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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Tissue Deposition of Gadolinium

Gadolinium can be deposited in the bone tissue of normal individuals. Deposition in bone was examined in patients with normal kidney function undergoing hip replacement after gadolinium-enhanced MRI.^[47] Gadolinium was administered 3-8 days before surgery and levels in operative bone fragments were measured. The concentration of gadolinium was four times higher (1.77 ppm) in patients who received gadodiamide than in those who received gadoteridol (0.477 ppm). This difference was attributed to the increased stability of cyclic gadoteridol compared with linear gadodiamide.^[47,48]

There are two published reports of gadolinium deposition being detected in skin affected by NSF. High et al. analyzed thirteen affected skin samples from seven patients.^[49] Gadolinium had been deposited in four of thirteen samples (four of the seven patients with NSF) at an average concentration of 70 ppm. A sample of uninvolved skin (with actinic keratosis) from a patient with NSF had a gadolinium concentration of only 5 ppm. In patients with detectable levels of gadolinium, a tissue residence time of 4-11 months was postulated on the basis of exposure history.^[49,50] There has been one report of a patient with NSF whose affected skin was examined using scanning electron microscopy and energy-dispersive X-ray spectroscopy.^[51] Interestingly, gadolinium was detected only in areas at which calcium phosphate had been deposited in blood vessels.

On the basis of the above findings, the proposed etiology for NSF is the deposition of free gadolinium in tissue, secondary to prolonged gadolinium clearance time in patients with decreased renal function. Once deposited in tissue, free gadolinium is not readily cleared by the kidney because of the poor water solubility of the agent. The most consistent improvement in NSF occurs in patients whose renal dysfunction reverses. Taken together, these findings indicate that gadolinium deposition alone cannot be the sole cause of NSF. The pathophysiologic interaction between gadolinium deposition and reduced GFR remains to be determined.