NSF cases have been reported in patients with AKI or CKD and in renal or liver transplant recipients with compromised renal function. All patients with documented NSF had renal impairment with either ESRD, AKI, or CKD with an estimated glomerular filtration rate (GFR) below 30 mL/min per 1.73m2. Patients with ESRD appear to be at the highest risk for NSF, and those with CKD Stage 4 also appeared to be at elevated risk. Peritoneal dialysis appears to be associated with a greater risk for NSF compared to hemodialysis.4
Risk for NSF appears to increase with repeated administration with an odds ratio of 2.618.10,11 Risk for NSF appears to increase with use of double-dose (0.2 mmol/kg) compared with single-dose (0.1 mmol/kg) gadodiamide administration with an odds ratio of 12.19. Acidosis was initially reported as a risk factor favoring NSF occurrence with mean bicarbonate level of 19.5 ± 1.7 mmol/L versus 22.95 ± 0.58 mmol/L in unaffected cases.8
Mean bicarbonate level was 22.5 mmol/L, 23.5 ± 1.1 mmol/L and 22.3 ± 2.74 in three subsequent reports with no association found with NSF. Higher rHuEpo doses have been reportedly in cases with NSF but this could be a result of inflammation and resistance to rHuEpo.4,6,12 ACE inhibitors were thought to be protective but this was not consistently observed.7 Pro-inflammatory state may be a predisposing factor.10
Given the significant morbidity and mortality associated with NSF, the FDA has stated that the benefits and risks associated with using a GBCA upon recommending or performing an MRI or MRA should be carefully weighed in light of recent reports of NSF observed following administration of these agents. Alternative imaging methods and/or contrast agents should be used whenever possible. A total of five GBCA (Omniscan, OptiMARK, Magnevist, ProHance, and MultiHance) are currently approved for use in the United States.
There is no consistently successful treatment for NSF. It is not known if hemodialysis post-exposure prevents it. A current recommendation is to initiate hemodialysis within two to three hours of a GBCA administration, followed by a second session within 24 hours.13
Treatments that have been used with some success and continue to be investigated include oral steroids, plasmapher-esis, extracorporeal photopheresis and sodium thiosulfate. Additional information on NSF is available on the International Center for Nephrogenic Fibrosing Dermopathy Research Web site (www.icnfdr.org).
Dr. Abu-Alfa is associate professor of medicine at the Yale University School of Medicine in New Haven, Conn., where he is also director of the peritoneal dialysis program and associate medical director for outpatient dialysis. This information was abstracted from a presentation at the National Kidney Foundation meeting in Orlando in April 2007.
- Cowper SE, Robin HS, Steinberg SM, et al. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet. 2000;356:1000-1001.
- Jiménez SA, Artlett CM, Sandorfi N, et al. Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin. Arthritis Rheum. 2004;50:2660-2666.
- DeHoratius DM, Cowper SE. Nephrogenic systemic fibrosis: an emerging threat among renal patients. Semin Dial. 2006;19:191-194.
- Centers for Disease Control and Prevention. Nephrogenic fibrosing dermopathy associated with exposure to gadolinium-containing contrast agents—St. Louis, Missouri, 2002-2006. MMWR. 2007;56:137-141.
- Streams BN, Liu V, Liégeois N, Moschella SM. The clinical and pathologic features of nephrogenic fibrosing dermopathy: a report of two patient cases. J Am Acad Dermatol. 2003;48:42-47.
- Marckmann P, Skov L, Rossen K, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol. 2006;17:2359-2362.
- Cowper SE, Su LD, Bhawan J, et al. Nephrogenic fibrosing dermopathy. Am J Dermatopathol. 2001;23:383-393.
- Grobner T. Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant. 2006;21:1104-1108.
- Broome DR, Girguis MS, Baron PW, et al. Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. AJR Am J Roentgenol. 2007;188:586-592.
- Sadowski EA, Bennett LK, Chan MR, et al. A Study of Nephrogenic systemic fibrosis: risk factors and incidence estimation. Radiology. 2007;243(1):148-157.
- Deo A, Fogel M, Cowper SE. Nephrogenic systemic fibrosis: a population study examining the relationship of disease development to gadolinium exposure. Clin J Am Soc Nephrol. 2007;2:264-267.
- Swaminathan S, Ahmed I, McCarthy JT, et al. Nephrogenic fibrosing dermopathy and high-dose erythropoietin therapy. Ann Intern. Med 2006;145(3):234-235.
- Kuo PH, Kanal E, Abu-AlfaAK, Cowper SE. Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis. Radiology. 2007;242(3):647-649.