Gadolinium-Based Contrast Agents: Updates and Answers to Typical Questions Regarding Gadolinium Use.

Gadolinium-based contrast agents have expanded the diagnostic usefulness and capability of magnetic resonance imaging. Despite their highly favorable safety profile, these agents have been associated with nephrogenic systemic fibrosis in a small number of patients who have advanced kidney disease. Recently, trace amounts of gadolinium deposition in the brain and other organs have been reported after contrast exposure, even in patients with normal renal function. In this review, we provide a brief overview of recent updates and discuss typical clinical situations related to the use of gadolinium-based contrast agents.

Long-term safety of Gadofosveset in clinical practice.

PURPOSE: The purpose of this study was to systematically search for long-term complications, including Nephrogenic Systemic Fibrosis (NSF), in patients who were previously administered the gadolinium-based contrast agent Gadofosveset at our institute. MATERIALS AND METHODS: All patients who were administered Gadofosveset at our institute between 2006 and 2009 were identified in our Radiological Information System (RIS). Clinical data such as cause of death during follow-up, and dermatological or nephrological diseases were systematically searched for in electronic patient records (EPR). RESULTS: During 2006-2009, Gadofosveset was administered a total of 67 times to 62 patients. One patient was unavailable for follow-up. The remaining 61 patients were followed up for up to 14 (median 12) years based on RIS and EPR data. There were 13 deaths among the 61 patients, all assessed as unrelated to Gadofosveset administration. No dermatological or renal disease suggestive of NSF, or potentially related to Gadofosveset administration, was found. At the time of examination, six patients were diagnosed with various stages of renal insufficiency, three of whom were on hemodialysis. Another three patients were diagnosed with renal insufficiency during the follow-up period, but none of these diagnoses were suspected to be related to the administration of Gadofosveset. CONCLUSIONS: Based on the results of this retrospective safety analysis of up to 14 years following 1-2 exposures, we conclude that Gadofosveset in clinical practice is safe in the long-term.

The Use of Contrast Agents in Interventional Pain Procedures: A Multispecialty and Multisociety Practice Advisory on Nephrogenic Systemic Fibrosis, Gadolinium Deposition in the Brain, Encephalopathy After Unintentional Intrathecal Gadolinium Injection, and Hypersensitivity Reactions.

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.

Nephrogenic Systemic Fibrosis in the Setting of Transient Renal Insufficiency.

Nephrogenic systemic fibrosis (NSF) is a rare disease that can present in patients with kidney injury who have been exposed to gadolinium-based contrast agents (GBCAs). These patients can easily be misdiagnosed as having another disease because they do not fit the usual presentation of being on hemodialysis. We report a case of NSF occurring in a patient with resolved transient renal insufficiency and no history of chronic renal disease.

Late Onset Nephrogenic Systemic Fibrosis in a Patient with Stage 3 Chronic Kidney Disease: a Case Report.

Nephrogenic systemic fibrosis (NSF) is a progressive systemic fibrosing disease that may occur after gadolinium contrast exposure. It can lead to severe complications and even death. NSF is highly prevalent among patients with advanced chronic kidney disease (CKD). In this report, however, we describe the case of a patient with NSF that occurred during early CKD. A 65-year-old man with stage 3a CKD was transferred to our hospital because of lower extremity edema. The medical history revealed that he was exposed to gadolinium 185 days earlier, and the result of his tibial skin biopsy was consistent with NSF. The patient underwent a combined therapy with ultraviolet-A1 phototherapy and methotrexate and steroid therapy for 6 months. The combined therapy stopped the systemic progression of NSF.

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.

Evaluating the Patient with Reported Gadolinium-Associated Illness.

INTRODUCTION: Gadolinium-based contrast agents (GBCAs) have been increasingly used in clinical practice since their introduction in the 1980s. Recently, increased public attention has been given to patients who report new symptoms following GBCA exposure. This review details the current knowledge surrounding GBCAs, with a focus on the known and proposed disease states that may be associated with GBCAs. Recommendations for the appropriate clinical workup of a patient suspected of having symptoms attributable to gadolinium exposure are included. DISCUSSION: GBCAs are known to precipitate the disease state nephrogenic systemic fibrosis (NSF), a syndrome characterized by skin thickening in patients with preexisting renal disease. An additional syndrome, termed gadolinium deposition disease, has been proposed to describe patients with normal renal function who develop an array of symptoms following GBCA exposure. While there is a potential physiologic basis for the development of this condition, there is no conclusive evidence to support a causal relationship between GBCA administration and the reported symptoms yet. Clinical evaluation revolves around focused history-taking and physical examination, given the absence of a reliable link between patient symptoms and measured gadolinium levels. There are no recommended treatments for suspected gadolinium deposition disease. Chelation therapy, which is not approved for this indication, carries undue risk without documented efficacy. CONCLUSIONS: The extent to which GBCAs contribute to clinically relevant adverse effects remains an important and evolving field of study. NSF remains the only proven disease state associated with GBCA exposure. Additional data are required to evaluate whether other symptoms should be attributed to GBCAs.

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®.

[Nephrogenic fibrosing dermatosis: From clinic to microscopy]. / Dermatose fibrosante néphrogénique : de la clinique à la microscopie.

Nephrogenic systemic fibrosis is a rare entity occurred in patients with renal failure. It is related to toxicity to gadolinium, which is used as a contrast agent in magnetic resonance imaging. Clinic manifestations are variable. They begin by a thickening of the skin in the lower limbs and extending to the upper limbs. We report a new case of nephrogenic systemic fibrosis where cutaneous lesions begin in the upper right limb as indurated and ulcerated nodules. The diagnosis is histological.

A unique case of nephrogenic systemic fibrosis from gadolinium exposure in a patient with normal eGFR.

A 57-year-old woman presented with swelling and thickening of the skin of the lower extremities. Three months prior to presentation, patient had MRI with gadolinium as part of an evaluation for suspected pancreatic malignancy. Creatinine levels at the time of gadolinium exposure were 0.9-1.2 mg/dL, with a corresponding estimated glomerular filtration rate of 64 mL/min/1.73m2 by modification of diet in renal disease equation. Twenty-four-hour urine creatinine clearance was performed as an outpatient following development of symptoms. This revealed a creatinine clearance of 23 mL/min, suggestive of advanced chronic kidney disease despite an estimated glomerular filtration rate of 64 mL/min/1.73m2 Skin biopsy was positive for sclerosing dermopathy. These findings, in addition to the temporal association with gadolinium exposure, led to the diagnosis of nephrogenic systemic fibrosis.

European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).

Erythema nodosum masking nephrogenic systemic fibrosis as initial skin manifestation.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a complication of the gadolinium-based contrast agent used in imaging studies. It is typically characterised by hard, erythematous and indurated skin plaques with surrounding subcutaneous oedema. Distinct papules and subcutaneous nodules can also be seen. Fibrocytes in NSF are immunohistochemically positive for CD34. CASE PRESENTATION: We present a case of NSF occurred after gadolinium exposure in which the initial presentation mimics an erythema nodosum (EN)-like picture. An initial skin biopsy showed EN. Subsequently the patient developed progressive skin and joints contracture. A repeated skin biopsy done three months later confirmed the diagnosis of NSF. As far as we are aware, this is the second reported case of NSF that mimicked the presentation of EN in the early phase of the disease. CONCLUSIONS: The appearance of EN-like disease can be one of the early manifestations of NSF. We hope that early recognition of this unusual presentation can alert the physician or nephrologist to the potential diagnosis of NSF.

Gadolinium contrast agents - are they really safe?

Gadolinium-based contrast agents (GBCA) are used worldwide for enhanced MRI examinations, including heart and vessels. Gadolinium is a highly toxic heavy metal. If used in GBCA it must be tightly bound to ligands. The configuration of ligands influences the stability of the GBCA and two types of chelates have been used. Macrocyclic chelates offer better protection and binding of gadolinium ion than linear chelates with a flexible open chain - gadolinium could be more easily released from the latter ones. GBCAs are excreted from the body mostly by the kidneys, which is of importance in chronic kidney disease.Two states are related to gadolinium: nephrogenic systemic fibrosis (NSF) and gadolinium body storage. NSF is a severe and debilitating disease, directly connected to gadolinium toxicity, proven after the use of linear chelates. Due to strict recommendations of radiology societies, NSF was practically eradicated. Gadolinium deposition was observed especially in bones and in some brain areas: in dentate nucleus and in globus pallidus, even years after the GBCA administration. The form of the storage (chelated or free), as well as their clinical impact, are not clear, but first observations of "gadolinium deposition disease" have been reported.

Gadolinium-Induced Nephrogenic Systemic Fibrosis.

The column in this issue is supplied by Anita H. Shah, M.D., and Juan Jose Olivero, M.D. Dr. Shah obtained her medical degree at The University of Texas Medical Branch in Galveston and is currently an internal medicine resident at Houston Methodist Hospital. Dr. Olivero is a nephrologist at Houston Methodist Hospital and a member of the hospital's Nephrology Fellowship Training Program. He obtained his medical degree from the University of San Carlos School of Medicine in Guatemala, Central America, and completed his residency and nephrology fellowship at Baylor College of Medicine in Houston, Texas.