Role of gadolinium complexes in the mechanism of nephrogenic systemic fibrosis
type: Distribution
access URL: https://theses.hal.science/tel-00843108
format: HTML
issued: 2026-05-10T09:54:22.614118
modified: 2026-05-10T09:54:22.592234

test_moissonnage_selune
type: Agent

Role of gadolinium complexes in the mechanism of nephrogenic systemic fibrosis
type: Dataset
contact point: Organization
  fn: CCSD
keyword: theses
keyword: complexes-de-gadolinium
keyword: gadolinium-complexes
keyword: gadolinium
keyword: relaxometrie
keyword: chimothechemical-sciencesother
keyword: fibrosis
keyword: infoeu-reposemanticsdoctoralthesis
keyword: fibrose-systemique-nephrogenique
keyword: dissociation
keyword: fibrose
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: nephrogenic-systemic-fibrosis
keyword: insuffisance-renale
keyword: renal-failure
keyword: relaxometry
landing page: https://theses.hal.science/tel-00843108
description: Nephrogenic systemic fibrosis (NSF) is a rare systemic fibrosing disorder which has been described in patients with severe or end stage renal failure. NSF is associated with prior administration of certain gadolinium complexes (GCs), used as magnetic resonance imaging contrast agents, particularly those which have the lowest thermodynamic stability. The most widely accepted hypothesis regarding the mechanism is based on profibrotic effects of free Gd3+ following in vivo dissociation of the less stable GCs. Nevertheless, there is no conclusive evidence so far. The pathophysiology is not completely understood, especially due to the lack of relevant non-clinical models. The purpose of our thesis was to investigate the relationship between physicochemical properties of GCs (molecular structure, thermodynamic stability) and the risk of chronic toxicity (especially fibrosis), in order to enhance our understanding of their role in the mechanism of NSF. We have set-up various non-clinical models of NSF in renally-impaired rats. We also compared the effects of all categories of GCs on these models. A high systemic toxicity, associated with macroscopic skin lesions and dermal fibrosis, was observed after the administration of gadodiamide (a linear and nonionic GC with a low thermodynamic stability). Whereas more stable, macrocyclic GCs were well tolerated. These findings seem clinically-relevant because the vast majority of NSF cases are associated with gadodiamide. We also showed that systemic and skin toxicities depend on the baseline renal function, and that hyperphosphataemia sensitizes renally-impaired rats to the fibrotic effects of gadodiamide. Our data suggest that these factors are, actually, risk factors for NSF. We observed in vivo dissociation of two linear GCs, gadodiamide and gadopentetic acid, with gradual release of soluble Gd3+, in renally-impaired rats. Macrocyclic agents remained stable. This observation was also confirmed both in rat and human serum by the…
identifier: NNT: 2013PA05P609
issued: 2026-05-10T09:54:22.607810
language: fr
modified: 2026-05-10T09:54:22.607815