The need for prophylactic hemodialysis to protect against nephrogenic systemic fibrosis in patients with end-stage renal disease receiving gadolinium-based contrast agents.

BACKGROUND: The risk of gadolinium (Gd)-based contrast agent (GBCA)-induced nephrogenic systemic fibrosis (NSF) in patients with end-stage renal disease (ESRD) and the efficacy of prophylactic hemodialysis (HD) for protection against NSF are not well understood or summarized in the literature. PURPOSE: To determine the risk for NSF related to frequency and time per dialysis session after Gd-magnetic resonance imaging (MRI) by emphasizing the safety of Gd-MRI in patients with ESRD. MATERIAL AND METHODS: This retrospective observational study identified all GBCA injections for MRI examinations performed at two tertiary referral hospitals between 2005 and 2020. All clinical data, including dialysis records and medical history, were investigated for each patient through 2021. The end of follow-up coincided with the last hospital visit. RESULTS: Overall, 1129 patients with ESRD underwent 1461 Gd-MRI scans (41.5% gadoterate, 39.4% gadobutrol, and 7.7% gadoxetate); a total of 958 patients with 1229 (84.1%) examinations underwent HD on the day of the MRI study, within 2.1 ± 2.0 h (range = 0.2-15.7 h) immediately after Gd exposure. In 53.4% of scans, frequent HD had been performed urgently and then twice more on consecutive days to prophylactically avoid NSF. No cases of NSF were identified during the follow-up period (mean = 81.7 ± 50.5 months) regardless of dose of HD. CONCLUSION: No cases of NSF were reported in 1461 Gd-MRI examinations of 1129 inpatients with ESRD on HD. Our findings support the lack of benefit of frequent prophylactic HD being performed urgently within 4 h of the receipt of GBCA.

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.

Gadolinium-based contrast agents: What we learned from acute adverse events, nephrogenic systemic fibrosis and brain retention. / Gadolinium-haltige Kontrastmittel nach anaphylaktoiden Reaktionen, nephrogener systemischer Fibrose und Hirnretention ­ was haben wir gelernt?

BACKGROUND: Radiologists have been administering gadolinium-based contrast agents (GBCA) in magnetic resonance imaging for several decades, so that there is abundant experience with these agents regarding allergic-like reactions, nephrogenic systemic fibrosis (NSF) and gadolinium retention in the brain. METHODS: This review is based on a selective literature search and reflects the current state of research on acute adverse effects of GBCA, NSF and brain retention of gadolinium. RESULTS: Due to the frequent use of GBCA, data on adverse effects of these compounds are available in large collectives. Allergic-like reactions occurred rarely, whereas severe acute reactions were very rarely observed. Systemic changes in NSF also occur very rarely, although measures to avoid NSF resulted in a significantly reduced incidence of NSF. Due to gadolinium retention in the body after administration of linear MR contrast agents, only macrocyclic preparations are currently used with few exceptions. Clear clinical correlates of gadolinium retention in the brain could not be identified so far. Although the clinical added value of GBCA is undisputed, individual risks associated with the injection of GBCA should be identified and the use of non-contrast enhanced MR techniques should be considered. Alternative contrast agents such as iron oxide nanoparticles are not clinically approved, but are currently undergoing clinical trials. CONCLUSION: GBCA have a very good risk profile with a low rate of adverse effects or systemic manifestations such as NSF. Gadolinium retention in the brain can be minimized by the use of macrocyclic GBCA, although clear clinical correlates due to gadolinium retention in the brain following administration of linear GBCA could not be identified yet. KEY POINTS: · Acute adverse effects are predominantly mild/moderate, rarely severe reactions occur.. · International guidelines resulted in significant reduction of nephrogenic systemic fibrosis.. · Application of macrocyclic contrast agents minimizes gadolinium retention in the brain.. CITATION FORMAT: · Bäuerle T, Saake M, Uder M. Gadolinium-based contrast agents: What we learned from acute adverse events, nephrogenic systemic fibrosis and brain retention. Fortschr Röntgenstr 2021; 193: 1010 - 1018.

Risks and Benefits of Gadolinium-Based Contrast-Enhanced MRI.

The responsible use of gadolinium-based contrast agents (GBCAs) requires a balance between safety and clinical utility. While nephrogenic systemic fibrosis (NSF) has been associated with most linear GBCAs few, if any, new cases have been verified since the successful implementation of screening programs to detect renal impairment and prevent susceptible patients from receiving these higher-risk agents. The likelihood of developing nephrogenic systemic fibrosis has been shown to be negligible with macrocyclic agents, prompting the American College of Radiology and other regulatory agencies to suggest that no screening is necessary when they are used. There is no solid evidence of negative clinical effect from the retention of macrocyclic agents in the brain while there is evidence that they wash out of the brain over time. GBCAs have many important clinical uses that can help prevent morbidity or death. This article reviews the risks and benefits of GBCA administration.

Practical administration of intravenous contrast media in children: screening, prophylaxis, administration and treatment of adverse reactions.

Administration of intravenous contrast media to children is a routine practice at many clinical imaging centers, that can involve special considerations. In this paper, we provide practical information to facilitate optimal performance and oversight of this task. We provide targeted screening questions that can help to identify high-risk pediatric patients for both iodine-based and gadolinium-based intravenous contrast media administration. These include children at risk for allergic-like reactions, thyroid dysfunction, contrast-induced nephropathy, and nephrogenic systemic fibrosis. We make recommendations for addressing "yes" responses to screening questions using risk stratification schema that are specific to children. We also present criteria for selecting children for premedication prior to intravenous contrast administration, and suggest pediatric regimens. Additionally, we discuss practical nuances of intravenous contrast media administration to children and provide a quick-reference table of appropriate treatments with pediatric dosages for adverse contrast reactions.

Imaging patients with renal impairment.

Imaging with intravascular contrast media is generally considered safe, particularly in patients without renal failure. However, as renal function deteriorates, the potential risk of nonallergic-type adverse events increases. This presents a unique challenge, particularly when the use of intravenous contrast media is deemed essential for diagnostic purposes. Following a discussion regarding the definition and epidemiology of kidney injury, this review focuses on the evolving understanding of both contrast-induced nephropathy and nephrogenic systemic fibrosis and discusses preventative strategies aimed at minimizing the risk of developing these entities. Alternative non-contrast imaging techniques are also discussed.

Safe use of iodinated and gadolinium-based contrast media in current practice in Japan: a questionnaire survey.

PURPOSE: To help establish consensus on the safe use of contrast media in Japan. MATERIALS AND METHODS: Questionnaires were sent to accredited teaching hospitals with radiology residency programs. RESULTS: The reply rate was 45.4% (329/724). For contrast-induced nephropathy (CIN), chronic and acute kidney diseases were considered a risk factor in 96.7 and 93.6%, respectively, and dehydration in 73.9%. As preventive actions, intravenous hydration (89.1%) and reduction of iodinated contrast media dose (86.9%) were commonly performed. For nephrogenic systemic fibrosis (NSF), chronic and acute kidney diseases were considered risk factors in 98.5 and 90.6%, respectively, but use of unstable gadolinium-based contrast media was considered a risk factor in only 55.6%. A renal function test was always (63.5% in iodinated; 65.7% in gadolinium) or almost always (23.1; 19.8%) performed, and estimated glomerular filtration rate (eGFR) was the parameter most frequently used (80.8; 82.6%). For the patients with risk factors for acute adverse reaction (AAR), steroid premedication or/and change of contrast medium were frequent preventive actions, but intravenous steroid administration immediately before contrast media use was still performed. CONCLUSION: Our questionnaire survey revealed that preventive actions against CIN were properly performed based on patients' eGFR. Preventive actions against NSF and AAR still lacked consensus.

Do ASARM peptides play a role in nephrogenic systemic fibrosis?

Nephrogenic systemic fibrosis (NSF) is a devastating condition associated with gadolinium (Gd3+)-based contrast agents (GBCAs) in patients with kidney disease. The release of toxic Gd3+ from GBCAs likely plays a major role in NSF pathophysiology. The cause and etiology of Gd3+ release from GBCAs is unknown. Increased Acidic Serine Aspartate Rich MEPE-associated peptides (ASARM peptides) induce bone mineralization abnormalities and contribute to renal phosphate-handling defects in inherited hypophosphatemic rickets and tumor-induced osteomalacia. The proteolytic cleavage of related bone matrix proteins with ASARM motifs results in release of ASARM peptide into bone and circulation. ASARM peptides are acidic, reactive, phosphorylated inhibitors of mineralization that bind Ca2+ and hydroxyapatite. Since the ionic radius of Gd3+ is close to that of Ca2+, we hypothesized that ASARM peptides increase the risk of NSF by inducing release of Gd3+ from GBCAs. Here, we show 1) ASARM peptides bind and induce release of Gd3+ from GBCAs in vitro and in vivo; 2) A bioengineered peptide (SPR4) stabilizes the Gd3+-GBCA complex by specifically binding to ASARM peptide in vitro and in vivo; and 3) SPR4 peptide infusion prevents GBCA-induced NSF-like pathology in a murine model with increased ASARM peptide (Hyp mouse). We conclude ASARM peptides may play a role in NSF and SPR4 peptide is a candidate adjuvant for preventing or reducing risk of disease.

Half-dose gadoxetic acid-enhanced liver magnetic resonance imaging in patients at risk for nephrogenic systemic fibrosis.

PURPOSE: To evaluate the feasibility of half-dose gadoxetic acid (0.0125mmol/kg) for liver MRI at 3-T compared to standard-dose (0.025mmol/kg) in patients at risk for nephrogenic systemic fibrosis (NSF). MATERIALS AND METHODS: Forty patients who underwent both half-dose and standard-dose gadoxetic acid-enhanced MRIs were included. Contrast enhancement index (CEI) was calculated for liver, aorta, pancreas and kidney. Two observers independently rated and performed a one-to-one direct comparison of enhancement quality for both groups. RESULTS: Liver CEIs were not significantly different on arterial phase between the two groups but CEIs of standard-dose MRIs were greater than half-dose MRIs on other phases (P<0.001). CEIs were not significantly different on arterial phase for the aorta or on any phases for the pancreas. Kidney CEIs of standard-dose MRIs were greater than half-dose MRIs on all phases (P<0.05). Enhancement quality of both groups was diagnostic and did not significantly differ for any organs. In one-to-one direct comparisons of enhancement quality, equal ratings were given in 87.5% (35/40) of cases by observer 1 and 85.0% (34/40) by observer 2. CONCLUSION: Liver MRI using half-dose gadoxetic acid at 3-T can be a feasible alternative for standard-dose MRI in patients at risk for NSF.

Breast magnetic resonance imaging performance: safety, techniques, and updates on diffusion-weighted imaging and magnetic resonance spectroscopy.

Dynamic contrast-enhanced breast magnetic resonance imaging (MRI) is a well-established, highly sensitive technique for the detection and evaluation of breast cancer. Optimal performance of breast MRI continues to evolve. This article addresses breast MRI applications, covers emerging breast MRI safety concerns; outlines the technical aspects of breast MRI, including equipment and protocols at 3 T and 1.5 T; and describes current promising areas of research including diffusion-weighted imaging and magnetic resonance spectroscopy.

Fibrosis sistémica nefrogénica: la pandemia que no fue / Causal relationship between the use of gadolinium based contrast media and nephrogenic systemic fibrosis

Nephrogenic systemic fibrosis (NSF) is a severe iatrogenic disease that affect patients with impaired renal function exposed to gadolinium-based contrast agents. Clinically, symptoms develop within days or weeks after the exposure and mimic a scleromyxedema. The causal relationship between use of gadolinium-based contrast agents and NSF led to develop clinical guidelines aiming to limit the use of this contrast medium in high risk patients. These guidelines decreased the incidence of NSF in the last years. Unfortunately there is no specific treatment for NSF yet. Thus, strict adherence to current guidelines is key to prevent new cases. Renal dysfunction is increasingly common in our population. Therefore, practicing physicians should be aware of this potential complication of the use of gadolinium based contrast media.

[Gadolinium-based contrast agents for magnetic resonance imaging]. / Contrastes basados en gadolinio utilizados en resonancia magnética.

Gadolinium-based contrast agents are increasingly being used in magnetic resonance imaging. These agents can improve the contrast in images and provide information about function and metabolism, increasing both sensitivity and specificity. We describe the gadolinium-based contrast agents that have been approved for clinical use, detailing their main characteristics based on their chemical structure, stability, and safety. In general terms, these compounds are safe. Nevertheless, adverse reactions, the possibility of nephrotoxicity from these compounds, and the possibility of developing nephrogenic systemic fibrosis will be covered in this article. Lastly, the article will discuss the current guidelines, recommendations, and contraindications for their clinical use, including the management of pregnant and breast-feeding patients.