24-hour Urine Samples Research Articles

SLIPS-LAB-A bioinspired bioanalysis system for metabolic evaluation of urinary stone disease.

Urinary stone disease is among the most common medical conditions. Standard evaluation of urinary stone disease involves a metabolic workup of stone formers based on measurement of minerals and solutes excreted in 24-hour urine samples. Nevertheless, 24-hour urine testing is slow, expensive, and inconvenient for patients, which has hindered widespread adoption in clinical practice. Here, we demonstrate SLIPS-LAB (Slippery Liquid-Infused Porous Surface Laboratory), a droplet-based bioanalysis system, for rapid measurement of urinary stone-associated analytes. The ultra-repellent and antifouling properties of SLIPS, which is a biologically inspired surface technology, allow autonomous liquid handling and manipulation of physiological samples without complicated sample preparation procedures and supporting equipment. We pilot a study that examines key urinary analytes in clinical samples from patients with urinary stone. The simplicity and speed of SLIPS-LAB hold the potential to provide actionable diagnostic information for patients with urinary stone disease and rapid feedback for responses to dietary and pharmacologic treatments.

Balanço Nitrogenado na UTI Pediátrica

RESUMO
 OBJETIVO: Avaliar a situação nutricional aguda de um grupo de pacientes em uma UTI pediátrica através da medida do balanço nitrogenado e estudar o impacto de um maior aporte de dieta nesse balanço. MÉTODO: Estudo de coorte prospectivo realizado de março a junho de 2018, envolvendo crianças com idade entre 29 dias e 14 anos, com sonda vesical de demora pela necessidade do próprio tratamento. Realizada coleta da urina de 24 horas para o cálculo do balanço nitrogenado, que foi classificado como positivo (BN > 0) ou negativo (BN < 0) para as análises. RESULTADOS: Foram avaliados 40 pacientes, sendo possível a coleta de uma segunda amostra em 7 deles. Das 47 amostras, 25 (53%) apresentaram um balanço nitrogenado positivo. Das amostras com balanço nitrogenado positivo, a média de aporte proteico e calórico foi de 1,4 g/kg/dia e 61 Kcal/kg/dia, respectivamente. Dos pacientes que obtivemos uma segunda coleta da urina de 24 horas, realizada com um maior aporte nutricional, os balanços nitrogenados da segunda coleta foram estatisticamente maiores que os da primeira, com um valor p de 0,018. CONCLUSÃO: A melhora no aporte calórico e proteico do paciente crítico pediátrico se reflete em uma melhora do balanço nitrogenado. Os valores encontrados de aporte calórico e proteico para atingir um balanço nitrogenado positivo foram semelhantes aos da literatura. 
 Palavras-chave: Balanço Nitrogenado, UTI Pediátrica

Prospective Randomized Study on the Effects of Improved Sleep Quality After Craniotomy on Melatonin Concentrations and Inflammatory Response in Neurosurgical Intensive Care Patients

Sleep disorders in intensive care units after a craniotomy can decrease melatonin secretion and increase the inflammatory stress response. The aim of this study was to investigate the influence of improving sleep quality via eye patches and earplugs on melatonin secretion and inflammatory mediator release. The study enrolled 41 patients who underwent craniotomy. Patients were randomized into 2 groups. "Group Intervention" received a sleep-promoting intervention with eye patches and earplugs to provide light and noise isolation, while "Group Control" received standard care. Blood levels of C-reactive protein and interleukin 1 and interleukin 6 along with urine levels of 6-sulphatoxymelatonin (aMT6) were measured preoperatively (baseline) and on postoperative days 1 and 3. Sleep quality was assessed with the Richards-Campbell Sleep Questionnaire. Sleep quality was higher in the intervention group (Richards-Campbell score:80.61 ± 11.96 vs. 33.50 ±16.32; P < 0.001). Urine aMT6 levels increased significantly in the intervention group in spot urine samples from 10.15 (5.38-14.40) ng/mL at baseline to 14.52 (6.24-29.11) and 11.51 (7.88-29.05) ng/mL on postoperative days 1 and 3. They also increased in 24-hour urine samples from 25.73 (8.24-52.73) ng/mL at baseline to 35.38 (11.48-95.65) and 39.18 (2.36-125.23) ng/mL on postoperative days 1 and 3 (P= 0.001 and P= 0.005, respectively). The aMT6 concentration did not change significantly in the control group. The C-reactive protein concentrations increased postoperatively compared with baseline concentrations in both groups (P= 0.001 and P < 0.001). Melatonin secretion significantly increased as a result of improving postoperative sleep quality by noise and light isolation in neurosurgical intensive care unit patients after craniotomy.

OR29-07 A Novel Estimate of Creatinine Excretion to Determine Adequacy of 24-Hr Urine Collection

24-hour urine collections are used to assess excretion of various analytes. Although concomitant measurement of creatinine excretion adjusted for body weight (BW) is utilized to determine adequacy of collection, no gold standard exists for determining completeness of a collection. Use of current reference ranges for daily creatinine excretion/BW of 15–20 mg creatinine/kg BW/day in women and 20–25 mg creatinine/kg/d in men established prior to the rising prevalence of obesity has resulted in a large proportion of contemporary individuals appearing to have “incomplete” urine collections.Our objective was to evaluate the range of creatinine excretion in accurately collected urine specimen from adults with a wide spread of age and BW, and to generate an equation that accurately predicts 24-hour urine creatinine excretion rate from readily available clinical parameters to aid in assessing adequacy of a 24-hour urine collection.We analyzed data from participants who completed two consecutive 24-hour urine collections while consuming a fixed metabolic diet during inpatient research admissions. Results from participants with 24-hour urine creatinine excretion rate differing by >10% between the two consecutive collections were excluded. In the initial 115 pairs of inpatient 24-hour urine collections (50 female, 65 male) participants, creatinine excretion/BW fell outside the currently accepted reference ranges in >50% of collections. The proportion below the reference range increased with higher BMI. In this derivation dataset, linear regression models were then constructed to predict 24-hr urine creatinine excretion from race, sex, age, weight and height. Reliable prediction of observed 24-hr urine creatinine excretion was confirmed in a validation dataset that included 50 pairs of 24-hour urine samples similarly collected in an inpatient research setting.This new prediction model performed significantly better than the currently used reference ranges in a large outpatient dataset including 1,399 pairs of 24-hour urine collections. In women, actual creatinine excretion fell within the 95% prediction intervals for our derived equation in 90% of cases using the new interval vs 46% using the current reference range. The corresponding values were 90% and 33% in men. In both genders, the superiority of the new prediction over the current reference range was more pronounced at higher BMI.We therefore propose revision of currently used criteria to define adequacy of 24-hour urine collection to account for the impact of obesity. The proposed equation incorporates readily available demographic parameters to predict urine creatinine excretion. These findings have wide implications on patient care and research studies, and future studies should test this equation in different settings, diets, and populations.

Prevalence of thyroid dysfunction in healthy adults according to the estimated iodine intake in 24-hour urine samples: The SALMEX cohort.

The aim of this study was to evaluate the prevalence of thyroid dysfunction in a cohort of healthy individuals in Mexico City, as well as to investigate the potential associations of these results with their estimated iodine intake (EII) as reflected by their 24-hour urinary iodine excretion (24-h UIE). From the SALMEX cohort, 683 adults provided an appropriate 24-h urine sample. Thyroid function tests and thyroid antibody concentrations were determined in the participants' sera. We analyzed discrepancies between the commonly used urinary parameters to determine the iodine intake status and the performance of thyroglobulin (Tg) as a biomarker of its status in the adult population. The prevalence of dysthyroidism was high, being similar to other studies. Subclinical hypothyroidism was detected in 5.0% of individuals, clinical hypothyroidism in 1.8% of individuals, and sub-clinical hyperthyroidism in 2.8% of individuals. The median EII was 285 μg/d (IQR 215.0-369.0); 94% of individuals had EII >150 µg/d recommended daily allowance (RDA) in adults. The urinary iodine concentration (UIC) and the UIE had relative biases in their averages of 34.4%. The Tg median was 7.21 ng/mL. The prevalence of increased Tg was 6.15%. There was no correlation between Tg and EII (r= 0.019, p=0.606). Thyroid dysfunction was highly prevalent in this population. Our cohort revealed a slight discrepancy between dysthyroidism manifestations and iodine intake markers; the latter represent a population with adequate iodine intake. Further studies are necessary to clearly define the prevalence of thyroid dysfunction as well as the iodine nutritional status in Mexico.

The optimization and assessment of the method for inducing hyperuricemia in rats

Objective: To explore an effective method for inducing a rat model with hyperuricemia in a short period and assess the effects of the model. Methods: Sprague-Dawley rats were adopted as donors and randomly divided into control group (CT group, n=6) and 5 model groups (M1-M5 groups, n=8 in each group). M1 group (gavage with 10 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, in the 7th day of model inducing), M2 group (gavage with 10 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, in the 1st, 3rd and 7th day of model inducing),M3 group (gavage with 10 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, once per day during the model inducing), M4 group (gavage with 20 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, once per day during the model inducing), M5 group (gavage with 30 g/kg yeast extracts and 100 mg/kg adenine, twice per day, 300 mg/kg oxonic acid potassium by intraperitoneal injection, once per day during the model inducing), and group CT (gavaged with equal volume sterilized water and intraperitoneal injected with normal saline according to the weight and at the same frequency as the model groups). The model inducing lasted for 7 days. After the inducing was finished, blood and 24-hour urine were sampled for uric acid and creatinine determination. Then rats were maintained for 2 weeks and blood and 24-hour urine samples were collected, the concentration of uric acid and creatinine were detected. The kidney and stomach were weighed,morphological changes in kidney were observed. Results: After model inducing, the body weight of rats in all model groups was lower than that of the control group (P＜0.01). Deaths occurred in all the rats with model treatments except M2. M4 and M5 groups were failed to be analyzed because of the high mortality, model 1 and 3 groups had 4 and 2 deaths, respectively. The uric acid levels in blood and urine of the model groups were significantly elevated (P＜ 0.01) at the end of model inducing. The model 2 group's blood uric acid was highest among the model groups (P＜0.05). It sustained a higher concentration than CT group in the three model groups after 2 weeks feeding (P＜0.05). The kidneys in model groups obviously swelling and were heavier than CT group (P＜0.01). The inflammation and structural damages were observed in kidneys of all model groups.Conclusion: The yeast extract (10 g/kg), adenine (100 mg/kg) gavage combined with intraperitoneal injections(the 1st, 3rd, 7th day during inducing) of potassium oxonate can be an rapid and effective method for inducing the rat model with hyperuricemia, which can be suggested to the related research.

Association of a Province-Wide Intervention With Salt Intake and Hypertension in Shandong Province, China, 2011-2016

High salt intake is associated with hypertension, which is a leading modifiable risk factor for cardiovascular disease. To assess the association of a government-led, multisectoral, and population-based intervention with reduced salt intake and blood pressure in Shandong Province, China. This cross-sectional study used data from the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) program, a 5-year intervention to reduce sodium consumption in Shandong Province, China. Two representative samples of adults (aged 18-69 years) were surveyed in 2011 (15 350 preintervention participants) and 2016 (16 490 postintervention participants) to examine changes in blood pressure, and knowledge, attitudes, and behaviors related to sodium intake. Urine samples were collected from random subsamples (2024 preintervention participants and 1675 postintervention participants) for measuring sodium and potassium excretion. Data were analyzed from January 20, 2017, to April 9, 2019. Media campaigns, distribution of scaled salt spoons, promotion of low-sodium products in markets and restaurants, and activities to support household sodium reduction and school-based sodium reduction education. The primary outcome was change in urinary sodium excretion. Secondary outcomes were changes in potassium excretion, blood pressure, and knowledge, attitudes, and behaviors. Outcomes were adjusted for likely confounders. Means (95% CIs) and percentages were weighted. Among 15 350 participants in 2011, 7683 (50.4%) were men and the mean age was 40.7 years (95% CI, 40.2-41.2 years); among 16 490 participants in 2016, 8077 (50.7%) were men and the mean age was 42.8 years (95% CI, 42.5-43.1 years). Among participants with 24-hour urine samples, 1060 (51.8%) were men and the mean age was 40.9 years (95% CI, 40.5-41.3 years) in 2011 and 836 (50.7%) were men and the mean age was 40.7 years (95% CI, 40.1-41.4 years) in 2016. The 24-hour urinary sodium excretion decreased 25% from 5338 mg per day (95% CI, 5065-5612 mg per day) in 2011 to 4013 mg per day (95% CI, 3837-4190 mg per day) in 2016 (P < .001), and potassium excretion increased 15% from 1607 mg per day (95% CI, 1511-1704 mg per day) to 1850 mg per day (95% CI, 1771-1929 mg per day) (P < .001). Adjusted mean systolic blood pressure among all participants decreased from 131.8 mm Hg (95% CI, 129.8-133.8 mm Hg) to 130.0 mm Hg (95% CI, 127.7-132.4 mm Hg) (P = .04), and diastolic blood pressure decreased from 83.9 mm Hg (95% CI, 82.6-85.1 mm Hg) to 80.8 mm Hg (95% CI, 79.4-82.1 mm Hg) (P < .001). Knowledge, attitudes, and behaviors associated with dietary sodium reduction and hypertension improved significantly. The findings suggest that a government-led and population-based intervention in Shandong, China, was associated with significant decreases in dietary sodium intake and a modest reduction in blood pressure. The results of SMASH may have implications for sodium reduction and blood pressure control in other regions of China and worldwide.

Factors Associated With Compliance With 24-Hour Urine Collection

To identify how demographic factors, stone-associated medical comorbidities, and treatment predict compliance with 24-hour urine collection. A retrospective medical record review of patients treated for urolithiasis between August 2014 and March 2017 was performed. Patient demographics, medical characteristics, stone factors, type of treatment, and compliance data were included for patients requested to submit a collection. Variables that were statistically significant on bivariate analysis were then used to formulate a model predicting submission of a 24-hour urine sample. Of the 303 patients who met inclusion criteria, 183 (60.4%) submitted an initial 24-hour urine collection. On bivariate analysis, patients older than 50 were more likely to submit a 24-hour urine collection (71.4% vs 51.5%; P <.001), patients with a metabolic predisposition for stones were more likely to submit a 24-hour urine collection (70.6% vs 53.1%; P <.003), and patients who did not have surgery were more likely to submit a 24-hour urine collection (97.9% vs 53.5%; P <.001). Our 3-variable prediction model found that not undergoing surgery was a strong predictor of 24-hour urine collection. We suspect that patients perceive surgery as a more definitive treatment for kidney stones than conservative management. Patient education on the natural history and role of metabolic management in the prevention of nephrolithiasis is essential in improving compliance with 24-hour urine collection.

PD04-09 BROWN ADIPOCYTES SUPPRESS KIDNEY STONE FORMATION VIA HEAT-PRODUCING PROTEIN, UNCOUPLING PROTEIN 1

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I (PD04)1 Apr 2020PD04-09 BROWN ADIPOCYTES SUPPRESS KIDNEY STONE FORMATION VIA HEAT-PRODUCING PROTEIN, UNCOUPLING PROTEIN 1 Teruaki Sugino*, Yutaro Tanaka, Rei Unno, Kazumi Taguchi, Shuzo Hamamoto, Ryosuke Ando, Atsushi Okada, Tohru Mogami, Hitoshi Yamashita, and Takahiro Yasui Teruaki Sugino*Teruaki Sugino* More articles by this author , Yutaro TanakaYutaro Tanaka More articles by this author , Rei UnnoRei Unno More articles by this author , Kazumi TaguchiKazumi Taguchi More articles by this author , Shuzo HamamotoShuzo Hamamoto More articles by this author , Ryosuke AndoRyosuke Ando More articles by this author , Atsushi OkadaAtsushi Okada More articles by this author , Tohru MogamiTohru Mogami More articles by this author , Hitoshi YamashitaHitoshi Yamashita More articles by this author , and Takahiro YasuiTakahiro Yasui More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000824.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Our recent studies have revealed that adipocytokine secreted by adipocytes are important for the formation of kidney stones. Brown adipocytes are reported to suppress inflammatory adipocytokine expression via a specific protein—uncoupling protein 1 (UCP1). In this study, we investigated the effect of brown adipocytes and UCP1 on kidney stone formation. METHODS: Study 1: Nine-week-old male C57BL/6 mice underwent sham or brown adipose tissue transplant surgery (sham group, transplant group, n = 6 in each group). Three weeks after surgery, renal crystal deposits were introduced via daily intra-abdominal injections of 80 mg/kg glyoxylate (GOX). Study 2: Renal crystal deposits were introduced via daily intra-abdominal injections of 80 mg/kg GOX in wild-type and defective type 8-week-old male UCP1-deficient mice (B6.129-Ucp1tm1Kz/J) (WT group, KO group, n = 6 in each group). Fat tissues, kidneys, and 24-hour urine samples of the mice were collected in both studies. RESULTS: Study 1: In the transplant group, the amount of renal crystal deposits was significantly lower (3.28 times) than that in the sham group (Fig. 1a), and lower expression of inflammatory markers, such as chemokine (C-C motif) ligand 2 (Ccl2), EGF module-containing mucin-like receptor 1 (Emr1), tumor necrosis factor (Tnf), and secreted phosphoprotein 1 (Spp1)was observed in the kidney. Inductive brown adipocytes were observed in the perirenal fat tissue in the transplant group. Study 2: In the KO group, the amount of renal crystal deposits was significantly higher (3.28 times) than that in the WT group (Fig. 1b), and higher expression of Emr1, Tnf, and Spp1 was observed in the kidney. Infiltration of inflammatory cells was strongly observed in brown adipose tissue in the KO group. There were no significant differences in the 24-hour urine samples throughout the two studies. CONCLUSIONS: Brown adipose tissue transplantation suppressed renal crystal formation via anti-inflammatory effects, and UCP1 would be necessary in this mechanism. Brown adipocytes can be the therapeutic target for kidney stone formation. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e81-e82 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Teruaki Sugino* More articles by this author Yutaro Tanaka More articles by this author Rei Unno More articles by this author Kazumi Taguchi More articles by this author Shuzo Hamamoto More articles by this author Ryosuke Ando More articles by this author Atsushi Okada More articles by this author Tohru Mogami More articles by this author Hitoshi Yamashita More articles by this author Takahiro Yasui More articles by this author Expand All Advertisement PDF downloadLoading ...

Estimating 24-Hour Sodium Excretion from Spot Urine Samples in Chinese Adults: Can Spot Urine Substitute 24-Hour Urine Samples?

Several estimating equations for predicting 24-h urinary sodium (24-hUNa) excretion using spot urine (SU) samples have been developed, but have not been readily available to Chinese populations. We aimed to compare and validate the six existing methods at population level and individual level. We extracted 1671 adults eligible for both 24-h urine and SU sample collection. Mean biases (95% CI) of predicting 24-hUNa excretion using six formulas were 58.6 (54.7, 62.5) mmol for Kawasaki, −2.7 (−6.2, 0.9) mmol for Tanaka, −24.5 (−28.0, −21.0) mmol for the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) with potassium, –26.8 (−30.1, −23.3) mmol for INTERSALT without potassium, 5.9 (2.3, 9.6) mmol for Toft, and −24.2 (−27.7, −20.6) mmol for Whitton. The proportions of relative difference >40% with the six methods were nearly a third, and the proportions of absolute difference >51.3 mmol/24-h (3 g/day salt) were more than 40%. The misclassification rate were all >55% for the six methods at the individual level. Although the Tanaka method could offer a plausible estimation for surveillance of the population sodium excretion in Shandong province, caution remains when using the Tanaka formula for other provincial populations in China. However, these predictive methods were inadequate to evaluate individual sodium excretion.

Abstract MP43: Urine And Plasma Metabolome of Healthy Adults Consuming the Dietary Approaches to Stop Hypertension Diet: A Pilot Study

The mechanisms of the Dietary Approaches to Stop Hypertension (DASH) diet on various health markers remain unclear. The objective of this study was to identify plasma and urine metabolites altered by DASH that may elucidate mechanisms of benefit and suggest biomarkers to facilitate research and monitoring. We tested metabolomics differences in a controlled feeding study of 20 people consuming a Control diet for one wk followed by 2 wks of random assignment to Control or DASH. Fasting plasma and 24-hour urine samples collected at the end of each wk were profiled for metabolites using non-targeted GC/MS and amino acids and acylcarnitines were measured in plasma using a targeted panel. Linear models compared metabolite levels between DASH and Control during the final two randomized feeding wks [nominal p&lt;0.05 and false discovery rate (FDR) adjusted p&lt;0.2]. Compared to Control, DASH is designed to be lower in total fat and saturated fat, but higher in protein, fiber, potassium, magnesium and calcium. Overall, we found 161 identifiable urine metabolites. In FDR adjusted tests, urine excretion of a variety of polyphenolic acids were higher on DASH. In plasma, gamma tocopherol, acylcarnitine C5 from branched chain amino acid (BCAAs) metabolism, and amino acids including BCAAs leucine/isoleucine and valine were lower on DASH (Table 1). Several small and medium chain dicarboxylic acylcarnitines were higher on DASH. Consumption of DASH increases urine levels of a set of polyphenolic compounds many of which have been linked to lower blood pressure in animal and small human studies. In plasma, BCAAs are lower on DASH despite higher protein intake. Further research is needed to investigate these metabolites as a panel for dietary monitoring in hypertension. Table 1. Nontargeted and targeted metabolites (Selected metabolites are shown here) in DASH and Control.

SUN-308 URINARY EPIDERMAL GROWTH FACTOR/CREATININE RATIO AND GRAFT FAILURE IN KIDNEY TRANSPLANT RECIPIENTS: A PROSPECTIVE COHORT STUDY

Graft failure remains a major clinical challenge to improving long-term outcomes in kidney transplant recipients (KTR). Early identification of KTR at higher risk of graft failure is key to potentially improve this outcome. Epidermal growth factor (EGF) is involved in kidney tissue proliferation and integrity, with a reduction of its urinary excretion being associated with early fibrotic processes and a wide range of kidney diseases. We aimed to investigate whether, in KTR, urinary EGF (uEGF) is prospectively associated with graft failure. In this prospective cohort study, KTR with a functioning allograft ≥1-year were recruited and followed-up for three years. uEGF was measured at baseline by ELISA in 24-hours urine samples and normalized by urinary creatinine (Cr). Its association with risk of graft failure was assessed by multivariable Cox-regression analyses and its predictive ability by C-statistic. In 706 patients, uEGF/Cr ratio at enrollment was 6.43 (IQR, 4.07–10.77) ng/mg. During follow-up, 41 (6%) KTR developed graft failure. uEGF/Cr ratio was inversely associated with the risk of GF (HR 0.68, 95% CI 0.59‒0.78; P<0.001), which remained independent of adjustment for several potential confounders including immunosuppressive therapy, human leukocyte antigen mismatch, estimated glomerular filtration rate and proteinuria. C-statistic of uEGF/Cr ratio for graft failure was 0.81 (P<0.001) and when added to urinary protein excretion significantly improved its predictive ability (C-statistic from 0.76 to 0.81; P<0.00 1). Kaplan Meier curves by tertiles of uEGF/Cr on graft failure. Tertile 1:<4.78 ng/mg; Tertile 2:4.78-8.80 ng/mg; Tertile 3:>8.80 ng/mg. P value was obtained from the log-rank (Mantel cox) test. uEGF/Cr, urinary epidermal growth factor/creatinine ratio. In KTR, uEGF/Cr ratio is independently and inversely associated with the risk of graft failure and depicts strong prediction ability for this outcome. Further studies seem warranted to elucidate whether uEGF might be a promising biomarker for clinical uptake post-kidney transplantation.

Time course of phthalate cumulative risks to male developmental health over a 27-year period: Biomonitoring samples of the German Environmental Specimen Bank

In several human biomonitoring surveys, changes in the usage patterns of phthalates have come to light, but their influence on the risks associated with combined exposures is insufficiently understood. Based on the largest study to date, the 27-year survey of urinary phthalate metabolite levels in 24-hour urine samples from the German Environmental Specimen Bank, we present a deep analysis of changing phthalate exposures on mixture risks. This analysis adopts the Hazard Index (HI) approach based on the five phthalates DBP, DIBP, BBP, DEHP and DINP. Calculations of the hazard index for each study participant included updated phthalate reference doses for anti-androgenicity (RfDAAs) that take account of new evidence of phthalates’ developmental toxicity.The Maximum Cumulative Ratio (MCR) approach was used to establish whether a subject’s combined exposure was dominated by one phthalate or was influenced by several phthalates simultaneously. Generally, over the years there was a shift towards lower HIs and higher MCRs, reflecting an increased complexity of the combined exposures. The decade from 1988 to about 1999 was characterised by rather high HIs of between 3 and 7 (95th percentile) which were driven by exposure to DBP and DEHP, often exceeding their single acceptable exposures. Traditional single phthalate risk assessments would have underestimated these risks by up to 50%. From 2006 onwards, no study participant experienced exposures above acceptable levels for a single phthalate, but combined exposures were still in excess of HI = 1. From 2011 onwards most individuals stayed below HI = 1. In interpreting these results, we caution against the use of HI = 1 as an acceptable limit and develop proposals for improved and more realistic mixture risk assessments that take account of co-exposures to other anti-androgenic substances also capable of disrupting the male reproductive system. From this perspective, we regard HIs between 0.1 and 0.2 as more appropriate for evaluating combined phthalate exposures. Assessed against lowered HIs of 0.1 – 0.2, the combined phthalate exposures of most study participants exceeded acceptable levels in all study years, including 2015. Continued monitoring efforts for phthalate combinations are required to provide the basis for appropriate risk management measures.

Mycotoxin exposure assessments in a multi-center European validation study by 24-hour dietary recall and biological fluid sampling

The European Food Consumption Validation (EFCOVAL) project includes 600 men and women from Belgium, the Czech Republic, France, the Netherlands, and Norway, who had given serum and 24-hour urine samples, and completed 24-hour dietary recall (24-HDR) interviews. Consumption, according to 24-HDR, was matched against the European Food Safety Authority (EFSA) databases of mycotoxin contaminations, via the FoodEx1 standard classifications, producing an indirect external estimate of dietary mycotoxin exposure. Direct, internal measurements of dietary mycotoxin exposure were made in serum and urine by ultra-performance liquid chromatography coupled to tandem mass spectrometry. For the first time, mycotoxin exposures were thoroughly compared between two 24-HDRs, and two 24-hour urine samples collected during the same days covered by the 24-HDRs. These measurements were compared to a single-time point serum measurement to investigate evidence of chronic mycotoxin exposure. According to 24-HDR data, all 600 individuals were exposed to between 4 and 34 mycotoxins, whereof 10 found to exceed the tolerable daily intake. Correlations were observed between two time points, and significant correlations were observed between concentrations in serum and urine. However, only acetyldeoxynivalenol, ochratoxin A, and sterigmatocystin were found to have significant positive correlations between 24-HDR exposures and serum, while aflatoxin G1 and G2, HT-2 toxin, and deoxynivalenol were associated between concurrent 24-HDR and 24-hour urine. Substantial agreements on quantitative levels between serum and urine were observed for the groups Type B Trichothecenes and Zearalenone. Further research is required to bridge the interpretation of external and internal exposure estimates of the individual on a time scale of hours. Additionally, metabolomic profiling of dietary mycotoxin exposures could help with a comprehensive assessment of single time-point exposures, but also with the identification of chronic exposure biomarkers. Such detailed characterization informs population exposure assessments, and aids in the interpretation of epidemiological health outcomes related to multi-mycotoxin exposure.

Nutrimetabolomics reveals food-specific compounds in urine of adults consuming a DASH-style diet

Although health benefits of the Dietary Approaches to Stop Hypertension (DASH) diet are established, it is not understood which food compounds result in these benefits. We used metabolomics to identify unique compounds from individual foods of a DASH-style diet and determined if these Food-Specific Compounds (FSC) are detectable in urine from participants in a DASH-style dietary study. We also examined relationships between urinary compounds and blood pressure (BP). Nineteen subjects were randomized into 6-week controlled DASH-style diet interventions. Mass spectrometry-based metabolomics was performed on 24-hour urine samples collected before and after each intervention and on 12 representative DASH-style foods. Between 66–969 compounds were catalogued as FSC; for example, 4-hydroxydiphenylamine was found to be unique to apple. Overall, 13–190 of these FSC were detected in urine, demonstrating that these unmetabolized food compounds can be discovered in urine using metabolomics. Although linear mixed effects models showed no FSC from the 12 profiled foods were significantly associated with BP, other endogenous and food-related compounds were associated with BP (N = 16) and changes in BP over time (N = 6). Overall, this proof of principle study demonstrates that metabolomics can be used to catalog FSC, which can be detected in participant urine following a dietary intervention.

The Utility of the Random Urine Uric Acid-to-Creatinine Ratio for Patients with Gout Who Need Uricosuric Agents: Retrospective Cross-Sectional Study.

BackgroundThe 24-hour uric acid excretion measurement is important in assessing disease status and helping to select the appropriate uric acid-lowering agent for patients with gout, however, it is inconvenient. The authors investigated the efficacy of the random urine uric acid-to-creatinine (UA/CR) ratio to screen the patients who under-secreted 24-hour urine uric acid.MethodsThis was a retrospective cross-sectional study. Ninety patients with gout, without undergoing uric acid-lowering treatment were enrolled. Twenty-four-hour urine and random urine samples were obtained on the same day. Six hundred mg of uric acid in the 24-hour urine sample was used as a standard for distinguishing between over and under-excretion groups.ResultsThe random urinary UA/CR ratio showed positive correlation with 24-hour urine uric acid excretion (γ = 0.398, P < 0.001). All the patients with the random UA/CR less than 0.2 excreted less than 600 mg uric acid in 24-hour urine collection. When the random urine UA/CR ratio < 0.2 was regarded as a positive result, the positive predictive value, negative predictive value, sensitivity, and specificity in the uric acid under-excretion were 100% (8 of 8), 64.6% (53 of 82), 21.6% (8 of 37), and 100% (53 of 53), respectively.ConclusionThere is a moderate positive correlation between the random urinary UA/CR ratio and 24-hour urine uric acid excretion, so that UA/CR ratio may not be a good predictor of 24-hour urine uric acid excretion. However, the random urine UA/CR ratio 0.2 can be a useful predictor to screen the gouty patients who need to be treated with uricosuric drugs.

94 When the gut affects the heart

Abstract A 59-year-old man came to our attention with progressive shortness of breath associated with lower limb oedema. He complained also of recurrent malar flushing, diarrhea and weight loss (14 kg in the last 8 months). At physical examination, a holosystolic murmur best heard over the fourth left sternal border, intensified upon inspiration, and a palpable tender liver with irregular surface were noted. Transthoracic and transesophageal echocardiogram revealed dilated right chambers. The tricuspid annulus was dilated and the leaflets thickened, shortened and retracted with restricted mobility and incomplete coaptation, leading to severe tricuspid regurgitation (Panels A-B). Moderate pulmonary regurgitation was also detected (Panel C). Cardiac MR confirmed the morphology of the tricuspid valve (Panels D-E, arrows) and the severity of the tricuspid regurgitation (regurgitant fraction 66%). The pulmonary valve leaflets were also thickened and fixed (Panel F, arrow), with moderate pulmonary regurgitation (regurgitant fraction 21%). With the suspicion of carcinoid syndrome, 5-hydroxyindoleacetic acid (5-HITT) was tested by 24-hour urine sample and a value of 929.5 µmol/24h was found (n.v. 10.5-47.1). Whole body 18-F DOPA PET was performed. Axial views and reconstructed images revealed a short segment of mural thickening (2.4 cm and 1.1 cm) in the jejunum with a moderate/high uptake (Panels G, arrow). Adjacent to this lesion, a mesenteric spiculated mass (4.0 x 2.8 cm) with moderate uptake was visible (Panels H, arrow). Multiple enhancing nodules with high uptake were present in the liver (Panel I). One of the liver nodules was biopsied. The biopsy revealed extensive infiltration by well differentiated neuroendocrine tumor (Panel J, blue arrow). The tumor cells were arranged in nests and were composed of cells with round to oval nuclei and eosinophilic cytoplasm (Panel K). The neuroendocrine nature of the tumor was confirmed by strong diffuse positivity with synaptophysin (Panel L), chromogranin and CD 56. Ki-67 showed a proliferative index of less than 3%. The tumor morphology, combined with the immunohistochemical features, was in keeping with a well differentiated neuroendocrine tumor. Carcinoid heart disease is a rare cause of primary tricuspid and pulmonary valve disease leading to significant morbidity and mortality caused by right heart failure. The characteristic pathological findings are endocardial plaques of fibrous tissue that may involve the tricuspid valve and, rarely, the pulmonary valve. The fibrous tissue in the plaques results in distortion of the valves leading to either stenosis, regurgitation, or both. Abstract 94 Figure.

Value of the urea/creatinine index in isolated urine to estimate severe protein hypercatabolism in ventilated patients.

ObjectiveTo study the ability of the urea/creatinine index to identify severe protein catabolism from the isolated urine of critically ventilated patients.MethodsThis was a prospective, observational study. It included 52 patients without kidney failure. Variables: total urinary nitrogen estimated from the urea in 24-hour urine on the second (T1) and fourth days (T2) and urea/creatinine index in isolated urine before 24-hour urine collection.ResultsSevere protein hypercatabolism (estimated total urinary nitrogen > 15g) was present in 14 patients (26.9%) at T1 and in 29 (55.7%) at T2. Eighty-four percent of patients had low nutritional risk by the Nutrition Risk in the Critically Ill score. At T1, the Pearson correlation between the estimated total urinary nitrogen and the urea/creatinine index was 0.272 (p = 0.051), and at T2 it was 0.276 (p = 0.048). The urea/creatinine index at T2 had a tendency to better discriminate severe protein hypercatabolism than Acute Physiology and Chronic Health Evaluation II and Nutrition Risk in the Critically Ill (AUC 0.741 versus 0.669 and 0.656, 95%CI: 0.602 - 0.880; 0.519 - 0.818 and 0.506 - 0.806, respectively). The optimal cutoff value of the urea/creatinine index for the diagnosis of severe protein hypercatabolism was 16.15, with a sensitivity of 79.31% (95%CI: 59.74 - 91.29), specificity of 60.87% (95%CI: 38.78 - 79.53), positive predictive value 71.88% (95%CI: 53.02 - 85.60), negative predictive value 70.0% (95%CI: 45.67 - 87.18), LR (+) 2.03 (95%CI: 1.18 - 3.49), and LR (-) 0.34 (95%CI: 0.16 - 0.74).ConclusionThe urea/creatinine index measured on the fourth day has a certain ability to estimate severe protein hypercatabolism (as defined by estimated total urinary nitrogen) but does not replace total urinary nitrogen in critically ventilated patients without kidney failure. Due to its reasonable sensitivity, it could be used as a screen to identify which patients to take a 24-hour urine sample from.

ACTIVITY OF 137CS IN HUMAN BODY OF INHABITANTS OF THE CZECH REPUBLIC.

The time course of 137Cs activity in general population of the Czech Republic has been systematically followed since the Chernobyl accident in 1986. Either whole body counting or the determination of 137Cs content in 24-hour urine samples were used as a method of determination of body activity. Environmental and effective half-lives were calculated from the data. In the time period from 1986 to 1990 the effective half-life was 1.3years; since 1990 up to present the half-life is 15years. The older data on whole body activity of 137Cs from 1965 to 1985 were compiled and are presented as well. Apart from the general population, a group of people who have special dietary habits in terms of increased game meat consumption, namely wild boar meat, has been monitored since 2000. In this group, the body content of 137Cs is about two orders of magnitude higher than in the general population.

Urinary Leukotriene E4 and 2,3-Dinor Thromboxane B2 Are Biomarkers of Potential Harm in Short-Term Tobacco Switching Studies.

Modified risk tobacco products (MRTP) can reduce harm by decreasing exposure to combustion-related toxicants. In the absence of epidemiologic data, biomarkers of potential harm (BoPH) are useful to evaluate the harm-reducing potential of MRTPs. This study evaluated whether arachidonic acid (AA)-derived metabolites serve as short-term BoPH for predicting harm reduction in tobacco product-switching studies. We used 24-hour urine samples from participants in a series of short-term studies in which smokers switched from combustible to noncombustible tobacco products [oral smokeless tobacco products or electronic nicotine delivery system (ENDS)] or abstinence. Pre- and postswitching samples were analyzed by LC/MS-MS for alterations in select AA metabolites, including prostaglandins, isoprostanes, thromboxanes, and leukotrienes. Switching to abstinence, dual use of combustible and noncombustible products, or exclusive use of noncombustible products resulted in reduced 2,3-d-TXB2 levels. Moreover, switching smokers to either abstinence or exclusive use of oral tobacco products resulted in reduced LTE4, but dual use of combustible and oral tobacco products or ENDS did not. A two-biomarker classification model comprising 2,3-d-TXB2 and LTE4 demonstrated the highest performance in distinguishing smokers switched to either abstinence or to ENDS and oral smokeless tobacco products. Urinary 2,3-d-TXB2 and LTE4 can discriminate between combustible tobacco users and combustible tobacco users switched to either abstinence or noncombustible products for 5 days. 2,3-d-TXB2 and LTE4, which are linked to platelet activation and inflammation, represent BoPH in short-term tobacco product-switching studies. Thus, from a regulatory perspective, 2,3-d-TXB2 and LTE4 may aid in assessing the harm reduction potential of MRTPs.