Nephrogenic systemic fibrosis and gadolinium-based contrast media: updated ESUR Contrast Medium Safety Committee guidelines.

PURPOSE: To update the guidelines of the Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) on nephrogenic systemic fibrosis and gadolinium-based contrast media. AREAS COVERED: Topics reviewed include the history, clinical features and prevalence of nephrogenic systemic fibrosis and the current understanding of its pathophysiology. The risk factors for NSF are discussed and prophylactic measures are recommended. The stability of the different gadolinium-based contrast media and the potential long-term effects of gadolinium in the body have also been reviewed.

Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines.

PURPOSE: The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). AREAS COVERED: Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml/min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR ≥ 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally.

Late adverse reactions to intravascular iodine based contrast media: an update.

DEFINITION: Late adverse reactions (LAR) to contrast media (CM) are defined as reactions occurring 1 h to 1 week after exposure. NEED FOR REVIEW: In view of more prospective studies of LAR and new data about their pathophysiology, the Contrast Medium Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) reviewed the literature on LAR and updated their guidelines. CLINICAL FEATURES AND PATHOLOGY: LAR after CM include symptoms such as nausea, vomiting, headache, itching, skin rash, musculoskeletal pain, and fever. Skin reactions are well-documented LAR to CM with an incidence of approximately 2%-4% after nonionic monomers. LAR are commoner by a factor of three to four after nonionic dimers. The commonest skin reactions are maculopapular rashes, erythema and skin swelling. These reactions are T cell-mediated immune reactions, and the diagnosis may be confirmed using skin tests (patch or delayed reading intradermal). The main risk factors for LAR are a previous reaction to contrast medium, a history of allergy, and interleukin-2 treatment. Most skin reactions are mild or moderate and self-limiting. MANAGEMENT: Management is symptomatic and similar to the management of other drug-induced skin reactions. To reduce the risk of repeat reactions avoidance of the relevant CM and any cross-reacting agents identified by skin testing is recommended.

Risk of contrast-medium-induced nephropathy in high-risk patients undergoing MDCT--a pooled analysis of two randomized trials.

The incidence of contrast-medium-induced nephropathy (CIN) following intravenous (IV) CM administration of contrast media to renally impaired patients undergoing multidetector computed tomography (MDCT) is not well characterized. Our objective was to investigate the incidence of CIN in patients with glomerular filtration rate (GFR) <60 ml/min undergoing contrast-enhanced MDCT examinations and to compare the rates of CIN following the IV administration of low-osmolar contrast media (LOCM, iopamidol and iomeprol) and an iso-osmolar contrast medium (IOCM, iodixanol). A total of 301 adult patients with moderate-to-severe renal failure received a similar IV contrast dose (40 gI). Serum creatinine (SCr) was measured at screening, baseline and 48-72 +/- 6 h after the MDCT examination. Primary CIN outcome was an increase in SCr >or=0.5 mg/dl (>or=44.2 micromol/l) from baseline. The CIN rates were 2.3% in the total population, 0.6% when GFR >40 ml/min, 4.6% when GFR <40 ml/min and 7.8% in patients with GFR <30 ml/min. The incidence of CIN was significantly higher after iodixanol than after LOCM (seven patients, 4.7% following IOCM, no CIN cases following the LOCM; p = 0.007). Significant differences in favor of the LOCM were also observed in patients with GFR <40 ml/min and GFR <30 ml/min. Following the IV administration of nonionic contrast agents in patients with moderate-to-severe renal insufficiency, the risk of significant CIN seems to be low. The IOCM iodixanol caused a higher rate of CIN than the LOCM iopamidol and iomeprol, especially in high-risk patients. Differences in osmolality between these LOCM and iodixanol do not play a role in the genesis of CIN.

The ACTIVE Trial: comparison of the effects on renal function of iomeprol-400 and iodixanol-320 in patients with chronic kidney disease undergoing abdominal computed tomography.

BACKGROUND: We performed a multicenter, double-blind, randomized, parallel-group study to compare the renal effects of iomeprol-400 and iodixanol-320 in patients with preexisting chronic kidney disease undergoing contrast-enhanced multidetector computed tomography of the liver. METHODS: One hundred forty-eight patients with moderate-to-severe chronic kidney disease, ie, serum creatinine (SCr) > or =1.5 mg/dL (132.6 micromol/L) and/or calculated creatinine clearance (CrCl) <60 mL/min, undergoing contrast-enhanced multidetector computed tomography of the liver were randomized to equi-iodine doses (40 gI) of either the low-osmolar agent iomeprol-400 (400 mgI/mL, 726 mOsm/kg, N = 76) or the isotonic agent iodixanol-320 (320 mgI/mL, 290 mOsm/kg, N = 72), injected intravenously at 4 mL/S, followed by a bolus of 20 mL normal saline solution at the same rate. SCr was obtained at screening, baseline and at 48 to 72 hours postdose. SCr measurements and CrCl calculations were performed by a central laboratory. Contrast-induced nephropathy (CIN) was defined as an absolute SCr increase of > or =0.5 mg/dL (44.2 micromol/L) from baseline to 48 to 72 hours postdose. Mean SCr changes from baseline were also assessed. A Renal Safety Review Board comprised 3 medical experts reviewed the renal safety data, demographics, medical history, CIN risk factors, concomitant medications, and hydration status of each subject in a blinded manner. RESULTS: The 2 study groups were comparable with regard to age, gender distribution, concomitant nephrotoxins, hydration status, and total iodine dose; however, the iomeprol-400 group showed a significantly higher proportion of patients with diabetes mellitus (P = 0.02). Baseline SCr was 1.7 +/- 0.6 mg/dL (150.3 +/- 53.0 micromol/L) in the iomeprol-400 group and 1.7 +/- 0.7 mg/dL (150.3 +/- 61.9 micromol/L) in the iodixanol-320 group (P = 0.87). Predose CrCl was 41.5 +/- 13.1 mL/Min in the iomeprol-400 group and 43.0 +/- 13.3 mL/Min in the iodixanol-320 group (P = 0.49). Five of 72 patient receiving iodixanol-320 (6.9%) and none of the patients receiving iomeprol-400 showed an increase of > or =0.5 mg/dL (44.2 micromol/L) from baseline [P = 0.025, 95% CI (-12.8%, -1.1%)]. The mean SCr change from baseline was significantly higher (P = 0.017 ANCOVA) after iodixanol-320 (0.06 +/- 0.27) than after iomeprol-400 (-0.04 +/- 0.19). CONCLUSIONS: The incidence of CIN was significantly higher after IV administration of iodixanol-320 than iomeprol-400. The mean rise in SCr from baseline was also higher in patients receiving iodixanol.

Reducing the risk of iodine-based and MRI contrast media administration: recommendation for a questionnaire at the time of booking.

This paper presents a practical questionnaire to be used when a contrast medium examination is requested. The questionnaire is based on the guidelines from the European Society of Urogenital Radiology. Its aim is to identify patients at increased risk of clinically relevant renal and non-renal adverse reactions to iodine-based and MRI contrast agents. The questionnaire should be completed by the referring physician when the examination is requested.

Total gadolinium tissue deposition and skin structural findings following the administration of structurally different gadolinium chelates in healthy and ovariectomized female rats.

OBJECTIVE: To assess the retention of gadolinium (Gd) in skin, liver, and bone following gadodiamide or gadoteric acid administration. METHODS: Gd was measured in skin, liver and femur bone in female rats 10 weeks after administration of 17.5 mmol Gd/kg over 5 days of Gd agents. Rat skin microscopy, energy filtering transmission electron microscopy and elemental analysis were performed, and repeated after receiving the same dosage of gadodiamide in rats with osteoporosis induced with bilateral ovariectomy (OVX). The OVX was performed 60 days after the last injection of gadodiamide and animals sacrificed 3 weeks later. RESULTS: Gd concentration was 180-fold higher in the skin, 25-fold higher in the femur, and 30-fold higher in the liver in rats received gadodiamide than rats received gadoteric acid. The retention of Gd in the skin with gadodiamide was associated with an increase in dermal cellularity, and Gd encrustation of collagen fibers and deposition inside the fibroblasts and other cells. No differences in Gd concentration in liver, skin, and femur were observed between rats receiving gadodiamide with or without OVX. CONCLUSIONS: Gd tissue retention with gadodiamide was higher than gadoteric acid. Tissues Gd deposition did not alter following gadodiamide administration to ovariectomized rats.

Can selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphadiesterase type 5 (PDE 5) offer protection against contrast induced nephropathy?

Parenchymal hypoxia within the renal outer medulla plays an important role in the pathogenesis of contrast induced nephropathy (CIN). Nitric oxide (NO) is crucial for medullary oxygenation by enhancing regional blood flow. Augmenting the effect of NO in the renal medulla by the use of selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphadiesterase type 5 (PDE 5) such as sildenafil (Viagra™), vardenafil (Levitra™) or tadalafil (Cialis™) could reduce the severity of the hypoxic insult induced by the contrast medium and reduce the risk of CIN. Prophylactic administration of one of these drugs particularly the long acting one tadalafil before and after the administration of CM could offer a simple and rational approach to reduce the risk of this complication. This hypothesis deserves serious investigation to determine its clinical efficacy.

Evidence based imaging strategies for solitary pulmonary nodule.

Solitary pulmonary nodule (SPN) is defined as a rounded opacity ≤3 cm in diameter surrounded by lung parenchyma. The majority of smokers who undergo thin-section CT have SPNs, most of which are smaller than 7 mm. In the past, multiple follow-up examinations over a two-year period, including CT follow-up at 3, 6, 12, 18, and 24 months, were recommended when such nodules are detected incidentally. This policy increases radiation burden for the affected population. Nodule features such as shape, edge characteristics, cavitation, and location have not yet been found to be accurate for distinguishing benign from malignant nodules. When SPN is considered to be indeterminate in the initial exam, the risk factor of the patients should be evaluated, which includes patients' age and smoking history. The 2005 Fleischner Society guideline stated that at least 99% of all nodules 4 mm or smaller are benign; when nodule is 5-9 mm in diameter, the best strategy is surveillance. The timing of these control examinations varies according to the nodule size (4-6, or 6-8 mm) and the type of patients, specifically at low or high risk of malignancy concerned. Noncalcified nodules larger than 8 mm diameter bear a substantial risk of malignancy, additional options such as contrast material-enhanced CT, positron emission tomography (PET), percutaneous needle biopsy, and thoracoscopic resection or videoassisted thoracoscopic resection should be considered.

Implications of Web of Science journal impact factor for scientific output evaluation in 16 institutions and investigators' opinion.

Journal based metrics is known not to be ideal for the measurement of the quality of individual researcher's scientific output. In the current report 16 contributors from Hong Kong SAR, India, Korea, Taiwan, Russia, Germany, Japan, Turkey, Belgium, France, Italy, UK, The Netherlands, Malaysia, and USA are invited. The following six questions were asked: (I) is Web of Sciences journal impact factor (IF) and Institute for Scientific Information (ISI) citation the main academic output performance evaluation tool in your institution? and your country? (II) How does Google citation count in your institution? and your country? (III) If paper is published in a non-SCI journal but it is included in PubMed and searchable by Google scholar, how it is valued when compared with a paper published in a journal with an IF? (IV) Do you value to publish a piece of your work in a non-SCI journal as much as a paper published in a journal with an IF? (V) What is your personal view on the metric measurement of scientific output? (VI) Overall, do you think Web of Sciences journal IF is beneficial, or actually it is doing more harm? The results show that IF and ISI citation is heavily affecting the academic life in most of the institutions. Google citation and evaluation, while is being used and convenient and speedy, has not gain wide 'official' recognition as a tool for scientific output evaluation.

Gadolinium contrast agent associated stimulation of human fibroblast collagen production.

OBJECTIVES: Nephrogenic systemic fibrosis occurs in patients with poor renal function who receive gadolinium-based contrast agents (Gd-CAs). Several reports suggest that this is more likely to occur with the less stable forms of Gd chelates, suggesting a release of cytotoxic free Gd ions from these. There is evidence that Gd can stimulate human fibroblast proliferation but the evidence is less clear concerning the production of collagen by these cells. Our aim was to assess effects of Gd chelates on human skin cell activity and collagen production. MATERIALS AND METHODS: Keratinocytes and fibroblasts were cultured with 3 Gd chelates (Gd-EDTA, Omniscan [nonionic linear Gd-CA], and Dotarem [ionic macrocyclic Gd-CA]) for up to 7 days, and cell viability and collagen production were assessed using the colorimetric assays of MTT (3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide) and Sirius Red, respectively. The uptake of Gd by cultured fibroblasts was also undertaken using the techniques of inductively coupled plasma mass spectrometry and relaxometry. RESULTS: Our data show that Gd-EDTA and Omniscan significantly stimulated both fibroblast and keratinocyte viability and fibroblast (but not keratinocyte) collagen production. In contrast, Dotarem had little, if any, effect on these cultured cells. The Omniscan-induced increase in fibroblast collagen was around 40% over 7 days-a similar increase to that seen for cell viability, suggesting that collagen production was secondary to an initial stimulatory effect on fibroblast viability. Studies of the uptake of Gd by the cultured fibroblasts showed that these took up Gd when cultured with Omniscan for 7 days, and our study also suggests that some of this Gd was in a free dissociated form. CONCLUSIONS: We conclude that these results support a simple nephrogenic systemic fibrosis causative role of low-stability nonionic linear Gd-CA inducing dermal collagen via the release of dissociated Gd which enters fibroblasts and stimulates their activity and associated collagen production.

Pathophysiology of nephrogenic systemic fibrosis: A review of experimental data.

Since the association between nephrogenic systemic fibrosis (NSF) and gadolinium contrast agents (Gd-CAs) was suggested in 2006, several experimental studies have been published to elucidate the role of these agents in the pathogenesis of NSF. Low stability Gd-CAs have a stimulant effect on human skin and fibroblasts in culture and modulate the production of collagen by these cells. Low stability agents have also induced NSF-like skin changes in a rat model with normal renal function after multiple repeat administrations. The role of the 5/6 subtotal nephrectomy rat model in investigating NSF remains under evaluation.

Computed tomography urography technique, indications and limitations.

PURPOSE OF REVIEW: The review discusses the different techniques of computed tomography urography reported in the literature and presents the author's preferred approach. RECENT FINDINGS: Multiphase computed tomography urography offers a comprehensive evaluation of the urinary tract but at the cost of a large dose of contrast medium (100-150 ml), high radiation dose and massive number of images for interpretation. Diuresis induced by frusemide (10 mg) is reported to improve the depiction of ureters in the excretory phase of the examination. The author's preferred approach is a limited computed tomography urography which includes precontrast scanning of the kidneys, followed by an excretory phase 5 min after intravenous injection of 50 ml of contrast medium and 10 mg of frusemide. This limited examination in the author's experience provides a satisfactory evaluation of the urinary tract in the majority of patients, without inflicting a high radiation dose on the patient. SUMMARY: A limited computed tomography urography examination is adequate for the majority of patients requiring excretory urography and a superior replacement of conventional intravenous urography. Information provided by a multiphase computed tomography urography examination is beneficial only in a small number of patients.

Contrast-medium-induced nephropathy: is there a new consensus? A review of published guidelines.

The interest in contrast-medium-induced nephropathy has increased considerably during the last few years. Various guidelines regarding identifying patients at risk and measures to reduce the incidence of this complication have been proposed. The aim of this review was to analyse whether there is some consistency amongst these guidelines. A Medline search for the keyword "contrast medium induced nephropathy" during the period from the beginning of 2003 through the end of September 2005 was carried out. Only papers in English were reviewed. Thirteen guidelines were identified. Inconsistency was observed regarding advise on the prophylactic use of drugs and the isoosmolar dimer to reduce the incidence of contrast-medium-induced nephropathy. Consistency was found in relation to the importance of hydration, cessation of intake of nephrotoxic drugs and administration of the lowest possible dose of contrast medium. No new consensus has been observed in comparison to the European Society for Urogenital Radiology (ESUR) guidelines, which were published in 1999.

Effects of iodinated contrast media on blood and endothelium.

The aim of the study was to assess the effects of iodinated contrast media on blood components and endothelium based on experimental and clinical studies and to produce clinically relevant guidelines for reducing thrombotic and hematologic complications following the intravascular use of contrast media. A report was drafted after review of the literature and discussions among the members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology. The final report was produced following discussion at the 12th European Symposium on Urogenital Radiology in Ljubljana, Slovenia (2005). Experimental data indicate that all iodinated contrast media produce an anticoagulant effect and that this effect is greater with ionic contrast media. Several of the in vitro and experimental in vivo studies on haematological effects of contrast media have not been confirmed by clinical studies. Low- or iso-osmolar contrast media should be used for diagnostic and interventional angiographic procedures, including phlebography. Meticulous angiographic technique is the most important factor for reducing the thrombotic complications associated with angiographic procedures. Drugs and interventional devices that decrease the risk of thromboembolic complications during interventional procedures minimize the importance of the effects of contrast media.