Safety of Gadolinium-Based Contrast Agents in Patients with Stage 4 and 5 Chronic Kidney Disease: a Radiologist's Perspective.

Abstract

Gadolinium-based contrast agents (GBCAs) have been used for contrast-enhanced magnetic resonance imaging (MRI) since 1988 with >450 million intravenous GBCA doses administered worldwide and overall have had an excellent safety record (1,2). Numerous studies have demonstrated the benefit of GBCAs for a variety of diagnostic indications including improving sensitivity and specificity for malignancy, demyelination, central nervous system malignancy, and infection (3⇓⇓⇓–7). Initially, it was thought that GBCAs would be safer than iodinated contrast media for patients with kidney disease because they are less nephrotoxic at clinically administered doses (8). Although some case reports have linked AKI to GBCA administration, most cases involve patients with advanced renal disease or diabetes and with doses that exceed US Food and Drug Administration (FDA) recommendations (8). The safety of GBCAs in patients with kidney disease came into question in 2006 when a strong association was found between the use of GBCAs in patients with severe kidney disease and the development of nephrogenic systemic fibrosis (NSF) (9⇓–11). NSF results in fibrosis of the skin and internal organs and can be fatal. A conclusive mechanism of causation for NSF has not been determined. Several mouse models of NSF have been developed to investigate the underlying pathophysiology; however, they tend to use doses which are higher than those approved by the FDA and older linear agents (12⇓–14). A confounding issue is that many people with severe kidney disease received multiple exposures to GBCAs and did not develop NSF. Conversely, patients with only one administration of a GBCA have developed NSF (15,16). It is unclear if this could at least partially relate to interspecies differences. Multiple factors may contribute, most notably patient-specific risk factors and the stability of the GBCA, which is …