Timed Urine Samples Research Articles

Correcting for Plasma Aldosterone Improves the Accuracy of Repeated Timed Urine Sampling for Estimation of Dietary Sodium Intake.

Long-term sodium balance studies show that sodium can be temporarily stored and released in tissues, mediated by circaseptan rhythms of aldosterone and cortisol. This complicates the reliability of a single 24-h urine collection to estimate individual sodium intake. We investigated whether repeated timed urine collection with and without correction for plasma aldosterone is a more accurate alternative for estimating daily sodium intake. We conducted a post hoc analysis of a metabolic ward study in which 16 healthy male adults consumed a diet with a fixed sodium content (50 or 200 mmol/day) for 7 days. Each day, urine was collected in 4 intervals (7:00-13:00 h, 13:00-19:00 h, 19:00-23:00 h, and 23:00-07:00 h). Plasma aldosterone was measured at 6:30 h, 12:30 h, and 18:30 h. Sodium intakes were estimated by various formulas using 3 timed urines of day 5-7. During a 200-mmol daily sodium intake, sodium intake estimates based on three repeated timed urine samples and the Toft equation differed 10 [IQR: 3-14], 8 [6-19], 36 [16-49], and 20 [10-43] mmol from the actual intake for intervals 7:00-13:00 h, 13:00-19:00 h, 19:00-23:00 h, 23:00-7:00 h, respectively. These measurements did not significantly differ from a single 24-h urine (20 [12-55] mmol). During a 50-mmol daily sodium intake, repeated timed urine collection performed worse than a single 24-h urine collection. On both diets, correction for plasma aldosterone increased accuracy and sodium intake estimates were significantly more accurate than a single 24-h urine. In a controlled environment, repeated timed urine collection corrected for plasma aldosterone is more accurate than a single 24-h urine collection.

The effect of renal function on the pharmacokinetics and pharmacodynamics of enavogliflozin, a potent and selective sodium-glucose cotransporter-2 inhibitor, in type 2 diabetes.

To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). An open-label, two-part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL). A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single- (r = 0.7866, p < 0.0001) and multiple-dose administration (r = 0.6606, p = 0.0438). Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m2) in a subsequent larger study.

Comparative Determination of Glomerular Filtration Rate Estimation Formulae in Type 2 Diabetic Patients: An Observational Study.

Assessing glomerular filtration rate (GFR) involves collecting timed urine samples for 24 hours, requiring significant time and resources in the clinical setting. Using predictive GFR formulae to assess renal function may be a better alternative. Our goal was to determine which predictive GFR formula had the highest level of concordance with the GFR that has been measured in a resource-poor setting. This is an observational study. We selected fifty (50) individuals diagnosed with type 2 diabetes (T2DM) in Kumasi, Ghana. The sociodemographic and clinical characteristics were obtained using a structured questionnaire. Urine was obtained from each subject over 24 hours. The levels of glucose (FBG) and creatinine in patients' blood, as well as the levels of creatinine in their urine, were measured after the patients had fasted overnight. Participants had a mean age of 57.4 ± 10.7 (years), BMI of 27.8 ± 4.1 (kg/m2), FBG of 9.0 ± 3.1 (mmol/L), and creatinine concentrations of 95.6 ± 29.1 (μmol/L). A Krouwer plot was used to compare the measured GFR with three formulae: Chronic Kidney Disease Epidemiology (CKD-EPI), Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault (CG) for GFR prediction. Among the 3 estimates, CG showed nonsignificance (p > 0.05) with the measured GFR. The primary finding was that the GFR calculated using the CG formula was not different from the GFR measured, suggesting that CG is the most appropriate alternative GFR estimate among a cross-section of T2DM patients in Ghana.

It is strongly recommended to not conduct, fund, or publish research studies that use spot urine samples with estimating equations to assess individuals' sodium (salt) intake in association with health outcomes: a policy statement of the World Hypertension League, International Society of Hypertension and Resolve to Save Lives.

Spot urine samples with estimating equations have been used to assess individuals' sodium (salt) intake in association with health outcomes. There is large random and systematic error in estimating sodium intake using this method and spurious health outcome associations. Substantial controversy has resulted from false claims the method is valid. Hence, the World Hypertension League, International Society of Hypertension and Resolve to Save Lives, supported by 21 other health organizations, have issued this policy statement that strongly recommends that research using spot urine samples with estimating equations to assess individuals' sodium (salt) intake in association with health outcomes should not be conducted, funded or published. Literature reviews on the health impacts of reducing dietary sodium that include studies that have used spot and short duration timed urine samples with estimating equations need to explicitly acknowledge that the method is not recommended to be used and is associated with spurious health outcome associations.

Timed Creatinine Clearance and Measured Glomerular Filtration Rate in Living Kidney Donors

Assessment of predonation glomerular filtration rate (GFR) is a key aspect of the evaluation of potential living kidney donors. In the United States, measurement of donor GFR is a regulatory requirement and most commonly assessed using 24-hour timed creatinine clearance (CrCl24), despite the potential for error due to incorrectly timed urine sample collection and tubular creatinine secretion.1,2 We aimed to determine the real-world performance of CrCl24 in living donor candidates.

Metabolomic Profiling Identifies New Endogenous Markers of Tubular Secretory Clearance.

The proximal tubules eliminate protein-bound toxins and drugs through secretion. Measurements or estimates of GFR do not necessarily reflect the physiologically distinct process of secretion. Clinical assessment of this important intrinsic kidney function requires endogenous markers that are highly specific for secretory transport. We used metabolomics profiling to identify candidate markers of tubular secretory clearance in 50 participants from a kidney pharmacokinetics study. We measured metabolites in three sequential plasma samples and a concurrent 10-hour timed urine sample using hydrophilic interaction liquid chromatography/high-resolution mass spectrometry. We quantified the association between estimated kidney clearance and normalized plasma peak height of each candidate solute to the clearance of administered furosemide, a protein-bound, avidly secreted medication. We identified 528 metabolites present in plasma and urine, excluding pharmaceuticals. We found seven highly (>50%) protein-bound and 49 poorly bound solutes with clearances significantly associated with furosemide clearance and 18 solute clearances favoring an association with furosemide clearance by the 90th percentile compared with GFR. We also found four highly bound and 42 poorly bound plasma levels that were significantly associated with furosemide clearance. We found several candidate metabolites whose kidney clearances or relative plasma levels are highly associated with furosemide clearance, an avidly secreted tracer medication of the organic anion transporters, highlighting their potential as endogenous markers of proximal tubular secretory clearance.

Variability of lead in urine and blood in healthy individuals

BackgroundLead is a non-essential toxic trace element. Lead in blood (BPb) is the most common biomarker of lead exposure but lead in urine (UPb) has also been used. There is, however, limited data on the variability of UPb in the general population and the association with BPb. ObjectivesOur aims were to assess variability of lead in repeated blood and urine samples. The diurnal variation of UPb was also examined as well as associations with BPb. MethodsWe established an openly available biobank including 60 healthy non-smoking individuals, 29 men and 31 women, 21–64 years of age (median 31 years), with repeated sampling of blood and urine. Timed urine samples were collected at six fixed time points in two 24 h periods, about one week apart, and adjusted for creatinine and specific gravity (SG). BPb and UPb were analyzed by inductively coupled plasma mass spectrometry. The within- and between-individual variabilities and intra-class correlation coefficients (ICCs; ratios of the between-individual to total observed variances) were calculated using mixed-effects models. ResultsThe ICCs for UPb samples were mostly above 0.5, when adjusted for creatinine or SG, and higher for overnight samples compared with daytime samples. The highest ICCs were obtained for BPb (ICC = 0.97) and for urine samples corrected for dilution by SG or creatinine. The ICC was 0.66 for overnight samples adjusted for creatinine. High correlations with BPb were found for 24 h UPb (rs = 0.77) and overnight samples, e.g. rs = 0.74 when adjusted for SG. There was diurnal variation of UPb with lowest excretion rate in overnight samples. There was also a significant association between the Pb excretion rate and urinary flow rate. ConclusionsIn addition to BPb, UPb adjusted for creatinine or SG seems to be a useful biomarker for exposure assessment in epidemiological studies.

Effect of diuretics on kidney stone-forming risk – an investigation using multiple timed urine collections

Introduction: Thiazide diuretics can lower urinary calcium excretion, helping to prevent recurrent calcium kidney stones. As dietary intake and urine chemistry varies throughout the day, a 24-h urine collection may not provide sufficient information to guide the optimal management in individual patients. Using multiple timed urine collections, we sought to identify times during the day when stone-forming risk is higher, allowing for therapy to be more accurately targeted. Methods: In a prospective study, healthy adult volunteers took a 4-week course of either hydrochlorothiazide (HCTZ) 25 mg/d or indapamide 2.5 mg/d. They were assessed at baseline, and at days 7, 14 and 28. At each time point, blood samples were taken for analysis and multiple timed urine samples were collected throughout the day, together with one overnight sample. Results: Diuretic treatment was well tolerated. Daily calcium and citrate excretion decreased, while ionized calcium and phosphate excretion were unchanged. Ionized calcium-divalent phosphate and ionized calcium-oxalate products were unchanged. In the timed urine samples, calcium excretion was decreased, particularly by indapamide, in the morning. Indapamide, but not HCTZ, decreased urinary citrate excretion, most obviously in overnight and early morning urines. No changes in ionized calcium were observed. Decreased divalent phosphate excretion was observed at several time points in the indapamide group. The ionized calcium-divalent phosphate product tended to decrease at most time points in both groups but no significant changes were observed in the ionized calcium-oxalate product. Conclusions: Indapamide 2.5 mg/d has a stronger protective effect against forming calcium kidney stones than HCTZ 25 mg/d. Most of the benefits appear to be achieved during the daytime and it may therefore be beneficial to prescribe medication twice daily or in the evening to maximize the protective effects of these agents. The benefits of indapamide treatment were attenuated by a reduction in urinary citrate excretion, an effect which has not been previously described. Keywords: hydrochlorothiazide, indapamide, kidney stones, urine collection

DIABETES INDUCED MICROALBUMINURIA - A CRITICAL REVIEW

Microalbuminuria is a marker and a risk factor of diabetic renal complications commences its role in path-ogenesis of nephropathy at its third stage, the stage of incipient nephropathy. Microalbuminuria is followed by overt nephropathy and end- stage renal disease of irreversible renal damage. Early detection of microal-buminuria has a decisive role in the healthy survival of diabetics. Urine albumin excretion rate and albumin creatinine ratio on timed urine samples, early morning samples or spot urine are of beneficial use. Ayurve-da describes diabetes mellitus as Prameha roga in which the major pathogenesis takes precedence in Moot-rasaya. Microalbuminuria can be described as Prameha Janya Vrikka Roga. It occurs due to Sanga (ob-struction), Vimarga Gamana (abnormal movement) of albumin; one of the constituents of Raktadhatu (blood) through Rakta and Mootra Vaha Srotas (channels of blood and urine). Medicines which are Pramehaghna (anti-diabetic), Mootra and Raktavaha Srothosodhana (cleanse the channels) may be of good worth to rectify the pathology of microalbuminuria providing an improved life for diabetics.

Whole Blood Ionized Magnesium, a Novel Nutrition Biomarker for Magnesium Intake

Abstract Objectives Most studies used serum magnesium concentration and total urine magnesium as nutrition biomarkers of magnesium, but whether these biomarkers are sensitive to changes in dietary intake of magnesium is uncertain. Whole blood ionized magnesium (iMg2+) is the free bioactive form of magnesium in the body, and therefore it could be more sensitive to the changes in magnesium intake. Thus, we aimed to compare the responses of iMg2+, serum magnesium concentration, and total urine magnesium following an oral dose of magnesium. Methods Healthy adults participated in a randomized, single-blind, placebo-controlled crossover trial. They were randomly assigned to 300 mg of magnesium chloride (MgCl2, ReMag®) or placebo, taken with a low-magnesium breakfast after 8-hours of fasting. Timed blood and urine samples were obtained beginning 15-minutes before breakfast, and then at 0, 0.5, 1, 2, 4, 6, 8, and 24-hours timepoints following breakfast. Pharmacokinetic analyses included area under the curve (AUC), the maximum concentration (Cmax), and the time to maximum concentration (Tmax) for iMg2+, serum magnesium concentration, and total urine magnesium. Data were analyzed using paired t-test and Wilcoxon signed-rank test, and reported as mean ± standard deviation, or as median and range, depending on normality. Results Seventeen participants were included in the data analyses. Responses were observed following MgCl2 compared to placebo for iMg2+ (AUC = 1.51 ± 0.96 vs. 0.84 ± 0.82, and Cmax = 1.38 ± 0.13 vs. 1.32 ± 0.07, both P &amp;lt; 0.05). We saw no response following MgCl2 versus placebo for serum magnesium concentration (AUC = 27.00 [0, 172.93] vs. 14.55 [0, 91.18], and Cmax = 2.38 [1.97, 4.01] vs. 2.24 [1.98, 4.31]), and for total urine magnesium (AUC = 201.74 ± 161.63 vs. 139.30 ± 92.84, and Cmax = 26.12 [12.91, 88.63] vs. 24.38 [13.51, 81.51]), both P &amp;gt; 0.05. Conclusions The response of iMg2+ to a single oral dose of magnesium was more pronounced than the responses of serum magnesium concentration and total urine magnesium. Therefore, iMg2+ may be a more sensitive nutrition biomarker for magnesium intake. Funding Sources Funding for this study was provided through an unrestricted educational grant from Think Healthy Group Inc.

Validez y limitaciones de los métodos para medir la ingesta y la eliminación de sal

High blood pressure (HBP) is the main modifiable cardiovascular risk factor. HBP can be related to high salt intake. To measure intake, not all feeding surveys are comparable and valid. The reference procedure for assessing salt intake consists of measuring the urinary excretion of sodium in urine collected during 24hours, although alternative methods have been proposed, such as the collection of punctual and timed urine samples. In this review, we analyze which instruments allow the assessment of salt intake and which of them have provided greater validity and reliability through studies of concordance with the elimination of sodium in urine. Current food consumption surveys are inadequate because of their wide variability and relatively low correlation with the elimination of sodium in 24-hour urine. Its main limitation is the need for validation in different population groups. In primary care, salt intake should be assessed by using frequency-of-consumption questionnaires that collect foods with a high salt content, the consumption of preprepared dishes and questions that quantify the addition of salt in the preparation of food or at the table. For the validation of these questionnaires, the standard gold elimination of 24-hour urine sodium adjusted according to creatinine clearance should be used.

Fluctuation of Water Intake and of Hydration Indices during the Day in a Sample of Healthy Greek Adults.

Mild dehydration may occur during specific periods of the day because of poor hydration habits and/or limited access to a variety of beverages or foods, for example, in work environments. Measurement of hydration indices in spot or in 24 h urine samples may mask mild dehydration in specific periods of the day. Healthy subjects (n = 164; 74 females; age 38 ± 12 years) living in Athens, Greece were enrolled in the study. Subjects recorded their solid food and drink intakes and recorded and collected all urinations for three consecutive days. Water intake was analyzed in 24 h and 6 h periods from wake-up time and scored for variety. Urine hydration indices (osmolality, volume, color, specific gravity) were analyzed in 24 h samples, in morning urine samples and in samples collected in 6 h periods from wake-up time. Fluctuations during the day were significant for the intake of drinking water, hot beverages, milk, fruit and vegetable juices, and alcoholic drinks and for urine osmolality, volume, color, and specific gravity. The urine volume of the first 6 h period after wake-up time (557 ± 231 mL/day) reflects by 76% the 24 h urine collection (1331 ± 144 mL/day). Water intake from all beverages, with the exception of alcoholic beverages, was greater in the first 6h period (morning period) and decreased throughout the day. Hydration indices changed accordingly. The 6 h timed urine sample collected reflects indices in samples collected over 24 h better than any spot urine sample.

Abstract P226: Changes of Blood Pressure and Urinary Sodium Over 18 Years in Rural China: Results From the INTERMAP China Prospective Study

Background: Tremendous dietary pattern changes could be a driver of the increasing burden of high blood pressure (BP) in developing countries. However, data on nutrition transitions and associated BP changes are scarce. Objective: To explore BP changes and sodium (Na) consumption over 18 years in China. Methods: International Collaborative Study of Macro-/Micro-nutrients and Blood Pressure (INTERMAP) enrolled 839 men and women aged 40-59 years from three geographically diverse regions (Beijing, Shanxi in the north and Guangxi in the south) in 1997. INTERMAP China Prospective (ICP) Study followed up these three populations in 2015-2016. Seated BP were measured at least twice following at least 5 minutes of rest, using a random zero sphygmomanometer for the INTERMAP (baseline) and an oscillometric device (Omron HEM-907) for the ICP (follow-up). When calculating BP changes, baseline values were converted using equations developed in a calibration study. Timed 24-hr urine samples were collected at baseline and follow-up using the same protocol. Urinary Na and creatinine (Cr) were measured by emission flame photometry method at baseline and ion-selective electrode method at follow-up. BP and dietary Na changes over time were compared using student t test. Results: Systolic BP increased considerably in all three sites; largest increment in Guangxi (18.6, 95% CI: 16.0-21.1 mm Hg, P&lt;0.001) and smallest in Beijing (9.1, 6.3-11.8 mm Hg, P&lt;0.001) (Table 1). Level of urinary Na was almost double in north (Beijing and Shanxi) than south (Guangxi) at follow-up (P&lt;0.001), similar as baseline. On average, participants consumed 10.8 (4.7) and 11.8 (4.7) grams of salt at Beijing and Shanxi and 6.3 (3.0) grams of salt at Guangxi at follow-up, though a trend of reduction in Na/Cr (-3.7, 95% CI: -4.7- -2.6, P&lt;0.001) overall was documented. Conclusions: Systolic BP levels increased considerably in this cohort between 1997 and 2015 in rural China. Na consumption might have a declining trend, but still at a very high level at northern China.

Bioavailability of Isothiocyanates From Broccoli Sprouts in Protein, Lipid, and Fiber Gels.

ScopeOptimization of bioavailability of dietary bioactive health‐beneficial compounds is as important as increasing their concentration in foods. The aim of this study is to explore the change in bioavailability of isothiocyanates (ITCs) in broccoli sprouts incorporated in protein, fiber, and lipid gels.Methods and resultsFive participants took part in a cross‐over study and collected timed urine samples up to 24 h after consumption of proteins, dietary fibers, and lipid gels containing broccoli sprouts powder. Sulforaphane and iberin metabolites were determined in the urine samples. Samples in which sulforaphane and iberin were preformed by myrosinase led to a higher bioavailability of those compounds. Compared to the control broccoli sprout, incorporation of sprouts in gels led to lower bioavailability for preformed sulforaphane and iberin (although for sulforaphane the lower bioavailability was not significantly different) whereas for the gels rich in their precursors, glucoraphanin and glucoiberin, the opposite trend was observed (although not significantly different).ConclusionThis explorative study suggests that ITCs bioavailability can be modulated by food structure and composition and further and deeper investigations are needed to develop food products that lead to an optimized ITCs bioavailability.

Random urine testing for carcinoid tumours in paediatric subjects using a LC-MSMS method with age specific normalised reference intervals

Introduction: In clinical practice, tests for urine catecholamine metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) is often used for diagnosis of carcinoid tumours of the stomach, colon and lung.1,2 Paediatric reference intervals have been traditionally based on timed urine collections. However, there is difficulty in collecting timed urine samples in infants and children.

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

Conventional methods to diagnose and monitor chronic kidney disease (CKD) in children, such as creatinine level and cystatin C-derived estimated glomerular filtration rate (eGFR) and assessment of proteinuria in spot or timed urine samples, are of limited value in identifying patients at risk of progressive kidney function loss. Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in adults. To determine whether elevated suPAR levels are associated with renal disease progression in children with CKD. Post hoc analysis of 2 prospectively followed up pediatric CKD cohorts, ie, the ESCAPE Trial (1999-2007) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. In the 2 trials, a total of 898 children were observed at 30 (ESCAPE Trial; n = 256) and 55 (4C Study; n = 642) tertiary care hospitals in 13 European countries. Renal diagnoses included congenital anomalies of the kidneys and urinary tract (n = 637 [70.9%]), tubulointerstitial nephropathies (n = 92 [10.2%]), glomerulopathies (n = 69 [7.7%]), postischemic CKD (n = 42 [4.7%]), and other CKD (n = 58 [6.5%]). Total follow-up duration was up to 7.9 years, and median follow-up was 3.1 years. Analyses were conducted from October 2016 to December 2016. Serum suPAR level was measured at enrollment, and eGFR was measured every 2 months in the ESCAPE Trial and every 6 months in the 4C Study. The primary end point of CKD progression was a composite of 50% eGFR loss, eGFR less than 10 mL/min/1.73 m2, or initiation of renal replacement therapy. The primary end point in this study was renal survival, defined as a composite of 50% loss of GFR that persisted for at least 1 month, the start of renal replacement therapy, or an eGFR less than 10 mL/min/1.73 m2. Of the 898 included children, 560 (62.4%) were male, and the mean (SD) patient age at enrollment was 11.9 (3.5) years. The mean (SD) eGFR was 34 (16) mL/min/1.73 m2. The 5-year end point-free renal survival was 64.5% (95% CI, 57.4-71.7) in children with suPAR levels in the lowest quartile compared with 35.9% (95% CI, 28.7-43.0) in those in the highest quartile (P < .001). By multivariable analysis, the risk of attaining the end point was higher in children with glomerulopathies and increased with age, blood pressure, proteinuria, and lower eGFR at baseline. In patients with baseline eGFR greater than 40 mL/min/1.73 m2, higher log-transformed suPAR levels were associated with a higher risk of CKD progression after adjustment for traditional risk factors (hazard ratio, 5.12; 95% CI, 1.56-16.7; P = .007). Patients with high suPAR levels were more likely to have progression of their kidney disease. Further studies should determine whether suPAR levels can identify children at risk for future CKD.

Steatorrhea and Hyperoxaluria in Severely Obese Patients Before and After Roux-en-Y Gastric Bypass

Hyperoxaluria after Roux-en-Y gastric bypass (RYGB) is generally attributed to fat malabsorption. If hyperoxaluria is indeed caused by fat malabsorption, magnitudes of hyperoxaluria and steatorrhea should correlate. Severely obese patients, prior to bypass, ingest excess dietary fat that can produce hyperphagic steatorrhea. The primary objective of the study was to determine whether urine oxalate excretion correlates with elements of fat balance in severely obese patients before and after RYGB. Fat balance and urine oxalate excretion were measured simultaneously in 26 severely obese patients before and 1 year after RYGB, while patients consumed their usual diet. At these time points, stool and urine samples were collected. Steatorrhea and hyperoxaluria were defined as fecal fat >7 g/day and urine oxalate >40 mg/day. Differences were evaluated using paired 2-tailed t tests. Prior to RYGB, 12 of 26 patients had mild to moderate steatorrhea. Average urine oxalate excretion was 61 mg/day; there was no correlation between fecal fat and urine oxalate excretion. After RYGB, 24 of 26 patients had steatorrhea and urine oxalate excretion averaged 69 mg/day, with a positive correlation between fecal fat and urine oxalate excretions (r= 0.71, P < .001). For each 10 g/day increase in fecal fat output, fecal water excretion increased only 46 mL/day. Steatorrhea and hyperoxaluria were common in obese patients before bypass, but hyperoxaluria was not caused by excess unabsorbed fatty acids. Hyperphagia, obesity, or metabolic syndrome could have produced this previously unrecognized hyperoxaluric state by stimulating absorption or endogenous synthesis of oxalate. Hyperoxaluria after RYGB correlated with steatorrhea and was presumably caused by excess fatty acids in the intestinal lumen. Because post-bypass steatorrhea caused little increase in fecal water excretion, most patients with steatorrhea did not consider themselves to have diarrhea. Before and after RYGB, high oxalate intake contributed to the severity of hyperoxaluria.

Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents' Exposure.

Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i) develop a robust analytical method, ii) determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii) measure the metabolites in samples collected as part of a large investigation of rural residents’ exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites. Three volunteers received a single oral dose of 0.03 mg/kg body weight and timed urine samples were collected and analysed. The volunteer study demonstrated that both penconazole-OH and penconazole-COOH are excreted in humans following an oral dose and are viable biomarkers. Excretion is rapid with a half-life of less than four hours. Mean recovery of the administered dose was 47% (range 33%–54%) in urine treated with glucuronidase to hydrolyse any conjugates. The results from the residents’ study showed that levels of penconazole-COOH in this population were low with >80% below the limit of detection. Future sampling strategies that include both end of exposure and next day urine samples, as well as contextual data about the route and time of exposure, are recommended.

Tubular Secretion in CKD.

Renal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation.

Transfer of Methamphetamine (MA) into Breast Milk and Urine of Postpartum Women who Smoked MA Tablets during Pregnancy

Methamphetamine (MA) use by pregnant women remains a growing problem in South East Asia. After delivery, a negative maternal urine MA assay is assumed to reflect the absence of MA in breast milk and marks breastfeeding initiation. To date, no data exist that describe the relationship between the peripartum and postpartum transfer of MA into breast milk and its urinary excretion in women, following recreational use by smoking. This study aimed to determine the pharmacokinetic of smoked MA in breast milk and its relationship to urinary MA excretion in postpartum women who tested positive for MA before delivery. Timed urine and breast milk samples of 33 women who had positive urine drug screens for MA prior to delivery were analyzed for MA using Acquity Ultra Performance Liquid Chromatography (Waters, Milford, Massachusetts, USA) with the ACQUITY UPLC Photodiode Array Detector (Waters). Those participants with 4 or more timed breast milk samples were included for pharmacokinetic calculation using log-linear trapezoidal rule. Pharmacokinetic data from 2 women were analyzed. The half-life values for MA in the breast milk were 11.3 and 40.3 hours. The absolute infant doses were 21.3 and 51.7 µg/kg/day. Methamphetamine disappears from breast milk approximately 1 day before the maternal urine MA becomes negative. Smoked MA shows a similar breast milk pharmacokinetic pattern to previously reported intravenous MA. Breastfeeding can be safely initiated in mothers whose urine MA screen has turned negative for ≥ 24 hours. However, concurrent maternal substance use treatment and screening is necessary for continued promotion of lactation.