MRI with Contrast (Gadolinium-Containing) Policy

Guidelines on the Administration of Intravenous Gadolinium-Containing Contrast Media

Updated 9/14/2014 by Dr. Christopher Hess, Ben Mow, and Charlene Fong

Formulated by the UCSF Department of Radiology MRI Safety Committee, and based on FDA recommendations, ACR guidelines, and published medical literature

Risk of gadolinium administration in patients with impaired kidney function

The administration of intravenous gadolinium-containing contrast media was historically considered safe in patients with impaired renal function. In 2006 the FDA first reported the association between nephrogenic systemic fibrosis (NSF) and intravenous gadolinium  administration. This rare but serious systemic disease is characterized by fibrosis of the skin and other tissues throughout the body. NSF is generally seen in the middle-aged, but has also been reported in the elderly and in children. The exact etiology of NSF is unclear but most reported cases have been documented in patients with severe acute or chronic renal failure, with a glomerular filtration rate (GFR) < 30. Only two cases of NSF have been reported in patients with a GFR > 301. In 2009, the FDA determined that moderate renal impairment (eGFR of 30-60) was NOT a risk factor for NSF, reversing the position it had taken in December 2006, and stated2 “The December information was based upon reports of NSF among patients with purportedly moderate renal insufficiency.  Since issuing the information in December 2006, FDA has received new information regarding these patients.  Additional details have clarified that the patients actually were in acute renal failure at the time they received a gadolinium based contrast agent. Considering this clarification, FDA has not received reports of NSF among patients with normal renal function or moderate renal insufficiency”. Many of the reported cases of NSF have been in patients before or after liver transplant. Other comorbidities have been described in patients who developed NSF, including acute pro-inflammatory states, metabolic acidosis, increased iron, calcium or phosphate levels, immunosuppression, vasculopathy, high dose erythropoietine therapy and infection3. Many published series have suggested an increased risk of NSF development in patients exposed to high doses and multiple doses of gadolinium, however cases with single doses (0.1 mmol/kg) have also been reported. One meta-analysis including the seven large series of patients with NSF reported an odds ratio of 26.7 (95% CI = 10.3-69.4) for development of NSF after gadolinium administration in patients with impaired renal function (GFR < 30)4. The incidence of NSF in patients with severe renal dysfunction (GFR < 30) varies from 0.19 to 4%5-7. As of October 2007, of the 431 of the cases reported from the FDA Freedom of Information system to the authors of a review paper in the topic, 283 were associated with Omniscan, 125 were associated with Magnevist, 20 were associated with Opti-MARK, 9 were associated with ProHance (8 of which were also exposed to other agents), and 10 were associated with MultiHance (8 of which were also exposed to other agents)8. A recent publication from a single institution has recently demonstrated a positive impact of screening for NSF risk factors prior to administration of gadolinium. After guidelines based on ACR/FDA recommendations where applied, the incidence of the disease fell from 36.5/100,000 patients to 4/100,000 patients9.

Key point:  Nephrogenic systemic fibrosis (NSF) is associated with the administration of intravenous gadolinium. The primary risk factor is acute or chronic renal failure (especially dialysis dependence and/or estimated GFR < 30). 

  1. Sadowski EA, Bennett LK, Chan MR, et al. Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology 2007; 243:148-157.
  2. FDA Drug Safety Newsletter. Updated 8/13/2009. Available at http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNewsletter/ucm142889.htm.
  3. ACR Manual on Contrast Media Version 7, 2010. ACR Committee on Drugs and Contrast Media.
  4. Agarwal R, Brunelli SM, Williams K, Mitchell MD, Feldman HI, Umscheid CA. Gadolinium-based contrast agents and nephrogenic systemic fibrosis: a systematic review and meta-analysis. Nephrol Dial Transplant 2009;24: 856-863.
  5. Broome DR, Girguis MS, Baron PW, Cottrell AC, Kjellin I, Kirk GA. Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. AJR Am J Roentgenol 2007;188: 586-592.
  6. Hope TA, Herfkens RJ, Denianke KS, Leboit PE, Hung YY, Weil E. Nephrogenic Systemic Fibrosis in Patients With Chronic Kidney Disease Who Received Gadopentetate Dimeglumine. Invest Radiol 2009.
  7. Shabana WM, Cohan RH, Ellis JH, et al. Nephrogenic systemic fibrosis: a report of 29 cases. AJR Am J Roentgenol 2008;190:736-741.
  8. Penfield JG, Reilly RF. Nephrogenic systemic fibrosis risk: is there a difference between gadolinium-based contrast agents? Semin Dial 2008; 21:129-134.
  9. Perez-Rodriguez J, Lai S, Ehst BD, Fine DM, Bluemke DA. Nephrogenic systemic fibrosis: incidence, associations, and effect of risk factor assessment--report of 33 cases. Radiology 2009;250: 371-377.

Choice of gadolinium-containing contrast medium

The ACR recognizes three categories of gadolinium-containing contrast media with respect to risk of nephrogenic systemic fibrosis1. These are listed below. For simplicity, only those agents approved for use in the United States by the FDA are included:

This categorization suggests that Gadobutrol (Gadavist), gadobenate dimeglumine (MultiHance) and gadoteridol (ProHance) are preferable agents for patients at high risk for NSF (patients with acute or chronic renal insufficiency). It should be noted that the FDA does not differentiate between GCBAs with respect to the risk of NSF, regarding existing evidence as insufficient to make a definitive determination2. Based on the FDA approach and our departmental experience, we use Gadobutrol (Gadavist) as our routine gadolinium containing contrast medium.

Key point: Gadobutrol (Gadavist)is the standard gadolinium containing contrast medium used in our department for all patients, including those that are deemed high risk for nephrogenic systemic fibrosis.

    1. ACR Manual on Contrast Media Version 7, 2010. ACR Committee on Drugs and Contrast Media.
    2. FDA Drug Safety Newsletter. Updated 8/13/2009. Available at http://www.fda.gov/Drugs/DrugSafety/DrugSafetyNewsletter/ucm142889.htm
    3. FDA Drug Safety Newsletter, 9/13/2010. Available at http://www.fda.gov/Drugs/DrugSafety/ucm223966.htm

    Approach to intravenous gadolinium use in patients with impaired kidney function

    The relative risk to benefit of intravenous gadolinium in patients with severely impaired kidney function should be carefully considered by the referring physician and radiologist with input from a nephrologist if necessary. Particular caution should be considered in patients with acute renal failure or evidence of co-existing severe liver disease. No patient should be denied any imaging investigation that is critical to clinical management, which takes precedent over any other cautionary measures. Informed consent should be obtained by the radiologist if intravenous gadolinium is to be given to high risk patients.

    Key point: Gadolinium should only be given to a patient who is on dialysis or has a GFR < 30 if the contrast is considered critical to imaging for clinical management AND informed consent has been obtained by a radiologist.

    Role of dialysis after gadolinium administration in patients with renal impairment

    Dialysis does not protect patients from developing NSF1. Studies have shown that the serum concentration of gadolinium is significantly decreased after hemodialysis, however, there is no information regarding residual tissue amounts2. Theoretically, the sooner the dialysis session is performed the less amount of contrast agent is deposited in the tissues. Therefore, all patients already receiving dialysis treatment should be scheduled for dialysis as soon as practical following the gadolinium-enhanced MRI and preferably within 24 hours. This should be arranged by the requesting physician in consultation with the patient’s outpatient nephrologist and dialysis unit. Routine MRI studies should be scheduled in the morning and dialysis scheduled in the afternoon following the study; radiology scheduling staff will give morning slot priority to dialysis patients. Administration of hemodialysis promptly after gadolinium may require altering the patient’s regular outpatient dialysis schedule and advance communication several days in advance with the nephrologist and dialysis unit. There is general consensus that a patient with chronic kidney disease who is not already dialysis dependent should not be started on dialysis after administration of gadolinium for precautionary purposes only, since there is no data to support the benefits of this intervention.

    Key point: Dialysis should preferably be performed within 24 hours of gadolinium administration to patients already on dialysis. The institution of dialysis is not required in patients with severe renal impairment who are not already on dialysis after gadolinium administration.

    1. Broome DR, Cottrell AC, Kanal E. Response to "Will dialysis prevent the development of nephrogenic systemic fibrosis after gadolinium-based contrast administration?" AJR Am J Roentgenol 2007;189: W234-235.
    2. Joffe P, Thomsen HS, Meusel M. Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Acad Radiol 1998; 5: 491-502.

    Creatinine testing prior to gadolinium administration

    Laboratory results should be checked for the most recent serum creatinine on ALL patients (by the technologist performing the study). For patients with the following risk factors, serum creatinine with calculation of eGFR should be performed within 6 weeks of the MRI study:

    • Age over 60 years
    • History of “kidney disease” as an adult, including renal tumor or transplant
    • Diabetes treated with insulin or other prescribed medications
    • Hypertension (high blood pressure) requiring medication
    • Multiple myeloma
    • Solid organ transplant
    • History of severe hepatic disease/liver transplant/pending liver transplant. For patients in this category only, it is recommended that the patient's GFR assessment be nearly contemporaneous with the MR examination for which the gadolinium is to be administered.

    Estimated glomerular filtration rate (eGFR) calculation

    Estimated Glomerular Filtration Rate (eGFR) is calculated using the patient’s latest serum creatinine, documented within the past 6 weeks. In those patients who have known CKD or other risk factors for CIN as noted above, the referring provider should place a new order for serum creatinine at the time the examination is ordered if the most recent creatinine will be greater than 6 weeks old on the date of the examination. Other patients will have point-of-care creatinine values drawn at the time of the examination using the i-STAT® system. For consistency, eGFR calculation should be based on the MDRD GFR equation, which requires the creatinine level (mg/dL), age, race (African American versus other) and gender of the patient:

    eGFR  175 x Serum Cr-1.154 * age-0.203 * 1.212 (if patient is African American) * 0.742 (if female)

    An online calculator for eGFR with this formula can be found on the Internet at the following link to the National Kidney Foundation:

    http://www.kidney.org/professionals/KDOQI/gfr_calculator.cfm

    eGFR and intravenous gadolinium administration

    *If no alternative imaging technique is possible and gadolinium contrast enhanced MRI is considered critical to patient care, informed consent should be obtained by an attending radiologist using the green surgical procedure form (number 862-001Z).  A lower-risk GCBA such as Gadavist® should be used.  Annotation must be made in Radiant by the radiologist obtaining consent. The informed consent should also be documented in the dictated report.

    **The decision to administer gadolinium in a patient with moderate renal impairment (eGFR of 30-45) will always require review by a radiologist, to ensure that the risk/benefit balance merits the administration of contrast. This is a matter of physician judgment and is made on an individualized case by case basis; rigid criteria cannot be formulated to account for every conceivable scenario and are not appropriate in this setting. That said, patients with an eGFR closer to 30 are obviously of greater concern that those with an eGFR closer to 45. For example, while the FDA no longer regards moderate renal impairment (eGFR of 30-45) as a risk factor for NSF1, the ACR has suggested patients with an eGFR of 30-45 should be treated with greater caution2. The ACR also notes that acute renal impairment may be more concerning than chronic renal impairment, so that an eGFR that has recently declined to 40 may be more worrying than a chronically low eGFR of 40. Radiologists deciding to administer gadolinium to patients with an eGFR in the 30-45 range should adjust their risk/benefit analysis accordingly, requiring a more compelling clinical indication and performing a more detailed review of prior renal function. For example, a declining or fluctuating eGFR of 35 would be of more concern than a persistently stable eGFR of 35.

      1. ACR Manual on Contrast Media Version 9, 2013. ACR Committee on Drugs and Contrast Media.
      2. Kidney International Supplements (2012) 2, 19–36; doi:10.1038/kisup.2011.32.

      Pediatric eGFR and intravenous gadolinium administration

      According to the National Kidney Disease Education Program, the best equation for estimating glomerular filtration rate (GFR) from serum creatinine in children is the Bedside Isotope Dilution Mass Spectrometry (IDMS)-traceable Schwartz equation:

      http://nkdep.nih.gov/lab-evaluation/gfr-calculators/children-conventional-unit.asp

      Bedside IDMS-traceable Schwartz Equation for Children

      GFR (mL/min/1.73 m2) = (0.41 x Height in cm) / Creatinine in mg/dL)

      Off-label use of contrast media and power injectors

      Excerpt from the ACR Manual on contrast media1: “Radiologists commonly use contrast media for clinical purpose not contained in the labeling, i.e. off label use. By definition such usage is not FDA approved and the legal ramifications are unclear. Physicians have some latitude in using gadolinium chelates off label as guided by clinical circumstances but must be prepared to justify such usage in individual cases eg MR angiography, cardiac applications and pediatric applications in patients younger than 2 years. No gadolinium chelate is approved in the United States for use in a power injector”. Although gadolinium administration via a power injector is a commonly accepted practice, it is technically an off-label use of the power injector.

      1. ACR Manual on Contrast Media Version 7, 2010. ACR Committee on Drugs and Contrast Media. 

      Gadolinium and Pregnancy

      See departmental policy on CT & MRI During Pregnancy.