Contrast Medium: Using Gadolinium or Iodine in Patients with Kidney Problems

Prof Stacy Goergen

What is contrast medium?

Contrast media are most frequently used in conjunction with CT and MRI. Iodine-containing contrast media are used for procedures involving X-rays, such as CT, angiography, coronary angiography, arthrography, myelography and gastrointestinal fluoroscopic studies. Gadolinium contrast agents are used for MRI studies.

Both kinds of contrast agents act similarly, but through different physical mechanisms. Iodinated agents attenuate the X-ray beam, whereas gadolinium contrast agents cause enhanced proton relaxivity.

In both cases, iodinated and gadolinium contrast media are excreted from the body via the kidneys.

What are the generally accepted indications for use of contrast medium?

Both types of agents are used to highlight neoplastic and inflammatory processes by reflecting the increased tumour circulation and inflammatory neovascularity, respectively. Contrast within fluid of hollow structures, such as blood vessels, intestines, the gall bladder and cerebrospinal fluid, enhances fluid visibility on imaging studies.

Contrast enhancement can enable diagnoses, such as active gastrointestinal bleeding, bowel rupture, liver metastases, meningitis, synovitis and blockage of a vessel detectable using medical imaging.

What are the prerequisites for using contrast medium?

  1. Clinical: providing a clear question to the radiologist on the referral form will help them to decide if contrast is required for the test or procedure.
  2. Imaging: often, but not always, part of the examination will be carried out without contrast and another part after contrast. This allows ‘contrast enhancement’ to be detected by comparing the two types of imaging. If your patient has had prior relevant imaging elsewhere, it is important to provide this or to advise the radiologist how or where it can be obtained. Comparison with prior studies might obviate the need for contrast administration, and the associated risks to the patient.
  3. Laboratory tests: patients with diabetes, known kidney disease or who are taking metformin require renal function testing for non-emergency procedures involving iodinated contrast agent administration. How recent this testing needs to be depends on consultation with the specialist radiologist and referring practitioner.

What are the absolute contraindications for the use of contrast medium?

For gadolinium contrast: previous or pre-existing nephrogenic systemic fibrosis.

For iodine contrast: there are no absolute contraindications. For each patient, the risks of iodine-containing contrast medium administration by any route must be weighed against the perceived clinical benefit to the patient of the diagnostic or therapeutic procedure (see risk factor discussion in Iodine-Containing Contrast Medium for more information).

What are the relative contraindications for the use of contrast medium?

For gadolinium contrast:

  • Previous anaphylactic/anaphylactoid reaction to gadolinium-containing contrast agent.
  • Patients with eGFR below 30 mL/min/1.73 m2. In patients with poor renal function, there is an increased risk of NSF (see below).
  • Acutely deteriorating renal function.
  • Pregnancy: the administration of contrast to a pregnant patient will be at the discretion of the supervising radiologist after consultation with the referring specialist, based on a risk–benefit assessment. Where there is uncertainty about pregnancy status, and gadolinium injection is deemed critical to the quality of the MRI examination, a pregnancy test (serum beta human chorionic gonadotropin (hCG)) should be obtained to guide the risk assessment.
  • Breast-feeding is not a contraindication to gadolinium administration (there is minimal excretion into breast milk, at levels much less than are allowed for intravenous doses in neonatal MRI). There is no requirement to express breast milk or withhold breast-feeding.

For iodine contrast:

  • Severe renal impairment, where the benefits of the iodine-containing contrast medium administration do not outweigh the small risk of contrast induced acute kidney injury (CI-AKI). However, there are risks to withholding iodine-containing contrast medium, such as reduced diagnostic accuracy, and these need to be considered in weighing risk versus benefit. Discussion with a radiologist can help to clarify the risk / benefit balance and other possible diagnostic strategies that may obviate the need for iodine-containing contrast medium in patients with severe renal impairment.
  • Active, untreated thyrotoxicosis is a relative contraindication to iodine-containing contrast medium if the procedure is not a medical emergency.
  • Active myasthenia gravis: patients should be advised about the small risk of a temporary worsening of symptoms.

Asthma, multiple allergies, severe (eGFR <30 mL/min) renal function impairment and current hyperthyroidism (clinical or biochemical) increase the risk of iodine-containing contrast medium administration. Beta-blockade can reduce or eliminate the effectiveness of adrenaline in the event of an anaphylactic reaction.

These relative contraindications to iodine-containing contrast medium administration need to be notified to the medical imaging practice/hospital because of the increased risk for the patient and to identify the patient as potentially requiring additional preparation or monitoring after iodine-containing contrast medium administration.

What are nephrogenic systemic fibrosis and contrast-induced nephropathy?

Nephrogenic systemic fibrosis (NSF) (also known as nephrogenic fibrosing dermopathy) This condition is rare and, so far, has occurred only in people with severe kidney disease. No cases were reported before 1997. It causes swelling and tightening of the skin of the arms and legs, and less often the body. It develops over days to weeks, and might reduce movement of the joints. In rare cases, it can also cause damage to internal organs. Approximately 5% of people with the most severe level of kidney function reduction will develop NSF after a gadolinium injection, and less than 5% of these people (or 3 in every 10,000 people with severely reduced kidney function) will die of it. The risk of NSF is much more common with some gadolinium contrast agents than others, and is more common after a patient has had multiple doses of gadolinium-based contrast media. It is not seen in people with normal kidney function who have gadolinium.

Improvements in kidney function, through kidney transplant or other measures, have been shown in some cases to result in remission of NSF, but this is not always the case. Certain medical conditions and procedures can increase the risk of NSF in patients with kidney function impairment and these include: vascular procedures (e.g. dialysis fistula revision, angioplasty), those with thrombotic tendency (for example, deep venous thrombosis) and those with recent onset of acute kidney failure (including transplant failure) in the weeks before developing NSF.

The risk of NSF needs to be seen in the context of how rare it is. On 8 June 2006, the American Food and Drug Administration (FDA) issued a public health advisory indicating that 25 patients who had received a gadolinium compound (Omniscan (gadodiamide)) had developed NSF. All of these patients had kidney failure, and of the 25 cases (which were reported by the Danish Medicines Agency), 20 were in Denmark and 5 in Austria. An updated warning from the FDA was issued in May 2007, and confirmed cases of NSF in patients receiving other gadolinium compounds (Omniscan, Magnevist (gadopentetate dimeglumine) and Optimark (gadoversetamide)).

Patients at greatest risk were again identified as those with acute or chronic kidney impairment, and the risk increased for patients who had received multiple doses of gadolinium compounds.

It appears that the contrast agents, Gadovist (Bayer Schering Pharma), Dotarem (Guerbet) and Prohance, are associated with a much lower chance of NSF even in patients with poor kidney function, so these are often used when it is felt that gadolinium administration is essential for diagnosis in patients with very poor kidney function. An example of this might be in a patient with cancer and neurological symptoms who needs a brain MRI to search for spread of the tumour, but who also has very poor kidney function. The use of gadolinium contrast in this situation makes it much easier in many cases for the radiologist to see evidence of early metastatic disease; that is, where the cancer has spread from the original tumour to another part of the body. One of the contrast media listed above, that are known to be much lower risk in terms of causing NSF, might be used in this situation after explaining the risk versus benefit to the patient.

Contrast-induced nephropathy There is an increased risk of this condition occurring in patients with an already reduced kidney function. The risk is increased if a patient has large amounts of iodine-containing contrast medium or multiple procedures using iodine-containing contrast medium over a short period of time; that is, hours to a few days.

Permanent decrease in kidney function would be expected in approximately 5% of people with a severe level of abnormal kidney function if they had a moderate dose of iodine contrast, say for a CT scan or an angiogram.

It can result in temporary, prolonged or permanent worsening of kidney function, which could result in the need for temporary or permanent dialysis in the most severely affected patients.

There is a clinical prediction rule available for health professionals to estimate the probability of contrast-induced nephropathy in a patient, based on risk factors.

Gadolinium does not have the potential to cause contrast-induced nephropathy.

PLEASE NOTE: If a patient has a kidney problem, the radiologist is very likely to completely avoid using gadolinium or iodine if a diagnosis can be confirmed using another test, or by carrying out a CT or MRI without gadolinium or iodine.

What are the comparative risks of gadolinium contrast medium versus iodine contrast medium?

Reference: Acta Radiologica (2007)

  Iodinated Contrast Gadolinium Contrast

The risk of a severe allergic reaction occurring

1:100,000 of people having iodinated contrast

Less than 1:170,000 of people having gadolinium contrast.

The risk of renal failure  if eGFR <30 ml/min):

20-40% will get contrast induced nephropathy (CIN)
5% will experience permanent decrease in renal function

No risk

The risk of NSF if eGFR < 15ml/min):

No risk

5%

The risk of a missed diagnosis if contrast medium is not used:

If CT scanning is inferior to MRI for the particular symptom or disease, the consequences of a missed diagnosis from the scanning procedure needs to be taken into consideration as a risk

If MRI is inferior to CT scanning for the particular symptom or disease, the consequences of a missed diagnosis from the scanning procedure needs to be taken into consideration as a risk.

The effect of a patient receiving dialysis soon after gadolinium contrast medium is given, to reduce the risk of developing NSF:

Haemodialysis

No effect

Reduces risk if performed fairly soon after the gadolinium contrast medium is given. Haemodialysis itself carries risks and unless the patient is already on haemodialysis the risks involved in starting haemodialysis probably outweigh the benefits.

Chronic ambulatory peritoneal dialysis (CAPD)

No significant effect at removing or reducing the amount of gadolinium in the circulation and tissues for many days.

What are the adverse effects of contrast medium?

Iodinated contrast

Immediate:
  1. Allergic/anaphylactic reaction.
  2. Extravasation at injection site. This is treated with warm or cold compresses and simple analgesia. Compartment syndrome or thrombophlebitis are rare complications of extravasation, and are usually seen in cases where a power injector is used and large amounts of contrast extravasated.
Delayed:
  1. Anaphylactic/allergic reactions.
  2. Thyrotoxicosis/occasionally hypothyroidism.
  3. Blockade of the thyroid preventing effectiveness of radioiodine for 8–12 weeks post-iodine contrast administration.
  4. Swelling of salivary glands.
  5. Contrast-related kidney function impairment: this is seen in less than 20% of patients with eGFR <30 mL/min, is generally biochemical only and temporary. Periprocedural hydration with intravenous saline for a few hours before and after the procedure with re-checking of renal function 72 hours after contrast administration might reduce the risk.
  6. Metformin associated lactic acidosis: this is extremely rare, and was more commonly seen when phenformin was in use. Patients with severely reduced or actively declining renal function should stop taking metformin at the time of contrast injection (this side effect is only seen with intravascular administration, as it relates entirely to the risk of renal function decrement). Renal function should be retested at about 72 hours post-administration before recommencing metformin.

Gadolinium contrast

Immediate:
  1. Allergic/anaphylactic reaction
  2. Extravasation at injection site
Delayed:
  1. Nephrogenic systemic fibrosis. For patients who are already on haemodialysis, and for whom it is decided require gadolinium chelate administration, more frequent dialysis in the 24–48 hours after gadolinium administration might reduce this risk.

Is there any specific post procedural care required following the use of contrast medium?

For side effects other than those associated with renal disease, please go to the dedicated gadolinium and iodine contrast medium topics in InsideRadiology.

Last saved on 6 October 2016.

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