Urinary Concentrations Research Articles

Unraveling the contribution of melamine tableware for human internal exposure to melamine and its derivatives: Insights from crossover and biomonitoring studies

Melamine tableware can release melamine in daily-use; however, currently there is insufficient evidence to support whether the amount released could pose human exposure risk. We therefore conducted two studies, one is 8-day randomized crossover trial involving 27 volunteers who used melamine and stainless-steel tableware in turn (n = 648) and the other is cross-sectional study including 113 college students and 200 residents (n = 313) to further provide population-based evidence. The crossover study results showed that using melamine tableware could promote urinary concentrations of melamine, cyanuric acid (CYA), and ammelide by 42.1 %, 66.9 %, and 36.2 %, respectively. In the biomonitoring survey, students who are more accessible to melamine tableware in the canteen had 1.47-fold higher median urinary concentrations of melamine-related compounds than that of common residents (393 vs 267 nmol/L, p < 0.01). Additionally, positive associations between exposure to melamine and an oxidative stress indicator, 8-oxo-7,8-dihydroguanine (β = 1.13, 95 % CI: 0.32, 1.94), and CYA and 8-hydroxy-2′-deoxyguanosine (β = 0.87, 95 % CI: 0.22, 1.53) were observed in students (p < 0.01), indicating long-term chronic exposure to these chemicals may induce molecular damage to nucleic acids. Our findings provide compelling evidence that frequent use of melamine tableware continues to be a potential threat to human health.

Calculation of continuous reference intervals for biological parameters exhibiting strong age-dependent level changes: Its application to glycosaminoglycans and sialic acid in urine.

Glycosaminoglycan (GAG) and sialic acid (total and free) assays are used as first-line screening tests for the diagnosis of mucopolysaccharidoses and glycoproteinoses, respectively. There is a pronounced age-dependent variation in the urinary concentrations of these metabolites in the normal population, and the stratification of the reference values into discrete age ranges may lead to an undesirably high number of false-positive or false-negative results. The aim of this study was to design a method for calculating continuous reference intervals as a function of age and its application to the analysis of GAGs and sialic acid (total, free, and conjugated) in urine. In the postpubertal period, concentrations of urinary GAGs and sialic acid have reached a plateau, so a traditional calculation of the reference range in this specific age group was considered appropriate. In the prepubertal period, a nonlinear regression performed with the Excel add-in Solver was used to fit the logarithmized concentrations of the controls to a curve that represents the mean values as a function of age. A uniform distribution of the residuals was obtained, which allowed the calculation of the reference intervals by adding the values of their 2.5 and 97.5 percentiles to the independent variable of the regression curve to calculate the upper and lower reference curves. The main advantages of the developed method are (1) a reduction in the number of control samples needed to obtain adequate reference intervals and (2) an improvement in the reliability of diagnostic screening by reducing the uncertainty generated by the gaps in the traditional age-stratified method.

Association of volatile organic compound exposure and metabolic syndrome

The cumulative toxicity of volatile organic compounds (VOCs) cause many medical diseases. We analyzed the evidence of association between VOCs and risk of metabolic syndrome in the Korean population using 1,771 participants from the 2023 National Health and Nutrition Examination Survey. The creatinine-corrected urinary concentrations of BMA, 2-MHA, PGA, SPMA, 3-HPMA, BPMA and DHBMA were higher in the metabolic syndrome group than in the non-metabolic syndrome group. Urine N-Acetyl-S-(phenyl)-L-cysteine (SPMA) levels were significantly associated with metabolic syndrome after adjusting for confounders (odds ratio: 1.71). 2-MHA (OR 1.29, P=0.035) and SPMA (OR 2.84, P<0.001) were associated with the risk of elevated FBG impairment and SPMA (OR 1.57) was positively connected with the high blood pressure (P=0.016). In conclusion, the findings indicated significant association between the metabolic syndrome and a number of VOCs. Among them, there was a substantial positive correlation between the urinary SPMA levels and metabolic syndrome.

Exposure of young German adults to the anti-dandruff agent climbazole from 2002 to 2022: Analysis of specific biomarkers in urinary samples

The fungicide climbazole is mainly used as an anti-dandruff (AD) agent in cosmetics, such as shampoos or other hair care products. Consequently, an exposure of the general population seems likely because many people suffer from dandruff. We have analyzed urine samples from the German Environmental Specimen Bank (ESB) for two specific climbazole biomarkers, namely (OH)2-climbazole and cx-OH-climbazole, in samples collected in the years 2002, 2007, 2012, 2017 and 2022. (OH)2-Climbazole was determined diastereoselectively, hence three analytes are discussed ((OH)2-climbazole 1, (OH)2-climbazole 2 and cx-OH-climbazole). The study population consisted of 300 students (150 male, 150 female) aged between 20 and 29 at the time of sampling from Halle/Saale in Germany. Most samples under scrutiny did not contain any climbazole metabolites in levels above the limit of quantification (LOQ, 0.5 μg/L for either analyte), only in 16 samples at least one analyte could be quantitated. Even the sample with the highest metabolite concentrations (10.23 μg/L (OH)2-climbazole and 2.53 μg/L cx-OH-climbazole) barely reached the urinary concentrations found in an excretion kinetics study after the typical application of a climbazole-containing shampoo in three volunteers. As a result, estimated daily intakes (max. 1.8 μg/kg bw/d) lay below the subchronic NOAEL (15 mg/kg bw/d) and NOEL (5 mg/kg bw/d) by a factor of more than 8300 and 2700, respectively. The evaluation of the climbazole burden of the general population gives valuable insights for the authorities on the effect of legal restrictions.

Can Acetylation of Lysine 282 of Aquaporin 3 Improve Urinary Concentration in Mice with Lithium-Induced Nephrogenic Diabetes Insipidus?

Can Acetylation of Lysine 282 of Aquaporin 3 Improve Urinary Concentration in Mice with Lithium-Induced Nephrogenic Diabetes Insipidus?

Evaluation of Antiurolithiatic Effects of Moringa oleifera Lam. Leaves Extract: In-vitro, in-silico and in-vivo Approaches.

Objective: Moringa oleifera Lam. (Moringaceae), has traditionally been used for various renal diseases including urolithiasis. Considering the therapeutic and nutritional values, the present study was designed to investigate the antiurolithiatic potential of M. oleifera leaves through in-vitro, in-silico and in-vivo approaches. Methods: Methanolic aqueous extract of M. oleifera. leaves (MoL.Cr) was prepared and screened for phytoconstituents through FTIR and HPLC analysis, while antioxidant potential was determined by DPPH assay. Crystal nucleation, aggregation and growth assays were carried out to ascertain the in-vitro inhibitory effects of MoL.Cr. Molecular docking was performed to analyze the interactions between phytoconstituents and targeted proteins (Glycolate oxidase, Albumin and Tamm-Horsfall). Whereas, ethylene glycol-induced urolithiasis model (1% ammonium chloride +0.75% ethylene glycol) was used for in-vivo study. Presence of alkaloids, phenols, glycosides and flavonoids was confirmed by FTIR and HPLC analysis. Results: MoL.Cr significantly inhibited the CaOx crystal nucleation, aggregation as well as growth and normalized urinary and serum parameters. Histological studies showed that MoL.Cr significantly restored hyperoxaluria-induced irregular epithelial lining, interstitial inflammation and dilated proximal tubules. Conclusions: Thus, M. oleifera demonstrated marked stone inhibiting potential which can be due to its antioxidant, lowering of urinary concentration of stone forming constituents and anti-crystallization effects.

Use of multiparametric MRI to noninvasively assess iodinated contrast-induced acute kidney injury

PurposeTo gauge the utility of multiparametric MRI in characterizing pathologic changes after iodinated contrast-induced acute kidney injury (CI-AKI) in rats. MethodsWe randomly grouped 24 rats injected with 8 g iodine/kg of body weight (n = 6 each) and 6 rats injected with saline as controls. All rats underwent T1, T2 mapping and diffusion kurtosis imaging (DKI) after contrast injection at 0 (control), 1, 3, 7, 13 days. T1, T2, and mean kurtosis (MK) values were performed in renal outer/inner stripes of outer medulla (OSOM and ISOM) and cortex (CO), and their diagnosis performance for CI-AKI also been evaluated. Serum creatinine (SCr), insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor metalloproteinase 2 (TIMP-2), aquaporin-1 (AQP1), α-smooth muscle actin (α-SMA), and histologic indices were examined. ResultsCompared with controls, urinary concentrations of both TIMP-2 and IGFBP7 were obviously elevated from Day 1 to Day 13 (all p < 0.05). T2 values were significantly higher than control group for Days 1 and 3, and T1 and MK increased were more remarkable at all time points (Days 1–13) in CI-AKI (all p < 0.05) than control group. Changes in T1 and MK strongly correlated with renal injury scores of all anatomical compartments and with expression levels of AQP1 and moderately correlated with α-SMA. Changes in T2 values correlating moderately with renal scores of CO, ISOM and OSOM and AQP1. The MK obtained the highest area under the receiver operating characteristic (ROC) curve of 0.846 with a sensitivity of 70.8 % and specificity of 88.9 %. ConclusionsCombined use of multiparametric MRI could be a valid noninvasive method for comprehensive monitoring of CI-AKI. Among these parameters, MK may achieve the best diagnostic performance for CI-AKI.

Safety, pharmacokinetics, and food-effect of pivmecillinam after single- and multiple-dose in healthy Chinese subjects: a phase I study.

Urinary tract infection (UTI) is one of the most prevalent bacterial infectious diseases worldwide. However, the resistance of urinary pathogens to other UTI antibiotics such as trimethoprim and trimethoprim/sulphamethoxazole increased. Pivmecillinam is a prodrug of mecillinam, which is effective for the treatment of urinary tract infections. The purpose of this study was to assess the safety, and pharmacokinetics of pivmecillinam and mecillinam after single- and multiple-dose oral administration of pivmecillinam tablets in healthy Chinese subjects. The study also investigated the profile of urinary excretion of mecillinam, as well as the effect of food and gender on the pharmacokinetics of pivmecillinam and mecillinam. This study was a single-center, open-label phase I study carried out in three groups. In total, 34 subjects were included in the study: group 1-food effect study with pivmecillinam 200mg (n = 12); group 2-single- and multiple-dose study with pivmecillinam 400mg (n = 12); group 3-single dose study with pivmecillinam 600mg (n = 10). The plasma and urine concentrations of pivmecillinam and mecillinam were measured, and their pharmacokinetics were calculated. Treatment-emergent adverse events were evaluated and recorded in safety assessments for three groups. No severe adverse events were found in this study. After a single dose of pivmecillinam was taken orally, the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) of pivmecillinam increased in a dose-proportional manner, nor did mecillinam. Food had significant effects on Cmax and AUC0-t of pivmecillinam and Cmax of mecillinam. The mean cumulative percentage of urine excretion of mecillinam at 0 to 24h ranged from 35.5 to 44.0%. Urinary cumulative excretion is relative to the drug dose, but the diet and multiple-dose administration did not affect the urinary cumulative excretion rate. The safety and pharmacokinetics of pivmecillinam and mecillinam after single- (200/400/600mg) or multiple-dose (400mg) administration were demonstrated in healthy Chinese subjects. Food affected the pharmacokinetics of pivmecillinam and mecillinam.

Dietary protein intake and the tubular handling of indoxyl sulfate.

Chronic kidney disease (CKD) patients are advised to limit their protein intake. A high protein diet is known to induce glomerular hyperfiltration, as well as hypertrophy of the remnant kidney, and glomerulosclerosis. Whether the diet causes changes in kidney tubule transport via gut microbiome metabolites is still unknown. We hypothesized that protein intake affects not only the intestinal generation and absorption, but also the kidney disposal of microbial amino acid metabolites. We combined data from animal models and human studies. 5/6th nephrectomy rats were administered a high (HP) or low-protein (LP) diet for 7 weeks. Plasma and urine concentration of the uremic toxins (UTs) indoxyl sulfate (IS), p-cresyl sulfate (PCS), and p-cresyl glucuronide (PCG) were measured. Their fractional excretion (FE) was calculated. The expression of kidney membrane transporters OAT1, OAT3, BCRP, OCT2 and MRP4 was analyzed. Differences in FE of UTs between individuals with higher and lower protein intake in two CKD cohorts were sought. CKD rats on an HP diet showed increased plasma levels of PCS and PCG but not IS compared to rats on a LP diet. Conversely, urinary excretion and FE of IS were higher in the HP CKD group. BCRP, MRP4 and OCT2 were not influenced by the diet. OAT1 and OAT3 were upregulated in the HP CKD group. In two independent cohorts of CKD patients, individuals with a high dietary protein intake showed a significantly higher FE of IS. A HP diet leads to a higher generation and/or absorption of aminoacid-derived UT precursors in CKD rodent models and humans, most likely via gut microbiome modulation. We demonstrate that dietary protein intake modulates transcription and expression of OAT1 and OAT3, corroborating the existence of the remote sensing and signaling hypothesis. Dietary protein intake influences kidney physiology beyond glomerular filtration.

Trends in NHANES Biomonitored Exposures in California and the United States following Enactment of California's Proposition 65.

The prevalence of toxic chemicals in US commerce has prompted some states to adopt laws to reduce exposure. One with broad reach is California's Proposition 65 (Prop 65), which established a list of chemicals that cause cancer, developmental harm, or reproductive toxicity. The law is intended to discourage businesses from using these chemicals and to minimize consumer exposure. However, a key question remains unanswered: Has Prop 65 reduced population-level exposure to the listed chemicals? We used national biomonitoring data from the Centers for Disease Control and Prevention (CDC) to evaluate the impact of Prop 65 on population-level exposures. We evaluated changes in blood and urine concentrations of 37 chemicals (including phthalates, phenols, VOCs, metals, PAHs, and PFAS), among US National Health and Nutrition Examination Survey (NHANES) participants in relation to the time of chemicals' Prop 65 listing. Of these, 11 were listed prior to, 11 during, and 4 after the biomonitoring period. The remaining 11 were not listed but were closely related to a Prop 65-listed chemical. Where biomonitoring data were available from before and after the date of Prop 65 listing, we estimated the change in concentrations over time for Californians compared with non-Californians, using a difference-in-differences model. We used quantile regression to estimate changes in exposure over time, as well as differences between Californians and non-Californians at the 25th, 75th, and 95th percentiles. We found that concentrations of biomonitored chemicals generally declined nationwide over time irrespective of their inclusion on the Prop 65 list. Median bisphenol A (BPA) concentrations decreased 15% after BPA's listing on Prop 65, whereas concentrations of the nonlisted but closely related bisphenol S (BPS) increased 20% over this same period, suggesting chemical substitution. Californians generally had lower levels of biomonitored chemicals than the rest of the US population. Our findings suggest that increased scientific and regulatory attention, as well as public awareness of the harms of Prop 65-listed chemicals, prompted changes in product formulations that reduced exposure to those chemicals nationwide. Trends in bisphenols and several phthalates suggest that manufacturers replaced some listed chemicals with closely related but unlisted chemicals, increasing exposure to the substitutes. Our findings have implications for the design of policies to reduce toxic exposures, biomonitoring programs to inform policy interventions, and future research into the regulatory and market forces that affect chemical exposure. https://doi.org/10.1289/EHP13956.

Direct Contact Membrane Distillation of Artificial Urine and Its Application in Plasticizing Lunar Regolith

Direct Contact Membrane Distillation (DCMD) uses low heat sources to separate water from urea, which was then used as a plasticizer in regolith-based cement to make it more workable. The work investigated separating potable water and urea from artificial urine using DCMD and then characterizing the products. Water was successfully separated from the artificial urine solution as characterized by density, conductivity, pH, and substance concentrations. The concentrated urine solution was used in regolith-based cement cured under vacuum at temperatures that simulated temperatures that would be expected in construction on the Moon. Workability and other properties were improved by replacing water with concentrated urine solution in the mix.

Phthalate Exposure and Pediatric Asthma: A Case Control Study Among Egyptian Children

Background: Phthalates, which are diesters of phthalic acid, are commonly used as plasticizers and additives in various consumer products. Several phthalates have been identified as substances of high concern. Exposure to phthalate esters (PAEs) has been linked to asthma in children, but the specific impacts of PAEs on asthmatic children were not well understood. Objective: The objective of this study was to compare urinary phthalate concentrations in asthmatic and non-asthmatic children and to identify potential sources of exposure as risk factors for asthma. Methods: A case control study was conducted for 100 Egyptian children aged 8-16 years (50 asthmatics and 50 healthy controls). Asthma was identified using GINA guidelines. Socio-demographic and probable risk factors were assessed, in addition to measuring phthalate levels in urine samples using high-performance liquid chromatography. Results and conclusion: Mean urinary Mono-methyl as well as Mono-benzyl levels were highly significant in asthmatic children compared to control group (895.26ng/ mL vs 548.55 ng/mL and 13.5 ng/mL vs 2.07 ng/mL respectively) (p= 0.001). The number of asthmatic children living in houses painted with non-plastic paint was significantly lower (P&lt;0.05) than children living in houses painted with other paints. No association between floor type and asthma was reported. The frequent use of personal care products and plastic painting of walls were identified by multiple logistic regression analysis as the highly significant predictors of asthma in the studied subjects. The declared higher levels of urinary phthalate metabolites (Mono-methyl and Mono-benzyl) in Egyptian asthmatic children may reveal the probable risk of phthalate exposure in triggering bronchial asthma.

Application of Surface Plasmon Resonance Imaging Biosensors for Determination of Fibronectin, Laminin-5, and Type IV Collagen in Plasma, Urine, and Tissue of Renal Cell Carcinoma.

Laminin, fibronectin, and collagen IV are pivotal extracellular matrix (ECM) components. The ECM environment governs the fundamental properties of tumors, including proliferation, vascularization, and invasion. Given the critical role of cell-matrix adhesion in malignant tumor progression, we hypothesize that the concentrations of these proteins may be altered in the plasma of patients with clear cell renal cell carcinoma (ccRCC). This study aimed to evaluate the serum, urine, and tissue levels of laminin-5, collagen IV, and fibronectin among a control group and ccRCC patients, with the latter divided into stages T1-T2 and T3-T4 according to the TNM classification. We included 60 patients with histopathologically confirmed ccRCC and 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Collagen IV, laminin-5, and fibronectin were detected using Surface Plasmon Resonance Imaging biosensors. Significant differences were observed between the control group and ccRCC patients, as well as between the T1-T2 and T3-T4 subgroups. Levels were generally higher in plasma and tissue for fibronectin and collagen IV in ccRCC patients and lower for laminin. The ROC (Receiver operating characteristic) analysis yielded satisfactory results for differentiating between ccRCC patients and controls (AUC 0.84-0.93), with statistical significance for both fibronectin and laminin in plasma and urine. Analysis between the T1-T2 and T3-T4 groups revealed interesting findings for all examined substances in plasma (AUC 0.8-0.95). The results suggest a positive correlation between fibronectin and collagen levels and ccRCC staging, while laminin shows a negative correlation, implying a potential protective role. The relationship between plasma and urine concentrations of these biomarkers may be instrumental for tumor detection and staging, thereby streamlining therapeutic decision-making.

Development of an LC-HRMS non-targeted method for comprehensive profiling of the exposome of nicotine and tobacco product users – A showcase for cigarette smokers

The global prevalence of electronic cigarettes, heated tobacco products, and other smokeless alternatives has grown significantly in the last ten years. These products have been suggested as combustion-free alternatives for conventional tobacco products like cigarettes, aiming to reduce the negative health impacts associated with smoking. However, the impact of those products on the health and safety of the general population are still unclear, as the absolute exposure from those products has not been thoroughly studied, yet. In this project, a non-targeted LC-HRMS method was developed comprising four different analytical modes for the investigation of the exposure profile in urine of the product users. The method is characterized by its high sensitivity and reproducibility, as shown during method validation. As a proof of concept, we first applied this method to detect significant differences in biomarkers of exposure (BoEs) between smokers and non-smokers. We observed a total of 171 BoEs significantly elevated in smokers, including several well-known biomarkers of smoke exposure like nicotine and its metabolites, mercapturic acid derivatives, and phenolic compounds. Some of the detected biomarkers are present at low ng/mL concentrations in urine, proving the high sensitivity needed for a holistic exploration of the exposome. Moreover, we were able to identify BoEs that have not been reported previously for smoking, such as 2,6-dimethoxyphenol and 7-methyl-1-naphthol glucuronide.

Exploring the association between urinary bisphenol A, S, and F levels and semen quality parameters: Findings from Led-Fertyl cross-sectional study

Infertility is recognized as a multifaceted condition affecting approximately 15% of couples globally, influenced by various factors including genetic predisposition and environmental exposures. Among these environmental factors, bisphenol A (BPA) emerges as a prominent Endocrine-disrupting chemical (EDCs) widely distributed, leading to chronic human exposure in daily life. As regulations on BPA became more stringent, alternative substances such as bisphenol S (BPS) and bisphenol F (BPF) have emerged. Animal studies have demonstrated a dose-dependent decline in fertility and embryotoxicity following chronic exposure to BPA. However, literature data on human studies are limited and heterogeneous. Additionally, even less is known about the relationship between exposure to the BPA analogues (BPS and BPF) and sperm quality. Therefore, the present study aimed to examine the association between urinary concentrations of BPA, BPF, and BPS and semen quality parameters among 195 adult Spanish men from the Led-Fertyl study cohort using multiple linear regression models adjusted by potential confounding variables. Our results revealed an inverse association between log-transformed creatinine-adjusted concentration (ng/mg) of BPA and BPF levels and the percentage of sperm vitality (β: 3.56 %; 95%CI: 6.48 to −0.63 and β: 4.14 %; 95%CI: 6.97 to −1.31; respectively). Furthermore, participants in the highest quartile of BPA and BPF urinary concentration exhibited lower sperm vitality compared to those in the lowest quartile (β: 6.90 %; 95%CI: 11.60 to −2.15 and β: 9.68 %; 95%CI: 14.43 to −4.94; respectively). These results supply epidemiological evidence establishing a relationship between bisphenols urine exposure and sperm quality, suggesting that a re-evaluation of the overall safety of BPA alternatives is warranted.

Association of multiple urinary metals/metalloids with obesity defined by body fat percentage: A cross-sectional study among Guangxi Zhuang ethnic in China

BackgroundPrevious studies confirmed a link between urinary metals/metalloids and obesity; however, the majority of these studies defined obesity using body mass index (BMI) or waist circumference (WC), and their results were not constantly consistent. Studies defining obesity based on body fat percentage (BFP) is less reported. MethodsA total of 5405 participants aged 35–74 from Guangxi Zhuang ethnic group in China were included in the analysis. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the concentrations of 22 metals/metalloids in urine. Using a binary logistic regression model, the impact of individual metal/metalloid on the risk of BFP/obesity was analyzed, and the LASSO regression model was employed to choose metals/metalloids independently related with BFP/obesity to construct a multiple-metal models. The quantile g-computation model was used to evaluate the combined impacts of metals/metalloids on BFP/obesity. ResultsIn multiple-metal models, compared with the lowest quartile, the highest quartile of urinary concentrations of Mg, Cd, and Ti was significantly associated with a reduced risk of BFP/obesity (Mg: OR=0.66, 95 %CI: 0.51, 0.85; Cd: OR=0.63, 95 %CI: 0.49, 0.82; Ti: OR=0.73, 95 %CI: 0.57, 0.93). Conversely, the highest quartiles of urinary concentrations of Zn, V, and Sb was significantly associated with an increased risk of BFP/obesity (Zn: OR=1.75, 95 %CI: 1.39, 2.22; V: OR=1.63, 95 %CI: 1.25, 2.14; Sb: OR=1.38, 95 %CI: 1.06, 1.79). In quantile g-computation analysis, Mg, Cd, and Sn were the main contributors to negative effects, while Zn, V, and Sb were the main contributors to positive effect, although no significant relationship was observed between the multiple metal/metalloid mixtures and BFP/obesity. ConclusionsAccording to our study, urinary Mg, Cd, and Ti levels were negatively associated with BFP/obesity risk, and Zn, V, and Sb levels were positively associated with BFP/obesity risk. However, these associations need to be further verified by longitudinal studies, and the molecular mechanisms need to be further explored by animal and cell experiments.

Assessment of brain-derived neurotrophic factor and irisin concentration in children with chronic kidney disease: a pilot study

Patients suffering from chronic kidney disease (CKD) are particularly placed at risk of multiorgan complications. One of them is malnutrition, which adds up to a higher mortality factor among them. This study was designed to determine the usefulness of brain-derived neurotrophic factor (BDNF) and irisin assays in the assessment of CKD development. The study group included 28 children with CKD at stages 2-5 treated conservatively. The outcome of our study revealed decreased serum BDNF and irisin levels in CKD patients, whereas urine concentrations were increased for BDNF and decreased for irisin, comparing to healthy controls. There was a positive correlation between anthropometric measures and urine BDNF concentration, as well as anthropometric measures and both serum and urine irisin levels in the study group, however no dependence of the tested markers on the stage of CKD was observed. In recent years, a role of myokines was described as vital for maintaining metabolic homeostasis therefore we suspect a potential role of these multifaceted markers in detecting malnutrition in CKD children.

Effect of age, sex, and chronic kidney disease on urinary creatinine excretion in Japanese patients.

Urinary creatinine levels are used to estimate the excretion rates of certain analytes from the respective analyte-to-creatinine ratios. We clarified the influence of age and sex on estimated daily urinary creatinine excretion (eUCrE) based on the urinary creatinine level and daily urine volume. All inpatients aged ≥ 18years who attended the Kochi Medical School Hospital with serum and urinary creatinine measurement results were enrolled. Serum and urinary creatinine concentrations were extracted from the database and fluctuations with sex and age were investigated. The eUCrE was calculated for patients with early morning spot urine protein excretion (UPE), and daily urine volume was measured on the same day. Overall, 643 participants (322 men, 321 women) were enrolled. The eUCrE levels of men and women aged 18 - 64 and 18 - 44years, respectively, significantly exceeded 1g/day. Those of women aged 65-74 and ≥ 75years were significantly lower than 1g/day. Each age group was further categorised into Groups A (patients with eGFR ≥ 30mL/min/1.73 m2 and UPE < 0.5g/gCr), B (eGFR ≥ 30mL/min/1.73 m2 and UPE ≥ 0.5g/gCr), and C (eGFR < 30mL/min/1.73 m2 and UPE ≥ 0.5g/gCr). The eUCrE levels were the highest in Group A, followed by Groups B and C. This study revealed age-, sex-, and renal function-related biases in adjusted values using urinary biomarkers, including proteinuria and creatinine ratio.

Association of maternal thyroglobulin with gestational thyroid function and offspring IQ and brain morphology.

Low maternal urinary iodine concentration (UIC) during pregnancy is associated with adverse offspring neurodevelopment. Thyroglobulin (Tg) has been suggested as a more sensitive biomarker than UIC of long-term iodine status, but associations of Tg with neurodevelopment and the possible mediating role of thyroid function remain unknown. To study whether maternal Tg is associated with i) maternal and newborn thyroid function and ii) offspring IQ and brain morphology. Participants were selected from two population-based prospective cohorts: Generation R (the Netherlands, iodine-sufficient) and INfancia y Medio Ambiente (Spain, mildly iodine-deficient) with maternal Tg and thyroid function data in the first half of pregnancy or in cord blood, early childhood IQ (age 4.5 and 6 years), late childhood IQ (age 9 and 13), or brain morphology at 10 years. Associations of Tg with TSH, FT4, IQ and brain morphology were studied with multivariable linear regression. i) Tg was associated with lower TSH (-0.12[-0.16; -0.08]) and higher FT4 (0.08[0.05;0.12]) in pregnancy (N=4,367), but not with cord blood TSH or FT4 (N=2,008). ii) Tg was associated with lower IQ in early childhood (β[95% CI]:-0.06 [-0.10; -0.01], N=2,919), but not with IQ (N=2,503) or brain morphology (N=1,180) in later childhood. None of the associations of Tg with the studied outcomes differed by the iodine-to-creatinine ratio (i.e. effect modification) or changed when adjusted for thyroid function. Higher Tg is associated with lower IQ in early childhood and higher thyroid function during pregnancy, but not with IQ or brain morphology in later childhood. Further research should determine the value of Tg in addition to UIC for defining iodine status.

Pilot study: Unveiling the impact of bisphenol A and phthalate exposure on women with asthma.

Endocrine disruptors are considered estrogenic disruptors, and recent researches suggested that they may have a link to the severity of asthma. We aim to validate the correlation between endocrine disruptors and various clinical measurements of asthma, depending on the menopausal status. A pilot case-control study was performed in female asthmatic patients who visited allergy clinic in SMG-SNU Boramae Medical Center. Medical information and the urinary concentrations of 4 endocrine disruptors on their first visit were collected and analyzed: bisphenol A, mono (2-ethyl-5-hydroxyhexyl) phthalate, mono (2-ethyl-5-oxohexyl) phthalate, and mono-n-butyl phthalate. A total of 35 female participants enrolled in the study, including 20 asthmatic patients and 15 healthy controls. The average concentrations of urinary endocrine disruptors in patient and control group did not demonstrate significant differences. Twenty asthmatic patients were divided into 2 groups according to their menstrual state. Using the Spearman rank correlation test in premenopausal asthmatic patients (n = 7), we found negative correlations between urinary concentration of mono-n-butyl phthalate and asthma control test score, as well as postbronchodilator forced expiratory flow at 25% to 75% of forced vital capacity (P-value = .007 and .04, respectively). In contrast, it did not show any correlation with asthma control test or postbronchodilator forced expiratory flow at 25% to 75% of forced vital capacity (P-value = 1.00 and .74, respectively) in postmenopausal group (n = 13). Endocrine disruptors might have an impact on the decline of small airway function and asthma management among premenopausal, but not postmenopausal, female asthmatic patients.