Nephrogenic systemic fibrosis: a serious adverse reaction to gadolinium – 1997–2006–2016. Part 2

Most reports have been based on pathological or nephrological registers rather than the prospective examination of the skin of exposed patients. The prevalence of nephrogenic systemic fibrosis (NSF) after exposure to gadodiamide has been reported to be in the range of 3–7% in patients with reduced renal function (1). In patients with CKD 5 (GFR less than 15mL/min 1.73m) reviewed prospectively, it may be as much as 18% (2); all patients with suspicious lesions had a skin biopsy. The prevalence was higher after two or more injections (36%) than after a single injection (12%), indicating a cumulative effect (2). In Boston 30% of patients on dialysis had developed NSF based on a systematic examination of the patients in five dialysis centers, but skin biopsies were only taken in a few patients (3). In the peer-reviewed literature only one center has reported a large number (>10) of NSF cases after gadopentetate dimeglumine (3), but many centers have reported more than 10 cases after gadodiamide (1). This difference is not just a reflection of the market share of the two products, because gadopentetate dimeglumine has been administered to as many as 4–5 times the number of patients who have had gadodiamide. In the Four American University Study, the overall incidence was 0.039% after gadodiamide and 0.003% after gadopentetate dimeglumine (4). The benchmark incidence of NSF was one in 2913 patients who underwent gadodiamide-enhanced magnetic resonance imaging (MRI) and one in 44,224 patients who underwent gadopentetate dimeglumine-enhanced MRI (P< 0.001). The study was based on patient records from databases of dermatology, pathology, internal medicine, nephrology, transplant surgery, and radiology departments and not on a systematic examination of patients with reduced renal function exposed to a gadolinium-based contrast agent. By 1 February 2008, 190 cases (confirmed by biopsy and clinical examination) had been reported in the peerreviewed literature: 157 had had gadodiamide, eight gadopentetate, three gadoversetamide, and in five no exposure could be verified. In 18, the agent could not be identified and four received several agents (5). Up to 2012, a total of 711 NSF cases were published (6), but it is likely that they are only a small percentage of all cases. The true number of patients who developed NSF is not known because only two studies included systematic inspection of the skin in patients with reduced renal failure or on dialysis, so patients may have died with or of undiagnosed NSF between 1996 and 2006. Simple review of patient records is not enough to determine the true prevalence.