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Review
. 2021 Jan 13;10(2):271.
doi: 10.3390/jcm10020271.

Gadolinium-Based Contrast Media Nephrotoxicity in Kidney Impairment: The Physio-Pathological Conditions for the Perfect Murder

Francesca Martino  1   2 , Gianpaolo Amici  3 , Mitchell Rosner  4 , Claudio Ronco  1   2 , Giacomo Novara  5
Affiliations
Review

Gadolinium-Based Contrast Media Nephrotoxicity in Kidney Impairment: The Physio-Pathological Conditions for the Perfect Murder

Francesca Martino et al. J Clin Med. .

Abstract

Gadolinium-based contrast media (GBCM) toxicity in patients with kidney disease is a concern for the possible development of systemic nephrogenic fibrosis and possible renal complications. This review focuses on the pathological mechanisms underlying the potential kidney toxicity of gadolinium. Gadolinium, as a free compound (Gd3+), is highly toxic in humans because it competes with divalent calcium (Ca2+) and magnesium (Mg2+) ions, interfering in some relevant biologic processes. Its toxicity is blunted by the complexing of Gd3+ with a carrier, allowing its use in magnetic resonance imaging. The binding reaction between gadolinium and a carrier is thermodynamically reversible. Consequently, under some conditions, gadolinium can be released in the interstitial space as a free Gd3+ compound with the possibility of toxicity. Other metals such as iron, copper, and calcium can interfere with the binding between gadolinium and its carrier because they compete for the same binding site. This process is known as transmetallation. In patients with kidney impairment, conditions such as low clearance of the Gd-carrier complex, acid-base derangements, and high serum phosphorous can increase the presence of free Gd3+, leading to a higher risk for toxicity.

Keywords: gadolinium-based contrast media; kidney damage; toxicity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Transmetallation is a dynamic process where the presence of other metals such as Zn2+, Cu2+, and Ca2+ can interfere with Gd3+-carrier complex by competing for the binding site. In this example, Zn2+ displaces Gd3+ with the release of free Gd3+.
Figure 2
Figure 2
Estimated Gd3+ retention in the simulation model after linear and nonionic GBCM exposure in chronic kidney disease (CKD) patients (modified from [14]): with progressive kidney function impairment, there is an increasing GBCM retainment with higher odds of transmetallation. Furthermore, transmetallation seems to be influenced by other conditions such as the type of GBCM, the GBCM dose exposure, the hydration status, the phosphorus level, the acidosis status, and the fraction of free ligand in GBCM. Specifically, higher doses of GBCM, metabolic acidosis, hyperphosphotemia, and hypoidydration may increase the risk of transmetallation.
Figure 3
Figure 3
Proposed mechanism of osmolality and viscosity damage in the kidney after GBCM exposure.
See this image and copyright information in PMC

References

    1. Perazella M.A., Rodby R.A. Gadolinium Use in Patients with Kidney Disease: A Cause for Concern. Semin. Dial. 2007;20:179–185. doi: 10.1111/j.1525-139X.2007.00269.x. - DOI - PubMed
    1. Wagner B., Drel V., Gorin Y. Pathophysiology of Gadolinium-Associated Systemic Fibrosis. Am. J. Physiol. Ren. Physiol. 2016;311:F1–F11. doi: 10.1152/ajprenal.00166.2016. - DOI - PMC - PubMed
    1. Lmståhl B., Nyman U., Leander P., Chai C.M., Golman K., Björk J., Almén T. Gadolinium Contrast Media Are More Nephrotoxic Than Iodine Media. The Importance of Osmolality in Direct Renal Artery Injections. Eur. Radiol. 2006;16:2712–2720. doi: 10.1007/s00330-006-0357-4. - DOI - PubMed
    1. Deray G., Rouviere O., Bacigalupo L., Maes B., Hannedouche T., Vrtovsnik F., Rigothier C., Billiouw J.M., Campioni P., Ferreiros J., et al. Safety of Meglumine Gadoterate (Gd-DOTA)-enhanced MRI Compared to Unenhanced MRI in Patients with Chronic Kidney Disease (RESCUE Study) Eur. Radiol. 2013;23:1250–1259. doi: 10.1007/s00330-012-2705-x. - DOI - PMC - PubMed
    1. Ergün I., Keven K., Uruc I., Ekmekci Y., Canbakan B., Erden I., Karatan O. The Safety of Gadolinium in Patients with Stage 3 and 4 Renal Failure. Nephrol. Dial. Transplant. 2006;21:697–700. doi: 10.1093/ndt/gfi304. - DOI - PubMed

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