Explore the vast range of titles available.

Gadolinium-based contrast agents (GBCAs) have transformed magnetic resonance imaging (MRI) by facilitating the use of contrast-enhanced MRI to allow vital clinical diagnosis in a plethora of disease that would otherwise remain undetected. Although over 500 million doses have been administered worldwide, scientific research has documented the retention of gadolinium in tissues, long after exposure, and the discovery of a GBCA-associated disease termed nephrogenic systemic fibrosis, found in patients with impaired renal function. An understanding of the pharmacokinetics in humans and animals alike are pivotal to the understanding of the distribution and excretion of gadolinium and GBCAs, and ultimately their potential retention. This has been well studied in humans and more so in animals, and recently there has been a particular focus on potential toxicities associated with multiple GBCA administration. The purpose of this review is to highlight what is currently known in the literature regarding the pharmacokinetics of gadolinium in humans and animals, and any toxicity associated with GBCA use.

Risks of diagnostic imaging include cancer from radiation exposure and nephrogenic systemic fibrosis. The increase in volume of imaging between 1980 and 2006 has led to a sixfold increase in annual per capita radiation exposure. It is predicted that 2 percent of future cancers will be caused by radiation from computed tomography (CT) exposure. Gadolinium contrast media should be avoided in patients with stage 4 or 5 chronic kidney disease because of the risk of nephrogenic systemic fibrosis. Appropriate use of imaging based on guidelines for specific clinical conditions can reduce these risks. Although noncontrast CT of the head is needed to rule out bleeding in patients with suspected stroke within the first three hours of symptom onset, diffusion-weighted imaging with magnetic resonance of the head and neck is superior to CT within three to 24 hours of symptom onset. Headache merits neuroimaging in special circumstances only. Sestamibi radioisotope has less radiation than thallium for myocardial perfusion imaging. Use of intravenous contrast media with abdominopelvic CT significantly increases the diagnostic accuracy for appendicitis. Cholescintigraphy has better discrimination to diagnose acute cholecystitis than CT in patients with equivocal ultrasonography results. Limited three-view intravenous urography is recommended in pregnancy to evaluate urolithiasis if initial ultrasonography findings are negative or equivocal. Given that many asymptomatic adults have abnormal findings on lumbar spine magnetic resonance imaging, this modality generally should not be performed for nonspecific chronic low back pain in the absence of red flags. Whole body scanning is not supported by current evidence.

NSF is a rare fibrosing disorder characterised by skin thickening on the extremities and trunk and dermal fibrosis.12 This disease only occurs in patients with kidney failure.2 Development of NSF is most commonly linked to gadolinium exposure, as in gadolinium-based contrast agents (GB-CAs).1 GB-CAs are excreted nearly exclusively by the kidney. Patients' glomerular filtration rates determine the risk of NSF development after gadolinium exposure, which has been reported to be approximately 3–7% in patients with reduced renal function.3 There is no proven therapy for NSF, although it is thought that renal transplantation may halt the progression of NSF.2 Additionally, the likelihood of developing NSF varies between the two types of GB-CAs: cyclic and linear.2 Linear agents are flexible open chains with a relatively weak bond to gadolinium, while cyclic agents cage the gadolinium in a cavity and offer better protection, stability and binding to gadolinium.2 Cyclic GB-CAs are less likely to release free gadolinium, which is toxic in vivo and are thought to be safer and less likely to cause NSF than linear agents are.2 If GB-CAs must be used in patients with renal failure, cyclic GB-CAs are recommended over linear agents.2 Our patient developed NSF after exposure to a linear GB-CA. Contributors AH substantially contributed to the analysis and interpretation of data for the study, drafted the manuscript, approved the final version and is accountable for all aspects of the study.

-Nephrogenic systemic fibrosis (NSF) is a rare but serious disorder initially described as a purely dermatologic process. Isolated autopsy reports have described multiorgan involvement by this disease. -To further illustrate the varied and systemic involvement of NSF by describing the autopsy experience at the Massachusetts General Hospital. -We describe the findings in a series of 4 autopsy cases of patients diagnosed with NSF. This report describes the history of renal dysfunction, exposure to gadolinium-containing contrast agents, specific laboratory parameters, and the extent of systemic involvement identified by postmortem examination. -Causes of death included systemic thromboembolic disease (n = 3) and pneumonia (n = 1). Laboratory parameters and type, dose, or timing of gadolinium-containing contrast-agent exposure did not correlate with clinical findings and outcomes. All patients demonstrated cutaneous manifestations of the disease and nephrocalcinosis, with some exhibiting calcification and fibrosis of the dura, thyroid, and heart including the cardiac conduction system, on postmortem examination. Soft tissue calcification was associated with concurrent hyperparathyroidism or high serum parathyroid hormone levels. -Thromboembolic disease can be a significant clinical complication of NSF. Patients with NSF may also develop characteristic histologic features of fibrosis and calcification in multiple organs, with significant morbidity and mortality. This autopsy series highlights the variability of systemic manifestations of NSF.

ObjectivesRecent safety concerns regarding gadolinium-based contrast agents (GdCAs) concluded with the suspension of some agents from the European market, yet a clinical consequence remains unknown. We used electronic health records to investigate the incidence of potential toxicity to gadoteric acid (Dotarem®) within our local population, including those with renal insufficiency (RI).MethodsData for patients who underwent contrast-enhanced MRI were identified, stratified by renal function at time of scan and retrospectively followed using routinely collected health data. Searches performed were: records of hypersensitivity reactions; diagnoses of nephrogenic systemic fibrosis (NSF); onset of chronic pain, a symptom that has been associated with NSF and the theorised gadolinium deposition disease (GDD); and post-contrast acute kidney injury (PC-AKI). Comparisons were made between patients and controls (those who underwent non-contrast scans) via chi-square and ANOVA statistical tests.ResultsOf the 22,897 contrast-enhanced MRI scans performed locally from 2004–2016 (adult, n = 22,325 and paediatric, n = 572), 14% were performed on patients with RI (30 ≤ eGFR < 60, n = 2,622; 15 ≤ eGFR < 30, n = 464; eGFR < 15, n = 123). Two adult patients (0.01%) suffered hypersensitivity reactions. Zero cases of NSF were reported, with an average follow-up time of 6.0 ± 2.5 years (range, 8 months–15 years). Analysis failed to highlight statistically higher rates of chronic pain onset post-MRI (adult: p = 0.777, paediatric: p = 0.578), or PC-AKI (adult: p = 0.566, paediatric: p = 0.841), in the patient groups compared to controls.ConclusionsThese data indicate that administration of gadoteric acid to RI patients does not result in a higher rate of signs or symptoms that may be associated with gadolinium toxicity when compared to controls.Key Points• Following 22,897 administrations of gadoteric acid to a local population, there was no association with symptoms that may be associated with gadolinium toxicity.• Zero cases of nephrogenic systemic fibrosis were reported following 3,209 gadoteric acid administrations to a cohort of renally insufficient patients.• A low number of hypersensitivity reactions were observed (0.01%) and no higher rate of chronic pain or post-contrast acute kidney injury were noted when compared with a control cohort of non-contrast-enhanced examinations.

Nephrogenic systemic fibrosis (NSF) is a debilitating fibrosing disorder that develops in patients with underlying kidney disease following exposure to gadolinium-containing contrast agents. NSF presents with cutaneous hyperpigmentation and induration and joint contractures, but fibrosis may also develop in other organs. NSF has been observed in up to 18% of patients receiving chronic haemodialysis and also may occur in individuals with stages 3 and 4 chronic kidney disease and, occasionally, in individuals who had experienced acute renal failure. Mortality is increased significantly among individuals with NSF. Although no medical treatment has been proved to be universally effective in patients with NSF, imatinib mesylate shows potential as a therapeutic agent and is currently being studied in these patients.

Nephrogenic fibrosing dermopathy (NFD) is an entity of unknown etiology that has only been reported in patients with impaired kidney function. It has characteristic diagnostic findings by skin biopsy and due to its systemic involvement in some reported cases, the term \"nephrogenic systemic fibrosis\" has been recently suggested as more appropriate for the nomenclature of this entity. There is no curative treatment currently available and very few cases have been reported in children. We hereby report two cases so as to alert pediatric health care providers about the existence of this disorder.

Nephrogenic fibrosing dermopathy (NFD) is a rare fibrosing skin disease of unknown etiology occurring in patients with terminal renal disease. It was first described in the year 2000. The histology of NFD shows an increased number of dendritic cells, fibroblasts and thickened collagen fibers resembling scleromyxedema. It can be distinguished from scleromyxedema by a different distribution pattern of the skin lesions with indurated plaques mainly on the extremities and the absence of paraproteinemia. As yet, no treatment for NFD has been proven to be uniformly efficient. We describe the case of a 40-year old patient with renal insufficiency who was treated with hemodialysis and who had undergone kidney transplantation. Two years after transplantation, she developed sclerodermiform brownish plaques on her extremities. The induration improved significantly after 4 cycles of extracorporeal photopheresis.