Consistency Analysis of the UF-1500 and UF-5000 Automated Urine Particle Analyzers.

BACKGROUND: The aim was to evaluate the consistency of the results between the UF-1500 and UF-5000, fully automated urine particle analyzers. METHODS: A total of 554 randomly selected inpatient and outpatient urine samples were collected for analysis using the UF-1500, the UF-5000, and by manual microscopic examination. The coincidence rate, intraday repeatability, and interday reproducibility were evaluated on the UF-1500 and UF-5000. To analyze the review flags from the UF-1500, the UF-1500 results were compared to manual microscopy as the gold standard. RESULTS: The repeatability of red blood cells (RBCs), white blood cells (WBCs), epithelial cells (ECs), casts, and bacteria using the UF-1500 and UF-5000 is expressed as the relative standard deviations of the intraday and inter-day measurements. For the UF-1500, the relative standard deviation values ranged from 5.9% to 12.6% and 4.9% to 17.2% for the low and 1.6% to 9.3% and 2.3% to 16.9% for the high samples, respectively. The correlation co-efficient for RBCs, WBCs, ECs, SECs, casts, crystals, and bacteria for the UF-1500 were 0.981, 0.993, 0.968, 0.963, 0.821, 0.783, and 0.992, respectively. Review samples from the UF-1500 were confirmed by microscopic examination. Review flags for all 554 samples included 3 samples with "DEBRIS High" and 23 samples with "RBCs/YLC Abnormal classification". CONCLUSIONS: The identification of various urine components by both instruments meets laboratory requirements. These two instruments with different performances have specific characteristics and should be used based upon the needs of each laboratory.

New microfluidic paper-based analytical device for iron determination in urine samples.

Iron is an important micronutrient involved in several mechanisms in the human body and can be an important biomarker. In this work, a simple and disposable microfluidic paper-based analytical device (µPAD) was developed for the quantification of iron in urine samples. The detection was based on the colorimetric reaction between iron(II) and bathophenanthroline and the reduction of iron(III) to iron(II) with hydroxylamine. The developed µPAD enabled iron determination in the range 0.07-1.2 mg/L, with a limit of detection of 20 µg/L and a limit of quantification of 65 µg/L, thus suitable for the expected values in human urine. Additionally, targeting urine samples, the potential interference of the samples color was overcome by incorporating a sample blank assessment for absorbance subtraction. Stability studies revealed that the device was stable for 15 days prior to usage and that the formed colored product was stable for scanning up to 3 h. The accuracy of the developed device was established by analyzing urine samples (#26) with the developed µPAD and with the atomic absorption spectrometry method; the relative deviation between the two sets of results was below 9.5%.

Adduct annotation in liquid chromatography/high-resolution mass spectrometry to enhance compound identification.

Annotation and interpretation of full scan electrospray mass spectra of metabolites is complicated by the presence of a wide variety of ions. Not only protonated, deprotonated, and neutral loss ions but also sodium, potassium, and ammonium adducts as well as oligomers are frequently observed. This diversity challenges automatic annotation and is often poorly addressed by current annotation tools. In many cases, annotation is integrated in metabolomics workflows and is based on specific chromatographic peak-picking tools. We introduce mzAdan, a nonchromatography-based multipurpose standalone application that was developed for the annotation and exploration of convolved high-resolution ESI-MS spectra. The tool annotates single or multiple accurate mass spectra using a customizable adduct annotation list and outputs a list of [M+H]+ candidates. MzAdan was first tested with a collection of 408 analytes acquired with flow injection analysis. This resulted in 402 correct [M+H]+ identifications and, with combinations of sodium, ammonium, and potassium adducts and water and ammonia losses within a tolerance of 10 mmu, explained close to 50% of the total ion current. False positives were monitored with mass accuracy and bias as well as chromatographic behavior which led to the identification of adducts with calcium instead of the expected potassium. MzAdan was then integrated in a workflow with XCMS for the untargeted LC-MS data analysis of a 52 metabolite standard mix and a human urine sample. The results were benchmarked against three other annotation tools, CAMERA, findMAIN, and CliqueMS: findMAIN and mzAdan consistently produced higher numbers of [M+H]+ candidates compared with CliqueMS and CAMERA, especially with co-eluting metabolites. Detection of low-intensity ions and correct grouping were found to be essential for annotation performance. Graphical abstract.

Proteinuria is independently associated with carotid atherosclerosis: a multicentric study.

BACKGROUND AND AIMS: Atherosclerosis is a vital cause of cardiovascular diseases. The correlation between proteinuria and atherosclerosis, however, has not been confirmed. This study aimed to assess whether there is a relationship between proteinuria and atherosclerosis. METHODS: From January 2016 to September 2020, 13,545 asymptomatic subjects from four centres in southern China underwent dipstick proteinuria testing and carotid atherosclerosis examination. Data on demography and past medical history were collected, and laboratory examinations were performed. The samples consisted of 7405 subjects (4875 males and 2530 females), excluding subjects failing to reach predefined standards and containing enough information. A multivariate logistic regression model was used to adjust the influence of traditional risk factors for atherosclerosis on the results. RESULTS: Compared with proteinuria-negative subjects, proteinuria-positive subjects had a higher prevalence rate of carotid atherosclerosis. The differences were statistically significant (22.6% vs. 26.7%, χ2 = 10.03, p = 0.002). After adjusting for common risk factors for atherosclerosis, age, sex, BMI, blood lipids, blood pressure, renal function, hypertensive disease, diabetes mellitus and hyperlipidaemia, proteinuria was an independent risk factor for atherosclerosis (OR = 1.191, 95% CI 1.015-1.398, p = 0.033). The Hosmer-Lemeshow test was used to test the risk prediction model of atherosclerosis, and the results showed that the model has high goodness of fit and strong independent variable prediction ability. CONCLUSIONS: Proteinuria is independently related to carotid atherosclerosis. With the increase in proteinuria level, the risk of carotid atherosclerotic plaque increases. For patients with positive proteinuria, further examination of atherosclerosis should not be ignored.

The Level of Urine Dipstick Proteinuria and Its Relation to the Risk of Incident Cholelithiasis.

BACKGROUND: Previous studies have suggested the potential association between renal diseases and gallstone. The extent of proteinuria is recognized as a marker for the severity of chronic kidney disease. However, little data is available to identify the risk of incident gallstone according to the level of proteinuria. METHODS: Using a data of 207,356 Koreans registered in National Health Insurance Database, we evaluated the risk of gallstone according to the levels of urine dipstick proteinuria through an average follow-up of 4.36 years. Study subjects were divided into 3 groups by urine dipstick proteinuria (negative: 0, mild: 1+ and heavy: 2+ or greater). Multivariate Cox-proportional hazard model was used to assess the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cholelithiasis according to urine dipstick proteinuria. RESULTS: The group with higher urine dipstick proteinuria had worse metabolic, renal, and hepatic profiles than those without proteinuria, which were similarly observed in the group with incident cholelithiasis. The heavy proteinuria group had the greatest incidence of cholelithiasis (2.39%), followed by mild (1.54%) and negative proteinuria groups (1.39%). Analysis for multivariate Cox-proportional hazard model indicated that the heavy proteinuria group had higher risk of cholelithiasis than other groups (negative: reference, mild proteinuria: HR 0.97 [95% CI, 0.74-1.26], and heavy proteinuria: HR 1.46 [95% CI, 1.09-1.96]). CONCLUSION: Urine dipstick proteinuria of 2+ or greater was significantly associated with increased risk for incident gallstone.

Prognostic significance of urinary protein and urinary ketone bodies in acute ischemic stroke.

BACKGROUND AND AIMS: Prior studies have shown an association between positive urinary protein and an elevated risk of long-term mortality in patients with acute ischemic stroke (AIS); however, data on the short-term prognostic significance of urinary protein and urinary ketone bodies in patients with AIS is sparse. METHODS AND RESULTS: A total of 2842 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. Patients were divided into urinary protein positive and negative, urinary ketone bodies positive and negative by urine dipstick. Cox and logistic regression models were used to estimate the effect of urinary protein and urinary ketone bodies on all cause in-hospital mortality and poor outcome upon discharge (modified Rankin Scale score ≥3) in AIS patients. Patients with positive urinary protein was associated with a 2.74-fold and 1.62-fold increase in the risk of in-hospital mortality (adjusted HR 2.74; 95% CI, 1.54-4.89; P-value = 0.001) and poor outcome upon discharge (aOR, 1.62; 95% CI 1.26-2.08; P-value <0.001) in comparison to negative urinary protein after adjusting for potential covariates. Moreover, Patients with positive urinary ketone bodies was associated with 2.11-fold in the risk of poor outcome upon discharge (aOR 2.11; 95% CI 1.52-2.94; P-value <0.001) but not in-hospital mortality (P-value = 0.066) after adjusting for potential covariates. CONCLUSIONS: Urinary protein at admission was independently associated with in-hospital mortality and poor functional outcome at hospital discharge in acute stroke patients and urinary ketone bodies also associated with poor functional outcome at hospital discharge.

Weight loss reduces the incidence of dipstick proteinuria: a cohort study from the Japanese general population.

BACKGROUND: Though elimination of obesity is one of main therapeutic goal for lifestyle-related diseases, the impact of appropriate weight loss on reduction of the incidence of proteinuria in the general population is still unclear. METHODS: The study cohort was based on a general population of 9,33,490 from 40 to 74 years of age who had undergone annual specific health checkups. The subjects who were finally included were the 2,74,598 people for whom all the data necessary for this study were available. The incidence of proteinuria in this study was defined as negative proteinuria at the primary and secondary survey years, and newly developed proteinuria during subsequent follow-up years. RESULTS: Whereas people with rapidly decreased weight tended to have a high incidence of proteinuria in the underweight (BMI < 18.5 kg/m2) and normal weight (18.5-24.9 kg/m2) groups, the obese group (≥ 25.0 kg/m2) with rapidly decreased weight had a lower incidence compared to those with stable weight. In the obese population, a rapid decline of BMI (- 1 to - 5 kg/m2 per year) was associated with a reduced risk (hazard ratio [95% confidence interval]; 0.89 [0.80-0.98], P = 0.02) of proteinuria. CONCLUSIONS: Weight reduction can lead to a risk reduction of 11% in the incidence of proteinuria in obese Japanese adults. This is the first study to report the effects of weight reduction on the early phase of chronic kidney disease in obesity relevant to the characteristics of the Japanese general population. The present findings might have a role in renal health promotion in Japan.

The association between frailty and chronic kidney disease; cross-sectional analysis of the Nambu Cohort Study.

BACKGROUND: Both frailty and chronic kidney disease (CKD) increase with age and share many similarities. Many studies have demonstrated an association between frailty and chronic kidney disease (CKD), but an association with dipstick proteinuria is limited. METHODS: This is the cross-sectional analysis of the Nambu Cohort Study at the beginning of observation. Frailty was diagnosed using Kihon Checklist. Logistic analysis was used to evaluate the association between frailty and CKD or dipstick proteinuria. RESULTS: Among a total of 630 outpatients [age, 78 (70-84) years, men, 50%], the prevalence of patients with pre-frailty and frailty was 32% and 40%, respectively. The proportion of patients with pre-frailty and frailty increased with decreasing estimated glomerular filtration rate (eGFR) and increasing dipstick proteinuria levels. The odds ratios (95% confidence intervals) for CKD stage of 60 < eGFR ≤ 45 ml/min/1.73 m2, and 45 ml/min/1.73 m2 < eGFR for frailty was 0.87 (0.56-1.35) and 2.54 (1.46-4.53), respectively, compared with non-CKD as a reference. Furthermore, the odds ratios for the frailty of dipstick proteinuria with ± and + or over were 1.36 (0.88-2.09) and 1.78 (1.00-3.17), respectively, when dipstick proteinuria-was used as a reference. Moreover, the combination of eGFR and dipstick proteinuria levels increased the odds ratio for pre-frailty and frailty. CONCLUSION: Elderly patients with CKD had a higher prevalence of pre-frailty and frailty. By adding urinary protein information to eGFR, the link between CKD and frailty becomes even more robust.

Evaluation of the Atellica® UAS 800: a new member of the automated urine sediment analyzer family.

BACKGROUND: In 2017 the Atellica® UAS 800 urine sediment analyzer was introduced by Siemens Healthineers. We investigated its applicability in the standardization and automation of the laboratory urinalysis workflow, including the prediction of urine culture outcome and glomerular pathology. METHODS: We evaluated the performance characteristics of the Atellica® UAS 800 and its correlation with the iQ200 (Beckman Coulter). In addition, we studied the agreement between Atellica® UAS 800 and CLINITEK Novus® and determined the predictive value of bacteria and leukocyte counts for urine culture outcome. Furthermore, we investigated the ability of Atellica® UAS 800 to identify pathological casts and dysmorphic erythrocytes in comparison to manual microscopy. RESULTS: Erythrocyte and leukocyte analyses indicated high intra- and inter-run precisions and good correlations with the iQ200. We found that the Atellica® UAS 800 detects bacteria with higher sensitivity than the iQ200. The Atellica® UAS 800 and CLINITEK Novus® showed a high degree of conformity. We determined seven combinations of clinical cut-off values of bacteria and leukocytes for predicting urine culture outcome with sensitivity, specificity, and negative predictive values of 95%, 52%, and 93%, respectively. Using the Atellica® UAS 800, hyaline casts, erythrocyte casts, leukocyte casts, and dysmorphic erythrocytes were correctly recognized in 76%, 22%, 2%, and 39% of the samples, respectively. CONCLUSIONS: The Atellica® UAS 800 is a robust, fast, and user-friendly analyzer, which accurately quantifies erythrocytes, leukocytes, bacteria and squamous epithelial cells, and may be utilized for predicting positive urine cultures. The detection of clinically important pathological casts and dysmorphic erythrocytes proved insufficient.

A performance comparison of the fully automated urine particle analyzer UF-5000 with UF-1000i and Gram staining in predicting bacterial growth patterns in women with uncomplicated urinary tract infections.

BACKGROUND: The aim of this study was to compare the performance of the new flow cytometer UF-5000 with the UF-1000i and Gram staining for determining bacterial patterns in urine samples. METHODS: Women who attended our clinic with symptoms suggestive of urinary tract infection were enrolled in the study. Mid-stream urine samples were collected for gram staining, urine analysis and urine cultures. Bacterial patterns were classified using the UF-1000i (none, cocci bacteria or rods/mixed growth), the UF-5000 (none, cocci, rods or mixed growth) and Gram staining. RESULTS: Among the 102 included samples, there were 10 g-positive cocci, 2 g-positive bacilli, 66 g-negative rods, and 24 mixed growth. The sensitivity/specificity of the UF-1000i was 81.8/91.1% for gram-negative rods and 23.5/96.9% for cocci/mixed. The sensitivity/specificity of the UF-5000 was 80.0/88.2% for gram negative rods and 70.0/86.5% for gram-positive cocci. CONCLUSIONS: The UF-5000 demonstrated good sensitivity and specificity for Gram-negative bacilli and demonstrated an improved sensitivity for detecting Gram-positive cocci compared with the UF-1000i.

Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis : An Individual Participant-Based Meta-analysis.

BACKGROUND: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead. OBJECTIVE: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging. DESIGN: Individual participant-based meta-analysis. SETTING: 12 research and 21 clinical cohorts. PARTICIPANTS: 919 383 adults with same-day measures of ACR and PCR or dipstick protein. MEASUREMENTS: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g). RESULTS: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR. LIMITATION: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample. CONCLUSION: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

Single Extracellular Vesicle Analysis Performed by Imaging Flow Cytometry and Nanoparticle Tracking Analysis Evaluate the Accuracy of Urinary Extracellular Vesicle Preparation Techniques Differently.

Small extracellular vesicles isolated from urine (uEVs) are increasingly recognized as potential biomarkers. Meanwhile, different uEV preparation strategies exist. Conventionally, the performance of EV preparation methods is evaluated by single particle quantification, Western blot, and electron microscopy. Recently, we introduced imaging flow cytometry (IFCM) as a next-generation single EV analysis technology. Here, we analyzed uEV samples obtained with different preparation procedures using nanoparticle tracking analysis (NTA), semiquantitative Western blot, and IFCM. IFCM analyses demonstrated that urine contains a predominant CD9+ sEV population, which exceeds CD63+ and CD81+ sEV populations. Furthermore, we demonstrated that the storage temperature of urine samples negatively affects the recovery of CD9+ sEVs. Although overall reduced, the highest CD9+ sEV recovery was obtained from urine samples stored at -80 °C and the lowest from those stored at -20 °C. Upon comparing the yield of the different uEV preparations, incongruencies between NTA and IFCM data became apparent. Results obtained by both NTA and IFCM were consistent with Western blot analyses for EV marker proteins; however, NTA results correlated with the amount of the impurity marker uromodulin. Despite demonstrating that the combination of ultrafiltration and size exclusion chromatography appears as a reliable uEV preparation technique, our data challenge the soundness of traditional NTA for the evaluation of different EV preparation methods.

Design and Functionalization of a µPAD for the Enzymatic Determination of Nitrate in Urine.

In this work, the design of a microfluidic paper-based analytical device (µPAD) for the quantification of nitrate in urine samples was described. Nitrate monitoring is highly relevant due to its association to some diseases and health conditions. The nitrate determination was achieved by combining the selectivity of the nitrate reductase enzymatic reaction with the colorimetric detection of nitrite by the well-known Griess reagent. For the optimization of the nitrate determination µPAD, several variables associated with the design and construction of the device were studied. Furthermore, the interference of the urine matrix was evaluated, and stability studies were performed, under different conditions. The developed µPAD enabled us to obtain a limit of detection of 0.04 mM, a limit of quantification of 0.14 mM and a dynamic concentration range of 0.14-1.0 mM. The designed µPAD proved to be stable for 24 h when stored at room temperature in air or vacuum atmosphere, and 60 days when stored in vacuum at -20 °C. The accuracy of the nitrate µPAD measurements was confirmed by analyzing four certified samples (prepared in synthetic urine) and performing recovery studies using urine samples.

Voltammetric pH Measurements in Unadulterated Foodstuffs, Urine, and Serum with 3D-Printed Graphene/Poly(Lactic Acid) Electrodes.

The pH of a system is a critical descriptor of its chemistry-impacting reaction rates, solubility, chemical speciation, and homeostasis. As a result, pH is one of the most commonly measured parameters in food safety, clinical, and environmental laboratories. Glass pH probes are the gold standard for pH measurements but suffer drawbacks including frequent recalibration, wet storage of the glass membrane, difficulty in miniaturization, and interferences from alkali metals. In this work, we describe a voltammetric pH sensor that uses a three-dimensional (3D)-printed graphene/poly(lactic acid) filament electrode that is pretreated to introduce quinone functional groups to the graphene surface. After thoroughly characterizing the pretreatment parameters using outer-sphere and inner-sphere redox couples, we measured pH by reducing the surface-bound quinones, which undergo a pH-dependent 2e-/2H+ reduction. The position of the redox peak was found to shift -60 ± 2 mV pH-1 at 25 °C, which is in excellent agreement with the theoretical value predicted by the Nernst Equation (-59.2 mV pH-1). Importantly, the sensors did not require the removal of dissolved oxygen prior to successful pH measurements. We investigated the impact of common interfering species (Pb2+ and Cu2+) and found that there was no impact on the measured pH. We subsequently challenged the sensors to measure the pH of unadulterated complex samples, including cola, vinegar, an antacid tablet slurry, serum, and urine, and obtained excellent agreement compared to a glass pH electrode. In addition to the positive analytical characteristics, the sensors are extremely cheap and easy to fabricate, making them highly accessible to a wide range of researchers. These results pave the way for customizable pH sensors that can be fabricated in (nearly) any geometry for targeted applications using 3D printing.

An immunoassay cassette with a handheld reader for HIV urine testing in point-of-care diagnostics.

Currently, most HIV tests are performed with blood samples, or alternatively saliva samples are used for HIV testing. Simple HIV tests need to be performed in hospitals or other medical agencies instead of more invasive HIV blood tests. To enable point-of-care (POC) HIV diagnostics, based on a recently developed lateral flow strip for HIV urine testing, a microfluidic immunoassay cassette with a handheld optical reader is developed. Based on lateral flow strip with gold colloid reporter, the integrated immunoassay cassette can perform sample introduction, metering, discharging, applying and detection which simplifies HIV testing. An indicator is incorporated into the cassette to guide sample introduction based on color change, and further, the excess test sample is stored inside the sealed cassette to avoid any contamination. The low-cost handheld optical reader can provide a test result within a few seconds, which is useful for simple, sensitive and affordable HIV onsite detection. Instead of using normal white LEDs, a customized back light module embedded with green LEDs is adopted to illuminate the lateral flow strip with an appropriate working current to achieve optimal performance. Compared to the standard lateral flow strips using a benchtop reader, with the disposable immunoassay cassette assisted by the handheld optical reader, more convenient, easier-to-operate, and more affordable HIV urine testing can be achieved in POC diagnostics.

Nanocomposites of poly(l-methionine), carbon nanotube-graphene complexes and Au nanoparticles on screen printed carbon electrodes for electrochemical analyses of dopamine and uric acid in human urine solutions.

A sensitive electrochemical sensor featuring novel composites of gold and carbon nanocomplexes alongside a polymerized amino acid was developed for the determination of uric acid (UA) and dopamine (DA) concentrations in both buffer and human urine sample solutions. The sensor was fabricated by electropolymerization of l-methionine (l-Met) followed by coating of carbon nanotube-graphene complexes and electrodeposition of gold nanoparticles on a screen printed carbon electrode surface. The electrode surfaces were characterized by field emission scanning electron microscopy and energy dispersive spectroscopy, and the electrochemical properties were investigated by cyclic voltammetry and differential pulse voltammetry. Linear ranges of 0.05-3 µM and 1-35 µM with limits of detection of 0.0029 and 0.034 µM were achieved for DA and UA, respectively. In addition, the developed sensor was applied for the analysis of native UA and DA concentrations in undiluted and diluted human urine samples. The UA analysis results were compared to those obtained using high performance liquid chromatography and a fluorometric assay kit while the DA analysis results were compared to those obtained using liquid chromatography-tandem mass spectrometry.

Renal tubular epithelial cells add value in the diagnosis of upper urinary tract pathology.

Background Diagnosis of upper urinary tract infections (UTI) is challenging. We evaluated the analytical and diagnostic performance characteristics of renal tubular epithelial cells (RTECs) and transitional epithelial cells (TECs) on the Sysmex UF-5000 urine sediment analyzer. Methods Urinary samples from 506 patients presenting with symptoms of a UTI were collected. Only samples for which a urinary culture was available were included. Analytical (imprecision, accuracy, stability and correlation with manual microscopy) and diagnostic performance (sensitivity and specificity) were evaluated. Results The Sysmex UF-5000 demonstrated a good analytical performance. Depending on the storage time, storage conditions (2-8 °C or 20-25 °C) and urinary pH, RTECs and TECs were stable in urine for at least 4 h. Using Passing-Bablok and Bland-Altman analysis, an acceptable agreement was observed between the manual and automated methods. Compared to TECs, RTECs demonstrated an acceptable diagnostic performance for the diagnosis of upper UTI. Conclusions While TECs do not seem to serve as a helpful marker, increased urinary levels of RTECs add value in the diagnosis of upper UTI and may be helpful in the discrimination between upper and lower UTIs.

Role of dipstick proteinuria for predicting cardiovascular events: a Japanese cardiovascular hospital database analysis.

Initial screening for proteinuria by urine dipstick test (UDT) may be useful for predicting clinical outcomes. The Shinken Database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. Patients for whom UDT was performed at their initial visit between 2004 and 2010 (n = 7131) were divided into three groups according to the test results: negative, trace, and positive (1+ to 4+) proteinuria. During the mean follow-up period of 3.4 years, 233 (3.1%) deaths, 255 (3.6%) heart failure (HF) events, and 106 (1.5%) ischemic stroke (IS) events occurred. Prevalence of atherothrombotic risks increased with an increase in the amounts of proteinuria. The incidence of all-cause death, HF and IS events increased significantly from negative to trace to positive proteinuria groups (log rank test, P for trend < 0.001). Multivariate analysis revealed independent association between proteinuria and all-cause death [hazard ratio (HR): 1.50, 95% confidence interval (CI) 1.07-2.10], HF (HR: 1.55, 95% CI 1.14-2.12), and IS (HR: 2.08, 95% CI 1.26-3.45). Even trace proteinuria was independently associated with HF (HR: 1.64, 95% CI 1.07-2.53) and IS (HR: 2.17, 95% CI 1.14-4.11) and with all-cause death (HR: 1.56, 95% CI 0.99-2.47). In conclusions, dipstick proteinuria was independently associated with cardiovascular events and death, suggesting that the UDT is a useful tool for evaluating patients' risk for such adverse events.

Usefulness of the quantitative measurement of urine protein at a community-based health checkup: a cross-sectional study.

BACKGROUND: The dipstick urinalysis for proteinuria has been used for chronic kidney disease (CKD) screening at community-based health checkups; however, it has major drawbacks in that the result is only semi-quantitative and is influenced by urine concentration. METHODS: We conducted urine protein/creatinine ratio (UPCR) measurements of 590 participants who showed a result of more than trace proteinuria on a dipstick analysis and evaluated the usefulness of UPCR measurements in community-based health checkups. RESULTS: The UPCR values increased in accordance with the severity of the dipstick test findings, but statistical significance was only obtained between (±) and (1+), between (±) and (2+), and between (±) and (3+) groups. When the participants with (±) proteinuria were subjected to CGA classification (a classification of CKD by cause, glomerular filtration rate category, and albuminuria category) according to their UPCR data, a significant proportion of subjects (277, 77.0%) moved from the A2 category into A1, which is a less severe category. Conversely, 21 subjects (5.8%) were reclassified into a more severe category (A3). Thus, a dipstick test may produce a non-negligible number of false negatives as well as a large number of false positives. Similarly, the classifications of more than half of the subjects with (1+) or more severe proteinuria were changed based on their UPCR results. CONCLUSION: The dipstick urinalysis for proteinuria appears less reliable than expected, suggesting that the quantitative measurement of urine protein should be performed even during mass health checkups to ensure the early detection and prevention of CKD.

Diagnostic accuracy of urine dipstick for proteinuria category in Japanese workers.

BACKGROUND: Urine dipstick tests are often used to evaluate proteinuria during health checkups. We examined the dipstick's accuracy in assessing the proteinuria levels among Japanese workers. METHODS: We assessed subjects aged ≥ 18 years who had a health checkup at the University of Tokyo in 2016 or 2017 (n = 5383). Proteinuria was stratified by urine protein-to-creatinine ratio (PCR): A1, < 150 mg/gCre; A2, 150-499 mg/gCre; and A3, ≥ 500 mg/gCre. The accuracy of a dipstick result of ± or higher to detect a PCR level of ≥ A2 was examined. We compared changes in dipstick results and PCR level in 136 subjects evaluated twice with a median interval of 119 days. RESULTS: The subjects' mean age was 40 years, and half were women. The dipstick results were - in 94.9%, ± in 4.1%, and ≥ 1 + in 1.0%. The PCR level was A1, A2, A3 in 98.6%, 1.2%, and 0.2% of the subjects, respectively. The sensitivity, specificity, and positive and negative predictive values of a ± or higher dipstick result to detect A2 or higher were 66.2%, 95.6%, 17.5%, and 99.5%, respectively. Among the 136 subjects examined twice, 134 (98.5%) had no change in PCR level (A1 in all cases) despite a decrease or increase in dipstick results. CONCLUSION: Urine dipstick results of ± or above had a high specificity but low sensitivity and positive predictive value to detect PCR proteinuria of A2 or higher. Confirmation by quantitative protein measurement should be recommended for individuals at high risk of chronic kidney disease.