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Kidney International Apr 2021Using data (2655 observations from 928 participants) from the Chronic Kidney Disease in Children Study, we developed and internally validated new glomerular filtration...
Using data (2655 observations from 928 participants) from the Chronic Kidney Disease in Children Study, we developed and internally validated new glomerular filtration rate estimating equations for clinical use in children and young adults: two forms of K × [heigh(ht) / serum creatinine(sCr)] and two forms of K × [1 / cystatin C(cysC)]. For each marker, one equation used a sex-dependent K; in the other, K is sex-and age-dependent. Glomerular filtration rate (GFR) was measured directly by plasma iohexol disappearance. The equations using ht⁄sCr had sex-specific constants of 41.8 for males and 37.6 for females. In the age- dependent models, K increased monotonically for children 1-18 years old and was constant for young adults 18-25 years. For males, K ranged from 35.7 for one-year-olds to 50.8 for those 18 and older. For females, the values of K ranged from 33.1 to 41.4. Constant K values for cystatin-C equations were 81.9 for males and 74.9 for females. With age-dependency, K varied non-monotonically with the highest values at age 15 for males (K of 87.2) and 12 years for females (K of 79.9). Use of an age-dependent K with ht/sCr models reduced average bias, notably in young children and young adults; age-dependent cystatin-C models produced similar agreement to using a constant K in children under 18 years, but reduced bias in young adults. These age-dependent proposed equations were evaluated alongside estimated GFRs from 11 other published equations for pediatrics and young adults. Only our proposed equations yielded non- significant bias and within 30% accuracy values greater than 85% in both the pediatric and young adult subpopulations.
Topics: Adolescent; Biomarkers; Child; Child, Preschool; Creatinine; Female; Glomerular Filtration Rate; Humans; Infant; Iohexol; Male; Renal Insufficiency, Chronic; Young Adult
PubMed: 33301749
DOI: 10.1016/j.kint.2020.10.047 -
BMJ Case Reports Aug 2021
Topics: Bronchi; Bronchography; Contrast Media; Humans; Iohexol
PubMed: 34353841
DOI: 10.1136/bcr-2021-244942 -
Redox Biology Nov 2023Contrast-induced acute kidney injury(CI-AKI) is the third cause of AKI. Although tubular injury has been regarded as an important pathophysiology of CI-AKI, the...
Contrast-induced acute kidney injury(CI-AKI) is the third cause of AKI. Although tubular injury has been regarded as an important pathophysiology of CI-AKI, the underlying mechanism remains elusive. Here, we found arginase2(ARG2) accumulated in the tubules of CI-AKI mice, and was upregulated in iohexol treated kidney tubular cells and in blood samples of CI-AKI mice and patients, accompanied by increased nitrosative stress and apoptosis. However, all of the above were reversed in ARG2 knockout mice, as evidenced by the ameliorated kidney dysfunction and the tubular injury, and decreased nitrosative stress and apoptosis. Mechanistically, HO-1 upregulation could alleviate iohexol or ARG2 overexpression mediated nitrosative stress. Silencing and overexpressing ARG2 was able to upregulate and downregulate HO-1 expression, respectively, while HO-1 siRNA had no effect on ARG2 expression, indicating that ARG2 might inhibit HO-1 expression at the transcriptional level, which facilitated nitrosative stress during CI-AKI. Additionally, CREB1, a transcription factor, bound to the promoter region of ARG2 and stimulated its transcription. Similar findings were yielded in cisplatin- or vancomycin-induced AKI models. Taken together, ARG2 is a crucial target of CI-AKI, and activating CREB1/ARG2/HO-1 axis can mediate tubular injury by promoting nitrosative stress, highlighting potential therapeutic strategy for treating CI-AKI.
Topics: Animals; Humans; Mice; Acute Kidney Injury; Apoptosis; Cisplatin; Iohexol; Kidney; Mice, Inbred C57BL; Nitrosative Stress; Transcription Factors; Arginase
PubMed: 37856999
DOI: 10.1016/j.redox.2023.102929 -
Korean Journal of Radiology 2016This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary CT angiography in healthy subjects.
MATERIALS AND METHODS
Volunteers were randomized to receive 420 mgI/kg of either iohexol-350 or iohexol-380 using a flow rate of 4 mL/sec. All adverse events were recorded. Two blinded readers independently reviewed the CT images and conflicting results were resolved by a third reader. Luminal attenuations (ascending aorta, left main coronary artery, and left ventricle) in Hounsfield units (HUs) and image quality on a 4-point scale were calculated.
RESULTS
A total of 225 subjects were given contrast media (115 with iohexol-380 and 110 with iohexol-350). There was no difference in number of adverse drug reactions between groups: 75 events in 56 (48.7%) of 115 subjects in the iohexol-380 group vs. 74 events in 51 (46.4%) of 110 subjects in the iohexol-350 group (p = 0.690). No severe adverse drug reactions were recorded. Neither group showed an increase in serum creatinine. Significant differences in mean density between the groups was found in the ascending aorta: 375.8 ± 71.4 HU with iohexol-380 vs. 356.3 ± 61.5 HU with iohexol-350 (p = 0.030). No significant differences in image quality scores between both groups were observed for all three anatomic evaluations (all, p > 0.05).
CONCLUSION
Iohexol-380 provides improved enhancement of the ascending aorta and similar attenuation of the coronary arteries without any increase in adverse drug reactions, as compared with iohexol-350 using an identical amount of total iodine.
Topics: Adult; Aged; Aorta; Computed Tomography Angiography; Contrast Media; Coronary Vessels; Creatinine; Double-Blind Method; Electrocardiography; Female; Gastrointestinal Diseases; Healthy Volunteers; Humans; Image Interpretation, Computer-Assisted; Iohexol; Male; Middle Aged; Nervous System Diseases; Skin Diseases; Young Adult
PubMed: 27134522
DOI: 10.3348/kjr.2016.17.3.330 -
American Journal of Kidney Diseases :... Jul 2020Glomerular filtration rate (GFR) estimation based on creatinine or cystatin C level is currently the standard method for assessing GFR in epidemiologic research and... (Comparative Study)
Comparative Study
RATIONALE & OBJECTIVE
Glomerular filtration rate (GFR) estimation based on creatinine or cystatin C level is currently the standard method for assessing GFR in epidemiologic research and clinical trials despite several important and well-known limitations. Plasma iohexol clearance has been proposed as an inexpensive method for measuring GFR that could replace estimated GFR in many research projects. However, lack of standardization for iohexol assays and the use of different protocols such as single- and multiple-sample methods could potentially hamper comparisons across studies. We compared iohexol assays and GFR measurement protocols in 3 population-based European cohorts.
STUDY DESIGN
Cross-sectional investigation.
SETTING & PARTICIPANTS
Participants in the Age, Gene/Environment Susceptibility-Kidney Study (AGES-Kidney; n=805), the Berlin Initiative Study (BIS, n=570), and the Renal Iohexol Clearance Survey Follow-up Study (RENIS-FU; n=1,324).
TESTS COMPARED
High-performance liquid chromatography analyses of iohexol. Plasma iohexol clearance calculated using single- versus multiple-sample protocols.
OUTCOMES
Measures of agreement between methods.
RESULTS
Frozen samples from the 3 studies were obtained and iohexol concentrations were remeasured in the laboratory at the University Hospital of North Norway. Lin's concordance correlation coefficient ρ was>0.96 and C (accuracy) was>0.99 for remeasured versus original serum iohexol concentrations in all 3 cohorts, and Passing-Bablok regression did not find differences between measurements, except for a slope of 1.025 (95% CI, 1.006-1.046) for the log-transformed AGES-Kidney measurements. The multiple-sample iohexol clearance measurements in AGES-Kidney and BIS were compared with single-sample GFRs derived from the same iohexol measurements. Mean bias for multiple-sample relative to single-sample GFRs in AGES-Kidney and BIS were-0.25 and-0.15mL/min, and 99% and 97% of absolute differences were within 10% of the multiple-sample result, respectively.
LIMITATIONS
Lack of comparison with an independent gold-standard method.
CONCLUSIONS
Agreement between the iohexol assays and clearance protocols in the 3 investigated cohorts was substantial. Our findings indicate that plasma iohexol clearance measurements can be compared across these studies.
Topics: Aged; Aged, 80 and over; Aging; Biomarkers; Cohort Studies; Contrast Media; Cross-Sectional Studies; Female; Follow-Up Studies; Gene-Environment Interaction; Germany; Glomerular Filtration Rate; Humans; Iceland; Iohexol; Kidney Function Tests; Male; Metabolic Clearance Rate; Middle Aged; Norway; Population Surveillance
PubMed: 31879216
DOI: 10.1053/j.ajkd.2019.10.008 -
The British Journal of Radiology Feb 2022With optimized technique, the water-soluble contrast challenge is effective at triaging patients for operative non-operative management of suspected small bowel... (Review)
Review
With optimized technique, the water-soluble contrast challenge is effective at triaging patients for operative non-operative management of suspected small bowel obstruction. Standardized study structure and interpretation guidelines aid in clinical efficacy and ease of use. Many tips and tricks exist regarding technique and interpretation, and their understanding may assist the interpreting radiologist. In the future, a CT-based water-soluble contrast challenge, utilizing oral contrast given as part of the initial CT examination, might allow for a more streamlined algorithm and provide more rapid results.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Algorithms; Colon; Conservative Treatment; Contrast Media; Diatrizoate Meglumine; Gastrointestinal Transit; Humans; Intestinal Obstruction; Intestine, Small; Intubation, Gastrointestinal; Iohexol; Middle Aged; Radiography, Abdominal; Treatment Outcome; Triage
PubMed: 34826227
DOI: 10.1259/bjr.20210791 -
BMJ Case Reports Aug 2018
Topics: Abdominal Cavity; Acute Kidney Injury; Catheterization, Central Venous; Computed Tomography Angiography; Contrast Media; Dextrocardia; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Iohexol; Male; Treatment Outcome; Urinary Bladder
PubMed: 30097550
DOI: 10.1136/bcr-2018-226024 -
Journal of Neuroimaging : Official... Jul 2021Evaluation and treatment of acute ischemic syndromes, in the heart and brain, require vessel visualization by iodinated X-ray contrast agents. However, these contrast...
BACKGROUND AND PURPOSE
Evaluation and treatment of acute ischemic syndromes, in the heart and brain, require vessel visualization by iodinated X-ray contrast agents. However, these contrast agents can induce injury, in both the kidneys and target organs themselves. Sulfobutylether beta cyclodextrin (SBECD) added to iohexol (SBECD-iohexol) (Captisol Enabled-iohexol, Ligand Pharmaceuticals, Inc, San Diego, CA) is currently in clinical trials in cardiovascular procedures, to determine its relative renal safety in high-risk patients. Preclinical studies showed that SBECD-iohexol reduced contrast-induced acute kidney injury in rodent models by blocking apoptosis. The current study was undertaken to determine whether SBECD-iohexol is also cardioprotective, in the male rat ischemia-reperfusion model, compared to iohexol alone.
METHODS
After anesthesia, the left coronary artery was ligated for 30 min and the ligation released and reperfusion followed for 2 h prior to sacrifice. Groups 1-4 were injected in the tail vein 10 min prior to ischemia with: (1) vehicle; (2) iohexol; (3) SBECD; and (4) SBECD-iohexol. Infarct size, hemodynamics, and serum markers were measured.
RESULTS
An eight-fold increase in serum creatine kinase in the iohexol-alone group was observed, compared with no increase in the SBECD-iohexol group. The mean arterial pressure and rate pressure product were depressed in the iohexol-alone group, but not in the SBECD-iohexol group, or controls. No difference in infarct size or serum creatinine among the groups was observed.
CONCLUSION
The results of this study suggest that SBECD-iohexol is superior to iohexol alone, for both the preservation of cardiomyocyte integrity and preservation of myocardial function in myocardial ischemia.
Topics: Acute Kidney Injury; Animals; Contrast Media; Humans; Iohexol; Kidney; Male; Pilot Projects; Rats
PubMed: 33979019
DOI: 10.1111/jon.12873 -
British Journal of Clinical Pharmacology Nov 2022Immunosuppressant and kidney function monitoring are crucial for kidney transplant recipient follow-up. Microsamples enable remote sampling and minimise patient burden...
AIMS
Immunosuppressant and kidney function monitoring are crucial for kidney transplant recipient follow-up. Microsamples enable remote sampling and minimise patient burden as compared to conventional venous sampling at the clinic. We developed a liquid chromatography-tandem mass spectrometry assay to quantify tacrolimus, mycophenolic acid (MPA), creatinine and iohexol in dried blood spot (DBS), and volumetric absorptive microsample (VAMS) samples.
METHODS
The assay was successfully validated analytically for all analytes. Clinical validation was conducted by direct comparison of paired DBS, VAMS and venous reference samples from 25 kidney transplant recipients. Patients received iohexol 5-15 minutes before immunosuppressant intake and were sampled 0, 1, 2 and 3 hours thereafter, enabling tacrolimus and MPA area under the concentration-time curve (AUC) and creatinine-based and iohexol-based glomerular filtration rate (GFR) estimation. Method agreement was evaluated using Passing-Bablok regression, Bland-Altman analysis and the percentages of values within 15-30% of the reference (P -P ) with a P acceptance threshold of 80%.
RESULTS
For DBS samples, method agreement was excellent for tacrolimus trough concentrations (n = 25, P = 92.0%) and AUCs (n = 25; P = 95.8%) and adequate for creatinine-based GFR trend monitoring (n = 25; P = 80%). DBS-based MPA AUC assessment showed suboptimal agreement (n = 16; P = 68.8%), but was considered acceptable given its P of 100%. The assay performed inadequately for DBS-based iohexol GFR determination (n = 24; P = 75%). The VAMS technique generally showed inferior performance, but can be considered for certain situations.
CONCLUSION
The assay was successfully validated for tacrolimus, MPA and creatinine quantification in DBS samples, enabling simultaneous remote kidney function trend monitoring and immunosuppressant therapeutic drug monitoring in kidney transplant recipients.
Topics: Creatinine; Dried Blood Spot Testing; Drug Monitoring; Humans; Immunosuppressive Agents; Iohexol; Kidney; Kidney Transplantation; Mycophenolic Acid; Outpatients; Tacrolimus
PubMed: 35670960
DOI: 10.1111/bcp.15433 -
Acta Crystallographica. Section D,... Sep 2022Small-angle X-ray scattering (SAXS) has become an indispensable tool in structural biology, complementing atomic-resolution techniques. It is sensitive to the...
Small-angle X-ray scattering (SAXS) has become an indispensable tool in structural biology, complementing atomic-resolution techniques. It is sensitive to the electron-density difference between solubilized biomacromolecules and the buffer, and provides information on molecular masses, particle dimensions and interactions, low-resolution conformations and pair distance-distribution functions. When SAXS data are recorded at multiple contrasts, i.e. at different solvent electron densities, it is possible to probe, in addition to their overall shape, the internal electron-density profile of biomacromolecular assemblies. Unfortunately, contrast-variation SAXS has been limited by the range of solvent electron densities attainable using conventional co-solutes (for example sugars, glycerol and salt) and by the fact that some biological systems are destabilized in their presence. Here, SAXS contrast data from an oligomeric protein and a protein-RNA complex are presented in the presence of iohexol and Gd-HPDO3A, two electron-rich molecules that are used in biomedical imaging and that belong to the families of iodinated and lanthanide-based complexes, respectively. Moderate concentrations of both molecules allowed solvent electron densities matching those of proteins to be attained. While iohexol yielded higher solvent electron densities (per mole), it interacted specifically with the oligomeric protein and precipitated the protein-RNA complex. Gd-HPDO3A, while less efficient (per mole), did not disrupt the structural integrity of either system, and atomic models could be compared with the SAXS data. Due to their elevated solubility and electron density, their chemical inertness, as well as the possibility of altering their physico-chemical properties, lanthanide-based complexes represent a class of molecules with promising potential for contrast-variation SAXS experiments on diverse biomacromolecular systems.
Topics: Contrast Media; Iohexol; Lanthanoid Series Elements; Proteins; RNA; Scattering, Small Angle; Solvents; X-Ray Diffraction
PubMed: 36048152
DOI: 10.1107/S2059798322007392