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AbstractBackground and Purpose: Dacryocystography or visualization of nasolacrimal duct has been widely used in the assessment of the nasal lacrimal system. The water-soluble agent iohexol is currently widely used in nervous and vascular lesion in diagnostic radiology and also employed in dacryocystography. This study was performed to determine the effects of iohexol on tear parameters in normal donkey as a large animal model.Materials and Methods: We examined 10 normal donkeys mean age approximately 4.5 years. The donkeys received iohexol once a day. All donkeys were housed out doors throughout the study. Different tear parameters (total protein, lysozyme, sodium, and potassium and protein electrophoresis of tear) were measured at 0, 2 hours and 2 weeks after dacryocystography with iohexol.Results: The results showed that mean and standard deviation of total protein of tear were 5.882.15 mg/ml before dacryocystography and after 2 hours was 4.100.96 and after two weeks was 7.363.68. Mean and standard deviation of lysozyme was 858.39170.88 units in Mg of protein of tear and after two hours was 1013.19178.67 and after two week was 702.54360.50. Mean  SD of sodium of tear before dacryocystography was 3084.90725.44 µ/ml and after two hours and two weeks were 3508.401372.52 and 8026.202953.88 respectively. Mean  SD of Potassium of tear before dacryocystography was 863.3752.55 µ/ml and after two hours and two weeks were 753.8446.81 and 1564.2027641 respectively. Results of SDS-PAGE of donkeys tear confirmed that nine protein bands with molecular weights between 10 kDa and 15 kDa are present. No differences found in protein electrophoresis pattern before and after iohexol administration. No significant changes were present in measured factors at different times.Conclusion: In conclusion iohexol is a safe and suitable contrast media for dacryocystography.Key words: Iohexol, Dacryocystography, Protein, Electrophoresis, LysozymeJ Mazand Univ Med Sci 2008; 18(63): 46-54 (Persian)

[Display omitted] • A Cu x O-loaded carbon felt with carbon nanotubes as an interlayer was fabricated. • PMS could be effectively activated by the electrically enhanced Cu x O/CNT/CF. • The catalytic performance and stability of the electrodes can be improved by CNT. • The degradation efficiency of iohexol (IOH) could reach 100 % within 25 min. • Both nonradical and radical-mediated PS activation are involved in the degradation. Persulfate (PS) activation by means of transition metals has been extensively applied to eliminate persistent organic pollutants, but the slow rate of metal redox cycling between high-valence and low-valence states inhibits the degradation reaction. Here, a Cu x O-loaded carbon felt with carboxylated multi-walled carbon nanotubes (MWCNT-COOH) as an interlayer (Cu x O/CNT/CF) has been successfully prepared. This assembly was then employed in a process of peroxymonosulfate (PMS) activation with the assistance of an electric field (Cu x O/CNT/CF-PMS-EC). PMS could be effectively activated by the electrically enhanced Cu x O/CNT/CF due to faster metal redox cycling, and the system could be applied over a broad pH range (3.0–11.0). The degradation efficiency of iohexol (IOH) could reach 100 % within 25 min, and around 62.7 % of total organic carbon (TOC) was removed within 120 min in the Cu x O/CNT/CF-PMS-EC system. Both non-radical (1O 2)- and radical-mediated (· SO 4 -, · O 2 –, and · OH) PS activation are involved in the degradation process. According to the results of DFT calculations and LC-MS, the degradation of IOH involves deiodination, amide hydrolysis, amine oxidation, C-OH oxidation, addition of –OH, hydrogen abstraction, and elimination reactions. The present study shows electrocatalysis coupled with transition-metal-activated PS to be a highly efficient technique for the removal of iodinated contrast media (ICMs). [ABSTRACT FROM AUTHOR]

[Display omitted] • Perylene diimide/peroxymonosulfate/visible light (PDI/PMS/Vis) system showed excellent performance for iohexol removal. • 0.56% of chloride ions (Cl−) absorbed on the surface of hydrochloric acid-induced self-assembled PDI (P C). • The Cl− adsorbed on the surface of P C improved the electrostatic potential distribution and promoted the charge transfer. • Holes, singlet oxygen, and superoxide radical were the dominant active species for iohexol elimination. The presence of iohexol (IOX) in the environment has attracted widespread attention. Acetic acid, hydrochloric acid, and nitric acid tailored self-assembled perylene diimides (P A , P C and P N) were prepared and utilized in different visible-light-driven activation of peroxymonosulfate (PMS/Vis) systems for the degradation of IOX. As an electron acceptor, PMS can significantly hinder the recombination of photogenerated electron-hole pairs. The removal rate of 5 mg/L IOX by P C /PMS/Vis system reached 99.1% at 30 min, which was 2.0 times and 1.3 times higher than that of P A /PMS/Vis and P N /PMS/Vis system. The boosted oxidation activity with P C was due to the pH dependence of perylene diimide (PDI) self-assembly and the small amount of Cl− (0.56%) absorbed on P C , which can promote the transfer of electron-hole pairs, change the surface charge distribution and energy band position, and enhance π-electron conjugation. Based on density functional theory and electrostatic potential calculation, the Cl− adsorbed on the surface of PDI brings an effect on the electrostatic potential distribution. Furthermore, the built-in intermolecular electric field leads to accelerated charge transfer of PDI. In the P C /PMS/Vis system, holes, singlet oxygen and superoxide radical were perceived as the dominant contributors. The degradation of IOX carried out via pathways of amide hydrolysis, amino oxidation, hydrogen abstraction, deiodination reaction, and OH attack. This work provides a new method for the pollution control of IOX and scientific guidance for the tailored self-assembly of organic supramolecules. [ABSTRACT FROM AUTHOR]

The results of randomized controlled trials are unclear about the long-term effect of blood pressure (BP) on kidney function assessed as the glomerular filtration rate (GFR) in persons without chronic kidney disease or diabetes. The limited duration of follow-up and use of imprecise methods for assessing BP and GFR are important reasons why this issue has not been settled. Since a long-term randomized trial is unlikely, we investigated the association between 24-h ambulatory BP (ABP) and measured GFR in a cohort study with a median follow-up of 11 years. The Renal Iohexol Clearance Survey (RENIS) cohort is a representative sample of persons aged 50 to 62 years without baseline cardiovascular disease, diabetes, or kidney disease from the general population of Tromsø in northern Norway. ABP was measured at baseline, and iohexol clearance at baseline and twice during follow-up. The study population comprised 1589 persons with 4127 GFR measurements. Baseline ABP or office BP components were not associated with the GFR change rate in multivariable adjusted conventional regression models. In generalized additive models for location, scale, and shape (GAMLSS), higher daytime systolic, diastolic, and mean arterial ABP were associated with a slight shift of the central part of the GFR distribution toward lower GFR and with higher probability of GFR < 60 mL/min/1.73 m 2 during follow-up (p < 0.05). The use of a distributional regression method and precise methods for measuring exposure and outcome were necessary to detect an unfavorable association between BP and GFR in this study of the general population., (© 2023. Springer Nature Limited.)

Recent clinical studies have reported additive nephrotoxicity with the combination of vancomycin and piperacillin-tazobactam. However, preclinical models have failed to replicate this finding. This study assessed differences in iohexol-measured glomerular filtration rate (GFR) and urinary injury biomarkers among rats receiving this antibiotic combination. Male Sprague-Dawley rats received either intravenous vancomycin, intraperitoneal piperacillin-tazobactam, or both for 96 h. Iohexol-measured GFR was used to quantify real-time kidney function changes. Kidney injury was evaluated with the urinary biomarkers kidney injury molecule-1 (KIM-1), clusterin, and osteopontin. Compared to the control, rats that received vancomycin had numerically lower GFRs after drug dosing on day 3. Rats in this group also had elevations in urinary KIM-1 on experimental days 2 and 4. Increasing urinary KIM-1 was found to correlate with decreasing GFR on experimental days 1 and 3. Rats that received vancomycin plus piperacillin-tazobactam (vancomycin+piperacillin-tazobactam) did not exhibit worse kidney function or injury biomarkers than rats receiving vancomycin alone. The combination of vancomycin and piperacillin-tazobactam does not cause additive nephrotoxicity in a translational rat model. Future clinical studies investigating this antibiotic combination should employ more sensitive biomarkers of kidney function and injury, similar to those utilized in this study., Competing Interests: The authors declare a conflict of interest. M.S. has ongoing research contracts with Nevakar and SuperTrans Medical as well as having filed patent US10688195B2. All other authors have no other related conflicts of interest to declare.

Background: Incomplete recovery of kidney function is an important adverse outcome in survivors of critical illness. However, unlike eGFR creatinine, eGFR cystatin C is not confounded by muscle loss and may improve identification of persistent kidney dysfunction., Methods: To assess kidney function during prolonged critical illness, we enrolled 38 mechanically ventilated patients with an expected length of stay of >72 hours near admission to intensive care unit (ICU) in a single academic medical center. We assessed sequential kidney function using creatinine, cystatin C, and iohexol clearance measurements. The primary outcome was difference between eGFR creatinine and eGFR cystatin C at ICU discharge using Bayesian regression modeling. We simultaneously measured muscle mass by ultrasound of the rectus femoris to assess the confounding effect on serum creatinine generation., Results: Longer length of ICU stay was associated with greater difference between eGFR creatinine and eGFR cystatin C at a predicted rate of 2 ml/min per 1.73 m 2 per day (95% confidence interval [CI], 1 to 2). By ICU discharge, the posterior mean difference between creatinine and cystatin C eGFR was 33 ml/min per 1.73 m 2 (95% credible interval [CrI], 24 to 42). In 27 patients with iohexol clearance measured close to ICU discharge, eGFR creatinine was on average two-fold greater than the iohexol gold standard, and posterior mean difference was 59 ml/min per 1.73 m 2 (95% CrI, 49 to 69). The posterior mean for eGFR cystatin C suggested a 22 ml/min per 1.73 m 2 (95% CrI, 13 to 31) overestimation of measured GFR. Each day in ICU resulted in a predicted 2% (95% CI, 1% to 3%) decrease in muscle area. Change in creatinine-to-cystatin C ratio showed good longitudinal, repeated measures correlation with muscle loss, R =0.61 (95% CI, 0.50 to 0.72)., Conclusions: eGFR creatinine systematically overestimated kidney function after prolonged critical illness. Cystatin C better estimated true kidney function because it seemed unaffected by the muscle loss from prolonged critical illness., Clinical Trial Registry Name and Registration Number: Skeletal Muscle Wasting and Renal Dysfunction After Critical Illness Trauma - Outcomes Study (KRATOS), NCT03736005 ., (Copyright © 2023 by the American Society of Nephrology.)

Significance Statement: eGFR from creatinine, cystatin C, or both has been primarily used in search of biomarkers for GFR decline. Whether the relationships between biomarkers and eGFR decline are similar to associations with measured GFR (mGFR) decline has not been investigated. This study revealed that some biomarkers showed statistically significant different associations with eGFR decline compared with mGFR decline, particularly for eGFR from cystatin C. The findings indicate that non-GFR-related factors, such as age, sex, and body mass index, influence the relationship between biomarkers and eGFR decline. Therefore, the results of biomarker studies using eGFR, particularly eGFRcys, should be interpreted with caution and perhaps validated with mGFR., Background: Several serum protein biomarkers have been proposed as risk factors for GFR decline using eGFR from creatinine or cystatin C. We investigated whether eGFR can be used as a surrogate end point for measured GFR (mGFR) when searching for biomarkers associated with GFR decline., Methods: In the Renal Iohexol Clearance Survey, GFR was measured with plasma iohexol clearance in 1627 individuals without diabetes, kidney, or cardiovascular disease at baseline. After 11 years of follow-up, 1409 participants had one or more follow-up GFR measurements. Using logistic regression and interval-censored Cox regression, we analyzed the association between baseline levels of 12 serum protein biomarkers with the risk of accelerated GFR decline and incident CKD for both mGFR and eGFR., Results: Several biomarkers exhibited different associations with eGFR decline compared with their association with mGFR decline. More biomarkers showed different associations with eGFRcys decline than with eGFRcre decline. Most of the different associations of eGFR decline versus mGFR decline remained statistically significant after adjustment for age, sex, and body mass index, but several were attenuated and not significant after adjusting for the corresponding baseline mGFR or eGFR., Conclusions: In studies of some serum protein biomarkers, eGFR decline may not be an appropriate surrogate outcome for mGFR decline. Although the differences from mGFR decline are attenuated by adjustment for confounding factors in most cases, some persist. Therefore, proposed biomarkers from studies using eGFR should preferably be validated with mGFR., (Copyright © 2023 by the American Society of Nephrology.)

Background: Ischemic colitis (IC) is common, rising in incidence and associated with high mortality. Its presentation, disease behavior and severity vary widely, and there is significant heterogeneity in therapeutic strategies and prognosis. The common causes of IC include thromboembolism, hemodynamic insufficiency, iatrogenic factors and drug-induced. However, contrast-induced IC, especially isolated right colon ischemia is rarely reported., Case Summary: A 52-year-old man was admitted to the hospital due to intermittent chest distress accompanied by palpitation. Coronary angiography was performed using 60 mL of the iodinated contrast agent iohexol (Omnipaque 300), and revealed moderate stenosis of the left anterior descending artery and right coronary artery. At 3 h post-procedure, he complained of epigastric pain without fever, diarrhea and vomiting. Vital signs remained normal. An iodixanol-enhanced abdominal computed tomography (CT) scan revealed thickening, edema of the ascending and right transverse colonic wall and inflammatory exudate, without thrombus in mesenteric arteries and veins. Following 4 days of treatment with antibiotic and supportive management, the patient had a quick and excellent recovery with disappearance of abdominal pain, normalization of leucocyte count and a significant decrease in C reactive protein. There was no recurrence of abdominal pain during the patient's two-year follow-up., Conclusion: This case emphasizes that contrast-induced IC should be considered in the differential diagnosis of unexplained abdominal pain after a cardiovascular interventional procedure with the administration of contrast media. Timely imaging evaluation by CT and early diagnosis help to improve the prognosis of IC., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Significance Statement: Large discordances between eGFR on the basis of creatinine (eGFR cr ) or cystatin C (eGFR cys ) are common in clinical practice. However, which GFR estimating equation (eGFR cr , eGFR cys , or eGFR cr-cys ) is most accurate in these settings is not known. In this real-world study of 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance, all three equations performed similarly when eGFR cr and eGFR cys were similar (45% of cases). However, with large discordances (55% of cases), eGFR cr-cys was much more accurate than either alone. These findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer who have been underrepresented in research cohorts. Thus, when eGFR cr and eGFR cys are largely discordant in clinical practice, eGFR cr-cys is more accurate than eGFR cr or eGFR cys ., Background: Cystatin C is recommended as a confirmatory test to eGFR when more precise estimates are needed for clinical decision making. Although eGFR on the basis of both creatinine and cystatin (eGFR cr-cys ) is the most accurate estimate in research studies, it is uncertain whether this is true in real-world settings, particularly when there are large discordances between eGFR based on creatinine (eGFR cr ) and that based on cystatin C (eGFR cys )., Methods: We included 6185 adults referred for measured GFR (mGFR) using plasma clearance of iohexol in Stockholm, Sweden, who had 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance. The performance of eGFR cr , eGFR cys , and eGFR cr-cys was assessed against mGFR with median bias, P30 , and correct classification of GFR categories. We stratified analyses within three categories: eGFR cys at least 20% lower than eGFR cr (eGFR cys eGFR cr )., Results: eGFR cr and eGFR cys were similar in 4226 (45%) samples, and among these samples all three estimating equations performed similarly. By contrast, eGFR cr-cys was much more accurate in cases of discordance. For example, when eGFR cys eGFR cr (8% of samples), the median biases were -4.5, 8.4, and 1.4 ml/min per 1.73m 2 . The findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer., Conclusions: When eGFR cr and eGFR cys are highly discordant in clinical practice, eGFR cr-cys is more accurate than either eGFR cr or eGFR cys ., (Copyright © 2023 by the American Society of Nephrology.)

Purpose: This multicenter prospective study aimed to evaluate the quality and diagnostic effectiveness of cerebral angiography images obtained using low-concentration iodinated contrast agents (iohexol 240 mgI/mL, iopamidol 250 mgI/mL, and iodixanol 270 mgI/mL) and to assess the safety thereof. The study addresses the need for safer contrast agent alternatives without compromising the diagnostic quality of identifying cerebrovascular disease., Materials and Methods: Conducted in 5 medical centers in South Korea, we enrolled patients aged 19 years or older who were referred for diagnostic cerebral angiography under non-emergency conditions, excluding those with specific health conditions and sensitivities. The study design included a prospective, observational approach with a 1-way analysis of variance (ANOVA) for sample size calculation, aiming for a total sample of 231 participants for adequate power. Image quality was evaluated using a 4-level scale by 2 independent, blinded radiologists, and adverse reactions were monitored both immediately and up to 7 days post-procedure. Statistical analysis involved 1-way ANOVA and Kruskal-Wallis tests to assess the image quality and safety profiles of the contrast agents., Results: Among 266 patients screened, 243 were included in the final analysis. The evaluation revealed no statistically significant differences in image quality among the 3 types of low-concentration contrast agents. Adverse events were observed in 28.8% of patients, with 27.2% experiencing acute reactions, primarily mild reactions, and 3.3% experiencing delayed reactions. The overall safety profile showed no significant changes in vital signs or electrocardiogram readings before and after contrast agent injection., Conclusion: Using low-concentration iodinated contrast agents for cerebral angiography provides image quality comparable to that of conventional high-concentration agents, with no significant increase in adverse events, suggesting a safer alternative for patients.

Contrast-induced nephropathy (CIN) is one of the most common causes of acute kidney injury (AKI). However, management is still limited, and the cellular response to radiocontrast removal for CIN remains unclear. This study aimed to explore the latent effects of iohexol in cultured renal tubular cells with or without the removal of iohexol by medium replacement. HK2 renal tubular cells were subcultured 24 h before use in CIN experiments. Three treatment groups were established: the control, a radiocontrast (iohexol)-only group at 75 mg I/mL (I-75), and iohexol exposure for 24 h with culture medium replacement (I-75/M). Cell cycle arrest, fibrogenic mediator assays, cell viability, cell function, and cell-cycle-related protein expression were compared between groups. Iohexol induced numerous changes in HK2 renal tubular cells, such as enlarged cell shape, cell cycle arrest, increased apoptosis, and polyploidy. Iohexol inhibited the expression of cyclins, CDKs, ZO-1, and E-cadherin but conversely enhanced the expression of p21 and fibrosis-related genes, including TGF-β1, CTGF, collagen I, collagen III, and HIF-1α within 60 hr after the exposure. Except for the recovery from cell cycle arrest and cell cycle gene expression, notably, the removal of iohexol by medium replacement could not fully recover the renal tubular cells from the formation of polyploid cells, the adhesion or spreading, or the expression of fibrosis-related genes. The present study demonstrates, for the first time, that iohexol exerts latent cytotoxic effects on cultured renal tubular cells after its removal, suggesting that these irreversible cell changes may cause the insufficiency of radiocontrast reduction in CIN, which is worth investigating further.

The present study investigated the biodegradation of three iodinated X-ray contrast media (ICM), namely, iopamidol, iohexol, and iopromide, in simultaneous nitrification-denitrification (SND) system maintained in a sequencing batch reactor (SBR). The results showed that variable aeration patterns (anoxic-aerobic-anoxic) and micro-aerobic condition were most effective in the biotransformation of ICM while achieving organic carbon and nitrogen removal. The highest removal efficiencies of iopamidol, iohexol, and iopromide were 48.24%, 47.75%, and 57.46%, respectively, in micro-aerobic condition. Iopamidol was highly resistant to biodegradation and possessed the lowest K bio value, followed by iohexol and iopromide, regardless of operating conditions. The removal of iopamidol and iopromide was affected by the inhibition of nitrifiers. The transformation products after hydroxylation, dehydrogenation, and deiodination of ICM were detected in the treated effluent. Due to the addition of ICM, the abundance of denitrifier genera Rhodobacter and Unclassified Comamonadaceae increased, and the abundance of class TM7-3 decreased. The presence of ICM affected the microbial dynamics, and the diversity of microbes in SND resulted in improving the biodegradability of the compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

RATIONALE: Mass spectrometry has been developed as one of the common tools for the analysis of the organometallic systems in the gas phase over decades. The study of the fragmentation of organics-metal complexes has attracted much attention since the interesting dissociation pathways exhibited by these compounds are usually different from the protonated analogues. METHODS: In this work, iohexol complexed with different dications such as Mg2+, Cu2+ and Zn2+ have been investigated by electrospray ionization (ESI) tandem mass spectrometry. Additionally, deuterium-labeling experiments and an analogue of iohexol were utilized to confirm the reaction mechanisms. A computational chemistry method was used to identify the coordination conformation between iohexol and metal ions in the gas phase. UV detection was also used to identify the interaction between iohexol and metal ions in the liquid phase. RESULTS: A special gas-phase open-loop reaction of iohexol induced by Mg2+, leading to the formation of [iohexol + Mg - H - HI - C3H4O]+, was observed in the collision-induced dissociation of [2(iohexol) + Mg]2+ complexes. Moreover, theoretical calculation shows the proposed coordination configuration of iohexol/Mg2+ complexes. The Mg2+ could have tetrahedral coordination with two iohexol molecules. CONCLUSIONS: The percent study is a case for better understanding the formation of a typical organic/metal complex and its gas-phase fragmentation reaction. In addition, it provides useful information for researchers working on analysis or structural elucidation of complicated compounds which contain the iohexol analogues. [ABSTRACT FROM AUTHOR]

The removal of pharmaceuticals by constructed wetlands (CWs) has been gaining more interest in the last decade. However, it is still unclear which are the key factors influencing the removal process. The aim of the present study is to investigate the removal efficiency of ibuprofen (IBU) and iohexol (IOH) by saturated CW mesocosms, depending on type of mesocosm (planted with Typha latifolia, Phragmites australis , Iris pseudacorus , Juncus effusus , Berula erecta or unplanted control), season (summer and winter), hydraulic loading rate (HLR) (0.7, 1.8, 3.4, 6.9 and 13.8 cm d −1 ) and initial spiking concentration (10 and 100 μg L −1 ). The results show that the presence of IBU and IOH had no influence on the monitored water parameters, while the type of mesocosm (different plant species and unplanted control) and season were the main factors explaining the differences observed in pH, dissolved oxygen (DO), oxygen saturation (SAT), total nitrogen (TN), ammonium (NH 4 -N) and phosphate (PO 4 -P). IBU was more efficiently removed (>80%) by mesocosms planted with J. effusus and B. erecta under low HLR and low initial spiking concentration in summer. For IOH, higher removal efficiency (>80%) was achieved by B. erecta -planted mesocosms under low HLR and high initial spiking concentration. Data on IBU removal from mesocosms could be fitted by the first-order kinetic model, with removal rate constants ranging from 0.2 to 4.0 d −1 . For IOH, however, different kinetic models were applied but none could sufficiently describe the removal rate. Regression analysis on IBU demonstrated that 64% of the variation in removal efficiency could be explained by temperature, NH 4 -N and DO. In contrast, IOH removal correlation with any of the variables studied only accounted for 10.6% of the removal variation observed. [ABSTRACT FROM AUTHOR]

To develop an equation for the evaluation of renal function in rats using three dilutions of plasma samples and to validate this method by comparison with a reference method. The investigation was conducted in Sprague-Dawley (SD) rats after delivery of three doses of iohexol, with blood samples collected before and after dosage using a quantitative blood collection method. Plasma iohexol concentrations were detected by high performance liquid chromatography (HPLC). The extraction recovery of iohexol from plasma was >97.30% and the calibration curve was linear ( r2 = 0.9997) over iohexol concentrations ranging from 10 to 1000 µg/mL. The method had an RE of <9.310 and intra- and inter-day RSD of <5.137% and <3.693%, respectively. The plasma clearance values obtained from the equation correlated closely ( r = 0.763) with those obtained using the reference method. The relatively correlation in the results obtained using the method under investigation and the reference method indicate that this new equation can be used for preliminary assessment of renal function in rats. [ABSTRACT FROM AUTHOR]

With the rapid development of imaging diagnosis and interventional therapy, contrast media (CM) are widely used in clinics. However, contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure accounting for 10-12% of all causes of hospital-acquired renal failure. Recent study found that inflammation may participate in the pathogenesis of CIN, but the role of it remains unclear. HK-2 cells were treated with Iohexol, Urografin, and mannitol. Two types of CM increased the release of HMGB1 in cell supernatant accompanied by increased expression of TLR2 and CXCR4. Iohexol and Urografin also caused a significant increase in NF-κB followed by the release of IL-6 and MCP-1. To clarify the role of HMGB1, TLR2, and CXCR4, glycyrrhizin, anti-TLR2-IgG, and AMD3100 were used to inhibit HMGB1, TLR2, and CXCR4, respectively. Significant decrease in the expression of TLR2, CXCR4, nuclear NF-κB, and the release of IL-6 and MCP-1 were observed. These results indicate that TLR2 and CXCR4 signaling are involved in CM-induced HK-2 cell injury model in an HMGB1-dependent pathway, which may provide a new target for the prevention and the treatment of CIN. [ABSTRACT FROM AUTHOR]

Background Low-osmolar non-ionic radiocontrast media ( RCMs) are commonly used throughout hospitals. However, the incidence of immediate adverse drug reactions ( ADRs) to various low-osmolar non-ionic RCMs is not well studied. We compared the incidence of immediate ADRs among different low-osmolar non-ionic RCMs used in computed tomography ( CT). Methods Severance Hospital has collected data for adverse reactions occurring in-hospital using an internally developed system. Using this data, we reviewed 1969 immediate ADRs from 286 087 RCM-contrasted CT examinations of 142 099 patients and compared the immediate ADRs of iobitridol, iohexol, iopamidol, and iopromide. We analysed the incidence of immediate ADRs to different RCMs, as well as the effect of single or multiple CT examinations per day. Results Iopromide showed the highest incidence of immediate ADRs (1.03%) and was followed by iopamidol (0.67%), iohexol (0.64%), and iobitridol (0.34%). In cases of anaphylaxis, iopromide also showed the highest incidence (0.041%), followed by iopamidol (0.023%), iohexol (0.018%), and iobitridol (0.012%). Risk of immediate ADR due to multiple CT examinations (1.19%) was significantly higher than the risk due to a single CT examination (0.63%). Risk of anaphylaxis was also higher for multiple CT examinations (0.052%) than for a single CT examination (0.020%). Conclusions and Clinical Relevance The incidence of immediate ADRs varied according to the low-osmolar non-ionic RCM used. Iopromide-induced immediate ADRs were more frequent, while iobitridol was associated with fewer immediate ADRs than other RCMs. Multiple CT examinations per day resulted in a higher incidence of immediate ADRs and anaphylaxis than a single CT examination. Clinicians should consider these risk differences of immediate ADRs when prescribing contrasted CT examinations. [ABSTRACT FROM AUTHOR]

Iohexol clearance testing was used to determine glomerular filtration rates (GFR) for 12 juvenile Kemp's ridley turtles ( Lepidochelys kempii) that stranded because of cold-stunning. Iohexol was injected intravenously at 75 mg/kg, with subsequent plasma collection at 4, 8, and 24 h post-injection for measurement of iohexol iodine concentrations by inductively coupled plasma mass spectrometry (ICP-MS). Initial GFR was determined on median day 4 of hospitalization (range day 2-5) at an average body temperature of 19°C (66°F) (range 18-21°C [64-70°F]). Mean initial GFR was 4.6 mL/kg/h (range 1.9-8.7 mL/kg/h, n = 10). Convalescent GFR was determined on median day 126 of hospitalization (range day 108-232) at an average body temperature of 24°C (75°F) (range 23-25°C [74-77°F]). Mean convalescent GFR was 13.5 mL/kg/h (range 8.5-21.5 mL/kg/h, n = 10). Statistical analysis of paired initial and convalescent data demonstrated a significantly lower initial GFR, body weight, straight carapace length, and body temperature and significantly greater initial plasma concentrations of iohexol iodine, uric acid, and sodium. Initial GFR was negatively correlated with initial plasma uric acid concentrations. Initial GFR could not be calculated for two turtles because of minimal change in plasma iohexol iodine concentrations over time. Convalescent results could not be determined for two turtles due to death. These results provide the first direct evidence of reduced renal function in cold-stunned turtles. [ABSTRACT FROM AUTHOR]

Background Chronic kidney disease (CKD) is diagnosed and explored through the determination of the glomerular filtration rate (GFR). Our goal was to develop a simple LC-MS method for the determination in serum of 2 popular GFR markers, contrast agents iohexol and iothalamate, for routine use and comparison studies between the two markers. A similar contrast agent, ioversol, was used as an internal standard and the method underwent a rigorous validation protocol based on β-expectation tolerance intervals. Methods We adapted the HPLC-UV method from Cavalier et al. to our LC-MS system. Data treatment for the validation was performed using Multiquant 3.0 (Sciex, Framingham, MA, USA) and e.noval 3.0 software (Arlenda, Liège, Belgium). Results According to the validation results our method will give accurate and reliable results for concentrations ranging from 6.8 to 250 μg/ml for iohexol and 6.15 μg/ml to 250 μg/ml for iothalamate. In our practice these intervals are sufficient to determine both compounds in most patient samples. Samples with higher detected concentrations can always be diluted into range. Conclusion With its internal standard and extensive validation, our method is now ready for routine and clinical research use. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Clinical complications like thrombosis or anaphylaxis have been described to go along with the intravenous or intra-arterial injection of iodinated contrast media (CM). It has been suggested that the administration of CM affects rheological parameters and thereby causes reduced blood velocity in microvessels. In vitro studies revealed significant buckling of endothelial cells after exposure to CM reducing the lumen of vessels. The aim of this study was to test the influence of CM on three-dimensional microvascular tubules with open lumina within an organotypic soft-tissue co-culture assay in vitro. This model, which is based on the co-culture of endothelial cells and fibroblasts, allows the analysis and quantitation of different parameters of microvascular endothelial capillary structures. MATERIAL AND METHODS: Human dermal fibroblasts and human dermal microvascular endothelial cells were co-cultured for 10 days. Fibroblasts were adapted to the endothelial cell medium before co-culture and allowed to proliferate as well as produce extracellular matrix. The co-cultures were exposed to three different CM, i.e., Iomeprol (Imeron 400MCT), Iodixanol (Visipaque 320) or Iohexol (Accupaque 350) for 1.5 minutes or 5.0 minutes, respectively. For this, a mixture of CM and cell culture medium in a ratio of 30% CM by volume was prepared. After fixation in methanol/acetone, the endothelial cells were immunolabeled with the endothelial marker anti-CD31 and the tubular structures were assessed morphometrically. RESULTS: In the organotypic soft-tissue co-cultures with fibroblasts, the endothelial cells developed three-dimensional capillary-like structures which expanded via sprouting branches. After incubation with the different CM, the numbers of endothelial tubes (p = 0.001) and their lengths (p = 0.003) were significantly lower after the 5 minutes incubation time, when compared to the 1.5 minutes incubation time. The tubular diameters were significantly reduced after 5 minutes (p< 0.001), when compared to the 1.5 minutes incubation duration. Interestingly, Iomeprol and Iodixanol induced an elongation of the tubular branches during incubation duration of 1.5 minutes (p = 0.015). However, after 5 minutes incubation, the tubular branches were drastically shorter in the presence of Iomeprol and Iodixanol than the tubular branches of the control (p = 0.007). SUMMARY AND CONCLUSION: All CM exerted a negative effect on the parameters of in vitro blood vessel development. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is associated with significant morbidity and mortality, particularly in unstable critically ill patients. In this context, serum creatinine concentration is an imperfect tool for estimating glomerular filtration rate (GFR), an index of renal function. The objective of this pilot study was to evaluate the feasibility of measuring iohexol clearance for GFR assessment in critically ill patients with acute circulatory failure at intensive care unit (ICU) admission. Methods: ICU patients were prospectively included within 12 h of acute circulatory failure; a non-toxic dose of iohexol (5 mL) was infused intravenously and iohexol plasma concentration decrease was measured over 24 h. Urinary iohexol concentration was measured in urine samples collected four times, every 6 h for 24 h. The Kidney Disease Improving Global Outcome score, measuring AKI, was calculated each day. Results: Among 18 patients with acute circulatory failure, AKI developed in 15; 14 showed decreased serum creatinine concentration during the first 24 h even though 10 presented AKI. The absolute variation in serum creatinine concentration was correlated with fluid balance over 24 h. Median [min; max] plasma clearance of iohexol was 39.4 mL/min [6.1; 154.0] and iohexol urinary clearance 32.8 mL/min [0.8-170.4]. The correlation between plasma and urinary clearance was ρ = 0.97, p <0.0001. Conclusions: GFR may be estimated by plasma iohexol clearance in unstable critically ill patients. This method is reliable, correlates very well with urinary iohexol clearance and does not depend on input/output fluid balance and fluid infusion, as compared with serum creatinine concentration. [ABSTRACT FROM AUTHOR]

A reliable assessment of glomerular filtration rate (GFR) is of paramount importance in clinical practice as well as epidemiological and clinical research settings. It is recommended by Kidney Disease: Improving Global Outcomes guidelines in specific populations (anorectic, cirrhotic, obese, renal and non-renal transplant patients) where estimation equations are unreliable. Measured GFR is the only valuable test to confirm or confute the status of chronic kidney disease (CKD), to evaluate the slope of renal function decay over time, to assess the suitability of living kidney donors and for dosing of potentially toxic medication with a narrow therapeutic index. Abnormally elevated GFR or hyperfiltration in patients with diabetes or obesity can be correctly diagnosed only by measuring GFR. GFR measurement contributes to assessing the true CKD prevalence rate, avoiding discrepancies due to GFR estimation with different equations. Using measured GFR, successfully accomplished in large epidemiological studies, is the only way to study the potential link between decreased renal function and cardiovascular or total mortality, being sure that this association is not due to confounders, i.e. non-GFR determinants of biomarkers. In clinical research, it has been shown that measured GFR (or measured GFR slope) as a secondary endpoint as compared with estimated GFR detected subtle treatment effects and obtained these results with a comparatively smaller sample size than trials choosing estimated GFR. Measuring GFR by iohexol has several advantages: simplicity, low cost, stability and low interlaboratory variation. Iohexol plasma clearance represents the best chance for implementing a standardized GFR measurement protocol applicable worldwide both in clinical practice and in research. [ABSTRACT FROM AUTHOR]

While there is general agreement on the necessity to measure glomerular filtration rate (GFR) in many clinical situations, there is less agreement on the best method to achieve this purpose. As the gold standard method for GFR determination, urinary (or renal) clearance of inulin, fades into the background due to inconvenience and high cost, a diversity of filtration markers and protocols compete to replace it. In this review, we suggest that iohexol, a non-ionic contrast agent, is most suited to replace inulin as the marker of choice for GFR determination. Iohexol comes very close to fulfilling all requirements for an ideal GFR marker in terms of low extra-renal excretion, low protein binding and in being neither secreted nor reabsorbed by the kidney. In addition, iohexol is virtually non-toxic and carries a low cost. As iohexol is stable in plasma, administration and sample analysis can be separated in both space and time, allowing access to GFR determination across different settings. An external proficiency programme operated by Equalis AB, Sweden, exists for iohexol, facilitating interlaboratory comparison of results. Plasma clearance measurement is the protocol of choice as it combines a reliable GFR determination with convenience for the patient. Single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations. In low GFRs one or more late samples should be included to improve accuracy. In patients with large oedema or ascites, urinary clearance protocols should be employed. In conclusion, plasma clearance of iohexol may well be the best candidate for a common GFR determination method. [ABSTRACT FROM AUTHOR]

Purpose: Gastrointestinal toxicity is the most common adverse effect of chemotherapy. Chemotherapeutic drugs damage the intestinal mucosa and increase intestinal permeability. Intestinal permeability is one of the key markers of gastrointestinal function and measuring intestinal permeability could serve as a useful tool for assessing the severity of chemotherapy-induced gastrointestinal toxicity.Methods: Male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg) or irinotecan (200 mg/kg). Clinical signs of gastrointestinal toxicity were assessed daily by weighing the animals and by checking for diarrhea. After 48 h, intestinal permeability to iohexol was measured in vivo by giving the animals 1 ml of 647 mg/ml iohexol solution by oral gavage and collecting all the excreted urine for 24 h. All of the animals were euthanized 72 h after drug administration and tissue samples were harvested from the jejunum and colon.Results: All chemotherapeutics caused significant body weight loss and diarrhea. Intestinal permeability to iohexol was also increased in all treatment groups and histological analysis revealed significant intestinal damage in both jejunum and colon. Iohexol permeability correlated with the severity of clinical signs of gastrointestinal toxicity and with acute colonic injury.Conclusions: Chemotherapeutic drugs, such as 5-fluorouracil, oxaliplatin, and irinotecan, increase intestinal permeability to iohexol. Measuring intestinal permeability to iohexol could provide a simple marker for assessing chemotherapy-induced gastrointestinal toxicity. [ABSTRACT FROM AUTHOR]

A simple and rapid method based on micro-liquid chromatography using a synthetic monolithic capillary column was developed for determination of iohexol in human serums, a marker to evaluate the glomerular filtration rate. A hydrophilic methacrylic acid-ethylene dimethacrylate monolith provided excellent selectivity and efficiency for iohexol with separation time of 3 min using a mobile phase of 40:60 v/v 50 mM phosphate buffer pH 5/methanol. Four serum protein removal, methods using perchloric acid, 50% acetonitrile, 0.1 M zinc sulfate, and centrifuge membrane filter were examined. The method of zinc sulfate was chosen due to its simplicity, compatibility with the mobile phase system, nontoxicity, and low cost. Interday calibration curves were conducted over iohexol concentrations range of 2-500 mg/L ( R2 = 0.9997 ± 0.0001) with detection limit of 0.44 mg/L. Intra- and interday precisions for peak area and retention time were less than 2.8 and 1.4%, respectively. The method was successfully applied to serum samples with percent recoveries from 102 to 104. The method was applied to monitor released iohexol from healthy subject. Compared with the commercially available reversed-phase high-performance liquid chromatography method, the presented method provided simpler chromatogram, faster separation with higher separation efficiency and much lower sample and solvent consumption. [ABSTRACT FROM AUTHOR]

Background Concern for contrast-induced nephropathy (CIN) may result in administration of more costly agents. We prospectively compared outpatient CIN incidence of iodixanol to iohexol. Methods Patients were randomized to receive 100 ml of iohexol ( n = 47) or iodixanol ( n = 55). We compared patients who developed CIN using the Wilson score interval and also calculated an odds ratio for the development of CIN. Results CIN rate for iohexol was 2% compared to 9% for iodixanol. Those receiving iodixanol were almost 5 times more likely to experience CIN. Conclusion These results do not suggest a benefit of iodixanol over iohexol in the study population. [ABSTRACT FROM AUTHOR]

The Swedish radiologist Torsten Almén is the first clinical radiologist ever to have made a fundamental contribution to intravascular contrast medium design, the development of non-ionic contrast media. He became emotionally triggered by the patients' severe pain each time he injected the ionic "high-osmolar" contrast media when performing peripheral arteriographies in the early 1960s. One day he got a flash of genius that combined the observation of pain, a pathophysiological theory and how to eliminate it with suitable contrast media chemistry. After self-studies in chemistry he developed the concept of iodine contrast media not dissociating into ions in solution to reduce their osmolality and even reach plasma isotonicity. He offered several pharmaceutical companies his concept of mono- and polymeric non-ionic agents but without response, since it was considered against the chemical laws of that time. Contrast media constructed as salts and dissociating into ions in solution was regarded an absolute necessity to achieve high enough water solubility and concentration for diagnostic purposes. Finally a small Norwegian company, Nyegaard & Co., took up his idea 1968 and together they developed the essentially painless "low-osmolar" monomeric non-ionic metrizamide (Amipaque) released in 1974 and iohexol (Omipaque) in 1982 followed by the "iso-osmolar" dimeric non-ionic iodixanol (Visipaque) released in 1993. This has implied a profound paradigm shift with regard to reduction of both hypertonic and chemotoxic side effects, which have been a prerequisite for the today's widespread use of contrast medium-enhanced CT and advanced endovascular interventional techniques even in fragile patients. [ABSTRACT FROM AUTHOR]

In mice, renal function evaluated by serum creatinine has limitations. Gold standard methods using radioactive markers are cumbersome. We aimed to develop the iohexol plasma clearance as a simple assessment of renal function in conscious mice. We used two groups of mice: testing and validation, formed by 16 animals (8 male and 8 female) each. Iohexol was injected intravenously into the tail vein (6.47 mg), and tail tip blood samples were collected at 1, 3, 7, 10, 15, 35, 55, and 75 min. Iohexol plasma clearances were calculated in two ways: (1) two-compartment model (CL2) using all time points and (2) one-compartment model (CL1) using only the last four points. In the testing group, CL1 overestimated the true clearance (CL2). Therefore, CL1 was recalculated applying a correction factor calculated as the ratio between CL2/CL1. The latter was considered as the simplified method. CL2 averaged 223.3 ± 64.3 μl/min and CL1 252.4 ± 76.4 μl/min, which lead to a CF of 0.89. Comparable results for CL2, CL1, and simplified method were observed in the validation group. Additionally, we demonstrated the capacity of the simplified method to quantitatively assess different degrees of renal function in three mouse models: hyperoxaluric-CKD (87.4 ± 28.3 μl/min), heminephrectomized (135-0 ± 50.5 μl/min), and obese (399.6 ± 112.1 μl/min) mice. We have developed a simple and reliable method to evaluate renal function in conscious mice under diverse clinical conditions. Moreover, the test can be repeated in the same animal, which makes the method useful to examine renal function changes over time. [ABSTRACT FROM AUTHOR]

Objective To evaluate incidences of adverse reaction after the administration of contrast media. Study design Retrospective observational study. Animals Animals included 356 dogs and 58 cats receiving non-ionic iodinated contrast agents, and 425 dogs and 49 cats receiving gadolinium-based contrast agents. Methods Anaesthesia records of dogs and cats receiving intravenous ( IV) gadobutrol for magnetic resonance imaging ( MRI) or IV iohexol for computed tomography ( CT) were reviewed. Changes in pulse rate, respiratory rate and mean arterial pressure at 5 minutes after administration of the contrast medium were evaluated. Changes of 10-20% were considered mild, those of >20% moderate, and reactions that required immediate treatment were considered severe. Associations of sex, age and weight with contrast reaction were investigated using logistic regression. Differences in the incidences of reactions to CT and MRI contrast media were examined with chi-squared tests. A p-value of <0.05 was considered to indicate statistical significance. Results Of cats receiving iohexol, eight (13.8%) had mild and 10 (17.2%) had moderate reactions. Of cats receiving gadobutrol, six (12.2%) had mild and six (12.2%) had moderate reactions. No cats had severe reactions and the risk for reaction was not associated with type of medium, age, weight or sex ( p > 0.2). Of dogs receiving iohexol, 64 (18.0%) had mild, 65 (18.3%) had moderate and three (0.8%) had severe reactions. Of dogs receiving gadobutrol, 42 (9.9%) had mild, 87 (20.5%) had moderate and one (0.2%) had a severe reaction. When dogs receiving iohexol were compared with those receiving gadobutrol, the odds ratio of a moderate reaction was 2.0 (95% confidence interval 1.34-3.10; p = 0.001). These estimates did not change substantially after adjustment for age, weight and sex. Conclusions and clinical relevance Severe reactions to iohexol and gadobutrol are rare in dogs and cats; moderate reactions are more likely with iohexol than with gadobutrol. [ABSTRACT FROM AUTHOR]

Radiocontrast-induced nephropathy (RCN) is the third most common cause of acute renal failure among inpatients. Although the number of patients undergoing exams using radiocontrast is increasing, little progress has been made for RCN treatment. The pathophysiology of RCN is known as tubular injury due to oxidative stress. As autophagy regulates cellular damage under stressful conditions, we investigated the role of autophagy in RCN. RCN was induced in male C57BL/6 J mice by intraperitoneal injection of iohexol, and 3-methyladenine (3-MA) was used as an autophagy inhibitor. Tubular injury caused by iohexol was also examined in vitro using rat tubular cells (NRK-52E). Increased autophagy after iohexol administration was demonstrated by the increase of light chain 3-II in the damaged kidney tubules both in vivo and in vitro. Serum creatinine and tubular injury were significantly increased at 24 h after iohexol treatment, as compared to control group. Further they worsened with autophagy inhibition by 3-MA. In vitro studies also demonstrated that decreased cell viability by iohexol was aggravated with 3-MA pretreatment. Malondialdehyde measured for oxidative stress was increased by iohexol, and it was accentuated by autophagy inhibition, which resulted in increase of cytochrome c. Apoptosis, increased by iohexol treatment, was augmented with autophagy inhibition. Macrophage infiltration and increase of monocyte chemotactic protein-1 in kidneys were induced by iohexol, and it was aggravated with autophagy inhibition. This study showed that autophagy was involved with the pathophysiology of RCN, and the role of autophagy in modulation of apoptosis, oxidative stress, and inflammatory cell infiltration was supposed as mechanisms mitigating RCN. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor23 (FGF23), an early marker of kidney dysfunction, is associated with cardiovascular death. Its role in HIV-positive individuals is unknown. We measured FGF23 in 100 HIV-negative and 191 HIV-positive nondiabetic adults with normal baseline estimated glomerular filtration rate (GFR). We measured GFR by iohexol annually, albumin-creatinine ratio (ACR) every 6 months, as well as pulse wave velocity, carotid plaque, and carotid intima media thickness (IMT) at baseline and 2 years. Progressive albuminuria was defined as follow-up ACR ≥2-fold than baseline and ≥30 mg/g. Regression models assessed associations of FGF23 with baseline factors and longitudinal changes in disease markers. FGF23 levels were similar in HIV serostatus. Among HIV-positive persons, factors independently associated with higher baseline FGF23 levels included female (adjusted ratio of geometric means [95% CI],1.46 [1.21,1.76]), serum phosphorus (1.20 [1.03,1.40]), HCV (1.31 [1.10,1.56]) and non-suppressed HIV RNA (1.27 [1.01,1.76]). At baseline, FGF23 was not associated with GFR, albuminuria, carotid plaque, or carotid IMT in cross-sectionally adjusted analysis of HIV-positive individuals. However, higher baseline FGF23 was associated with progressive albuminuria (odds ratio1.48 [95% CI]:1.05,2.08) and a more rapid increase in IMT (13 μm/year, 95% CI,3,24). These findings suggest a role for FGF23 in HIV-positive populations in identifying patients at greater risk for cardiovascular and kidney disease. [ABSTRACT FROM AUTHOR]

The role of the intrinsic properties of graphene oxide (GO) and partially reduced graphene oxide (rGO), and their use as redox mediator (RM) is reported, for the first time, on the chemical transformation of iopromide (IOP), an iodinated X-ray contrast medium, under anaerobic conditions. The structural and physicochemical properties of GO containing different types of oxygenated groups, were analyzed by Boehm titrations, point of zero charge (pH PZC ), pKa's distribution, scanning electron microscopy (SEM), electrochemical analysis, as well as by Raman, Fourier transform infrared and UV–Vis spectroscopy. Complete characterization of GO-based materials revealed the removal of different oxygenated groups, such as epoxy and hydroxyl groups, and a transition from an amorphous to a more crystalline structure on partially reduced GO. Moreover, when rGO materials were tested as RM, they promoted a faster and greater extent of IOP transformation up to 5.2-fold with sulfide as electron donor. Results showed a correlation between the reduction degree of GO and its ability to act as RM, which was reflected in the dehalogenation and transformation degree of IOP. Additionally, the chemical transformation pathway of IOP is proposed based on HPLC-MS analysis. [ABSTRACT FROM AUTHOR]

Glomerular iltration rate (GFR) is the amount of fluid the kidney filters through the glomeruli per unit time. It is used to evaluate renal function, since a low value indicates poor kidney function. Serial plasma concentrations of an exogenous marker over time can be used to estimate GFR. In this paper, we will demonstrate how the delta method can be applied to approximate the standard error of estimated GFR, thus allowing the provision of an interval estimate for GFR, using two pharmakinetic models: the single compartment and the non-compartmental. These results were applied to canine observations of plasma iohexol concentrations. We found that the non-compartmental model results in narrow confidence intervals (CI) and that the GFR estimate from a single compartment model is close to that of the non-compartmental model. In the single compartment model, the size of the standard error, and thus the width of the interval, increases as GFR increases. The closeness of the two GFR estimates is reassuring to practitioners who routinely use the single compartment model for simplicity. However, the width of the CI for the single compartment model is of concern when concentration is observed at only a few time points. The non-compartmental model offers the advantage of relatively small standard errors and narrow CIs. This work contributes to the body of knowledge on the estimation of GFR by showing how routinely derived estimates vary due to sampling, indicating the level of importance that clinicians can ascribe to a single estimate of GFR. [ABSTRACT FROM AUTHOR]