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      Two cases of nephrogenic systemic fibrosis after exposure to the macrocyclic compound gadobutrol

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          Abstract

          Nephrogenic systemic fibrosis (NSF) is a disease with progressive fibrosis. We describe two cases of NSF after exposure to a macrocyclic gadolinium-based contrast agent (GBCA) gadobutrol, which has been considered as a low-risk agent compared to linear GBCAs. The first case had chronic kidney disease (CKD) Stage 3 and was exposed to 17.5 ml of gadobutrol. The second case has been exposed twice to GBCA: 10 ml of gadodiamide (in 2001) and 15 ml of gadobutrol (in 2008). Before the second exposure, he had CKD Stage 5 and was in haemodialysis. Both patients have been diagnosed with NSF. Our cases suggest that cyclic GBCAs can also cause NSF.

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          Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging.

          Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases of nephrogenic systemic fibrosis (n = 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. The delay from exposure to first sign of the disease was 2 to 75 d (median 25 d). Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P < 0.0001). Seven (54%) patients became severely disabled, and one died 21 mo after exposure. No other exposure/event than gadodiamide that was common to more than a minority of the patients could be identified. These findings indicate that gadodiamide plays a causative role in nephrogenic systemic fibrosis.
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            Scleromyxoedema-like cutaneous diseases in renal-dialysis patients.

            15 renal dialysis patients have been identified with a skin condition characterised by thickening and hardening of the skin of the extremities and an increase in dermal fibroblast-like cells associated with collagen remodelling and mucin deposition. The disease closely resembles scleromyxoedema, yet has significant enough clinical and histopathological differences to warrant its designation as a new clinicopathological entity.
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              Role of thermodynamic and kinetic parameters in gadolinium chelate stability.

              In recent years there has been a renewed interest in the physicochemical properties of gadolinium chelates (GC). The aim of this review is to discuss the physicochemical properties of marketed GC with regard to possible biological consequences. GC can be classified according to three key molecular features: 1) the nature of the chelating moiety: either macrocyclic molecules in which Gd(3+) is caged in the preorganized cavity of the ligand, or linear, open-chain molecules; 2) ionicity: the ionicity of the molecule varies from neutral to tri-anionic agents; and 3) the presence or absence of an aromatic lipophilic moiety, which has a profound impact on the biodistribution of the GC. These parameters can also explain why GC differ considerably with regard to their thermodynamic stability constants and kinetic stability, as demonstrated by numerous studies. The concept of thermodynamic and kinetic stability is critically discussed, as it remains somewhat controversial, especially in predicting the amount of free gadolinium that may result from decomplexation of chelates in physiologic or pathologic situations. This review examines the possibility that the high kinetic stability provided by the macrocyclic structure combined with a high thermodynamic stability (reinforced by ionicity for macrocyclic chelates) can minimize the amount of free Gd(3+) released in the body. J. Magn. Reson. Imaging 2009;30:1249-1258. (c) 2009 Wiley-Liss, Inc.
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                Author and article information

                Journal
                NDT Plus
                NDT Plus
                ckj
                ndtplus
                NDT Plus
                Oxford University Press
                1753-0784
                1753-0792
                June 2010
                19 March 2010
                19 March 2010
                : 3
                : 3
                : 285-287
                Affiliations
                [1 ]MR Research Centre
                [2 ]Institute of Clinical Medicine
                [3 ]Department of Dermatology
                [4 ]Department of Nephrology
                [5 ]Department of Pathology, Aarhus University Hospital , Aarhus, Denmark
                Author notes
                Michael Pedersen; E-mail: michael@ 123456mr.au.dk
                Article
                sfq028
                10.1093/ndtplus/sfq028
                5477958
                48129758-26b8-4130-98ef-9d87f3ea3048
                © The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 2 February 2010
                : 18 February 2010
                : 22 February 2010
                Categories
                Case Report

                Nephrology
                chronic kidney disease,contrast-enhanced mri,gadobutrol,nephrogenic systemic fibrosis

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