Long-term retention of gadolinium in tissues from nephrogenic systemic fibrosis patient after multiple gadolinium-enhanced MRI scans: case report and implications.

Nephrogenic systemic fibrosis (NSF) is a painful and debilitating fibrosing disorder of the skin and systemic tissues. It is associated with exposure to Gd, used in MRIs and MRAs, in patients with renal insufficiency. We here present an illustrative example of a young patient who underwent multiple Gd-enhanced scans, both before and after developing severe NSF. We examined biopsy tissues for quantification of detectable insoluble Gd deposits using automated scanning electron microscopy/energy dispersive X-ray spectroscopy. High concentrations of Gd associated with calcium and phosphorus in skin persisted even 3 years after the last exposure to Gd. Such long-term retention of Gd raises further concerns about the utility and safety of Gd-based contrast agents. Residual Gd chelates, after initial and rapid renal clearance, can dissociate into insoluble, toxic Gd(3+) that precipitates with tissue anions. Bone serves as a site for Gd storage. Subsequent clearance and mobilization from such stores may explain the variable latency of onset of NSF. We hypothesize that long-term persistence and slow release of Gd(3+) from bone stores can be a cause for concern of Gd-associated toxicity with long latency.

[1]  L. Skov,et al.  Case-control study of gadodiamide-related nephrogenic systemic fibrosis. , 2007, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[2]  J. L. Abraham,et al.  Automated scanning electron microscopy and x-ray microanalysis for in situ quantification of gadolinium deposits in skin. , 2007, Journal of electron microscopy.

[3]  A. Djamali,et al.  Nephrogenic systemic fibrosis: risk factors and incidence estimation. , 2007, Radiology.

[4]  E. Kanal,et al.  Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis. , 2007, Radiology.

[5]  S. Cowper,et al.  Nephrogenic systemic fibrosis: a population study examining the relationship of disease development to gadolinium exposure. , 2007, Clinical journal of the American Society of Nephrology : CJASN.

[6]  W. C. O'Neill Vascular calcification: not so crystal clear. , 2007, Kidney international.

[7]  Gerald A Kirk,et al.  Gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned. , 2007, AJR. American journal of roentgenology.

[8]  J. Zic,et al.  Gadolinium deposition in nephrogenic fibrosing dermopathy. , 2007, Journal of the American Academy of Dermatology.

[9]  S. Cowper,et al.  Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis. , 2007, Journal of the American Academy of Dermatology.

[10]  M. Port,et al.  Clinical and biological consequences of transmetallation induced by contrast agents for magnetic resonance imaging: a review , 2006, Fundamental & clinical pharmacology.

[11]  Lone Skov,et al.  Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. , 2006, Journal of the American Society of Nephrology : JASN.

[12]  G. Spasovski,et al.  Evolution of bone and plasma concentration of lanthanum in dialysis patients before, during 1 year of treatment with lanthanum carbonate and after 2 years of follow-up. , 2006, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[13]  Sophie Laurent,et al.  Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents. , 2006, Contrast media & molecular imaging.

[14]  T. Grobner Gadolinium--a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? , 2006, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[15]  S. Cowper,et al.  Nephrogenic systemic fibrosis: An update , 2006, Current rheumatology reports.

[16]  M. Tweedle,et al.  Comparison of Gd(DTPA-BMA) (Omniscan) Versus Gd(HP-DO3A) (ProHance) Relative to Gadolinium Retention in Human Bone Tissue by Inductively Coupled Plasma Mass Spectroscopy , 2006, Investigative radiology.

[17]  R. Bucala,et al.  Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis--setting the record straight. , 2006, Seminars in arthritis and rheumatism.

[18]  T. Ishiguchi,et al.  Human comparative study of zinc and copper excretion via urine after administration of magnetic resonance imaging contrast agents. , 2005, Radiation medicine.

[19]  P. Leboit,et al.  Scleromyxoedema-like cutaneous diseases in renal-dialysis patients , 2000, The Lancet.

[20]  S. Hirano,et al.  Exposure, metabolism, and toxicity of rare earths and related compounds. , 1996, Environmental health perspectives.

[21]  J. Hagan,et al.  Reaction of gadolinium chelates with endogenously available ions. , 1991, Magnetic resonance imaging.

[22]  M. Markowitz,et al.  Immobilization-related lead toxicity in previously lead-poisoned children. , 1990, Pediatrics.

[23]  C. Evans Biochemistry of the Lanthanides , 1990, Biochemistry of the Elements.

[24]  W. Cacheris,et al.  The relationship between thermodynamics and the toxicity of gadolinium complexes. , 1990, Magnetic resonance imaging.

[25]  J. Hagan,et al.  Comparative chemical structure and pharmacokinetics of MRI contrast agents. , 1988 .

[26]  V. Runge Gd-DTPA: an i.v. contrast agent for clinical MRI. , 1988, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.