Morning Void Research Articles

Urinary inorganic arsenic in residents living in close proximity to a nickel and copper smelter in Ontario, Canada.

The current study determines whether internal exposure to inorganic arsenic for residents living in close proximity to an operating smelter is any different from that for residents living in a similar community without anthropogenic sources of inorganic arsenic. Furthermore, the study examines factors that may contribute to internal inorganic arsenic exposure in these populations. A cross-sectional study was used to determine whether recent internal exposure to inorganic arsenic for residents living in close proximity to an operating smelter with known elevated soil arsenic content is any different from exposure for residents living in a similar socio-demographic community without point sources of arsenic. Personal information was collected from participants during in-home interviews, and first morning void urine samples were obtained to assess recent internal exposure to arsenic. The mean concentration of urinary inorganic arsenic of residents living in the exposed community was 7.11 ug/L (Standard deviation (SD) 4.53, N = 368) and in the non-exposed community was 7.19 ug/L (SD 5.63, N = 321). The difference in urinary inorganic concentration was not statistically significant (p = 0.83). Regression analysis showed that age and sex were significant predictors of internal exposure, with males and younger age groups having higher exposure levels. Based on analyses of data collected, the results did not demonstrate a statistically significant difference in recent internal exposure to inorganic arsenic between the community with and the one without industrial or other point sources of environmental arsenic contamination. However, individual characteristics such as age and sex are important contributors to urinary inorganic arsenic levels.

Effect of exercise on albuminuria in people with diabetes

Spot urine measurement of albumin is now the most commonly accepted approach to screening for proteinuria. Exertion prior to the collection may potentially influence the result of spot urine albumin estimation. We aim to evaluate the effect of exercise on albuminuria in subjects at various stages of diabetic nephropathy in comparison with healthy control volunteers. Thirty-five people with diabetes (19 with normoalbuminuria (NA), nine with microalbuminuria (MA) and seven with overt proteinuria (OP)) and nine control subjects were assessed. A 1 km treadmill walk was performed. Four spot urine specimens were collected: first morning void, immediately prior to exercise, and 1 h and 2 h after exercise. A random effects linear regression mixed model was used to assess the effect of exercise on albumin/creatinine ratio (uACR). Results are presented separately for male and female subjects with diabetes due to a significant exercise/gender interaction (P < 0.05). No significant effect of exercise on uACR was seen in control subjects. In NA males with diabetes no effect of exercise was seen, while in females uACR 1 h after exercise was significantly higher than the early morning sample (3.55 mg/mmol (96% confidence interval 0.27-6.83). Both female and male diabetes subjects with MA have increase in uACR 1 h after exercise (87.8, -24.3-199.4 and 6.7, 2.1-11.3). For both males and females with OP, uACR was significantly increased 1 h post exercise (67.5, 22-113 and 21.6, 8.4-34.8, respectively). In all groups uACR at 2 h after exercise was not significantly different to the early morning sample. Exercise increased uACR estimation in normoalbuminuric subjects with diabetes with a larger effect in females. Whether exercise unmasks early diabetic nephropathy in NA subjects requires further study.

Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2in healthy adults

25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18–23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2 was 9·6 (sd 0·9) nmol/l at 4·4 (sd 1·8) h. The terminal slope of 25(OH)D2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2 was 13·4 (sd 2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life.

Ethyl Glucuronide, Ethyl Sulfate, and Ethanol in Urine after Intensive Exposure to High Ethanol Content Mouthwash

To determine the degree of ethanol absorption and the resultant formation and urinary excretion of its conjugated metabolites following intensive use of high ethanol content mouthwash, 10 subjects gargled with Listerine(®) antiseptic 4 times daily for 3¼ days. First morning void urine specimens were collected on each of the four study days and post-gargle specimens were collected at 2, 4, and 6 h after the final gargle of the study. Urine ethanol, ethyl glucuronide (EtG), ethyl sulfate (EtS), and creatinine were measured. Ethanol was below the positive threshold of 20 mg/dL in all of the urine specimens. EtG was undetectable in all pre-study urine specimens, but two pre-study specimens had detectable EtS (6 and 82 ng/mL; 16 and 83 μg/g creatinine). Only one specimen contained detectable EtG (173 ng/mL; 117 μg/g creatinine). EtS was detected in the urine of seven study subjects, but was not detected in the single specimen that had detectable EtG. The maximum EtS concentrations were 104 ng/mL and 112 μg/g creatinine (in different subjects). Three subjects produced a total of eight (non-baseline) urinary EtS concentrations above 50 ng/mL or 50 μg/g creatinine and three EtS concentrations exceeding 100 ng/mL or 100 μg/g creatinine. In patients being monitored for ethanol use by urinary EtG and EtS concentrations, currently accepted EtG and EtS cutoffs of 500 ng/mL are adequate to distinguish between ethanol consumption and four times daily use of high ethanol content mouthwash.

A Comparative Study of Clinical Utility of Spot Urine Samples with 24-h Urine Albumin Excretion for Screening of Microalbuminuria in Type 2 Diabetic Patients

Twenty-four hour urinary albumin excretion (UAE) is considered as gold standard method for albuminuria measurement, but collection of 24-h urine is inconvenient. The aim of present study was to evaluate whether albumin: creatinine ratio (ACR) and urinary albumin concentration (UAC) in different spot urine samples correlate or not with 24-h UAE for screening of microalbuminuria in type 2 diabetic patients. We collected first morning void (FMV), random urine sample (RUS) and 24-h urine, separately on consecutive days from 104 type 2 diabetic patients. ACR and UAC in each spot urine sample compared with 24-h UAE with regard to Pearson correlation coefficient. Pearson's correlation of albumin: creatinine ratio (ACR) with 24-h UAE was (r=0.802 and 0.623) in first morning void (FMV) and random urine sample (RUS), respectively. Pearson's correlation coefficient of urinary albumin concentration (UAC) compared with 24-h UAE was (r=0.943 and 0.920), in FMV and RUS, respectively, P<0.01. Results revealed that values in first morning void (FMV) were better correlated with 24-h urinary albumin excretion (UAE), than the values in random urine sample (RUS). We conclude that the first morning void (FMV) may be able to replace 24-h urine collection, preferably urinary albumin concentration (UAC) in the initial screening of microalbuminuria in diabetic patients. The online version of this article (doi:10.1007/s12291-011-0136-0) contains supplementary material, which is available to authorized users.

Effect of Laser Acupuncture for Monosymptomatic Nocturnal Enuresis on Bladder Reservoir Function and Nocturnal Urine Output

The alternative treatments for enuresis have been reported with high efficacy but in noncontrolled studies. Therefore, using a prospective, single-blind, randomized, placebo controlled design we evaluated the effect of laser acupuncture on bladder reservoir function and enuresis frequency in cases of monosymptomatic nocturnal enuresis with reduced maximal voided volume. A total of 31 patients with monosymptomatic nocturnal enuresis, with at least 3 enuretic nights per week and less than 70% of normal age related maximal voided volume without first morning void (Koff's formula), no constipation, urinary tract abnormalities, or daytime incontinence were randomized into group 1--active laser acupuncture, group 2--placebo treatment with red light and skin contact and group 3--placebo treatment with red light without skin contact. After a 2-week run-in period (when patients made home recordings of nocturnal urinary production and during 2 weekends frequency-volume charts), the patients started a 5-week treatment. During the last 2 weeks of treatment patients performed the same recordings as during the run-in period. We found no significant effect of active laser acupuncture on maximal voided volume (first morning void excluded), maximal morning voided volume, voiding frequency, enuresis frequency before and after treatment or nocturnal urine production among the patient groups. However, we found that laser acupuncture resulted in a significant increase in average daytime voided volume. We found no effect of skin contact during placebo laser acupuncture. Laser acupuncture is a safe but inefficient treatment for monosymptomatic nocturnal enuresis with reduced maximal voided volume. However, we found subtle effects on bladder reservoir function.

Variability of Urinary Concentrations of Bisphenol A in Spot Samples, First Morning Voids, and 24-Hour Collections

Background: Human exposure to bisphenol A (BPA) is widespread. After exposure, BPA is rapidly metabolized and eliminated in urine. Therefore, there is considerable within-person and between-person variability of BPA concentrations in spot urine samples. However, no information exists on the within-day variability of urinary BPA concentrations.Objectives: We examined the between-person and within-person and between-day and within-day variability in the urinary BPA concentrations of eight adults who collected all voids for 1 week to investigate the impact of sampling strategy in the exposure assessment of BPA using spot, first morning, or 24-hr urine collections.Methods: We determined the urinary concentrations of BPA using on-line solid-phase extraction coupled to isotope dilution high-performance liquid chromatography/tandem mass spectrometry.Results: The between-day and within-person variability was the primary contributor to the total variance both for first morning voids (77%) and 24-hr urine collections (88%). For the spot collections, we observed considerable within-day variance (70%), which outweighed the between-person (9%) and between-day and within-person (21%) variances.Conclusions: Regardless of the type of void (spot, first morning, 24-hr collection), urinary BPA concentrations for a given adult changed considerably—both within a day and for the 7 days of the study period. Single 24-hr urine collections accurately reflect daily exposure but can misrepresent variability in daily exposures over time. Of interest, when the population investigated is sufficiently large and samples are randomly collected relative to meal ingestion times and bladder emptying times, the single spot–sampling approach may adequately reflect the average exposure of the population to BPA.

Aromatase inhibition causes increased amplitude, but not frequency, of hypothalamic-pituitary output in normal women

To better understand the site and mode of action of aromatase inhibitors. Prospective study. Academic research environment. Five eumenorrheic (without polycystic ovary syndrome), early follicular phase women with a normal body mass index (mean: 20.47±0.68 kg/m2), and 12 normal weight, midreproductive aged, early follicular phase women with a normal body mass index (mean: 20.8±1.7 kg/m2) as historical controls. 2.5 mg letrozole daily for 7 days, with daily urine collection (first morning void), thrice weekly blood sampling, and 4 hours of blood sampling every 10 minutes. Serum luteinizing hormone (LH) measured by a well-characterized immunofluorometric assay with LH pulse characteristics compared between treated and control groups using t tests. Mean LH and LH pulse amplitude more than doubled in the women who had taken letrozole compared with the controls, but the LH pulse frequency did not differ between the women taking letrozole and the controls. These results indicate that the release of negative feedback inhibition of estradiol on the hypothalamic-pituitary axis in normal women by aromatase inhibitors creates an amplitude-related increase in endogenous hypothalamic-pituitary drive. The finding that the mean LH and LH pulse amplitude, but not the frequency, increased after letrozole suggests a possible pituitary site of action.

Effect of a rehydration intervention on markers of hydration status in tennis players

Tennis players have repeatedly been shown to present with signs of dehydration before training or competition. To date no study has investigated the role of post-exercise rehydration in tennis players. Therefore the aim of this study was to assess the efficacy of a post-training rehydration strategy on markers of hydration status in high-performance tennis players. Using a nonblinded randomised crossover design the participants (12 male elite tennis players; mean±SD; age 21±2 years, national ranking 13±8; range 2-25) completed their normal daily training and dietary routine followed by ad libitium consumption (CON) of a commercially available carbohydrate-electrolyte solution (Lucozade Sport Hydro Active PLUS; 4 g carbohydrate and 91 mg sodium per 100 ml) or 20 ml per kg body mass (EXP) of the same solution. An array of markers of hydration status were assessed after rest days (baseline) and each training and intervention day (CON, EXP) including but not limited to: urine osmolality (first morning void, freezing point depression method); total body water, intra and extracellular water (multifrequency bioelectrical impedance). All markers of hydration status were measured in the morning before any activity or meals and normalised as a percentage of baseline. A magnitude-based inferences approach1 was used to determine the main effect of the intervention on the markers of hydration status. The mean (±SD% normalised to baseline) in CON vs EXP for urine osmolality, total body water, extracellular and intracellular water were 104±25% vs 95±31%; 99±2% vs 100±2%; 100±2% vs 102±7% and 98±5% vs 100±2%. The probability of a beneficial or positive effect on these markers of hydration status was 87%, 67%, 84% and 59%, respectively. The probability of a harmful or negative effect was 2%, 3%, 8% and 4%, respectively. Therefore this post-exercise rehydration intervention has an unclear effect as the probability of a negative effect on these markers of hydration status was too great.

Dual effect of adipose tissue on bone health during growth

Recent studies suggest association between body fat and childhood bone health, although conflicting findings have also been reported. The aim of the present study was to examine the association between body fat content and areal BMD, volumetric BMD, bone turnover markers, and calcitropic factors in apparently healthy children and adolescents. The study was carried out as a school based cross-sectional cohort study with 186 subjects (61% girls) aged from 7 to 19 years. Background characteristics, including medical history and lifestyle factors, were collected. Anthropometry, BMD and body composition measurements with DXA and pQCT, a fasting blood sample and a second morning void urine sample were obtained. The subjects were divided into three groups, representing low, intermediate and high adiposity, based on age and gender specific fat percentage Z-scores. Multivariate analysis was performed to all bone variables using lean body mass, pubertal development, dietary intake of calcium and intensity of physical activity as covariates. In pQCT, a significant difference between the groups was observed in cortical BMD (MANOVA; p = 0.02) in proximal radius, the intermediate group having the highest values. Similarly, DXA-derived LS and WB BMD Z-scores differed significantly between the groups (MANOVA; p = 0.026 and p = 0.036, respectively), with highest values in the intermediate group. High body fat content associated also with low bone turnover markers, low PTH, high S-Ca and high urinary calcium excretion. The differences in biochemical markers explain our and others' findings of bone health in children and adolescents with different body fat content. These findings suggest that normal body fat content is beneficial for bone health in growing children and adolescents while both low and high body fat content have adverse skeletal effects.

Urine Albumin-to-Creatinine Ratio

The evaluation of urinary protein is a cornerstone for the diagnosis and treatment of kidney disease. Quantification of proteinuria is used to inform fundamental clinical decisions, such as whether to refer to a nephrologist, perform a kidney biopsy, or initiate therapy. Furthermore, minute interindividual differences in proteinuria associate with future risks for heart disease, kidney failure, and cancer in general population studies.1–3 These findings motivate optimal and consistent methods to quantify proteinuria in the clinical setting. In this issue of JASN , Heerspink et al. 4 compare, among 701 participants in the Reduction In Endpoints in Noninsulin Dependent Diabetes Mellitus with the Angiotensin-II Antagonist Losartan (RENAAL) trial, four standard methods for measuring urine protein: 24-hour urine protein excretion, 24-hour urine albumin excretion, first morning void spot urine albumin concentration, and first morning void spot urine albumin-to-creatinine ratio (ACR). Unlike most previous studies, which related spot urine albumin or urine protein measurements to the gold standard, 24-hour urine collection, the study by Heerspink et al. 4 addresses which of the four methods most strongly associates with the clinical outcome of …

Bone mass, vitamin D levels and immunosuppressive treatment in patients with liver transplant and risedronate treatment

As bone matures type I collagen undegoes β isomerisation at the DG motif of the CTX epitope. Measurements of αCTX and βCTX allow us to distinguish between bone turnover in newly formed and mature bone, respectively. In states of pathologically high bone turnover such as Paget's and malignant bone diseases, there is a relatively greater increase in the resorption of newly formed bone. Treatment of these with bisphosphonates results in a relatively greater decrease in the resorption of newly formed bone. The aims were to investigate 1) the relative increase in αCTX in postmenopausal osteoporosis and 2) the relative decrease in αCTX with bisphosphonate treatment. We recruited 60 postmenopausal women (mean age 68: range 55-85) with a BMD T-score of <2.5 or <1 and a fracture. They were randomised into 3 treatment groups: ibandronate (n=19), alendronate (n=23) and risedronate (n=18). 75 healthy premenopausal women (mean age 38: range 30-45) were recruited. We measured α and βCTX (Nordic Biosciences Diagnostics, Copenhagen, Denmark) in second morning void urine samples and serum βCTX (Roche Diagnostics, Pensberg, Germany). The median urinary α and βCTX and serum βCTX were significantly lower in healthy premenopausal compared to postmenopausal osteoporotic women at baseline 62%, 110% and 65% respectively (P<0.0001). The median urinary α and βCTX and serum βCTX showed a significant decrease by 68%, 88%, and 79% from baseline respectively (P<0.0001) after 13 weeks of treatment. The α/β CTX ratio increased by 62% (P<0.05). We conclude that resorption of type I collagen in postmenopausal osteoporosis is greater compared to healthy premenopausal women. There is no relative greater increase in the resorption of newly formed bone. With bisphosphonate treatment, the resorption of type I collagen is decreased after 13 weeks of treatment, but there is no greater decrease in the relative resorption of newly formed bone. In fact, there is a preferential decrease in the resorption of mature bone.

Reliability of spot urine samples in assessing arsenic exposure.

Urinary arsenic concentration is often used as a biomarker of arsenic exposure. First morning void (FMV) and spot urine samples from 131 participants in southeastern Michigan were analyzed using an HPLC-IC-PMS system for six different arsenic species: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsonous acid MMA[III], methylarsenic acid MMA[V], and dimethylarsenic DMA[V]. Bland-Altman plots, intraclass correlation coefficients (ICCs), and Pearson correlation procedures were used to evaluate the relationship between the arsenic species in FMV and spot urine collections after normalizing the samples by specific gravity. DMA[III] and MMA[III] were not detected in any of the samples. The sum of As[III], As[V], MMA[V], and DMA[V] was designated SumAs. The ICC between SumAs in FMV and SumAs in spot samples was 0.90. The ICC showed that 90% of variation comes from between individuals and not within individuals. A significant correlation (r=0.80 p<0.001) was observed between FMV and spot samples for SumAs. The spot sample were a good predictor of the MMA[V] (r=0.83 p<0.0001), and DMA[V] (r=0.77 p<0.0001) in the FMV sample. These associations suggest that either FMV or spot samples can be used as an adequate bioindicator of arsenic metabolites in human urine. The benefit of using spot urine samples, instead of 24-h or FMV urine samples, is the potential reduction in budgetary and logistic requirements in epidemiological studies.

Rationale and design of the Eplerenone combination Versus conventional Agents to Lower blood pressure on Urinary Antialbuminuric Treatment Effect (EVALUATE) trial: a double-blinded randomized placebo-controlled trial to evaluate the antialbuminuric effects of an aldosterone blocker in hypertensive patients with albuminuria

Although inhibitors of the renin-angiotensin system are effective as first-line antihypertensive drugs in hypertensive patients with chronic kidney disease, they cannot completely prevent the progression of renal injury. Many animal studies, including our own, and a few human studies suggest that mineralocorticoid receptor blockade could inhibit the ongoing renal damage in chronic kidney disease. Thus, we designed this double-blinded, randomized, placebo-controlled trial to evaluate the antialbuminuric effect of a low dose (50 mg day(-1)) of the mineralocorticoid receptor antagonist eplerenone. The study subjects will include 340 hypertensive patients (blood pressure: 130-180/80-100 mm Hg) with albuminuria (urinary albumin/creatinine ratio: 30-600 mg g(-1) in the first morning void urine), who are treated with an inhibitor of the renin-angiotensin system. Other classes of antihypertensive drugs may be added as needed to achieve the target blood pressure (<130/80 mm Hg). The primary study end point is the change in the urinary albumin/creatinine ratio after a 1-year study period. This trial is expected to show whether a low dose of mineralocorticoid receptor antagonists can exert an antialbuminuric effect in patients with chronic kidney disease.

Comparison of the yield of different screening approaches to detect chronic kidney disease

Screening for chronic kidney disease (CKD) has been advised in high-risk populations. The present study aims to compare the yields of four approaches to select high-risk subjects for CKD screening, which are defined as follows: Approach 1, history of cardiovascular (CV) disease, diabetes mellitus or hypertension (=high CV risk); Approach 2, high CV risk or age >55 years; Approach 3, urinary albumin concentration (UAC) ≥20 mg/L; or Approach 4, UAC ≥10 mg/L at pre-screening. The study population is a sample of the general population of Groningen, the Netherlands (n = 3398). UAC was measured (nephelometry) in a first morning void urine sample collected at home and sent to a laboratory by post. Information on demographics and the presence of CV risk factors was obtained by a questionnaire. The presence of CKD was determined during examination at an outpatient clinic. At baseline, 12% of the subjects met the criteria of Approach 1, 33% of Approach 2, 8% of Approach 3 and 25% of Approach 4. CKD was diagnosed in 370 subjects (11%). Approach 2 detected the most CKD patients (sensitivity 65%), while Approach 3 resulted in the lowest number needed to screen (1.9). During a follow-up of 7 years, only the UAC pre-screening approaches detected CKD patients who had both significantly accelerated renal function loss and increased CV risk compared to subjects without CKD. Only 28% of CKD patients detected by the UAC approaches used antihypertensive/angiotensin-converting enzyme inhibitor treatment prior to screening. This study suggests that pre-screening based on UAC should be favoured in comparison to screening based on CKD risk factors to detect CKD patients at high renal and CV risk.

Age Related Nocturnal Urine Volume and Maximum Voided Volume in Healthy Children: Reappraisal of International Children's Continence Society Definitions

We determined normal, age related reference data regarding maximum voided volume and nocturnal urine production using the same methodology as in clinical practice. A total of 62 girls and 86 boys without enuresis (mean +/- SD age 9.64 +/- 2.63 years, range 3 to 15) completed 4 days (2 weekends) of frequency-volume charts and 14 days of home recording of nocturnal urine production. From these recordings maximum voided volume with and without first morning void was derived for each subject. Also, average nocturnal urine volume with and without nocturia was calculated. Percentiles were produced by dividing the population into 1-year age groups. Based on 2,836 daytime voids and 1,977 overnight recordings, maximum voided volume and nocturnal urine volume showed a significant linear relationship with age but not with gender. Maximum voided volume with first morning void was significantly higher than without (403 +/- 137 ml vs 281 +/- 112 ml, p <0.0001) and the 50th percentile line of maximum voided volume with first morning void was 80 to 100 ml higher than Koff's formula (30 x [age + 1] ml). Conversely the 50th percentile of maximum voided volume without first morning void was almost identical to Koff's formula. Regarding nocturnal measurements, nocturia was noted on 128 nights (6.5%) and nocturnal urine volume on nights with nocturia was significantly higher than on nights without nocturia (365 +/- 160 ml vs 248 +/- 75 ml, respectively, p <0.0001). The 97.5th nocturnal urine volume percentile line of healthy children deviated markedly from the current International Children's Continence Society definition of nocturnal polyuria, especially at low and high ages. We demonstrate clearly that the universally used formula 30 x (age + 1) ml is indeed valid for a population of healthy Danish children but only if the first morning void is disregarded. Furthermore, we question the validity of the current International Children's Continence Society formula for nocturnal polyuria (nocturnal urine volume greater than 130% of maximum voided volume for age), and instead we propose the formula, nocturnal urine volume greater than 20 x (age + 9) ml.

A prospective study of protein excretion using short-interval timed urine collections in patients with lupus nephritis

The 24-h urine protein-to-creatinine ratio is the gold standard in evaluating proteinuria in lupus nephritis; however, the urine collection is inconvenient to the patient. Random spot urine protein-to-creatinine ratios, although convenient, have poor agreement with the 24-h ratios in these patients. Here, we sought to define a timed collection interval providing accurate and precise data and patient convenience. Urine from 41 patients, in 2 medical centers, with biopsy-proven lupus nephritis was collected at 6-h intervals for 24 h. The protein-to-creatinine ratio of each short collection was then compared with that of a 24-h collection made by combining the 6-h samples. A first morning void and spot urine samples were collected before and after the 24-h collection, respectively. There was significant diurnal variation with peak proteinuria at 6-12 h and nadir at 18-24 h. Each 6-h collection showed excellent correlation and concordance with the 24-h protein-to-creatinine ratio, but the 12-24-h interval had the best agreement. In contrast to the random spot urines, the first morning void also had excellent correlation and concordance, but underestimated the 24-h protein-to-creatinine ratio. Our study shows that a 12-h overnight urine collection is the best surrogate, with excellent agreement with the 24-h protein-to-creatinine ratio, and it is convenient for patients. There was little variability between centers, an important feature for clinical trials.

Repeated Measures of Validated and Novel Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons in Individuals Living Near an Aluminum Plant in Quebec, Canada

A longitudinal biomonitoring study was conducted to assess exposure to polycyclic aromatic hydrocarbons (PAH) in non-occupationally exposed nonsmoking adults living in the vicinity of an aluminum plant. Metabolites of several PAH (pyrene, naphthalene, chrysene, fluoranthene, benz[a]anthracene) were measured in the urine of the participants, including 1-hydroxypyrene (1-OHP) as a validated biomarker and pyrene diones as novel biomarkers. In total, 73 individuals living about 1 km away from the plant (taken as the exposed group) were compared repeatedly with 71 individuals living at least 11 km from the smelter (used as the control group). Complete first morning voids were collected twice, at a 2-wk interval, in the fall of 2005 and twice weekly for 2 consecutive weeks in the spring of 2006. Urinary biomarker concentrations were then measured by an ultra-performance liquid chromatography (UPLC) method with time-of-flight mass spectrometry detection (MS-TOF) (UPLC-MS-TOF). For most sampling days, individuals living near the plant showed significantly higher excretion values of both 1-OHP and pyrene diones (mean ratio up to 2- and 2.4-fold, respectively) than individuals living further from the plant. In the group living near the plant, geometric mean concentrations of 1-OHP varied from 0.047 to 0.058 μmol/mol creatinine, depending on the sampling day, as compared to 0.025 to 0.04 μmol/mol creatinine in the reference group. Corresponding mean values for pyrene diones were 0.017–0.056 μmol/mol creatinine and 0.014–0.039 μmol/mol creatinine, respectively. Urinary 1- and 2-naphthols were also measured as a reference and showed no significant differences between the two groups for most sampling days; metabolite concentrations of the other monitored PAH (chrysene, fluoranthene, benz[a]anthracene) were mostly below the analytical limit of detection of 0.005 to 0.01 μg/L, depending on the metabolite, with a detection rate varying from 0 to at most 21%. Individuals living near the aluminum plant thus appeared to be repeatedly exposed to higher pyrene levels than the control group, on the basis of both 1-OHP and pyrene dione excretions. However, 1-OHP concentrations observed in this first group were similar to those of other reference populations of nonsmokers studied in the past. Uptake of the other PAH associated with plant emissions was too small to significantly increase the excretion of their metabolites.

Evaluation of urinary arsenic as an indicator of exposure to residents of Tarkwa, Ghana

In Ghana, mining plays a significant role in the economic recovery programme. However, the gains are achieved at the cost of environmentaland human health. For many years, the extraction of gold involved roasting which released airborne particles and large quantities of arsenic(As). Sampling for this study was conducted in March 2004 to assess the contamination status of trace elements, especially As, in water andmine workers in Tarkwa, which has nearly a century of gold mining history. Water and human urine samples were collected from Tarkwa, inaddition to control samples taken from Accra, the capital of Ghana. Arsenic excretion was assessed in the first morning void urine. Concentrations of As and Mn in some water samples from Tarkwa were above the WHO drinking water guidelines. A potential health risk of As and Mn is a concern for the people consuming the contaminated water in this area. Levels of trace elements in water from control site were low compared to levels from Tarkwa. The mean urinary As concentration of 260 ìgl-1 from the study area was comparable to those in Asendemic areas of the world. This indicates relatively high degree of human exposure to As in Tarkwa, Ghana. Relatively low levels of As in water and no significant difference of As concentrations in urine between Tarkwa and Accra may suggest the presence of other sources of As contamination in Ghana, possibly food. This is the first study reporting 23 trace elements in human urine samples from a mining town in Ghana.

Heavy/Light-Chain Analysis of Monoclonal Gammopathies

Monoclonal gammopathies (M proteins) are associated with an extraordinarily broad array of clinical conditions that range from monoclonal gammopathy of undetermined significance (MGUS)1 to multiple myeloma. Three basic goals of the methods used to investigate M proteins are detection, immunochemical characterization, and quantification. Serum protein electrophoresis (SPE) techniques have undergone considerable improvements in the past few decades and now provide crisp resolution (especially in the β region) to detect many subtle electrophoretic differences in M proteins not readily distinguished by older 5-band gel techniques. Immunofixation (IFE) has replaced immunoelectrophoresis to become the gold standard for detecting an M protein and characterizing its isotype. Despite these advances, however, problems in detecting and especially in quantifying M proteins persist. By SPE, M proteins can migrate anywhere from the α to the γ region. They can be obscured by large proteins, such as haptoglobin in the α2 region or more commonly by transferrin and complement component 3 (C3) in the β region (1). Occasionally, IgM M proteins self-aggregate, creating problems with detection and measurement. Although most cases of multiple myeloma feature relatively large M protein peaks that are readily detected, even with low-resolution 5-band methods, 15%–20% of patients with multiple myeloma produce only free immunoglobulin light chains that, because of their relatively small molecular weights, are rapidly cleared into the urine, often producing no detectable M protein spike after SPE. Indeed, many cases of monoclonal free light chains (Bence Jones protein) cannot be identified by IFE of serum; however, IFE of concentrated early morning void (or 24-h urine) remains a reliable means to detect such small molecular weight M proteins. Unfortunately, urine samples too often are not submitted along with serum samples for the initial evaluation. With the development by Bradwell et al. in 2001 of highly specific assays for free …