Establishing Reference Intervals for Gadolinium Concentrations in Blood, Plasma, and Urine in Individuals Not Previously Exposed to Gadolinium-Based Contrast Agents.


Journal

Investigative radiology
ISSN: 1536-0210
Titre abrégé: Invest Radiol
Pays: United States
ID NLM: 0045377

Informations de publication

Date de publication:
07 2020
Historique:
pubmed: 20 2 2020
medline: 10 4 2021
entrez: 20 2 2020
Statut: ppublish

Résumé

Over the recent years, there have been increasing concerns that exposure to gadolinium-based contrast agents (GBCAs) may be associated with retention of Gd within the skin, bones, and solid organs in patients with normal renal function, although the clinical implications of this deposition remain to be established. There are no published data available to guide the development of reference intervals for Gd concentrations in biological samples from healthy people. The aims of this study were to (1) determine whether healthy individuals who have not received GBCAs have detectable concentrations of Gd in their blood and urine, and (2) to develop a reference range for Gd concentrations in blood and spot urine samples for healthy individuals. Whole blood, plasma, and spot urine samples were taken from 120 healthy volunteers with estimated glomerular filtration rate 70 mL/min per 1.73 m or greater. Gd concentrations were measured in these samples using inductively coupled plasma mass-spectrometry. The reference intervals for Gd concentrations in whole blood, plasma, and urine were estimated as the 2.5th percentile and the upper reference limit as the 97.5th percentile. Ten (8.33%) of the 120 subjects had detectable concentrations of Gd in their whole blood (n = 5) or spot urine (n = 5) samples; no subjects had detectable concentrations of Gd in their plasma samples. Our proposed reference intervals for Gd are as follows: whole blood, <0.008 ng/mL or <0.050 nmol/L; plasma, <0.009 ng/mL or <0.057 nmol/L; spot urine, <0.036 μg/g or <0.0250 nmol/mmol. The results of this study provide reference intervals for whole blood, plasma, and urine Gd concentrations in healthy subjects who have not previously received GBCAs and will assist clinicians in assessing patients who have concerns regarding potential Gd retention postexposure and help guide further clinical studies to explore the pharmacokinetics of GBCAs in patients with normal renal function.

Identifiants

pubmed: 32073420
doi: 10.1097/RLI.0000000000000657
pii: 00004424-202007000-00001
doi:

Substances chimiques

Contrast Media 0
Gadolinium AU0V1LM3JT

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

405-411

Références

Layne KA, Dargan PI, Archer JRH, et al. Gadolinium deposition and the potential for toxicological sequelae—a literature review of issues surrounding gadolinium-based contrast agents. Br J Clin Pharmacol. 2018;84:2522–2534.
Lohrke J, Frenzel T, Endrikat J, et al. 25 years of contrast-enhanced MRI: developments, current challenges and future perspectives. Adv Ther. 2016;33:1–28.
Forsting M, Palkowitsch P. Prevalence of acute adverse reactions to gadobutrol—a highly concentrated macrocyclic gadolinium chelate: review of 14,299 patients from observational trials. Eur J Radiol. 2010;74:e186–e1892.
Bruder O, Schneider S, Nothnagel D, et al. Acute adverse reactions to gadolinium-based contrast agents in CMR: multicenter experience with 17,767 patients from the EuroCMR registry. JACC Cardiovasc Imaging. 2011;4:1171–1176.
Gibby WA, Gibby KA, Gibby WA. Comparison of Gd DTPA-BMA (Omniscan) versus Gd HP-DO3A (ProHance) retention in human bone tissue by inductively coupled plasma atomic emission spectroscopy. Invest Radiol. 2004;39:138–142.
White GW, Gibby WA, Tweedle MF. 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. Invest Radiol. 2006;41:272–278.
Darrah TH, Prutsman-Pfeiffer JJ, Poreda RJ, et al. Incorporation of excess gadolinium into human bone from medical contrast agents. Metallomics. 2009;1:479–488.
Xia D, Davis RL, Crawford JA, et al. Gadolinium released from MR contrast agents is deposited in brain tumors: in situ demonstration using scanning electron microscopy with energy dispersive x-ray spectroscopy. Acta Radiol. 2010;51:1126–1136.
Kanda T, Fukusato T, Matsuda M, et al. Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology. 2015;276:228–232.
Kanda T, Ishii K, Kawaguchi H, et al. High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology. 2014;270:834–841.
Kanda T, Osawa M, Oba H, et al. High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology. 2015;275:803–809.
Errante Y, Cirimele V, Mallio CA, et al. Progressive increase of T1 signal intensity of the dentate nucleus on unenhanced magnetic resonance images is associated with cumulative doses of intravenously administered gadodiamide in patients with normal renal function, suggesting dechelation. Invest Radiol. 2014;49:685–690.
Murata N, Gonzalez-Cuyar LF, Murata K, et al. Macrocyclic and other non-group 1 gadolinium contrast agents deposit low levels of gadolinium in brain and bone tissue: preliminary results from 9 patients with normal renal function. Invest Radiol. 2016;51:447–453.
McDonald RJ, McDonald JS, Kallmes DF, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology. 2015;275:772–782.
McDonald RJ, McDonald JS, Kallmes DF, et al. Gadolinium deposition in human brain tissues after contrast-enhanced MR imaging in adult patients without intracranial abnormalities. Radiology. 2017;285:546–554.
Lord ML, McNeill FE, Grafe JL, et al. Self-identified gadolinium toxicity: comparison of gadolinium in bone and urine to healthy gadolinium-based contrast agent exposed volunteers. Physiol Meas. 2018;39:115008.
Semelka RC, Commander CW, Jay M, et al. Presumed gadolinium toxicity in subjects with normal renal function: a report of 4 cases. Invest Radiol. 2016;51:661–665.
Nehra AK, McDonald RJ, Bluhm AM, et al. Accumulation of gadolinium in human cerebrospinal fluid after gadobutrol-enhanced MR imaging: a prospective observational cohort study. Radiology. 2018;288:416–423.
Layne KA, Wood DM, Dargan PI. Gadolinium-based contrast agents—what is the evidence for 'gadolinium deposition disease' and the use of chelation therapy? Clin Toxicol (Phila). 2019;1–10.
Gadolinium-Containing Contrast Agents: Removal of Omniscan and IVMagnevist, Restrictions to the Use of Other Linear Agents. Available at: https://www.gov.uk/drug-safety-update/gadolinium-containing-contrast-agents-removal-of-omniscan-and-iv-magnevist-restrictions-to-the-use-of-other-linear-agents. Accessed February 2019.
FDA Warns that Gadolinium-Based Contrast Agents (GBCAs) Are Retained in the Body; Requires New Class Warnings. Available at: https://www.fda.gov/downloads/Drugs/DrugSafety/UCM589442.pdf. Accessed February 2019.
Semelka RC, Ramalho J, Vakharia A, et al. Gadolinium deposition disease: initial description of a disease that has been around for a while. Magn Reson Imaging. 2016;34:1383–1390.
Mayo Clinic Laboratories: Gadolinium, Serum. Available at: https://www.mayocliniclabs.com/test-catalog/Overview/89299. Accessed July 2019.
Mayo Clinic Laboratories: Gadolinium/Creatinine Ratio, Random, Urine. Available at: https://www.mayocliniclabs.com/test-catalog/Overview/60428. Accessed July 2019.
Mayo Clinic Laboratories: Gadolinium, 24 hour, Urine Overview. Available at: https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/89301. Accessed July 2019.
Hodnett D, Wood DM, Raja K, et al. A healthy volunteer study to investigate trace element contamination of blood samples by stainless steel venepuncture needles. Clin Toxicol (Phila). 2012;50:99–107.
Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145:247–254.
Schmidt RL, Straseski JA, Raphael KL, et al. A risk assessment of the Jaffe vs enzymatic method for creatinine measurement in an outpatient population. PLoS One. 2015;10:e0143205.
Yalew A, Terefe B, Alem M, et al. Hematological reference intervals determination in adults at Gondar university hospital, Northwest Ethiopia. BMC Res Notes. 2016;9:483.
Curcio R, Stettler H, Suter PM, et al. Reference intervals for 24 laboratory parameters determined in 24-hour urine collections. Clin Chem Lab Med. 2016;54:105–116.
Slack SD, Turley P, Allgar V, et al. Cerebrospinal fluid lactate: measurement of an adult reference interval. Ann Clin Biochem. 2016;53(pt 1):164–167.
Horn PS, Pesce AJ. Reference intervals: an update. Clin Chim Acta. 2003;334:5–23.
Boyd JC. Defining laboratory reference values and decision limits: populations, intervals, and interpretations. Asian J Androl. 2010;12:83–90.
Pavlov IY, Wilson AR, Delgado JC. Reference interval computation: which method (not) to choose? Clin Chim Acta. 2012;413:1107–1114.
Katayev A, Balciza C, Seccombe DW. Establishing reference intervals for clinical laboratory test results: is there a better way? Am J Clin Pathol. 2010;133:180–186.
Solberg H. Approved recommendation (1987) on the theory of reference values. Part 5. Statistical treatment of collected reference values. Determination of reference limits. Clin Chim Acta. 1987;170:S13–S32.
Ozarda Y. Reference intervals: current status, recent developments and future considerations. Biochem Med (Zagreb). 2016;26:5–16.
Ozarda Y, Sikaris K, Streichert T, et al. Distinguishing reference intervals and clinical decision limits - a review by the IFCC committee on reference intervals and decision limits. Crit Rev Clin Lab Sci. 2018;55:420–431.
Ichihara K, Ozarda Y, Barth JH, et al. A global multicenter study on reference values: 1. Assessment of methods for derivation and comparison of reference intervals. Clin Chim Acta. 2017;467:70–82.
Hallquist A, Jansson P. Self-reported diagnostic x-ray investigation and data from medical records in case-control studies on thyroid cancer: evidence of recall bias? Eur J Cancer Prev. 2005;14:271–276.
Nielsen FH. Chapter 43 - nonessential trace minerals: basic nutritional and toxicological aspects. In: Collins JF, ed. Molecular, Genetic, and Nutritional Aspects of Major and Trace Minerals. Cambridge, MA: Elsevier Inc; 2017.
Liebscher K, Smith H. Essential and nonessential trace elements. A method of determining whether an element is essential or nonessential in human tissue. Arch Environ Health. 1968;17:881–890.
Rogowska J, Olkowska E, Ratajczyk W, et al. Gadolinium as a new emerging contaminant of aquatic environments. Environ Toxicol Chem. 2018;37:1523–1534.
Klaus K, Eckard H. Hospital effluents as a source of gadolinium in the aquatic environment. Environ Sci Technol. 2000;34:573–577.
Bau M, Dulski P. Distribution of yttrium and rare-earth elements in the Penge and Kuruman iron-formations Transvaal Supergroup, South Africa. Precambrian Res. 79:37–55.
Elbaz-Poulichet F, Seidel JL, Othoniel C. Occurrence of an anthropogenic gadolinium anomaly in river and coastal waters of southern France. Water Res. 2002;36:1102–1105.
Lerat-Hardy A, Coynel A, Dutruch L, et al. Rare earth element fluxes over 15years into a major European estuary (Garonne-Gironde, SW France): hospital effluents as a source of increasing gadolinium anomalies. Sci Total Environ. 2019;656:409–420.
Pedreira RMA, Pahnke K, Boning P, et al. Tracking hospital effluent-derived gadolinium in Atlantic coastal waters off Brazil. Water Res. 2018;145:62–72.
Telgmann L, Sperling M, Karst U. Determination of gadolinium-based MRI contrast agents in biological and environmental samples: a review. Anal Chim Acta. 2013;764:1–16.
Kulaksiz S, Bau M. Rare earth elements in the Rhine River, Germany: first case of anthropogenic lanthanum as a dissolved microcontaminant in the hydrosphere. Environ Int. 2011;37:973–979.
Ebrahimi P, Barbieri M. Gadolinium as an emerging microcontaminant in water resources: threats and opportunities. Geosciences. 2019;9:93.
Kulaksiz S, Bau M. Anthropogenic gadolinium as a microcontaminant in tap water used as drinking water in urban areas and megacities. Appl Geochem. 2011;26:1877–1885.
Christensen KN, Lee CU, Hanley MM, et al. Quantification of gadolinium in fresh skin and serum samples from patients with nephrogenic systemic fibrosis. J Am Acad Dermatol. 2011;64:91–96.
Saussereau E, Lacroix C, Cattaneo A, et al. Hair and fingernail gadolinium ICP-MS contents in an overdose case associated with nephrogenic systemic fibrosis. Forensic Sci Int. 2008;176:54–57.
Nowak S, Kunnemeyer J, Terborg L, et al. Analysis of whole blood samples with low gas flow inductively coupled plasma-optical emission spectrometry. Anal Bioanal Chem. 2015;407:1023–1026.
Liang Q, Yin H, Li J, et al. Investigation of rare earth elements in urine and drinking water of children in mining area. Medicine (Baltimore). 2018;97:e12717.
Hao J, Bourrinet P, Desche P. Assessment of pharmacokinetic, pharmacodynamic profile, and tolerance of gadopiclenol, a new high relaxivity GBCA, in healthy subjects and patients with brain lesions (phase I/IIa study). Invest Radiol. 2019;54:396–402.
McDonald RJ, Levine D, Weinreb J, et al. Gadolinium retention: a research roadmap from the 2018 NIH/ACR/RSNA workshop on gadolinium chelates. Radiology. 2018;289:517–534.
Alwasiyah D, Murphy C, Jannetto P, et al. Urinary gadolinium levels after contrast-enhanced MRI in individuals with normal renal function: a pilot study. J Med Toxicol. 2019;15:121–127.
Semelka RC, Ramalho M, Jay M, et al. Intravenous calcium−/zinc-diethylene triamine penta-acetic acid in patients with presumed gadolinium deposition disease: a preliminary report on 25 patients. Invest Radiol. 2018;53:373–379.
Spinazzi A, Lorusso V, Pirovano G, et al. Safety, tolerance, biodistribution, and MR imaging enhancement of the liver with gadobenate dimeglumine: results of clinical pharmacologic and pilot imaging studies in nonpatient and patient volunteers. Acad Radiol. 1999;6:282–291.
Le Mignon MM, Chambon C, Warrington S, et al. Gd-DOTA. Pharmacokinetics and tolerability after intravenous injection into healthy volunteers. Invest Radiol. 1990;25:933–937.
Allard M, Doucet D, Kien P, et al. Experimental study of DOTA-gadolinium. Pharmacokinetics and pharmacologic properties. Invest Radiol. 1988;23(suppl 1):S271–S274.
Staks T, Schuhmann-Giampieri G, Frenzel T, et al. Pharmacokinetics, dose proportionality, and tolerability of gadobutrol after single intravenous injection in healthy volunteers. Invest Radiol. 1994;29:709–715.

Auteurs

Miriam Dixon-Zegeye (M)

From the Departments of General Medicine.

Kishor Raja (K)

Viapath Analytics, King's College Hospital NHS Foundation Trust, London, United Kingdom.

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