TY - JOUR

T1 - Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis

AU - Abraham, J.L.

AU - Thakral, C.

AU - Skov, L.

AU - Rossen, K.

AU - Marckmann, P.

N1 - Times Cited: 7ArticleEnglishAbraham, J. LSUNY Upstate Med Univ, Dept Pathol, Syracuse, NY 13210 USACited References Count: 31253BZBLACKWELL PUBLISHING9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLANDOXFORD

PY - 2008

Y1 - 2008

N2 - Background Gadolinium (Gd)-based magnetic resonance contrast agents (GBMCA), including gadodiamide, have been identified as the probable causative agents of the serious disease, nephrogenic systemic fibrosis (NSF). Objectives To investigate retained Gd-containing deposits in skin biopsies from patients with NSF and to determine their relative concentrations over time from administration of GBMCA. Methods An investigator-blinded retrospective study, analysing 43 skin biopsies from 20 patients with gadodiamide-related NSF and one NSF-negative gadodiamide-exposed dialysis patient, ranging from 16 days to 1991 days after Gd contrast dose. Utilizing automated quantitative scanning electron microscopy/energy-dispersive X-ray spectroscopy we determined the concentration of Gd and associated elements present as insoluble deposits in situ in the tissues. Results We detected Gd in skin lesions of all 20 patients with NSF, whereas Gd was undetectable in the NSF-negative patient. Gd concentration increased over time in 60% of patients with multiple sequential biopsies (n = 10), decreasing only when the initial sampling time was > 23 months after first gadodiamide dose. All Gd-containing deposits contained phosphorus, calcium and sodium. The ratio of Gd to calcium in tissue deposits correlated positively with the gadodiamide dose and with serum ionized calcium at the time of Gd exposure. Conclusions These findings demonstrate the in vivo release (through transmetallation) of the toxic free Gd3+ from gadodiamide, and its retention in apatite-like deposits. We suggest that Gd may be mobilized over time from bone stores, explaining variably delayed onset of NSF and increasing skin concentration over time in patients with NSF Udgivelsesdato: 2008/2

AB - Background Gadolinium (Gd)-based magnetic resonance contrast agents (GBMCA), including gadodiamide, have been identified as the probable causative agents of the serious disease, nephrogenic systemic fibrosis (NSF). Objectives To investigate retained Gd-containing deposits in skin biopsies from patients with NSF and to determine their relative concentrations over time from administration of GBMCA. Methods An investigator-blinded retrospective study, analysing 43 skin biopsies from 20 patients with gadodiamide-related NSF and one NSF-negative gadodiamide-exposed dialysis patient, ranging from 16 days to 1991 days after Gd contrast dose. Utilizing automated quantitative scanning electron microscopy/energy-dispersive X-ray spectroscopy we determined the concentration of Gd and associated elements present as insoluble deposits in situ in the tissues. Results We detected Gd in skin lesions of all 20 patients with NSF, whereas Gd was undetectable in the NSF-negative patient. Gd concentration increased over time in 60% of patients with multiple sequential biopsies (n = 10), decreasing only when the initial sampling time was > 23 months after first gadodiamide dose. All Gd-containing deposits contained phosphorus, calcium and sodium. The ratio of Gd to calcium in tissue deposits correlated positively with the gadodiamide dose and with serum ionized calcium at the time of Gd exposure. Conclusions These findings demonstrate the in vivo release (through transmetallation) of the toxic free Gd3+ from gadodiamide, and its retention in apatite-like deposits. We suggest that Gd may be mobilized over time from bone stores, explaining variably delayed onset of NSF and increasing skin concentration over time in patients with NSF Udgivelsesdato: 2008/2

M3 - Journal article

VL - 158

SP - 273

EP - 280

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

IS - 2

ER -