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Metabolites of a tobacco-specific carcinogen in urine from newborns.

BACKGROUND: Cigarette smoking during pregnancy can result in fetal exposure to carcinogens that are transferred from the mother via the placenta, but little information is available on fetal uptake of such compounds. We analyzed samples of the first urine from newborns whose mothers did or did not smoke cigarettes for the presence of metabolites of the potent tobacco-specific transplacental carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). METHODS: The urine was collected and analyzed for two metabolites of NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc). Gas chromatography and nitrosamine-selective detection, with confirmation by mass spectrometry, were used in the analyses, which were performed without knowledge of the origin of the urine samples. RESULTS: NNAL-Gluc was detected in 22 (71%) of 31 urine samples from newborns of mothers who smoked; NNAL was detected in four of these 31 urine samples. Neither compound was detected in the 17 urine samples from newborns of mothers who did not smoke. The arithmetic mean level of NNAL plus NNAL-Gluc in the 27 newborns of smokers for which both analytes were quantified was 0.14 (95% confidence interval [CI] = 0.083-0.200) pmol/mL. The levels of NNAL plus NNAL-Gluc in the urine from these babies were statistically significantly higher than those in the urine from newborns of nonsmoking mothers (geometric means = 0.062 [95% CI = 0.035-0.110] and 0.010 [considered as not detected; no confidence interval], respectively; two-sided P<.001). NNAL plus NNAL-Gluc levels in the 18 positive urine samples in which both analytes were quantified ranged from 0.045 to 0.400 pmol/mL, with an arithmetic mean level of 0.20 (95% CI = 0.14-0.26) pmol/mL, about 5%-10% of the levels of these compounds detected in the urine from adult smokers. CONCLUSIONS: Two metabolites of the tobacco-specific transplacental carcinogen NNK can be detected in the urine from newborns of mothers who smoked cigarettes during pregnancy.

Adult↗

Detection of depleted uranium in urine of veterans from the 1991 Gulf War.

American soldiers involved in "friendly fire" accidents during the 1991 Gulf War were injured with depleted-uranium-containing fragments or possibly exposed to depleted uranium via other routes such as inhalation, ingestion, and/or wound contamination. To evaluate the presence of depleted uranium in these soldiers eight years later, the uranium concentration and depleted uranium content of urine samples were determined by inductively coupled plasma mass spectrometry in (a) depleted uranium exposed soldiers with embedded shrapnel, (b) depleted uranium exposed soldiers with no shrapnel, and (c) a reference group of deployed soldiers not involved in the friendly fire incidents. Uranium isotopic ratios measured in many urine samples injected directly into the inductively coupled plasma mass spectrometer and analyzed at a mass resolution m/delta m of 300 appeared enriched in 235U with respect to natural abundance (0.72%) due to the presence of an interference of a polyatomic molecule of mass 234.81 amu that was resolved at a mass resolution m/delta m of 4,000. The 235U abundance measured on uranium separated from these urines by anion exchange chromatography was clearly natural or depleted. Urine uranium concentrations of soldiers with shrapnel were higher than those of the two other groups, and 16 out of 17 soldiers with shrapnel had detectable depleted uranium in their urine. In depleted uranium exposed soldiers with no shrapnel, depleted uranium was detected in urine samples of 10 out of 28 soldiers. The median uranium concentration of urines with depleted uranium from soldiers without shrapnel was significantly higher than in urines with no depleted uranium, though substantial overlap in urine uranium concentrations existed between the two groups. Accordingly, assessment of depleted uranium exposure using urine must rely on uranium isotopic analyses, since urine uranium concentration is not an unequivocal indicator of depleted uranium presence in soldiers with no embedded shrapnel.

Firearms↗

Urine detection of survivin is a sensitive marker for the noninvasive diagnosis of bladder cancer.

PURPOSE: In a preliminary study urine detection of survivin, an integrator of cell death and mitosis, accurately detected bladder cancer. The objectives of this study were to confirm these findings in a large cohort of subjects undergoing cystoscopy, to assess the diagnostic performance of urine survivin and to test whether evaluation of urine survivin adds independent value to urine NMP22 (Matritech, Cambridge, Massachusetts) and cytology for the detection of bladder cancer. MATERIALS AND METHODS: Urine survivin was measured using a Bio-Dot microfiltration detection system (Bio-Rad, Hercules, California) in voided urine specimens collected before cystoscopy in 117 cases and 92 controls. Bladder washout samples for cytology were collected in 174 subjects. Urine levels of NMP22 were measured using a commercially available enzyme-linked immunosorbent assay. RESULTS: Higher levels of urine survivin were associated with an increased risk of bladder cancer (p <0.001) and tumors of higher grade (p = 0.037), but not with invasive stage, after adjustment for the effects of urine cytology, NMP22 and age. The sensitivity, specificity, and positive and negative predictive values of survivin for the diagnosis of bladder cancer (64%, 93%, 92% and 67%, respectively), are superior to those of NMP22 and cytology. Survivin had the highest specificity and positive predictive value for the detection of bladder cancer across each tumor stage and grade. CONCLUSIONS: Urine survivin was a strong, independent predictor of the presence of bladder cancer and higher tumor grade. Urine detection of survivin is an accurate diagnostic test for bladder cancer that retains its efficiency regardless of cancer stage and grade.

Adult↗

Effect of glucose and pH on uropathogenic and non-uropathogenic Escherichia coli: studies with urine from diabetic and non-diabetic individuals.

It is generally assumed that one of the reasons why diabetics are more susceptible to urinary tract infections than non-diabetics is their 'sweet urine'. However, very little information is available on this subject. Therefore, the growth rates of different Escherichia coli strains were studied in human urine with and without added glucose and with and without a constant pH, and compared with their growth rates in Mueller-Hinton broth (MHB). Eight isolates were used (three from blood cultures from urosepsis patients, two urinary isolates, two faecal isolates and one laboratory strain K12). All isolates grew better in MHB than in urine, but with the exception of the laboratory strain, they had the same growth rate in urine. No significant difference was found between the growth rate in urine from diabetics without glucosuria and that in urine from non-diabetics. The addition of glucose (up to a concentration of 1000 mg/dl) to urine and MHB enhanced the growth rate of all isolates. However, very high concentrations of glucose (up to 10000 mg/dl) in urine and MHB caused a decrease in bacterial growth rate when the urinary pH was not kept constant. The stationary phase was reached later and the final bacterial yield was greater when the urine was made less acidic. As the uropathogenic strains did not grow better in urine than the other isolates, it may be concluded that better growth in urine is not one of the causes of the greater virulence of these strains.

Bacteriuria↗

Intravesical instillation of human urine after oral administration of trospium, tolterodine and oxybutynin in a rat model of detrusor overactivity.

OBJECTIVE: To study the effects of antimuscarinics excreted into human urine on normal bladder in a rat model of detrusor overactivity. MATERIALS AND METHODS: Two 'normal' adult volunteers collected voided urine after taking trospium (20 mg, twice daily), tolterodine LA (4 mg, four times daily), or oxybutynin XL (10 mg, four times daily). The drugs were taken in a random order for 5 days with a 7-day washout period between the drugs. The urine collected from the two volunteers was mixed together and then blindly labelled and used for testing. Control human urine (no oral antimuscarinics) was also used. The effect of intravesical administration of human urine on carbachol-induced bladder overactivity was studied in female Sprague-Dawley rats anaesthetised with urethane. Cystometric variables during continuous infusion (0.04 mL/min) for >1 h each of saline, human urine, then a mixture of carbachol (30 microm) and human urine were compared in the four groups (control and the three different antimuscarinics tested; six rats per group). RESULTS: Human urine, with or with no intake of antimuscarinic agents, had no effect on normal bladder function. Bladder capacity and intercontraction intervals were significantly decreased after adding carbachol to urine containing vehicle, tolterodine or oxybutynin. However, urine collected from the humans who had taken trospium prevented the carbachol-induced reduction in bladder capacity and intercontraction intervals. Maximum voiding pressure and pressure threshold were not changed in any case. CONCLUSION: This is the first report that the urine excreted after oral ingestion of trospium (20 mg, twice daily) has a significant inhibitory effect in a rat model of detrusor overactivity. This suggests that antimuscarinic agents have a local bladder effect during the bladder-storage phase in addition to the smooth muscle-mediated voiding phase.

Administration, Intravesical↗

Flow meter urine testing: a practical proposition in patients attending for urodynamics?

OBJECTIVE: To find a practical way of detecting urinary tract infection (UTI) before invasive urodynamic testing, as UTIs after urodynamics are well documented, but there are no standard guidelines about when urine should be analysed before urodynamics. PATIENTS AND METHODS: Before urodynamics all patients are asked to provide a free urine flow; the patient is then catheterized to obtain a catheter-specimen of urine that is tested for infection by a urine dipstick. If the dipstick is found positive for nitrites and/or leukocytes, the test is abandoned and the sample sent for microscopy, culture and sensitivity. In the present study, patients were asked to provide a free urine flow into the flowmeter as usual. Between patients, the flowmeter was washed with soap and water and dried, so that there would be no cross-contamination between patients' urine results. Urine was collected as usual and tested using a dipstick, the patient was then catheterized and another dipstick test done on the catheter specimen of urine (CSU), to compare results. RESULTS: Pairs of urine samples, when positive for nitrite were 100% consistent, and 89% of pairs positive for leukocytes were the same before and after catheterization. The remaining 11% (all women) of the positive leukocyte group had leukocytosis on testing the flowmeter urine but not on the CSU, possibly due to contamination from the vagina. CONCLUSION: Testing urine by dipstick in the sample from the flowmeter is a feasible option, thus saving the patient an inappropriate catheterization, with the risk of bacteraemia during urodynamics, and allowing the flowrate to be measured.

Female↗

Inhibition of amplification of Chlamydia trachomatis plasmid DNA by the ligase chain reaction associated with female urines.

OBJECTIVE: To determine the rate of inhibition of ligase chain reaction (LCR) amplification of Chlamydia trachomatis plasmid DNA in urines from pregnant and non-pregnant women, to correlate inhibitors with urinary substances through urinalysis, and to explore methods of removing inhibitors from urine. METHODS: First-void urines (FVUs) from 287 non-pregnant and 101 pregnant women (15--40 years of age) in Hamilton, Canada were tested for urinary factors by urinalysis and for C. trachomatis by LCR. A sample of each urine was 'spiked' with a positive control containing approximately one infectious unit of C. trachomatis L2 serovar. RESULTS: Complete inhibition of DNA amplification was observed in nine of 287 (3.1%) urines from non-pregnant women and in one of 101 (1%) who were pregnant. Partial inhibition (> 20% reduction in signal) was observed in an additional five of 388 (1.3%) urines. Nine urines contained C. trachomatis plasmid DNA, but none of these contained inhibitors of LCR. By multivariate analysis, the only substances in urine which were significantly and independently related to LCR inhibition were nitrites. Holding the urines at 4C or minus sign70C overnight reduced the numbers which were inhibitory by approximately 50%. Diluting the urines 1:10 or extracting with phenol/chloroform removed all inhibition and retained amplifiable DNA. CONCLUSIONS: We conclude that urinary inhibitors of C. trachomatis DNA amplification by LCR are minimal and appear to be related to the presence of nitrites. We anticipate that most would disappear in transit or during processing and that a positive control for every urine is not warranted, considering the added cost and work associated with duplicate testing.

Journal Article↗

Detection of canine microalbuminuria using semiquantitative test strips designed for use with human urine.

BACKGROUND: Commercial testing for microalbuminuria in human urine is often performed with point-of-care semiquantitative test strips followed by quantitative testing when indicated. An ELISA that quantifies canine urine albumin concentration has been developed, but semiquantitative test strips for use in the dog are not available. OBJECTIVE: The purpose of this study was to prospectively determine the concordance of canine urine albumin concentrations measured by a commercial human test strip and by ELISA. METHODS: Urine samples were obtained from 67 dogs evaluated for a variety of clinical conditions. Dipstick urinalyses were performed on all samples; clinician discretion determined method of urine collection and performance of urine sediment examination and/or urine culture. Urine albumin concentration was determined using test strips (Clinitek Microalbumin, Bayer Corporation, Elkhart, Ind, USA), and results were compared with those obtained by ELISA. RESULTS: The Clinitek strips correctly determined albumin concentration in 42 of 67 (63%) urine samples tested. Concordance was lowest (48%) for dogs with microalbuminuria (10-300 microg/mL by ELISA). Clinitek strip sensitivity and specificity for correct identification of microalbuminuria were 48% and 75%, respectively. Concordance was lower in dogs with urinary tract infection or hematuria and in samples collected by catheterization. Sensitivity and specificity for correct identification of microalbuminuria after exclusion of dogs with urinary tract infection or hematuria were 59% and 83%, respectively. CONCLUSIONS: These results suggest that the Clinitek strips lack sufficient concordance with results obtained by ELISA to be a reliable screening for test microalbuminuria in the dog. A reliable semiquantitative point-of-care test for canine urine albumin concentrations below those detected by standard urine dipsticks is still needed.

Albuminuria↗

[Detection of Chlamydia trachomatis from urine sediment by PCR diagnostic reagent kit].

Chlamydia trachomatis detection by both swab CHLAMYDIAZYME and urine sediment AMPLICOR were performed on 61 males and 54 females who were suspected to have C. trachomatis genital infection (CTGI). Positive agreement between swab CHLAMYDIAZYME and urine sediment AMPLICOR was good, 96.9% in males and 96.6% in females. Negative agreement was 100% in males and 84.0% in females. "Swab CHLAMYDIAZYME positive-Urine sediment AMPLICOR negative specimen" were not obtained. "Swab CHLAMYDIAZYME negative-urine sediment AMPLICOR positive" resulted in four females who were finally diagnosed to have CTGI by repeated specimens on CHLAMYDIAZYME. Positive result by AMPLICOR was obtained on un-spun urine specimen that was in agreement with the laboratory result that the sensitivity of AMPLICOR reaches one thousand fold of CHLAMYDIAZYME. Detection on every separately collected urine specimen of one urination showed AMPLICOR positive all through the last cup specimen in both male and female. Those results seem to certify the reliability of C. trachomatis detection by urine sediment AMPLICOR. False negative by interference substance in urine and false positive by contamination were not experienced. On asymptomatic young male and female, positive rates of urine sediment AMPLICOR were 7.5% in male and 12.1% in female which are far more than the positive rate obtained by CHLAMYDIAZYME. Non invasive C. trachomatis detection method applicable to asymptomatic female is needed for control of CTGI. C. trachomatis detection could be facilitated by non invasive urine sediment AMPLICOR.

Adult↗

Elevated interleukin-8 levels in the urine of patients with urinary tract infections.

Pyuria is one of the main features of urinary tract infections (UTI). Nevertheless, the mechanism of polymorphonuclear leukocyte (PMN) recruitment into the urine remains to be investigated. We examined whether interleukin-8 (IL-8), a potent neutrophil chemoattractant and activator, was involved in pyuria seen in UTI. Of 113 patients, 112 had elevated levels of IL-8 in their urine (1,078.0 +/- 181.5 pg/ml), regardless of whether they had an upper or lower UTI; this was in contrast to undetectable levels (less than 16 pg/ml) in the urine of all of the 20 normal individuals and 74 control patients without UTI. A concomitant study revealed increases in urine IL-6, but not IL-1 beta, and tumor necrosis factor alpha levels in patients with UTI. In addition to gram-negative bacteria, a wide spectrum of microorganisms was capable of inducing IL-8 production in urine. Local production of IL-8 in the urinary tract was suggested by a urine IL-8 level that was higher than the paired serum IL-8 level. The urine IL-8 level correlated with the number of PMN in the urine, and an average of half of the chemotactic activity in urine from patients with UTI could be abrogated by anti-IL-8 antibody treatment in vitro. Furthermore, urine IL-8 purified from patients was bioactive and showed multiple forms on immunoblotting analysis. This is the first documentation of IL-8 in the urine of patients with UTI, and these results imply that IL-8 is involved in inducing PMN migration into the urinary tract.

Adolescent↗

Identification of genes in an extraintestinal isolate of Escherichia coli with increased expression after exposure to human urine.

The identification of genes with increased expression in vivo may lead to the identification of novel or unrecognized virulence traits and/or recognition of environmental signals involved in modulating gene expression. Our laboratory is studying an extraintestinal isolate of Escherichia coli as a model pathogen. We had previously used human urine ex vivo to identify the unrecognized urovirulence genes guaA and argC and to establish that arginine and guanine (or derivatives) were limiting in this body fluid (T. A. Russo et al., Mol. Microbiol. 22:217-229, 1996). In this study, we have continued with this approach and identified three additional genes that have increased expression in human urine relative to Luria-Bertani (LB) medium. Expression of ure1 (urine-responsive element) is increased a mean of 47.6-fold in urine but completely suppressed by exogenous glucose. This finding suggests that ure1 is regulated by catabolite repression and that limiting glucose in urine is a regulatory signal. ure1 is present in the E. coli K-12 genome, but its function is unknown. Although disruption of ure1 results in diminished growth in human urine, limiting concentrations of amino acids, nucleosides, or iron (Fe), or changes in osmolarity or pH do not affect the expression of ure1. Therefore, Ure1 appears to have a role independent of the synthesis or uptake of these nutrients and does not appear to be involved in osmoprotection. iroN(E. coli) is a novel E. coli gene with 77% DNA homology to a catecholate siderophore receptor gene recently identified in Salmonella. Its expression is increased a mean of 27.2-fold in urine and is repressed by exogenous Fe and a urinary pH of 5.0. This finding supports the contention that Fe is a limiting element in urine and that alteration of pH can affect gene expression. It is linked to the P-pilus (prs) and F1C fimbrial (foc) gene clusters on a pathogenicity island and appears to have been acquired by IS1230-mediated horizontal transmission. The homologous iroN(E. coli) sequence is significantly more prevalent in urinary tract and blood isolates of E. coli compared to fecal isolates. Last, the expression of ArtJ, an arginine periplasmic binding protein, is increased a mean of 16.6-fold in urine. This finding implicates arginine concentrations as limited in urine and, in combination with previous data demonstrating that argC is important for urovirulence, suggests that the ability of E. coli to synthesize or acquire arginine is important for urovirulence. ure1, iroN(E. coli), and artJ all have increased expression in human blood and ascites relative to LB medium as well. The identification of these genes increases our understanding of regulatory signals present in human urine, blood, and ascites. Ure1, IroN(E. coli), and ArtJ also warrant further evaluation as virulence traits both within and outside the urinary tract.

Ascites↗

Urine electrolytes and osmolality: when and how to use them.

The purpose of this review is to provide an update on the use of the urine electrolyte and osmolality measurements in patients with disorders of fluid, electrolytes, and/or acid-base metabolism. It is critical to appreciate that there are no 'normal values' for these parameters, only 'expected values' relative to clinical situations. Pitfalls in the interpretation of each electrolyte in the urine are also provided. To detect a mild to moderate degree of reduction of the 'effective' intravascular volume, both urine sodium (Na) and chloride (Cl) concentrations should be measured. Pitfalls in this assessment are abnormal renal and adrenal function and the use of diuretics. Insights into the etiology of the low 'effective' intravascular volume can be deduced by comparing the urine Na, potassium (K), and Cl concentrations. The urine net charge (Cl vs. Na + K) is the most reliable way to estimate the urine ammonium concentration short of its direct measurement, an assay that is not provided by most laboratories. This measurement is important in the differential diagnosis of hyperchloremic metabolic acidosis. To examine the renal response to hypokalemia or hyperkalemia, the two components of K excretion (K secretion and urine flow rate) should be examined separately. The former is evaluated using the transtubular K, concentration gradient. The urine osmolality is used to assess antidiuretic hormone action and the osmolality of the renal medulla and to determine the etiology of polyuria and/or hypernatremia. The urine osmolality can also be used to assess the ammonium concentration, using the urine osmolal gap, and to detect unusual urine osmoles.

Acid-Base Imbalance↗

Excretion of arsenic in urine as a function of exposure to arsenic in drinking water.

Urinary arsenic (As) concentrations were evaluated as a biomarker of exposure in a U.S. population chronically exposed to inorganic As (InAs) in their drinking water. Ninety-six individuals who consumed drinking water with As concentrations of 8-620 microg/L provided first morning urine voids for up to 5 consecutive days. The study population was 56% male, and 44% was younger than 18 years of age. On one day of the study period, all voided urines were collected over a 24-hr period. Arsenic intake from drinking water was estimated from daily food diaries. Comparison between the concentration of As in individual urine voids with that in the 24-hr urine collection indicated that the concentration of As in urine was stable throughout the day. Comparison of the concentration of As in each first morning urine void over the 5-day study period indicated that there was little day-to-day variation in the concentration of As in urine. The concentration of As in drinking water was a better predictor of the concentration of As in urine than was the estimated intake of As from drinking water. The concentration of As in urine did not vary by gender. An age-dependent difference in the concentration of As in urine may be attributed to the higher As dosage rate per unit body weight in children than in adults. These findings suggest that the analysis of a small number of urine samples may be adequate to estimate an individual's exposure to InAs from drinking water and that the determination of the concentration of InAs in a drinking water supply may be a useful surrogate for estimating exposure to this metalloid.

Adolescent↗

Analysis of proteinuria: reference limits for urine excretion of albumin, protein HC, immunoglobulin G, kappa- and lambda-immunoreactivity, orosomucoid and alpha 1-antitrypsin.

Efficient use of assessment of urine protein excretion in nephrological practice requires adequate reference intervals. To determine the upper reference limits of urine albumin, protein HC (alpha 1-microglobulin, immunoglobulin G (IgG), orosomucoid (alpha 1-acid glycoprotein, alpha 1-antitrypsin, and kappa- and lambda-chain immunoreactivities, the concentrations of these proteins were measured in urine samples from 95 healthy, adult individuals, using rapid, generally available methods and with conditions for urine collection which secured stable protein levels. The obtained values were expressed in mg 1(-1), as the urine protein-creatinine index and as fractional protein-creatinine clearance. No differences were found between the upper reference limits in the first voided morning urine samples and the randomly collected urine samples, nor between the upper reference limits in urine samples collected from males and females. The urinary excretion of the tested proteins did not correlate to age, positive dipsticks for haematuria nor to granular casts in urine sediment. Thus, the same upper reference limits can be used for both sexes and regardless of the type of urine collection. The upper reference limits of urine protein-creatinine index found in this study were: for albumin, 3.8 mg mmol(-1); for protein HC, 0.7 mg mmol; for IgG, 0.8 mg mmol(-1); for orosomucoid, 0.7 mg mmol(-1); for alpha 1-antitrypsin, 0.2 mg mmol(-1), and for kappa-immunoreactivity 0.7 mg mmol(-1). The upper reference limit for lambda-immunoreactivity was below the detection limit.

Adult↗

Food intake and body positional change alter the circadian rhythm of atrial natriuretic peptides excretion into human urine.

The 98 amino acid (a.a.) N-terminus of the 126 a.a. atrial natriuretic factor prohormone contains two natriuretic and vasodilatory peptides consisting of a.a. 1-30 (proANF 1-30) and a.a. 31-67 (proANF 31-67). The N-terminus and C-terminus (a.a. 99-126, i.e., ANF--also a vasodilatory peptide) circulate normally in humans with a circadian peak at 04:00 h in plasma. To determine if the N-terminus and C-terminus of the ANF prohormone are present in urine and possibly have a circadian variation in urine, six healthy volunteers had urine samples hourly while awake and every 3 h during sleep for five consecutive days obtained for radioimmunoassay. The sleep-awake pattern was varied so that after 2 days of normal sleep (supine)-awake (upright) positions, these volunteers were supine from 15:00 h on the third day until 10:00 h of the fourth day. They were then upright until 19:00 h that day when they became supine again until 02:30 h, and then were upright until 10:00 h of day 5. Three radioimmunoassays that immunologically recognize (a) the whole N-terminus (i.e., amino acids 1-98), (b) the midportion of the N-terminus (amino acids 31-67), and (c) the C-terminus of the ANF prohormone were utilized. ProANF 1-98, proANF 31-67, and the ANF radioimmunoassays each detected their respective peptides in urine. A circadian peak for each of these peptides was detected at 04:00 to 05:00 h whether the person was supine or upright during the night, which were significantly (p less than 0.001) higher than their concentrations in the afternoon of the previous days. Assuming a supine position during the day caused a significant (p less than 0.01) two- to threefold increase in these peptides in the urine. Food intake also increased the concentrations of proANF 1-98, proANF 31-67, and ANF in urine (p less than 0.001). Fluid intake when abstaining from food throughout the day lowered the concentration of these peptides in the urine. It was concluded that there is a circadian rhythm in both the N-terminus and C-terminus of the ANF prohormone excretion into urine with a peak at 04:00 h irrespective of posture, but that both posture and food and fluid intake throughout the day significantly influence the excretion of these peptides into the urine, with supine posture and food increasing their concentrations in the urine while fluid intake decreases their concentrations in the urine.

Adult↗

Decreasing the variability observed in urine analysis.

Urine analysis is affected significantly by biological variability. The objective of this study was to study the feasibility of reducing the biological variability of excretion of various analytes in urine, especially albumin in children with diabetes, by mixing small volumes of early morning samples. Twenty-two male children with type 1 diabetes collected early morning aliquots of approximately 10 ml of urine on 3 consecutive days and kept them refrigerated in sealed containers. The urine collection was repeated every 4-6 months in the diabetic children. Ten normal children and 10 normal adults participated as controls. The specimens were analyzed individually and as mixed samples for each subject. Mixing the 3 urine samples before analysis decreased the biological variability of all urine assays (albumin, glucose, creatinine, total protein, potassium). The diabetic children had 3 times higher variability of urine albumin (as a ratio to creatinine) compared to normal children, when the urine samples were collected individually (61% vs 19%, respectively). The variability in the diabetic children decreased when the 3 specimens were analyzed as a single sample after mixing, especially when urine albumin was expressed as a ratio to creatinine. Blood glycated hemoglobin levels correlated better with urine glucose levels when 3 urine samples were mixed before analysis.

Adolescent↗

Urine macrophage migration inhibitory factor reflects the severity of renal injury in human glomerulonephritis.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a pathogenic role in experimental crescentic glomerulonephritis (GN). Renal expression of MIF is also upregulated in human GN and correlates with leukocytic infiltration, histologic damage, and renal dysfunction. The study presented here examined whether MIF can be measured in urine and if so, whether the urine MIF concentration reflects the degree of renal injury. Urine and serum MIF was measured by enzyme-linked immunosorbent assay in 10 normal healthy volunteers and in a cohort of 63 patients with GN (2 thin basement membrane disease [TBM], 15 membranous GN, 10 focal segmental glomerular sclerosis, 20 IgA glomerularnephritis, 11 crescentic GN, 10 systemic lupus erythematosis World Health Organization class IV). Renal MIF expression was assessed by immunostaining of biopsy tissue. MIF was detected in urine from normal volunteers (mean +/- SD; 191 +/- 132 pg MIF/micromol creatinine). The urine MIF concentration was unchanged in patients with nonproliferative nephropathies (343 +/- 397 pg MIF/micromol Cr) but was increased 3.4-fold in proliferative nephropathies (645 +/- 527 pg MIF/micromol Cr; P < 0.05 versus normal and nonproliferative). Stratified analysis showed the greatest increase in urine MIF in crescentic GN (4.5-fold). In contrast, serum MIF levels were not different between normal patients and any patient group. Immunostaining demonstrated a significant increase in renal MIF expression in proliferative glomerulonephritides that was associated with macrophage and T cell infiltration. There was a significant correlation between the urine MIF concentration and renal MIF expression, but not with serum MIF, indicating a renal origin for the excreted urine MIF. The urine MIF concentration also correlated with the degree of renal dysfunction, histologic damage, and leukocytic infiltration, but not with the amount of proteinuria. In conclusion, this study shows that the urine MIF concentration is significantly increased in proliferative forms of GN and correlates with the degree of renal injury. Urine MIF levels reflect MIF expression within the kidney and may be a useful noninvasive tool for monitoring patients with crescentic GN, particularly in disease exacerbation.

Adult↗

[A further study on potential of microsatellite analysis of urine in diagnosis of bladder cancer].

OBJECTIVES: To investigate the application value of microsatellite analysis of voided urine in diagnosis of bladder cancer and compare the advantages and disadvantages of this method and urine cytology. METHODS: Thirteen microsatellite markers, including the nine markers used in the authors' previous study and another four new markers, were tested on urine DNA from 143 individuals with or without bladder lesions in a blinded fashion. Urine cytology was applied at the same time. RESULTS: The urine DNA from 89% (97/109) of the patients with bladder cancer, 86% (6/7) of the patients with inverted papilloma of the bladder, 3 out of 7 patients with cystitis and one patient with hematuria of unknown cause showed alterations, at least, in one of the 13 microsatellite markers, while the 19 individuals without bladder lesion had no change at any of these loci. Nucleic atypia or suspicious cancer cells were detected by routine cytology in the urine of the 3 patients with cystitis and one patient with hematuria of unknown cause who showed alterations of microsatellite in their urine sediments. Among the 81 cases of bladder cancer whose urine was examined by both microsatellite analysis and routine cytology, 73 cases (90%), of various stage or grade, were identified by microsatellite analysis, while only 41 cases (51%), mainly at advanced stage, were detected by cytology. Cancer cells were detected in the urine sediments of 4 of the 12 cases that were not identified by microsatellite analysis. CONCLUSION: Microsatellite analysis of urine is useful for detection of bladder cancer. Microsatellite analysis and urine cytology could be complementary to each other.

Female↗