DOI: 10.1148/radiol.2401051442
(Radiology 2006;240:301-302.)
© RSNA, 2006
Renal Safety of Gadolinium-based Contrast Agent for Ionizing Radiation Imaging
Joshua Becker, MD* and
Henrik Thompson, MD
*Department of Radiology, NYU Medical Center, 550 First Avenue, New York, NY 10016
e-mail: joshua.becker{at}med.nyu.edu
Department of Diagnostic Radiology, Copenhagen University Hospital at Herlev, Herlev, Denmark
Editor:
In the article "Safety and Effectiveness of Gadolinium-enhanced Multi–Detector Row Spiral CT Angiography of the Chest: Preliminary Results in 37 Patients with Contraindications to Iodinated Contrast Agents" (1), which was published in the June 2005 issue of Radiology, Dr Remy-Jardin and colleagues described their experience with the substitution of gadolinium-based contrast medium as a contrast agent for x-ray–based imaging. This article, along with other publications listed in the article's reference list, addresses the safety of gadolinium-based contrast material. The amount of gadolinium-based contrast material administered was 0.3 or 0.4 mmol per kilogram of body weight, with patients receiving a potential maximum of 65 mL. Gadolinium-based media, similar to iodinated radiopaque contrast media, most likely cause nephrotoxicity, which is in part associated with the administered dose. The historical safety of gadolinium-based contrast media has been, in most instances, the result of the limited amount of contrast material used.
The authors followed up their patients for 24 hours after the injection of gadolinium-based contrast material for the determination of nephrotoxicity. This is inadequate. Articles in the nephrology literature describe the nephrotoxic effect as not being detected, based on serum creatinine levels, in some patients for up to 72 hours and uniquely, if ever, detected at 24 hours. Some patients in this study may have had contrast medium–induced nephropathy but were not identified because of the limited monitoring interval. It is also presumed that the authors determined creatinine clearance with a formula such as the Gault-Cockcroft formula (which is based on serum creatinine level) rather than by using classical creatinine clearance.
Although there is a concept of safety of gadolinium-based media with administered doses not exceeding 40 mL at 0.1 mmol of gadolinium per milliliter, documentation of impaired renal function has appeared in the literature (2).
The European Society of Urogenital Radiology, in a consensus document (3), noted that the use of gadolinium-based contrast media as a substitute for iodinated contrast media is contraindicated in patients with increased risk of nephrotoxicity. Better attenuation is obtained with iodinated contrast agents in a lower molecular dose, because one benzene ring contains three attenuating iodine atoms, whereas the gadolinium chelate contains only one attenuating gadolinium atom. In pigs, gadolinium-based contrast agents are more nephrotoxic than are radiopaque agents when administered intraarterially in equimolar doses (4).
It is not appropriate to advocate the substitution of gadolinium-based contrast agents, especially in off-label high doses, as a "renal-safe" procedure (5–9). The evidence is not there.
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References
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- Remy-Jardin M, Dequiedt P, Ertzbischoff O, et al. Safety and effectiveness of gadolinium-enhanced multi–detector row spiral CT angiography of the chest: preliminary results in 37 patients with contraindications to iodinated contrast agents. Radiology 2005;235(3):819–826.[Abstract/Free Full Text]
- Thomsen HS. Gadolinium-based contrast media may be nephrotoxic even at approved doses. Eur Radiol 2004;14:1654–1656.[Medline]
- Thomsen HS. Guidelines for contrast media from the European Society of Urogenital Radiology. AJR Am J Roentgenol 2003;181:1463–1471.[Free Full Text]
- Elmstahl B, Nyman U, Leander P, et al. Gadolinium contrast media are more nephrotoxic than a low osmolar iodine medium employing doses with equal x-ray attenuation in renal arteriography: an experimental study in pigs. Acad Radiol 2004;11:1219–1228.[CrossRef][Medline]
- Gemery J, Geldon I, Reid S, et al. Acute renal failure after arteriography with a gadolinium-based contrast agent. AJR Am J Roentgenol 1998;171:1277–1278.[Free Full Text]
- Nyman U, Elmstahl B, Leander P, Nilsson M, Golman K, Almen T. Are gadolinium-based contrast media really safer than iodinated media for digital subtraction angiography in patients with azotemia? Radiology 2002;223:311–318.[Abstract/Free Full Text]
- Sam AD 2nd, Morasch MD, Collins J, Song G, Chen R, Pereles FS. Safety of gadolinium contrast angiography in patients with chronic renal insufficiency. J Vasc Surg 2003;38(2):313–318.[CrossRef][Medline]
- Erley CM, Bader BD, Berger ED, et al. Gadolinium-based contrast media compared with iodinated media for digital subtraction angiography in azotaemic patients. Nephrol Dial Transplant 2004;19(10):2526–2531.[Abstract/Free Full Text]
- Morcos SK. Prevention of contrast media-induced nephrotoxicity after angiographic procedures. J Vasc Interv Radiol 2005;16:13–23.[Medline]
Response
Martine Remy-Jardin, MD, PhD*,
Jacques Remy, MD* and
Philippe Dequiedt, MD
Departments of Thoracic Imaging* and Nephrology, Calmette Hospital, Blvd Jules Leclercq, 59037 Lille, France
e-mail: mremy-jardin{at}chru-lille.fr
We have read with great interest the comments of Drs Becker and Thompson on our article entitled "Safety and Effectiveness of Gadolinium-enhanced Multi–Detector Row Spiral CT Angiography of the Chest: Preliminary Results in 37 Patients with Contraindications to Iodinated Contrast Agents" (1).
They are totally correct to underline that gadolinium-based contrast media may be responsible for nephrotoxicity, which is often overlooked by clinicians and/or radiologists, who are more aware of the potential nephrotoxicity of iodinated contrast agents than that of gadolinium-based contrast agents. With regard to the evaluation of the biologic tolerance of gadolinium-based contrast material in our investigation, it was assessed 24 hours after computed tomographic (CT) angiography, whereas the time interval often considered in the literature dealing with acute contrast agent–induced renal failure is 48 hours. Consequently, Drs Becker and Thompson are totally correct to underline that this protocol may have led to an underestimation of contrast agent–induced renal failure in our population; this is an important point also underlined by ourselves in the discussion of the above-mentioned article. However, this limitation was outweighed by the fact that our population was composed of inpatients who underwent periodic biologic evaluation. None of the evaluations obtained within 1 week of the gadolinium-enhanced CT examination as part of the clinical management revealed changes in the patients' renal function, especially in patients with underlying renal insufficiency. With regard to the method of determining creatinine clearance, we confirm that it was calculated by using the Gault-Cockroft formula. This parameter should have been detailed in the methodology of our article.
The last comment from Drs Becker and Thompson concerns the choice between gadolinium-based contrast media or low-concentration iodinated contrast agents in patients with increased risk of nephrotoxicity, which is a very important issue that was not addressed in our study. The cautious management of patients with chronic renal insufficiency aimed at avoiding any contrast agent–induced renal damage should not overshadow other ways of minimizing the side effects of iodinated contrast agent administration in patients with altered renal function. In this specific subset of patients, special treatments such as use of prehydration, mannitol, and frusemide have been reported to ameliorate contrast agent–induced reductions in renal function (2). Tepel et al (3) have also reported that prophylactic administration of the antioxidant acetylcysteine, along with hydration, prevented the reduction in renal function induced by a nonionic, low-osmolality iodine contrast agent in patients with renal insufficiency. The debate has recently been further enlarged by the results of a prospective, randomized, multicenter study (4) in which the likelihood of contrast medium–induced nephropathy in high-risk patients was significantly reduced when an iso-osmolar iodinated contrast medium was used instead of a low-osmolar nonionic iodinated contrast medium. Therefore, there is a need to evaluate such different approaches to define the optimal means of preventing renal damage caused by the administration of iodinated or gadolinium-based contrast agents in patients with chronic renal insufficiency.
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References
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- Remy-Jardin M, Dequiedt P, Ertzbischoff O, et al. Safety and effectiveness of gadolinium-enhanced multi-detector row spiral CT angiography of the chest: preliminary results in 37 patients with contraindications to iodinated contrast agents. Radiology 2005;235(3):819–826.[Abstract/Free Full Text]
- Solomon R, Werner C, Mann D, D'Elia J, Silva P. Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents. N Engl J Med 1994;331:1416–1420.[Abstract/Free Full Text]
- Tepel M, Van der Giet M, Schwarzfeld C, Laufer U, Lierman D, Zidek W. Prevention of radiographic-contrast-agent-induced reactions in renal function by acetylcysteine. N Engl J Med 2000;343:180–184.[Abstract/Free Full Text]
- Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491–499.[Abstract/Free Full Text]
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