What Nephrologists Need to Know About Gadolinium

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Author(s)

Jeffrey G Penfield, MD

Staff Physician, Section of Nephrology, Veterans Affairs North Texas Health Care System, Dallas, Texas; Assistant Professor of Medicine, Department of Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas

Disclosures

Disclosure: Jeffrey G. Penfield, MD, has disclosed no relevant financial relationships.

Robert F Reilly, Jr, MD

Professor of Medicine; Fredric L. Coe Professor of Nephrolithiasis Research; Chief, Division of Nephrology, VA North Texas Health Care System, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas

Disclosures

Disclosure: Robert F. Reilly, Jr., MD, has disclosed no relevant financial relationships.

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Nephrogenic Systemic Fibrosis

NSF was first observed in 1997 and the initial case series published in 2000.^[31] The condition was originally known as 'nephrogenic fibrosing dermopathy' because it manifested primarily in skin. Later cases revealed more-diffuse involvement including subcutaneous tissue, striated muscle, the diaphragm and pleurae, the pericardium, and the myocardium. The name of the disorder was changed to NSF in 2005.^[32]

Potential etiological agents for NSF remained elusive for many years, but the condition was known to occur exclusively in patients with decreased renal function.^[33] The association with gadolinium chelates was first described in January 2006 in an Austrian study by Grobner.^[34] Five of nine patients who received gadodiamide developed NSF within 2-4 weeks of exposure. These patients had metabolic acidosis whereas the four patients without NSF did not, but this association was not confirmed in later reports. In May 2006, the Danish Medicines Agency reported 25 cases of NSF that had occurred after gadodiamide exposure.^[35] Five of these cases had been reported previously by Grobner, and twenty were newly reported cases from Denmark. The FDA issued a black box warning in June 2006 that was updated in December 2006 and again in May 2007. The warning reiterated the association of gadolinium chelates with NSF.

Although there is good evidence that only three of the five FDA-approved gadolinium chelates are associated with NSF, the FDA warned that all gadolinium chelates had the potential to cause NSF. The FDA recommended that gadolinium chelates be used in patients with advanced kidney failure (i.e. those on dialysis or with an estimated glomerular filtration rate [GFR] <15 ml/min per 1.73 m²) only if absolutely necessary, and that it might be prudent to initiate hemodialysis promptly after gadolinium administration in these patients. This recommendation was formulated on the basis of studies by Okada and colleagues^[36] that showed gadolinium excretion rates of 78.2%, 95.6%, 98.7% and 99.5% in the first, second, third and fourth post-gadolinium dialysis sessions, respectively.