The role of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: A critical update

Abstract

Nephrogenic systemic fibrosis (NSF) is an iatrogenic scleroderma-like fibrosing systemic disorder occurring in patients with severe or end-stage renal disease. It was established as a new clinical entity in the year 2000. A causal role for gadolinium chelates (GC), widely used as contrast agents for magnetic resonance imaging, was suggested six years later. It rapidly appeared that the occurrence of NSF was associated with prior administration of GCs with lower thermodynamic stability, leading to warnings being published by health authorities and learned societies worldwide. Although a role for the chelated form of the less stable GCs has been proposed, the most commonly accepted hypothesis involves the gradual release of dissociated gadolinium in the body, leading to systemic fibrosis. However, the entire chain of events is still not fully understood in a causal way and many uncertainties remain.

Keywords:

• contrast agents
• circulating fibrocytes
• fibroblasts
• gadolinium
• gadolinium chelates
• kidney diseases
• magnetic resonance imaging
• nephrogenic systemic fibrosis
• transmetallation

Acknowledgments

The authors thank Dr Stéphanie Louguet for helpful discussions and Dr Anthony Saul for reviewing the English version of the manuscript.

Declaration of interest

All authors are employees of Guerbet. Guerbet markets contrast agents and specifically gadoteric acid, a gadolinium chelate subject to the present review among other agents. The authors do not appear in any regulatory and legal proceedings related to the molecules under review. The article was reviewed by in-house legal counsel. The findings and conclusions of this compilation are those of the individual authors and do not necessarily state or reflect those of Guerbet.