Arginase2 mediates contrast-induced acute kidney injury via facilitating nitrosative stress in tubular cells.

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.

Renal function, sex and age influence purines and pyrimidines in urine and could lead to diagnostic misinterpretation.

Glomerular filtration rate (GFR) is commonly used in clinical practice for the diagnosis and follow-up of chronic kidney disease. Screening for inborn errors of metabolism (IEM) is based on analysis of biomarkers in urine, reported by their ratio to urinary creatinine (crn). Impaired renal function may complicate the interpretation of several biomarkers used for screening of IEM. Our goal was to investigate the influence of kidney function, in terms of measured GFR (mGFR) on purines and pyrimidines in urine, in addition to the relationship to sex, age, pH and ketosis. Children (n = 96) with chronic kidney disease (CKD), in different CKD stages, were included. Urine samples were obtained prior to the injection of iohexol. Serum samples at 7 time-points were used to calculate mGFR based on iohexol plasma clearance. The association with sex, age, ketosis and pH was examined in samples of the laboratory production from 2015 to 2021 (n = 8192). Age was a highly significant covariate for all markers. GFR correlated positively to several purines and pyrimidines; the ratios hypoxanthine/crn, xanthine/crn and urate/crn (p = 2.0 × 10-14, < 3 × 10-15 and 7.2 × 10-4, respectively), and the ratios orotic acid/crn, uracil/crn, and carbamyl-ß-alanine/crn (p = 0.03, 1.4 × 10-6 and 0.003, respectively). The values of urate/crn, xanthine/crn, uracil/crn, and carbamyl-ß-alanine/crn were higher in females above 16 years of age. Ketosis and pH influenced some markers. In conclusion, decreased renal function interferes with the excretion of urinary purines and pyrimidines, and this could change decision limits substantially, e.g. result in false negative results in Lesch-Nyhan syndrome. SYNOPSIS: GFR influences purines and pyrimidines in urine. Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2.

Ox-LDL aggravates contrast-induced injury of renal tubular epithelial cells.

Hypercholesterolemia can aggravate contrast-induced acute kidney injury, and the exacerbation of renal tubular epithelial cell (RTEC) injury is a major cause. However, the exact mechanisms remain obscure. Mitophagy, a type of autophagy, selectively eliminates damaged mitochondria and reduces mitochondrial oxidative stress, which is strongly implicated in cell homeostasis and acute kidney injury. Oxidized low-density lipoprotein (Ox-LDL) is accumulated in hypercholesterolemia and has a cytotoxic effect. This study aimed to determine whether and how ox-LDL exacerbates contrast-induced injury in RTECs and to further explore whether PINK1/Parkin-dependent mitophagy is involved in this process. Iohexol and ox-LDL were used alone or in combination to treat HK-2 cells. Rapamycin pretreatment was utilized to enhance mitophagy. Cell viability, apoptosis, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS) were detected by cell counting kit-8, TUNEL staining, JC-1 kit and MitoSOX fluorescence, respectively. The expression of mitophagy-related proteins (including PINK1, Parkin, and so on) and cleaved caspase-3 was confirmed by western blot. Colocalization of MitoTracker-labeled mitochondria and LysoTracker-labeled lysosomes was observed by fluorescence microscopy to evaluate mitophagy. The results of our study showed that ox-LDL aggravated MMP decline, mtROS release and apoptosis in iohexol-treated HK-2 cells, accompanied by a further increased autophagy level. Enhancement of PINK1/Parkin-dependent mitophagy by rapamycin alleviated apoptosis and mitochondrial injury in HK-2 cells in response to iohexol under ox-LDL condition. Therefore, our findings indicate that ox-LDL aggravates contrast-induced injury of RTECs by increasing mitochondrial damage and mitochondrial oxidative stress, which may be associated with the relative insufficiency of PINK1/Parkin-dependent mitophagy.

Characterization of hepatitis B viral forms from patient plasma using velocity gradient: Evidence for an excess of capsids in fractions enriched in Dane particles.

Hepatitis B virus (HBV) morphogenesis is characterized by a large over-production of subviral particles and recently described new forms in parallel of complete viral particles (VP). This study was designed to depict circulating viral forms in HBV infected patient plasmas, using velocity gradients and most sensitive viral markers. Plasmas from chronic hepatitis B (CHB) patients, HBeAg positive or negative, genotype D or E, were fractionated on velocity and equilibrium gradients with or without detergent treatment. Antigenic and molecular markers were measured in plasma and in each collected fraction. Fast Nycodenz velocity gradients revealed good reproducibility and provided additional information to standard equilibrium sucrose gradients. HBV-RNAs circulated as enveloped particles in all plasmas, except one, and at lesser concentrations than VP. Calculations based on standardized measurements and relative virion and subviral particle molecular stoichiometry allowed to refine the experimental approach. For the HBeAg-positive plasma, VP were accompanied by an overproduction of enveloped capsids, either containing HBs, likely corresponding to empty virions, or for the main part, devoid of this viral envelope protein. Similarly, in the HBeAg-negative sample, HBs enveloped capsids, likely corresponding to empty virions, were detected and the presence of enveloped capsids devoid of HBs protein was suspected but not clearly evidenced due to the presence of contaminating high-density subviral particles. While HBeAg largely influences HBcrAg measurement and accounts for two-thirds of HBcrAg reactivity in HBeAg-positive patients, it remains a 10 times more sensitive marker than HBsAg to characterize VP containing fractions. Using Nycodenz velocity gradients and standardized biomarkers, our study proposes a detailed characterization of circulating viral forms in chronically HBV infected patients. We provide evidence for an excess of capsids in fractions enriched in Dane particles, likely due to the presence of empty virions but also by capsids enveloped by an HBs free lipid layer. Identification of this new circulating viral particle sets the basis for studies around the potential role of these entities in hepatitis B pathogeny and their physiological regulation.

Rosiglitazone Alleviates Contrast-Induced Acute Kidney Injury in Rats via the PPARγ/NLRP3 Signaling Pathway.

Background: This study investigated the effect and mechanism of rosiglitazone on a rat model with contrast-induced acute kidney injury (CI-AKI). Materials and Methods: The CI-AKI rat model was established from Sprague Dawley rats by furosemide injection (10 ml/kg) to the caudal vein followed by iohexol (11.7 ml/kg). The experimental grouping was randomly allocated into control, model, rosiglitazone, and T0070907 groups. Blood samples were collected from the abdominal aorta. Serum creatinine, urea nitrogen, MDA, and SOD contents were detected by biochemical analysis. TNF-α and IL-10 expression was detected by ELISA. Urine creatinine and urine protein were measured following 24-h urine biochemistry testing. Cell pathology and apoptosis were detected by H&E and TUNEL staining, respectively. PPARγ, NLRP3, eNOS, and caspase-3 mRNA expression were detected by qPCR. Caspase-3 and NLRP3 expression were detected by immunohistochemistry. Results: The CI-AKI rat model was successfully established because the results showed that compared with control, serum creatinine, urea nitrogen, MDA, SOD, TNF-α, and IL-10, urine creatinine and urine protein levels were significantly increased in the model group, indicating AKI, but was significantly decreased with rosiglitazone treatment, indicating recovery from injury, while opposite results were obtained with SOD. Apoptosis rate was significantly increased in the model group and significantly decreased with rosiglitazone treatment. NLRP3 and eNOS increased significantly in the model group and decreased significantly with rosiglitazone treatment, while opposite results were obtained with PPARγ. NLRP3 and caspase-3 protein expression was significantly increased in the model group and significantly decreased with rosiglitazone treatment. Conclusion: Rosiglitazone could alleviate acute renal injury in the CI-AKI rat model by regulating the PPARγ/NLRP3 signaling pathway and should be further investigated as a potential treatment in clinical studies.

Exploring the effects of edaravone in rats with contrast-induced acute kidney injury.

AIMS: Oxidative stress and inflammatory response play a vital role in the pathogenesis of contrast-induced acute kidney injury (CI-AKI). This study investigated the effects of edaravone in rats with CI-AKI. MAIN METHODS: Male Sprague Dawley rats were randomly assigned into four groups (n = 11-14/group): control, edaravone (30 mg/kg/day intraperitoneally (IP)), CI-AKI, and edaravone with CI-AKI. The induction of CI-AKI was performed by dehydration and the administration of contrast media (iohexol) and inhibitors of prostaglandin (indomethacin) and nitric oxide synthesis (L-NAME: N-nitro L-arginine methyl ester). Edaravone was administered for two weeks before the induction of CI-AKI. Serum creatinine and urea, renal oxidative stress and inflammatory biomarkers, and histopathological alterations were evaluated after 48 h of contrast exposure. KEY FINDINGS: Rats with CI-AKI showed a significant increase in serum creatinine and urea. The levels of antioxidant biomarkers including glutathione peroxidase, superoxide dismutase and reduced glutathione were significantly decreased in CI-AKI group versus control. Pre-treatment of rats with edaravone normalized kidney function and protected the kidney from oxidative damage as demonstrated by normalization of previous biomarkers. Furthermore, edaravone partially ameliorated renal histopathological alterations relative to the CI-AKI group, notably in the nephrons. No changes were observed in inflammatory biomarkers including tumour necrosis factor-alpha and interleukin-6 among all groups. SIGNIFICANCE: The current findings suggest that edaravone could be a potential strategy to ameliorate developing CI-AKI possibly by improving renal antioxidant capacity. Further studies are warranted to expand the current understanding of the use of edaravone in the various models of AKI.

Metabolomic Study on Iohexol-Induced Nephrotoxicity in Rats Based on NMR and LC-MS Analyses.

Iohexol, the raw material of nonionic X-ray computed tomography (X-CT) contrast medium, is usually injected into the vein before CT angiography diagnosis. It is used for angiography, urography, and lymphography. With the advantages of low contrast density and good tolerance, it is currently one of the most popular contrast media. However, the renal toxicity of iohexol seriously affects its safety use. Therefore, it is of great importance to identify new potential diagnostic biomarkers and therapeutic targets in the process of contrast medium-induced acute kidney injury (CI-AKI) in order to safely use iohexol in clinical practice. In this study, in order to understand the metabolic mechanism of CI-AKI, ultra-high-performance liquid chromatography/quadrupole-Orbitrap-mass spectrometry and 1H NMR-based metabolomic techniques were utilized to study the metabolic spectra of kidney, plasma, and urine from CI-AKI rats, and a total of 30 metabolites that were closely related to kidney injury were screened out, which were mainly related to 9 metabolic pathways. The results further indicated that iohexol might intensify kidney dysfunction in vivo by disrupting the metabolic pathways in the body, especially through blocking energy metabolism, amino acid metabolism, and promoting inflammatory reactions.

Comparison of cystatin C, creatinine, and iohexol clearance in pediatric liver transplantation-a retrospective cohort study.

Impaired renal function after pediatric (LT) is a recognized problem. Accurate monitoring of (GFR) is imperative to detect declining renal function. GFR can be estimated via s-creatinine and/or p-cystatin C or measured by inulin and or/iohexol clearances. We retrospectively compared eGFRcrea and eGFRcyst, to mGFRiohex after LT. Data from 91 children with 312 concomitant measurements of s-creatinine, p-cystatin C, and iohexol clearance, obtained between 2007 and 2015, were analyzed. eGFR was calculated by using the p-cystatin C-based CAPA and CKD-EPI formulas, and the s-creatinine-based Schwartz-LYON, FAS, revised Schwartz and MDRD formulas. Also, the arithmetic means of cystatin C-based and creatinine-based equations were used. Every calculated eGFR was compared to mGFRiohex in statistical correlation, accuracy, precision, bias, and misclassifications. Among the different equations, p-cystatin C-based formulas (CAPA and CKD-EPI) as well as the s-creatinine-based Schwartz-LYON formula showed the most correct estimates regarding accuracy (84-87.5%), bias (0.19-4.0 ml/min/1.73 m2 ), and misclassification rate (24.7-25%). In patients with renal function <75 ml/min/1.73 m2 , cystatin C-based formulas were significantly more accurate and less biased than creatinine-based formulas. In conclusion, S-creatinine could be used in a clinical setting on a regular basis in liver transplanted pediatric patients, with reliable results, if eGFR is calculated by the Schwartz-LYON formula. When suspected renal dysfunction, cystatin C-based eGFR should be calculated, since it gives more accurate and less biased estimates than creatinine-based eGFR, and should be confirmed by mGFR (iohexol).

Iohexol plasma clearance simplified by Dried Blood Spot (DBS) sampling to measure renal function in conscious mice.

There is no simple method to measure glomerular filtration rate (GFR) in mice, which limits the use of mice in models of renal diseases. We aimed at simplifying the plasma clearance of iohexol in mice, using dried blood spot (DBS) sampling in order to reduce the amount of blood taken for analysis. GFR was measured simultaneously by a reference method in total blood-as described before-and tested method using DBS in fifteen male and six female C57BL/6J mice. Total blood extraction was 50 µL for the reference methods and 25µL for the tested methods, distributed in 5 samples. The agreement of GFR values between both methods was analyzed with the concordance correlation coefficient (CCC), total deviation index (TDI) and coverage probability (CP). The agreement between both methods was excellent, showing a TDI = 8.1%, which indicates that 90% of the GFR values obtained with DBS showed an error ranging from - 8 to + 8% of the reference method; a CCC of 0.996 (CI: 0.992), reflecting high precision and accuracy and a CP of 94 (CI: 83), indicating that 6% of the GFR values obtained with DBS had an error greater than 10% of the method in blood. So, both methods are interchangeable. DBS represent a major simplification of GFR measurement in mice. Also, DBS improves animal welfare by reducing the total blood required and refining the procedure.

A Machine Learning Approach to Estimate the Glomerular Filtration Rate in Intensive Care Unit Patients Based on Plasma Iohexol Concentrations and Covariates.

OBJECTIVE: This work aims to evaluate whether a machine learning approach is appropriate to estimate the glomerular filtration rate in intensive care unit patients based on sparse iohexol pharmacokinetic data and a limited number of predictors. METHODS: Eighty-six unstable patients received 3250 mg of iohexol intravenously and had nine blood samples collected 5, 30, 60, 180, 360, 540, 720, 1080, and 1440 min thereafter. Data splitting was performed to obtain a training (75%) and a test set (25%). To estimate the glomerular filtration rate, 37 candidate potential predictors were considered and the best machine learning approach among multivariate-adaptive regression spline and extreme gradient boosting (Xgboost) was selected based on the root-mean-square error. The approach associated with the best results in a ten-fold cross-validation experiment was then used to select the best limited combination of predictors in the training set, which was finally evaluated in the test set. RESULTS: The Xgboost approach yielded the best performance in the training set. The best combination of covariates comprised iohexol concentrations at times 180 and 720 min; the relative deviation from these theoretical times; the difference between these two concentrations; the Simplified Acute Physiology Score II; serum creatinine; and the fluid balance. It resulted in a root-mean-square error of 6.2 mL/min and an r2 of 0.866 in the test set. Interestingly, the eight patients in the test set with a glomerular filtration rate < 30 mL/min were all predicted accordingly. CONCLUSIONS: Xgboost provided accurate glomerular filtration rate estimation in intensive care unit patients based on two timed blood concentrations after iohexol intravenous administration and three additional predictors.

Comparability of Plasma Iohexol Clearance Across Population-Based Cohorts.

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 Cb (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.

[Measurement of glomerular filtration rate using a reference method]. / Mesure du débit de filtration glomérulaire par méthode de référence.

Direct measurement methods of glomerular filtration rate (GFR) are considered as the gold standard to assess kidney function. Following the withdrawal of the Proinuline Serb® specialty by the French National Health Surveillance Agency, iohexol remains the most suitable marker to replace inulin as the marker for GFR in France. The assay is performed by high performance liquid chromatography (HPLC) coupled with ultraviolet (UV) detection or by mass spectrometry. Plasma clearance measurement is the protocol of choice: single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations to improve accuracy. In some cases, urinary clearance protocols may be proposed. National and international recommendations suggest using a GFR measurement as a confirmatory test in cases where the creatinine-based estimated GFR is inappropriate, ie clinical situations characterized by a significant alteration of muscle mass or volume distribution. The indications retained by the working group were graded according to the level of recommendations. The essential indications are the evaluation of living kidney donor, the monitoring of kidney allograft function at one year post-transplantation, drugs with narrow therapeutic range (anticoagulant, chemotherapy) in patients with inadequate estimation of GFR by creatinine and clinical research.

Glomerular Hyper- and Hypofiltration During Acute Circulatory Failure: Iohexol-Based Gold-Standard Descriptive Study.

OBJECTIVE: To assess glomerular filtration rate in the early phase of acute circulatory failure by measuring iohexol plasma clearance. DESIGN: Interventional prospective multicentric study. SETTING: Three French ICUs in tertiary teaching hospitals. PATIENTS: Patients with acute circulatory failure within 12 hours after ICU admission. INTERVENTIONS: IV administration of a nontoxic 5-mL dose of iohexol. Collection of nine arterial blood samples over 24 hours for iohexol plasma concentration measurements. Iohexol clearance calculation with a population pharmacokinetic model. Iohexol clearance was an estimation of the mean glomerular filtration rate over 24 hours. MEASUREMENTS AND MAIN RESULTS: Among 99 included patients, we could calculate iohexol clearance for 85. The median iohexol clearance was 31 mL/min (interquartile range, 16-44). According to iohexol clearance, 41 patients (48%) had severe hypofiltration (clearance, < 30 mL/min), 29 (34%) had moderate hypofiltration, and 10 (12%) had mild hypofiltration (clearance, 30-60 and 60-90 mL/min, respectively). Four patients (5%) had normal glomerular filtration rate, and only one (1%) showed hyperfiltration (clearance, > 130 mL/min). Urinary creatinine clearance underestimated renal impairment in one patient out of two; the bias of iohexol clearance toward 24-hour urinary creatinine clearance over the same period was -18.1 mL/min (limits of agreement, -73.5 to 37.4). CONCLUSIONS: We demonstrated the feasibility of iohexol clearance measurement in unstable critically ill patients. Normal kidney function is exceptional during the early phase of acute circulatory failure. Glomerular filtration rate estimation by urinary creatinine clearance frequently fails to detect renal impairment. Hyperfiltration is very infrequent.

Tikhonov gamma variate adaptive regularization applied to technetium Tc 99m diethylenetriamine pentaacetic acid plasma clearance, compared with three other methods, for measuring glomerular filtration rate in cats.

OBJECTIVE: To evaluate agreement of 4 methods (Tikhonov gamma variate adaptive regularization of plasma concentration-time curve fitting applied to technetium Tc 99m diethylenetriamine pentaacetic acid [99mTc-DTPA] plasma clearance [Tk-GV], plasma clearance of exogenous creatinine [CrCL], Gates gamma camera-based measurement method with 99mTc-DTPA renal clearance and dynamic scintigraphy [GTS], and iohexol renal clearance assessed with dynamic CT with Patlak plotting [CT-Pp]) for measuring glomerular filtration rates (GFR) in healthy cats. ANIMALS: 7 healthy, laboratory-raised cats. PROCEDURES: Each method for measuring GFR was performed twice in 7 cats at 24-day intervals. The Wilcoxon signed-rank sum test was used to compare the results obtained from the 14 studies for each method. Results from the 4 methods were assessed for agreement and correlation. RESULTS: The median GFR values were 2.75, 2.83, 3.14, and 4.26 mL/min/kg, for Tk-GV, CT-Pp, plasma CrCL, and GTS, respectively. Analysis with Wilcoxon signed-rank sum tests identified significant pairwise differences between results obtained with the Tk-GV versus the plasma CrCL method, the Tk-GV versus the GTS method, and the plasma CrCL versus the GTS method. The least variable method was Tk-GV, with an SD of 1.27 (mL/min/kg). CONCLUSIONS AND CLINICAL RELEVANCE: Findings indicated that Tk-GV yielded GFR measurements comparable with those obtained with CT-Pp, plasma CrCL, and GTS; however, the Tk-GV method yielded the tightest range of results among the methods evaluated.

Comparison of inert and non-inert cathode in cathode/Fe3+/Peroxymonosulfate processes on iohexol degradation.

To investigate the effect of cathode materials on organics degradation in a cathode/Fe3+/PMS process, different cathode materials (platinum, copper and iron) were selected and their performances were compared with iohexol as target organics. The optimal conditions were found to be different for different cathode/Fe3+/PMS processes. With a relatively high cathodic current input (2.0 mA/cm2), similar results were found for all the three cathode/Fe3+/PMS processes. With a small cathodic current input (not higher than 1.0 mA/cm2), the iohexol removal followed the order of Fe-cathode/Fe3+/PMS > Cu-cathode/Fe3+/PMS > Pt-cathode/Fe3+/PMS, due to the corrosion of Cu-cathode and Fe-cathode and the more serious corrosion of Fe-cathode than Cu-cathode. The corrosion of non-inert cathode materials (Cu-cathode and Fe-cathode) meant that these cathodes not only transmitted electrons but also participated in aqueous reactions, which complicated the mechanisms of cathode/Fe3+/PMS processes. The radical identification experiments indicated that SO4- was more important than OH for iohexol degradation in Cu-cathode/Fe3+/PMS process, while OH played a major role in Pt-cathode/Fe3+/PMS and Fe-cathode/Fe3+/PMS processes. The different reaction mechanisms resulted in different iohexol transformation pathways in cathode/Fe3+/PMS processes with different cathode materials.

Iohexol-measured glomerular filtration rate in children and adolescents with chronic kidney disease: a pilot study comparing venous and finger stick methods.

BACKGROUND: Measurement of glomerular filtration rate by iohexol disappearance (iGFR) has become a gold standard in the pediatric chronic kidney disease (CKD) population. The need for serial phlebotomy can be difficult and minimizing venipunctures would be beneficial. Furthermore, finger stick collection for dried blood spot (DBS) may be more tolerable in the pediatric population, and equivalence between these two methods may further simplify the process. METHODS: This was a cross-sectional study in children and adolescents 1 to 21 years with stages I-IV CKD. Iohexol was infused and blood drawn 10, 30, 120, and 300 min later. Blood spots on filter paper were collected by finger stick after each of the latter two blood draws. The rate of iohexol plasma disappearance was used to calculate GFR. Pearson's correlation coefficient and bias, Students t test, and Bland-Altman graphical representations were used to compare methods. RESULTS: Forty-one patients were recruited. The mean creatinine was 1.13 mg/dL (SD 0.45), the mean 4-point iGFR was 73.2 ml/min/1.73m2 (SD 27.5) and the mean 2-point iGFR was 75.6 ml/min/1.73m2 (SD 27.3). Correlation between 2-point and 4-point venous GFR was r = 0.97; p < 0.001. The correlation between the DBS and the 2-point venous GFR was r = 0.95; p < 0.001, with no significant bias. Ninety-four percent of the 2-point GFR's were within 10% of the 4-point GFR's and 80% of DBS-GFRs were within 10% of the 2-point GFR's. CONCLUSIONS: The 2-point iGFR was highly correlated and agreed well with the 4-point iGFR. The same was true for the DBS method and the 2-point venous method. DBS sampling by finger stick sampling at 2 time points after iohexol infusion gave an acceptably accurate measurement of GFR.

Microbial community metabolic profiles in saturated constructed wetlands treating iohexol and ibuprofen.

The aim of the present study was to elucidate the microbial community metabolic profiles in saturated constructed wetland (CW) mesocosms planted with five different wetland plant species fed with water individually spiked with 100 µg L-1 ibuprofen or iohexol. Community-level physiological profiling (CLPP) using Biolog Ecoplates was performed and coupled with the assessment of water quality parameters (water temperature, pH, DO and TOC, TN, NH4-N, PO4-P removal efficiency). The microbial community metabolic profiles (microbial activity, richness, and carbon source utilization), as well as the water quality parameters revealed similar trends among the control mesocosms and the mesocosms fed with water spiked with iohexol and ibuprofen. Significant differences were observed between the planted and unplanted mesocosms and between seasons (summer and winter) within each of the feeding lines (control, iohexol or ibuprofen). The microbial community metabolic profiles in the saturated CW were shaped by plant presence and plant species, while no negative impact of iohexol and ibuprofen presence was noticed at the 100 µg L-1. In addition, the microbial activity and richness were generally higher in planted mesocosms than in the unplanted systems in the summer. For the first time, a positive correlation between iohexol removal and the microbial community metabolic profiles (activity, richness and amines and amides utilization in summer, and carbohydrates utilization in winter) in the saturated mesocosms was observed. Putrescine utilization in the summer and d-cellobiose, d,l-alpha-glycerol phosphate in winter were linked with the metabolic processing of iohexol, while glycogen in summer and l-phenylalanine, Glycyl-l-glutamic acid in winter were linked with ibuprofen removal efficiency in the saturated CW.

Estimating glomerular filtration rate in children: evaluation of creatinine- and cystatin C-based equations.

BACKGROUND: Glomerular filtration rate (GFR) estimated by creatinine- and/or cystatin C-based equations (eGFR) is widely used in daily practice. The purpose of our study was to compare new and old eGFR equations with measured GFR (mGFR) by iohexol clearance in a cohort of children with chronic kidney disease (CKD). METHODS: We examined 96 children (median age 9.2 years (range 0.25-17.5)) with CKD stages 1-5. A 7-point iohexol clearance (GFR7p) was defined as the reference method (median mGFR 66 mL/min/1.73 m2, range 6-153). Ten different eGFR equations, with or without body height, were evaluated: Schwartzbedside, SchwartzCKiD, SchwartzcysC, CAPA, LMREV, (LMREV + CAPA) / 2, FAScrea, FAScysC, FAScombi, FASheight. The accuracy was evaluated with percentage within 10 and 30% of GFR7p (P10 and P30). RESULTS: In the group with mGFR below 60 mL/min/1.73 m2, the SchwartzcysC equation had the lowest median bias (interquartile range; IQR) 3.27 (4.80) mL/min/1.73 m2 and the highest accuracy with P10 of 44% and P30 of 85%. In the group with mGFR above 60 mL/min/1.73 m2, the SchwartzCKiD presented with the lowest bias 3.41 (13.1) mL/min/1.73 m2 and P10 of 62% and P30 of 98%. Overall, the SchwartzcysC had the lowest bias - 1.49 (13.5) mL/min/1.73 m2 and both SchwartzcysC and SchwartzCKiD showed P30 of 90%. P10 was 44 and 48%, respectively. CONCLUSIONS: The SchwartzcysC and the combined SchwartzCKiD present with lower bias and higher accuracy as compared to the other equations. The SchwartzcysC equation is a good height-independent alternative to the SchwartzCKiD equation in children and can be reported directly by the laboratory information system. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2.

Accuracy of iohexol plasma clearance for GFR-determination: a comparison between single and dual sampling.

BACKGROUND: Current guidelines regarding plasma-sampling techniques for glomerular filtration rate (GFR) determination are inconsistent. Single-sample methods are commonly believed not to be precise enough to meet clinical demands. The present study compared the agreement between single- and dual- plasma sampling methods with a three-point plasma clearance of iohexol. METHODS: A total of 46 healthy volunteers and 124 chronic kidney disease (CKD) patients with varying degrees of renal dysfunction received 5 ml iohexol (300 mgI/ml) i.v. and plasma samples were drawn at 2-, 3- and 4-h post-injection. Plasma-iodine concentrations were detected by high-performance liquid chromatography (HPLC). RESULTS: Bias was similar among single-plasma sampling methods (SPSM) and dual-plasma sampling methods (DPSM). The best correlation was obtained from the 2- and 4-h DPSM (concordance correlation coefficient [CCC]: 0.9988) with none of the estimates differed by more than 30% from the reference GFR and only one (0.06%) estimate differed by more than 10% (P30, 100%; P10, 99.4%). SPSM using samples around 3- or 4-h demonstrated acceptable accuracy at a GFR level of ≥60 ml/min/1.73m2 (P30 = 100% and P10 > 75% for both measurements). CONCLUSION: 4-h SPSM is advantageous in clinical practice in subjects with GFR ≥ 60 ml/min/1.73m2. For patients with an expected GFR < 60 ml/min/1.73m2, a prolonged sampling time is more reliable.

Novel application of magnetic nano-carbon composite as redox mediator in the reductive biodegradation of iopromide in anaerobic continuous systems.

The redox-mediating capacity of magnetic reduced graphene oxide nanosacks (MNS) to promote the reductive biodegradation of the halogenated pollutant, iopromide (IOP), was tested. Experiments were performed using glucose as electron donor in an upflow anaerobic sludge blanket (UASB) reactor under methanogenic conditions. Higher removal efficiency of IOP in the UASB reactor supplied with MNS as redox mediator was observed as compared with the control reactor lacking MNS. Results showed 82% of IOP removal efficiency under steady state conditions in the UASB reactor enriched with MNS, while the reactor control showed IOP removal efficiency of 51%. The precise microbial transformation pathway of IOP was elucidated by high-performance liquid chromatography coupled to mass spectroscopy (HPLC-MS) analysis. Biotransformation by-products with lower molecular weight than IOP molecule were identified in the reactor supplied with MNS, which were not detected in the reactor control, indicating the contribution of these magnetic nano-carbon composites in the redox conversion of this halogenated pollutant. Reductive reactions of IOP favored by MNS led to complete dehalogenation of the benzene ring and partial rupture of side chains of this pollutant, which is the first step towards its complete biodegradation. Possible reductive mechanisms that took place in the biodegradation of IOP were stated. Finally, the novel and successful application of magnetic graphene composites in a continuous bioreactor to enhance the microbial transformation of IOP was demonstrated.