Random Urine Specimens Research Articles

Evaluation of the URiSCAN 2 ACR Strip to estimate the urine albumin/creatinine ratios.

The urine albumin/creatinine ratio (ACR) test is used to screen patients with chronic diseases, such as diabetes, hypertension and cardiovascular diseases that put them at an increased risk of developing kidney disease. Here, we evaluated the performance of the URiSCAN 2 ACR Strip (URiSCAN; YD diagnostics, Yongin, Korea), a semiquantitative point-of-care testing (POCT) assay, and we compared to an existing POCT assay and a quantitative assay. A total of 1,020 random urine specimens were analyzed using the semiquantitative URiSCAN 2 ACR Strip and semiquantitative CLINITEK Microalbumin 2 Strip (CLINITEK; Siemens, New York, USA). We evaluated the precision of the URiSCAN 2 ACR Strip and compared the results of the ACR obtained from URiSCAN to those of CLINITEK with the quantitative results of a quantitative assay as a reference. The precision evaluation of the URiSCAN revealed a range between the cutoff (C50 )-20% and C50 +20% bounds, the C5 -C95 interval, with 85.8% confidence. URiSCAN and CLINITEK showed sensitivity and specificity of 87.7% and 72.2%, and 90.2% and 83.0%, respectively. The concordance rates of URiSCAN with CLINITEK and the quantitative assay were 75.6% and 79.1%, respectively. The concordance rate in the abnormal range (≥30mg/g) between URiSCAN and the quantitative assay were higher than that between CLINITEK and the quantitative assay (78.8% vs 75.4%). URiSCAN showed good precision and comparable sensitivity with lower specificity than those of CLINITEK.

Microalbuminuria in Diabetic Patients in the Bamenda Health District

Diabetic nephropathy (DN) is the most common cause of end stage renal disease (ESRD) and it accounts for one third of all patients requiring renal replacement therapy in Africa. Diabetic patients with microalbuminuria (MA) have an increased risk of progression to macroalbuminuria and later to ESRD. So detecting MA which is a marker of DN helps to alert the clinician to intervene at a time when future renal damage is still preventable. The main goal of this study was to determine the prevalence of MA in diabetic patients at the Bamenda Regional Hospital. This study was a prospective cross sectional study involving diabetic patients at the Bamenda Regional Hospital. A random (spot) or first morning urine specimen was collected and MA was measured by a semi quantitative dipstick method using the URS-14H urine test strips. The prevalence of MA in the present study was 34.6%, which is high but similar to the results of other studies done in sub-Saharan Africa. Although MA was more common (50%) in individuals with diabetes more than 16 years, a high proportion (42.85%) of patients with MA had a duration of diabetes of ≤ 5years. There was no significant difference in the occurrence of MA with respect to age, gender and duration of diabetes. This study showed a high prevalence of MA in the diabetic population presenting at the Bamenda Regional Hospital. Consequently, measures of glycemic control should be enhanced in this population to prevent the progression to macroalbuminuria and ESRD.

Urinary oxalate to creatinine ratios in healthy Turkish schoolchildren

Aim: we aimed to establish reference values for urinary oxalate to creatinine ratios in healthy children aged 6–15 years and to investigate the relationship between their nutritional habits and oxalate excretion.Materials and methods: Random urine specimens from 953 healthy children aged 6–15 years were obtained and analyzed for oxalate and creatinine. Additionally, a 24-h dietary recall form was prepared and given to them. The ingredient composition of the diet was calculated. The children were divided into three groups according to age: Group I (69 years, n = 353), Group II (10–12 years, n = 335), and Group III (13–15 years, n = 265).Results: The 95th percentile of the oxalate to creatinine ratio for subjects aged 6–9, 10–12, and 13–15 years were 0.048, 0.042, and 0.042 mg/mg, respectively. The oxalate to creatinine ratio was significantly higher in Group 1 than in Group 2 and Group 3. Urinary oxalate excretion was positively correlated with increased protein intake and negatively correlated with age. A significant positive correlation was determined between urinary oxalate excretion and the proline, serine, protein, and glycine content of diet. Dietary proline intake showed a positive correlation with the urine oxalate to creatinine ratio and was found to be an independent predictor for urinary oxalate.Conclusions: These data lend support to the idea that every country should have its own normal reference values to determine the underlying metabolic risk factor for kidney stone disease since regional variation in the dietary intake of proteins and other nutrients can affect normal urinary excretion of oxalate.

Four to seven random casual urine specimens are sufficient to estimate 24-h urinary sodium/potassium ratio in individuals with high blood pressure.

This study was done to clarify the optimal number and type of casual urine specimens required to estimate urinary sodium/potassium (Na/K) ratio in individuals with high blood pressure. A total of 74 individuals with high blood pressure, 43 treated and 31 untreated, were recruited from the Japanese general population. Urinary sodium, potassium and Na/K ratio were measured in both casual urine samples and 7-day 24-h urine samples and then analyzed by correlation and Bland–Altman analyses. Mean Na/K ratio from random casual urine samples on four or more days strongly correlated with the Na/K ratio of 7-day 24-h urine (r=0.80–0.87), which was similar to the correlation between 1 and 2-day 24-h urine and 7-day 24-h urine (r=0.75–0.89). The agreement quality for Na/K ratio of seven random casual urine for estimating the Na/K ratio of 7-day 24-h urine was good (bias: −0.26, limits of agreements: −1.53–1.01), and it was similar to that of 2-day 24-h urine for estimating 7-day 24-h values (bias: 0.07, limits of agreement: −1.03 to 1.18). Stratified analyses comparing individuals using antihypertensive medication and individuals not using antihypertensive medication showed similar results. Correlations of the means of casual urine sodium or potassium concentrations with 7-day 24-h sodium or potassium excretions were relatively weaker than those for Na/K ratio. The mean Na/K ratio of 4–7 random casual urine specimens on different days provides a good substitute for 1–2-day 24-h urinary Na/K ratio for individuals with high blood pressure.

Elevated levels of protein in urine in adulthood after exposure to the Chinese famine of 1959-61 during gestation and the early postnatal period.

Animal models have suggested that undernutrition during gestation and the early postnatal period may adversely affect kidney development and compromise renal function. As a natural experiment, famines provide an opportunity to test such potential effects in humans. We assessed whether exposure to the Chinese famine of 1959-1961 during gestation and early postnatal life was associated with the levels of proteinuria among female adults three decades after exposure to the famine. We measured famine intensity using the cohort size shrinkage index and we constructed a difference-in-difference model to compare the levels of proteinuria, measured with a dipstick test of random urine specimens, among Chinese women (n = 70 543) whose exposure status to the famine varied across birth cohorts (born before, during or after the famine) and counties of residence with different degrees of famine intensity. Famine exposure was associated with a greater risk [odds ratio (OR) = 1.54; 95% confidence interval (CI): 1.04, 2.28; P = 0.029) of having higher level of proteinuria among women born during the famine years (1959-61) compared with the unexposed post famine-born cohort (1964-65) in rural samples. No association was observed among urban samples. Results were robust to adjustment for covariates. Severe undernutrition during gestation and the early postnatal period may have long-term effects on levels of proteinuria in humans, but the effect sizes may be small.

Six random specimens of daytime casual urine on different days are sufficient to estimate daily sodium/potassium ratio in comparison to 7-day 24-h urine collections

The objective of this study was to determine the optimal number and type of casual (spot) urine specimens required to estimate an individual's urinary sodium/potassium (Na/K) ratio. A total of 48 participants, 25 men and 23 women, aged between 25 and 59 years, was recruited from healthy volunteers. The Na/K ratio in each casual urine and 7-day 24-h urine sample was measured. Correlation analysis and the quality of agreement by the Bland and Altman method between casual urine and 24-h urine were analyzed. The mean Na/K ratio of 7-day 24-h urine was 4.3. The mean Na/K ratio of six random specimens of daytime (collected between 09 and 17 hours) casual urine correlated most strongly with the Na/K ratio of 7-day 24-h urine (r=0.87). The bias for the mean Na/K ratio between 7-day 24-h urine and daytime casual urine was almost negligible (0.03), and the quality of agreement for the mean of the six random, daytime casual urine specimens on different days was similar to that of the 2-day 24-h urine samples for estimating 7-day 24-h values. Our findings show that the mean Na/K ratio of six random daytime casual urine specimens on different days was a good substitute for the 2-day 24-h urine Na/K ratio.

The Urinary Protein-to-Creatinine Ratio in Canadian Women at Risk of Preeclampsia: Does the Time of Day of Testing Matter?

ObjectivesTo determine the performance of a protein-to-creatinine ratio threshold of 30mg/mmol in pregnant women investigated for hypertension according to the time of day of the sample MethodsThis prospective study included ambulatory pregnant women investigated for hypertensive disorders. A single voided random urine specimen was obtained to determine the protein-to-creatinine ratio, followed immediately by a 24-hour urine collection. Statistical analyses included Spearman correlation, sensitivity, specificity, predictive values, likelihood ratios, and receiver-operator characteristic curves with 95% confidence intervals. A P value<0.05 was considered statistically significant. ResultsAmong the 91 specimens analyzed, 47.3% showed significant proteinuria in the 24-hour collection and 33% were first morning samples. The protein-to-creatinine ratio and 24-hour urinary protein excretion were highly correlated (r=0.92, P<0.001). The diagnostic accuracy of the protein-to-creatinine ratio threshold of 30mg/mmol was lower in first morning samples than in samples obtained during the rest of the day, with sensitivity 58% and 90%, specificity 93% and 100%, positive predictive value 88% and 100%, negative predictive value 72% and 92%, positive likelihood ratio 8 and not calculable, and negative likelihood ratio 0.45 and 0.1, respectively. The receiver-operator characteristic area under the curve was 0.94 (95% CI 0.86 to 1) for first morning samples and 1.0 (95% CI 0.99 to 1) for other samples. ConclusionA protein-to-creatinine ratio threshold of 30mg/mmol reliably identifies significant proteinuria, but its reliability is reduced in first morning samples. Consequently, such samples should not be used for this purpose.

Urinary thyroid hormone parameters test for evaluating the thyroid function during pregnancy

It is necessary to regularly monitor thyroid function status during pregnancy. The repeated tests on serum thyroid hormones are invasive and can be uncomfortable. Sampling urine may provide an effective alternative. The primary aim of this study was to investigate if there is a correlation between the serum and urine levels of thyroid hormones during pregnancy. The secondary aim was to investigate their variation during pregnancy. This study collected the serum specimens of 30 healthy pregnant women at 9–12, 14–17, 23–26, and 37–40 weeks of gestation, respectively, simultaneously along with random urine specimens. This study compared the median levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) in serum and urine among four gestational stages. The differences were statistically significant (p < 0.05). There were positive correlations between serum FT3 (sFT3) and uFT3/uRBP (the ratio of urine FT3(uFT3) and urine retinol binding protein (uRBP)), r = 0.38 (I2 = 0%, 95% CI: 0.21 ∼ 0.54), serum FT4 (sFT4) and uFT4/uRBP (the ratio of urine FT4 (uFT4) and uRBP), r = 0.29 (I2 = 68.9%, 95% CI: 0.07 ∼ 0.51), and no correlation between serum TSH (sTSH) and uTSH/uRBP (the ratio of urine TSH (uTSH) and uRBP), r = 0.11 (I2 = 86.7%, 95% CI: −0.24 ∼ 0.45). In conclusion, the levels of sFT3, sFT4, uFT3/uRBP, and uFT4/uRBP continued to decrease until the 27th week of gestation, when it was almost invariant. The levels of uFT3/uRBP and uFT4/uRBP correlated well with the sFT3 and sFT4 during pregnancy, which may provide a more convenient and secure way to monitor the maternal thyroid function status during pregnancy.

Comparison of urinary protein creatinine index in normal and heavy exercise performing individuals

Background: Physical exercise is the performance of some activity in order to develop or maintain physical fitness and overall health. Exercise induce proteinuria is generally benign and a function of the intensity- rather than the duration of the exercise. Quantification using a 24 hours urine collection for protein is being replaced by the urine protein creatinine ration from a random urine specimen, ideally from the first morning void. Aims & Objective: To compare protein creatinine index between normal and heavy exercise performing individual. Materials and Methods: Total 40 controls (who were not doing exercise) and 34 subjects) who were doing heavy exercise daily) were selected for the study. Their early morning urine sample was taken for estimating urinary protein by quantitative sulfosalycylic acid method and creatinine by Jaffe’s method using colorimetry. Results: The normal range of the PCI which was stabilized in this study was 62- 220. On comparison of the PCI between the control and the subject, it was found to be significantly elevated in the person who does heavy exercise (controls = 114.64 ± 47.96 and in the person who does heavy exercise = 326.98 ± 117.99) (p

Albuminuria according to status of autoimmunity and insulin sensitivity among youth with type 1 and type 2 diabetes.

OBJECTIVETo evaluate whether etiologic diabetes type is associated with the degree of albuminuria in children with diabetes.RESEARCH DESIGN AND METHODSSEARCH is an observational, longitudinal study of children with diabetes. Youth with newly diagnosed diabetes were classified according to diabetes autoantibody (DAA) status and presence of insulin resistance. We defined insulin resistance as an insulin sensitivity score <25th percentile for the United States general youth population. DAA status was based on positivity for the 65-kD isoform of glutamate decarboxylase and insulinoma-associated protein 2 antigens. The four etiologic diabetes type groups were as follows: DAA+/insulin-sensitive (IS) (n = 1,351); DAA+/insulin-resistant (IR) (n = 438); DAA−/IR (n = 379); and DAA−/IS (n = 233). Urinary albumin:creatinine ratio (UACR) was measured from a random urine specimen. Multivariable regression analyses assessed the independent relationship between the four diabetes type groups and magnitude of UACR.RESULTSAdjusted UACR means across the four groups were as follows: DAA+/IS = 154 μg/mg; DAA+/IR = 137 μg/mg; DAA−/IR = 257 μg/mg; and DAA−/IS = 131 μg/mg (P < 0.005). Only DAA−/IR was significantly different. We performed post hoc multivariable regression analysis restricted to the two IR groups to explore the contribution of DAA status and insulin sensitivity (continuous) to the difference in UACR between the IR groups. Only insulin sensitivity was significantly associated with UACR (β = −0.54; P < 0.0001).CONCLUSIONSIn youth with diabetes, the DAA−/IR group had a greater UACR than all other groups, possibly because of the greater magnitude of insulin resistance. Further exploration of the relationships between severity of insulin resistance, autoimmunity, and albuminuria in youth with diabetes is warranted.

Apparent Insufficiency of Iodine Supplementation in Pregnancy

Pregnant woman are at increased risk for iodine deficiency, which may induce thyroid insufficiency and have damaging effects not only on the mother but also the fetus. We hypothesize that iodine supplementation during pregnancy reduces the risk for iodine deficiency. Cross-sectional study to assess iodine levels in random urine specimens during pregnancy in New York City. One hundred eighty-two women visited a clinic where free iodine supplementation was offered (150 μg of potassium iodide daily; Group A), and 183 women were seen at a practice at which no supplementation was offered (Group B). Overall, more than one out of two pregnant women in New York City were at risk for iodine deficiency with a spot urinary iodine (UI) level less than 150 μg/L and could be defined as at risk for iodine deficiency. The median urine iodine concentration for the entire group was 152.5 μg/L, but there was considerable variation from 10.9 to 1210 μg/L. The median UI level of the supplemented Group A (169.8 μg/L) was significantly greater than that of Group B (128.4 μg/L; p<0.01). Based on World Health Organization (WHO) guidelines, 38.9% of Group B women were at risk for mild, moderate, or severe iodine deficiency, compared with 22.8% of Group A women. New York City pregnant women were significantly less prone to iodine deficiency when provided with iodine supplementation. Nevertheless, when spot UI levels were used to estimate iodine sufficiency, more than 20% of supplemented women were still at risk for iodine deficiency according to WHO guidelines, suggesting that current supplementation practices remain insufficient.

Retrospective study of quantitative free light chain levels in random urine of patients with multiple myeloma

The traditional method to quantify the immunoglobulin free light chains (FLCs) in patients with multiple myeloma (MM)is based on either their serum levels or on 24-hour urine collections. The latter method is cumbersome and ofteninaccurate, and serum levels are currently the preferred method for quantifying FLCs in MM. Scarce data exist on the FLCquantification in random urine samples. In this study, we first compared serum and urine levels of FLCs measured in24-hour specimens obtained from 56 consecutive MM patients. We subsequently examined the same correlation in 209random urine specimens obtained from a second cohort of 117 consecutive MM patients. Serum FLCs were highlycorrelated, both with the 24-hour and the random urine specimens. With the latter, the Pearson coefficient r was 0.805 and0.748 for kappa and lambda light chains, respectively (p&lt;0.001), even in the presence of renal insufficiency. Random urineFLCs levels &gt;1.2 mg/dL predicted a positive urine immunofixation with a specificity and sensitivity of 52.7% and 95.8%,respectively. Since random urine quantification of kappa and lambda FLCs paralleled their serum counterparts over time,this method could represent an additional non-invasive test for assessing disease activity in MM patients.

Protocol of an observational study to evaluate diabetic nephropathy through detection of microalbuminuria in Indian patients

Aim:To assess the prevalence of persistent microalbuminuria (MAU), its clinical correlates by dip stick method, its predictive value for potential kidney disease and the utility of this test as objective cue for health care seeking behavior in adult Indian patients with type 2 diabetes mellitus.Materials and Methods:Approximately 400,000 patients shall be enrolled in this multicentric, cross sectional study. Patients meeting eligibility criteria shall be screened for MAU through urine dipstick test using random daytime single spot urine specimen. Result shall be expressed either positive or negative based on the presence or absence of albumin in the urine and will be correlated with the corresponding random blood glucose. Height, weight, waist circumference and blood pressure shall be assessed. There will be three visits with a minimum interval of 28 days between two visits, to be completed within 180 days, and at least two of three urine tests measured in this period must show elevated albumin levels to diagnose MAU.Conclusion:Detection of MAU through the dipstick method is postulated to be a rapid, reliable test for early detection of diabetic nephropathy, which, in turn will help the physician to plan treatment strategy. Further, it will help to identify the disease burden on the individual and society, and may serve as an objective cue for improved health care seeking behavior, as well as a catalyst for health policy change.

A Cost-Benefit and Accurate Method for Assessing Microalbuminuria: Single versus Frequent Urine Analysis

Background. The purpose of this study was to answer the question whether a single testing for microalbuminuria results in a reliable conclusion leading costs saving. Methods. This current cross-sectional study included a total of 126 consecutive persons. Microalbuminuria was assessed by collection of two fasting random urine specimens on arrival to the clinic as well as one week later in the morning. Results. In overall, 17 out of 126 participants suffered from microalbuminuria that, among them, 12 subjects were also diagnosed as microalbuminuria once assessing this factor with a sensitivity of 70.6%, a specificity of 100%, a PPV of 100%, a NPV of 95.6%, and an accuracy of 96.0%. The measured sensitivity, specificity, PVV, NPV, and accuracy in hypertensive patients were 73.3%, 100%, 100%, 94.8%, and 95.5%, respectively. Also, these rates in nonhypertensive groups were 50.0%, 100%, 100%, 97.3%, and 97.4%, respectively. According to the ROC curve analysis, a single measurement of UACR had a high value for discriminating defected from normal renal function state (c = 0.989). Urinary albumin concentration in a single measurement had also high discriminative value for diagnosis of damaged kidney (c = 0.995). Conclusion. The single testing of both UACR and urine albumin level rather frequent testing leads to high diagnostic sensitivity, specificity, and accuracy as well as high predictive values in total population and also in hypertensive subgroups.

Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease

BackgroundKlotho is a single-pass transmembrane protein, which appears to be implicated in aging. The purpose of the present study was to characterize the relationship between the soluble Klotho level and renal function in patients with various degrees of chronic kidney disease (CKD).MethodsThe levels of soluble Klotho in the serum and urine obtained from one hundred thirty-one CKD patients were determined by a sandwich enzyme-linked immunosorbent assay system.ResultsThe amount of urinary excreted Klotho during the 24 hr period ranged from 1.6 to 5178 ng/day (median 427 ng/day; interquartile range [IR] 56.8-1293.1), and the serum Klotho concentration ranged from 163.9 to 2123.7 pg/ml (median 759.7 pg/ml; IR 579.5-1069.1). The estimated glomerular filtration rate (eGFR) was significantly correlated with the log-transformed values of the amount of 24 hr urinary excreted Klotho (r = 0.407, p < 0.01) and the serum Klotho levels (r = 0.232, p < 0.01). However, a stepwise multiple regression analysis identified eGFR to be a variable independently associated only with the log-transformed value of the amount of 24-hr urinary excreted Klotho but not with the log-transformed serum Klotho concentration. Despite the strong correlation between random urine protein-to-creatinine ratio and the 24 hr urinary protein excretion (r = 0.834, p < 0.01), a moderate linear association was observed between the log-transformed value of the amount of 24 hr urinary excreted Klotho and that of the urinary Klotho-to-creatinine ratio (Klotho/Cr) in random urine specimens (r = 0.726, p < 0.01).ConclusionsThe amount of urinary Klotho, rather than the serum Klotho levels, should be linked to the magnitude of the functioning nephrons in CKD patients. The use of random urine Klotho/Cr as a surrogate for the amount of 24-hr urinary excreted Klotho needs to be evaluated more carefully.

Chronic kidney disease and measurement of albuminuria or proteinuria: a position statement

Optimal detection and subsequent risk stratification of people with chronic kidney disease (CKD) requires simultaneous consideration of both kidney function (glomerular filtration rate [GFR]) and kidney damage (as indicated by albuminuria or proteinuria). Measurement of urinary albuminuria and proteinuria is hindered by a lack of standardisation regarding requesting, sample collection, reporting and interpretation of tests. A multidisciplinary working group was convened with the goal of developing and promoting recommendations that achieve consensus on these issues. The working group recommended that the preferred method for assessment of albuminuria in both diabetic and non-diabetic patients is urinary albumin-to-creatinine ratio (UACR) measurement in a first-void spot urine specimen. Where a first-void specimen is not possible or practical, a random spot urine specimen for UACR is acceptable. The working group recommended that adults with one or more risk factors for CKD should be assessed using UACR and estimated GFR every 1-2 years, depending on their risk-factor profile. Recommended testing algorithms and sex-specific cut-points for microalbuminuria and macroalbuminuria are provided. The working group recommended that all pathology laboratories in Australia should implement the relevant recommendations as a vital component of an integrated national approach to detection of CKD.

Assessment of prenatal mercury exposure in a predominately Caribbean immigrant community in Brooklyn, NY

Prenatal mercury exposure and its fetotoxic effects may be of particular concern in urban immigrant communities as a result of possible contributing cultural factors. The most common source of exposure in these communities is ingestion of fish and shellfish contaminated with methylmercury. Other sources of exposure may occur in ritualistic practices associated with Hispanic and Caribbean-based religions. This study 1) assessed total mercury levels in both random urine specimens from pregnant women, and in cord blood; and 2) examined environmental sources of exposure from a convenience sample in a predominantly Caribbean immigrant population in Brooklyn, New York. A questionnaire designed in collaboration with health professionals from the Caribbean community assessed the frequency of fish consumption, ritualistic practices, occupational exposures, and use of dental amalgams and mercury-containing skin and household products. The geometric mean for total mercury in cord blood was 2.14 μg L(-1) (95%CI: 1.76-2.60) (n = 78), and 0.45 μg L(-1) (95%CI: 0.37-0.55) (n = 183) in maternal urine corrected for creatinine (μg g(-1)). Sixteen percent of cord blood mercury levels exceeded the estimated equivalent of U.S. Environmental Protection Agency's Reference Dose (5.8 μg L(-1) blood). Predictors of cord blood mercury included maternal fish consumption and foreign birth of the mother. Predictors of urine mercury included foreign birth of the mother, number of dental amalgams, and special product use. There were no reports of mercury use in ritualistic practices or in cosmetics; however some women reported use of religious medals and charms. This study characterized risk factors for mercury exposure in a sample of urban, predominantly Caribbean-born blacks. Findings may help target interventions in this population, which might include appropriate fish selection and consumption frequency during pregnancy, and safe handling of mercury-containing products in the home.

A HPLC-MS method to detect and quantify guanfacine in urine

Guanfacine, an α2-adrenergic α2A)agonist long indicated to treat hypertension, is now being used to treat attention deficit-hyperactivity disorder (ADHD) in adolescents. This new therapeutic use may require urine testing to document compliance or abuse. A simple rapid high pressure liquid chromatography-mass spectrometry (HPLC-MS) method to detect and quantify guanfacine in urine following therapeutic administration is presented. Guanfacine and protriptyline internal standard were extracted from alkalinized urine with ethyl acetate. The organic layer was evaporated, reconstituted with mobile phase and analyzed on a YMC Basic S-5 micron, 2.0 × 150 mm HPLC column connected to an MS detector operated in positive electrospray ionization mode with selected ion resonance. Elution times were <5 min. The analytical measurement range for guanfacine was 20-2000 ng/mL. The limit of detection and quantitation were 5 ng/mL and 20 ng/mL, respectively. Precision as %CV was <15% at 40, 100 and 500 ng/mL (n=6). Percentage recovery using the same concentrations was >89%. Interference with drugs and biological constituents was assessed; no interferences were noted. Analysis of 100 random post-diagnostic urine specimens yielded 11 guanfacine positive results with concentrations ranging from 11 to 6390 ng/mL. This HPLC-MS method provides a simple and rapid method for the routine detection and quantitation of guanfacine in urine specimens.

Age-related medical decision limits for urinary free (unconjugated) metadrenalines, catecholamines and metabolites in random urine specimens from children

Neuroblastoma is the most common extracranial solid tumour in childhood (8% of all childhood cancers), the most frequently diagnosed in infancy, and has one of the highest death rates, while chromaffin tumours rarely present in childhood. Both tumour types produce catecholamines and their metabolites. It is difficult to produce reference ranges for tests in children, and currently, no age-related medical decision limits for free metadrenalines (free metanephrines) in random urine specimens exist in the paediatric literature. Results of vanillylmandelic acid (VMA), 5-hydroxyindoleacetic acid, homovanillic acid (HVA), noradrenaline (NA), adrenaline, dopamine (DA), free normetadrenaline (fNMA), free metadrenaline and free 3-methoxytyramine (f3MT) in 1658 random urines obtained from infants, children and young adults were measured by high performance liquid chromatography with electrochemical detection. Specimens were excluded from consideration if obtained from the following categories, i.e. (a) harbouring neuroblastic, chromaffin, carcinoid or other tumours or malignancies; (b) medical conditions having known association with excess catecholamine excretion; (c) patients administered catecholamine or paracetamol; (d) overly dilute urine; and (e) manifesting outlying values following visual inspection. There remained 872 specimens that were grouped into seven age ranges (<1; 1 or 2; 3 or 4; 5-7; 8-10; 11-13; 14-19 y) for which medical decision limits were determined for each analyte. There was no significant difference between the results for boys or girls. In 55 patients harbouring neuroblastic tumours, HVA (54/55), f3MT (14/16), VMA (45/53) and DA (43/53) were the most frequently elevated analytes at time of diagnosis. In 11 patients presenting in childhood with chromaffin tumours, fNMA (11/11) followed by NA (10/11) were the most frequently elevated. Discussion The likely reasons for outlying or missing values, together with the reasons for variation in the distinctive biochemical patterns of analytes exhibited in individuals harbouring either neuroblastic or chromaffin tumours are discussed.

A Method to Quantify Illicit Intake of Drugs from Urine: Methamphetamine

Qualitative urinalysis can verify abstinence of drug misuse but cannot detect changes in drug intake. For drugs with slow elimination, such as methamphetamine (MA), a single episode of abuse can result in up to 5 days of positive urine drug screens. Thus, interventions that produce substantial decreases in drug use but do not achieve almost complete abstinence are classified as ineffective. Using nonpharmacologic doses of deuterium-labeled l-methamphetamine (l-MA-d(3)) we have developed a simple, robust method that reliably estimates changes in MA intake. Twelve subjects were dosed with 5 mg of l-MA-d(3) daily and challenged with 15, 30, and 45 mg of nonlabeled d-MA (d-MA-d(0)) after reaching plasma steady status of l-MA-d(3). Urinary concentration ratios of d-MA-d(0) to l-MA-d(3) provided clear separation of the administered doses with as little as 15-mg dose increments. Administered doses could not be resolved using d-MA-d(0) concentrations alone. In conclusion, the urinary [d-MA-d(0)]:[l-MA-d(3)] provides a quantitative, continuous measure of illicit MA exposure. The method reliably detects small, clinically relevant changes in illicit MA intake from random urine specimens, is amenable to deployment in clinical trials, and can be used to quantify patterns of MA abuse.