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What Nephrologists Need to Know About Gadolinium: Nephrotoxicity of Gadolinium Chelates


Nephrotoxicity of Gadolinium Chelates

MRI and/or MRA with gadolinium enhancement is often used instead of iodinated-contrast radiographic methods. MRI provides superior image quality to iodinated contrast methods, and methods that use iodinated contrast are associated with a risk of acute kidney injury (AKI); for many years, gadolinium chelates were thought to be risk-free. Gadolinium is used in X-ray angiography in place of iodinated contrast, particularly in patients with chronic kidney disease (CKD). Early investigations reported that gadolinium chelates were not associated with AKI in patients with CKD (Table 2).[15-24] The limitations of these reports include small sample size, lack of control groups, poor uniformity of pretreatment regimens, variable gadolinium doses and routes of administration, and different definitions of contrast-induced nephropathy (CIN). Higher than recommended doses of gadolinium chelates (>0.2 mmol/kg) were used in several of the studies. In response to these early reports and the desire to avoid CIN, gadolinium chelates were frequently used for standard venography and arteriography, and higher doses than those approved by the FDA were administered.

Subsequent reports (Table 3) detected an increased risk of AKI associated with gadolinium chelates in patients with CKD.[25-28] These studies included more patients, one study was prospective, and the doses used were, on average, higher than those used in earlier series. There is at least one biopsy-documented case report of gadolinium-induced AKI; histological examination of the sample showed acute tubular necrosis, similar to that associated with CIN caused by iodinated contrast.[29] One case report describes a patient with CKD who received iodinated contrast for coronary angiography but suffered no nephrotoxic effects.[5] Three years later he developed AKI after receiving just 0.14 mmol/kg of gadodiamide for an MRA, indicating that gadolinium could be more nephrotoxic than iodinated contrast even at doses less than 0.2 mmol/kg.

It is not known whether the cause of nephrotoxicity associated with gadolinium chelates is the chelate itself or free gadolinium. As both gadolinium chelates and iodinated contrast cause acute tubular necrosis, it is reasonable to recommend avoiding high doses of gadolinium and maintaining adequate hydration in patients with CKD. In a 2000 position paper, the Contrast Media Safety Committee of the European Society of Urogenital Radiology recommended, on the basis of nephrotoxicity data, that gadolinium chelates should not be used in place of iodinated contrast media for radiographic examinations in patients with CKD.[30]

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