed worldwide (Table 2). 20% of patients received gadopentetate for which a few cases have been reported [7]. 1% received gadobenate for which a few confounded cases have been reported [8]. Only 2% of patients received gadodiamide, the gadolinium chelate most often linked to NSF in CKD patients [9] (Table 2). Gadolinium chelate has been suggested to trigger NSF in CKD patients through a transmetalation mechanism [10], in which gadolinium chelate is replaced by another metal inside the chelate, leading to an exchange with the gadolinium. Gadolinium, in a free state, is highly reactive and would be expected to immediately generate a new but different molecular complex or chelate [11]. This reaction occurs readily in vitro, and there is some evidence that it may occur in vivo [12]. The main ions involved are zinc, copper, iron and calcium. Transmetalation might occur when gadolinium chelate remains in the body for lengthy periods, as demonstrated in patients with ESRD [11,13]. Thus, the stability of the chelate may determine the risk of gadolinium release and, thus, of NSF. However, patient-related factors may also contribute to creating a favorable environment for transmetalation, free gadolinium release, and NSF. Our results, together with published data and the fact that NSF has never been linked to gadoterate alone, suggest that macrocyclic gadolinium chelates may be safer than linear chelates. In 2006 and 2007, the Food and Drug Administration (FDA), the European Agency for the Evaluation of Medicinal Products (EMEA) and the French medicines agency (AFSSAPS) published recommendations on the use of gadolinium chelates in CKD patients. For the EMEA and the AFSSAPS, the use of Omniscan® (gadodiamide) and Magnevist® (gadopentetate) is now contra-indicated in patients with GFR <30 mL/min/1.73 m2 and should be used with caution in patients with moderate renal impairment (GFR 30–59 ml/min/1.73 m2 ). The FDA does not differentiate between contrast agents but rather considers that “the use of gadolinium-based contrast media in patients with moderate renal disease should be reconsidered” [14]. Furthermore, some authors suggest that Omniscan® should be avoided in all patients with CKD, whatever the stage of renal dysfunction [15,16]. Others consider that macrocyclic gadolinium chelates, which are the most stable products and have a higher affinity constant, should be preferred for patients with advanced renal impairment (GFR <25 mL/min/1.73 m2 ) [17]. For patients with GFR <30 mL/min/1.73 m2 , there are now three options. The first is to perform MRI without a gadolinium chelate, as was the case in 25% of our patients. The second option is to perform a computed tomography exam with iodinated contrast media in place of MRI with a gadolinium chelate. The problem with this approach is the potential risk of contrast-induced nephropathy (CIN) in patients with pre-existing renal impairment [18]. As such, an overall incidence of CIN in the general population have been reported to be 0.6–2.3% [19]. Additional risk factors have been described, such as pre-existing cardiovascular disease that may increase the incidence of CIN to over 20% [20]. A third option may be to use a gadolinium
N. Janus et al. / European Journal of Radiology 73 (2010) 357–359
chelate with an acceptably low risk of inducing NSF, when medical necessity warrants it. Continued accumulation of peer-reviewed published experience from centers using more stable gadolinium chelates will play an important role in validating this third option. The limitations of the study were the absence of doses, cumulative doses and the absence of systemic dermatologic exploration due to the retrospective design of the study. In our study, 77% (135/176) of patients who received an ionic macrocyclic gadolinium chelate (gadoterate) had GFR <30 mL/min/1.73 m2 , and none developed NSF (Table 3). Acknowledgments FINEST Study Group (alphabetical order): Dupuis E., Paris; Glowacki F., Lille; Jacquot C., Paris; Nivet H., Tours; Noel C., Lille; Ortiz J.P., Cabestany; Poignet J.L., Marseille; Rostoker G., Quincysous-Sénart; Vrtovsnik F., Paris. All from France. References [1] Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000;356:1000–1. [2] Broome DR. Nephrogenic systemic fibrosis associated with gadolinium based contrast agents: a summary of the medical literature reporting. Eur J Radiol 2008;66:230–4. [3] Grobner T. Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 2006;21:1104–8. [4] 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;17:2359–62. [5] Levey AS, Eckardt KU, Tsukamoto Y, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005;67:2089–100.
359
[6] Rydahl C, Thomsen HS, Marckmann P. High prevalence of nephrogenic systemic fibrosis in chronic renal failure patients exposed to gadodiamide, a gadoliniumcontaining magnetic resonance contrast agent. Invest Radiol 2008;43: 141–4. [7] Todd DJ, Kagan A, Chibnik LB, Kay J. Cutaneous changes of nephrogenic systemic fibrosis: predictor of early mortality and association with gadolinium exposure. Arthritis Rheum 2007;56:3433–41. [8] Sadowski EA, Bennett LK, Chan MR, et al. Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology 2007;243:148–57. [9] Kanal E, Broome DR, Martin DR, Thomsen HS. Response to the FDA’s May 23, 2007 nephrogenic systemic fibrosis update. Radiology 2008;246:11–4. [10] Perazella MA. Nephrogenic systemic fibrosis, kidney disease, and gadolinium: is there a link? Clin J Am Soc Nephrol 2007;2:200–2. [11] Idee JM, Port M, Raynal I, Schaefer M, Le Greneur S, Corot C. Clinical and biological consequences of transmetallation induced by contrast agents for magnetic resonance imaging: a review. Fundam Clin Pharmacol 2006;20: 563–76. [12] Laurent S, Elst LV, Muller RN. Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents. Contrast Media Mol Imaging 2006;1:128–37. [13] 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;61:905–6. [14] Chewning RH, Murphy KJ. Gadolinium-based contrast media and the development of nephrogenic systemic fibrosis in patients with renal insufficiency. J Vasc Interv Radiol 2007;18:331–3. [15] Lin SP, Brown JJ. MR contrast agents: physical and pharmacologic basics. J Magn Reson Imaging 2007;25:884–99. [16] Thomsen HS. European Society of Urogenital Radiology guidelines on contrast media application. Curr Opin Urol 2007;17:70–6. [17] Morcos SK. 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 2007;80:73–6. [18] Solomon R, Deray G. How to prevent contrast-induced nephropathy and manage risk patients: practical recommendations. Kidney Int Suppl 2006: S51–3. [19] McCullough PA, Sandberg KR. Epidemiology of contrast-induced nephropathy. Rev Cardiovasc Med 2003;4(Suppl. 5):S3–9. [20] Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int Suppl 2006:S11–5.
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Prevalence of nephrogenic systemic fibrosis in renal insufficiency patients: Results of the FINEST study Nicolas Janus a,∗ , Vincent Launay-Vacher a , Svetlana Karie a , Olivier Clement b , Elena Ledneva a , Camille Frances c , Gabriel Choukroun d , Gilbert Deray a a
Department of Nephrology, Pitié-Salpêtrière Hospital, 83 boulevard de l’Hôpital, 75013 Paris, France Department of Radiology, Georges Pompidou European Hospital, Paris, France Department of Dermatology, Tenon Hospital, Paris, France d Department of Nephrology, Amiens University Hospital, Amiens, France b c
a r t i c l e
i n f o
Article history: Received 25 August 2008 Received in revised form 6 November 2008 Accepted 21 November 2008 Keywords: Nephrognic systemic fibrosis MRI examination Gadolinium chelate
a b s t r a c t Purpose: Nephrogenic systemic fibrosis (NSF) is characterized by widespread tissue fibrosis, mainly affecting the skin. Gadolinium chelates have been implicated in the onset of NSF in patients with renal impairment (RI). The FINEST study (FIbrose Néphrogénique SysTémique) was designed to determine the prevalence of NSF after magnetic resonance imaging (MRI) in French RI patients. Materials and methods: We studied all patients with RI who had at least one MRI examination during a one-year period, with or without gadolinium chelate administration. Data were collected retrospectively from 9 Nephrology Departments in France, and included sex, age, renal function, type of gadolinium administered, and subsequent cutaneous disorders. If a patient presented a cutaneous disorder, a skin biopsy was performed to confirm the diagnostic. Results: The 308 eligible patients had a mean age of 59.9 years, 59% were men, and 54% had stage 5 RI. 75% of those 308 patients received a Gadolinium chelate. Among those patients who received a gadolinium chelate, 76% received gadoterate, 20% gadopentetate, 3% gadodiamide and 1% gadobenate. No cutaneous disorders were recorded after MRI. Conclusion: These results confirm that NSF is a rare disease. Based on a reported frequency, ∼3.5% in patients with glomerular filtration rate <30 ml/min/1.73 m2 ), some cases should have been observed in our study which included 308 patients. Most patients received gadoterate, a macrocyclic gadolinium chelate for which no case of NSF has been observed worldwide. This suggests that more stable macrocyclic agents may be less likely to induce NSF. © 2008 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
2. Materials and methods
First described in 2000, nephrogenic systemic fibrosis (NSF) is an emerging cutaneous and systemic disorder characterized by widespread tissue fibrosis [1]. About 190 biopsy-proven cases of NSF have now been published in the literature [2]. In 2006 it was suggested that gadolinium chelates might be responsible for NSF in patients with renal impairment (RI) [3,4]. There are no data on the prevalence of NSF in French RI patients. The FINEST study (FIbrose Néphrogénique SysTémique) was thus designed to determine the prevalence of NSF in French RI patients after magnetic resonance imaging (MRI), with or without gadolinium chelate administration.
FINEST was a French national retrospective study conducted in 9 Nephrology centers. Patients were eligible if they were at least 18 years old, had a reduced glomerular filtration rate (GFR), and had at least one MRI examination, with or without gadolinium chelate administration, between 1 July 2005 and 1 July 2006. The following data were collected, from the nephrological medical file of the patients, in each case: age, sex, renal function and type of gadolinium chelate used for the MRI examination. The study was intentionally performed retrospectively in order not to influence the choice of gadolinium chelate by the physician and this in order to give a clean picture of the actual practice in France. Patients were stratified according to their renal function, by using the K/DOQI–KDIGO (kidney disease outcomes quality initiative–kidney disease improving global outcomes) classification of chronic kidney disease (CKD) from the nephrological medical file of the patients [5]. The medical files were also examined for reports
∗ Corresponding author. Tel.: +33 1 42 17 72 86; fax: +33 1 42 17 72 12. E-mail address: [email protected] (N. Janus). 0720-048X/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2008.11.021
358
N. Janus et al. / European Journal of Radiology 73 (2010) 357–359
of cutaneous disorders occurring within 4 months following MRI, including swelling, thickening, hardening of the skin, hyperpigmented patches and plaques, and burning or itching of the skin of the extremities (arms and legs) and trunk. The follow-up period was fixed to 4 months after the MRI examination. Indeed, NSF most often occurred during the first 3 months after MRI, according to the literature [4]. Patients were routinely seen by nephrologist(s) during the follow-up period. In addition, the local physicians of the 9 centres were asked if they had detected any case of NSF among their patients. The doses and the cumulative doses were not collected. 3. Results A total of 308 patients were enrolled. Their mean age was 59.9 years (18–106), and 59% of patients (181/308) were men. All patients had CKD in the K/DOQI–KDIGO classification [5] (Table 1). Among the 165 patients with stage 5 CKD, 60% (99/165) were on regular dialysis (93 on hemodialysis and 6 on peritoneal dialysis). A gadolinium chelate was administered to 75% (232/308) of the patients. Four products were used, one macrocyclic and the other three linear (Table 2). Most patients (76%, 176/232) received gadoterate; 20% (46/232) of patients received gadopentetate, and only a minority received gadodiamide (3%, 7/232) or gadobenate (1%, 3/232). Fifty-five per cent (96/176) of patients who received gadoterate had stage 5 RI (Table 3). The medical records mentioned no cutaneous disorders occurring within 4 months after MRI. All these patients were alive after the follow-up and were seen by a physician during this period.
Table 1 Renal function of FINEST study patients according to the K/DOQI–KDIGO classification (n = 308). GFR (mL/min/1.73 m2 )
Number of patients
Percent of patients
60–90 30–60 15–30 <15 No data available
22 56 62 165 3
7.1% 18.2% 20.1% 53.6% 1%
K/DOQI: kidney disease outcomes quality initiative. KDIGO: kidney disease improving global outcomes. GFR: glomerular filtration rate.
Table 2 Use of gadolinium chelates in FINEST study patients (n = 232 patients with Gd-MRI). Trade name
Chemical compound
Number of patients
Percent of patients
Dotarem® (Guerbet, France) Magnevist® (Berlex, Inc., NJ, USA/Canada and Schering AG, Germany) Omniscan® (Nycomed, Princeton, NJ, USA and GE Healthcare SA) MultiHance® (Bracco Diagnostics, Pricenton, NJ, USA)
Gadoterate Gadopentetate
176 46
75.9% 19.8%
Gadodiamide
7
3%
Gadobenate
3
1.3%
Table 3 Renal function of patients receiving gadoterate, according to the K/DOQI–KDIGO classification (n = 176). GFR (mL/min/1.73 m2 )
Number of patients
Percent of patients
60–90 30–60 15–30 <15 No data available
10 29 39 96 2
5.7% 16.5% 22.2% 54.5% 1.1%
K/DOQI: kidney disease outcomes quality initiative. KDIGO: kidney disease improving global outcomes. GFR: glomerular filtration rate.
Furthermore, after the end of the data collection, when asking the nephrologists if any case of NSF had been detected in their patients, nephrologists from two centers detected two patients with NSF (diagnosed by skin biopsy). Both patients had MRI examinations outside of the inclusion criteria for time of examination (from July 2005 to July 2006) and were therefore not included. 4. Discussion In previous study, the prevalence/incidence of NSF in stage 5 CKD patients was about 18% after gadodiamide exposure (with biopsy confirmation) [6] and about 30% after gadopentetate exposures (without biopsy confirmation) [7]. In our study, most patients received a macrocyclic gadolinium chelate (gadoterate) for which no case of NSF has been observed worldwide (Table 2). 20% of patients received gadopentetate for which a few cases have been reported [7]. 1% received gadobenate for which a few confounded cases have been reported [8]. Only 2% of patients received gadodiamide, the gadolinium chelate most often linked to NSF in CKD patients [9] (Table 2). Gadolinium chelate has been suggested to trigger NSF in CKD patients through a transmetalation mechanism [10], in which gadolinium chelate is replaced by another metal inside the chelate, leading to an exchange with the gadolinium. Gadolinium, in a free state, is highly reactive and would be expected to immediately generate a new but different molecular complex or chelate [11]. This reaction occurs readily in vitro, and there is some evidence that it may occur in vivo [12]. The main ions involved are zinc, copper, iron and calcium. Transmetalation might occur when gadolinium chelate remains in the body for lengthy periods, as demonstrated in patients with ESRD [11,13]. Thus, the stability of the chelate may determine the risk of gadolinium release and, thus, of NSF. However, patient-related factors may also contribute to creating a favorable environment for transmetalation, free gadolinium release, and NSF. Our results, together with published data and the fact that NSF has never been linked to gadoterate alone, suggest that macrocyclic gadolinium chelates may be safer than linear chelates. In 2006 and 2007, the Food and Drug Administration (FDA), the European Agency for the Evaluation of Medicinal Products (EMEA) and the French medicines agency (AFSSAPS) published recommendations on the use of gadolinium chelates in CKD patients. For the EMEA and the AFSSAPS, the use of Omniscan® (gadodiamide) and Magnevist® (gadopentetate) is now contra-indicated in patients with GFR <30 mL/min/1.73 m2 and should be used with caution in patients with moderate renal impairment (GFR 30–59 ml/min/1.73 m2 ). The FDA does not differentiate between contrast agents but rather considers that “the use of gadolinium-based contrast media in patients with moderate renal disease should be reconsidered” [14]. Furthermore, some authors suggest that Omniscan® should be avoided in all patients with CKD, whatever the stage of renal dysfunction [15,16]. Others consider that macrocyclic gadolinium chelates, which are the most stable products and have a higher affinity constant, should be preferred for patients with advanced renal impairment (GFR <25 mL/min/1.73 m2 ) [17]. For patients with GFR <30 mL/min/1.73 m2 , there are now three options. The first is to perform MRI without a gadolinium chelate, as was the case in 25% of our patients. The second option is to perform a computed tomography exam with iodinated contrast media in place of MRI with a gadolinium chelate. The problem with this approach is the potential risk of contrast-induced nephropathy (CIN) in patients with pre-existing renal impairment [18]. As such, an overall incidence of CIN in the general population have been reported to be 0.6–2.3% [19]. Additional risk factors have been described, such as pre-existing cardiovascular disease that may increase the incidence of CIN to over 20% [20]. A third option may be to use a gadolinium
N. Janus et al. / European Journal of Radiology 73 (2010) 357–359
chelate with an acceptably low risk of inducing NSF, when medical necessity warrants it. Continued accumulation of peer-reviewed published experience from centers using more stable gadolinium chelates will play an important role in validating this third option. The limitations of the study were the absence of doses, cumulative doses and the absence of systemic dermatologic exploration due to the retrospective design of the study. In our study, 77% (135/176) of patients who received an ionic macrocyclic gadolinium chelate (gadoterate) had GFR <30 mL/min/1.73 m2 , and none developed NSF (Table 3). Acknowledgments FINEST Study Group (alphabetical order): Dupuis E., Paris; Glowacki F., Lille; Jacquot C., Paris; Nivet H., Tours; Noel C., Lille; Ortiz J.P., Cabestany; Poignet J.L., Marseille; Rostoker G., Quincysous-Sénart; Vrtovsnik F., Paris. All from France. References [1] Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000;356:1000–1. [2] Broome DR. Nephrogenic systemic fibrosis associated with gadolinium based contrast agents: a summary of the medical literature reporting. Eur J Radiol 2008;66:230–4. [3] Grobner T. Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 2006;21:1104–8. [4] 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;17:2359–62. [5] Levey AS, Eckardt KU, Tsukamoto Y, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005;67:2089–100.
359
[6] Rydahl C, Thomsen HS, Marckmann P. High prevalence of nephrogenic systemic fibrosis in chronic renal failure patients exposed to gadodiamide, a gadoliniumcontaining magnetic resonance contrast agent. Invest Radiol 2008;43: 141–4. [7] Todd DJ, Kagan A, Chibnik LB, Kay J. Cutaneous changes of nephrogenic systemic fibrosis: predictor of early mortality and association with gadolinium exposure. Arthritis Rheum 2007;56:3433–41. [8] Sadowski EA, Bennett LK, Chan MR, et al. Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology 2007;243:148–57. [9] Kanal E, Broome DR, Martin DR, Thomsen HS. Response to the FDA’s May 23, 2007 nephrogenic systemic fibrosis update. Radiology 2008;246:11–4. [10] Perazella MA. Nephrogenic systemic fibrosis, kidney disease, and gadolinium: is there a link? Clin J Am Soc Nephrol 2007;2:200–2. [11] Idee JM, Port M, Raynal I, Schaefer M, Le Greneur S, Corot C. Clinical and biological consequences of transmetallation induced by contrast agents for magnetic resonance imaging: a review. Fundam Clin Pharmacol 2006;20: 563–76. [12] Laurent S, Elst LV, Muller RN. Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents. Contrast Media Mol Imaging 2006;1:128–37. [13] 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;61:905–6. [14] Chewning RH, Murphy KJ. Gadolinium-based contrast media and the development of nephrogenic systemic fibrosis in patients with renal insufficiency. J Vasc Interv Radiol 2007;18:331–3. [15] Lin SP, Brown JJ. MR contrast agents: physical and pharmacologic basics. J Magn Reson Imaging 2007;25:884–99. [16] Thomsen HS. European Society of Urogenital Radiology guidelines on contrast media application. Curr Opin Urol 2007;17:70–6. [17] Morcos SK. 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 2007;80:73–6. [18] Solomon R, Deray G. How to prevent contrast-induced nephropathy and manage risk patients: practical recommendations. Kidney Int Suppl 2006: S51–3. [19] McCullough PA, Sandberg KR. Epidemiology of contrast-induced nephropathy. Rev Cardiovasc Med 2003;4(Suppl. 5):S3–9. [20] Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int Suppl 2006:S11–5.