What nephrologists need to know about gadolinium

Gadolinium chelates are commonly used to improve tissue contrast in MRI. Until recently the use of gadolinium was thought to be risk-free compared with alternative contrast agents. Recent studies, however, have raised serious concerns regarding the safety of gadolinium chelates. Although safe in patients with normal kidney function, administration of these agents in people with renal dysfunction can result in up to three clinical problems that the nephrologist should be familiar with. The first is nephrogenic systemic fibrosis (NSF), which was initially observed in 1997. Although manifesting primarily in skin, NSF can also cause systemic fibrosis, leading to disabling contractures and even death. Gadodiamide is the agent that has been most frequently associated with NSF, but other chelates might also pose a risk. The second clinical problem is that gadolinium chelates cause acute kidney injury, especially at high doses required for angiography. The third problem is that several laboratory artifacts are associated with gadolinium administration, with pseudohypocalcemia being the most important. The risk of a patient experiencing all three of these complications increases as renal function declines. In light of these problems, nephrologists need to re-evaluate the risks and benefits of gadolinium administration in patients with chronic kidney disease stage 3 or greater, as well as in those with acute kidney injury.

[1]  H. Thomsen,et al.  Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. , 1998, Academic radiology.

[2]  John Gosbee,et al.  ACR guidance document for safe MR practices: 2007. , 2007, AJR. American journal of roentgenology.

[3]  G. Kost,et al.  Spurious hypocalcemia after Omniscan- or OptiMARK-enhanced magnetic resonance imaging: an algorithm for minimizing a false-positive laboratory value. , 2004, Archives of pathology & laboratory medicine.

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

[5]  J. Voorhees,et al.  UV-A1 phototherapy improves nephrogenic fibrosing dermopathy. , 2004, Archives of dermatology.

[6]  R. Dolan,et al.  MS-325: albumin-targeted contrast agent for MR angiography. , 1998, Radiology.

[7]  M. Lucia,et al.  A case of nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis , 2007, Nature Clinical Practice Nephrology.

[8]  J. Wittenberg,et al.  Gd-DOTA: characterization of a new paramagnetic complex. , 1988, Radiology.

[9]  W. Gibby,et al.  Human in vivo comparative study of zinc and copper transmetallation after administration of magnetic resonance imaging contrast agents. , 1996, Investigative radiology.

[10]  S. Jimenez,et al.  Involvement of skeletal muscle in dialysis‐associated systemic fibrosis (nephrogenic fibrosing dermopathy) , 2004, Muscle & nerve.

[11]  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.

[12]  T. Kumazaki,et al.  Safety of gadolinium contrast agent in hemodialysis patients. , 2001, Acta radiologica.

[13]  W. Ting,et al.  Nephrogenic fibrosing dermopathy with systemic involvement. , 2003, Archives of dermatology.

[14]  R. Prayson,et al.  Multiorgan involvement in nephrogenic fibrosing dermopathy: an autopsy case and review of the literature. , 2006, Archives of pathology & laboratory medicine.

[15]  S. Nehlsen-Cannarella,et al.  Nephrogenic Fibrosing Dermopathy After Liver Transplantation Successfully Treated With Plasmapheresis , 2003, The American Journal of dermatopathology.

[16]  M. Tweedle,et al.  Physicochemical properties of gadoteridol and other magnetic resonance contrast agents. , 1992, Investigative radiology.

[17]  Yoshiaki Tanaka,et al.  Dialyzability of gadodiamide in hemodialysis patients , 2006, Radiation Medicine.

[18]  G. R. Stevens,et al.  Pharmacokinetics, safety, and tolerability of gadoversetamide injection (OptiMARK) in subjects with central nervous system or liver pathology and varying degrees of renal function , 1999, Journal of magnetic resonance imaging : JMRI.

[19]  H. Thomsen,et al.  Enhanced computed tomography or magnetic resonance imaging: a choice between contrast medium-induced nephropathy and nephrogenic systemic fibrosis? , 2007, Acta radiologica.

[20]  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.

[21]  K. Chung,et al.  Nephrogenic fibrosing dermopathy: response to high‐dose intravenous immunoglobulin , 2004, The British journal of dermatology.

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

[23]  S. Cowper Nephrogenic fibrosing dermopathy: the first 6 years , 2003, Current opinion in rheumatology.

[24]  C. Ayers,et al.  Renal insufficiency: usefulness of gadodiamide-enhanced renal angiography to supplement CO2-enhanced renal angiography for diagnosis and percutaneous treatment. , 1999, Radiology.

[25]  K. Keven,et al.  The safety of gadolinium in patients with stage 3 and 4 renal failure. , 2006, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[26]  R. Swartz,et al.  Nephrogenic fibrosing dermopathy: a novel cutaneous fibrosing disorder in patients with renal failure. , 2003, The American journal of medicine.

[27]  V. Runge,et al.  Nephrogenic Systemic Fibrosis: A Review of 6 Cases Temporally Related to Gadodiamide Injection (Omniscan) , 2007, Investigative radiology.

[28]  J. Kern,et al.  Lower extremity arteriography with use of iodinated contrast material or gadodiamide to supplement CO2 angiography in patients with renal insufficiency. , 2000, Journal of vascular and interventional radiology : JVIR.

[29]  M. Bellin,et al.  Gd-DOTA: evaluation of its renal tolerance in patients with chronic renal failure. , 1992, Magnetic resonance imaging.

[30]  L. Truong,et al.  Are gadolinium-based contrast media nephrotoxic? A renal biopsy study. , 2009, Archives of pathology & laboratory medicine.

[31]  R. Elenitsas,et al.  Histopathologic comparison of nephrogenic fibrosing dermopathy and scleromyxedema , 2005, Journal of cutaneous pathology.

[32]  C. Cortese,et al.  Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis: report of a new case with literature review. , 2005, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[33]  M. Taupitz,et al.  Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging. , 1995, Radiology.

[34]  Teut Risler,et al.  Gadolinium-based contrast media compared with iodinated media for digital subtraction angiography in azotaemic patients. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[35]  H. Thomsen,et al.  Contrast-media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR). , 1999, European radiology.

[36]  T. Sancak,et al.  Gadodiamide as an Alternative Contrast Agent in Intravenous Digital Subtraction Angiography and Interventional Procedures of the Upper Extremity Veins , 2002, CardioVascular and Interventional Radiology.

[37]  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.

[38]  F. Nestle,et al.  Successful treatment of three cases of nephrogenic fibrosing dermopathy with extracorporeal photopheresis , 2005, The British journal of dermatology.

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

[40]  F. Mendoza,et al.  Description of 12 cases of nephrogenic fibrosing dermopathy and review of the literature. , 2006, Seminars in arthritis and rheumatism.

[41]  R. Fennell,et al.  Nephrogenic fibrosing dermopathy in pediatric patients , 2004, Pediatric Nephrology.

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

[43]  T. Sauerbruch,et al.  MDRD Equations for Estimation of GFR in Renal Transplant Recipients , 2005, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[44]  A. Spinazzi,et al.  Gadobenate dimeglumine (Gd-BOPTA). An overview. , 1998, Investigative radiology.

[45]  Y. Araki,et al.  Permeability of gadolinium-DTPA through two types of hemodialysis membrane. , 1998, Investigative radiology.

[46]  B. Thiers Gadodiamide-Associated Nephrogenic Systemic Fibrosis: Why Radiologists Should Be Concerned , 2008 .

[47]  L. V. Rao,et al.  Gadolinium magnetic resonance contrast agents produce analytic interference in multiple serum assays. , 2004, American journal of clinical pathology.

[48]  J. Frisoli,et al.  Nephrotoxicity of high‐dose gadolinium compared with iodinated contrast , 1996, Journal of magnetic resonance imaging : JMRI.

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

[50]  F. S. Pereles,et al.  Safety of gadolinium contrast angiography in patients with chronic renal insufficiency. , 2003, Journal of vascular surgery.

[51]  M. Port,et al.  Interference of magnetic resonance imaging contrast agents with the serum calcium measurement technique using colorimetric reagents. , 1999, Journal of pharmaceutical and biomedical analysis.

[52]  K. Higashino,et al.  Permeability of iodinated and MR contrast media through two types of hemodialysis membrane. , 1999, European journal of radiology.

[53]  Henrik S. Thomsen,et al.  Gadolinium-based contrast media may be nephrotoxic even at approved doses , 2004, European Radiology.

[54]  P. Goffette,et al.  Gadolinium dimeglumine: an alternative contrast agent for digital subtraction angiography , 1999, European Radiology.

[55]  A. Colombo,et al.  Gadolinium‐based contrast agents and nephrotoxicity in patients undergoing coronary artery procedures , 2006, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[56]  K Bensel,et al.  Safety of intravenous gadolinium (Gd-BOPTA) infusion in patients with renal insufficiency. , 2000, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[57]  S. Nedorost,et al.  A variant of nephrogenic fibrosing dermopathy with osteoclast‐like giant cells: a syndrome of dysregulated matrix remodeling? , 2004, Journal of cutaneous pathology.

[58]  J. Gerberding,et al.  Nephrogenic fibrosing dermopathy associated with exposure to gadolinium-containing contrast agents--St. Louis, Missouri, 2002-2006. , 2007, MMWR. Morbidity and mortality weekly report.

[59]  D. Siegel,et al.  Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis with diaphragmatic involvement in a patient with respiratory failure. , 2006, Journal of the American Academy of Dermatology.

[60]  P. Choyke,et al.  Clearance of gadolinium chelates by hemodialysis: An in vitro study , 1995, Journal of magnetic resonance imaging : JMRI.

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

[62]  M. Edward,et al.  Cutaneous mucinosis associated with dermatomyositis and nephrogenic fibrosing dermopathy: fibroblast hyaluronan synthesis and the effect of patient serum , 2007, The British journal of dermatology.

[63]  J. Callen,et al.  Nephrogenic fibrosing dermopathy in a patient with acute renal failure never requiring dialysis , 2006, International journal of dermatology.

[64]  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.

[65]  P. Normann,et al.  Interference of gadodiamide injection (OMNISCAN) on the colorimetric determination of serum calcium. , 1995, Scandinavian journal of clinical and laboratory investigation.

[66]  J. Caridi,et al.  Spurious hypocalcemia after gadodiamide-enhanced magnetic resonance imaging: a case report and review of the literature. , 2006, Reviews in urology.

[67]  N. Rofsky,et al.  Renal lesion characterization with gadolinium-enhanced MR imaging: efficacy and safety in patients with renal insufficiency. , 1991, Radiology.

[68]  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.

[69]  J. Kaufman,et al.  Gadolinium-based contrast agents as an alternative at vena cavography in patients with renal insufficiency--early experience. , 1999, Radiology.

[70]  H. P. Kang,et al.  Model for predicting the impact of gadolinium on plasma calcium measured by the o-cresolphthalein method. , 2004, Clinical chemistry.

[71]  A. García‐Díez,et al.  Osseous metaplasia in the setting of nephrogenic fibrosing dermopathy , 2005, Journal of cutaneous pathology.

[72]  K. Kent,et al.  Gadodiamide administration causes spurious hypocalcemia. , 2003, Radiology.

[73]  A. V. Moore Commentary on “ACR Guidance Document for Safe MR Practices: 2007” , 2007 .

[74]  G. Saab,et al.  Nephrogenic systemic fibrosis: a mysterious disease in patients with renal failure--role of gadolinium-based contrast media in causation and the beneficial effect of intravenous sodium thiosulfate. , 2007, Clinical journal of the American Society of Nephrology : CJASN.

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

[76]  L. Schad,et al.  Elimination of gadolinium-DTPA by peritoneal dialysis. , 1995, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[77]  T. Balzer,et al.  Interference of Gadolinium-Containing Contrast-Enhancing Agents With Colorimetric Calcium Laboratory Testing , 2005, Investigative radiology.

[78]  J. Caillé,et al.  Gadolinium as a contrast agent for NMR. , 1983, AJNR. American journal of neuroradiology.

[79]  H. Thomsen,et al.  Gadolinium-containing contrast media for radiographic examinations: a position paper , 2002, European Radiology.

[80]  D. Cohen,et al.  Nephrogenic fibrosing dermopathy (scleromyxedema-like illness of renal disease). , 2003, Journal of the American Academy of Dermatology.

[81]  S. Swan,et al.  Safety and pharmacokinetic profile of gadobenate dimeglumine in subjects with renal impairment. , 1999, Investigative radiology.

[82]  J. Barkun,et al.  Poor prediction of the glomerular filtration rate using current formulas in de novo liver transplant patients. , 2004, Transplantation.

[83]  M. Jarmulowicz,et al.  Scleromyxoedema‐like changes in four renal dialysis patients , 2003, The British journal of dermatology.

[84]  A. Levey,et al.  A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation , 1999, Annals of Internal Medicine.

[85]  S. Jimenez,et al.  Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin. , 2004, Arthritis and rheumatism.

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

[87]  N. Liégeois,et al.  Clinical and pathologic features of nephrogenic fibrosing dermopathy: a report of two cases. , 2003, Journal of the American Academy of Dermatology.

[88]  Ulrich Linsenmaier,et al.  Gadolinium as an alternative contrast agent for diagnostic and interventional angiographic procedures in patients with impaired renal function. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

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

[90]  W. Gibby,et al.  Comparison of Gd DTPA-BMA (Omniscan) versus Gd HP-DO3A (ProHance) Retention in Human Bone Tissue by Inductively Coupled Plasma Atomic Emission Spectroscopy , 2004, Investigative radiology.

[91]  G. Krestin,et al.  Pharmacokinetics of Gd-DTPA in patients with chronic renal failure. , 1991, Investigative radiology.

[92]  T. Kumazaki,et al.  Effect of the surface potential of the hemodialysis membrane and the electrical charge of the gadolinium contrast medium on dialyzability. , 2003, Journal of Nippon Medical School = Nippon Ika Daigaku zasshi.