Incidence of Nephrogenic Systemic Fibrosis at Two Large Medical Centers

Nephrogenic systemic fibrosis (NSF) is a potentially severe systemic disease typically characterized by fibrosis of the skin and connective tissues. The etiology of NSF is still unknown but is likely to be multifactorial. Specific triggers under scientific evaluation have included surgery and/or the occurrence of thrombosis or other vascular injury, proinflammatory state, the administration of high doses of erythropoietin, and more recently the use of gadolinium-based contrast agents (GBCAs). The aim of this review is to summarize knowledge regarding the pathogenesis of NSF and the potential role of GBCAs in its pathology, with a focus on animal experiments. The potential role of complex stability of GCBAs will be highlighted by results from several in vitro and in vivo experiments in rodent models of NSF.

Section: Discussionsupporting

confidence: 52%

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Sieber

Steger‐Hartmann

Lengsfeld

et al. 2009

“…One article looked at the difference in NSF risk with acute renal failure between injecting high-dose GBCA while serum creatinine was rising (NSF incidence ¼ 19%) versus injecting after serum creatinine had peaked (0 cases of NSF in 41 patients) or after regular hemodialysis was started (0 cases of NSF in 32 patients) (57). This suggests that NSF risk can be substantially reduced in acute renal failure patients by either dialyzing shortly after GBCA injection or by delaying the MRI until after the serum creatinine has peaked and the renal failure is beginning to resolve.…”

Section: Acute Vs Chronic Renal Failurementioning

confidence: 99%

“…This is consistent with the widely held belief that prompt effective dialysis protects against NSF. The only article addressing this topic on patients receiving high-dose GBCA reports a 0.4% incidence of NSF in dialysis patients and 0% incidence if the dialysis is performed within 24 hours of high-dose GBCA administration, but an 8.8% incidence of NSF in patients with GFR <15 mL/ min who are not on dialysis at the time of high-dose GBCA (57). These data support the hypothesis that prompt dialysis reduces NSF risk, perhaps on the order of 20-fold.…”

Section: Timely Dialysismentioning

confidence: 99%

Risk factors for NSF: A literature review

Prince

Zhang

Roditi

et al. 2009

Self Cite

109

Emerging evidence linking gadolinium-based contrast agents (GBCAs) to nephrogenic systemic fibrosis (NSF) has changed medical practice patterns toward forgoing GBCA-enhanced magnetic resonance imaging (MRI) or substituting other imaging methods, which are potentially less accurate and often radiation-based. This shift has been based on reports of high NSF incidence at sites where a confluence of risk factors occurred in patients with severe renal dysfunction. This review article explores the factors that affect NSF risk, compares risks of alternative imaging procedures, and demonstrates how risk can be managed by careful selection of GBCA dose, timing of injection with respect to dialysis, and other factors. Nearly half of NSF cases are a milder form that does not cause contractures or reduce mobility. It appears that eliminating even a single risk factor can reduce NSF incidence/risk at least 10-fold. Elimination of multiple risk factors by using single-dose GBCA, dialyzing dialysis patients quickly following GBCA administration, avoiding GBCA in acute renal failure while serum creatinine is rising, and avoiding nonionic linear GBCA in renal failure patients may reduce NSF risk more than a thousand-fold, thereby allowing safe GBCA-enhanced MRI in virtually all patients.

“…Specifically, in this serum system there were differences in the release of Gd between Magnevist and Omniscan (Magnevist behavior appeared to be similar to the macrocyclic GBCA Dotarem and ProHance) but both Magnevist and Omniscan are associated with the greatest number of cases of NSF. The theory also does not take into account many other patient-associated factors thought to play a role-not least the fact that only a small minority of ESRD patients develop NSF (2,5). Other observations that demonstrate that other factors play a significant role in the development of NSF include:…”

Section: The Phagocytosis Of Gd Triggers Inflammatorymentioning

confidence: 99%

“…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). NSF, which was first recognized by Cowper et al (1) and linked to GBCA in 2006 (11), is characterized by induration, thickening, and tightening of the skin.…”

mentioning

confidence: 99%

Mechanism of NSF: New evidence challenging the prevailing theory

Newton¹,

Jimenez

2009

Nephrogenic systemic fibrosis (NSF) has been associated with the administration of gadolinium‐based contrast agents in patients with severely impaired renal function (SIRF), endstage renal disease (ESRD), or acute renal failure (ARF). Since the vast majority of these patients do not get NSF, it is highly likely that patient factors play a role in its development. Although “free” or dechelated gadolinium is thought by some to be the only trigger of NSF, recent evidence suggests that chelated gadolinium may be important. Chelated gadolinium such as Omniscan (gadodiamide) and Magnevist (gadopentetate) can directly stimulate macrophages and monocytes in vitro to release profibrotic cytokines and growth factors capable of initiating and supporting the tissue fibrosis that is characteristic of NSF. In addition, an effect of chelated gadolinium on fibroblasts has also been demonstrated. Chelated gadolinium in the form of Omniscan, Magnevist, MultiHance, and ProHance increased proliferation of human dermal fibroblasts. Indeed, increased numbers of macrophages, together with activated fibroblasts and fibrocytes, are essential cells in the fibrotic process and are present in NSF skin. Accordingly, it is important that chelated gadolinium, in combination with patient cofactors, is considered in the etiology of NSF associated with enhanced scans. J. Magn. Reson. Imaging 2009;30:1277–1283. © 2009 Wiley‐Liss, Inc.