Application of Extracellular Gadolinium-based MRI Contrast Agents and the Risk of Nephrogenic Systemic Fibrosis

Abstract

!Nephrogenic systemic fibrosis (NSF) is a serious, sometimes fatal disease. Findings in recent years have shown that a causal association between gadolinium containing contrast media and NSF is most likely. Therefore, the regulatory authorities have issued guidelines on the use of gadolinium-containing contrast media which have reduced the number of new cases of NSF to almost zero. However, it is for precisely this reason that the greatest care must still be taken to ensure that these guidelines are complied with. The most important factors are renal function, the quantity of gadolinium administered and coexisting diseases such as inflammation. All of these factors crucially influence the quantity of gadolinium released from the chelat in the body. This free gadolinium is thought to be the trigger for NSF. Other important factors are the stability of the gadolinium complex and furthermore the route of its elimination from the body. Partial elimination via the liver might be an additional protective mechanism. In conclusion, despite the NSF risk, contrast-enhanced MRI is a safe diagnostic procedure which can be used reliably and safely even in patients with severe renal failure, and does not necessarily have to be replaced by other methods.

Diagnosis and Treatment of Insufficient Dialysis Vascular Access

“…In principle, gadolinium-enhanced DSA is a further effective method for angiographic vessel visualization. However, this is not recommended due to the risk of nephrogenic systemic fibrosis in dialysis patients [44]. For treating dialysis vascular access, alternatives such as CT and MRI-guided interventions are currently neither more user-friendly nor more technically successful than angiography.…”

“…Limited renal function is specified as the most important patient factor for the development of NSF in the guidelines of the European Society for Urogenital Radiology [55]. However, in the case of only moderate limitation of renal function, the use of contrast agent containing gadolinium with a low or moderate NSF risk can be considered [44]. Adaptation of the contrast agent dose and protocol results in a reduced incidence of new NSF cases even in dialysis patients [56].…”

“…However, both patients had received linear gadolinium complexes with a high NSF risk. Therefore, gadolinium-enhanced MRI examination should still not be used in dialysis patients in particular if methods equivalent or superior to sonography and angiography are available for clarifying a vascular access insufficiency [44]. If MRI examination is clinically indicated for another issue, only highly stable macrocyclic gadolinium complexes with a low NSF risk should be used at the lowest possible dose in dialysis patients [59].…”

A Multicenter MRI Protocol for the Evaluation and Quantification of Deep Vein Thrombosis

“…Individuals with hip/ knee replacements and other metal implants such as screws cannot be imaged if the material is made of ferromagnetic substances. The use of Gd-based contrast agents is also contraindicated in individuals with impaired renal function due to nephrogenic systemic fibrosis (NSF) 25 .…”

The Benefits of High Relaxivity for Brain Tumor Imaging: Results of a Multicenter Intraindividual Crossover Comparison of Gadobenate Dimeglumine with Gadoterate Meglumine (The BENEFIT Study)

“…In this latter case, a clear understanding of the differences between GBCAs in terms of relaxivity and enhancement potential is fundamental to avoid misinterpretation of imaging findings (ie, to avoid interpretations of disease progression or therapy response, which, in reality, may be due solely to the different enhancement potential of various agents at equivalent doses). In regard to the risk of delayed adverse reactions, whereas gadoterate has a macrocyclic structure and is widely considered a safe GBCA based on in vitro stability data, 25 no cases of nephrogenic systemic fibrosis have yet been reported after the sole administration of gadobenate, [26][27][28] and gadobenate, like gadoterate, is considered a low-risk agent for nephrogenic systemic fibrosis by the American College of Radiology and other regulatory authorities, including the US Food and Drug Administration. 29,30 Moreover, unlike gadoterate, gadobenate has a dual route of elimination from the body, meaning that Gd 3ϩ is still eliminated via the hepatobiliary pathway in even greater amounts in patients with severely impaired renal function or end-stage renal disease.…”