Nephrogenic Systemic Fibrosis

Abstract

Nephrogenic systemic fibrosis (NSF) is a devastating complication of severe renal failure. Recent reports suggest that exposure to gadolinium-containing contrast agents (GCCA) is associated with the occurrence of NSF. The population of patients with ESRD in and around Bridgeport, CT, was studied during an 18-mo period. The incidence of NSF was 4.3 cases per 1000 patient-years. Each radiologic study using gadolinium presented a 2.4% risk for NSF. The association between gadolinium exposure and NSF was highly significant (P < 0.001). It is concluded that GCCA exposure is a major risk factor for NSF in the ESRD population. Because of the significant morbidity and mortality with NSF, it is believed that gadolinium exposure should be avoided in patients with ESRD. In the event that exposure cannot be avoided, careful consideration of the potential consequences, including a thorough discussion of the risks and benefits of GCCA, is advised.Clin J Am Soc Nephrol 2: 264 -267, 2007264 -267, . doi: 10.2215 N ephrogenic systemic fibrosis (NSF) is a systemic disorder that is characterized by thickening and tightening of the skin and subcutaneous tissues (1). First observed in 1997, NSF was originally known as nephrogenic fibrosing dermopathy because of its classic presentation of symmetric, brawny, or erythematous indurated cutaneous plaques that develop in the setting of renal insufficiency (2,3). Recognition that this syndrome can include fibrosis of skeletal muscle, lung, liver, testes, or myocardium with possible fatal outcomes led to the adoption of the more recent nomenclature: Nephrogenic systemic fibrosis (4,5).The cause of NSF remains speculative. Hypercoagulation syndromes, anti-phospholipid antibodies, deep vein thrombosis, metabolic acidosis, erythropoietin administration, and surgical or vascular interventions all have been implicated as possible contributing factors (6 -9). Several recent reports described the development of NSF after gadolinium exposure (9 -11). To follow up on these reports, we reviewed the use of gadolinium in our long-term dialysis population during an 18-mo period and analyzed its relationship to the development of NSF. Materials and MethodsWe retrospectively analyzed data from a population of patients who had ESRD and were living in the nine urban and suburban communities that surround Bridgeport, CT. The study population consisted of patients who had ESRD and were treated at one of three hemodialysis facilities or one peritoneal dialysis facility on July 1, 2006. These four programs were the only dialysis facilities in this geographic area, thus providing a population based study.Within this population, three cases of NSF were diagnosed in the 18-mo period that ended on July 1, 2006. Patients were identified on clinical grounds with confirmatory skin biopsies. The relationship between gadolinium exposure and NSF was documented, and details of the cases were recorded. The remaining patients who had ESRD and did not develop NSF served as the control group.We manually reviewed data from al...

Mechanism of NSF: New evidence challenging the prevailing theory

“…To date, it has only been reported in patients with severely impaired renal function (SIRF), endstage renal disease (ESRD), and those in acute renal failure (ARF) (2)(3)(4)(5). The many other risk factors thought to be associated with NSF include: edema (6), metabolic acidosis, thrombotic events, high-dose erythropoietin (EPO) (7,8), systemic inflammation (9), recent surgery, kidney disease (10), and gadolinium (Gd 3þ )-based contrast agent (GBCA) exposure (11,12), especially when used at relatively high dose GBCA (5,13).…”

The pitfalls of a purely clinical definition of nephrogenic systemic fibrosis: Comment on the article by Todd et al

“…Although we applaud the efforts of the investigators to elucidate information about this potentially devastating condition, we encourage caution in using the clinical scoring system they describe to define nephrogenic systemic fibrosis (NSF). Although there have been few systematic investigations to date, it is worthwhile to note that in the study by Todd and colleagues, the reported 13% prevalence of NSF among dialysis patients is much higher than that observed in 2 other investigations (2,3). A study from Scotland used skin biopsy, full clinical examination, and laboratory data to establish the diagnosis of NSF, and the reported prevalence among a cohort of 1,826 dialysis patients was 0.77% (2).…”

“…A study from Scotland used skin biopsy, full clinical examination, and laboratory data to establish the diagnosis of NSF, and the reported prevalence among a cohort of 1,826 dialysis patients was 0.77% (2). Similarly, a study of hemodialysis patients in Connecticut identified 3 (0.64%) of 467 dialysis patients as having NSF, based on clinical examination and skin biopsy (3). We suggest that the substantial difference in the prevalence of NSF reported by Todd et al compared with that observed in other available studies, as well as the potentially low specificity of their clinical criteria for NSF, combine to make the reported prevalence of 13% an overestimate.…”

Nephrogenic systemic fibrosis: Clinical spectrum of disease

“…In a retrospective population-based study in nine urban and suburban communities of Connecticut (January 2005 to June 2006) the absolute risk for development of NSF was 3.4% when a patient with ESRD received Gd-CA (three of 87 patients; two patients received gadodiamide, one patient gadopentetate). No cases of NSF occurred without Gd-CA exposure (n ¼ 380) (29). In a retrospective review of the medical charts from two hospitals in New York (January 1997 to June 2007), 15 patients developed NSF.…”

“…Therefore, variations in prevalence and incidence of NSF are not surprising. Nevertheless, the studies provide important insight to estimate the risk of NSF: a) patients who did not receive Gd-CA and/or have a normal renal function have virtually no risk to develop NSF (29). b) patients receiving a standard Gd-CA dose have a lower risk to develop NSF compared to patients receiving a high single dose or multiple doses (28,30).…”