Nonionic Low-osmolar Contrast Media Research Articles

Hidden risk of gadolinium-based contrast agents during interventional pain medicine procedures: a retrospective chart review

IntroductionEpidural steroid injections and epidural blood patches commonly involve the injection of a small amount of radiocontrast media under fluoroscopy to properly identify the target tissue or anatomic space and...

CARD24: Protective Effect of HemoTech - Blood Substitute Against Contrast Media-Induced Endothelial Toxicity: An In Vitro Study

Background: Although the most common complication after intravascular administration of iodinated contrast media (CM) is contrast-induced nephropathy (CIN) there is some evidence suggesting CM toxicity to endothelial cells (EC). CIN mechanism is well defined and includes medullary ischemia and direct toxicity to renal tubular cells. The mechanism of CM-associated EC damage is still unclear. The purpose of this study was twofold: (1) to determine the response of normal and ischemic coronary artery EC to low-osmolar nonionic CM commonly used in percutaneous coronary interventions (PCI) and (2) to evaluate the protective effect of HemoTech used concomitantly with CM. HemoTech is Hb-based blood substitute pharmacologically modified with vasodilators, anti-inflammatory and antioxidant agents: ATP, adenosine and reduced glutathione (GSH), and is in the preclinical development phase of its intended use as perfusion fluid for PCI. Methods: In this study human coronary artery EC (Clonetics, Bio-Whittaker, San Diego, CA) were subcultured in EGM-MV medium to confluence on cover slips and 6-well cell cultured plates in a humidified atmosphere of 5% CO2 and 37 deg C. To mimic ischemia, EC were depleted from GSH by 24 hr treatment with 200 uM of BSO (L-buthionine-[S,R]-sulphoximine).Then, normal and ischemic EC were exposed for 1, 2, 4 and 18 hrs to 50 uL/mL of low-osmolar nonionic iodinated CM Optiray 350 (Ioversol Injection 74%, Mallinckrodt Pharmaceuticals) alone or with 0.4 mM of HemoTech and assessed for cellular redox state and oxidative stress (GSH, TBARS), inflammatory response (VCAM-1) and early and late apoptosis. Results: The results demonstrate a different response of normal and ischemic EC to CM. While normal EC showed delayed mild reaction, a response of ischemic EC was immediate and intensifies with time. In normal EC there was a depletion of GSH from 24.1±1.5 to 18.5±1.1 nM/mg protein (p<0.05) at 18 hr; however without changes in TBARS and only insignificant expression of VACAM-1 in the absence of apoptosis. On the contrary, CM showed to strongly affect ischemic EC causing further redox imbalance. At 2 hr GSH dropped from 13.6±0.9 to 10.3±0.6 (p<0.05) and progressively decreased to 9.1±0.5 (p<0.01) at 4 hr and 7.5±0.4 (p<0.001) at 18 hr. TBARS progressively increased from 0.84±0.03 to 0.98±0.04 nM/mg protein (p<0.05) at 2 hr, 1.1±0.07 (p<0.01) at 4 hr and 1.44±0.12 (p<0.001) at 18 hr. A slight expression of VACAM-1 was noted at 4 hr that reached the peak at 18 hr (p<0.01). Early apoptosis was detected at 18 hr. HemoTech treatment effectively restored the redox balance in ischemic EC and alleviated inflammatory and apoptotic responses to CM. All tested parameters were in normal range. Conclusions: Low-osmolar nonionic iodinated CM is well tolerated by normal but not ischemic coronary artery EC. HemoTech blood substitute with pharmacological properties of ATP, adenosine and GSH protects ischemic EC against CM-induced toxicity.

Incidence and severity of nonionic low-osmolar iodinated contrast medium-related adverse drug reactions in the Republic of Korea: Comparison by generic.

We aimed to report the incidence and severity of nonionic low-osmolar iodine contrast medium (ICM)-related adverse drug reactions (ADRs) in the Republic of Korea, by analyzing data from our single tertiary institution and published Korean reports, and to determine whether there is a difference in the incidence of ICM-related ADR by ICM generics. A total of 1,161,419 consecutive contrast-enhanced computed tomography (CT) examinations between January 2016 and December 2021 at Asan Medical Center were included. A systematic search of the literature investigating the incidence of ICM-related ADR in the Republic of Korea published up to December 31, 2021 was performed. We pooled these outcomes with those of our study using a binomial-normal model, and the pooled incidences of ADRs were compared among ICM generics using chi-square tests. Seven studies with a total of 2,570,986 contrast-enhanced CT examinations from 12 institutions were included. The pooled incidences of overall, mild, moderate, and severe ICM-related ADRs in the Republic of Korea were 0.82% (95% CI: 0.61%-1.10%), 0.72% (95% CI: 0.50%-1.04%), 0.11% (95% CI: 0.08%-0.15%), and 0.013% (95% CI: 0.010%-0.018%), respectively. In multiple pairwise comparisons, there were no significant differences in the overall incidence of ADRs between ICM generics, except iomeprol versus iobitridol and iomeprol versus iohexol. For moderate and severe ADRs, there were no significant differences in ADR incidence between ICM generics. The incidence of moderate and severe ICM-related ADRs did not differ among ICM generics. Our results suggest that no restriction is required for selection among nonionic low-osmolar ICMs.

Development of Frog Neck After Coronary Angiography: Contrast-Induced Sialadenitis

Iodine-related submandibular sialadenitis is a rare complication among the causes of sialadenitis. To date, the pathogenesis of iodide mumps has not yet been ascertained. This situation is a late reaction to iodinecontaining contrast agents and can manifest in any patient receiving iodinated contrast agents and repeated exposure. Fortunately, this condition does not require specific treatment and resolution can be expected within one or two weeks. We report an 82-year-old man suffering from iodide-induced sialadenitis following coronary angiography with the use of non-ionic low osmolar contrast media.

MicroRNA expression profile by next-generation sequencing in a novel rat model of contrast-induced acute kidney injury.

MicroRNAs (miRNAs) are known to regulate most biological processes including contrast-induced acute kidney injury (CI-AKI). Few studies have investigated microRNA (miRNAs) expressions in a novel rat model of CI-AKI using nonionic low-osmolar iodic contrast medium Ultravist, and performed gene ontology (GO) categories analysis. In this study, kidney tissues were collected from Sprague-Dawley rats at 24 h after contrast-exposure (CI-AKI) and saline-administration (control). MiRNAs microarray assays were used to detect miRNAs in the kidney tissue by next-generation sequencing. Real-time PCR was performed to verify the microarray assays results. All significant differently expressed miRNAs were analyzed by GO categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Of the 173 detected miRNAs, 22 were down-regulated (miR-328a-5p, miR-31a-5p, miR-377-3p, et al.) and 19 were up-regulated (miR-3558-5p, miR-34c-3p, miR-384-5p, et al.) in the kidneys of CI-AKI rats according to log2 (fold change, control) >1, P<0.001 as significant differently expressed miRNAs, which included new differently expressed miRNAs, such as miRNA-1949 and miR-3558. The results showed that a large set of genes involved in essential biological processes were targeted by these miRNAs, such as dysfunction metabolic process, apoptotic process, and endoplasmic reticulum stress, in addition to genes implicated in signaling pathways involved in inflammation and dysfunctional metabolism, including AGE-RAGE signaling pathway and glycerophospholipid metabolism. The 41 miRNAs identified were differentially expressed in the kidneys of a novel rat model of CI-AKI, and thus possess the potential to serve as novel biological markers and new molecular targets for CI-AKI.

Outcomes of corticosteroid prophylaxis for hypersensitivity reactions to low osmolar contrast media in high-risk patients

BackgroundCorticosteroid prophylaxis has been widely adopted for the prevention of acute allergic-like reactions to iodinated contrast media, but its use is still controversial because there is no strong evidence supporting its efficacy before administration of nonionic low osmolar contrast media (LOCM). ObjectiveTo assess the outcomes of premedication in patients with previous acute allergic-like reactions to LOCM in clinical practice. MethodsA retrospective study was performed on 322 high-risk patients who were reexposed to LOCM after premedication composed of antihistamines and/or systemic corticosteroids because of a previous history of acute allergic-like reactions to LOCM. ResultsAfter premedication, 275 patients (85.4%) did not experience any reaction, but 47 patients (14.6%) still experienced a breakthrough reaction. The premedication rate and amount of corticosteroid administered were significantly higher in the nonrecurrence group than in the recurrence group (P = .04 and P = .04, respectively), and a linear trend was observed in the use of corticosteroid premedication and the efficacy of prevention (P for trend = .02). Multivariate binary logistic regression revealed that corticosteroid premedication was effective in preventing recurrence (odds ratio, 0.284; 95% confidence interval, 0.103–0.784). Nonetheless, despite corticosteroid premedication, 3.4% of high-risk patients still experienced moderate to severe reactions, and 14.3% of patients with a severe index reaction again had a severe reaction. ConclusionPremedication with corticosteroids seems to be helpful in reducing the overall rate of recurrence of acute allergic-like reactions to LOCM in high-risk patients, but patients with severe index reactions are still at risk of developing severe reactions despite corticosteroid premedication.

Clinical characteristics of adverse reactions to nonionic low osmolality contrast media in patients transferred from the CT room to the emergency room

Nonionic low osmolality contrast media (LOCMs) are used universally in computed tomography (CT) imaging. Although adverse reactions due to nonionic LOCMs are a common cause of emergency room (ER) admissions, few studies have investigated these adverse reactions. In the present study, we evaluated the characteristics of patients who were transferred from the CT room to the ER due to adverse reactions to contrast media, and we determined the risk factors for severe adverse reactions. A single-center retrospective study was conducted over a 41-month period. Baseline and clinical characteristics were evaluated and analyzed according to moderate and severe severity. In particular, risk factors of severe reactions were determined using logistic regression analysis. In total, 70 patients were admitted to the ER with adverse reactions due to nonionic LOCMs. Of these, 33 developed a moderate reaction, and 37 developed a severe reaction. Compared with the moderate reaction group, the severe reaction group was older, had higher blood pressures, showed more symptoms indicating the cardiovascular and central nervous system, and developed faster reactions to LOCMs. According to the multivariate logistic regression analysis, the age of the patient and time to onset of reaction demonstrated a statistical relationship with severe adverse reactions. In the receiver operating characteristic analysis, the optimal cutoff values for age and time to onset were 60 years and 5 min. In conclusion, clinicians should be attentive to anaphylaxis due to nonionic LOCM, in particular, for elderly patients aged older than 60 years and a time to reaction onset of less than 5 min.

The Lack of Benefit of a Combination of an Angiotensin Receptor Blocker and Calcium Channel Blocker on Contrast-Induced Nephropathy in Patients with Chronic Kidney Disease

Aim: Contrast-induced nephropathy (CIN) is a relatively common and serious complication, which occurs after the administration of contrast materials to patients. Although the pathophysiology of CIN is not exactly understood, ischemia of the medulla, oxidative stress, and direct toxicity of the contrast material are some of the factors that are implicated for the pathogenesis of CIN. To date, the only therapy that reduces the risk of CIN is volume expansion. There are conflicting results about the roles of angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) in studies on CIN. For this reason the aim of this study was to compare the efficiency of the prophylactic use of amlodipine/valsartan plus hydration versus hydration only for the prevention of CIN in patients undergoing coronary angiography (CAG). Patients and methods: We prospectively enrolled 90 patients whose baseline serum creatinine levels were under 2.1 mg/dL and who were scheduled for CAG. Patients were divided into two groups. Group I (n = 45), consisted of patients who received amlodipine/valsartan plus hydration, group II (n = 45) consisted of patients who received only hydration. The patients in group I were given amlodipine/valsartan 5/160 mg once a day for a total of 3 days, starting one day before CAG and continuing on the day of and the day after the procedure. A 1 mL/kg/h sodium chloride infusion was administered for a total of 24 h, starting 12 h before the procedure and 12 h after, in all patients. The baseline serum creatinine (Scre) level was obtained before the procedure and repeated 48 h after. CIN was defined as an increase of ≥0.5 mg/dL or an increase of >25% in baseline Scre on the second day after CAG. Results: The baseline clinical characteristics of the treatment groups were similar. Baseline Scre was 1.13 ± 0.33 in group I and 1.07 ± 0.23 mg/dL in group II (p = 0.31). There was a significant difference between the Scre levels 48 h after CAG between the two groups (1.18 ± 0.33–1.05 ± 0.23) (p = 0.03). The reason for this was the increase of Scre in group I. CIN occurred in 17.8% (8/45) of patients in group I and in 6.7% (3/45) of patients in group II (p = 0.197). In the diabetic subgroup, CIN occurred in 10.5% (2/19) of patients taking amlodipine/valsartan and in none of the patients in group II (p = 0.486). The Mehran scores of the patients who developed CIN were significantly higher than those patients who did not develop CIN. Conclusion: Amlodipine/valsartan therapy plus hydration did not reduce the risk of CIN in chronic kidney disease (CKD) Stage 2 patients who underwent elective CAG using a low-osmolar nonionic contrast medium. This is because there was a decrease in the glomerular filtration rate (GFR) using the Levey Modification of Diet in Renal Disease (MDRD) formula in the amlodipine/valsartan group and CIN occurred at a higher frequency in this group; ARBs and CCBs may be withheld before CAG in high-risk patients.

Evidence‐based management of patients undergoing PCI: Contrast‐induced acute kidney injury

Contrast-induced acute kidney injury (CI-AKI) is one of the leading causes of hospital-acquired acute kidney injury. CI-AKI is highly prevalent in patients with well-known risk factors, including older age, chronic renal insufficiency, congestive heart failure, and diabetes. Thus far, no strategies have been shown to be effective in preventing CI-AKI beyond thorough patient selection, minimizing the amount of contrast agent, and meticulous hydration of the patient. The role of various drugs in preventing CI-AKI is still controversial and warrants future studies. Despite the remaining uncertainty regarding the degree of nephrotoxicity produced by various contrast agents, nonionic low-osmolar contrast media may be preferred in patients at high risk for CI-AKI.

Are there any differences in acute adverse reactions among five low-osmolar non-ionic iodinated contrast media?

The differences regarding adverse reactions in different low-osmolar non-ionic contrast media had not been investigated previously. Thus, the aims of this study were to identify differences in the incidence of adverse reactions in five different low-osmolar non-ionic contrast media. We prospectively recorded all adverse events associated with five different low-osmolar non-ionic contrast media used in 8,931 consecutive patients for CT. Patients were randomly assigned to five groups: iomeprol 300 mgI/ml, iopamidol 300 mgI/ml, iohexol 300 mgI/ml, iopromide 300 mgI/ml and ioversol 320 mgI/ml. Adverse events were observed in 241 patients (2.7%). The incidence of acute adverse reactions was significantly higher in the following groups: (1) iomeprol (3.9%) and iopromide (3.5%) groups, (2) patients aged 59 years or less (4.5%) compared with those aged 60 years or over (1.9%), (3) the first period (3.5%) compared with the late period (2.3%), (4) those with a past history of adverse reactions to contrast media (11.2%), and (5) patients receiving contrast media for the first time (3.3%) compared with those had received it previously (2.0%). The incidence of acute adverse reactions may be reduced in younger patients by using iopamidol, iohexol and ioversol.

Prevention and treatment of contrast-associated nephropathy in interventional cardiology

Contrast-induced nephropathy (CIN) is a common complication after diagnostic and therapeutic cardiovascular procedures that is associated with significant mortality and morbidity. CIN is highly prevalent in patients with well-known risk factors, including older age, chronic renal insufficiency, congestive heart failure, and diabetes. Thus far, no strategies have been shown to be effective in preventing CIN beyond thorough patient selection, minimizing the amount of contrast agent, and meticulous hydration of the patient. The role of various drugs in preventing CIN is still controversial and warrants future studies. Despite the remaining uncertainty regarding the degree of nephrotoxicity produced by various contrast agents, nonionic low-osmolar contrast media may be preferred in patients at high risk for CIN.

Low osmolar contrast medium induces cellular injury and disruption of calcium homeostasis in rat glomerular endothelial cells in vitro

The mechanisms of contrast medium (CM)-induced renal impairment at cellular level are not fully understood. The purpose of this study was to investigate the toxic effects of non-ionic low osmolar contrast medium (LOCM) on glomerular endothelial cells (GECs). Ioversol, the most representative LOCM used in clinic, was chosen to act on primary cultured rat GECs. When rat GECs were treated with various amount of ioversol, a dose-dependent reduction in cell viability was observed by tetrazolium dye (MTT) assay. After exposure to ioversol at dose of 100 μl/ml for 24 h, nuclear condensation, nuclear fragmentation, cell apoptosis and necrosis were found in GECs. The intracellular free Ca 2+ concentrations ([Ca 2+]i) detected by confocal laser scanning were markedly elevated in GECs treated with ioversol. The [Ca 2+]i increase, LDH release and expression changes of apoptotic associated proteins in GECs induced by ioversol could be reversed by pretreatment with intracellular Ca 2+ chelator, 1,2-bis ( o-aminophenoxy) ethane- N, N, N′, N′-tetra-acetic acid (BAPTA/AM). These results suggest that LOCM can decrease cell viability and cause cell injury of GECs. The elevation of [Ca 2+]i released from intracellular calcium stores likely contribute to the LOCM-induced cell injury of GECs.

Prevention of Radiocontrast-induced Nephropathy with N-acetylcysteine after Cardiac Angiography in Diabetic Patients with Renal Dysfunction

Purpose. To examine the effects of N-acetylcysteine (NAC) in a homogeneous high-risk population. Methods. This is a prospective randomized single-blinded placebo-controlled clinical study. Diabetic patients with pre-existing renal insufficiency (serum creatinine concentration (SCC) above 1.6mg/dL, or estimated creatinine clearance (CCR) less than 40mL/min) who had received moderate to large amounts of non-ionic low osmolar contrast medium, Omnipaque (iohexol), during a diagnostic or interventional procedure were eligible to participate. All patients were adequately hydrated with half-saline (1mL/(kg•h) from 12 hours before to 12 hours after the procedure). They were randomized into one of two groups. Patients in the NAC group were given NAC 600mg orally twice a day, 4 doses in total; the first dose was given one day before the procedure. Patients in the control group were given placebo orally twice a day, 4 doses in total; the first dose was given one day before the procedure. SCC was assessed before hydration, 2 days after the procedure, and 5 days after the procedure. Radiocontrast-induced nephropathy (RCIN) was defined as a 25% rise from baseline or an absolute increase of 0.5mg/dL in SCC after the procedure. The primary end-point was risk of developing RCIN. Results. Twenty patients completed the study. There were no significant differences in age, sex, body mass index, blood pressure, duration of angiography, or mean volume of dye infused between the two groups. CCR did not change significantly in either group 2 days after angiography (NAC group 24.5±10.3 vs 29.6±10.6mL/min, N=11, p=0.34; control group 27.4±10.3 vs 29.6±10.6mL/min, N=9, p=0.57), or 5 days after angiography (NAC group 24.5±10.3 vs 27.4±11.8mL/min, N=11, p=0.40; control group 27.4±10.3 vs 24.2±8.8mL/min, N=9, p=0.43). None of the patients in the NAC group and five patients in the control group developed RCIN. The incidence of RCIN was lower in the NAC group (0% vs 56%, p=0.006, N=20). The average length of hospitalization was shorter in the NAC group (5.2 vs 8.1 days, p=0.04, N=20). None of the patients who developed RCIN required dialysis. Conclusion. NAC protects diabetic patients with renal dysfunction from iohexol-related RCIN after cardiac angiographic procedures.

Gadolinium:Nonionic Contrast Media (1:1) Coronary Angiography in Patients With Impaired Renal Function

This study was to test safety and efficacy of 1:1 mixture of gadolinium:nonionic contrast media in avoiding contrast nephropathy during coronary angiography in patients with renal dysfunction. Although "off label" for x-ray angiography, gadolinium has drawn attention for its potential to avoid contrast nephropathy during coronary angiography. Initial data seem promising. Patients with a baseline creatinine of 1.5 mg/dl or more were included. In order to minimize contrast nephropathy risk, all patients were thoroughly hydrated and treated by N-acetylcysteine. After coronary angiography and/or percutaneous coronary intervention, renal function tests were remeasured on days 1, 2, and 3. A rise of 0.5 mg/dl or more in creatinine value in the following 3 days or the need for dialysis were considered as a contrast nephropathy event. Twenty-six patients were enrolled in this study. Ten were women and 16 were men. The mean age was 65.7 +/- 11. Baseline creatinine value was 2.47 +/- 0.74 mg/dl. The total amount of contrast medium used on 1:1 fashion was 57.1 +/- 27.2 ml. No procedure-related cardiac complication or contrast nephropathy event occurred in this study. Although there was a slight loss in image quality, we felt that the results were adequate for interpretation. Although "off label," using gadolinium contrast media in a 1:1 mixture with standard nonionic low osmolar contrast media seems to be a viable option in decreasing the likelihood of contrast nephropathy. Further evaluation appears to be warranted.

Effects of non-ionic iodinated contrast media on patient heart rate and pressures during intra-cardiac or intra-arterial injection

Purpose To compare the effects on heart rate (HR), on left ventricular (LV) or arterial pressures, and the general safety of a non-ionic low-osmolar contrast medium (CM) and a non-ionic iso-osmolar CM in patients undergoing cardiac angiography (CA) or peripheral intra-arterial digital subtraction angiography (IA-DSA). Materials and methods Two double-blind, randomized studies were conducted in 216 patients who underwent CA ( n = 120) or peripheral IA-DSA ( n = 96). Patients referred for CA received a low-osmolar monomeric CM (iomeprol-350, n = 60) or an iso-osmolar dimeric CM (iodixanol-320; n = 60). HR and LV peak systolic and end-diastolic pressures were determined before and after the first injection during left and right coronary arteriography and left ventriculography. Monitoring for all types of adverse event (AE) was performed for 24 h following the procedure. t-tests were performed to compare CM for effects on HR. Patients referred for IA-DSA received iomeprol-300 ( n = 49) or iodixanol-320 ( n = 47). HR and arterial blood pressure (BP) were evaluated before and after the first 4 injections. Monitoring for AE was performed for 4 h following the procedure. Repeated-measures ANOVA was used to compare mean HR changes across the first 4 injections, whereas changes after the first injection were compared using t-tests. Results No significant differences were noted between iomeprol and iodixanol in terms of mean changes in HR during left coronary arteriography ( p = 0.8), right coronary arteriography ( p = 0.9), and left ventriculography ( p = 0.8). In patients undergoing IA-DSA, no differences between CM were noted for effects on mean HR after the first injection ( p = 0.6) or across the first 4 injections ( p = 0.2). No significant differences ( p > 0.05) were noted in terms of effects on arterial BP in either study or on LV pressures in patients undergoing CA. Non-serious AE considered possibly CM-related (primarily headache and events affecting the cardiovascular and digestive systems) were reported more frequently by patients undergoing CA and more frequently after iodixanol (14/60 [23.3%] and 2/47 [4.3%]; CA and IA-DSA, respectively) than iomeprol (10/60 [16.7%] and 1/49 [2%], respectively). Conclusions Iomeprol and iodixanol are safe and have equally negligible effects on HR and LV pressures or arterial BP during and after selective intra-cardiac injection and peripheral IA-DSA. Clinical application Iomeprol and iodixanol are safe and equally well tolerated with regard to cardiac rhythm and clinical preference should be based on diagnostic image quality alone.

Risk Factors and Therapy Strategies for Contrast-Induced Nephropathy

Contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality, as well as increased costs for medical care, particularly in patients with diabetes mellitus and chronic renal failure. A key step to safer CIN is to identify patients at risk and applying proven preventive interventions. Extracellular volume expansion, minimizing the dose of contrast media, using low-osmolar non-ionic contrast media, stopping the intake of nephrotoxic drugs, and avoiding short intervals between procedures have all been shown to be effective in reducing CIN. The aim of the present review is to summarize the knowledge about the risk factors and prophylactic treatments of CIN.

Contrast-induced nephropathy

How contrast medium-induced nephropathy (CIN) comes about is not fully understood, although CIN constitutes a leading cause of renal failure. Here, a short review of clinical trials and a more thorough outline of mechanisms thought to cause CIN are outlined. Osmolality is only one of several physicochemical properties of contrast media (CM). Iso-osmolar CM are dimers, not monomers. Thus, they have physicochemical features different from other CM, e.g., in terms of viscosity (which is over fivefold greater than plasma viscosity). This may be of considerable pathophysiologic and clinical importance. There are studies providing evidence for a greater perturbation in renal functions by iso-osmolar CM in comparison to nonionic low-osmolar CM. Conversely, some previous clinical trials indicate an advantage of the iso-osmolar CM. This review highlights altered rheological properties, perturbation of renal hemodynamics, regional hypoxia, auto- and paracrine factors (adenosine, endothelin, reactive oxygen species) and direct cytotoxic effects, which are all thought to participate in causing CIN. It is concluded that the use of CM in general, and high viscous iso-osmolar CM in particular, can be deleterious to the kidney due to augmented resistance in the renal tubules.

Assessment of Radiocontrast Nephropathy after Cardiac Catheterization in infants and children with Congenital Heart diseases.

ABSRTACT Background: Increasing numbers of patients are exposed to contrast medium (CM) during Cardiac Catheterization procedures. Radiocontrast use in all branches of medicine is reported to be the third most common cause of new onset renal failure in hospital patients. Objectives: To assess renal dysfunction induced by use of contrast media (CM) in infants and children with congenital heart diseases (CHD) undergoing Cardiac Catheterization. Methods: Serum creatinine (Cr), corrected creatinine clearance (c.Cr.Cl.), serum Beta 2 microglobulin (β2MG), urinary retinol binding protein (uRBP), fractional excretion of sodium (FENa), and urine to serum osmolality ratio (u/sOSM) were measured in 19 patients with congenital cyanotic heart diseases (CCHD) and 26 patients with congenital cyanotic heart diseases (CCHD) 24 hours before and 72 hours after cardiac Catheterization using low osmolar nonionic CM. Patients were compared to 31 healthy controls of matched age and sex. Results: Before Cardiac Catheterization, there was no significant difference in the studied parameters between CCHD and CAHD patients when compared either to each other or to the healthy controls. Only u/s OSM ratio was significantly reduced in CCHD patients when compared to CAHD (P=0.02) or controls (P=0.01). After cardiac Catheterization, all patients showed significant reduction of their c.Cr.Cl, u/s OSM (P <0.001& 0.002 respectively) and a significant increase of β2MG, uRBP & FENa (p <0.001, 0.002 and 0.003 respectively) and a non-significant change of Cr (p=0.23). Both before and after cardiac Catheterization; c.Cr.Cl correlated more significantly with β2MG (r=-0.65 & -0.79, p=0.001& 0.005 respectively) rather than with Cr (r=-0.41& -0.52, p=0.02 & 0.01 respectively). Out of the studied 45 patients; only 3patients matched the definition of CM nephropathy despite the significant change in different renal parameters. Conclusions: Children with CHD develop significant defects in glomerular and tubular parameters after CM use despite that their Cr may not increase. Revision of the currently used definition of CM nephropathy may be required.

Pathophysiology of contrast medium–induced nephropathy

Contrast medium-induced nephropathy (CIN) is a well-known cause of acute renal failure, but the development of CIN remains poorly understood. A number of studies have been performed with the one aim, to shed some light onto the pathophysiology of CIN. These have led to manifold interpretations and sometimes contradicting conclusions. This review critically surveys mechanisms believed to mediate CIN by highlighting the complex pathophysiologic entity, including altered rheologic properties, perturbation of renal hemodynamics, regional hypoxia, auto- and paracrine factors [adenosine, endothelin, and reactive oxygen species (ROS)], and direct cytotoxic effects. Moreover, the importance of physicochemical properties of contrast media are made clear. The more recently developed iso-osmolar contrast media are dimers, not monomers as the widely used nonionic low osmolar contrast media. The dimers have physicochemical features different from other contrast media which may be of clinical importance, not only with respect to osmolality. The viscosity of the commercially available dimers is considerably higher than blood. Many experimental studies provide evidence for a greater perturbation in renal functions by dimeric contrast media in comparison to nonionic monomeric contrast media. Clinical trials have yielded conflicting results.

Cost-effectiveness of iodixanol in patients at high risk of contrast-induced nephropathy

Acute renal failure after contrast-induced nephropathy is a clinically important and costly complication after the use of iodine-based contrast media. We investigated the cost and cost-effectiveness of 2 contrast media in patients at high risk of contrast-induced nephropathy. The analyses were based on a randomized, prospective, multinational clinical study comparing the nephrotoxic effects of an isosmolar nonionic contrast medium, iodixanol, with those of a low-osmolar nonionic contrast medium, iohexol. Resource utilization data were obtained from the study and from a retrospective review of patients' hospital records. Swedish, German, and French unit prices were applied to resources used. Between-group differences in average costs were analyzed using a nonparametric bootstrap method. Resource utilization data for 125 patients were analyzed. Seven contrast media-related serious adverse reactions, of which 6 were acute renal failures, were noted in 6 patients receiving iohexol. Two patients in the iodixanol group had 1 nonserious reaction each. The mean hospitalization cost per patient was Euros 489, Euros 573, and Euros 393 lower after iodixanol than after iohexol using Swedish, German, and French unit prices, respectively. The mean per-patient costs of treating adverse drug reactions were Euros 371, Euros 399, and Euros 445 lower after iodixanol than after iohexol, using the respective unit prices (P < or = 0.01). Iodixanol was cost-effective compared with iohexol, with both lower costs and better effects related to fewer adverse drug reactions. The isosmolar contrast medium iodixanol appears to be cost-effective when compared with a low-osmolar contrast medium, iohexol, in diabetic patients with renal impairment undergoing angiography.