Risk Of Nephrogenic Systemic Fibrosis Research Articles

MRI Gadolinium-Based Contrast Media: Meeting Radiological, Clinical, and Environmental Needs.

Gadolinium-based contrast agents (GBCAs) are routinely used in magnetic resonance imaging (MRI). They are essential for choosing the most appropriate medical or surgical strategy for patients with serious pathologies, particularly in oncologic, inflammatory, and cardiovascular diseases. However, GBCAs have been associated with an increased risk of nephrogenic systemic fibrosis in patients with renal failure, as well as the possibility of deposition in the brain, bones, and other organs, even in patients with normal renal function. Research is underway to reduce the quantity of gadolinium injected, without compromising image quality and diagnosis. The next generation of GBCAs will enable a reduction in the gadolinium dose administered. Gadopiclenol is the first of this new generation of GBCAs, with high relaxivity, thus having the potential to reduce the gadolinium dose while maintaining good in vivo stability due to its macrocyclic structure. High-stability and high-relaxivity GBCAs will be one of the solutions for reducing the dose of gadolinium to be administered in clinical practice, while the development of new technologies, including optimization of MRI acquisitions, new contrast mechanisms, and artificial intelligence may help reduce the need for GBCAs. Future solutions may involve a combination of next-generation GBCAs and image-processing techniques to optimize diagnosis and treatment planning while minimizing exposure to gadolinium. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

NSF evaluation of gadolinium biodistribution in renally impaired rats: Using novel metabolic Gd2O3 nanoparticles coated with β-cyclodextrin (Gd2O3@PCD) in MR molecular imaging

The use of conventional gadolinium(Gd)-based contrast agents in magnetic resonance imaging (MRI) poses a significant risk of Nephrogenic Systemic Fibrosis (NSF) syndrome in patients with impaired renal function (grades 4 and 5). To address this issue, a new study has introduced a novel metabolic Gadolinium oxide nanoparticle (Gd2O3 NPs) coated with β-cyclodextrin (βCD). The study aims to investigate NSF syndrome by quantifying tissue Gd deposition biodistribution in renal impairment rats using MR molecular imaging. This is the first study of its kind to use this approach.A group of 20 rats were divided into four groups, each containing five rats that underwent 5/6 nephrectomy. The rats received 12 intravenous injections of a novel homemade synthesized gadolinium oxide polycyclodextrin (Gd2O3@PCD) at a dose of 0.1 mmol/kg, conventional contrast agents (CAs) drugs of Omniscan (Gd-DTPA-BMA) and Dotarem (Gd-DOTA), at a dose of 2.5 mmol/kg, and 250 μl saline for two injections per week during six weeks. T1-weighted MR imaging was performed before the injections and once a week for six weeks to quantify Gd deposition in four different organs (skin, liver, heart, and lung) in rats using inductively coupled plasma mass spectrometry (ICP-MS). The relationship between Signal-to-Noise Ratio (SNR) and biodistribution of Gd deposition due to NSF-induced syndrome was also calculated.The results of the study showed that the Gd concentrations in tissues were significantly higher in the Gd2O3@PCD group compared to the other groups, without any significant histopathological changes (P < 0.05). In the Gd2O3@PCD group, Gd was mainly deposited in the skin, followed by the liver, lung, and heart, without any symptoms of thickening or hardening of the skin. The Gd concentrations in the skin, liver, lung, and heart were significantly lower in the Dotarem group than in the Omniscan group (P < 0.05). In the histopathological examinations, the Omniscan group showed increased cellularity in the dermis. A significant hyperintensity was observed in the Gd2O3@PCD-treated rats compared to the Dotarem and Omniscan groups in the liver, heart, and lung.Compared to conventional Gd-based CAs, the novel metabolically Gd2O3@PCD with increased SNR, biosafety, and a considerably lower probability of developing NSF, has potential applicability for diagnosing patients with renal diseases in clinical MR Molecular Imaging (MRMI).

Safety and incremental prognostic value of stress CMR in patients with known chronic kidney disease

Abstract Background Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established. We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD. Methods Between 2008 and 2021, we conducted a bi-center longitudinal study with all consecutive symptomatic patients with known CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m2, referred for vasodilator stress CMR. All patients with eGFR &amp;lt;30 ml/min/1.73 m² (n=62) were excluded due the risk of nephrogenic systemic fibrosis. All patients were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent nonfatal myocardial infarction (MI). Cox regressions were used to determine the prognostic value of stress CMR parameters. Results Of 825 patients with known CKD (71.4±8.8 years, 70% men), 769 (93%) completed the CMR protocol, and among those 702 (91%) completed the follow-up (median follow-up 6.4 (4.0–8.2) years). Stress CMR was well tolerated without occurrence of death or severe adverse event related to the injection of gadolinium or nephrogenic systemic fibrosis case. The presence of inducible ischemia was associated with the occurrence of MACE (hazard ratio [HR] 12.50; 95% confidence interval [CI]: 7.50–20.8; p&amp;lt;0.001). In multivariable analysis, ischemia and late gadolinium enhancement were independent predictors of MACE (HR 15.5; 95% CI: 7.72 to 30.9; and HR:4.67 [95%CI: 2.83-7.68]; respectively, both p&amp;lt;0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI=0.477; IDI=0.049). Conclusions In patients with known CKD, stress CMR is safe and its findings have an incremental prognostic value to predict MACE over traditional risk factors.Cumulative rates of MACECompeting risk analysis

Safety and incremental prognostic value of stress CMR in patients with known chronic kidney disease

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established. We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD. Methods Between 2008 and 2021, we conducted a bi-center longitudinal study with all consecutive symptomatic patients with known CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m2, referred for vasodilator stress CMR. All patients with eGFR &amp;lt;30 ml/min/1.73 m² (n=62) were excluded due the risk of nephrogenic systemic fibrosis. All patients were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent nonfatal myocardial infarction (MI). Cox regressions were used to determine the prognostic value of stress CMR parameters. Results Of 825 patients with known CKD (71.4±8.8 years, 70% men), 769 (93%) completed the CMR protocol, and among those 702 (91%) completed the follow-up (median follow-up 6.4 (4.0–8.2) years). Stress CMR was well tolerated without occurrence of death or severe adverse event related to the injection of gadolinium or nephrogenic systemic fibrosis case. The presence of inducible ischemia was associated with the occurrence of MACE (hazard ratio [HR] 12.50; 95% confidence interval [CI]: 7.50–20.8; p&amp;lt;0.001). In multivariable analysis, ischemia and late gadolinium enhancement were independent predictors of MACE (HR 15.5; 95% CI: 7.72 to 30.9; and HR:4.67 [95%CI: 2.83–7.68]; respectively, both p&amp;lt;0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI=0.477; IDI=0.049). Conclusions In patients with known CKD, stress CMR is safe and its findings have an incremental prognostic value to predict MACE over traditional risk factors.

Capability of constructive interference in steady state sequence versus postcontrast T1-weighted imaging in cerebellopontine angle and internal auditory canal masses

Background: The tumor size is one of the main factors in the treatment of cerebellopontine angle (CPA) tumors, and magnetic resonance imaging (MRI) with gadolinium-based contrast agent (GBCA) provides the best evaluation. However, administration of the gadolinium is time consuming and increasing in cost. There is a risk of nephrogenic systemic fibrosis in patients with renal failure and liver or renal transplantation. Objective: The purpose of this study was to assess the capability of constructive interference in steady state (CISS) sequence in measuring the tumor size of the CPA and internal auditory canal (IAC) masses compared to postcontrast T1-weighted images (T1-WI). Materials and Methods: The 118 MR studies with both CISS sequence and postcontrast T1-WI of 45 patients with CPA and IAC masses were retrospectively reviewed. Results: There was no significant difference between CISS and postcontrast T1-WI in measuring size in transverse diameter of the masses (p = 0.051-0.06). The longitudinal diameter measurement revealed a significant difference (p &lt; 0.001) and the measured size on postcontrast T1-WI was slightly larger than the CISS image. The difference in median measurement between two sequences was less than 0.9 mm. and Bland-Altman plots revealed that differences between the two sequences in longitudinal and transverse diameters of the masses were within the limits of agreement. Interobserver agreement showed excellent correlation (r = 0.994-0.999, p &lt; 0.001 by Pearson's product-moment correlation). Conclusions: The CISS sequence may be sufficient for assessing the size of CPA and IAC masses, which can be used interchangeably with postcontrast T1-weighted image as a contrast-free option, especially in follow-up studies and vulnerable settings of gadolinium administration.

Ferumoxytol-Enhanced MRI in Children and Young Adults: State of the Art.

Ferumoxytol is an ultrasmall iron oxide nanoparticle that was originally approved by the FDA in 2009 for IV treatment of iron deficiency in adults with chronic kidney disease. Subsequently, its off-label use as an MRI contrast agent increased in clinical practice, particularly in pediatric patients in North America. Unlike conventional MRI contrast agents that are based on the rare earth metal gadolinium (gadolinium-based contrast agents), ferumoxytol is biodegradable and carries no potential risk of nephrogenic systemic fibrosis. At FDA-approved doses, ferumoxytol shows no long-term tissue retention in patients with intact iron metabolism. Ferumoxytol provides unique MRI properties, including long-lasting vascular retention (facilitating high-quality vascular imaging) and retention in reticuloendothelial system tissues, thereby supporting a variety of applications beyond those possible with gadolinium-based contrast agents (GBCAs). This Clinical Perspective describes clinical and early translational applications of ferumoxytol-enhanced MRI in children and young adults through off-label use in a variety of settings, including vascular, cardiac, and cancer imaging, drawing on the institutional experience of the authors. In addition, we describe current advances in pre-clinical and clinical research using ferumoxytol in cellular and molecular imaging as well as the use of ferumoxytol as a novel potential cancer therapeutic agent.

Safety and incremental prognostic value of stress cardiovascular magnetic resonance in patients with known chronic kidney disease

BackgroundCardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD). Although several studies have demonstrated the consistently high prognostic value of stress cardiovascular magnetic resonance (CMR), its prognostic value in patients with CKD is not well established. We aimed to assess the safety and the incremental prognostic value of vasodilator stress perfusion CMR in consecutive symptomatic patients with known CKD. MethodsBetween 2008 and 2021, we conducted a retrospective dual center study with all consecutive symptomatic patients with known stage 3 CKD, defined by estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73 m2, referred for vasodilator stress CMR. All patients with eGFR < 30 ml/min/1.73 m2 (n = 62) were excluded due the risk of nephrogenic systemic fibrosis. All patients were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or recurrent nonfatal myocardial infarction (MI). Cox regression analysis was used to determine the prognostic value of stress CMR parameters. ResultsOf 825 patients with known CKD (71.4 ± 8.8 years, 70% men), 769 (93%) completed the CMR protocol. Follow-up was available in 702 (91%) (median follow-up 6.4 (4.0–8.2) years). Stress CMR was well tolerated without occurrence of death or severe adverse event related to the injection of gadolinium or cases of nephrogenic systemic fibrosis. The presence of inducible ischemia was associated with the occurrence of MACE (hazard ratio [HR] 12.50; 95% confidence interval [CI] 7.50–20.8; p < 0.001). In multivariable analysis, ischemia and late gadolinium enhancement were independent predictors of MACE (HR 15.5; 95% CI 7.72 to 30.9; and HR 4.67 [95% CI 2.83–7.68]; respectively, both p < 0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI = 0.477; IDI = 0.049). ConclusionsIn patients with known stage 3 CKD, stress CMR is safe and its findings have an incremental prognostic value to predict MACE over traditional risk factors.

Nephrogenic Systemic Fibrosis in Patients with Chronic Kidney Disease after the Use of Gadolinium-Based Contrast Agents: A Review for the Cardiovascular Imager.

Gadolinium-enhanced cardiac magnetic resonance has revolutionized cardiac imaging in the last two decades and has emerged as an essential and powerful tool for the characterization and treatment guidance of a wide range of cardiovascular diseases. However, due to the high prevalence of chronic renal dysfunction in patients with cardiovascular conditions, the risk of nephrogenic systemic fibrosis (NSF) after gadolinium exposure has been a permanent concern. Even though the newer macrocyclic agents have proven to be much safer in patients with chronic kidney disease and end-stage renal failure, clinicians must fully understand the clinical characteristics and risk factors of this devastating pathology and maintain a high degree of suspicion to prevent and recognize it. This review aimed to summarize the existing evidence regarding the physiopathology, clinical manifestations, diagnosis, and prevention of NSF related to the use of gadolinium-based contrast agents.

Renal Cell Carcinoma or Oncocytoma? The Contribution of Diffusion-Weighted Magnetic Resonance Imaging to the Differential Diagnosis of Renal Masses.

Background and Objectives: Renal Cell Carcinoma (RCC) accounts for 85% and oncocytomas constitute 3–7% of solid renal masses. Oncocytomas can be confused, especially with hypovascular RCC. The purpose of this research was to evaluate the contribution of diffusion-weighted imaging (DWI) and contrast-enhanced MRI sequences in the differential diagnosis of RCC and oncocytoma Materials and Methods: 465 patients with the diagnosis of RCC and 45 patients diagnosed with oncocytoma were retrospectively reviewed between 2009 to 2020. All MRI acquisitions were handled by a 1.5 T device (Achieva, Philips Healthcare, Best, The Netherlands) and all images were evaluated by the consensus of two radiologists with 10–15 years’ experience. The SPSS package program version 15.0 software was used for statistical analysis of the study. Chi-square test, Mann–Whitney U test or the Kruskal–Wallis tests were used in the statistical analysis. A receiver operating characteristic (ROC) curve was used to calculate the cut-off values Results: The results were evaluated with a 95% confidence interval and a significance threshold of p < 0.05. ADC values (p < 0.001) and enhancement index (p < 0.01) were significantly lower in the RCC group than the oncocytoma group. Conclusion: DWI might become an alternative technique to the contrast-enhanced MRI in patients with contrast agent nephropathy or with a high risk of nephrogenic systemic fibrosis, calculation of CI of the oncocytoma and RCCs in the contrast-enhanced acquisitions would contribute to the differential diagnosis.

Risk of nephrogenic systemic fibrosis (NSF) in oncology patients receiving gadoxetic acid and updated risk of estimate of NSF in patients receiving gadoxetic acid with moderate and severe renal impairment.

Gadoxetic acid (GA) is a half-biliary excreted gadolinium-based contrast agent (GBCA) administered at lower dose than gadobenic acid with similar ionic structure. Gadobenic acid is considered low-risk for nephrogenic systemic fibrosis (NSF) in patients with impaired renal function; however, safety of GA is unclear. The objective of this study was to determine the incidence of NSF in oncology patients undergoing GA-enhanced MRI and to update the risk estimate of NSF in patients receiving GA with severe renal impairment. We retrospectively identified GA-enhanced MRI performed for treatment planning in confirmed cancer patients between March 2011 and December 2020. Serum creatinine values within 180days of GA administration were retrieved and estimated glomerular filtration rate (eGFR) calculated. The eGFR value nearest to each MRI examination was used. The search result was linked to a prospectively maintained registry of reported cases of NSF. An updated literature review was conducted to identify published cases of NSF related to GA administration in patients with severe renal impairment (eGFR < 30mL/min/1.73 m2 or on dialysis) and the incidence of NSF with 95% confidence intervals (CI) was determined combining published data with our results. 192 oncology patients underwent GA-enhanced MRI, mean age was 65.6 ± 11.8years with 73 women. The mean eGFR was 89.6 ± 33.0mL/min/1.73 m2. There were 33 patients with moderate (eGFR 30-60mL/min/1.73 m2) and 1 patient with severe (eGFR < 30mL/min/1.73 m2) renal impairment. There were no reported cases of NSF. Updated literature review including our results identified 340 patients with severe renal impairment or on dialysis with zero cases of NSF (0/340; 95% confidence intervals 0% and 0.9%). No cases of NSF were documented in this study related to gadoxetic acid use in oncology patients, including those with moderate and severe renal impairment. Recent data indicate use of gadoxetic acid in patients with renal impairment can be considered low-risk.

Evaluation of Renal Allograft Vasculature Using Non-contrast 3D Inversion Recovery Balanced Steady-state Free Precession MRA and 2D Quiescent-interval Slice-selective MRA.

Background and objectives:Renal transplant patients often require periodic imaging to evaluate the transplant vessel anastomosis for potential vascular complications. The use of non-contrast enhanced magnetic resonance angiography (NCE-MRA) techniques is encouraged in these patients because they are at increased risk of nephrogenic systemic fibrosis (NSF) due to their renal insufficiency. This study aimed to evaluate the performance of two NCE-MRA techniques (three-dimensional [3D] balanced steady-state free precession [bSSFP] with inversion recovery and quiescent-interval slice-selective [QISS]) for the evaluation of renal allograft vasculature in patients with clinical suspicion, or Doppler ultrasound, or both of arterial anastomotic stenosis.Methods:A total of 43 patients were included in this retrospective study. Two radiologists independently scored the images from 3D bSSFP and QISS MRA sequences for image quality and confidence in anastomosis interpretation, and the degree of stenosis at the arterial anastomosis. Correlations with digital subtraction angiography (DSA) were carried out when available. In addition, inter-rater agreement was calculated.Results:In total, 43 patients underwent QISS and 3D bSSFP MRA. For QISS, all cases were adequate for evaluation. For 3D SSFP, 86% of cases were adequate for evaluation. There was a good-to-excellent inter-rater agreement for all scores and an excellent correlation between NCE-MRA and DSA results when available (12 patients).Conclusions:QISS and 3D SSFP showed good inter-rater agreement for image quality and stenosis grade, with more cases being of adequate image quality that used QISS. Further study is required; however, NCE-MRA shows potential as a risk-free alternative to CTA and contrast-enhanced MRA (CE-MRA) for the evaluation of arterial anastomoses in renal transplant patients.

Risk of nephrogenic systemic fibrosis in patients with impaired renal function undergoing fixed-dose gadoxetic acid-enhanced magnetic resonance imaging.

To assess the risk of nephrogenic systemic fibrosis (NSF) in patients with renal impairment undergoing gadoxetic acid-enhanced magnetic resonance imaging. This retrospective study included patients who had an estimated glomerular filtration rate (eGFR) below 60mL/min per 1.73m2 or had undergone dialysis around the time of gadoxetic acid exposure from January 2010 to November 2019. All patients received at least one intravenous injection of gadoxetic acid at a fixed dose of 2.5mmol. The primary endpoint was the development of NSF after exposure to gadoxetic acid based on Girardi's clinicopathological scoring system. A total of 204 patients with renal impairment received 424 injections of gadoxetic acid, of which 131 and 54 had an eGFR of 30-59 and < 30mL/min per 1.73m2, respectively, and 19 had undergone hemodialysis. Eighty-two patients received multiple injections, with 23 receiving five or more injections. The dose of each exposure ranged from 0.02 to 0.07mmol/kg and the cumulative doses ranged from 0.02 to 0.45mmol/kg. Thirty-three patients had concomitant Child-Pugh class B or C cirrhosis. No NSF was detected during follow-up (median 20months; range 6days to 111months). The upper bound of the 95% confidence interval for NSF risk was 2.2% and 1.1% per patient and examination, respectively. No NSF was detected in this study. However, it is premature to ascertain the risk of NSF using gadoxetic acid in patients with renal impairment and further studies are warranted.

Use of Intravenous Gadolinium-based Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Inaugural consensus statements were developed and endorsed by the American College of Radiology (ACR) and the National Kidney Foundation to improve and standardize the care of patients with kidney disease who have indication(s) to receive ACR-designated group II or group III intravenous gadolinium-based contrast media (GBCM). The risk of nephrogenic systemic fibrosis (NSF) from group II GBCM in patients with advanced kidney disease is thought to be very low (zero events following 4931 administrations to patients with estimated glomerular filtration rate [eGFR] <30 mL/min per 1.73 m2; upper bounds of the 95% confidence intervals: 0.07% overall, 0.2% for stage 5D chronic kidney disease [CKD], 0.5% for stage 5 CKD and no dialysis). No unconfounded cases of NSF have been reported for the only available group III GBCM (gadoxetate disodium). Depending on the clinical indication, the potential harms of delaying or withholding group II or group III GBCM for an MRI in a patient with acute kidney injury or eGFR less than 30 mL/min per 1.73 m2 should be balanced against and may outweigh the risk of NSF. Dialysis initiation or alteration is likely unnecessary based on group II or group III GBCM administration. This article is a simultaneous joint publication in Radiology and Kidney Medicine. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article.

Sensitivity of Pre-Contrast Multiphase versus Conventional Liver MRI in Diagnosing Hepatic Hemangioma

Hepatic hemangioma (HH) can be diagnosed noninvasively via dynamic contrast enhancement computed tomography, magnetic resonance imaging (MRI) or ultrasonography. Diagnosis HH is based on imaging features such as early arterial phase enhancement and persistence enhancement on portal or delayed phase. However, differentiating small or atypical hemangiomas from other hepatic masses using these imaging methods maybe be difficult, especially in patients with a medical history of malignant disease. Another challenge in clinical practice is when patients with acute or chronic renal insufficiency, use MRI contrast agent gadolinium (Gd) with the risk of nephrogenic systemic fibrosis. Differentiating hemangioma from its mimickers on preoperative imaging studies is of critical importance. Our study compared the diagnostic sensitivity of pre-contrast multiphase and conventional liver MRI. Total 80 patients with HH were participate to our study retrospectively. Imaging was performed using pre-contrast multiphase and conventional liver MRI methods. The size of the nodule/mass to be evaluated was ≥1 cm. All patients MRI images were obtained and classified into two groups based on the acquisition parameters. The first group with pre-contrast multiphase MRI sequences, and the second group of conventional liver MRI methods included pre-contrast multiphase MRI sequences, contrast-enhanced tri-phase sequences. The study was reviewed and analyzed by two independence gastrointestinal radiologists, who were blinded to the examination and follow-up study results. The diagnostic sensitivity was compared between pre-contrast multiphase MRI sequences only and conventional liver MRI sequences methods. Based on the observation of two gastrointestinal radiologists, our results showed mean sensitivity of 90.0% and 97.5% for pre-contrast multiphase MRI and conventional liver MRI, respectively. Pre-contrast multiphase MRI sequence methods may be reliably applied in the diagnosis of HH.

No Cases of Nephrogenic Systemic Fibrosis after Administration of Gadoxetic Acid.

Background Gadoxetic acid (GA) has distinctive pharmacokinetic properties with important applications in hepatobiliary imaging. However, there are limited data evaluating the safety of GA administration in patients with impaired kidney function and the incidence of nephrogenic systemic fibrosis (NSF). Purpose To evaluate safety of GA regarding risk of NSF in patients with impaired kidney function. Materials and Methods This retrospective study identified all GA-enhanced MRI (hereafter, GA MRI) examinations performed between July 2008 and December 2019 through a search of the electronic medical record. Serum creatinine values within 180 days or less of each GA MRI examination were retrieved and estimated glomerular filtration rate (eGFR) was calculated. The eGFR value nearest to each MRI examination was used. A separate search in the electronic medical record was also performed to identify patients with NSF. Dermatologists, nephrologists, and nephrologists at our institution were surveyed for any cases of NSF. In patients with NSF, all MRI examinations performed and contrast agents administered to these patients were recorded. Results Overall, 7820 GA MRI examinations were identified, performed in 5351 patients (3022 women and 2329 men). These included 299 examinations (242 patients) with eGFR of 30-44 mL/min/1.73 m2 and 183 examinations (157 patients) with eGFR less than 30 mL/min/1.73 m2. There were 109 examinations (in 94 patients) with eGFR of 15-29 mL/min/1.73 m2, 40 examinations (in 39 patients) with eGFR less than 15 mL/min/1.73 m2, and 34 examinations in 27 patients undergoing hemodialysis. Seventeen patients with eGFR less than 30 mL/min/1.73 m2 or undergoing dialysis underwent GA MRI two or more times. Eighteen patients with biopsy-confirmed NSF were identified, none of whom were exposed to GA. The mean follow-up period for GA MRI examinations performed in patients with severe kidney impairment was 4.2 years (range, 0.2-11.3 years). Conclusion Gadoxetic acid may be safe with respect to nephrogenic systemic fibrosis in this patient population, although further studies are needed to confirm this. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Davenport and Shankar in this issue.

Risk of Nephrogenic Systemic Fibrosis in Stage 4 and 5 Chronic Kidney Disease Following Group II Gadolinium-based Contrast Agent Administration: Subanalysis by Chronic Kidney Disease Stage.

The risk of nephrogenic systemic fibrosis in patients with stage 4 or 5 chronic kidney disease (CKD) who receive a group II gadolinium-based contrast agent is very low, including in patients with e...

Current and Future MR Contrast Agents: Seeking a Better Chemical Stability and Relaxivity for Optimal Safety and Efficacy.

This review summarizes 30 years of experience in the development and clinical use of magnetic resonance (MR) contrast agents. Despite their undisputable usefulness for disease diagnosis, gadolinium (Gd)-based contrast agents (GBCAs) have gone through 2 major safety crises. Approximately 10 years ago, the regulatory agencies decided to restrict the use of GBCAs to minimize the risk of nephrogenic systemic fibrosis in patients with severe renal insufficiency. Yet, following the recent discovery of Gd retention in brain, the same agencies adopted different positions ranging from suspension of marketing authorizations, changes in GBCA safety labeling, and performing preclinical and clinical studies to assess the potential long-term consequences of Gd accumulation on motor and cognitive functions. Besides, magnetic resonance imaging (MRI) has benefited from MR technological advances, which provide alternative solutions to increase the MR signal, generate new contrasts on MRI scans, and accelerate their acquisition and analysis. Altogether, GBCAs in combination with new MR techniques have found their place in the diagnostic pathway of various diseases. Despite the large research efforts to identify and develop alternative Gd-free MR agents, manganese- and iron-based contrast agents have failed to reach market approval. In this context, the development of next-generation MR contrast agents should focus on high-stability and high-relaxivity GBCAs, such as gadopiclenol, which offer the possibility to adapt the administered Gd dose to each indication while ensuring an optimal patient safety.

Risk for Nephrogenic Systemic Fibrosis After Exposure to Newer Gadolinium Agents

The risk for nephrogenic systemic fibrosis (NSF) after exposure to newer versus older gadolinium-based contrast agents (GBCAs) remains unclear. To synthesize evidence about NSF risk with newer versus older GBCAs across the spectrum of kidney function. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science for English-language references from inception to 5 March 2020. Randomized controlled trials, cohort studies, and case-control studies that assessed NSF occurrence after GBCA exposure. Data were abstracted by 1 investigator and verified by a second. Investigator pairs assessed risk of bias by using validated tools. Of 32 included studies, 20 allowed for assessment of NSF risk after exposure to newer GBCAs and 12 (11 cohort studies and 1 case-control study) allowed for comparison of NSF risk between newer and older GBCAs. Among 83291 patients exposed to newer GBCAs, no NSF cases developed (exact 95% CI, 0.0001 to 0.0258 case). Among the 12 studies (n= 118844) that allowed risk comparison between newer and older GBCAs, 37 NSF cases developed after exposure to older GBCAs (exact CI, 0.0001 to 0.0523 case) and 4 occurred (3 confounded) after exposure to newer GBCAs (exact CI, 0.0018 to 0.0204 case). Data were scant for patients with acute kidney injury or those at risk for chronic kidney disease. Study heterogeneity prevented meta-analysis. Risk of bias was high in most studies because of inadequate exposure and outcome ascertainment. Although NSF occurrence after exposure to newer GBCAs is very rare, the relatively scarce data among patients with acute kidney injury and those with risk factors for chronic kidney disease limit conclusions about safety in these populations. U.S. Department of Veterans Affairs. (PROSPERO: CRD42019135783).

Adverse Events to the Gadolinium-based Contrast Agent Gadoxetic Acid: Systematic Review and Meta-Analysis.

Background Gadoxetic acid is classified by the American College of Radiology as a group III gadolinium-based contrast agent (GBCA), which indicates that there are limited data regarding nephrogenic systemic fibrosis (NSF) risk, but there are few if any unconfounded cases of NSF. Purpose To perform a systematic review and meta-analysis of gadoxetic acid adverse events, including immediate hypersensitivity reactions, NSF, and intracranial gadolinium retention. Materials and Methods Original research studies, case series, and case reports that reported adverse events in patients undergoing gadoxetic acid-enhanced MRI were searched in MEDLINE (1946-2019), Embase (1947-2019), CENTRAL (March 2019), and Scopus (1946-2019). The study protocol was registered at Prospero (number 162811). Risk of bias was evaluated by using Quality Assessment of Diagnostic Accuracy Studies-2, or QUADAS-2. Meta-analysis of proportions was performed by using random-effects modeling. Upper bound of 95% confidence interval (CI) for risk of NSF was determined. Results Seventy-one studies underwent full-text review. From 17 studies reporting 14 850 administrations, hypersensitivity reactions occurred in 0.3% (31 of 14 850; 95% CI: 0.2%, 0.4%) with zero deaths. From four studies reporting 106 administrations in patients with stage 4 or 5 chronic kidney disease or undergoing dialysis, the upper bound 95% CI for the risk of NSF was 2.8%. Five studies evaluating intracranial retention of gadolinium after gadoxetic acid administration were at high risk of bias. Conclusion Gadoxetic acid had a similar safety profile to American College of Radiology group 2 gadolinium-based contrast agents for hypersensitivity reactions and nephrogenic systemic fibrosis (NSF) but had lower confidence for risk of NSF because of fewer administrations in patients with severe kidney impairment. There is incomplete information documenting intracranial gadolinium retention in patients administered gadoxetic acid. © RSNA, 2020 Online supplemental material is available for this article.

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

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. 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. 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). 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.