Random Urine Specimens Research Articles

Individual variability in concentrations of urinary sulindac sulfide

Among 70 patients with arthritis who were receiving satisfactory maintenance therapy with sulindac (300 to 400 mg daily), 64% had no detectable sulindac sulfide (active metabolite) in one to four random urine specimens. However, 36% had 1.0 to 7.8 (mean, 2.2 +/- 1.4) micrograms/ml sulindac sulfide in urine, similar to the therapeutically effective concentrations found in 24 concurrent plasma specimens (1.4 to 9.0 micrograms/ml). Ten patients had sulindac sulfide in only one or two of two to four urine specimens. Thus, 36% of the patients had pharmacodynamically significant concentrations of sulindac sulfide in urine, presumably capable of suppressing the cyclooxygenase pathway responsible for prostaglandin synthesis in the kidney and elsewhere. The findings suggest individual variability in the capacity for renal oxidation of sulindac sulfide to inactive metabolites, perhaps related to genetic or environmental factors or both. These findings may help to explain conflicting reports on the effects of sulindac on urinary prostaglandins and renal function.

The level of urinary epidermal growth factor is not influenced by the extent of psoriatic lesions

Epidermal growth factor (EGF) levels in the urine of 31 normal individuals and 33 psoriatic patients were measured. The amounts of urinary EGF secreted in a day by normal and psoriatic individuals were not significantly different nor were the levels of EGF in random urine specimens corrected for creatinine values. It is known that the urinary EGF content corrected for the creatinine value correlates very well with the EGF level in blood as well as in 24-h urine specimens. Our data indicate that EGF circulating in the blood may not be correlated with the extent of psoriatic lesions.

Urinary Porphyrin Excretion in Normal Children and Adults

The relationship of random urinary porphyrin and creatinine values as functions of age and sex was examined in a normal population. Total urinary porphyrin was measured by a solvent extraction technique, while urinary creatinine was evaluated by an alkaline picrate method. Random urine specimens from 120 healthy patients (81 children and 39 adults) were evaluated. In both pediatric and adult populations, a strong correlation was found between urinary concentrations of porphyrin and creatinine (r = 0.7, P less than 0.0001). Urinary porphyrin excretion in mumol/mol creatinine (micrograms/g) was inversely related to both age (r = -0.59, P less than 0.0001) and weight (r = -0.61, P less than 0.0001) until approximately 9 years of age or 30 kg. Urinary porphyrin excretion in children 9 to 18 years of age was lower than that of younger children (P less than 0.0001) and approached adult values. Sex was not found to be a factor until 9 to 18 years of age, when females had higher urinary creatinine concentrations (P less than 0.05), but lower urinary porphyrin excretions (P less than 0.05) than similarly aged males. The converse was observed when similar values of adult women were compared with those of adult men. Men also had higher urinary porphyrin concentrations than women (P less than 0.01). Men had increased urinary creatinine concentration (P less than 0.05) and decreased porphyrin excretion ratios (P less than 0.05) when compared with males 9 to 18 years of age. Women had significantly lower urinary creatinine (P less than 0.001) and porphyrin (P less than 0.001) concentrations than females 9 to 18 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of Random Urine Samples to Estimate Total Urinary Calcium and Phosphate Excretion

Calcium-to-creatinine and phosphate-to-creatinine ratios in random single-voided urine specimens were compared with 24-hour calcium and phosphate excretions, respectively, in 67 subjects who were selected prospectively to represent a wide range of renal and parathyroid function as well as urinary calcium and phosphate loss. Simple linear regression analysis revealed significant correlation between the spot urine calcium-to-creatinine ratio and 24-hour total calcium excretion and between the spot urine phosphate-to-creatinine ratio and 24-hour phosphate excretion. Calculating these simple ratios permits easy, rapid, correct, and inexpensive estimation of the daily urinary calcium and phosphate excretion.

Use of random urine samples to estimate total urinary calcium and phosphate excretion

Calcium-to-creatinine and phosphate-to-creatinine ratios in random single-voided urine specimens were compared with 24hour calcium and phosphate excretions, respectively, in 67 subjects who were selected prospectively to represent a wide range of renal and parathyroid function as well as urinary calcium and phosphate loss. Simple linear regression analysis revealed significant correlation between the spot urine calcium-to-creatinine ratio and 24-hour total calcium excretion and between the spot urine phosphate-to-creatinine ratio and 24-hour phosphate excretion. Calculating these simple ratios permits easy, rapid, correct, and inexpensive estimation of the daily urinary calcium and phosphate excretion. (<i>Arch Intern Med</i>. 1991;151:1587-1588)

Urinary leukocyte esterase screening for asymptomatic sexually transmitted disease in adolescent males

The objective of this study was to evaluate the effectiveness of urinary leukocyte esterase on random urine specimens as a screening test for chlamydial and gonococcal urethral infections in asymptomatic males. Random urine specimens were obtained on 106 consecutive asymptomatic adolescent males during intake physical examination at a residential vocational training program. Results of urinary leukocyte esterase were compared to those of urethral cultures for Chlamydia trachomatis and Neisseria gonorrhoeae. Five subjects had positive chlamydia cultures, three subjects had positive gonococcal cultures, and one patient had positive cultures for both organisms. Sixteen subjects had leukocyte esterase tests reported as “trace” or greater. When compared to positive culture results for either Chlamydia or gonorrhea, urinary leukocyte esterase activity had a sensitivity of 78%, specificity of 91%, and positive predictive value of 44%. A random urine specimen for urinary leukocyte esterase activity is a cost-effective screening method for chlamydial and gonococcal urethral infections in asymptomatic adolescent males.

Protein/creatine ratio in random urine specimens for quantitation of proteinuria in preeclampsia

Protein/creatinine ratio (mg/g) in random urine samples was measured in 35 preeclamptic patients and 70 healthy pregnant women. We found a close correlation between the protein/creatinine ratio in random urine samples and both the 24-hour protein excretion and the 24-hour protein/creatinine ratio in the preeclamptic patients. The ratio did not exceed 200 mg/g in any of the 70 healthy pregnant women; therefore, ratios below this value can be considered normal. We conclude that determination of the protein/creatinine ratio in random urine specimens may be a simple method for quantitation of proteinuria in preeclampsia.

Urinary Screening for Midazolam and Its Major Metabolites with the Abbott ADx and TDx Analyzers and the EMIT d.a.u. Benzodiazepine Assay with Confirmation by GC/MS

Midazolam is a short-acting 1,4-imidazole benzodiazepine with sedative-hypnotic, anxiolytic, and amnestic properties. It is administered orally for sleeping disorders and intravenously for sedation during surgery. This drug has a short half-life (1.5-3.5 h), with less than 1% of a midazolam dose being excreted unchanged. The major urinary metabolite is alpha-hydroxy midazolam glucuronide. The objective of this study was to characterize the reactivity of midazolam and its two major metabolites in the EMIT d.a.u. benzodiazepine assay and in the Abbott TDx and ADx urine benzodiazepine assays. Midazolam and alpha-OH midazolam gave an equivalent response to the EMIT low calibrator at 200 ng/mL. On both Abbott analyzers, midazolam and alpha-OH midazolam gave an equivalent net polarization at 500 ng/mL to the Abbott low control. All three screening assays were positive in all of 21 random urine specimens collected from midazolam-treated patients. Confirmation testing was performed by analyzing for alpha-OH midazolam after enzymatic hydrolysis and formation of a TMS derivative for GC/MS. All urine specimens were confirmed positive for alpha-OH midazolam. In conclusion, all three immunoassay screening assays are acceptable for detecting the presence of midazolam metabolites in urine.

Screening for Slight Albuminuria

Slight albuminuria predicts clinically significant nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) and early death in patients with non-insulin-dependent diabetes mellitus (NIDDM). This study compares four commercially available methods for measuring low concentrations of urinary albumin. We tested random spot urine specimens from 50 nondiabetic volunteers and 100 diabetic patients. This specimen was chosen to simplify collection in an outpatient setting. Two screening methods were evaluated for their ability to detect urinary albumin in the range of 15 to 200 mg/L. Sensitivity and specificity were 100% and 54.7%, respectively, for the Ames Micro-Bumintest; and 95.5% and 91.5%, respectively, for the Sclavo Albumin Screen. The high number of false-positive results made the Micro-Bumintest unacceptable. The Albumin Screen yielded fewer false-positive results, but also produced some false-negatives. Two quantitative methods, a radioimmunoassay (RIA) and a turbidimetric assay (the SPQ Microalbumin), yielded results that agreed well with each other.

Age-Dependent Excretion of Alanine Aminopeptidase, Alkaline Phosphatase, γ-Glutamyltransferase and N-Acetyl-β-D-Glucosaminidase in Human Urine

Urinary excretion of alanine aminopeptidase, alkaline phosphatase, gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase was determined in gel-filtered samples of morning random urine specimens of 442 subjects of various ages (5 days to 58 years). Enzyme excretion related to urinary creatinine (enzyme/creatinine ratio; U/mmol creatinine) significantly decreased with increasing age. Sex-related differences of some enzyme excretions were found in age groups over 6 years. From these investigations, we calculated upper reference intervals (97.5 percentiles) for 5 age-dependent groups of children and adolescents and for one group of adults.

Prevalence and risk factors for micro- and macroalbuminuria in diabetic subjects and entire population of Nauru.

Rates of elevated urinary albumin concentration, defined as microalbuminuria (30-299 micrograms/ml) and macroalbuminuria (greater than or equal to 300 micrograms/ml), were determined on random morning urine specimens in the population of Nauru, which has a high prevalence of non-insulin-dependent diabetes mellitus. The prevalence of elevated urinary albumin levels in the total Nauruan population was very high: 26 and 30% of men and women, respectively, had microalbuminuria, whereas 13% of both sexes had macroalbuminuria. Of the subjects with macroalbuminuria, 66% had diabetes. The prevalence increased with worsening glucose tolerance; 26% of subjects with normal glucose tolerance had either micro- or macroalbuminuria, increasing to 43% of subjects with impaired glucose tolerance, 63% of newly diagnosed diabetic subjects, and 75% of previously diagnosed diabetic subjects. Associations between elevated urinary albumin concentration and putative risk factors were assessed for both the total population (n = 1184) and the diabetic subgroup alone (n = 318). Fasting plasma glucose and hypertension were the most important independent correlates for the whole population, whereas plasma creatinine was also important in diabetic subjects. Age at onset and duration of diabetes were not found to be significantly associated with elevated albumin concentration. In subjects with normal glucose tolerance, hypertension and hyperuricemia were the most important associated factors. These results suggest that blood glucose, blood pressure, and possibly obesity and plasma uric acid are important modifiable risk factors for both micro- and macroalbuminuria in this population.

Renal function and electrolyte levels in hyperthyroidism: urinary protein excretion and the plasma concentrations of urea, creatinine, uric acid, hydrogen ion and electrolytes.

In order to help clarify the effects of hyperthyroidism on renal function and electrolyte metabolism, we measured the venous plasma concentrations of urea, creatinine, urate, hydrogen ion and electrolytes, and the urinary concentrations of total protein, albumin, retinol-binding protein, N-acetyl-beta-D-glucosaminidase activity, and creatinine in patients when hyperthyroid and again after they had been euthyroid for at least 4 months. Significant (P less than 0.05) decreases in the mean plasma concentrations of urate and chloride and significant increases in creatinine, total CO2 and hydrogen ion mean concentrations were observed when the patients became euthyroid. The mean concentrations of sodium, potassium and urea did not change significantly. The values of the ratios total protein/creatinine, albumin/creatinine, N-acetylglucosaminidase/creatinine and retinol-binding protein/creatinine were all significantly (P less than 0.05) elevated in random urine specimens obtained from hyperthyroid patients as compared to the values when euthyroid. Mild proteinuria occurs in most thyrotoxic patients which does not appear to be due predominantly to either glomerular or tubular renal injury. The changes in plasma analytes that were observed may be attributed to increases in glomerular filtration rate and tissue nucleic acid turnover and a tendency to respiratory alkalosis in the hyperthyroid patients.

Biologic variation of urinary albumin: consequences for analysis, specimen collection, interpretation of results, and screening programs.

Studies on the analytic and biologic variability of albumin concentration, albumin/creatinine ratio, and albumin excretion rate in first morning, random, and 24-hour urine specimens from healthy subjects suggest that (1) first morning specimens are preferred, (2) results should be expressed as albumin concentration, (3) assay of creatinine confers little advantage, (4) an analytical precision of coefficient of variation (CV) less than 18% is satisfactory, and (5) semiquantitative or qualitative analyses are suitable for screening programs. The intraindividual variation of albumin concentration in first morning specimens from diabetics is such that no threshold value gives the desired 100% nosological sensitivity. However, a threshold value of 30 mg/L confers 100% specificity, and a single abnormal result therefore requires initiation of therapy. Patients with negative results should continue to be monitored regularly.

Medium-chain acyl-CoA dehydrogenase deficiency. Diagnosis by stable-isotope dilution measurement of urinary n-hexanoylglycine and 3-phenylpropionylglycine.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, one of the most common inherited metabolic disorders, is often mistaken for the sudden infant death syndrome or Reye's syndrome. Diagnosing it has been difficult because of a lack of fast and reliable diagnostic methods. We developed a stable-isotope dilution method to measure urinary n-hexanoylglycine, 3-phenylpropionylglycine, and suberylglycine, and we retrospectively tested its accuracy in diagnosing MCAD deficiency. We measured the concentrations of these three acylglycines in 54 urine samples from 21 patients with confirmed MCAD deficiency during the acute and asymptomatic phases of the illness and compared the results with the concentrations in 98 samples from healthy controls and patient controls with various diseases. The levels of urinary hexanoylglycine and phenylpropionylglycine were significantly increased in all samples from the patients with MCAD deficiency, clearly distinguishing them from both groups of controls. Although urinary suberylglycine was increased in the patients, the range of values in the normal controls who were receiving formula containing medium-chain triglycerides was very wide, overlapping somewhat with the values in the patients with asymptomatic MCAD deficiency. These results indicate that the measurement of urinary hexanoylglycine and phenylpropionylglycine by our method is highly specific for the diagnosis of MCAD deficiency. The method is fast and can be applied to random urine specimens, without any pretreatment of patients.

Human urinary epidermal growth factor excretion: age, sex, and race dependence.

We measured the urinary excretion of immunoreactive epidermal growth factor (IR-EGF) in random urine specimens obtained from 358 ambulatory patients and normal subjects, aged 18-90 yr, with a homologous EGF RIA. We also measured IR-EGF excretion in 24-h urine collections from 40 additional normal subjects, aged either 20-29 or 60-69 yr, to detect possible artifacts introduced in the analysis of random urine specimens by the age-related decline in the glomerular filtration rate. Urinary IR-EGF excretion decreased in a linear fashion with increasing age. Women excreted more IR-EGF than men, and whites excreted more IR-EGF than blacks of the same age and sex, but the rate of decline with increasing age was similar for all groups. These findings may provide additional insight into the role of EGF in human renal physiology.

Optimisation of total urinary aldosterone estimation: Comparison with other laboratory methods for assessment of mineralocorticoid status

We have demonstrated that conventional methods for measuring total urinary aldosterone (TUA) may markedly and inconsistently underestimate aldosterone output, since under the conditions usually employed (pH 1.0), the hydrolysis of aldosterone conjugates in urine is incomplete. The use of more acidic hydrolysis conditions (pH 0.2) overcomes this problem. However free aldosterone may be damaged at this pH. Therefore to accurately measure TUA output, it is necessary to isolate the undamaged aldosterone chromatographically and to correct for procedural losses based on the recovery of aldosterone tracer added to the urine prior to hydrolysis. We compared a number of laboratory estimates of aldosterone status (including urinary free aldosterone) with the 24-h urinary sodium output in normal subjects, since this provides a good bioassay of aldosterone. Sodium output correlated best with “optimised” 24 h TUA, i.e. hydrolysed at pH 0.2, ( r = −0.589, P < 0.001), and with plasma aldosterone ( r = −0.504, P < 0.005). Both aldosterone in random urine specimens and plasma renin activity correlated poorly with 24-h sodium output. Therefore, while the measurement of optimised TUA excretion provides the best index of aldosterone activity, assay of aldosterone in random specimens of plasma, which is more convenient for patient and laboratory, may be adequate for many clinical purposes.

Amylase in urine as measured by a single-step chromolytic method.

We studied a new single-step direct chromolytic method (Behring D.A.T.) for measuring urinary amylase (1,4-alpha-D-glucan glucanohydrolase, EC 3.2.1.1) activity, comparing results with those by a similar, but two-step, procedure that requires an auxiliary (coupling) enzyme. The two methods gave virtually identical relative responses to purified human pancreatic and salivary amylases. Assay of four quality-control materials to evaluate the total (day-to-day) precision of the new method yielded CVs of 4 to 7%, similar to those of the comparison method for each of the four quality-control samples. Amylase activity was measured by both methods in 110 random (i.e., untimed) urine specimens. Linear regression analysis provided a slope and y-intercept of 0.947 and 4 U/L (x = comparison method, y = direct method), respectively, and a standard error of the estimate of 25 U/L for specimens in which the amylase activities ranged from 11 to 1465 U/L (mean = 358 U/L) by the comparison method. The mean rate of amylase excretion in 2-h timed urine specimens from 95 healthy volunteers, as measured by the new method, was 7.18 (SD = 3.18) U/h, and the nonparametric (95% confidence interval) reference interval was 1.6 to 15.2 U/h. We consider the new method a promising alternative to other kinetic assays that require the use of auxiliary enzymes.

Urinary screening for alprazolam, triazolam, and their metabolites with the EMIT d.a.u. benzodiazepine metabolite assay.

Alprazolam (Xanax) and triazolam (Halcion) are relatively new triazolobenzodiazepines that are anxiolytic and hypnotic. This study assesses the reactivity of these drugs and their major metabolites in the EMIT d.a.u. benzodiazepine metabolite assay. Analytical standards of drugs and metabolites and urine specimens from patients receiving these drugs were analyzed by EMIT. Alprazolam and alpha-OH alprazolam gave an equivalent response to the EMIT low calibrator between 0.2 and 0.3 microgram/mL. Triazolam and alpha-OH triazolam were reactive between 0.3 and 0.5 microgram/mL. The assay was positive in 24 out of 27 random urine specimens from alprazolam-treated patients and in 8 out of 19 urine specimens from triazolam-treated patients. Positive urine results were confirmed by measuring the major urinary metabolites alpha-OH alprazolam and alpha-OH triazolam by HPLC. The study demonstrates that the EMIT assay can detect significant amounts of alprazolam and metabolites in the urine. The assay was negative in 58% of the specimens from individuals receiving triazolam, however.

Alprazolam Abuse and Methadone Maintenance

To the Editor.— The contribution by Weddington and Carney 1 in the June 26, 1987, issue of JAMA entitled Alprazolam Abuse and Dependence demands my comments. In their Letter, the authors state that the usual urine toxicology screens for benzodiazepine metabolites give falsenegative results after alprazolam (Xanax) ingestion because alprazolam and metabolites are excreted in amounts below the detection limits of the assay. The authors did not state what screening method was used. Study.— Pure standards of alprazolam and αOH alprazolam were analyzed, in the Toxicology Laboratory, Victoria General Hospital, by the enzyme-multiplied immunosorbent (EMIT d.a.u.) assay. Both standard solutions gave an equivalent response to the EMIT low calibrator at 0.2 to 0.3 μg/mL. Random urine specimens from 27 inpatients receiving 0.25 to 7.0 mg/d of alprazolam (Xanax) were analyzed by the standard EMIT protocol for benzodiazepine metabolites. In this study, 24 of the specimens were positive (ie, reading greater

URINARY PROSTAGLANDIN (PG) EXCRETION IN PRIMARY AND SECONDARY HYPERTENSION

Hypertension may be due to volume overload, the pressor effect of circulating agents such as renin or, theoretically, to reduced levels of circulating vasodilator agents. Certain prostaglandins, e.g. PGE2 are known vasodilators. The renal medulla is known to be a source of PGE2, kidney damage could therefore result in reduced production and hence contribute to the development of hypertension. Experimental work suggests that there is decreased production of PGE2 in areas of induced renal scarring. We have previously established a normal range for the 24 hour urinary excretion of PGE2, PGF2α, 6 keto PGF1α and thromboxane B2 (TXB2) and have shown that relating the values obtained to urinary creatinine (Cr) is the most useful index of PG excretion. We therefore studied a group of children with secondary hypertension (due to reflux nephropathy or renovascular disease) and compared them with normal children and with children with primary hypertension. 24 hour urine collections were obtained from hypertensive children at diagnosis, and random urine specimens collected at follow-up clinic visits. No differences were found between hypertensives and normals in the PG:Cr ratios for PGF2α, 6 keto PGF1α and TXB2. However, PGE2:Cr ratios were substantially reduced in children with secondary hypertension when compared with normal (7.7 vs 17.5 ng/mmol Cr). Children with essential hypertension had PGE2:Cr ratios at the lower end of the normal range. Our data demonstrate reduced PGE2 excretion in secondary hypertension, which may be a contributory factor in its development.