Introduction 1 4 2 5 6 peau d’orange 1 5 9 2 4 10 6 8 11 12 5 6 8 13 14 1 5 6 8 11 15 16 17 21 Link with gadolinium-based contrast agents 22 23 24 25 26 2 P 27 28 Radiology 29 26 30 32 33 34 Pathophysiology 3+ 35 40 28 41 3+ 42 41 43 45 46 47 48 49 1 Table 1 CNS MRA N/A Chemical name Trade name Manufacturer Charge and chemical structure Conditional stability at pH 7.4 (log) Excess chelate (mg/ml) Thermodynamic stability constant (log) a Body region(s) approved Approval status Approved doses for imaging (mmol/kg) Approved doses for children (mmol/kg) NSF related to gadolinium Gadodiamide Omniscan GE Healthcare Nonionic linear 14.9 12 16.9 35 s CNS, whole body USA, EU, Japan Body 0.1–0.3, CNS 0.1–0.3, MRA 0.1–0.3 From 6 months: 0.1 Yes (180 cases worldwide) Gadopentetate dimeglumine Magnevist Bayer Schering Pharma Ionic linear 17.7 0.4 22.1 10 min CNS, whole body USA, EU, Japan Body 0.1, CNS 0.1–0.2, MRA 0.1–0.3 0.1 (doses of 0.2 may be used if necessary for children older than 2 years) Yes (78 cases worldwide) Gadobenate dimeglumine MultiHance Bracco Ionic linear 16.9 None 22.6 N/A CNS, liver USA, EU Liver 0.05, CNS 0.1, MRA not approved Not approved <18 years Yes (1 case in a patient coadministered Omniscan) Gadoversetamide OptiMARK Tyco Nonionic linear 15.0 28.4 16.6 N/A CNS, liver USA Body 0.1, CNS 0.1, MRA not approved Not approved <18 years Yes Gadoterate meglumine Dotarem Guerbet Ionic cyclic 18.8 None 25.8 >1 month CNS, whole body EU Body 0.1, CNS 0.1–0.3, MRA 0.2 0.1 No Gadoteridol ProHance Bracco Nonionic cyclic 17.1 0.23 23.8 3 h CNS, whole body USA, EU, Japan Body 0.1–0.3, CNS 0.1–0.3, MRA not approved 0.1 from 2 years, caution 6 months to 2 years, contraindicated <6 months No Gadobutrol Gadovist Bayer Schering Pharma Non-ionic cyclic N/A N/A 21.8 5 min CNS, MRA EU, Canada Body not approved, CNS 0.1–0.3, MRA (imaging 1 FOV) 0.1–0.15, MRA (imaging >1 FOV) 0.2–0.3 Not approved <18 years No Gadoxetic acid Primovist Bayer Schering Pharma Ionic linear N/A N/A 23.5 N/A Liver USA, EU Body 25 μmol/kg or 0.1 ml/kg, CNS not approved, MRA not approved Not approved <18 years No Gadofosveset Vasovist Bayer Schering Pharma Ionic linear N/A N/A N/A N/A Abdominal and limb vessels EU MRA 0.03 Not approved <18 years No a Table modified from Bellin MF (2006) Eur J Radiol 60:314–323. NSF in children https://listhost.uchicago.edu/mailman/private/pedneph/ 50 51 52 22 53 54 50 Our own hospital has a large paediatric renal unit with up to 30 renal transplants per year. We have actively used MRI both for concurrent conditions and complications to CKD, as well as for providing a presurgical vascular road-map, using contrast-enhanced MRA (Gd-DTPA, Magnevist, Schering, Germany, 0.1–0.3 mmol/kg, i.v.). A review of all contrast-enhanced scans in children referred via our nephrology service (March 2002 to March 2007) showed that 75 nephrology patients (neonate to 18 years of age; median 9.6 years) had had 93 MRI scans with a follow-up of at least 6 months. There were no patients with NSF in this high-risk cohort. Regulatory advice 2 2 http://www.mhra.gov.uk 2 2 Table 2 Websites for regulatory updates and for information and registration of cases (accessed on 20 September 2007) Organization Information provided URL European Medicines Agency Regulatory information http://www.emea.europa.eu/ US Food and Drug Administration Regulatory information http://www.fda.gov/cder/drug/infopage/gcca/default.htm Information for healthcare professionals http://www.fda.gov/cder/drug/InfoSheets/HCP/gcca_200705.htm International Center for Nephrogenic Fibrosing Dermopathy Research Updated information and contact details for registration of cases http://www.icnfdr.org/ Consequences for paediatric practice 2 The absolute risk of gadolinium exposure, as well as the risk associated with the suspected contributing clinical and biochemical factors, is unknown. Each case must therefore be assessed individually. The risk attributable to the kinetic stability of different gadolinium-based agents is not clear. The majority of cases have been reported in association with a less stable agent (gadodiamide); however, we are still in an early stage of recording cases, and also the market share and the actual use of different agents in this patient population is not fully known. Thus, it seems reasonable to discontinue the use of gadodiamide in at-risk patients. The relationship to dose is not completely known. Since there is no indication that we are dealing with a side effect not related to dose, it seems reasonable to reduce the dose of gadolinium if possible, and also to monitor the cumulative dose in at-risk patients. It is unclear whether acidosis correction before gadolinium administration and haemodialysis immediately after gadolinium administration can prevent the development of, or treat, NSF, but such actions should be considered in children already on haemodialysis. This underlines the necessity for good communication between radiologists and nephrologists, both for issuing local guidelines and for management of the individual child. It is often the case that MRI is requested after an inconclusive US examination. In our own experience, more meticulous patient preparation and dedicated rescanning of the patient with US can often give diagnostically adequate results. In patients with CKD not yet on dialysis CT is not a desirable alternative due to ionizing radiation and the nephrotoxicity of iodinated contrast agents. However, CT may provide an option in patients who are already on dialysis. MRI without intravenous contrast agent administration has not yet been validated for vascular anatomy prior to renal transplantation, but several techniques may be valuable, such as 3-D-balanced steady-state free precession imaging and time-of-flight angiography. Patients with renal impairment may be referred for MRI from non-nephrology units and a crucial question is how to identify them. Our approach would be to include a mandatory tick box on the referral form requiring the referring clinician’s statement about renal function, and also to include a question about any known renal problems on the patient/guardian prescan checklist. This is a pragmatic approach, which will need revision after an initial phase. Conclusion We would advocate prudence, and in practice suggest: Information collection from clinicians and patients/guardians on renal dysfunction and active collaboration with the local nephrology unit. A case-by-case assessment in terms of the necessity for gadolinium-enhanced MRI, and whether an alternative test (repeat US, noncontrast-enhanced MRI, CT) would be acceptable. Cumulative dose recording, reduction of the dose of any gadolinium-based contrast agent, and acting accordingly to guidance published in the literature. Longer follow-up, especially in high-risk children. GFR measurement or estimation should be part of a systematic prescan investigation in children with known or suspected renal dysfunction; however, a general screening is probably not justified. To minimize the risks, we should take advantage of the current knowledge, and would suggest using cyclic nonionic compounds as they are more stable in vitro and therefore theoretically less likely to undergo transmetallation.