Multiple Urine Samples Research Articles

Gestational phthalate exposure and behavioral problems in preschool-aged children with increased likelihood of autism spectrum disorder

BackgroundExperimental studies have shown associations between gestational phthalate exposure and behavioral problems among offspring; however, epidemiological evidence is still mixed. This study aims to investigate whether gestational phthalate exposure is associated with behavioral problems in preschool-aged children. MethodsParticipants include 178 mother-child pairs from MARBLES (Markers of Autism Risk in Babies – Learning Early Signs), a cohort with high familial likelihood of autism spectrum disorder (ASD). We quantified 14 phthalate metabolites in multiple maternal urine samples collected during the 2nd and 3rd trimesters. Preschool behavior problems were assessed using the Child Behavioral Checklist (CBCL), a standardized instrument for evaluating behavior problems of children aged 1.5–5 years. To examine associations of CBCL scores with both individual phthalate biomarker concentrations and their mixture, we used negative binomial regression and weighted quantile sum regression. ResultsOverall, maternal phthalate biomarker concentrations were not associated with child behavior problems. Monoisobutyl phthalate (MiBP) concentrations were inversely associated with child anxious/depressed symptoms and somatic complaints. Mono-hydroxy-isobutyl phthalate (MHiBP) and monobenzyl phthalate (MBzP) were also inversely associated with somatic complaints. When assessing trimester-specific associations, more behavior problems were associated with the 2nd trimester biomarker concentrations: mono(3-carboxypropyl) phthalate (MCPP) and monocarboxyisononyl phthalate (MCNP) were positively associated with somatic complaints. All associations became non-significant after false discovery rate correction. No association between a mixture of phthalates and CBCL scores was found. ConclusionsOur study observed no clear evidence of gestational phthalate exposure on child behavior problems. However, our findings based on the biomonitoring assessment of multiple samples per participant could improve our understanding of gestational phthalate exposure in association with behavior problems in preschool-aged children.

Pharmacokinetics of single-dose rivaroxaban under fed state in obese vs. non-obese subjects: An open-label controlled clinical trial (RIVOBESE-PK).

The evidence of rivaroxaban's pharmacokinetics in obese compared with non-obese populations remains inconclusive. We aimed to compare the pharmacokinetic profile of rivaroxaban between obese and non-obese populations under fed state. Participants who met the study's eligibility criteria were assigned into one of two groups: obese (body mass index ≥35 kg/m2) or non-obese (body mass index 18.5-24.9 kg/m2). A single dose of rivaroxaban 20 mg was orally administered to each participant. Nine blood samples over 48 h, and multiple urine samples over 18 h were collected and analyzed for rivaroxaban concentration using ultra-performance liquid chromatography coupled with tandem mass detector. Pharmacokinetic parameters were determined using WinNonlin software. Thirty-six participants were recruited into the study. No significant changes were observed between obese and non-obese participants in peak plasma concentration, time to reach peak plasma concentration, area under the plasma concentration-time curve over 48 h or to infinity, elimination rate constant, half-life, apparent volume of distribution, apparent clearance, and fraction of drug excreted unchanged in urine over 18 h. Rivaroxaban's exposure was similar between the obese and non-obese subjects, and there were no significant differences in other pharmacokinetic parameters between the two groups. These results suggest that dose adjustment for rivaroxaban is probably unwarranted in the obese population.

Estimation of glyphosate biological half-life among farmers and residents in Thailand

Glyphosate is a widely used herbicide worldwide. Research on human health effects has been limited and the toxicokinetics of glyphosate have not been widely examined. This research aimed to study the excretion profile and half-life of glyphosate in farmers and residents who use glyphosate to control weeds in their agricultural fields and near their households, respectively. Multiple spot urine samples per day were collected from the participants for 3 consecutive days after spraying glyphosate. The participants were interviewed about general characteristics, planting activities, glyphosate use, and their health problems related to glyphosate use. Glyphosate concentrations in urine samples were determined by HPLC with a fluorescence detector. The average age of residents (56.4 years) was significantly higher than that of farmers (45.5 years). The glyphosate excretion profile of most participants showed a gradual decline in glyphosate concentrations, but with or without additional exposures some of the profiles showed a jagged pattern of decline. The average urinary half-life of glyphosate in all participants was 24.58 h (95% CI: 18.43–30.73) and 20.95 h (95%CI: 16.85–25.05) for creatinine adjusted and non-adjusted measurements, respectively. The urinary glyphosate half-life measurements among the residents and farmers were not significantly different.

Exposure to chlorpyrifos and pyrethroid insecticides and symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in preschool children from the Odense Child Cohort

BackgroundAttention Deficit Hyperactivity Disorder (ADHD) is a common childhood psychiatric disorder with severe and lifelong impact on mental health and socioeconomic achievements. Environmental factors may play a role in the increasing incidens rates. Previous studies on associations between prenatal and childhood exposure to organophosphate and pyrethroid insecticides and ADHD symptoms have yielded mixed findings. ObjectivesTo investigate associations between prenatal and childhood exposure to chlorpyrifos and pyrethroids and ADHD symptoms in 5-year-old children from the Odense Child Cohort. MethodsSpot urine samples from pregnant women in gestational week 28 (n = 614) and offspring at 5 years of age (n = 814) were collected and analyzed for the specific metabolite of chlorpyrifos, TCPY (3,5,6-trichloro-2-pyridinol), as well as the generic pyrethroid metabolite, 3-PBA (3-phenoxybenzoic acid). Offspring ADHD symptoms were assessed at age 5 years using the parent reported “ADHD scale” from the “Child Behavior Checklist 1½-5” (n = 1114). Associations between insecticide exposure variables and an ADHD score ≥90th percentile were analyzed using logistic regression for all children and stratified by sex. ResultsMost pregnant women had detectable concentrations of 3-PBA (93%) and TCPY (91%) with median concentrations of 0.20 μg/L and 1.62 μg/L, respectively. In children, 3-PBA and TCPY concentrations were detectable in 88% and 82% of the samples, and the median concentrations were 0.17 and 1.16 μg/L. No statistically significant associations were observed between insecticide metabolites and an ADHD score ≥90th percentile at age 5. ConclusionIn this relatively large Danish birth cohort study with mainly low dietary insecticide exposure, we found no statistically significant associations between prenatal or childhood exposure to chlorpyrifos or pyrethroids, and excess ADHD-symptom load, in 5-year-old children. Prospective studies with multiple urine samples across vulnerable windows of neurodevelopment is warranted to improve assessment of safe exposure levels, which is particularly relevant for pyrethroids, since their use is increasing.

Concentrations of neonicotinoid insecticides and their metabolites in multiple urine samples collected from pregnant women in Japan

Exposure to low doses of neonicotinoid (NEO) insecticides during pregnancy may have a negative impact on the neurodevelopment of children. Biomarkers are frequently used to investigate the exposure and its health effects in environmental epidemiology. In the present study, we aimed to evaluate the utility of urinary biomarkers of NEO exposure by calculating intra-class correlation coefficients (ICCs). Urine samples were collected from 30 pregnant women who were non-smokers and living in a central part of Japan, between 12 and 22 weeks of gestation. We collected first morning voided (FMV) urine and afternoon spot (PM) urine samples on the same day on five occasions within a 2-week period. The urinary concentrations of NEO and their metabolites (NEO/m) were measured by liquid chromatography–tandem mass spectrometry. Normalisation to the specific gravity and creatinine concentration was used in the calculation of ICC. The number of urine samples required to obtain a reliable biomarker estimate of NEO exposure was calculated. The most frequently detected NEO/m was N-desmethyl-acetamiprid (N-dm-ACE), followed by clothianidin (CLO), thiamethoxam (THX) and dinotefuran (DIN), in both FMV and PM urine samples. The ICC calculations showed poor reproducibility for the measurement of CLO and THX concentrations (ICCs ≤0.25) in both FMV and PM urine samples and for DIN (ICC ≤0.29) in the FMV urine samples, and moderate reproducibility was identified for N-dm-ACE (ICC >0.60) in both FMV and PM urine samples and for DIN (ICC >0.40) in the PM urine samples. A minimum of 1–19 spot urine samples per individual was required to provide a reliable biomarker estimate over a 2 week period. These results suggest that pregnant Japanese women are frequently exposed to NEOs, and that, with the exception of urinary N-dm-ACE, a single measurement of urinary NEO concentrations may not be an appropriate method of characterising overall exposure.

A fast and accurate colorimetric assay for quantifying hippuric acid in human urine

Hippuric acid is an abundant metabolite in human urine. Urinary hippuric acid levels change with toxic exposure to aromatic compounds, consumption of fruits and vegetables, cancers, chronic kidney disease, schizophrenia and Crohn's disease. While urinary hippuric acid can be detected and quantified via mass spectrometry or nuclear magnetic resonance spectroscopy, a colorimetric assay would be preferable for a low-cost, point-of care clinical assay. Two colorimetric methods, that use p-dimethylaminobenzaldehyde (DMAB) or benzenesulfonyl chloride (PhSO2Cl), respectively, have been previously developed to detect hippuric acid but these assays have many limitations. We replaced PhSO2Cl with p-toluenesulfonyl chloride (p-TsCl), to create a simpler, faster and more accurate method that works with human urine. This modified colorimetric assay detects from 60 μM to 1000 μM hippuric acid in urine in 2 min. We also corrected for the effects of interfering compounds present in urine such that the assay works across many urine backgrounds. We validated this improved assay on multiple hippurate-spiked urine samples, observing an excellent correlation (R2 > 0.94) between observed and known hippurate concentrations. These data suggest that this colorimetric assay is accurate and should greatly facilitate the measurement of hippuric acid in urine to detect a variety of human conditions.

Pharmacokinetic modelling of orally administered cannabidiol and implications for medication control in horses.

Cannabidiol (CBD) products gain increasing popularity amongst animal owners and veterinarians as an alternative remedy for treatment of stress, inflammation or pain in horses. Whilst the use of cannabinoids is banned in equine sports, there is limited information available concerning CBD detection times in blood or urine. The aim of this study was to determine the pharmacokinetic properties of CBD following oral administration in the horse to assist doping control laboratories with interpreting CBD analytical results. Part 1: dose escalation study: Single oral administration of three escalating doses of CBD paste (0.2 mg/kg, n = 3 horses; 1 mg/kg, n = 3; 3 mg/kg, n = 5) with >7 days wash-out periods in between. Part 2: multiple dose study: oral administration of CBD paste (3 mg/kg, n = 6) twice daily for 15 days. Multiple blood and urine samples were collected daily throughout both studies. Following study part 2, blood and urine samples were collected for 2 weeks to observe the elimination phase. Concentrations of CBD, its metabolites and further cannabinoids were evaluated using gas-chromatography/tandem-mass-spectrometry. Pharmacokinetic parameters were assessed via two approaches: population pharmacokinetic analysis using a nonlinear mixed-effects model and non-compartmental analysis. AUC0-12 h and Cmax were tested for dose proportionality. During the elimination phase, the CBD steady-state urine to serum concentration ratio (Rss) was calculated. Oral CBD medication was well-tolerated in horses. Based on population pharmacokinetics, a three-compartment model with zero-order absorption most accurately described the pharmacokinetic properties of CBD. High volumes of distribution into peripheral compartments and high concentrations of 7-carboxy-CBD were observed in serum. Non-compartmental analysis identified a Cmax of 12.17 ± 2.08 ng/mL after single administration of CBD (dose: 3 mg/kg). AUC0-12 h showed dose proportionality, increase for Cmax leveled off at higher doses. Following multiple doses, the CBD terminal half-life was 161.29 ± 43.65 h in serum. Rss was 4.45 ± 1.04. CBD is extensively metabolized and shows high volumes of tissue distribution with a resulting extended elimination phase. Further investigation of the potential calming and anti-inflammatory effects of CBD are required to determine cut-off values for medication control using the calculated Rss.

Prenatal exposure to triclosan assessed in multiple urine samples and placental DNA methylation

A previous study reported positive associations of maternal urinary concentrations of triclosan, a synthetic phenol with widespread exposure in the general population, with placental DNA methylation of male fetuses. Given the high number of comparisons performed in -omic research, further studies were needed to validate and extend on these findings. Using a cohort of male and female fetuses with repeated maternal urine samples to assess exposure, we studied the associations between triclosan and placental DNA methylation. We assessed triclosan concentrations in two pools of 21 urine samples collected among 395 women from the SEPAGES cohort. We used Infinium Methylation EPIC arrays to measure DNA methylation in placental biopsies collected at delivery. We performed a candidate study restricted to a set of candidate CpGs (n = 500) identified in a previous work as well as an exploratory epigenome-wide association study to investigate the associations between triclosan and differentially methylated probes and regions. Analyses were conducted on the whole population and stratified by child's sex. Mediation analysis was performed to test whether heterogeneity of placental tissue may mediate the observed associations. In the candidate approach, we confirmed 18 triclosan-associated genes when both sexes were considered. After stratification for child's sex, triclosan was associated with 72 genes in females and three in males. Most of the associations were positive and several CpGs mapped to imprinted genes: FBRSL1, KCNQ1, RHOBTB3, and SMOC1. A mediation effect by placental tissue heterogeneity was identified for most of the observed associations. In the exploratory analysis, we identified a few isolated associations in the sex-stratified analysis. In line with a previous study on male placentas, our approach revealed several positive associations between triclosan exposure and placental DNA methylation. Several identified loci mapped to imprinted genes.

SuPreme Study: a protocol to study the neuroprotective potential of sulfate among very/extremely preterm infants

IntroductionAntenatal maternal magnesium sulfate (MgSO4) administration is a proven efficacious neuroprotective treatment reducing the risk of cerebral palsy (CP) among infants born preterm. Identification of the neuroprotective component with target...

Comparative Evaluation between Visual and Automated Dipstick Urinalyses in Dogs

Urine test strips are commercially available and can be assessed with semi-automated analyzers or by visual assessment. This study aimed to compare the visual and automated evaluations of dipstick variables in canine urine samples. One hundred and nineteen urine samples were evaluated. Automated analysis was performed on a veterinary urine analyzer URIT-50Vet (URIT Medical Electronic) with UC VET13 Plus strips. Multistix 10 SG dipsticks (Siemens Healthcare GmbH, Erlangen, Germany) were used for visual evaluation, along with a refractometer (Clinical Refractometer Atago T2-Ne, Atago Co., Tokyo, Japan) for urine specific gravity measurements. A linear relationship was observed between the pH measurements (p = 0.2) of the two methods; the Passing-Bablok procedure was valid since neither proportional nor systematic significant errors were observed. Comparing the two methods, the correlation for urine specific gravity was poor (p = 0.01, CI 0.667-1.000). Moderate agreement was demonstrated for proteins (κ = 0.431), bilirubin (κ = 0.434) and glucose (κ = 0.450). Agreement was substantial for blood (κ = 0.620) and poor for leukocytes (κ = 0.100). Poor agreement was observed for ketones (κ = -0.006). Apart from the pH analysis, visual and automated dipstick urinalyses should not be used interchangeably. Multiple urine samples obtained from the same dog during the day should be evaluated using the same method to overcome erroneous results.

Endocannabinoid and perceived stress: Association analysis of endocannabinoid levels in hair versus levels in plasma and urine

The endocannabinoid system is considered to play a role in a wide range of functions, including stress. Hair analysis of endocannabinoids presents a promising methodological advancement for the retrospective assessment of long-term cumulative endocannabinoid secretion. Despite promising pilot study results suggesting the usefulness of hair endocannabinoid assessments, it remains unclear whether hair endocannabinoid levels mirror systemic endocannabinoid levels accurately. Two independent studies were conducted to investigate to what extent hair endocannabinoid and N-Acylethanolamine levels reflect the systemic levels retrospectively. Endocannabinoid and N-Acylethanolamine levels were measured in 3 cm and 1 cm hair segments respectively, and compared with the averaged levels in multiple plasma samples collected during three months (Study I), and in multiple 24-hour urine samples collected over a month (Study II). In addition, the Perceived Stress Scale was used to assess the perceived stress throughout the studies. Against our hypothesis, no association was found between the endocannabinoid or N-Acylethanolamine levels in hair and plasma or urine. However, hair palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and stearoylethanolamide (SEA) levels were positively correlated with perceived stress in Study I. The current findings suggest that hair endocannabinoid or N-Acylethanolamine levels might not accurately reflect the levels of peripheral circulating endocannabinoid or N-Acylethanolamine. Nevertheless, hair N-Acylethanolamine levels might emerge as a useful strategy in the study of some psychological phenotypes, such as stress.

Biomonitoring of DEET and DCBA in Canadian children following typical protective insect repellent use

N,N-diethyl-m-toluamide (DEET) is an ingredient found in many consumer insect repellents and its use is recommended to Canadians by government agencies, including Health Canada, for protection against insect bites including mosquitos and ticks. The majority of research on DEET exposure and toxicokinetics in humans has focused on adult populations with little information from vulnerable populations, including children. We aimed to fill this knowledge gap by examining real-world exposure data for DEET and its metabolite 3-diethylcarbamoyl benzoic acid (DCBA) in a sample population of Canadian children. We conducted a 24-h observational exposure human biomonitoring study at three overnight summer camps in Ontario, Canada through July and August 2019. Participating children aged 7-13 years provided multiple spot urine samples over a 24-h period and completed a journal to document insect repellent use and factors that could influence absorption of DEET. Children were instructed to use insect repellent as they usually would while attending a summer camp. Exposure was quantified using the information from the participant's journal and the change in the mass of their insect repellent containers over the course of the study. A total of 389 urine samples were collected from 124 children. Among participants using insect repellent, urinary levels of DEET were elevated between 2 and 8h post-application and decreased thereafter but remained qualitatively higher than concentrations in participants who did not use insect repellent on the study day, even at 18-22h post-application. DCBA was the predominant metabolite of DEET exposure in urine. DCBA was elevated between 8 and 14h post-application, and declined thereafter, but not to the level observed among those who did not use insect repellent on the study day. Children who used more insect repellent, or used higher concentration insect repellent (10%-30% DEET) excreted higher levels of DEET and DCBA. Excreted DEET and DCBA accounted for 0.001% (median) and 1.3% (median) of the estimated applied DEET, respectively. Children did not reach an undetectable level of DEET or DCBA in urine, even among those not using insect repellent during the study day, indicating a potentially complex multi-route exposure to insect repellents in a real world scenario. This work provides targeted biomonitoring data for children intentionally using DEET-based insect repellents for normal protective use, and will support the risk re-evaluation of DEET by Health Canada.

Validation of spot urine in estimating 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets in healthy adults

Purpose To evaluate the validity of spot urine assay methods in estimating the 24-h urinary sodium, potassium and sodium-to-potassium ratio during three different sodium diets. Materials and methods Twelve healthy volunteers were asked to adhere to 3 dietary sodium targets (3.3–5.0g/day,<3.3 g/day and >5.0 g/day) for three consecutive weeks and to measure salt excretion daily in spot urine samples using a self-monitoring device. On day 7 of each week, 24-h urine was collected to compare measured with estimated 24-h salt excretion (by the Kawasaki, Tanaka and INTERSALT equations). Results Correlation coefficients relating measured and estimated 24-h sodium excretion were low and not significant for Kawasaki and INTERSALT and moderate for the Tanaka equation (τ 0.56–0.64,p<.05). Bland–Altman plots showed considerable differences between estimated and measured sodium excretion across all salt diets. Over 40% of the participants showed an absolute difference between measured and estimated 24-h sodium of more than 1000 mg/day. The correlation coefficients between 24-h and spot Na/K ratio were 0.67, 0.94 and 0.85(p<.05), and mean differences were 0.59, 0.06 and 0.48 for the intermediate, low and high sodium diets, respectively. Conclusion These findings do not support estimation of individual 24-h salt excretion from spot urine by the Kawasaki, Tanaka, or INTERSALT formula.

Prenatal and current phthalate exposure and cognitive development in 7-year-old children from the Odense child cohort

BackgroundPhthalates are endocrine disrupters used in a variety of consumer products. Human studies suggest an association between phthalate exposure and cognitive development but adverse effects of the recently introduced phthalate substitutes have only been sparsely studied. ObjectivesTo investigate associations between prenatal and concurrent exposure to phthalates and IQ in 7-year-old children from the Odense Child Cohort. MethodsPregnant women from the Odense Child Cohort had phthalate metabolites measured in urine samples during 3rd trimester in 2010 to 2012. In addition, phthalates were also measured in urine samples from their offspring at age 7 years. IQ was assessed at age 7 years using four subtests from Wechsler Intelligence Scale for Children. The total study population consisted of 585 mother-child pairs with available prenatal urinary phthalate metabolites concentrations and IQ data at age 7 years. A subset of those (N = 274) had urinary phthalate metabolites measured in child urine at age 7 years. Phthalate concentrations were grouped into tertiles and associations with IQ were investigated using multiple linear regression adjusting for sex, maternal education and maternal/child BMI. ResultsUrinary phthalate metabolite concentrations both in pregnant women and children were generally lower compared to previous cohorts. Children with high prenatal urinary concentrations of MEP and metabolites of DEHP (∑DEHPm)(3rd tertile) had −3.1 (95% CI: −5.5, −0.6) (MEP) and − 3.0 (−5.5, −0.6) (∑DEHPm) IQ points at age 7 years compared to children with low concentrations (1st tertile). High concurrent urinary phthalate concentrations of MCPP, ∑DnHxPm, ∑DiDPm and ∑DiNPm in the 3rd tertile was associated with −3.7 (−7.2, −0.2), −4.4 (−7.9, −0.9), −3.7 (−7.2, −0.2) and − 5.6 (−9.1, −2.2) IQ points, respectively, compared to those with the lowest concentrations (1st tertile). ConclusionWe found significant inverse associations between some prenatal and concurrent urinary phthalate concentrations and IQ at age 7 years in this low exposed population. This suggests that exposure to phthalates both prenatally and during early childhood could be hazardous to child neurodevelopment, however, large-scale prospective studies assessing phthalate exposure through multiple urine samples, and possibly investigating cocktail effects of the chemicals as well as long term follow-up are warranted.

Nephrolithiasis and nephrocalcinosis in children and adolescents

Nephro- or urolithiasis is acommon disease. The prevalence of the disease is increasing in both pediatric and adult patients. The genomic calculation of prevalence may reveal higher levels than the previous diagnosis rates. Monogenic kidney stone disease has been identified in 30% of pediatric and 10% of adult patients. Even if it seems legitimate to assume that there is no specific underlying disease in the case of aone-time stone episode, such adisease must be excluded in the pediatric patient. Therefore, the present study discusses in detail the evaluation and treatment of kidney stones in children. Repeated analysis of 24 h urine samples, or multiple spot urine samples in infants and young children, usually provides evidence of the underlying pathology. In addition, any stone removed should be analyzed. These findings are followed by directed genetic diagnostics. Ultrasonography is the preferred diagnostic method. For symptomatic stones, aminimally invasive method of stone removal is chosen if possible, but not every stone needs to be removed. Family workup must be performed, when aspecific diagnosis is made in an index case. Early diagnosis is important to avoid recurrences despite the few treatment options available. Delayed diagnosis can have catastrophic consequences for patients (e.g., renal failure). Standard treatment with hyperhydration and alkali citrate treatment alone often helps prevent recurrences. New therapeutic options give hope that stone diseases will become more treatable. Finally, early diagnosis often avoids problematic courses.

The effect of acid use as a preservative on the results of biochemical tests measured in 24-h urine

Twenty-four-hour urine measurements play a crucial role in the diagnosis, follow-up and treatment of various diseases. There are different approaches to the collection of urine in patients who need to collect multiple urine samples at a time, especially in hospitals with heavy workloads. In this study, we compared the sodium, potassium, chloride, amylase, calcium, creatinine, phosphorus, microalbumin, protein, magnesium, urea, uric acid, adrenaline, noradrenaline, dopamine, metanephrine, normetanephrine, vanillylmandelic acid, 5-hydroxyindoleacetic acid and homovanillic acid results of 24-h urine samples analyzed immediately without acid addition, which we accepted as the reference and baseline measurement, with the results of the samples analyzed after waiting for 24 h without acid addition, analyzed immediately with acid addition and analyzed after waiting for 24 h with acid addition. Chloride, microalbumin, amylase and protein tests, which are recommended to be measured in the sample without preservatives, are affected by acid addition. Adrenaline, noradrenaline and dopamine, which are the tests recommended to be measured in acid-added urine are degraded in the samples without acid, and the levels of metanephrine and normetanephrine were not significantly degraded in the absence of preservatives.

THE VALUE OF MULTIPLE 24-HOUR URINE SAMPLES FOR ESTIMATING SODIUM INTAKE

Objective: A single 24-hour urine collection is frequently used to estimate daily sodium intake. Long-term balance studies, however, observed large discrepancies between 24-hour sodium intake and sodium excretion. In a controlled setting with stable sodium intake, the use of up to 7 consecutive 24-hour urine samples has been shown to increase the accuracy of sodium intake estimates. The value of multiple 24-hour urine collections for estimation of sodium intake has not been investigated in the clinical setting with uncontrolled intake, use of natriuretic medication and comorbidities that may affect sodium excretion. Design and method: In a retrospective cohort study, we included adult subjects who collected an outpatient 24-hour urine sample between 1998 and 2000, and had collected at least 6 additional 24-hour urine collections during follow-up. Mean sodium excretion was calculated for 2, 3, 4, 5, 6, and 7 consecutive 24-hour urine collections. We calculated the absolute change in 24-hour urine sodium excretion with each added urine sample. We considered a 0.4-gram change in sodium (1 gram salt) intake clinically relevant. Results: We included 316 subjects with an average age of 44 years, and 46% were male. 50% of the subjects had a history of hypertension, 30% had diabetes and 9% had a history with a cardiovascular event. Diuretics were used by 22% of the subjects and 44% used ennin-angiotensin-aldosterone system inhibitors. The median follow-up period was 16.4 years. The median time to collection of 7 urine samples was 2.5 years (IQR 1.3–4.8). Mean sodium excretion was 159 mmol/day (SD 62). With addition of a second 24-hour urine sample, individual estimated sodium intake changed with 0.43 gram sodium (IQR 0.17–0.90) and changed &gt; 0.4 gram in 52% of the subjects. When a fifth or seventh collection was added, estimated sodium intake changed &gt; 0.4 gram in 14% and 7% of our cohort (Figure). Conclusions: Collection of multiple 24-hour urine samples substantially changes estimated individual sodium intake in the clinical setting. The added value of collecting &gt; 5 24-hour urine samples is limited and changes sodium intake estimations only in 14% of the subjects.

Multidrug-resistant Uro-associated Escherichia coli Populations and Recurrent Urinary Tract Infections in Patients Performing Clean Intermittent Self-catheterisation

BackgroundThe AnTIC trial linked continuous low-dose antibiotic prophylaxis treatments to a lower incidence of symptomatic urinary tract infections (UTIs) among individuals performing clean intermittent self-catheterisation (CISC). ObjectiveTo explore potential mechanisms underlying the protective effects of low-dose antibiotic prophylaxis treatments, blood and urine samples and uro-associated Escherichia coli isolates from AnTIC participants were analysed. Design, setting, and participantsBlood samples (n = 204) were analysed for TLR gene polymorphisms associated with UTI susceptibility and multiple urine samples (n = 558) were analysed for host urogenital responses. E.coli sequence data for 45 temporal isolates recovered from the urine samples of 16 trial participants in the prophylaxis (n = 9) and no-prophylaxis (n = 7) study arms, and characterised by multidrug resistance (MDR), were used to classify individual strains. Outcome measurements and statistical analysisTLR polymorphism data were analysed using Poisson regression. Concentrations of urine host defence markers were analysed using linear mixed-effects models, which accounted for repeated urine samples. Results and limitationsUrine samples from CISC users, irrespective of antibiotic treatment regimens, were associated with robust urothelial innate responses. No links were identified between TLR genotype and CISC user susceptibility to recurrent UTIs. Microbiological study data were limited to the predominant MDR E. coli population; participants prescribed low-dose prophylactic antibiotics were predominantly colonised by a single uro-associated E. coli strain, while participants given acute antibiotic treatments were each colonised by more than one E. coli strain. ConclusionsAntibiotic treatments did not impact urogenital responses to infection in CISC users. Host genetics in terms of TLR polymorphisms played no role in determining CISC user susceptibility to or protection from recurrent UTIs. Prophylactic antibiotic treatments associated with MDR E. coli were associated with colonisation by stable uro-associated E. coli genotypes. Patient summaryOur findings show that the natural urogenital defences of clean intermittent self-catheterisation (CISC) users were not impacted by antibiotic treatments. For some CISC users, prophylaxis with low-dose antibiotics selected for a stable, predominantly, Esherichia coli rich uromicrobiota.

24-Hour Urinary Sodium and Potassium Excretion and Cardiovascular Risk

BackgroundThe relation between sodium intake and cardiovascular disease remains controversial, owing in part to inaccurate assessment of sodium intake. Assessing 24-hour urinary excretion over a period of multiple days is considered to be an accurate method.MethodsWe included individual-participant data from six prospective cohorts of generally healthy adults; sodium and potassium excretion was assessed with the use of at least two 24-hour urine samples per participant. The primary outcome was a cardiovascular event (coronary revascularization or fatal or nonfatal myocardial infarction or stroke). We analyzed each cohort using consistent methods and combined the results using a random-effects meta-analysis.ResultsAmong 10,709 participants, who had a mean (±SD) age of 51.5±12.6 years and of whom 54.2% were women, 571 cardiovascular events were ascertained during a median study follow-up of 8.8 years (incidence rate, 5.9 per 1000 person-years). The median 24-hour urinary sodium excretion was 3270 mg (10th to 90th percentile, 2099 to 4899). Higher sodium excretion, lower potassium excretion, and a higher sodium-to-potassium ratio were all associated with a higher cardiovascular risk in analyses that were controlled for confounding factors (P≤0.005 for all comparisons). In analyses that compared quartile 4 of the urinary biomarker (highest) with quartile 1 (lowest), the hazard ratios were 1.60 (95% confidence interval [CI], 1.19 to 2.14) for sodium excretion, 0.69 (95% CI, 0.51 to 0.91) for potassium excretion, and 1.62 (95% CI, 1.25 to 2.10) for the sodium-to-potassium ratio. Each daily increment of 1000 mg in sodium excretion was associated with an 18% increase in cardiovascular risk (hazard ratio, 1.18; 95% CI, 1.08 to 1.29), and each daily increment of 1000 mg in potassium excretion was associated with an 18% decrease in risk (hazard ratio, 0.82; 95% CI, 0.72 to 0.94).ConclusionsHigher sodium and lower potassium intakes, as measured in multiple 24-hour urine samples, were associated in a dose–response manner with a higher cardiovascular risk. These findings may support reducing sodium intake and increasing potassium intake from current levels. (Funded by the American Heart Association and the National Institutes of Health.)

Estimation of urinary 24-hour sodium excretion in young Saudi professional soccer players

Aim: to estimate 24-hour urinary sodium concentration in young Saudi professional soccer players by using a single spot urine. Method: a cross sectional study design, conducted during the official Saudi Soccer League 2015/2016. A total of 25 players from Riyadh, Saudi Arabia participated in this study. Age, weight, height, body fat % and single urine sample were collected pre-training day. Sodium (Na) and creatinine (Cr) were analyzed. Estimation of 24-hour sodium and creatinine were calculated by the Kawasaki formula: 16.3 × [spot urine Na (mmol/l)/spot urine Cr (mmol/l) × estimated 24-hour urinary Cr (mg)0.5, and -4.72 ×age + 8.58 × weight (kg) + 5.09 × height (cm) – 79.9. A descriptive and Pearson correlation data analysis were used. Result: estimation of 24h sodium (27.1 mEq/L/24h) was lower than reference range. Strong relationship between anthropometric measurements (i.e., weight, height, % body fat) creatinine 24-h estimation. Age shows a strong relationship with sodium. The current study found a poor of estimation for 24-h urinary sodium concentration by using a single spot urine among soccer players. Conclusion: using single spot urine has shown a poor estimation of sodium in athletes population. However, future studies for collection of multiple spot urine samples methods in the estimation of 24-h urine Na is warranted.