Risks and Options With Gadolinium-Based Contrast Agents in Patients With CKD: A Review

Gadolinium-based contrast agents (GBCAs) improve the diagnostic capabilities of magnetic resonance imaging. Although initially believed to be without major adverse effects, GBCA use in patients with severe chronic kidney disease (CKD) was demonstrated cause nephrogenic systemic fibrosis (NSF). Restrictive policies CKD and selective GBCAs that bind free gadolinium more strongly have resulted virtual elimination NSF cases. Contemporary studies high binding affinity for demonstrate an absence NSF. Despite these observations limitations contemporary studies, physicians remain concerned about CKD. Concerns are magnified by recent demonstrating deposition brain a possible syndrome attributed GBCAs. Radiologic advances several new imaging modalities can used population do not require administration. In this article, we critically review provide recommendations regarding population. Magnetic (MR) is based on ability hydrogen atoms change their energy state when exposed radiofrequency waves applied subjected strong field, giving measurable signal probe tissue properties. Gadolinium lanthanide metal paramagnetic properties shortens T1 T2 relaxation times water protons, increasing between tissues allowing improved capability. Free ion (Gd3+) highly toxic minimize toxicity, Gd3+ combined chelating substrate.1Adding L.C. Bannenberg G.L. Gustafsson L.E. Basic experimental clinical aspects salts chelates.Cardiovasc Drug Rev. 2001; 19: 41-56Crossref PubMed Scopus (103) Google Scholar The first gadolinium-based agent (GBCA) approved US Food Administration (FDA) 1988, followed approval 8 others. Each year, 30 million doses administered than 450 been worldwide since introduction.2McDonald R.J. Levine D. 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Stability human serum at 37°C.Invest Radiol. 43: 817-828Crossref (415) Scholar). Binding strength measured vitro under conditions simulating extra- intracellular fluids conditional constants 1). measurements macrocylic average tighter GBCAs, nonionic 1).2McDonald Release occur process called transmetallation, which competing ions (specifically zinc, copper, iron) displace chelate. Transmetallation slow unlikely rapid excretion kidneys. setting decreased glomerular filtration rates (GFRs), retained longer, transmetallation occur. occurs readily compared because former, direct (and dissociation Gd3+), whereas latter, must acid-catalyzed before bind.6Le ScholarTable 1Chemical Pharmacologic Properties Gadolinium-Based Contrast AgentsChemical (Proprietary Name)StructureIonicityThermodynamic (log Ktherm)Conditional Kcond)Concentration, mmol/mLDoseHalf-Life, haHalf-life data package insert.GFR > 60GFR 30-59GFR 15-29Gadodiamide (Omniscan)LinearNonionic16.9pH 7.4: 14.9pH 4.0: 10.80.50.1 mmol/kg0.2 mL/kg1.3 ± 0.255.834.3 22.9Gadoversetamide (OptiMARK)LinearNonionic16.6pH 15.0pH 10.90.50.1 mL/kg1.72 0.36.9 2.5-8.74 5.1Gadopentetate (Magnevist)LinearIonic22.5pH 18.4pH 11.20.50.1 mL/kg1.6 0.134.2 2.010.8 6.9GadoxetatebHepatobiliary elimination, 50%. (Primovist, Eovist)LinearIonic23.5pH 18.7pH 11.50.250.025 mmol/kg0.1 mL/kg1.1-1.6GadobenatecHepatobiliary 0.6%-4.0%. (MultiHance)LinearIonic22.6pH 11.10.50.1 mL/kg1.17-2.026.1 3.09.5 3.1Gadofosveset (Vasovist, Ablavar)LinearIonic22.1pH 18.9pH 11.60.250.03 mmol/kg0.12 mL/kg16.3 2.64970Gadoteridol (ProHance)MacrocyclicNonionic23.8pH 17.1pH 9.90.50.1 mL/kg1.57 0.08Gadobutrol (Gadovist)MacrocyclicNonionic21.8pH 16.1pH 9.01.00.1 mL/kg1.815.8 2.417.6 6.2Gadoterate (Dotarem)MacrocyclicIonic24.7pH 17.2pH 9.50.50.1 mL/kg1.4-2.05.1 1.013.9 1.2Note: Ktherm pH ~11, no chelate thus reflects theoretical maximal GBCA. Kcond physiologic 7.4 4. At 4 (which seen some environments), constant declines significantly due concentration (Ktherm Kcond), higher values reflecting greater binding. Measurements GBCAs.2McDonald available range 1015 1019, means solution 1 mmol/L contains 3 nmol/L 10 pmol/L Gd3+.8Frenzel ScholarAbbreviation: GBCA, agent; GFR, rate (in mL/min/1.73 m2); Kcond, constant; Ktherm, constant.Based McDonald al,2McDonald Le Caravan,6Le Port al.7Port Scholara Half-life insert.b Hepatobiliary 50%.c Open table tab Note: Abbreviation: constant. Based 2000, Cowper al9Cowper S.E. Robin H.S. Steinberg S.M. Su L.D. Gupta S. LeBoit P.E. Scleromyxoedema-like cutaneous diseases renal-dialysis patients.Lancet. 2000; 356: 1000-1001Abstract (768) described series 15 hemodialysis who developed extensive thickening hardening skin histopathologic features haphazardly arranged dermal collagen bundles increased number fibroblast cells. abnormality fibrosing dermopathy. After recognition other organs may involved, including heart, lung, gastrointestinal tract, central nervous system, kidneys, skeletal muscle, diaphragm, renamed NSF.3Attari Scholar,10Daram S.R. Coortese C.M. 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