Gadolinium and Nephrogenic Systemic Fibrosis (NSF)
Gadolinium containing contrast agents have recently been associated with the development of Nephrogenic Systemic Fibrosis (NSF) and should be used with caution in patients with renal failure pending further study.
NSF, formerly known as Nephrogenic Fibrosing Dermopathy (NFD), is a rare scleroderma-like disease characterised by thickening, induration and hardening of the skin with predilection for the distal extremities and occurs only in patients with renal failure (receiving dialysis, particularly peritoneal dialysis or creatinine clearance <20mL/min). Over 200 cases have been recorded since it was originally described in 1997. Proximal involvement of the trunk and abdomen, including internal organs may occur 1,2. Sparing of the head and face in NSF is a distinguishing feature of NSF along with the absence of typical serological markers associated with scleroderma.
Diagnosis is confirmed by deep skin biopsy which demonstrates thickened collagen bundles with surrounding clefts, mucin deposition and proliferation of fibroblasts and elastic fibres. Signs of inflammation are absent histologically. 3 Disability due to limited mobility may occur in up to 58% of patients 4 and NSF has been associated with at least one patient death. 1
The US Food and Drug Administration (FDA) issued a Public Health Advisory warning in June 2006 following a notification by the Danish Health Authority of 25 cases of NSF following gadodiamide exposure. 5The European Society of Urogenital Radiology (ESUR) reports that 57 cases of NSF following gadolinium exposure have been referred to regulatory authorities with 49 cases associated with gadodiamide, 6 with gadopentetate and 2 with gadoversetamide. 6 In addition, gadolinium has been found to be present in affected tissue specimens of patients with NSF. 7,8
Gadolinium exposure has preceded the onset of NSF symptoms by 2-77 days. 3,4,9 Acidosis was implicated in one study of 9 dialysis patients exposed to gadodiamide 3 but was not confirmed in another study of 13 patients with NSF. 9 Cessation of gadolinium administration to patients with renal failure by this group resulted in no new cases of NSF. 9
The FDA has recommended that:
- “Gadolinium-containing contrast agents, especially at high doses, should be used only if clearly necessary in patients with advanced kidney failure (those currently requiring dialysis or with a Glomerular Filtration Rate (GFR) = 15 cc/min or less)”. 5
A more conservative creatinine clearance level of <30mL/min/1.73m2 has been advocated by the ESUR to help identify patients at risk. 6 In addition, the FDA has recommended instituting prompt dialysis in patients with renal failure who receive gadolinium due to previous studies demonstrating accelerated excretion of gadolinium during dialysis. 10 However, anecdotal evidence so far does not seem to support this strategy as being effective. 3
The FDA alert suggested that NSF may be a class effect and that all gadolinium-based magnetic resonance contrast agents are equally likely to cause this debilitating disease in susceptible patients. More recent evidence suggests that this may not be the case and certain agents may be more likely to cause NSF, though firm statements as to which agents are 'safest' is still pending. 11
Last reviewed May 2009.