Contrast Medium Iodixanol Research Articles

MiR-429 prohibited NF-κB signalling to alleviate contrast-induced acute kidney injury via targeting PDCD4

MiR-429 was reported to be downregulated in contrast-induced acute kidney injury (CI-AKI). However, whether miR-429 is functionally relevant with CI-AKI needs further investigation. Human renal tubular epithelial cell (HK-2) cells were stimulated with contrast media iodixanol to establish in vitro CI-AKI model. Cell Counting Kit-8 (CCK-8) was applied to access cell viability. Flow cytometry was performed to determine apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to evaluate level of programmed cell death 4 (PDCD4) mRNA and miR-429 while western blot was applied to evaluate level of proteins including PDCD4, B-cell leukaemia/lymphoma 2 (Bcl-2), BCL2-associated X protein (Bax), cleaved caspase 3, cleaved caspase 9, p65, phosphorylated p65. Dual luciferase assay was used to validate miR-429 targeting PDCD4. MiR-429 was downregulated whereas PDCD4 was upregulated in contrast media iodixanol-stimulated HK-2 cells. MiR-429 overexpression elevated cell viability and attenuated cell apoptosis. Moreover, the activation of nuclear factor kappa-B (NF-κB) signalling was suppressed after miR-429 overexpression, while PDCD4 overexpression reversed these effects. MiR-429 directly targeted PDCD4 and negatively regulated its expression. CI-AKI induced NF-κB signalling activation and PDCD4 overexpression further promoted NF-κB signalling activation. However, the treatment of BAY11-7082 reversed above results. Overexpression of miR-429 attenuated apoptosis and elevated cell viability in a CI-AKI cell model via targeting PDCD4 and thus restraining NF-κB signalling.

Effects of a High Dose of the Contrast Medium Iodixanol on Renal Function in Patients Following Percutaneous Coronary Intervention.

Iodixanol is associated with lower rates of contrast-induced acute kidney injury (CI-AKI). However, the effects of high volumes of iodixanol on renal function after percutaneous coronary intervention (PCI) have not been fully elucidated. This study evaluates the effects of high-dose (>300 mL) iodixanol on renal function within 72 hours of PCI. We retrospectively reviewed 676 consecutive patients who received high-dose (>300 mL) iodixanol during PCI between October 2015 and December 2017 in 4 centers. Logistic regression analysis was used to identify significant independent predictors for CI-AKI. The incidence of CI-AKI was 3.5% (23/651). In patients administered 300 to 500 mL and >500 mL iodixanol, the incidence of CI-AKI was 3.9% and 1.7%, respectively. In patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, the incidence of CI-AKI was 2.6%. In high-risk and very high-risk patients, stratified by the Mehran risk score, the incidence of CI-AKI was 3.3% and 4.3%, respectively. In patients received high-dose iodixanol (>300 mL), logistic regression analysis demonstrated that female sex, chronic kidney disease, and eGFR were independent risk factors for CI-AKI, but contrast volume was not. The administration of high (300-500 mL) and very high (>500 mL) dose of iodixanol is associated with low rates of CI-AKI.

Incidence of contrast-induced acute kidney injury (CI-AKI) in high-risk oncology patients undergoing contrast-enhanced CT with a reduced dose of the iso-osmolar iodinated contrast medium iodixanol.

ObjectivesTo determine the incidence of post-contrast acute kidney injury (PC-AKI) and presumed contrast-induced acute kidney injury (CI-AKI) following contrast-enhanced CT (CECT) with intravenous application of a reduced dose of the iso-osmolar contrast agent iodixanol in cancer patients with chronic kidney disease.Methods198 oncology patients with a baseline estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2 undergoing a total of 237 CECTs using a reduced dose of 60ml iodixanol were retrospectively analyzed. Statistical analysis was performed for the entire cohort and subgroups. The effect of additional risk factors on the occurrence of PC-AKI was evaluated.ResultsThe overall PC-AKI incidence was 6.3%. Excluding patients with concurrent medical conditions known to directly and independently impact kidney function and patients with AKI preceding the CT-scan resulted in a presumed CI-AKI incidence of 3.8%. No permanent post-contrast worsening of renal function and no AKI treatment were required. Subgroups considering baseline eGFR yielded PC-AKI incidences of 4.6% (eGFR 45-60ml/min/1.73m2, n = 130), 7.4% (eGFR 30-45ml/min/1.73m2, n = 95) and 16.7% (eGFR <30ml/min/1.73m2, n = 12). Additional patient related risk factors did not show any significant effect on the occurrence of PC-AKI.ConclusionsLow incidences of PC-AKI/CI-AKI suggest that a reduced dose of an iso-osmolar contrast agent is safe in high-risk oncological patients with impaired renal function.

MicroRNA-188 aggravates contrast-induced apoptosis by targeting SRSF7 in novel isotonic contrast-induced acute kidney injury rat models and renal tubular epithelial cells.

Contrast media (CM) is widely used in cardiac catheterization; however, it may cause contrast-induced acute kidney injury (CI-AKI) which severely increases mortality. MicroRNA (miRNA) has been found to participate in the process of acute kidney injury (AKI), and this discovery has great potential for diagnosis and treatment. However, the role of miRNA in CI-AKI is still unclear. This study aimed to investigate the regulatory effect miRNAs exert in CI-AKI. We established a novel, representative, isotonic CI-AKI model by using CM iodixanol, a CM which is commonly used in clinic. Next-generation sequencing and reverse transcription polymerase chain reaction (RT-qPCR) were performed to determine the expression of miRNA-188 in CI-AKI. Western blot analysis of the apoptosis regulator protein and TUNEL assay were ordered to evaluate apoptosis. Bioinformatics and double luciferin reporter gene assay were performed to predict and to confirm the interaction between microRNA-188 and SRSF7. The novel isotonic CI-AKI rat model we established exhibited typical characteristics of CI-AKI in serum creatinine, cystatin C, HE staining, and under electron microscope observation. Sequencing and RT-qPCR demonstrated that miRNA-188 was significantly up-regulated both in CI-AKI rat and HK-2 cell models while overexpression of miRNA-188 significantly aggravated apoptosis in CI-AKI cell models. SRSF7 was identified as a direct target gene of miRNA-188, and dual luciferase reporter assay determined the direct interaction between SRSF7 and miRNA-188. In addition, SRSF7 silencing reduced the cell viability rate of the CI-AKI cell model. The present study's findings indicate that miRNA-188 aggravated contrast-induced apoptosis by regulating SRSF7, which may serve as a potential drug target for CI-AKI intervention.

Iodixanol versus Iopromide at Coronary CT Angiography: Lumen Opacification and Effect on Heart Rhythm-the Randomized IsoCOR Trial.

Purpose To show that equal coronary lumen opacification can be achieved with iso- and low-osmolar contrast media when it is injected at the same iodine delivery rate with contemporary cardiac computed tomographic (CT) protocols and to investigate the cardiovascular effect of iso-osmolar contrast media and the image quality achieved. Materials and Methods Institutional review board approval and written informed consent were obtained for the Effect of Iso-osmolar Contrast Medium on Coronary Opacification and Heart Rhythm in Coronary CT Angiography, or IsoCOR, trial. Between November 2015 and August 2016, 306 patients (167 [55%] women) at least 18 years old (weight range, 50-125 kg), were prospectively randomized to receive iso-osmolar iodixanol 270 or low-osmolar iopromide 300 contrast media. All coronary segments were assessed for intraluminal opacification and image quality and were compared by using the Student t test. Heart rate, arrhythmia, patient discomfort, and adverse events also were monitored. Results Mean measured coronary attenuation values ± standard deviation were comparable between the iodixanol 270 and iopromide 300 contrast media groups (469 HU ± 167 vs 447 HU ± 166, respectively [P = .241]; 95% confidence interval: -15.1, 60.0), including those from subanalyses. Adjusted for the lower iodine concentration, the mean iodixanol 270 bolus was larger compared with that of iopromide 300 (76.8 mL ± 11.6 vs 69.7 mL ± 10.8, respectively; P < .001). The higher injection rate was associated with higher pressure (777 kPa ± 308 vs 630 kPa ± 252, respectively; P < .001). Although in the iodixanol 270 group patients experienced less heat discomfort (72% vs 86%, respectively; P < .001), no differences in heart rate or rhythm were observed. Conclusion If injected at comparable iodine delivery rates, the iso-osmolar contrast medium iodixanol 270 is not inferior to low-osmolar contrast medium iopromide 300 for assessment of coronary opacification. Iodixanol 270 was associated with less heat discomfort, but did not affect heart rate differently compared with iopromide 300. © RSNA, 2017 Online supplemental material is available for this article.

PP.09.16] PREDICTORS AND PROGNOSIS OF CONTRAST-INDUCED ACUTE KIDNEY INJURY IN PATIENTS WITH ELECTIVE PERCUTANEOUS INTERVENTION

Objective: Contrast-induced acute kidney injury (CI-AKI) is one of the most common complications after percutaneous coronary intervention (PCI) using intravascular radiocontrast media. CI-AKI has been associated with high in-hospital mortality and poor long-term survival. The aim of the study was to evaluate the incidence, risk factors and outcomes of CI-AKI in patients with elective PCI. Design and method: 150 patients with stable angina pectoris (SAP) and elective PCI (102 male, 61.3 ± 11.2 years (M ± SD), arterial hypertension 88%, previous MI 56%, diabetes mellitus 25%, known chronic kidney disease (CKD) 33%, anemia 17%, heart failure 67%, left ventricular ejection fraction 42 ± 16%) were examined. CI-AKI was defined using 2012 KDIGO Guidelines. Isoosmolar contrast media iodixanol (Visipaque-320) or low-osmolar contrast media iohexol (Omnipaque-350) were used. Transradial access for PCI was used in 98% of patients. Mann-Whitney test and multivariate logistic regression analysis were performed. P Results: 21 (14%) patients developed CI-AKI. Stages 1 and 2 of CI-AKI were found in 92 and 8% of cases accordingly. Main independent predictors of CI-AKI were contrast media volume (CV)/eGFR > 4.35 (odds ratio (OR) 20.2; 95% confidence interval (CI) 3.4–120.8; p 10 (OR 14.7; 95% CI 1.2–66.6; p 350 ml (OR 8.7; 95% CI 1.4–21.5; p 74.5 years (OR 6.9; 95% CI 1.4–34.1; p 96 μmol/l (OR 5.5; 95% CI 1.4–21.5; p Conclusions: CI-AKI in patients with SAP and elective PCI developed in 14% of cases, predominantly stage 1. Main independent predictors of CI-AKI were factors related to the contrast media (CV/eGFR, CV) and factors related to the patient (CKD, Mehran risk score > 10, age > 74.5 years, baseline eGFR 96 μmol/l, anemia). CI-AKI had negative impact on of 6 months rehospitalizations.

PP.09.01] IMPLEMENTATION OF ALGORITHM PREVENTING REDUCED RISK OF CONTRAST-INDUCED ACUTE KIDNEY INJURY IN CLINICAL PRACTICE IN PATIENT WITH PRIMARY PERCUTANEOUS CORONARY INTERVENTIONS

Objective: Patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) are at high risk of contrast-induced acute kidney injury (CI-AKI), a complication that negatively affects outcomes. In primary PCI we have limited time to assess the risk and preventing of CI-AKI. We performed a single-centre prospective study to determine the effect of implementation of algorithm preventing on the incidence of CI-AKI in patients with STEMI and primary PCI. Design and method: We used of historical control data for assessing of algorithm preventing CI-AKI in routine clinical practice. The study compared two groups of patients with ST-segment elevation myocardial infarction (STEMI) and primary PCI before and after implementation of algorithm preventing CI-AKI. In 1 Group - control group (n = 33) we used the routine prophylaxis CI-AKI: in patients with eGFR 10 received intravenous fluid administration hydration of 0.9% NaCl and N-Acetylcysteine (NAC): 0.9% NaCl x 500–1000 ml before PCI and 1 ml/kg/h post contrast administration with NAC 300 mg before PCI and 900 mg after PCI. Both groups were comparable in age (63 ± 11 and 62 ± 12 years), comorbidity (hypertension 89 and 85%, chronic kidney disease 14 and 15%, diabetes mellitus 19 and 17%) and received therapy. CI-AKI was defined using 2012 KDIGO Guidelines. Isoosmolar contrast media iodixanol (Visipaque-320) or low-osmolar contrast media iohexol (Omnipaque-350) were used. Transradial access for PCI was used in 98% of patients. Mann-Whitney test and multivariate logistic regression analysis were performed. P Results: The incidence of CI-AKI in intervention group was significantly lower than in the control group (20 and 11%, p Conclusions: Implementation of algorithm preventing of contrast-induced acute kidney injury significantly reduced the risk of CI-AKI in clinical practice in patient with STEMI and primary PCI.

Iodinated contrast media inhibit oxygen consumption in freshly isolated proximal tubular cells from elderly humans and diabetic rats: Influence of nitric oxide

Objectives Mechanisms underlying contrast medium (CM)-induced nephropathy remain elusive, but recent attention has been directed to oxygen availability. The purpose of this study was to evaluate the effect of the low-osmolar CM iopromide and the iso-osmolar CM iodixanol on oxygen consumption (QO2) in freshly isolated proximal tubular cells (PTC) from kidneys ablated from elderly humans undergoing nephrectomy for renal carcinomas and from normoglycemic or streptozotocin-diabetic rats.Materials PTC were isolated from human kidneys, or kidneys of normoglycemic or streptozotocin-diabetic rats. QO2 was measured with Clark-type microelectrodes in a gas-tight chamber with and without each CM (10 mg I/mL medium). L-NAME was used to inhibit nitric oxide (NO) production caused by nitric oxide synthase.Results Both CM reduced QO2 in human PTC (about –35%) which was prevented by L-NAME. PTC from normoglycemic rats were unaffected by iopromide, whereas iodixanol decreased QO2 (–34%). Both CM decreased QO2 in PTC from diabetic rats (–38% and –36%, respectively). L-NAME only prevented the effect of iopromide in the diabetic rat PTC.Conclusions These observations demonstrate that CM can induce NO release from isolated PTC in vitro, which affects QO2. Our results suggest that the induction of NO release and subsequent effect on the cellular oxygen metabolism are dependent on several factors, including CM type and pre-existing risk factors for the development of CM-induced nephropathy.

A method for estimating the glomerular filtration rate in conscious monkeys.

To establish a method for estimating the glomerular filtration rate (GFR) in conscious monkeys, the radiographic contrast medium iodixanol and the standard agent inulin were coadministered as tracers to male cynomolgus monkeys (Macaca fascicularis) as a bolus injection; blood was collected after 60, 90 and 120 min. An equation based on a single-blood-sample method derived from Jacobsson's formula was prepared using the data from healthy and saline- and gentamicin-treated monkeys by a multisample strategy with iodixanol. The GFR using the equation with iodixanol was in agreement with that from the multisample method with inulin or iodixanol. When the GFR decreased to more than 60% of the basal reference level, serum creatinine concentrations tended to increase, whereas serum blood urea nitrogen concentrations fluctuated. The results suggest that the single-sample-blood method with iodixanol is a practical tool for estimating the monkey GFR in a toxicological research setting therefore minimizing animal sufferings.

High Pitch Dual-Source Whole Aorta CT Angiography in the Detection of Coronary Arteries: A Feasibility Study of Using Iodixanol 270 and 100 kVp with Iterative Reconstruction

Discipline of Medical Imaging, Department of Imaging and App lied Physics, Curtin University, Perth, 6102, AustraliaTo assess the feasibility of detecting coronary arteries through high-pitch dual-source computed tomography(DSCT) thoracoabdominal angiography when using low-concentration contrast medium, low tube voltage, anditerative reconstruction. One hundred patients undergoing DSCT angiography with high-pitch data acquisitionmode were prospectively enrolled in this study. F ifty patients were assigned to receive Iodixanol 270 andscanned using the low tube voltage (100 kVp) technique and iterative reconstruction, while another Þfty patientswere assigned to Iopamidol 370 and scanned under the conventional tube voltage (120 kVp) with the imageswere reconstructed with Þltered back projection. Bo th subjective and objective assessment of image qualitywas performed and compared between the two groups by measuring the image noise, signal-to-noise ratio andcontrast-to-noise ratio in the coronary arteries. Diagnostic images were obtained for 1267 of the 1325 segments(95.6%). No signiÞcant differences in image quality wer e found between patients given Iodixanol 270 and Iopami-dol 370. The effective dose and contrast medium dose were 4.4 ± 0.5 mSv and 6.7 ± 0.6 mSv, 20.36 ± 2.65 gand 28 ± 1.98 g, corresponding to the Iodixanol 270 and Iopam idol 370 groups, respectively, with 34.3% dosereduction achieved in the low contrast medium Iodix anol 270 group. High-pitch DSCT angiography of the tho-racoabdominal aorta utilizing low iodine concentration contrast medium (Iodixanol 270), low tube voltage, anditerative reconstruction is a feasible protocol with signiÞcant reduction in r adiation dose and contrast medium,without compromising image quality.

Effects of iodinated contrast media in a novel model for cerebral vasospasm.

We developed an in vitro model for vasospasm post subarachnoid hemorrhage that was suitable for investigating brain vessel autoregulation. We further investigated the effects of iodinated contrast medium on the vascular tone and the myogenic response of spastic cerebral vessels. We isolated and perfused the superior cerebellar arteries of rats. The vessels were pressurized and studied under isobaric conditions. Coagulated blood was used to simulate subarachnoid hemorrhage. The contrast medium iodixanol was applied intraluminally. Vessels exposed to blood developed significantly stronger myogenic tone (65.7 ± 2.0% vs 77.1 ± 1.2% of the maximum diameter, for the blood and the control group, respectively) and significantly decreased myogenic response, compared with the control groups. The contrast medium did not worsen the myogenic tone or the myogenic response in any group. Our results show that deranged myogenic response may contribute to cerebral blood flow disturbances subsequent to subarachnoid hemorrhage. The contrast medium did not have any negative influence on vessel tone or myogenic response in this experimental setting.

Relationship of glomerular filtration rate based on serum iodixanol clearance to IRIS staging in cats with chronic kidney disease.

We examined the correlation between the glomerular filtration rate (GFR) estimated from an equation based on the serum iodixanol clearance technique and International Renal Interest Society (IRIS) stages of chronic kidney disease (CKD) in cats. The equation included the injection dose, sampling time, serum concentration and estimated volume of distribution (Vd) of the isotonic, nonionic, contrast medium iodixanol as a test tracer. The percent changes in the median basal GFR values calculated from the equation in CKD cats resembled those of IRIS stages 1–3. These data validate the association between the GFR derived from the simplified equation and IRIS stages based on the serum creatinine concentration in cats with CKD. They describe the GFR ranges determined using single-sample iodixanol clearance for healthy cats and cats with various IRIS stages of CKD.

Diadenosine pentaphosphate modulates glomerular arteriolar tone and glomerular filtration rate.

Mechanisms and participating substances involved in the reduction of glomerular filtration (GFR) in contrast-induced acute kidney injury (CI-AKI) are still matter of debate. We hypothesized that diadenosine polyphosphates are released by the action of contrast media on tubular cells and may act on glomerular arterioles and reduce GFR. Freshly isolated rat tubules were treated with the contrast medium iodixanol (47mg iodine per mL) at 37°C for 20min. The content of Apn A (n=3-6) in the supernatant of treated tubules and in the plasma of healthy persons and patients with AKI was analysed using reversed-phase chromatography, affinity chromatography and mass spectrometry. GFR was obtained in conscious mice by inulin clearance. Concentration response curves for Apn A (n=3-6, 10(-12) -10(-5) molL(-1) ) were measured in isolated perfused glomerular arterioles. Iodixanol treatment of tubules significantly increased the concentration of Apn A (n=3-5) in the supernatant. Ap6 A was below the detection limit. AKI patient shows higher concentrations of Apn A compared to healthy. Application of Ap5 A significantly reduced the GFR in conscious mice. Ap5 A reduced afferent arteriolar diameters, but did not influence efferent arterioles. The constrictor effect on afferent arterioles was strong immediately after application, but weakened with time. Then, non-selective P2 inhibitor suramin blocked the Ap5 A-induced constriction. The data suggest that Ap5 A plays a role in the pathophysiology of CI-AKI. We show a contrast media-induced release of Ap5 A from tubules, which might increase afferent arteriolar resistance and reduce the GFR.

Glomerular filtration rate in cows estimated by a prediction formula.

To testify the relevance of Jacobsson's equation for estimating bovine glomerular filtration rate (GFR), we prepared an integrated formula based on its equation using clinically healthy dairy (n=99) and beef (n=63) cows, and cows with reduced renal function (n=15). The isotonic, nonionic, contrast medium iodixanol was utilized as a test tracer. The GFR values estimated from the integrated formula were well consistent with those from the standard multisample method in each cow strain, and the Holstein equation prepared by a single blood sample in Holstein dairy cows. The basal reference GFR value in healthy dairy cows was significantly higher than that in healthy beef cows, presumably due to a breed difference or physiological state difference. It is concluded that the validity for the application of Jacobsson's equation to estimate bovine GFR is proven and it can be used in bovine practices.

Estimation of glomerular filtration rate in conscious mice using a simplified equation.

To develop an expedient procedure for estimating glomerular filtration rate (GFR) in conscious mice, we first established a simple technique for repeated blood collections from the tail vein using a microcapillary tube attached to a 24‐gauge needle without the hub. Then, we devised a definition equation for estimation of the GFR using the contrast medium iodixanol as a test tracer. Iodixanol was administered as a bolus injection at 1500 mg I/kg to ddY mice, and the GFR was determined by the conventional multisample strategy. Based on cumulative data from the multisample method, an equation for the single‐blood‐sample method including the iodixanol dose, estimated distribution volume (Vd), and plasma iodixanol concentration at 60 min later was sought. The GFR values from the multisample method were in good agreement with those calculated using the equation. In clinically healthy mice, the GFR decreased gradually with ages from 11 weeks old in both sexes, suggesting the necessity of the corresponding control in each protocol. In nephropathy mice induced by cisplatin, the GFR values decreased with rises in serum BUN and creatinine concentrations, and serum creatinine became elevated when the GFR decreased to approximately 70% of the basal value. The results suggest that the simplified equation using iodixanol, allowing for the repeated use of the same mice, is a versatile procedure for research purposes.

Post-marketing surveillance of the safety profile of iodixanol in the outpatient CT setting: a prospective, multicenter, observational study of patient risk factors, adverse reactions and preventive measures in 9953 patients.

Non-interventional study in outpatient, contrast-enhanced CT; 1. to determine the extent of preventive measures for risk reduction of adverse drug reactions after contrast-enhanced CT examinations. 2. to prospectively determine the incidence and severity of adverse drug reactions occurring after administration of the iso-osmolar contrast medium iodixanol. 3. to determine a possible influence of preventive measures on the incidence/severity of adverse drug reactions.. Evaluable documentation was provided for 9953 patients from 66 radiology centers across Germany. Patient characteristics, aspects of iodixanol administration, and adverse events with an at least "possible" relationship were documented on a standardized case report form (CRF) and were evaluated up to seven days after contrast medium administration. About 55.5 % of patients showed one or more risk factors (e. g. impaired renal function 4.4 %, diabetes mellitus 8.5 %, hypertension 20.6 %). One third of the sites did not implement any preventive measures. Patients with a known risk for an allergy-like reaction were more likely to receive pharmacologic preventive treatment (0.5 - 50.5 %). Oral hydration was the main preventive measure in patients with renal risk factors (< 8 %) followed by intravenous hydration (1 %). Adverse drug reactions, mainly hypersensitivity reactions, occurred in 77 patients (0.74 %), but were classified as serious in only 3 patients (0.03 %). No statistically significant correlation between risk factors, preventive measures, and adverse reactions could be found. The use of preventive measures for CT examinations in this outpatient setting was generally low with risk patients being pre-medicated more often, depending on their history. In the routine outpatient setting, iso-osmolar iodixanol was very well tolerated in almost 10,000 patients undergoing diagnostic CT. The rate of acute and delayed adverse reactions was low. No correlation could be found between risk factors, preventive measures and the incidence of adverse drug reactions. • Rare use of preventive measures for outpatient CT examinations.• Low rate of acute and late adverse drug reactions to iodixanol.• No correlation between risk factors, preventive measures and adverse drug reactions.

Technical note: Use of a simplified equation for estimating glomerular filtration rate in beef cattle1

This study was performed to clarify whether a formula (Holstein equation) based on a single blood sample and the isotonic, nonionic, iodine contrast medium iodixanol in Holstein dairy cows can apply to the estimation of glomerular filtration rate (GFR) for beef cattle. To verify the application of iodixanol in beef cattle, instead of the standard tracer inulin, both agents were coadministered as a bolus intravenous injection to identical animals at doses of 10 mg of I/kg of BW and 30 mg/kg. Blood was collected 30, 60, 90, and 120 min after the injection, and the GFR was determined by the conventional multisample strategies. The GFR values from iodixanol were well consistent with those from inulin, and no effects of BW, age, or parity on GFR estimates were noted. However, the GFR in cattle weighing less than 300 kg, aged<1 yr old, largely fluctuated, presumably due to the rapid ruminal growth and dynamic changes in renal function at young adult ages. Using clinically healthy cattle and those with renal failure, the GFR values estimated from the Holstein equation were in good agreement with those by the multisample method using iodixanol (r=0.89, P=0.01). The results indicate that the simplified Holstein equation using iodixanol can be used for estimating the GFR of beef cattle in the same dose regimen as Holstein dairy cows, and provides a practical and ethical alternative.

Glomerular filtration rate in Holstein dairy cows estimated from a single blood sample using iodixanol

The isotonic, nonionic, contrast medium iodixanol, as a test substance, was compared with the conventional glomerular filtration rate (GFR) tracer inulin to establish a simplified procedure for estimating the GFR in Holstein dairy cows. First, inulin and iodixanol were coadministered as a bolus intravenous injection to clinically healthy cows at 30mg/kg and 10mg of I/kg of body weight, respectively, followed by blood collection for multisample strategies. Serum iodixanol and inulin concentrations were separately determined by using HPLC and colorimetry, respectively, and blood urea nitrogen and creatinine concentrations in sera were measured. In the multisample method, the GFR values estimated by iodixanol were consistent with those estimated by inulin. No effects of body weight, age, or parity on GFR estimates were noted with either protocol used. No difference was observed between the GFR values obtained from nonlactating and lactating cows, suggesting that no transfer of iodixanol to milk occurred. An equation for calculating the GFR in the single-sample method was derived from the injected dose, sampling time, serum concentration, and estimated volume of distribution based on data from the multisample method in clinically healthy cows and cows with reduced renal function. The GFR values estimated by the single-sample method were in good agreement with those calculated by using the multisample method. These results demonstrate that the single-sample method using iodixanol can be applied as an alternative procedure for screening GFR in dairy cows.

Application of the single blood sample method to estimate feline glomerular filtration rate in a clinically relevant situation.

To compare glomerular filtration rate (GFR) estimated by a single blood sample method, the non-ionic contrast medium iodixanol (40 mg I/kg) and the standard GFR tracer inulin (50 mg/kg) were co-administered as a bolus intravenous injection to 12 cats, followed by blood collection 60 and 90 mins later. Serum iodixanol and inulin concentrations were measured separately by high-performance liquid chromatography and colourimetric assay. A correlation (r = 0.90, P <0.01) was noted between GFR values estimated by the single-blood-sample method using iodixanol and inulin, indicating that this procedure can apply to feline GFR estimates, even if different GFR tracers are used. In a feline kidney transplantation study, the GFR was monitored subsequently by this simplified iodixanol method throughout a 750-day observation period with no adverse reactions. The results demonstrate that the simplified method, including the volume of distribution, can be used as an alternative or expedient tool in a clinically relevant situation.

Iobitridol

Iobitridol is a water-soluble, non-ionic, monomeric, low-osmolar, iodine-based contrast medium in which the potential for interaction with membrane proteins in the body has been minimized by stable masking of the molecule's lipophilic tri-iodinated benzene ring. It is approved in various countries worldwide for use as an intravascular contrast medium in adults and children. This article reviews the diagnostic efficacy and tolerability of iobitridol use as an intravascular contrast agent in diagnostic imaging, and briefly overviews its pharmacological properties. In randomized controlled trials, the global image quality and diagnostic quality with iobitridol did not differ from those with other low-osmolar contrast media (iohexol, iopromide, iopamidol, iomeprol and ioxaglate) or the iso-osmolar contrast medium iodixanol in adults or children undergoing radiographic imaging. Large post-marketing surveillance studies have confirmed that iobitridol produces good or excellent opacification and is an effective contrast agent in the vast majority of patients. Iobitridol was generally well tolerated and had a tolerability profile similar to that of other low-osmolar and iso-osmolar contrast media. Thus, iobitridol is an effective intravascular agent for contrast enhancement in diagnostic imaging.