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Nephrogenic systemic fibrosis and its association with gadolinium exposure during MRI

Cleveland Clinic Journal of Medicine. 2008 February;75(2):95-97, 103, 106, 110-111
February 1, 2008|Cleveland Clinic Journal of Medicine
Naim Issa, MD;Emilio D. Poggio, MD;Richard A. Fatica, MD;Rajiv Patel, MD;Paul M. Ruggieri, MD;Robert J. Heyka, MD
Author and Disclosure Information

Naim Issa, MD
Department of Nephrology and Hypertension, Cleveland Clinic

Emilio D. Poggio, MD
Director of Renal Function Laboratory, Department of Nephrology and Hypertension, Cleveland Clinic

Richard A. Fatica, MD
Nephrology Fellowship Program Director, Department of Nephrology and Hypertension, Cleveland Clinic

Rajiv Patel, MD
Department of Dermatopathology, Cleveland Clinic

Paul M. Ruggieri, MD
Head, Section of Magnetic Resonance, Department of Diagnostic Radiology, Cleveland Clinic

Robert J. Heyka, MD
Director of Chronic Hemodialysis, Department of Nephrology and Hypertension, Cleveland Clinic

Address: Robert J. Heyka, MD, Department of Nephrology and Hypertension, A51, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail heykar@ccf.org.

ABSTRACTNephrogenic systemic fibrosis (NSF) is a newly recognized systemic disorder characterized by widespread tissue fibrosis in patients with impaired renal function. Recent reports suggest that NSF is associated with exposure to gadolinium-based contrast agents used in magnetic resonance imaging. NSF can be very debilitating and can lead to serious complications and death. Health care providers should exercise caution when considering the use of gadolinium-based imaging studies in patients with renal dysfunction.

KEY POINTS

  • NSF seems to arise in roughly 3% of patients with renal insufficiency who receive gadolinium, although the data are somewhat sketchy and the true incidence might be higher if the NSF is specifically looked for.
  • Manufacturers of all available gadolinium contrast agents now must include a boxed warning about the risk of NSF in patients with acute or chronic severe renal insufficiency (glomerular filtration rate < 30 mL/minute/1.73 m2) and in patients with acute renal insufficiency of any severity due to hepatorenal syndrome or in the perioperative liver transplantation period.
  • As yet, we have no effective treatment for NSF. If the patient is already on hemodialysis, it may be reasonable to perform hemodialysis immediately after exposure to gadolinium and again the next day.

TREATMENTS LACK DATA

There is no consistently successful treatment for NSF.

In isolated reports, successful kidney transplantation slowed the skin fibrosis, but these findings need to be confirmed.30,31 Data from case reports should be interpreted very cautiously, as they are by nature sporadic and anecdotal. Moreover most of the reports of NSF were published on Web sites or as editorials and did not undergo exhaustive peer review. Because the evidence is weak, kidney transplantation should not be recommended as a treatment for NSF.

Oral steroids, plasmapheresis, extracorporeal photopheresis, thalidomide, topical ultraviolet-A therapy, and other treatments have yielded very conflicting results, with only anecdotal improvement of symptoms. In a recent case report,32 the use of intravenous sodium thiosulfate in addition to aggressive physical therapy provided some benefit by reducing the pain and improving the skin lesions.

Because of the lack of strong evidence of efficacy, we cannot advocate the use of any of these treatments until larger clinical trial results are available. Aggressive physical therapy along with appropriate pain control may have benefits and should be offered to all patients suffering from NSF.

Avoid gadolinium exposure in patients with renal insufficiency

The FDA33 recently asked manufacturers to include a new boxed warning on the product labeling of all gadolinium-based contrast agents (Magnevist, MultiHance, Omniscan, Opti-MARK, ProHance), due to risk of NSF in patients with acute or chronic severe renal insufficiency (GFR < 30 mL/minute/1.73 m2) and in patients with acute renal insufficiency of any severity due to hepatorenal syndrome or in the perioperative liver transplantation period.

For the time being, gadolinium should be contraindicated in patients with acute kidney injury and chronic kidney disease stages 4 and 5 and in those who are on renal replacement therapy (either hemodialysis or peritoneal dialysis). If an MRI study with gadolinium-based contrast is absolutely required in a patient with end-stage renal disease or advanced chronic kidney disease, an agent other than gadodiamide should be used in the lowest possible dose.

Will hemodialysis prevent NSF?

In a patient who is already on hemodialysis, it seems prudent to perform hemodialysis soon after gadolinium exposure and again the day after exposure to increase gadolinium elimination. However, to date, there are no data to support the theory that doing this will prevent NSF.

Because peritoneal dialysis has been reported to clear gadolinium poorly, use of gadolinium is contraindicated. If gadolinium is absolutely needed, either more-aggressive peritoneal dialysis (keeping the abdomen “wet”) or temporary hemodialysis may be considered.

For patients with advanced chronic kidney disease who are not yet on renal replacement therapy, the use of gadolinium is contraindicated, and hemodialysis should not be empirically recommended after gadolinium exposure because we have no evidence to support its utility and because hemodialysis may cause harm.

Nephrology consultation should be considered before any gadolinium use in a patient with impaired renal function, whether acute or chronic.

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