Exploring sample treatment strategies for untargeted metabolomics: A comparative study of solid phase microextraction (SPME) and homogenization with solid-liquid extraction (SLE) in renal tissue.

BACKGROUND: The selection of the sample treatment strategy is a crucial step in the metabolomics workflow. Solid phase microextraction (SPME) is a sample processing methodology with great potential for use in untargeted metabolomics of tissue samples. However, its utilization is not as widespread as other standard protocols involving steps of tissue collection, metabolism quenching, homogenization, and extraction of metabolites by solvents. Since SPME allows us to perform all these steps in one action in tissue samples, in addition to other advantages, it is necessary to know whether this methodology produces similar or comparable metabolome and lipidome coverage and performance to classical methods. RESULTS: SPME and homogenization with solid-liquid extraction (Homo-SLE) sample treatment methods were applied to healthy murine kidney tissue, followed by comprehensive metabolomics and lipidomics analyses. In addition, it has been tested whether freezing and storage of the tissue causes alterations in the renal metabolome and lipidome, so the analyses were performed on fresh and frozen tissue samples Lipidomics analysis revealed the exclusive presence of different structural membrane and intracellular lipids in the Homo-SLE group. Conversely, all annotated metabolites were detected in both groups. Notably, the freezing of the sample mainly causes a decrease in the levels of most lipid species and an increase in metabolites such as amino acids, purines, and pyrimidines. These alterations are principally detected in a statistically significant way by SPME methodology. Finally, the samples of both methodologies show a positive correlation in all the analyses. SIGNIFICANCE: These results demonstrate that in SPME processing, as long as the fundamentals of non-exhaustive extraction in a pre-equilibrium kinetic regime, extraction in a tissue localized area, the chemistry of the fiber coating and non-homogenization of the tissue are taken into account, is an excellent method to use in kidney tissue metabolomics; since this methodology presents an easy-to-use, efficient, and less invasive approach that simplifies the different sample processing steps.

[Evaluation of efficacy of Dihuang Baoyuan Granules for diabetes mellitus and composition and in vivo distribution analysis based on UHPLC-LTQ-Orbitrap MS].

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.

Multifunctional laser-induced graphene circuits and laser-printed nanomaterials toward non-invasive human kidney function monitoring.

Faced with the increasing prevalence of chronic kidney disease (CKD), portable monitoring of CKD-related biomarkers such as potassium ion (K+), creatinine (Cre), and lactic acid (Lac) levels in sweat has shown tremendous potential for early diagnosis. However, a rapidly manufacturable portable device integrating multiple CKD-related biomarker sensors for ease of sweat testing use has yet to be reported. Here, a portable electrochemical sensor integrated with multifunctional laser-induced graphene (LIG) circuits and laser-printed nanomaterials based working electrodes fabricated by fully automatic laser manufacturing is proposed for non-invasive human kidney function monitoring. The sensor comprises a two-electrode LIG circuit for K+ sensing, a three-electrode LIG circuit with a Kelvin compensating connection for Cre and Lac sensing, and a printed circuit board based portable electrochemical workstation. The working electrodes containing Cu and Cu2O nanoparticles fabricated by two-step laser printing show good sensitivity and selectivity toward Cre and Lac sensing. The sensor circuits are fabricated by generating a hydrophilic-hydrophobic interface on a patterned LIG through laser. This sensor recruited rapid laser manufacturing and integrated with multifunctional LIG circuits and laser-printed nanomaterials based working electrodes, which is a potential kidney function monitoring solution for healthy people and kidney disease patients.

Distribution of copper in the Atlantic and Pacific Oceans using green turtles (Chelonia mydas) as a bioindicator.

Marine pollution by trace elements is a global concern due to potential toxicity to species and ecosystems. Copper is a fundamental trace element for many organisms; however, it becomes toxic at certain concentrations. The green turtle (Chelonia mydas) is a good sentinel species, due to its circumglobal distribution, long life cycle, coastal habits when juvenile, and is subject to environmental pollution. Quantifying and comparing copper levels makes it possible to understand the availability of this trace element in nature. During this research, comparisons were made between the levels of copper found in the liver, kidneys, and muscles of 35 turtles, from the United States (Hawaii and Texas), Brazil, and Japan. Copper was found in all specimens. In the liver, animals from Hawaii (91.08 µg g-1), Texas (46.11 µg g-1), and Japan (65.18 µg g-1) had statistically equal means, while those from Brazil (16. 79 µg g-1) had the lowest means. For the kidney, copper means were statistically equal for all Hawaii (3.71 µg g-1), Texas (4.83 µg g-1), Japan (2.47 µg g-1), and Brazil (1.89 µg g-1). In muscle, the means between Texas (0.75 µg g-1) and Japan (0.75 µg g-1) were the same, and the mean for Brazil (0.13 µg g-1) was the lowest. Among the organs, the highest levels of copper were found in the liver (28.33 µg g-1) followed by the kidney (2.25 µg g-1) and with the lowest levels in the muscle (0.33 µg g-1). This is the first study of copper levels among marine vertebrates in distant parts of the globe using similar comparative filters between different locations. Similar levels in turtles from such distant locations may indicate that there is a pantropical pattern of copper distribution in the biota, and that these animals are subject to the process of bioavailability of this metal in the environment and metabolic regulation.

Changes in the amount of nucleotide sugars in aged mouse tissues.

Aging affects tissue glycan profiles, which may alter cellular functions and increase the risk of age-related diseases. Glycans are biosynthesized by glycosyltransferases using the corresponding nucleotide sugar, and the availability of nucleotide sugars affects glycosylation efficiency. However, the effects of aging on nucleotide sugar profiles and contents are yet to be elucidated. Therefore, this study aimed to investigate the effects of aging on nucleotide sugars using a new LC-MS/MS method. Specifically, the new method was used to determine the nucleotide sugar contents of various tissues (brain, liver, heart, skeletal muscle, kidney, lung, and colon) of male C57BL/6NCr mice (7- or 26-month-old). Characteristic age-associated nucleotide sugar changes were observed in each tissue sample. Particularly, there was a significant decrease in UDP-glucuronic acid content in the kidney of aged mice and a decrease in the contents of several nucleotide sugars, including UDP-N-acetylgalactosamine, in the brain of aged mice. Additionally, there were variations in nucleotide sugar profiles among the tissues examined regardless of the age. The kidneys had the highest concentration of UDP-glucuronic acid among the seven tissues. In contrast, the skeletal muscle had the lowest concentration of total nucleotide sugars among the tissues; however, CMP-N-acetylneuraminic acid and CDP-ribitol were relatively enriched. Conclusively, these findings may contribute to the understanding of the roles of glycans in tissue aging.

Detection of selected antimicrobial residues in red meat and kidney of beef cattle slaughtered at Nekemte municipal abattoir, Ethiopia.

BACKGROUND: Antibiotics are commonly used drugs in farm animals for therapeutic, prophylactic and diagnosis purposes. As a result of the use of antibiotics in livestock, residues of antibiotics may be present in animal-derived foods, especially in meat. This study aimed at determining the antibiotic residues in cattle slaughtered at Nekemte municipal abattoir and assessing the knowledge, attitude and practice (KAP) level of the community about antibiotic residue in food of cattle origin. MATERIALS AND METHODS: A cross-sectional study was conducted on randomly selected kidney and muscle samples slaughtered at Nekemte municipal abattoir. The samples were collected aseptically and analysed using liquid chromatography mass spectrometer. In addition the KAP of cattle handlers, butcher men and meat users were collected using structured questionnaire. The data was analysed by SPSS and intercooled Stata version 7.0, 2001. RESULTS: Results are presented as percentages and frequency distributions in tabular and graphical form. From 120 individuals interviewed, only 25.83% knew about withdrawal time and had limited knowledge on effect of antibiotic residue on human health, whereas about 47.5% did not heard about antibiotic residue in meat. Tetracycline was detected in all the sampled meat 60 (100%), whereas oxytetracycline residues were detected in half 15 (50%) of the samples. In the current study doxycycline, sulphadiazine, penicillin G and enrofloxacin were not detected in all samples. Oxytetracycline residue levels ranged from 0.00 to 463.35 µg/kg for the kidney and 0.00 to 354.55 µg/kg for muscle samples. About 10% of kidney and 3.33% muscle samples collected had oxytetracycline residues above maximum residue limits. CONCLUSION: In general, the study revealed that oxytetracycline residues were prevalent among antimicrobial residues analysed from the study area. The study indicated the presence of high antimicrobial residue and hence exposes for antimicrobial resistance of pathogens warranting coordinated effort to mitigate its health effect on the animal and hence human being.

Development and validation of a GC-MS/MS method for the determination of iodoacetic acid in biological samples.

Iodoacetic acid (IAA) is a halogenated disinfection by-product of growing concern due to its high cytotoxicity, genotoxicity, endocrine disruptor effects, and potential carcinogenicity. However, the data on distribution and excretion of IAA after ingestion by mammals are still scarce. Here, we developed a reliable and validated method for detecting IAA in biological specimens (plasma, urine, feces, liver, kidney, and tissues) based on modified QuEChERS sample preparation combined with gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS/MS). The detection method for IAA exhibited satisfactory recovery rates (62.6-108.0%) with low relative standard deviations (RSD < 12.3%) and a low detection limit for all biological matrices ranging from 0.007 to 0.032 ng/g. The study showed that the proposed method was reliable and reproducible for analyzing IAA in biological specimens. It was successfully used to detect IAA levels in biological samples from rats given gavage administration. The results indicated that IAA was found in various tissues and organs, including plasma, thyroid, the liver, the kidney, the spleen, gastrointestinal tract, and others, 6 h after exposure. This study provides the first data on the in vivo distribution in and excretion of IAA by mammals following oral exposure.

Endothelium-related biomarkers enhanced prediction of kidney support therapy in critically ill patients with non-oliguric acute kidney injury.

Acute kidney injury (AKI) is a common condition in hospitalized patients who often requires kidney support therapy (KST). However, predicting the need for KST in critically ill patients remains challenging. This study aimed to analyze endothelium-related biomarkers as predictors of KST need in critically ill patients with stage 2 AKI. A prospective observational study was conducted on 127 adult ICU patients with stage 2 AKI by serum creatinine only. Endothelium-related biomarkers, including vascular cell adhesion protein-1 (VCAM-1), angiopoietin (AGPT) 1 and 2, and syndecan-1, were measured. Clinical parameters and outcomes were recorded. Logistic regression models, receiver operating characteristic (ROC) curves, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used for analysis. Among the patients, 22 (17.2%) required KST within 72 h. AGPT2 and syndecan-1 levels were significantly greater in patients who progressed to the KST. Multivariate analysis revealed that AGPT2 and syndecan-1 were independently associated with the need for KST. The area under the ROC curve (AUC-ROC) for AGPT2 and syndecan-1 performed better than did the constructed clinical model in predicting KST. The combination of AGPT2 and syndecan-1 improved the discrimination capacity of predicting KST beyond that of the clinical model alone. Additionally, this combination improved the classification accuracy of the NRI and IDI. AGPT2 and syndecan-1 demonstrated predictive value for the need for KST in critically ill patients with stage 2 AKI. The combination of AGPT2 and syndecan-1 alone enhanced the predictive capacity of predicting KST beyond clinical variables alone. These findings may contribute to the early identification of patients who will benefit from KST and aid in the management of AKI in critically ill patients.

Real-Time Tissue Classification Using a Novel Optical Needle Probe for Biopsy.

Core needle biopsy is a part of the histopathological process, which is required for cancerous tissue examination. The most common method to guide the needle inside of the body is ultrasound screening, which in greater part is also the only guidance method. Ultrasound screening requires user experience. Furthermore, patient involuntary movements such as breathing might introduce artifacts and blur the screen. Optically enhanced core needle biopsy probe could potentially aid interventional radiologists during this procedure, providing real-time information on tissue properties close to the needle tip, while it is advancing inside of the body. In this study, we used diffuse optical spectroscopy in a custom-made core needle probe for real-time tissue classification. Our aim was to provide initial characteristics of the smart needle probe in the differentiation of tissues and validate the basic purpose of the probe of informing about breaking into a desired organ. We collected optical spectra from rat blood, fat, heart, kidney, liver, lungs, and muscle tissues. Gathered data were analyzed for feature extraction and evaluation of two machine learning-based classifiers: support vector machine and k-nearest neighbors. Their performances on training data were compared using subject-independent k-fold cross-validation. The best classifier model was chosen and its feasibility for real-time automated tissue recognition and classification was then evaluated. The final model reached nearly 80% of correct real-time classification of rat organs when using the needle probe during real-time classification.

Development of simultaneous quantitation method for 20 free advanced glycation end products using UPLC-MS/MS and clinical application in kidney injury.

Advanced glycation end products (AGEs), derived from the non-enzymatic glycation reaction, are defined as glycotoxins in various diseases including aging, diabetes and kidney injury. Exploring AGEs as potential biomarkers for these diseases holds paramount significance. Nevertheless, the high chemical structural similarity and great heterogeneity among AGEs present a formidable challenge when it comes to the comprehensive, simultaneous, and accurate detection of multiple AGEs in biological samples. In this study, an UPLC/MS/MS method for simultaneous quantification of 20 free AGEs in human serum was firstly established and applied to quantification of clinical samples from individuals with kidney injury. Simple sample preparation method through protein precipitation without derivatization was used. Method performances including imprecision, accuracy, sensitivity, linearity, and carryover were systematically validated. Intra- and inter- imprecision of 20 free AGEs were 1.93-5.94 % and 2.30-8.55 %, respectively. The method accuracy was confirmed with good recoveries ranging from 96.40 % to 103.25 %. The LOD and LOQ were 0.1-3.13 ng/mL and 0.5-6.25 ng/mL, respectively. Additionally, the 20 free AGEs displayed excellent linearity (R2 >0.9974) across a wide linear range (1.56-400 ng/mL). Finally, through simultaneous quantitation of 20 Free AGEs in 100 participants including kidney injury patient and healthy controls, we identified six free AGEs, including N6-carboxyethyl-L-arginine (CEA), N6-carboxymethyl-L-lysine (CML), methylglyoxal-derived hydroimidazolones (MG-H), N6-formyl-lysine, N6-carboxymethyl-L-arginine (CMA), and glyoxal-derived hydroimidazolone (G-H), could well distinguish kidney injury patients and healthy individuals. Among them, the levels of four free AGEs including CML, CEA, MG-H, and G-H strongly correlate with traditionally clinical markers of kidney disease. The high area under the curve (AUC) values (AUC=0.965) in receiver operating characteristic (ROC) curve indicated that these four free AGEs can be served as combined diagnostic biomarkers for the diagnosis of kidney disease.

Metabolomics perspectives into the co-exposure effect of polycyclic aromatic hydrocarbons and metals on renal function: A meet-in-the-middle approach.

Studies on the dose effects of kidney impairment and metabolomes in co-exposure to polycyclic aromatic hydrocarbons (PAHs) and metals are limited. We aimed to identify overall associations and metabolic perturbations in 130 participants (53 petrochemical workers and 77 controls) exposed to a PAHs-metals mixture in Southern China. The urinary 7 hydroxylated PAHs and 15 metal(loid)s were determined, and serum creatinine, beta-2 microglobulin, and estimated glomerular filtration rate were health outcomes. The liquid chromatography-mass spectrometry-based method was applied to serum metabolomics. Generalized weighted quantile sum (gWQS) regressions were used to estimate the overall dose-response relationships, and pathway analysis, "meet-in-the-middle" approach, and mediation effect analyses were conducted to identify potential metabolites and biological mechanisms linking exposure with nephrotoxic effects. Our results indicated that renal function reduction was associated with a PAHs-metals mixture in a dose-dependent manner, and 1-hydroxynaphthalene and copper were the most predominant contributors among the two families of pollutants. Furthermore, the metabolic disruptions associated with the early onset of kidney impairment induced by the combination of PAHs and metals encompassed pathways such as phenylalanine-tyrosine-tryptophan biosynthesis, phenylalanine metabolism, and alpha-linolenic acid metabolism. In addition, the specifically identified metabolites demonstrated excellent potential as bridging biomarkers connecting the reduction in renal function with the mixture of PAHs and metals. These findings shed light on understanding the overall associations and metabolic mechanism of nephrotoxic effects of co-exposure to PAHs and metals.

Effect of urbanization on the trace element concentrations in the kidney, liver and spines of the European hedgehog (Erinaceus europaeus).

Urbanized environments may be suitable for some wild species, like the European hedgehog (Erinaceus europaeus). However, the (sub)urban areas are source of several pollutants, such as trace elements (TEs). The main objective of our study is to investigate the role of the European hedgehog as a potential bioindicator species for seven TEs (As, Cd, Cr, Cu, Ni, Pb, Zn) in a big urban agglomeration. We analyzed the kidney, liver and spines of 50 European hedgehogs. Moreover, we carried out geographic information system (GIS) with 31 individuals to examine the effects of human pressure (human density and urbanization) on TE concentrations in tissues. We detected the 7 TEs in all tissues. Trace elements, especially Pb and Zn, in the liver, kidney and spines seem to be influenced by human density and urbanization.

MicroRaman spectroscopy detects the presence of microplastics in human urine and kidney tissue.

There is a growing concern within the medical community about the potential burden of microplastics on human organs and tissues. In this study, we investigated by microRaman spectroscopy the presence of microplastics in human kidneys and urine. Moreover, an open-access software was developed and validated for the project, which enabled the comparison between the investigated spectra and a self-created spectral database, thus enhancing the ability to characterize polymers and pigments in biological matrices. Healthy portions of ten kidneys obtained from nephrectomies, as well as ten urine samples from healthy donors were analyzed: 26 particles in both kidney and urine samples were identified, with sizes ranging from 3 to 13 µm in urine and from 1 to 29 µm in kidneys. The most frequently determined polymers are polyethylene and polystyrene, while the most common pigments are hematite and Cu-phthalocyanine. This preclinical study proves the presence of microplastics in renal tissues and confirms their presence in urine, providing the first evidence of kidney microplastics deposition in humans.

Ambient ozone pollution impairs glucose homeostasis and contributes to renal function decline: Population-based evidence.

Particulate matter pollution could increase the risk of kidney disease, while evidence for ozone exposure is less well-established. Here, we aimed to evaluate the effect of ozone pollution on renal function and explore mechanisms. We first conducted a cross-sectional study based on Wuhan Chronic Disease Cohort Study baseline information. We recruited 2699 eligible participants, estimated their residential ozone concentrations, collected fasting peripheral blood samples for biochemical analysis and calculated the estimated glomerular filtration rate (eGFR). The linear regression model was applied to evaluate the long-term association between ozone pollution and eGFR. Then, we recruited another 70 volunteers as a panel with 8 rounds follow-up visits. We calculated the eGFR and measured fasting blood glucose and lipid levels. The linear mixed-effect model along with mediation analysis were performed to confirm the short-term association and explore potential mechanisms, respectively. For the long-term association, a 10.95 µg/m3 increment of 3-year ozone exposure was associated with 2.96 mL/min/1.73 m2 decrease in eGFR (95%CI: -4.85, -1.06). Furthermore, the drinkers exhibited a pronounced declination of eGFR (-7.46 mL/min/1.73 m2, 95%CI: -11.84, -3.08) compared to non-drinkers in relation to ozone exposure. Additionally, a 19.02 µg/m3 increase in 3-day ozone concentrations was related to 2.51 mL/min/1.73 m2 decrease in eGFR (95%CI: -3.78, -1.26). Hyperglycemia and insulin resistance mediated 12.2% and 16.5% of the aforementioned association, respectively. Our findings indicated that higher ozone pollution could affect renal function, and the hyperglycemia and insulin resistance linked to ozone might be the underlying mechanisms.

Exploring the association between two groups of metals with potentially opposing renal effects and renal function in middle-aged and older adults: Evidence from an explainable machine learning method.

BACKGROUND: Machine learning models have promising applications in capturing the complex relationship between mixtures of exposures and outcomes. OBJECTIVE: Our study aimed at introducing an explainable machine learning (EML) model to assess the association between metal mixtures with potentially opposing renal effects and renal function in middle-aged and older adults. METHODS: This study extracted data from two cycle years of the National Health and Nutrition Examination Survey (NHANES). Participants aged 45 years or older with complete data on six metals (lead, cadmium, manganese, mercury, and selenium) and related covariates were enrolled. The EML model was developed by the optimized machine learning model together with Shapley Additive exPlanations (SHAP) to assess the chronic kidney disease (CKD) risk with metal mixtures. The results from EML were further compared in detail with multiple logistic regression (MLR) and Bayesian kernel machine regression (BKMR). RESULTS: After adjusting for included covariates, MLR pointed out the lead and arsenic were generally positively associated with CKD, but manganese had a negative association. In the BKMR analysis, each metal was found to have a non-linear association with the risk of CKD, and interactions can exist between metals, especially for arsenic and lead. The EML ranked the feature importance: lead, manganese, arsenic and selenium were close behind in importance after gender, age or BMI for participants with CKD. Strong interactions between mercury and lead, manganese and cadmium and arsenic and manganese were identified by partial dependence plot (PDP) of SHAP and bivariate exposure-response effect plots of BKMR. The EML model determined the "trigger point" at which the risk of CKD abruptly changed. CONCLUSION: Co-exposure to metals with different nephrotoxicity could have different joint association with renal function, and EML can be a powerful method for studying complex exposure mixtures.

Extending the cystatin C based EKFC-equation to children - validation results from Europe.

BACKGROUND: A new cystatin C based European Kidney Function Consortium (EKFCCysC) equation was recently developed for adults, using the same mathematical form as the previously published full age spectrum creatinine based EKFC-equation (EKFCCrea). In the present study the cystatin C based EKFC-equation is extended to children, by defining the appropriate cystatin C rescaling factor QCysC. METHODS: Rescaling factor QCysC for cystatin C was defined as: a) 0.83 mg/L, exactly as it was defined for young adults in the adult equation, and b) a more complex QCysC-age relationship based on 4th degree cystatin C-age polynomials after evaluation of data from Uppsala, Stockholm and Canada and aggregated data from Germany. The EKFCCysC equation was then validated in an independent dataset in European children (n = 2,293) with measured GFR, creatinine, cystatin C, age, height and sex available. RESULTS: The EKFCCysC with the simple QCysC-value of 0.83 had a bias of -7.6 [95%CI -8.4;-6.5] mL/min/1.73 m2 and a P30-value of 85.8% [95%CI 84.4;87.3] equal to the EKFCCysC with the more complex 4th degree QCysC-value. The arithmetic mean of the EKFCCrea and EKFCCysC with the simple QCysC of 0.83 had a bias of -4.0 [95%CI -4.5;-3.1] mL/min/1.73 m2 and P30 of 90.4% [95%CI 89.2;91.6] similar to using the more complex 4th degree QCysC-polynomial. CONCLUSION: Using exactly the same QCysC of 0.83 mg/L, the adult EKFCCysC can easily be extended to children, with some bias but acceptable P30-values. The arithmetic mean of EKFCCrea and EKFCCysC results in bias closer to zero and P30 slightly over 90%.

Non-invasive detection of renal disease biomarkers through breath analysis.

Breath biomarkers are substances found in exhaled breath that can be used for non-invasive diagnosis and monitoring of medical conditions, including kidney disease. Detection techniques include mass spectrometry (MS), gas chromatography (GC), and electrochemical sensors. Biosensors, such as GC-MS or electronic nose (e-nose) devices, can be used to detect volatile organic compounds (VOCs) in exhaled breath associated with metabolic changes in the body, including the kidneys. E-nose devices could provide an early indication of potential kidney problems through the detection of VOCs associated with kidney dysfunction. This review discusses the sources of breath biomarkers for monitoring renal disease during dialysis and different biosensor approaches for detecting exhaled breath biomarkers. The future of using various types of biosensor-based real-time breathing diagnosis for renal failure is also discussed.

Fluoride exposure and pediatric kidney health in dry, wet and intermediate climatic zone communities in Sri Lanka: Implications from urinary Cystatin-C, and albumin-creatinine ratio.

BACKGROUND: High fluoride exposure is increasingly discussed attributing to kidney injury as a causative factor. Depending on geochemistry, differential fluoride levels in drinking water are identified in different regions in Sri Lanka. However, the levels of fluoride exposure, and associations with kidney health has not been adequately studied in Sri Lanka, particularly in pediatric communities. Hence, the present study aimed to assess fluoride exposure in selected pediatric communities in the dry, wet and intermediate climatic zones in Sri Lanka, along with an assessment of renal health using urinary Cystatin-C (uCys-C), and albumin-creatinine ratio (uACR). METHODS: We conducted a cross-sectional study with school students in selected education zones representing dry (N = 331), wet (N = 152), and intermediate (N = 292) climatic zones in Sri Lanka. Fluoride contents in urine and drinking water were assessed as measures of fluoride exposure. RESULTS: The median (interquartile distance) urinary fluoride levels of participants in the dry, wet and intermediate zones were 1.63(1.04-2.85), 1.29(0.85-2.21), and 1.07(0.61-1.98) mg/gCr while the fluoride contents of drinking water samples were 1.76(1.36-2.30), 0.25(0.18-0.37), and 0.43(0.26-0.63) ppm respectively with significant differences among the three groups. Median uCys-C level (ng/mgCr) of the participants in intermediate zone [30.26(8.49-71.44)] was significantly low (p < 0.05) compared to that of the participants in dry zone [56.19(7.08-211.8)], and wet zone [66.29(30.43-125.20)]. The incidences of elevated uCys-C levels above reference intervals in participants of dry zone (47.7%), and wet zone (50.0%) were significantly high (p < 0.001) compared to the intermediate zone (26.4%). CONCLUSION: Relatively high fluoride exposure is likely in dry and wet zone communities compared to the intermediate zone along with significantly higher incidence of uCys-C levels above reference intervals in study groups with higher fluoride exposure. However, to conclude a clear link between fluoride exposure and kidney health we need in-depth studies.

Precisely Constructing Renal-Clearable and LAP-Activatable Ratiometric Molecular Probes for Early Diagnosis of Acute and Chronic Kidney Injury Via Optimizing Asymmetric DPP Dyes.

Fluorescence analysis is an increasingly important contributor to the early diagnosis of kidney diseases. To achieve precise visualization of the kidneys and early diagnosis of related diseases, an asymmetric pyrrolopyrrolidone (DPP) dye platform with C-aromatic substituents and N-lipophilic/hydrophilic modification was constructed. Based on these, we developed the renal-clearable, water-soluble, and kidney injury biomarker leucine aminopeptidase (LAP) activated ratiometric fluorescent probe DPP-S-L. In the mouse model of cisplatin-induced acute kidney injury and during the development of type 2 diabetes to diabetic kidney disease, we visualized for the first time the upregulation of LAP in the kidney and urine by dual-channel ratiometric fluorescence signal and diagnosed the kidney injury earlier and more sensitively than blood/urine enzyme detection and tissue analysis. This study showcases an excellent asymmetric DPP dye platform and renal-clearable ratiometric fluorescent probe design strategy that is extended to determination and visualization of other biomarkers for early disease diagnosis.

Exploring the pathology of liver, kidney, muscle, and stomach of fledgling seabirds associated with plastic ingestion.

There remain significant gaps in knowledge about 'sub-lethal' impacts of plastic ingestion, particularly chronic impacts on cells, tissues, or organs. Few studies have applied traditional animal health tools, such as histopathology, to assess physiological damage to wildlife, with fewer still providing information on the dosage or exposure to plastics needed to elicit negative effects. Our study seeks to investigate a common hypothesis in plastic pollution research; that an increasing plastics burden will have an impact on an animal's health, examining two wild species with high levels of environmental exposure to plastic through their diet. Here we assess the histopathology of the muscle, upper digestive tract, liver and kidney of two seabird species that are known to be commonly exposed to plastic, comparing exposed and non-exposed individuals. Fledgling seabirds showed histopathological evidence of cumulative pressures such as starvation, disease, and endoparasite burden. However, we observed no evidence of chronic harm that could be explicitly linked to the plastics. We found one case of haemorrhage, reaffirming that large/sharp plastic foreign bodies may cause acute physical damage. Given the numerous interacting pressures on the health of fledging seabirds, including exposure to plastic, this study highlights the need to scrutinise plastic-animal interactions and research though a One Health lens.