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Henrik S. Thomsen - One of the best experts on this subject based on the ideXlab platform.
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nephrogenic systemic fibrosis a serious adverse reaction to gadolinium 1997 2006 2016 part 2
Acta Radiologica, 2016Co-Authors: Henrik S. ThomsenAbstract:Most reports have been based on pathological or nephrological registers rather than the prospective examination of the skin of exposed patients. The prevalence of nephrogenic systemic fibrosis (NSF) after exposure to Gadodiamide has been reported to be in the range of 3–7% in patients with reduced renal function (1). In patients with CKD 5 (GFR less than 15mL/min 1.73m) reviewed prospectively, it may be as much as 18% (2); all patients with suspicious lesions had a skin biopsy. The prevalence was higher after two or more injections (36%) than after a single injection (12%), indicating a cumulative effect (2). In Boston 30% of patients on dialysis had developed NSF based on a systematic examination of the patients in five dialysis centers, but skin biopsies were only taken in a few patients (3). In the peer-reviewed literature only one center has reported a large number (>10) of NSF cases after gadopentetate dimeglumine (3), but many centers have reported more than 10 cases after Gadodiamide (1). This difference is not just a reflection of the market share of the two products, because gadopentetate dimeglumine has been administered to as many as 4–5 times the number of patients who have had Gadodiamide. In the Four American University Study, the overall incidence was 0.039% after Gadodiamide and 0.003% after gadopentetate dimeglumine (4). The benchmark incidence of NSF was one in 2913 patients who underwent Gadodiamide-enhanced magnetic resonance imaging (MRI) and one in 44,224 patients who underwent gadopentetate dimeglumine-enhanced MRI (P< 0.001). The study was based on patient records from databases of dermatology, pathology, internal medicine, nephrology, transplant surgery, and radiology departments and not on a systematic examination of patients with reduced renal function exposed to a gadolinium-based contrast agent. By 1 February 2008, 190 cases (confirmed by biopsy and clinical examination) had been reported in the peerreviewed literature: 157 had had Gadodiamide, eight gadopentetate, three gadoversetamide, and in five no exposure could be verified. In 18, the agent could not be identified and four received several agents (5). Up to 2012, a total of 711 NSF cases were published (6), but it is likely that they are only a small percentage of all cases. The true number of patients who developed NSF is not known because only two studies included systematic inspection of the skin in patients with reduced renal failure or on dialysis, so patients may have died with or of undiagnosed NSF between 1996 and 2006. Simple review of patient records is not enough to determine the true prevalence.
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Nephrogenic systemic fibrosis: a serious adverse reaction to gadolinium – 1997–2006–2016. Part 2
Acta Radiologica, 2016Co-Authors: Henrik S. ThomsenAbstract:Most reports have been based on pathological or nephrological registers rather than the prospective examination of the skin of exposed patients. The prevalence of nephrogenic systemic fibrosis (NSF) after exposure to Gadodiamide has been reported to be in the range of 3–7% in patients with reduced renal function (1). In patients with CKD 5 (GFR less than 15mL/min 1.73m) reviewed prospectively, it may be as much as 18% (2); all patients with suspicious lesions had a skin biopsy. The prevalence was higher after two or more injections (36%) than after a single injection (12%), indicating a cumulative effect (2). In Boston 30% of patients on dialysis had developed NSF based on a systematic examination of the patients in five dialysis centers, but skin biopsies were only taken in a few patients (3). In the peer-reviewed literature only one center has reported a large number (>10) of NSF cases after gadopentetate dimeglumine (3), but many centers have reported more than 10 cases after Gadodiamide (1). This difference is not just a reflection of the market share of the two products, because gadopentetate dimeglumine has been administered to as many as 4–5 times the number of patients who have had Gadodiamide. In the Four American University Study, the overall incidence was 0.039% after Gadodiamide and 0.003% after gadopentetate dimeglumine (4). The benchmark incidence of NSF was one in 2913 patients who underwent Gadodiamide-enhanced magnetic resonance imaging (MRI) and one in 44,224 patients who underwent gadopentetate dimeglumine-enhanced MRI (P< 0.001). The study was based on patient records from databases of dermatology, pathology, internal medicine, nephrology, transplant surgery, and radiology departments and not on a systematic examination of patients with reduced renal function exposed to a gadolinium-based contrast agent. By 1 February 2008, 190 cases (confirmed by biopsy and clinical examination) had been reported in the peerreviewed literature: 157 had had Gadodiamide, eight gadopentetate, three gadoversetamide, and in five no exposure could be verified. In 18, the agent could not be identified and four received several agents (5). Up to 2012, a total of 711 NSF cases were published (6), but it is likely that they are only a small percentage of all cases. The true number of patients who developed NSF is not known because only two studies included systematic inspection of the skin in patients with reduced renal failure or on dialysis, so patients may have died with or of undiagnosed NSF between 1996 and 2006. Simple review of patient records is not enough to determine the true prevalence.
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Original Article Case-control study of Gadodiamide-related nephrogenic systemic fibrosis
2015Co-Authors: Peter Marckmann, Lone Skov, Kristian Rossen, James Goya Heaf, Henrik S. ThomsenAbstract:Background. Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic reso-nance imaging contrast agents. Most reported cases were associated with one particular agent, gadodia-mide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to Gadodiamide develop nephrogenic systemic fibrosis. Methods. We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to Gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records. Results. Cases had been exposed to a mean gadodi-amide dose of 0.29mmol/kg (range 0.18–0.50) shortly before first signs of nephrogenic systemic fibrosis. Controls had been exposed to 0.28mmol/kg (0.13–0.49). Cumulative Gadodiamide exposure while in chronic kidney disease stage 5 was significantly higher among cases compared with controls (0.41 vs 0.31mmol/kg, P 0.05) and among severe cases (n 9) compared with non-severe cases (0.49 vs 0.33mmol/kg, P 0.02). Severe cases developed primarily among patients in regular haemodialysis therapy at exposure. Cases had higher serum concentrations of ionized calcium and phosphate than controls and tended to receive higher doses of epoietin-b than controls at time of exposure. Severe cases were treated with higher doses of epoietin-b than non-severe cases at exposure (10.8 vs 4.4 103 IU/week, P 0.02). Conclusions. Increasing cumulative Gadodiamide exposure, high-dose epoietin-b treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of Gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients in regular haemodialysis therapy at exposure
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gadolinium induced nephrogenic systemic fibrosis the rise and fall of an iatrogenic disease
Ndt Plus, 2012Co-Authors: Charles L Bennett, Zaina P Qureshi, Oliver A Sartor, Leann B Norris, Alanna Murday, Sudha Xirasagar, Henrik S. ThomsenAbstract:Background. In 2006, nephrologists in Denmark unexpectedly identified chronic kidney disease (CKD) patients with a new syndrome, nephrogenic systemic fibrosis (NSF). Subsequently, 1603 NSF patients were reported to the Food and Drug Administration. Sixty hospitals in the USA account for 93% of these cases, and two hospitals in Denmark account for 4% of these reports. We review Denmark’s identification and subsequent rapid eradication of NSF. Methods. NSF reports from clinicians, the Danish Medicines Agency (DMA) and gadolinium-based contrast agents (GBCAs) manufacturers were reviewed (2002–11). Results. In 1994, the DMA approved a non-ionic linear GBCA, Gadodiamide (0.1 mmol/kg), for magnetic resonance imagings (MRIs), with a renal insufficiency contraindication. In 1996, 0.3 mmol/kg dosing received DMA approval. In 1998, the DMA removed renal contraindications. In 1997 and 2002, radiologists at Skejby Hospital and Herlev Hospital, respectively, began performing Gadodiamide-enhanced magnetic resonance angiography scans (0.3 mmol/kg) of CKD patients. In 2005, Herlev clinicians requested assistance in evaluating etiological causes of NSF occurring among 10 CKD patients who had developed NSF. This investigation, focusing on infectious agents, was inconclusive. In 2006, Herlev clinicians reported that of 108 CKD patients who had received Gadodiamide-enhanced MRI, 20 had developed probable NSF. Herlev radiologists voluntarily discontinued administering Gadodiamide to all patients and no new NSF cases at Herlev Hospital developed subsequently. After meeting with Herlev radiologists, Skejby radiologists also discontinued administering Gadodiamide to all patients. In 2007, the European Medicines Agency and the DMA contraindicated Gadodiamide administration to CKD patients. In 2008, in response to these advisories, radiologists at the other 36 Danish hospitals discontinued administering Gadodiamide to all patients, following on practices adopted at Skejby and Herlev Hospitals. In 2009, clinicians at Skejby Hospital reported that a look-back survey identified 33 CKD patients with NSF developing after undergoing GBCA-enhanced MRIs between 1999 and 2007. In 2010, an independent review, commissioned by the Minister of Health, concluded that the DMA had erred in rescinding Gadodiamide’s renal insufficiency contraindication in 1998 and that this error was a key factor in the development of NSF in Denmark. In 2011, three NSF cases associated with macrocyclic GBCA-associated NSF and three NSF patients with Stages 3 and 4 CKD disease from Skejby Hospital were reported. Conclusion. A confluence of factors led to the development and eradication of NSF in Denmark.
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clinical manifestation of Gadodiamide related nephrogenic systemic fibrosis
Clinical Nephrology, 2008Co-Authors: Peter Marckmann, Lone Skov, Kristian Rossen, Henrik S. ThomsenAbstract:Aims: To further characterize the clinical signs and symptoms of nephrogenic systemic fibrosis, a new and serious disease affecting renal failure patients and caused by some Gd-containing contrast agents, including Gadodiamide. Material: 22 cases of Gadodiamide-related nephrogenic systemic fibrosis followed at the nephrology department of Copenhagen University Hospital Herlev. Method: Retrospective cohort study based on medical records, personal interviews and physical examinations. Results: Typical first signs of the disease were skin discoloration, induration and warmth, itching, constant pain and other neuropathic symptoms localized to the lower legs. First sign appeared in a median of 14 days (range 0 - 53 days) after Gadodiamide exposure. Associated early symptoms included sleeplessness and transient, diffuse hair loss. The predominant late symptom was symmetrical skin stiffness of extremities with or without restricted joint motion. Ten of 22 patients (45, 95% CI: 27 - 66%) were severely disabled due to contractures on the average of 29 months after being exposed to Gadodiamide. Four patients died (18, 95% CI: 6 - 41). Patients perceived that intensive physiotherapy was effective in limiting disabling contractures. Conclusions: Signs and symptoms of nephrogenic systemic fibrosis vary over time and between patients. The disease leads to severe disability in a significant proportion of affected patients. Intensive physiotherapy may limit the development of contractures.
Peter Marckmann - One of the best experts on this subject based on the ideXlab platform.
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Original Article Case-control study of Gadodiamide-related nephrogenic systemic fibrosis
2015Co-Authors: Peter Marckmann, Lone Skov, Kristian Rossen, James Goya Heaf, Henrik S. ThomsenAbstract:Background. Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic reso-nance imaging contrast agents. Most reported cases were associated with one particular agent, gadodia-mide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to Gadodiamide develop nephrogenic systemic fibrosis. Methods. We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to Gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records. Results. Cases had been exposed to a mean gadodi-amide dose of 0.29mmol/kg (range 0.18–0.50) shortly before first signs of nephrogenic systemic fibrosis. Controls had been exposed to 0.28mmol/kg (0.13–0.49). Cumulative Gadodiamide exposure while in chronic kidney disease stage 5 was significantly higher among cases compared with controls (0.41 vs 0.31mmol/kg, P 0.05) and among severe cases (n 9) compared with non-severe cases (0.49 vs 0.33mmol/kg, P 0.02). Severe cases developed primarily among patients in regular haemodialysis therapy at exposure. Cases had higher serum concentrations of ionized calcium and phosphate than controls and tended to receive higher doses of epoietin-b than controls at time of exposure. Severe cases were treated with higher doses of epoietin-b than non-severe cases at exposure (10.8 vs 4.4 103 IU/week, P 0.02). Conclusions. Increasing cumulative Gadodiamide exposure, high-dose epoietin-b treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of Gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients in regular haemodialysis therapy at exposure
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an epidemic outbreak of nephrogenic systemic fibrosis in a danish hospital
European Journal of Radiology, 2008Co-Authors: Peter MarckmannAbstract:Abstract The nephrological department of Copenhagen University Hospital Herlev experienced an epidemic accumulation of patients developing nephrogenic systemic fibrosis in the period 2002–2006. Systematic studies of these patients revealed that they all had a Gadodiamide-enhanced magnetic resonance examination prior to their symptoms, and that they all had severe renal insufficiency (chronic kidney disease stage 5) at the time of their exposure to Gadodiamide. Besides exposure to Gadodiamide, our analyses indicated that increasing cumulative Gadodiamide exposure (i.e. repeated exposures), and higher serum concentrations of ionized calcium and phosphate were cofactors that raised the risk of developing nephrogenic systemic fibrosis. Higher cumulative Gadodiamide exposure, higher prescribed erythropoietin dosage at exposure, and being hemodialysis patient were three factors associated with nephrogenic systemic fibrosis in its most severe form. Retrospective reviews of patients records and patient interviews revealed the large variability in symptoms and clinical course of nephrogenic systemic fibrosis, but also highlighted that the typical initial symptoms were symmetric swelling, discoloration and pain of lower legs, whereas the typical late symptoms of severely affected patients were skin thickening, stiffness, contractures, and debilitating disabilities. In conclusion, nephrogenic systemic fibrosis is a serious iatrogenic disease of patients with renal insufficiency caused by some Gd-containing contrast agents, in particular Gadodiamide. Unfortunately, there is no proven curative treatment. It is therefore essential that future cases of nephrogenic systemic fibrosis are prevented.
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clinical manifestation of Gadodiamide related nephrogenic systemic fibrosis
Clinical Nephrology, 2008Co-Authors: Peter Marckmann, Lone Skov, Kristian Rossen, Henrik S. ThomsenAbstract:Aims: To further characterize the clinical signs and symptoms of nephrogenic systemic fibrosis, a new and serious disease affecting renal failure patients and caused by some Gd-containing contrast agents, including Gadodiamide. Material: 22 cases of Gadodiamide-related nephrogenic systemic fibrosis followed at the nephrology department of Copenhagen University Hospital Herlev. Method: Retrospective cohort study based on medical records, personal interviews and physical examinations. Results: Typical first signs of the disease were skin discoloration, induration and warmth, itching, constant pain and other neuropathic symptoms localized to the lower legs. First sign appeared in a median of 14 days (range 0 - 53 days) after Gadodiamide exposure. Associated early symptoms included sleeplessness and transient, diffuse hair loss. The predominant late symptom was symmetrical skin stiffness of extremities with or without restricted joint motion. Ten of 22 patients (45, 95% CI: 27 - 66%) were severely disabled due to contractures on the average of 29 months after being exposed to Gadodiamide. Four patients died (18, 95% CI: 6 - 41). Patients perceived that intensive physiotherapy was effective in limiting disabling contractures. Conclusions: Signs and symptoms of nephrogenic systemic fibrosis vary over time and between patients. The disease leads to severe disability in a significant proportion of affected patients. Intensive physiotherapy may limit the development of contractures.
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high prevalence of nephrogenic systemic fibrosis in chronic renal failure patients exposed to Gadodiamide a gadolinium containing magnetic resonance contrast agent
Investigative Radiology, 2008Co-Authors: Casper Rydahl, Henrik S. Thomsen, Peter MarckmannAbstract:Objective:Nephrogenic systemic fibrosis (NSF) is a serious disease affecting renal failure patients. It may be caused by some gadolinium (Gd)-containing contrast agents, including Gadodiamide. The study aimed at estimating the prevalence of NSF after Gadodiamide exposure for patients with chronic ki
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dermal inorganic gadolinium concentrations evidence for in vivo transmetallation and long term persistence in nephrogenic systemic fibrosis
British Journal of Dermatology, 2007Co-Authors: Jerrold L Abraham, Lone Skov, Kristian Rossen, Charu Thakral, Peter MarckmannAbstract:Summary Background Gadolinium (Gd)-based magnetic resonance contrast agents (GBMCA), including Gadodiamide, have been identified as the probable causative agents of the serious disease, nephrogenic systemic fibrosis (NSF). Objectives To investigate retained Gd-containing deposits in skin biopsies from patients with NSF and to determine their relative concentrations over time from administration of GBMCA. Methods An investigator-blinded retrospective study, analysing 43 skin biopsies from 20 patients with Gadodiamide-related NSF and one NSF-negative Gadodiamide-exposed dialysis patient, ranging from 16 days to 1991 days after Gd contrast dose. Utilizing automated quantitative scanning electron microscopy/energy-dispersive X-ray spectroscopy we determined the concentration of Gd and associated elements present as insoluble deposits in situ in the tissues. Results We detected Gd in skin lesions of all 20 patients with NSF, whereas Gd was undetectable in the NSF-negative patient. Gd concentration increased over time in 60% of patients with multiple sequential biopsies (n = 10), decreasing only when the initial sampling time was > 23 months after first Gadodiamide dose. All Gd-containing deposits contained phosphorus, calcium and sodium. The ratio of Gd to calcium in tissue deposits correlated positively with the Gadodiamide dose and with serum ionized calcium at the time of Gd exposure. Conclusions These findings demonstrate the in vivo release (through transmetallation) of the toxic free Gd3+ from Gadodiamide, and its retention in apatite-like deposits. We suggest that Gd may be mobilized over time from bone stores, explaining variably delayed onset of NSF and increasing skin concentration over time in patients with NSF.
Martin R Prince - One of the best experts on this subject based on the ideXlab platform.
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effects of gadopentetate dimeglumine and Gadodiamide on serum calcium magnesium and creatinine measurements
Journal of Magnetic Resonance Imaging, 2006Co-Authors: Hong Lei Zhang, Hale Ersoy, Martin R PrinceAbstract:Purpose To investigate the in vivo effects of Gadodiamide (Gd-DTPA-BMA) and gadopentetate dimeglumine (Gd-DTPA) on the laboratory measurements of serum calcium, magnesium, and creatinine. Materials and Methods Medical records from 1993 to 2004 were reviewed to identify inpatients for whom laboratory data were available regarding serum calcium, creatinine, and magnesium levels before and within one day after Gadodiamide and gadopentetate dimeglumine enhanced MRI. Patients who underwent both gadolinium (Gd)-enhanced MRI and iodinated contrast-enhanced examinations on separate days within a six-month period were also identified to compare changes in serum creatinine. Results Serum creatinine did not increase in 2788 cases following gadopentetate dimeglumine and Gadodiamide injection. By comparison, serum creatinine increased from 1.21 to 1.28 mg/dL following iodinated contrast, and there were 20 cases (2.6%) of contrast-induced nephrotoxicity (P < 0.01). Gadopentetate dimeglumine did not affect serum calcium or magnesium measurements. Following 1157 Gadodiamide-enhanced examinations, measured serum calcium spuriously dropped from 8.65 to 8.33 mg/dL (P < 0.0001) and 34 patients had spurious critical hypocalcemia (<6 mg/dL). Of 60 patients with high-dose Gadodiamide injection and renal insufficiency, 36.7% (N = 22) had spurious critical hypocalcemia immediately post MRI. In 216 patients with renal insufficiency, the mean serum magnesium level increased slightly from 1.69 to 1.77 mEq/L following Gadodiamide injection (P < 0.0001). Conclusion Gd-based contrast agents are safe for MRI and MR angiography (MRA), and do not induce nephrotoxicity. However, Gadodiamide interferes with serum calcium and magnesium measurements—particularly at high doses and/or with renal insufficiency. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.
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Effects of gadopentetate dimeglumine and Gadodiamide on serum calcium, magnesium, and creatinine measurements
Journal of magnetic resonance imaging : JMRI, 2006Co-Authors: Hong Lei Zhang, Hale Ersoy, Martin R PrinceAbstract:Purpose To investigate the in vivo effects of Gadodiamide (Gd-DTPA-BMA) and gadopentetate dimeglumine (Gd-DTPA) on the laboratory measurements of serum calcium, magnesium, and creatinine. Materials and Methods Medical records from 1993 to 2004 were reviewed to identify inpatients for whom laboratory data were available regarding serum calcium, creatinine, and magnesium levels before and within one day after Gadodiamide and gadopentetate dimeglumine enhanced MRI. Patients who underwent both gadolinium (Gd)-enhanced MRI and iodinated contrast-enhanced examinations on separate days within a six-month period were also identified to compare changes in serum creatinine. Results Serum creatinine did not increase in 2788 cases following gadopentetate dimeglumine and Gadodiamide injection. By comparison, serum creatinine increased from 1.21 to 1.28 mg/dL following iodinated contrast, and there were 20 cases (2.6%) of contrast-induced nephrotoxicity (P < 0.01). Gadopentetate dimeglumine did not affect serum calcium or magnesium measurements. Following 1157 Gadodiamide-enhanced examinations, measured serum calcium spuriously dropped from 8.65 to 8.33 mg/dL (P < 0.0001) and 34 patients had spurious critical hypocalcemia (
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Gadodiamide administration causes spurious hypocalcemia
Radiology, 2003Co-Authors: Martin R Prince, Hale Erel, Richard W Lent, Jon D Blumenfeld, Craig K Kent, Harry L Bush, Yi WangAbstract:PURPOSE: To evaluate the prevalence of spurious hypocalcemia after Gadodiamide-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: Eight hundred ninety-six inpatients with available serum calcium data obtained before and after Gadodiamide-enhanced MR imaging were identified. Changes in serum calcium measurements following Gadodiamide administration in 1,049 MR imaging examinations performed in these patients were correlated with Gadodiamide dose, renal function, and time between Gadodiamide administration and phlebotomy. RESULTS: Following 42 Gadodiamide-enhanced examinations, serum calcium measurements spuriously decreased by more than 2 mg/dL (0.5 mmol/L), resulting in laboratory reports of “critical” hypocalcemia (ie, calcium level < 6 mg/dL [1.5 mmol/L]) in 25 examinations. These reduced calcium measurements were correlated with serum creatinine level (r = 0.39, P < .001), Gadodiamide dose (r = 0.37, P < .001), and time between Gadodiamide injection and phlebotomy (r = −0.28, P < .001). S...
Kristian Rossen - One of the best experts on this subject based on the ideXlab platform.
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Original Article Case-control study of Gadodiamide-related nephrogenic systemic fibrosis
2015Co-Authors: Peter Marckmann, Lone Skov, Kristian Rossen, James Goya Heaf, Henrik S. ThomsenAbstract:Background. Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic reso-nance imaging contrast agents. Most reported cases were associated with one particular agent, gadodia-mide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to Gadodiamide develop nephrogenic systemic fibrosis. Methods. We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to Gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records. Results. Cases had been exposed to a mean gadodi-amide dose of 0.29mmol/kg (range 0.18–0.50) shortly before first signs of nephrogenic systemic fibrosis. Controls had been exposed to 0.28mmol/kg (0.13–0.49). Cumulative Gadodiamide exposure while in chronic kidney disease stage 5 was significantly higher among cases compared with controls (0.41 vs 0.31mmol/kg, P 0.05) and among severe cases (n 9) compared with non-severe cases (0.49 vs 0.33mmol/kg, P 0.02). Severe cases developed primarily among patients in regular haemodialysis therapy at exposure. Cases had higher serum concentrations of ionized calcium and phosphate than controls and tended to receive higher doses of epoietin-b than controls at time of exposure. Severe cases were treated with higher doses of epoietin-b than non-severe cases at exposure (10.8 vs 4.4 103 IU/week, P 0.02). Conclusions. Increasing cumulative Gadodiamide exposure, high-dose epoietin-b treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of Gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients in regular haemodialysis therapy at exposure
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clinical manifestation of Gadodiamide related nephrogenic systemic fibrosis
Clinical Nephrology, 2008Co-Authors: Peter Marckmann, Lone Skov, Kristian Rossen, Henrik S. ThomsenAbstract:Aims: To further characterize the clinical signs and symptoms of nephrogenic systemic fibrosis, a new and serious disease affecting renal failure patients and caused by some Gd-containing contrast agents, including Gadodiamide. Material: 22 cases of Gadodiamide-related nephrogenic systemic fibrosis followed at the nephrology department of Copenhagen University Hospital Herlev. Method: Retrospective cohort study based on medical records, personal interviews and physical examinations. Results: Typical first signs of the disease were skin discoloration, induration and warmth, itching, constant pain and other neuropathic symptoms localized to the lower legs. First sign appeared in a median of 14 days (range 0 - 53 days) after Gadodiamide exposure. Associated early symptoms included sleeplessness and transient, diffuse hair loss. The predominant late symptom was symmetrical skin stiffness of extremities with or without restricted joint motion. Ten of 22 patients (45, 95% CI: 27 - 66%) were severely disabled due to contractures on the average of 29 months after being exposed to Gadodiamide. Four patients died (18, 95% CI: 6 - 41). Patients perceived that intensive physiotherapy was effective in limiting disabling contractures. Conclusions: Signs and symptoms of nephrogenic systemic fibrosis vary over time and between patients. The disease leads to severe disability in a significant proportion of affected patients. Intensive physiotherapy may limit the development of contractures.
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dermal inorganic gadolinium concentrations evidence for in vivo transmetallation and long term persistence in nephrogenic systemic fibrosis
British Journal of Dermatology, 2007Co-Authors: Jerrold L Abraham, Lone Skov, Kristian Rossen, Charu Thakral, Peter MarckmannAbstract:Summary Background Gadolinium (Gd)-based magnetic resonance contrast agents (GBMCA), including Gadodiamide, have been identified as the probable causative agents of the serious disease, nephrogenic systemic fibrosis (NSF). Objectives To investigate retained Gd-containing deposits in skin biopsies from patients with NSF and to determine their relative concentrations over time from administration of GBMCA. Methods An investigator-blinded retrospective study, analysing 43 skin biopsies from 20 patients with Gadodiamide-related NSF and one NSF-negative Gadodiamide-exposed dialysis patient, ranging from 16 days to 1991 days after Gd contrast dose. Utilizing automated quantitative scanning electron microscopy/energy-dispersive X-ray spectroscopy we determined the concentration of Gd and associated elements present as insoluble deposits in situ in the tissues. Results We detected Gd in skin lesions of all 20 patients with NSF, whereas Gd was undetectable in the NSF-negative patient. Gd concentration increased over time in 60% of patients with multiple sequential biopsies (n = 10), decreasing only when the initial sampling time was > 23 months after first Gadodiamide dose. All Gd-containing deposits contained phosphorus, calcium and sodium. The ratio of Gd to calcium in tissue deposits correlated positively with the Gadodiamide dose and with serum ionized calcium at the time of Gd exposure. Conclusions These findings demonstrate the in vivo release (through transmetallation) of the toxic free Gd3+ from Gadodiamide, and its retention in apatite-like deposits. We suggest that Gd may be mobilized over time from bone stores, explaining variably delayed onset of NSF and increasing skin concentration over time in patients with NSF.
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case control study of Gadodiamide related nephrogenic systemic fibrosis
Nephrology Dialysis Transplantation, 2007Co-Authors: Peter Marckmann, Lone Skov, Kristian Rossen, James Goya Heaf, Henrik S. ThomsenAbstract:Background. Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic resonance imaging contrast agents. Most reported cases were associated with one particular agent, Gadodiamide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to Gadodiamide develop nephrogenic systemic fibrosis. Methods. We conducted a case-control study of 19 histologically verified cases and 19 sex- and agematched controls. All subjects had chronic renal failure when exposed to Gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records.
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Case-control study of Gadodiamide-related nephrogenic systemic fibrosis. Commentary
Nephrology Dialysis Transplantation, 2007Co-Authors: Joëlle Nortier, Lone Skov, Kristian Rossen, James Goya Heaf, Peter Marckmann, Véronique Del Marmo, Henrik S. ThomsenAbstract:Background. Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic resonance imaging contrast agents. Most reported cases were associated with one particular agent, Gadodiamide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to Gadodiamide develop nephrogenic systemic fibrosis. Methods. We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to Gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records. Results. Cases had been exposed to a mean Gadodiamide dose of 0.29 mmol/kg (range 0.18-0.50) shortly before first signs of nephrogenic systemic fibrosis. Controls had been exposed to 0.28 mmol/kg (0.13-0.49). Cumulative Gadodiamide exposure while in chronic kidney disease stage 5 was significantly higher among cases compared with controls (0.41 vs 0.31 mmol/kg, P = 0.05) and among severe cases (n = 9) compared with non-severe cases (0.49 vs 0.33 mmol/kg, P=0.02). Severe cases developed primarily among patients in regular haemodialysis therapy at exposure. Cases had higher serum concentrations of ionized calcium and phosphate than controls and tended to receive higher doses of epoietin-β than controls at time of exposure. Severe cases were treated with higher doses of epoietin-β than non-severe cases at exposure (10.8 vs 4.4 10 3 IU/week, P= 0.02). Conclusions. Increasing cumulative Gadodiamide exposure, high-dose epoietin-β treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of Gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients in regular haemodialysis therapy at exposure.
Lone Skov - One of the best experts on this subject based on the ideXlab platform.
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Original Article Case-control study of Gadodiamide-related nephrogenic systemic fibrosis
2015Co-Authors: Peter Marckmann, Lone Skov, Kristian Rossen, James Goya Heaf, Henrik S. ThomsenAbstract:Background. Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic reso-nance imaging contrast agents. Most reported cases were associated with one particular agent, gadodia-mide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to Gadodiamide develop nephrogenic systemic fibrosis. Methods. We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to Gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records. Results. Cases had been exposed to a mean gadodi-amide dose of 0.29mmol/kg (range 0.18–0.50) shortly before first signs of nephrogenic systemic fibrosis. Controls had been exposed to 0.28mmol/kg (0.13–0.49). Cumulative Gadodiamide exposure while in chronic kidney disease stage 5 was significantly higher among cases compared with controls (0.41 vs 0.31mmol/kg, P 0.05) and among severe cases (n 9) compared with non-severe cases (0.49 vs 0.33mmol/kg, P 0.02). Severe cases developed primarily among patients in regular haemodialysis therapy at exposure. Cases had higher serum concentrations of ionized calcium and phosphate than controls and tended to receive higher doses of epoietin-b than controls at time of exposure. Severe cases were treated with higher doses of epoietin-b than non-severe cases at exposure (10.8 vs 4.4 103 IU/week, P 0.02). Conclusions. Increasing cumulative Gadodiamide exposure, high-dose epoietin-b treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of Gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients in regular haemodialysis therapy at exposure
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clinical manifestation of Gadodiamide related nephrogenic systemic fibrosis
Clinical Nephrology, 2008Co-Authors: Peter Marckmann, Lone Skov, Kristian Rossen, Henrik S. ThomsenAbstract:Aims: To further characterize the clinical signs and symptoms of nephrogenic systemic fibrosis, a new and serious disease affecting renal failure patients and caused by some Gd-containing contrast agents, including Gadodiamide. Material: 22 cases of Gadodiamide-related nephrogenic systemic fibrosis followed at the nephrology department of Copenhagen University Hospital Herlev. Method: Retrospective cohort study based on medical records, personal interviews and physical examinations. Results: Typical first signs of the disease were skin discoloration, induration and warmth, itching, constant pain and other neuropathic symptoms localized to the lower legs. First sign appeared in a median of 14 days (range 0 - 53 days) after Gadodiamide exposure. Associated early symptoms included sleeplessness and transient, diffuse hair loss. The predominant late symptom was symmetrical skin stiffness of extremities with or without restricted joint motion. Ten of 22 patients (45, 95% CI: 27 - 66%) were severely disabled due to contractures on the average of 29 months after being exposed to Gadodiamide. Four patients died (18, 95% CI: 6 - 41). Patients perceived that intensive physiotherapy was effective in limiting disabling contractures. Conclusions: Signs and symptoms of nephrogenic systemic fibrosis vary over time and between patients. The disease leads to severe disability in a significant proportion of affected patients. Intensive physiotherapy may limit the development of contractures.
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dermal inorganic gadolinium concentrations evidence for in vivo transmetallation and long term persistence in nephrogenic systemic fibrosis
British Journal of Dermatology, 2007Co-Authors: Jerrold L Abraham, Lone Skov, Kristian Rossen, Charu Thakral, Peter MarckmannAbstract:Summary Background Gadolinium (Gd)-based magnetic resonance contrast agents (GBMCA), including Gadodiamide, have been identified as the probable causative agents of the serious disease, nephrogenic systemic fibrosis (NSF). Objectives To investigate retained Gd-containing deposits in skin biopsies from patients with NSF and to determine their relative concentrations over time from administration of GBMCA. Methods An investigator-blinded retrospective study, analysing 43 skin biopsies from 20 patients with Gadodiamide-related NSF and one NSF-negative Gadodiamide-exposed dialysis patient, ranging from 16 days to 1991 days after Gd contrast dose. Utilizing automated quantitative scanning electron microscopy/energy-dispersive X-ray spectroscopy we determined the concentration of Gd and associated elements present as insoluble deposits in situ in the tissues. Results We detected Gd in skin lesions of all 20 patients with NSF, whereas Gd was undetectable in the NSF-negative patient. Gd concentration increased over time in 60% of patients with multiple sequential biopsies (n = 10), decreasing only when the initial sampling time was > 23 months after first Gadodiamide dose. All Gd-containing deposits contained phosphorus, calcium and sodium. The ratio of Gd to calcium in tissue deposits correlated positively with the Gadodiamide dose and with serum ionized calcium at the time of Gd exposure. Conclusions These findings demonstrate the in vivo release (through transmetallation) of the toxic free Gd3+ from Gadodiamide, and its retention in apatite-like deposits. We suggest that Gd may be mobilized over time from bone stores, explaining variably delayed onset of NSF and increasing skin concentration over time in patients with NSF.
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case control study of Gadodiamide related nephrogenic systemic fibrosis
Nephrology Dialysis Transplantation, 2007Co-Authors: Peter Marckmann, Lone Skov, Kristian Rossen, James Goya Heaf, Henrik S. ThomsenAbstract:Background. Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic resonance imaging contrast agents. Most reported cases were associated with one particular agent, Gadodiamide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to Gadodiamide develop nephrogenic systemic fibrosis. Methods. We conducted a case-control study of 19 histologically verified cases and 19 sex- and agematched controls. All subjects had chronic renal failure when exposed to Gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records.
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Case-control study of Gadodiamide-related nephrogenic systemic fibrosis. Commentary
Nephrology Dialysis Transplantation, 2007Co-Authors: Joëlle Nortier, Lone Skov, Kristian Rossen, James Goya Heaf, Peter Marckmann, Véronique Del Marmo, Henrik S. ThomsenAbstract:Background. Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic resonance imaging contrast agents. Most reported cases were associated with one particular agent, Gadodiamide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to Gadodiamide develop nephrogenic systemic fibrosis. Methods. We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to Gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records. Results. Cases had been exposed to a mean Gadodiamide dose of 0.29 mmol/kg (range 0.18-0.50) shortly before first signs of nephrogenic systemic fibrosis. Controls had been exposed to 0.28 mmol/kg (0.13-0.49). Cumulative Gadodiamide exposure while in chronic kidney disease stage 5 was significantly higher among cases compared with controls (0.41 vs 0.31 mmol/kg, P = 0.05) and among severe cases (n = 9) compared with non-severe cases (0.49 vs 0.33 mmol/kg, P=0.02). Severe cases developed primarily among patients in regular haemodialysis therapy at exposure. Cases had higher serum concentrations of ionized calcium and phosphate than controls and tended to receive higher doses of epoietin-β than controls at time of exposure. Severe cases were treated with higher doses of epoietin-β than non-severe cases at exposure (10.8 vs 4.4 10 3 IU/week, P= 0.02). Conclusions. Increasing cumulative Gadodiamide exposure, high-dose epoietin-β treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of Gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients in regular haemodialysis therapy at exposure.
