Was There Something Rotten in Denmark: Nephrogenic System Fibrosis Cases Occurring in Copenhagen.

More than half of all serious adverse drug reactions are identified seven years after FDA approval. One recent and unusual example involves a syndrome initially termed nephrogenic dermatopathic fibrosis, and then called nephrogenic systemic fibrosis (NSF).

Nephrogenic Systemic Fibrosis as a Complication after Gadolinium-Containing Contrast Agents: A Rapid Review.

Introduction: Nephrogenic systemic fibrosis (NFS) is a generalized disorder occurring in people with kidney failure. This new disease entity can lead to significant disability or even death. Gadolinium-associated systemic fibrosis is related to exposure to contrast agents used for magnetic resonance imaging. The aim of this study was to review the literature in available scientific databases on NFS-complication after gadolinium-containing contrast agents. Methods: PubMed and Cochrane Library databases were searched using adequate key words. A literature review of the described cases of NSF occurrence after exposure to gadolinium-containing contrast agents was performed. A review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A review written protocol was not drafted. Results: Originally, 647 studies were searched in scientific databases. After rejecting the duplicate results, 515 results were obtained. Finally, nine studies were included in the review. A total of 173 cases with NSF were included in the analysis. The majority of patients were undergoing dialysis. The contrast agent used for MRI was most often gadodiamide and gadopentetate dimeglumine. The time from exposure to NSF symptoms was from two days to three years. Three authors pointed out other factors in their papers that could potentially influence the occurrence of NSF. These included: metabolic acidosis, ongoing infection, higher doses of erythropoietin and higher serum concentrations of ionized calcium and phosphate. Since 2008, the number of reported cases of NSF has decreased significantly. More recent guidelines and reports indicate that not all contrast agents are associated with the same risk of developing NSF. Conclusions: Most NSF occurs after exposure to linear contrast agents. Therefore, it is recommended to limit their use, especially in dialyzed patients and patients with a GFR < 30 mL/min.

Nephrogenic Systemic Fibrosis Risk Assessment and Skin Biopsy Quantification in Patients with Renal Disease following Gadobenate Contrast Administration.

BACKGROUND AND PURPOSE: Nephrogenic systemic fibrosis following administration of intravenous gadobenate during MR imaging is rare. This study aimed to analyze any nephrogenic systemic fibrosis-related risks and quantify skin gadolinium levels in patients with impaired renal function but without nephrogenic systemic fibrosis who had received gadobenate. MATERIALS AND METHODS: In this retrospective study with a prospective skin biopsy phase, patients with estimated glomerular filtration rates of <60 mL/min/1.73 m2 undergoing contrast-enhanced MR imaging from July 2007 through June 2014 were screened for nephrogenic systemic fibrosis using a questionnaire. This was highly sensitive but not specific and reliably excluded nephrogenic systemic fibrosis if responses to at least 6 of the 8 questions were negative. If no nephrogenic systemic fibrosis was detected, a skin biopsy was requested. RESULTS: Of 2914 patients who met these criteria, 1988 were excluded for various reasons. Of the remaining 926 patients, 860 were screened negative for nephrogenic systemic fibrosis. Of these, 17 (2%) had estimated glomerular filtration rates of <15 mL/min/1.73 m2, 51 (6%) had levels of 15 < 30 mL/min/1.73 m2, 234 (27%) had levels of 30 < 45 mL/min/1.73 m2, and 534 (62%) had levels of 45 < 60 mL/min/1.73 m2. Of the 66 who were not cleared of nephrogenic systemic fibrosis by the questionnaire, 6 patients were evaluated by a dermatologist and confirmed not to have nephrogenic systemic fibrosis (no biopsy required). CONCLUSIONS: A diagnosis of nephrogenic systemic fibrosis was excluded in 860 patients with impaired renal function who were followed up and received gadobenate during MR imaging. In 14 such patients who underwent at least 1 gadobenate-enhanced MR imaging examination and did not have nephrogenic systemic fibrosis, gadolinium levels in the skin were exceedingly low.

Observational study on the incidence of nephrogenic systemic fibrosis in patients with renal impairment following gadoterate meglumine administration: the NSsaFe study.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a rare life-threatening condition strongly associated with the administration of gadolinium-based contrast agents in patients with severe or endstage renal impairment. PURPOSE: To prospectively determine the incidence of NSF in patients with renal impairment after administration of gadoterate meglumine. STUDY TYPE: Prospective. POPULATION: In all, 540 patients with moderate, severe, or endstage renal impairment, scheduled to undergo a routine contrast-enhanced MRI with gadoterate meglumine. Mean age was 69.7 ± 12.7 years (range: 21-95) with 58.4% of males. FIELD STRENGTH/SEQUENCE: 1.5T or 3.0T, sequence according to each site practice. ASSESSMENT: Medical history, indication(s) for current MRI and adverse events were recorded for each patient. Patients were followed up over 2 years after administration with three visits separated by at least 3 months to detect any signs/symptoms suggestive of NSF. STATISTICAL TESTS: Descriptive. RESULTS: Renal impairment was graded as moderate for 69.4% of patients, severe for 16.0% and endstage for 12.1%; 2.6% had undergone a kidney transplant. Estimated glomerular filtration rate ranged from 4 to 59 mL/min/1.73 m2 except one value of 74 mL/min/1.73 m2 in a patient with kidney transplant. Central nervous system exploration was the main MRI indication (34.7%) and mean dose injected was 0.22 ± 0.09 mL/kg. Overall, 446 patients (82.6%) attended at least one follow-up visit and completed the NSF questionnaire and 329 (60.9%) attended the 2-year visit. No suspicion of NSF was reported in all 446 patients, including 119 patients with severe or endstage renal impairment. No deaths and no adverse events were reported during the MRI examination and the usual period of follow-up after gadoterate meglumine administration. DATA CONCLUSION: No cases of NSF were observed in the 446 patients with moderate to endstage renal impairment followed up over a maximum of 2 years after injection of gadoterate meglumine. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;51:607-614.

A Systematic Review of 639 Patients with Biopsy-confirmed Nephrogenic Systemic Fibrosis.

Background Although nephrogenic systemic fibrosis (NSF) affects the use of gadolinium-based contrast agents (GBCAs) in MRI, there continues to be limited knowledge because of the small number of patients with NSF. Purpose To perform a systematic review of NSF. Materials and Methods PubMed database was searched by using the term "Nephrogenic systemic fibrosis" from January 2000 to February 2019. Articles reporting details on individual patients with NSF diagnosis on the basis of both clinical presentations and biopsy confirmation were included. Data were pooled and authors were contacted for clarifications. Rates of NSF were compared through 2008 versus after 2008 and for group I versus group II GBCAs, assuming equal market share. Results Included were 639 patients from 173 articles. Data regarding sex were found for 295 men and 254 women. Age at NSF symptom onset was reported for 177 patients (mean, 49 years ± 16 [standard deviation]; age range, 6-87 years). There were 529 patients with documented exposure to GBCAs including gadodiamide (n = 307), gadopentetate dimeglumine (n = 49), gadoversetamide (n = 6), gadobutrol (n = 1), gadobenate dimeglumine (n = 1), multiple (n = 41), and unknown (n = 120). Among patients with previous exposure, only seven patients were administered GBCA after 2008, yielding a lower rate of NSF after 2008 (P < .001). There were motion limitations in 70.8% (296 of 418) of patients, indicating a more serious debilitation. Associated factors reported for NSF included exposure to GBCA group I (P < .001), dialysis, proinflammatory conditions, hyperphosphatemia, ß-blockers, and epoetin. For 341 patients with follow-up, 12 patients were cured and 72 patients partially improved including one during pregnancy. Among those 84 patients reported as cured or improved, in 34 patients cure or improvement occurred after renal function restoration. Four deaths were attributed to NSF. Conclusion Although 639 patients with biopsy-confirmed nephrogenic systemic fibrosis were reported, only seven were after gadolinium-based contrast agent exposure after 2008, indicating that regulatory actions and practice changes have been effective preventive measures. Improvement and sometimes cure with renal function restoration are now possible. © RSNA, 2019 See also the editorial by Davenport in this issue.

Renal Safety of Intravenous Gadolinium-enhanced MRI in Patients Following Liver Transplantation.

BACKGROUND: Intravenous contrast-enhanced imaging is invaluable in diagnosing pathology following liver transplantation. Given the potential risk of contrast nephropathy associated with iodinated computed tomography contrast, alternate contrast modalities need to be examined, especially in the setting of renal insufficiency. The purpose of this study was to examine the renal safety of MRI with gadolinium following liver transplantation. METHODS: The study involved a retrospective analysis of 549 cases of abdominal MRI with low-dose gadobenate dimeglumine in liver transplant recipients at a single center. For each case, serum creatinine values before and after the MRI were compared. In addition, cases were analyzed for the development of nephrogenic systemic fibrosis. RESULTS: Pre-MRI creatinine values ranged from 0.32 to 6.57 mg/dL (median, 1.28 g/dL), with 191 cases having values ≥1.5 mg/dL (median, 1.86 g/dL). A comparison of the pre- and post-MRI creatinine values showed no significant difference, including those patients with pre-MRI values ≥1.5 mg/dL (mean change of -0.04 [95% confidence interval, -0.07 to -0.01; P = 0.004]). No cases of nephrogenic systemic fibrosis were noted. CONCLUSIONS: Our findings suggest that, irrespective of baseline renal function, MRI with gadobenate dimeglumine is a nonnephrotoxic imaging modality in liver transplant recipients. Importantly, this intravenous contrast-enhanced imaging modality can be considered in those posttransplant patients who have a contraindication to computed tomography contrast due to renal insufficiency.

Influence of excess ligand on Nephrogenic Systemic Fibrosis associated with nonionic, linear gadolinium-based contrast agents.

BACKGROUND: The molecular structure, charge, thermodynamic and kinetic stability are approximately the same for gadodiamide and gadoversetamide, the main substantive difference is that gadodiamide is manufactured with 5% free ligand to form Omniscan® and gadoversetamide with 10% free ligand to form OptiMARK®. PURPOSE: To determine the relative risk of Nephrogenic Systemic Fibrosis (NSF) between gadodiamide (Omniscan®) and gadoversetamide (OptiMARK®) and to explore the potential contribution of the amount of excess ligand added to their commercial formulations. MATERIALS AND METHODS: In this retrospective observational study, the number of doses and NSF cases associated with these agents were calculated based on two different approaches: the number of doses was determined based on pharmaceutical companies' information, and the number of unconfounded NSF cases was obtained from the previously published literature based on a legal database. A second analysis estimates the number of doses and NSF cases from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). RESULTS: Approximately 87 million and 12 million doses of Omniscan® and OptiMARK®, respectively, have been administered worldwide since their original approval for use in the various countries throughout the world. A total of 197 and 8 unconfounded cases of NSF have been reported with Omniscan® and OptiMARK®, rendering an incidence of 2.3/million and 0.7/million for these agents, respectively. The FAERS analysis suggested reported incidences of 13.1/million and 5.0/million. CONCLUSION: There is an approximately 3-fold greater incidence of NSF from Omniscan® than OptiMARK®. The difference in incidence might reflect the lesser quantity of added free ligand to the formulation of Omniscan®.

10 Years of Nephrogenic Systemic Fibrosis: A Comprehensive Analysis of Nephrogenic Systemic Fibrosis Reports Received by a Pharmaceutical Company from 2006 to 2016.

OBJECTIVES: The aim of this study was to critically assess the evaluation and categorization process for nephrogenic systemic fibrosis (NSF) based on reports received by Bayer from 2006 to 2016. MATERIALS AND METHODS: A total of 779 NSF reports received by Bayer globally from 2006 to 2016 were included in the analysis. Arlington Medical Resources provided gadolinium-based contrast agent (GBCA) market share. Reports were conservatively categorized based on the Cowper/Girardi criteria. A statistical model simulated the impact of market share and market introduction on the number of unconfounded reports. RESULTS: For all reports, reported onset of disease ranged from 1996 and 2012. Of 779 reports, 325 involved a Bayer product only, 208 involved only products from other companies (or unknown GBCA), and 246 involved both Bayer and non-Bayer products. Most of all reports (86%) originated from the United States.Through 2006, Magnevist and Omniscan dominated the US market (>80% combined market share). All other GBCAs with fewer NSF reports comprised the remaining combined market share of less than 20% or were introduced after May 2007, after safety recommendations came into effect.A total of 563 reports (220 single-agent and 343 multiagent reports) involved Magnevist. In at least 150 of the 343 reports, a different GBCA (Omniscan, 118; OptiMARK, 15; MultiHance, 6; and macrocyclic agent, 11) showed the closest temporal relationship to onset of NSF-like symptoms.The simulation model demonstrated that patients receiving a GBCA with lower market share and late market introduction are less likely to be observed in an unconfounded setting. CONCLUSIONS: Year of market introduction, as well as US market share in 2000 to 2007, greatly influenced the absolute number of NSF reports for each GBCA, their a priori probability to cause NSF, as well as their a priori probability to be associated with unconfounded cases of NSF. Variability in case interpretation and pharmacovigilance approaches also influence the absolute number of unconfounded cases and should therefore not be used for comparative risk assessments. This should be primarily based on objective product parameters such as structure, stability, pharmacokinetics, and dose.

Notice of Withdrawal: No Incidence of Nephrogenic Systemic Fibrosis after Gadobenate Dimeglumine Administration in Patients Undergoing Dialysis or Those with Severe Chronic Kidney Disease.

The authors have requested to withdraw this manuscript from publication because the study was not conducted in full accordance with the relevant institutional IRB protocol. © RSNA, 2018.

Nephrogenic systemic fibrosis: A survey of the use of gadolinium-based contrast agents in Ghana.

INTRODUCTION: The aim of this study is to identify current practice of administration of gadolinium-based contrast agents (GBCAs) in Ghana. METHOD: A total of 13 MRI (magnetic resonance imaging) facilities were sent a survey questionnaire to request information on their current practice with the use of GBCAs. RESULTS: Gadodiamide, a high risk GBCA accounted for 67% of first line agents. 5 (42%) had a departmental protocol on the administration of GBCAs with regards to its association with nephrogenic systemic fibrosis (NSF). Of the 8 that use gadodiamide, 3 check kidney function in all patients, 2 check in selected patients, and 3 do not check at all. All 3 that screen all patients do not use contrast if the patient has an eGFR (estimated glomerular filtration rate) of 30-59 ml/min, 1 considers other modality; and if the patient has an eGFR of <30 ml/min, 2 do not use contrast but consider other modality, however 1 continues with the high risk agent. CONCLUSION: Gadodiamide is widely used, with varied practice in screening for renal function, and risk factors associated with NSF. Current evidence shows that it is advisable to administer macrocyclic agents in patients with compromised renal function. It is also imperative to establish local guidelines in line with international guidelines in order to minimize the incidence of NSF.

Observational study on the safety profile of gadoterate meglumine in 35,499 patients: The SECURE study.

PURPOSE: To investigate the safety of gadoterate meglumine and identify the incidence of nephrogenic systemic fibrosis (NSF). MATERIALS AND METHODS: An international prospective observational study was conducted from November 2008 to June 2013. A total of 35,499 adults and children who were scheduled to undergo contrast-enhanced MRI using gadoterate meglumine were analyzed (female, 53.1%; mean age: 49.5 years; range: 0-98 years). At least 3-month follow-up was planned for patients with an estimated creatinine clearance or glomerular filtration rate <60 mL/min (/1.73 m2) to detect any suspicion or occurrence of NSF. Adverse events (AEs) were prospectively recorded. Demographic data, risk factors, indications for MRI examinations, characteristics of gadoterate meglumine administration, and efficacy were documented. RESULTS: MRI examinations were mainly for central nervous system (61%). The most frequent risk factor was renal insufficiency (14.7%). Seventy AEs were observed in 44 patients (0.12%). Among the 70 AEs, 38 in 32 patients (0.09% of all patients) were considered related to gadoterate meglumine and classified as adverse drug reaction (ADR).The most frequent ADRs were urticaria (9 patients, 0.03%), nausea (7 patients, 0.02%), and vomiting (4 patients, 0.01%). Within the pediatric population (1,629 patients), only one AE (vomiting) was observed. Nine adult patients (0.03%) experienced serious AEs. Moderate to severe renal insufficiency at inclusion was reported in 514 patients (1.5%). Among them, 476 (92.6%) were followed-up. No patients were suspected of having NSF and no cases of NSF were observed. CONCLUSION: Our study confirms the excellent safety profile of gadoterate meglumine in routine practice. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:988-997.

Incidence of Nephrogenic Systemic Fibrosis Using Gadobenate Dimeglumine in 1423 Patients With Renal Insufficiency Compared With Gadodiamide.

OBJECTIVE: The purpose of this study was to assess the incidence of nephrogenic systemic fibrosis (NSF) before and after educational interventions, implementation of a clinical screening process, and change to gadobenate dimeglumine in patients who had an estimated glomerular filtration rate (eGFR) of 30 mL/min per 1.72 m or less. METHODS: This is a Health Insurance Portability and Accountability Act compliant, institutional review board exempt study. Two periods were studied-July 2005 to June 2006, during which gadodiamide was utilized as our magnetic resonance (MR) contrast agent, and November 2006 to August 2014, during which gadobenate dimeglumine was used as our MR contrast agent in patients who had an eGFR 30 mL/min per 1.72 m or less. In addition to a change in the MR contrast agent, education of our staff physician to the risks of NSF with MR contrast agents and the implementation of a clinical screening process occurred. The rate of NSF before and after the interventions was compared using the χ test. RESULTS: There was a statistically significant difference in the incidence of NSF in patients with an eGFR 30 mL/min per 1.72 m or less between the 2 periods: July 2005 to June 2006, 6 of 246 patients were diagnosed with NSF (P < 0.001), versus November 2006 to August 2014, 0 of 1423 patients were diagnosed with NSF. CONCLUSIONS: Our data demonstrates a marked decrease in the incidence of NSF after education of our referring physicians, implementation of clinical screening process, and change to gadobenate dimeglumine from gadodiamide in patients with renal insufficiency. This approach potentially provides an acceptable risk-benefit profile for patients with renal insufficiency that required MR imaging for clinical care.

Gadolinium-Based Contrast Agent Accumulation and Toxicity: An Update.

In current practice, gadolinium-based contrast agents have been considered safe when used at clinically recommended doses in patients without severe renal insufficiency. The causal relationship between gadolinium-based contrast agents and nephrogenic systemic fibrosis in patients with renal insufficiency resulted in new policies regarding the administration of these agents. After an effective screening of patients with renal disease by performing either unenhanced or reduced-dose-enhanced studies in these patients and by using the most stable contrast agents, nephrogenic systemic fibrosis has been largely eliminated since 2009. Evidence of in vivo gadolinium deposition in bone tissue in patients with normal renal function is well-established, but recent literature showing that gadolinium might also deposit in the brain in patients with intact blood-brain barriers caught many individuals in the imaging community by surprise. The purpose of this review was to summarize the literature on gadolinium-based contrast agents, tying together information on agent stability and animal and human studies, and to emphasize that low-stability agents are the ones most often associated with brain deposition.

Prospective Cohort Study of Nephrogenic Systemic Fibrosis in Patients With Stage 3-5 Chronic Kidney Disease Undergoing MRI With Injected Gadobenate Dimeglumine or Gadoteridol.

OBJECTIVE: The purpose of this study was to determine the incidence of nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD) and moderate-to-severe impairment of kidney function who had not previously been exposed to gadolinium-based contrast agents (GBCAs) or referred to undergo contrast-enhanced MRI with gadobenate dimeglumine or gadoteridol. SUBJECTS AND METHODS: Two multicenter prospective cohort studies evaluated the incidence of unconfounded NSF in patients with stage 3 CKD (estimated glomerular filtration rate [eGFR] in cohort 1, 30-59 mL/min/1.73 m(2)) or stage 4 or 5 CKD (eGFR in cohort 2, < 30 mL/min/1.73 m(2)) after injection of gadobenate dimeglumine (study A) or gadoteridol (study B). A third study (study C) determined the incidence of NSF in patients with stage 4 or 5 CKD who had not received a GBCA in the 10 years before enrollment. Monitoring for signs and symptoms suggestive of NSF was performed via telephone at 1, 3, 6, and 18 months, with clinic visits occurring at 1 and 2 years. RESULTS: For studies A and B, the populations evaluated for NSF comprised 363 and 171 patients, respectively, with 318 and 159 patients in cohort 1 of each study, respectively, and with 45 and 12 patients in cohort 2, respectively. No signs or symptoms of NSF were reported or detected during the 2 years of patient monitoring. Likewise, no cases of NSF were reported for any of the 405 subjects enrolled in study C. CONCLUSION: To our knowledge, and consistent with reports in the literature, no association of gadobenate dimeglumine or gadoteridol with unconfounded cases of NSF has yet been established. Study data confirm that both gadoteridol and gadobenate dimeglumine properly belong to the class of GBCAs considered to be associated with the lowest risk of NSF.

Gadobenate Dimeglumine Administration and Nephrogenic Systemic Fibrosis: Is There a Real Risk in Patients with Impaired Renal Function?

PURPOSE: To determine the incidence of nephrogenic systemic fibrosis (NSF) in patients with renal disease who received gadobenate dimeglumine at a single medical center. MATERIALS AND METHODS: This was an institutional review board-approved HIPAA-compliant retrospective study with waiver of informed consent. Patients either underwent dialysis or not, had an abnormal estimated glomerular filtration rate (eGFR), and underwent magnetic resonance (MR) imaging and/or MR angiography with gabobenate dimeglumine in 2010. Dialysis status, eGFR, time to transplantation, waiting list status, contrast material volume at index imaging, and additional imaging examinations between 2007 and 2014 were recorded. Clinical notes with and without integument examinations, pathologic records, and additional patient communication were evaluated for development of NSF through September 2014. Dates of latest documented integument examination and latest interaction were recorded. Mean, standard deviation, and median values were obtained, along with incidence percentage of NSF. RESULTS: Of 401 patients (172 women, 229 men; mean age, 50 years), 75.5% were dialysis dependent (n = 303) and 24.4% (n = 98) were not undergoing dialysis, with a mean eGFR ± standard deviation of 17 mL/min per 1.73 m(2) ± 5.6 (range, 6-41 mL/min per 1.73 m(2); median, 16.3 mL/min per 1.73 m(2)). Mean and median contrast material volume at index imaging were 24 mL ± 5.7 (range, 9-45 mL). Additional contrast material volume administered was 23 mL ± 12.9 (range, 6-64 mL; median, 20 mL; n = 66). One hundred twenty-six patients (31%) received a transplant; mean time to transplantation was 1.72 years ± 1.25 (range, 0-4.46 years; median, 1.4 years). No patients received diagnoses of NSF. Mean follow-up was 2.35 years ± 1.61 (range, 0.00-4.61 years; median, 2.75 years) with documented integument examination and 3.08 years ± 1.36 (range, 0.16-4.66 years; median, 3.66 years) with direct patient communication. CONCLUSION: No patients undergoing peritoneal dialysis, hemodialysis, or nondialysis who experienced renal failure developed NSF after administration of gadobenate dimeglumine after more than 2 years' mean follow-up. Gadobenate dimeglumine may be safe in this population.

Risk of nephrogenic systemic fibrosis is low in patients with chronic liver disease exposed to gadolinium-based contrast agents.

PURPOSE: To determine the risk of nephrogenic systemic fibrosis (NSF) in a cohort of patients with chronic liver disease. MATERIALS AND METHODS: This retrospective, Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study was performed at a single tertiary liver center. The study cohort comprised 1167 patients with chronic liver disease followed in a liver clinic and exposed to gadolinium-based contrast agents (GBCAs) between February 2004 and October 2007. A retrospective review of medical records was performed. For each patient, data were collected on demographics, history of GBCA exposure, presence of purported risk factors for NSF, and histopathological evidence of NSF. RESULTS: Of the 1167 patients with chronic liver disease, 58% (n = 678) had cirrhosis. The patients had a total of 2421 separate GBCA exposures. Fifty-five percent (n = 646) had a single exposure, 19% (n = 218) had two exposures, and 26% (n = 303) had three or more exposures. Seventy-two percent (n = 843) of patients had renal insufficiency, 25 patients (2.1%) had hepatorenal syndrome, 80 patients (6.8%) were in the perioperative liver transplant period, and 49 patients (4.2%) had one or more additional risk factors for NSF. None of the 1167 patients developed NSF. CONCLUSION: Chronic liver disease does not appear to be a significant risk factor for NSF.

Incidence of nephrogenic systemic fibrosis in patients undergoing dialysis after contrast-enhanced magnetic resonance imaging with gadolinium-based contrast agents: the Prospective Fibrose Nephrogénique Systémique study.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) has been related to the use of gadolinium-based contrast agents (GBCAs) in patients undergoing dialysis. The Prospective Fibrose Nephrogénique Systémique study, a French prospective study supported by the French drug regulatory agency (Agence Nationale de Sécurité du Médicament) and the French Societies of Nephrology, Dermatology, and Radiology, aimed at determining the incidence of NSF in patients undergoing long-term dialysis. MATERIALS AND METHODS: Adult patients undergoing long-term dialysis receiving a magnetic resonance imaging (MRI) examination prescribed between January 15, 2009 and May 31, 2011, with or without GBCA were included. The methodology was based on a patient form intended to detect any dermatological event (DE) that may occur within 4 months after the examination. Further investigations were planned with their physicians if a DE was reported. RESULTS: A total of 571 patients were included. A total of 50.3% received GBCA. Among them, 93.4% received a macrocyclic GBCA, usually gadoteric acid (88.9%). All in all, 22 patients (3.9%) reported a DE. Dermatological diagnoses did not reveal any evidence of NSF. CONCLUSIONS: The incidence of NSF after a single dose of a macrocyclic GBCA is null in our sample of 268 patients undergoing dialysis (hemodialysis and peritoneal dialysis). This incidence is just lower than 0.5%. When contrast-enhanced MRI can be essential, or even decisive, to the diagnosis, these results are important and reassuring if physicians need to perform contrast-enhanced MRI in patients undergoing dialysis.

Pediatric nephrogenic systemic fibrosis is rarely reported: a RADAR report.

BACKGROUND: Nephrogenic systemic fibrosis is a fibrosing disorder associated with exposure to gadolinium-based contrast agents in people with severely compromised renal function. OBJECTIVE: The purpose of this study was to determine the reported number of cases of nephrogenic systemic fibrosis in children using three distinct publicly available data sources. MATERIALS AND METHODS: We conducted systematic searches of the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), the International Center for Nephrogenic Systemic Fibrosis Research (ICNSFR) registry and published literature from January 1997 through September 2012. We contacted authors of individual published cases to obtain follow-up data. Data sets were cross-referenced to eliminate duplicate reporting. RESULTS: We identified 23 children with nephrogenic systemic fibrosis. Seventeen had documented exposure to gadolinium-based contrast agents. Six children had been reported in both the FAERS and the literature, four in the FAERS and the ICNSFR registry and five in all three data sources. CONCLUSION: Nephrogenic systemic fibrosis has been rarely reported in children. Although rules related to confidentiality limit the ability to reconcile reports, active pharmaco-vigilance using RADAR (Research on Adverse Drug events And Reports) methodology helped in establishing the number of individual pediatric cases within the three major data sources.

Nephrogenic systemic fibrosis in Denmark--a nationwide investigation.

BACKGROUND: Nephrogenic systemic fibrosis is a debilitating and painful disorder with an increased stimulation of the connective tissue in the skin and systemic tissues. The disease is associated with exposure to gadolinium-based contrast agent used in magnetic resonance imaging in patients with renal impairment. METHODS: The prevalence of nephrogenic systemic fibrosis has so far never been determined at a national level. In 2009, Denmark was the first country to design a guideline for the tracing of nephrogenic systemic fibrosis patients. The aim of this paper is to communicate the main findings of this quest. RESULTS: The outcome of the nationwide investigation revealed that Denmark had 65 patients with nephrogenic systemic fibrosis and thereby the highest prevalence of nephrogenic systemic fibrosis worldwide with 65 per 5.6 million inhabitants, or 12 per million. CONCLUSIONS: The nationwide investigation in Denmark revealed the highest prevalence of NSF worldwide. This may be rooted in a high level of awareness of NSF both among doctors, politicians and, not least, the media, combined with the fact that a nationwide NSF investigation was initiated.