Comments on the case report reported by Elmholdt et al.

Comments on the case report reported by Elmholdt et al. Sir, We read with interest the recent report by Elmholdt et al. [1], documenting two cases of nephrogenic systemic fibro-sis (NSF) following exposure to a large dose of the macro-cyclic gadolinium (Gd) contrast-enhancing agent (GdCA), gadobutrol (Gadovist, Bayer-Schering, Germany). However , we have several reservations about this report including the following: (i) In Case 1, in which the patient developed a mild form of NSF, the authors have not provided information either about the blood chemistry of the patient (serum creatin-ine, phosphate, calcium and parathyroid hormone) or about medications the patient was receiving at the time of administration of the GdCA. The serum creatinine cited had been measured a month before CA administration when estimated glomerular filtration rate (eGFR) was 34 mL/min. It is not clear from the report whether the renal function was stable during this month or whether there was a progressive decline. (ii) Case 2 was 'confounded' as the patient received both gadodiamide (Omniscan) (10 mL) in 2001 when renal function was normal (eGFR >60 mL/min) and gadobu-trol (15 mL) in 2008 when the patient was suffering from end-stage renal disease with eGFR 11 mL/min. The patient also had an elevated serum phosphate and parathyroid hormone at the time of the last MRI examination. The patient also developed severe peritonitis a week after the gadobutrol injection. Six months later, the patient developed NSF affecting mainly his hands. Again, no information was provided about medications the patient was receiving during this period. (iii) The authors concluded that these two cases were caused by gadobutrol but did not explore the possible role of a number of co-factors that may promote fibrosis; these include inflammation, hyperphosphataemia and medications such as erythropoietin. (iv) In Case 2, the patient received gadodiamide 7 years prior to the administration of gadobutrol. It is feasible that some Gd had been deposited in the bone after this gadodiamide injection [2]. The delayed development of NSF could have been due to mobilization of the Gd from the bone induced by the development of hyperparathyroidism in 2008. (v) It would have been useful to examine the biopsy specimens for the presence of Gd to confirm that the observed NSF is due to Gd exposure. (vi) The two patients received high doses of gadobutrol (17.5 mL in Case 1 and 15 mL in Case 2) which are equal to …