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.

Key Points:

• Despite the inherent risk of NSF, a MR investigation must not be denied to a patient provided there are sufficient indications and the possible benefits outweigh the risk.

• The risk of NSF can be minimized by adhering to the federal guidelines and using the minimal necessary Gd dose.

• It is recommended to measure the eGFR in all patients prior to the administration of a Gd-chelate. However, it is mandatory only when using agents of the high risk group.

• Gd-chelates should classified into two risk classes. No differences should be made between low and medium risk agents.

• Partial elimination of the agent by the liver may have a protective effect against NSF.

Citation Format:

• Heverhagen JT, Krombach GA, Gizewski E. Application of Extrcellular Gadolinium-based MRI Contrast Agents and the Risk of Nephrogenic Systemic Fibrosis. Fortschr Röntgenstr 2014; 186: 661 – 669

Zusammenfassung

Die Nephrogene Systemische Fibrose (NSF) ist eine schwerwiegende Erkrankung, welche auch zum Tode führen kann. Ein kausaler Zusammenhang zwischen gadoliniumhaltigen Kontrastmitteln und NSF ist aufgrund der Erkenntnisse der letzten Jahre als gegeben anzunehmen. Aus diesem Grund haben die Zulassungsbehörden die Kontraindikationen für die Anwendung gadoliniumhaltiger Kontrastmittel erweitert. Die Umsetzung dieser Anwendungseinschränkungen hat die Anzahl der neu aufgetretenen NSF-Fälle auf nahezu Null reduziert. Trotzdem sollte weiterhin streng auf die Einhaltung der Indikationen und Kontraindikationen geachtet werden, ohne dabei Patienten dringend indizierte Untersuchungen mit gadoliniumhaltigen Kontrastmitteln zu verwehren. Die wichtigsten Faktoren für die Entstehung einer NSF sind die eingeschränkte Nierenfunktion, die Menge des applizierten Gadoliniums sowie zusätzliche Erkrankungen wie beispielsweise Entzündungen und die hiermit einhergehende Absenkung des pH-Wertes. Diese Faktoren haben einen entscheidenden Einfluss auf die im Organismus aus dem Kontrastmittelchelat frei werdenden Gadoliniumionen, den mutmaßlichen Auslöser der NSF. Hinzu kommt die Stabilität des Gadoliniumkomplexes und weiterhin auch der Ausscheidungsweg aus dem Organismus. Vermutlich stellt eine partielle Ausscheidung über die Leber einen zusätzlichen protektiven Mechanismus dar. Zusammenfassend kann festgehalten werden, dass die kontrastverstärkte MRT trotz des NSF-Risikos ein sicheres diagnostisches Verfahren darstellt, welches bei Beachtung der Anwendungsrichtlinien und aktuellen Empfehlungen auch bei Patienten mit schwerer Niereninsuffizienz sicher eingesetzt werden kann und nicht zwingend durch andere Verfahren ersetzt werden muss.

Key words

MR-imaging - contrast agents - gadolinium - safety

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