GFR measurement in patients with CKD: Performance and feasibility of simplified iohexol plasma clearance techniques.

Implementing shortened one-compartment iohexol plasma clearance models for GFR measurement is crucial since the gold standard inulin renal clearance technique and the reference two-compartment, 10-hour, 16-samplings iohexol plasma clearance method are clinically unfeasible. Inulin may precipitate anaphylactic shock. Four-hour and 8-hour one-compartment iohexol plasma clearance models with Bröchner-Mortensen correction provide accurate GFR measurements in patients with estimated GFR (eGFR) > or ≤40 mL/min/1.73m2, respectively. We compared the performance of the simplified 5-hour, 4-samplings, two-compartment population pharmacokinetic model (popPK) with the performance of the reference two-compartment 10-hour iohexol method in 16 patients with GFR 15.2 to 56.5 mL/min/1.73 m2. We also compared the performance of shortened (5, 6 and 7-hour) one-compartment models with the performance of the standard 8-hour one-compartment model in 101 patients with eGFR ≤40 mL/min/1.73 m2. The performance of popPK and shortened methods versus reference methods was evaluated by total deviation index (TDI), concordance correlation coefficient (CCC) and coverage probability (CP). TDI <10%, CCC ≥0.9 and CP >90% indicated adequate performance. TDI, CCC and CP of popPK were 11.11%, 0.809 and 54.10%, respectively. All shortened, one-compartment models overestimated the GFR (p <0.0001 for all) as compared to the 8-hour model. TDI, CCC and CP were 7.02%, 0.815, and 75.80% for the 7-hour model, 7.26%, 0.803, and 74.20% for the 6-hour model, and 8.85%, 0.729 and 64.70% for the 5-hour model. The agreement of popPK model was comparable to that obtained with the Chronic-Kidney-Disease-Collaboration-Epidemiology (CKD-Epi) and the Modification-of-Diet-in-Renal-Disease (MDRD) serum-creatinine based equations for GFR estimation. PopPK model is remarkably unreliable for GFR measurement in stage III-IV CKD patients. In patients with eGFR ≤40 mL/min/1.73m2, shortened one-compartment models, in particular the 5-hour model, are less performant than the reference 8-hour model. For accurate GFR measurements, the iohexol plasma clearance should be measured with appropriate protocols. Over-simplified procedures should be avoided.

Creatinine-based formulas are not ideal to estimate glomerular filtration rate in selected pediatric patients: data from a tertiary pediatric nephrology center.

BACKGROUND: Evaluating glomerular filtration rate (GFR) remains challenging in pediatrics; new formulas were developed to increase performance of GFR estimation (eGFR). We aimed to evaluate the recently published formulas as applied to another pediatric population. METHODS: A retrospective study was conducted in a cohort of 307 patients with a "kidney risk" (mean age 12.1 ± 4.5 years, sex ratio 1/1) assessed in a tertiary pediatric nephrology center and a mean measured GFR (mGFR) using plasma iohexol clearance of 85.5 ± 25.3 mL/min/1.73 m2; creatinine levels were measured by IDMS-standardized enzymatic method and cystatin C by immunonephelometry. The following eGFRs were calculated: Schwartz2009, Schwartz-Lyon, CKiDU25creat, and EKFC for eGFR using creatinine (eGFR-creat), CKiDU25cys and FAScys for eGFR using cystatin (eGFR-cys) as well as combined SchwartzCreat-Cys, average (CKiDU25creat-CKiDU25cys), and average (EKFC-FAScys) for eGFR using both biomarkers. The performance of the different formulas was evaluated compared to mGFR by absolute bias measurement and accuracy (p10%, p30%). Results are expressed as mean ± SD. RESULTS: Creatinine-based formulas and especially the new CKiDU25 and EKFC overestimate GFR, even in children with normal kidney function. However, the bias is constant with these two formulas whatever the age group or gender, contrary to the previously published formulas. In contrast, cystatin C-based equations and combined formulas showed good performance in all age groups and all medical conditions with an acceptable bias and p30%. CONCLUSIONS: In our pediatric population, the performance of all creatinine-based formulas is inadequate with significant GFR overestimation, mainly in subjects with mGFR > 75 mL/min/1.73 m2. Conversely, cystatin C-based or combined formulas have acceptable performance in patients followed in a tertiary pediatric nephrology unit.

A physiological model for iohexol plasma clearance supporting diagnostics of kidney function.

BACKGROUND: There are several shortcomings in present methods for estimation of GFR from plasma clearance. The aim of the present study was therefore to develop a physiologically based method for calculation of plasma clearance of iohexol. METHODS: A mechanistic model founded on classical biochemical engineering principles where in- and outgoing molecular flows of iohexol between plasma and surrounding tissues were balanced over time. After intravenous injections of iohexol, plasma samples were taken from the investigated subjects until complete elimination of iohexol. After tuning of the model parameters, the clearance value was calculated from the injected dose and the integral of the iohexol concentrations over the investigated period. RESULTS: The mass balance model was able to predict the time course of iohexol distribution and elimination after parameterization of mass balance and kinetic equations. Four model structures were evaluated, all based on model parameters derived from published data and from internal tests, each complied at varying physiological conditions. Iohexol clearance was assessed through the model and compared with calculations from previously practiced methods. When testing the mass balance model on ten healthy subjects, clearance was estimated accurately. CONCLUSIONS: The physiological and mechanistic character of the mass balance model may suggest that its derived clearance comes closer to actual in vivo conditions than data derived from previously practiced calculation methods. Although here, only verified with the clearance marker iohexol, the mass balance model should be applicable also to other renal clearance markers.

Impact of humanized vancomycin infusion on kidney function and kidney injury in a translational rat model.

Allometric dose scaling aims to create isometric exposures between animals and humans and is often employed in preclinical pharmacokinetic/pharmacodynamic models. Bolus-administration with allometric scaling is the most simple and commonly used strategy in pre-clinical kidney injury studies; however, it is possible to humanize drug exposures. Currently, it is unknown if dose-matched, bolus-administration with allometric scaling results in similar outcomes compared to humanized infusions in the vancomycin induced kidney injury model. We utilized a preclinical Sprague-Dawley rat model to compare traditional allometrically-scaled, dose-matched, bolus-administration of vancomycin to an infusion-pump controlled, humanized infusion scheme to assess for differences in iohexol-measured kidney function and urinary kidney injury biomarkers. Following 24 h of vancomycin administration, rats in the humanized infusion group had equivalent area under the curve exposures to animals in the dose-matched bolus group (93.7 mg·h/L [IQR 90.2-97.2] vs. 99.5 mg·h/L [IQR 95.1-104.0], P = 0.07). No significant differences in iohexol-measured kidney function nor meaningful differences in urinary kidney injury biomarkers, kidney injury molecule-1, clusterin, and osteopontin, were detected. Administration of intravenous vancomycin as either a humanized infusion or dose-matched bolus resulted in similar vancomycin exposures. No differences in iohexol-measured GFR nor meaningful differences in urinary kidney injury biomarkers were observed among male Sprague-Dawley rats.

Estimation of cefepime, piperacillin, and tazobactam clearance with iohexol-based glomerular filtration rate in paediatric patients.

PURPOSE: Estimated glomerular filtration rate (eGFR) equations reflect kidney function imprecisely. We aimed to describe whether iohexol-based GFR or eGFRs predict clearance of cefepime, piperacillin, and tazobactam in pharmacokinetic (PK) models in this population and its clinical significance. METHODS: Hospitalized patients (0.5-25 years) with haemato-oncological disease and infection receiving cefepime or piperacillin/tazobactam were included. PK samples were collected at a steady state concomitantly with samples for iohexol-based GFR. PK models were developed in NONMEM. Weight, postmenstrual age, iohexol-based GFR, different eGFR equations (Schwartz updated, Lund-Malmö revised, CKD-EPI, Bouvet, Schwartz cystatin C-based) were tested as covariates. Probabilities of neurotoxic/therapeutic concentrations were assessed by simulations. RESULTS: Fifteen patients receiving cefepime and 17 piperacillin/tazobactam were included (median (range) age 16.2 (1.9-26.0) and 10.5 (0.8-25.6) years, iohexol-based GFR 102 (68-140) and 116 (74-137) mL/min/1.73 m2, respectively). Two-compartment model provided the best fit for all drugs. Weight was covariate for central and peripheral compartment, clearance and intercompartmental clearance (only tazobactam), and postmenstrual age for clearance (excluding cefepime). Iohexol-based GFR was the best predictor of clearance. The model of cefepime without vs with iohexol-based GFR underestimated the probability of neurotoxic concentrations (28.3-28.6% vs 52.1-69.3%) and overestimated the probability of therapeutic concentrations (> 90% vs 81.9-87.1%) in the case of iohexol-based GFR 70-80 and 130-140 mL/min/1.73 m2, respectively. CONCLUSION: Iohexol-based GFR can predict better than eGFRs the clearance of cefepime, piperacillin, and tazobactam in children and young adults with haemato-oncological disease and infection, warranting further investigation as an indicator of renal function to improve targeting of therapeutic window. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: EudraCT 2015-000,631-32, EudraCT 2016-003,374-40 (24.10.2016).

A single Bayesian estimator for iohexol clearance estimation in ICU, liver failure and renal transplant patients.

AIMS: Iohexol clearance has been proposed to estimate the glomerular filtration rate (GFR). A population pharmacokinetics (popPK) model was developed from heterogeneous patients. A Bayesian estimator (MAP-BE) based on a limited sampling strategy (LSS) was derived and evaluated in external patients. METHODS: Full pharmacokinetic data (7-12 samples) from 172 patients receiving iohexol for measurement of their GFR (unstable and stable ICU patients, liver failure patients and kidney transplant patients) were split into development (n = 136) and validation (n = 36) datasets. A PopPK model was developed in Monolix and was used to develop MAP-BE based on LSS. Its performance for GFR estimation was evaluated in the validation set. RESULTS: A two-compartment model with first-order elimination best described the data. The final model included the type of patients on volume of distribution (Vd), clearance and intercompartmental constants, serum creatinine on clearance and body weight on Vd. The best LSS included samples at 0.1-1-9 h exhibiting a relative mean prediction error (MPE) (RMSE) = -3.7% (14.3%) and better performance than the Bröchner-Mortensen formula (-3.0%/17%). Split by type of patients, the highest interindividual variability and imprecision was observed in unstable ICU patients (MPE (RMSE) = 3.7% (18.8%)) while the best performances were obtained for renal transplant patients (MPE (RMSE) = 1.0% (5.8%)). All LSS that included samples before 9 hours for the third sample were associated with an increased imprecision. CONCLUSION: A single MAP-BE of iohexol based on a three-sample LSS for four heterogeneous populations was developed and allowed accurate estimation of GFR in kidney transplant patients, slightly biased in stable ICU patients and slightly imprecise in unstable ICU patients.

Accuracy of single intravenous access iohexol GFR in children is hampered by marker contamination.

Measurement of glomerular filtration rate (GFR) in children by iohexol injection and blood sampling from the contralateral arm is widely used. A single intravenous access for iohexol injection and subsequent blood sampling has the obvious advantages of being less painful and easier to perform. The purpose of our study was to determine if blood samples drawn from the injection access are feasible and accurate for iohexol GFR (iGFR) measurements. Thirty-one children, median age 10.5 (range 6-17) years, with chronic kidney disease were given a bolus of iohexol followed by extended saline flushing and subsequent venous blood samples collected from the injection access as well as from a cannula in the contralateral arm, the latter serving as the reference method. Paired venous blood samples were collected at four time points (2, 3, 3.5 and 4 h) after the iohexol bolus. Blood sample discarding preceded and saline flushing followed each blood sampling to avoid marker contamination. iGFR based on samples drawn from the injection access at 2 and 3 h showed significantly lower iGFR than measurement from the contralateral arm (p < 0.01). Singlepoint iGFR did not differ significantly after 3-4 repeated procedures of blood discarding and saline flusing (3.5 and 4 h). Despite thorough saline flushing there is still a relatively high risk of falsely low iGFR due to marker contamination in blood samples from the injection site. Hence, blood sampling from a second intravenous access is recommended for routine iohexol GFR measurements in children.Clinical trial registration: ClinicalTrials.gov, Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2 .

Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function.

Plasma clearance of iohexol is a pivotal metric to quantify glomerular filtration rate (GFR), but the optimal timing and frequency of plasma sampling remain to be assessed. In this study, we evaluated the impact of a Bayesian estimation procedure on iohexol clearance estimates, and we identified an optimal sampling strategy based on data in individuals aged 70+. Assuming a varying number of random effects, we re-estimated previously developed population pharmacokinetic two- and three-compartment models in a model development group comprising 546 patients with iohexol concentration data up to 300 min post injection. Model performance and optimal sampling times were assessed in an evaluation group comprising 104 patients with reduced GFR and concentration data up to 1440 min post injection. Two- and three-compartment models with random effects for all parameters overestimated clearance values (bias 5.07 and 4.40 mL/min, respectively) and underpredicted 24-h concentrations (bias - 14.5 and - 12.0 µg/ml, respectively). Clearance estimates improved distinctly when limiting random effects of the three-compartment model to clearance and central volume of distribution. Two blood samples, one early and one 300 min post injection, were sufficient to estimate iohexol clearance. A simplified three-compartment model is optimal to estimate iohexol clearance in elderly patients with reduced GFR.

Water-Soluble Contrast Challenge for Suspected Small-Bowel Obstruction: Technical Success Rate, Accuracy, and Clinical Outcomes.

Among 109 iohexol-based water-soluble contrast (WSC) challenges performed for suspected small-bowel obstruction, 105 were technically adequate. Among technically adequate studies, colonic contrast (i.e., successful challenge) was seen on 66 abdominal radiographs obtained 8 hours after WSC challenge and 86 abdominal radiographs obtained 24 hours after WSC challenge. Fourteen patients underwent operative management, and 91 underwent nonoperative management (NOM). Successful challenge had a sensitivity of 91.2%, specificity of 78.5%, PPV of 96.5%, NPV of 57.8%, and odds ratio of 38.0 (95% CI, 8.7-165.2) for NOM. Three of 86 patients with successful challenge underwent operative management.

Iohexol plasma clearance for measuring glomerular filtration rate: effect of different ways to calculate the area under the curve.

BACKGROUND: Measuring glomerular filtration rate (GFR) using iohexol plasma clearance has been proposed as the preferred way for GFR determination. The extended multiple-sample protocol is based on fitting the full concentration-time decay-curve, and from the obtained fit-parameters, the area under the curve (AUC) and GFR (the injected dose divided by the AUC) were calculated. The goal of the current study is to evaluate the impact of different fitting procedures on the precision of GFR-results obtained from the full concentration-time curve, and compare these results with those obtained with simplified multiple-samples and single-sample protocols. METHODS: The concentration-time curves of 8 samples at times 30, 60, 90, 120, 150, 180, 240 and 300 min after bolus injection of iohexol of 570 adults, aged 70+, from the Berlin Initiative Study (BIS), were analysed. The fit-parameters for the two-compartment model (double-exponential decay curve), and from these, the AUC and GFR were obtained with 8 different fitting procedures. RESULTS: The two-compartmental non-linear least squares fitting procedure showed the best accuracy (541 out of 570 reported GFR-results were within 5% of the majority of the 8 fitting methods). The two-compartmental slope-intercept fitting procedure was not always applicable and the non-compartmental fitting procedures did not always allow to calculate the GFR. All correction formulas for the simplified late multiple-samples methods showed acceptable accuracy and precision with a preference for Ng's correction formula (Lin's CCC = 0.992, bias = 0.5 ± 2.5). Jacobsson's iterative method was the best one-sample method, with Lin's CCC = 0.983 and bias = - 0.6 ± 3.4. CONCLUSION: The fitting procedure has an important impact on the precision of the calculated AUC and GFR. The simplified late-sample protocols and one-sample methods did not suffer from fitting problems and showed acceptable equivalence when compared to the full compartment GFR-results. TRIAL REGISTRATION: The "Berlin Initiative Study" is officially registered with the German Register for Clinical Studies ("Deutschen Register Klinischer Studien"(DRKS)) under registration number DRKS00017058 , since April 12, 2019, and it is also visible on the WHO clinical trials registry platform (within the next 4 weeks after the registration date).

The correlation between kidney volume and measured glomerular filtration rate in an Asian ADPKD population: a prospective cohort study.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder that leads to end stage renal disease (ESRD). Cyst expansion in ADPKD is strongly associated with the decline in renal function. However, the correlation between total kidney volume (TKV) and glomerular filtration rate (GFR) at an early stage has not been well demonstrated. There is growing evidence that utilization of estimated GFR (eGFR) may induce misleading information in a population with near normal renal function. Therefore, a more accurate method is essential. METHODS: A prospective cohort of ADPKD patients was conducted with clinical data and laboratory collection. Measured GFR (mGFR) was assessed by iohexol plasma clearance method using ultra performance liquid chromatography. eGFR was calculated using the CKD-EPI equation. Kidney volumes were evaluated using MRI imaging protocol. RESULTS: Thirty two patients completed the study. The mean age was 56 years old. The mean initial mGFR was 83.8 mL/min/1.73m2. The mean change in mGFR per year was -2.99 mL/min/1.73m2/year. The mean initial height-adjusted TKV (htTKV) was 681.0 mL/m. The mean percentage change in htTKV per year (%ΔhtTKV/y) was 4.77 %/year. mGFR had a better association with clinical parameters than eGFR. Initial mGFR was significantly and inversely correlated with initial htTKV and age. The percentage change in mGFR per year was significantly and inversely correlated with the %ΔhtTKV/y and 24-hr urine albumin. The %ΔhtTKV/y was significantly correlated with initial htTKV. CONCLUSIONS: Our studies demonstrated that mGFR using iohexol is a more reliable and accurate method than eGFR for evaluating GFR changes in the early stages of ADPKD patients. There is a strong inverse correlation between kidney volume and mGFR in an Asian ADPKD population. The initial htTKV is a good predictor of kidney volume progression. The %ΔhtTKV/y is a good early surrogate marker for the decline in renal function. 24-hr urine albumin is also a good indicator for renal progression.

Prediction of Kidney Drug Clearance: A Comparison of Tubular Secretory Clearance and Glomerular Filtration Rate.

BACKGROUND: Although proximal tubular secretion is the primary mechanism of kidney drug elimination, current kidney drug dosing strategies are on the basis of eGFR. METHODS: In a dedicated pharmacokinetic study to compare GFR with tubular secretory clearance for predicting kidney drug elimination, we evaluated stable outpatients with eGFRs ranging from 21 to 140 ml/min per 1.73 m2. After administering single doses of furosemide and famciclovir (metabolized to penciclovir), we calculated their kidney clearances on the basis of sequential plasma and timed urine measurements. Concomitantly, we quantified eight endogenous secretory solutes in plasma and urine using liquid chromatography-tandem mass spectrometry and measured GFR by iohexol clearance (iGFR). We computed a summary secretion score as the scaled average of the secretory solute clearances. RESULTS: Median iGFR of the 54 participants was 73 ml/min per 1.73 m2. The kidney furosemide clearance correlated with iGFR (r=0.84) and the summary secretion score (r=0.86). The mean proportionate error (MPE) between iGFR-predicted and measured furosemide clearance was 30.0%. The lowest MPE was observed for the summary secretion score (24.1%); MPEs for individual secretory solutes ranged from 27.3% to 48.0%. These predictive errors were statistically indistinguishable. Penciclovir kidney clearance was correlated with iGFR (r=0.83) and with the summary secretion score (r=0.91), with similar predictive accuracy of iGFR and secretory clearances. Combining iGFR with the summary secretion score yielded only modest improvements in the prediction of the kidney clearance of furosemide and penciclovir. CONCLUSIONS: Secretory solute clearance measurements can predict kidney drug clearances. However, tight linkage between GFR and proximal tubular secretory clearance in stable outpatients provides some reassurance that GFR, even when estimated, is a useful surrogate for predicting secretory drug clearances in such patients.

Measured and Estimated Glomerular Filtration Rate in the ICU: A Prospective Study.

OBJECTIVES: To compare estimated glomerular filtration rate using classical static and kinetic equations with measured glomerular filtration rate assessed by plasma iohexol clearance in a mixed population of critical care patients. PATIENTS: Unselected patients older than 18 and admitted to a general ICU. DESIGN: Interventional prospective single center study. INTERVENTION: Measurement of glomerular filtration rate by the plasma clearance of an IV single dose of iohexol and estimation of glomerular filtration rate with creatinine or cystatin C-based standard and kinetic equations as well as urinary creatinine clearance. MEASUREMENTS AND MAIN RESULTS: Sixty-three patients were included with a median age of 66 years old. The median measured glomerular filtration rate was 51 mL/min/1.73 m (interquartile range, 19-85 mL/min/1.73 m). All used equations displayed significant biases, high errors, and poor accuracy when compared with measured glomerular filtration rate, overestimating renal function. The highest accuracy and lowest error were observed with cystatin C-based chronic kidney disease epidemiology collaboration equations. Both modification of diet in renal disease and Cockcroft-Gault equations displayed the lowest performance. Kinetic models did not improve performances, except in patients with unstable creatinine levels. Creatinine- but not cystatin C-based estimations largely derived over ICU stay, which appeared more related to sarcopenia than fluid balance. Finally, estimated glomerular filtration rate misclassified patients according to classical glomerular filtration rate categories in approximately half of the studied cases. CONCLUSIONS: All known estimated glomerular filtration rate equations displayed high biases and unacceptable errors when compared with measured glomerular filtration rate in a mixed ICU population, with the lowest performance related to creatinine-based equations compared with cystatin C. In the ICU, we advocate for caution when using creatinine based estimated glomerular filtration rate equations. Drifting of serum creatinine levels over time should also be taken into consideration when assessing renal function in the ICU.

Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker.

PURPOSE: Carboplatin dose is calculated based on kidney function, commonly estimated with imperfect creatinine-based formulae. Iohexol is used to measure glomerular filtration rate (GFR) and allows calculation of a more appropriate carboplatin dose. To address potential concerns that iohexol administered during a course of chemotherapy impacts that therapy, we performed in vitro and in vivo pharmacokinetic drug-drug interaction evaluations of iohexol. METHODS: Carboplatin was administered IV to female mice at 60 mg/kg with or without iohexol at 300 mg/kg. Plasma ultrafiltrate, kidney and bone marrow platinum was quantitated by atomic absorption spectrophotometry. Paclitaxel microsomal and gemcitabine cytosolic metabolism as well as metabolism of CYP and UGT probes was assessed with and without iohexol at 300 µg/mL by LC-MS/MS. RESULTS: In vivo carboplatin exposure was not significantly affected by iohexol co-administration (platinum AUC combination vs alone: plasma ultrafiltrate 1,791 vs 1920 µg/mL min; kidney 8367 vs 9757 µg/g min; bone marrow 12.7 vs 12.7 µg/mg-protein min). Paclitaxel microsomal metabolism was not impacted (combination vs alone: 6-α-OH-paclitaxel 38.3 versus 39.4 ng/mL/60 min; 3-p-OH-paclitaxel 26.2 versus 27.7 ng/mL/60 min). Gemcitabine human cytosolic elimination was not impacted (AUC combination vs gemcitabine alone: dFdU 24.1 versus 23.7 µg/mL/30 min). Iohexol displayed no relevant inhibition of the CYP and UGT enzymes in human liver microsomes. CONCLUSIONS: Iohexol is unlikely to affect the clinical pharmacokinetics of carboplatin, paclitaxel, gemcitabine, or other agents used in combination with carboplatin treatment. Measuring GFR with iohexol to better dose carboplatin is unlikely to alter the safety or efficacy of chemotherapy through pharmacokinetic drug-drug interactions.

Bismuth chelate as a contrast agent for X-ray computed tomography.

BACKGROUNDS: Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming. METHODS: In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. RESULTS: The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. CONCLUSIONS: This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.

GFR in Healthy Aging: an Individual Participant Data Meta-Analysis of Iohexol Clearance in European Population-Based Cohorts.

BACKGROUND: Population mean GFR is lower in older age, but it is unknown whether healthy aging is associated with preserved rather than lower GFR in some individuals. METHODS: We investigated the cross-sectional association between measured GFR, age, and health in persons aged 50-97 years in the general population through a meta-analysis of iohexol clearance measurements in three large European population-based cohorts. We defined a healthy person as having no major chronic disease or risk factors for CKD and all others as unhealthy. We used a generalized additive model to study GFR distribution by age according to health status. RESULTS: There were 935 (22%) GFR measurements in persons who were healthy and 3274 (78%) in persons who were unhealthy. The mean GFR was lower in older age by -0.72 ml/min per 1.73 m2 per year (95% confidence interval [95% CI], -0.96 to -0.48) for men who were healthy versus -1.03 ml/min per 1.73 m2 per year (95% CI, -1.25 to -0.80) for men who were unhealthy, and by -0.92 ml/min per 1.73 m2 per year (95% CI, -1.14 to -0.70) for women who were healthy versus -1.22 ml/min per 1.73 m2 per year (95% CI, -1.43 to -1.02) for women who were unhealthy. For healthy and unhealthy people of both sexes, both the 97.5th and 2.5th GFR percentiles exhibited a negative linear association with age. CONCLUSIONS: Healthy aging is associated with a higher mean GFR compared with unhealthy aging. However, both the mean and 97.5 percentiles of the GFR distribution are lower in older persons who are healthy than in middle-aged persons who are healthy. This suggests that healthy aging is not associated with preserved GFR in old age.

Diffusion of Radiodense Contrast Medium Following Perineural Injection of the Deep Branch of the Lateral Plantar Nerve Using Two Different Techniques in Horses: an In Vivo Study.

OBJECTIVES: This article evaluates and compares the diffusion pattern of radiopaque contrast medium following perineural analgesia of the deep branch of the lateral plantar nerve performed using two different techniques: weight-bearing or flexed. STUDY DESIGN: This was an in vivo experimental study. METHODS: Eight horses were enrolled. Perineural injection of the right and left deep branch lateral plantar nerves was performed with a weight-bearing or flexed technique, using radiopaque contrast medium (iohexol). Radiographic evaluation was performed after 5 (T5), 15 (T15) and 30 (T30) minutes. The diffusion of contrast medium was assessed independently by two blinded readers who analysed the extension of the main contrast medium bulk and the maximum diffusion of contrast medium in both proximal and distal directions. The effect of time and technique employed on contrast medium diffusion was assessed using two-way analysis of variance for repeated measures (p ≤ 0.05). RESULTS: There was no significant difference in the diffusion of the contrast medium between the two techniques at T15. However, at T30 the weight-bearing technique resulted in a significantly increased diffusion in the proximal direction (p = 0.02). In one case, belonging to the weight-bearing group, contrast medium was identified within the tarsal sheath. There was no evidence of contrast medium in the tarsometatarsal joint of any horse, regardless of the technique used. CONCLUSIONS: The two techniques resulted in a similar diffusion at T15. However, the use of a weight-bearing technique resulted in a significant increase in proximal contrast medium diffusion 30 minutes after injection.

Investigation of Various Intramuscular Volumes Delivered to the Semimembranosus Muscle of Cavia porcellus.

The goal of this study is to provide quantitative data on the ideal volume for intramuscular (IM) injections into the semimembranosus muscle of guinea pigs weighing between 320 to 410 grams. This evaluation comprised 2 experiments. The first was to assess dispersion leakage of intramuscularly injected iohexol, a radiocontrast agent commonly used in Computed Tomography (CT), based on analysis of in vivo imaging. The second used varying volumes of intramuscularly injected sodium chloride (0.9% NaCl) to assess pain and pathology associated with IM injection. Hartley guinea pigs were injected IM with varying volumes of either iohexol or sodium chloride (150, 300, 500, 1000 and 1500 µL). In the iohexol experiment, results suggest IM volumes of 150 and 300 µL remain within the target muscle. In the experiment using sodium chloride, pain and pathology did not increase as IM volume increased. The pathology noted was related to needle tract through the musculature rather than the volume size of the injectate. The results did not reveal a correlation between volume of IM 0.9% NaCl and pain levels. We conclude that volume size correlates more with precision and accuracy of delivery into the intended muscle tissue. Regarding tissue distribution, our findings also suggest that the optimal capacity for IM injection in the semimembranosus muscle should be less than 500 µL.