Point-of-care image-based quantitative urinalysis with commercial reagent strips: Design and clinical evaluation.

Urinalysis is a useful test as an indicator of health or disease and as such, is a part of routine health screening. Urinalysis can be undertaken in many ways, one of which is reagent strips used in the general evaluation of health and to aid in the diagnosis and monitoring of kidney disease. To be effective, the test must be performed properly, and the results interpreted correctly. However, different light conditions and colour perception can vary between users leading to ambiguous readings. This has led to camera devices being used to capture and generate the estimated biomarker concentrations, but image colour can be affected by variations in illumination and inbuilt image processing. Therefore, a new portable device with embedded image processing techniques is presented in this study to provide quantitative measurements that are invariant to changes in illumination. The device includes a novel calibration process and uses the ratio of RGB values to compensate for variations in illumination across an image and improve the accuracy of quantitative measurements. Results show that the proposed calibration method gives consistent homogeneous illumination across the whole image. Comparisons against other existing methods and clinical results show good performance with a correlation to the clinical values. The proposed device can be used for point-of-care testing to provide reliable results consistent with clinical values.

Urinary Tract Infections: Core Curriculum 2024.

Urinary tract infections (UTIs) are some of the most commonly encountered infections in clinical practice. Accurate diagnosis and evidence-based treatment of UTIs will lead to better clinical care for many patients and limit unnecessary antibiotic use. Urinalysis and urine cultures are helpful tools in the diagnosis of UTIs; however, it is important to recognize their limitations. Differentiating between asymptomatic bacteriuria (ASB) and true UTI is important because antibiotics are unnecessary in most nonpregnant patients with ASB and can even potentially cause harm if prescribed. Choice and duration of antibiotics varies across the spectrum of UTI syndromes such as acute uncomplicated cystitis, pyelonephritis, prostatitis, and catheter-associated UTIs. The treatment approach also depends on patients' degree of immunosuppression and their genitourinary anatomy. Therefore, patients with urological obstruction or kidney transplants may require a specialized and multidisciplinary management approach. For individuals prone to frequent UTIs, some preventative measures can be utilized, yet there is often not a "one size fits all" approach.

The EFLM European Urinalysis Guideline 2023.

BACKGROUND: The EFLM Task and Finish Group Urinalysis has updated the ECLM European Urinalysis Guidelines (2000) on urinalysis and urine bacterial culture, to improve accuracy of these examinations in European clinical laboratories, and to support diagnostic industry to develop new technologies. RECOMMENDATIONS: Graded recommendations were built in the following areas. MEDICAL NEEDS AND TEST REQUISITION: Strategies of urine testing are described to patients with complicated or uncomplicated urinary tract infection (UTI), and high or low-risk to kidney disease. SPECIMEN COLLECTION: Patient preparation, and urine collection are supported with two quality indicators: contamination rate (cultures), and density of urine (chemistry, particles). CHEMISTRY: Measurements of both urine albumin and α1-microglobulin are recommended for sensitive detection of kidney disease in high-risk patients. Performance specifications are given for urine protein measurements and quality control of multiproperty strip tests. PARTICLES: Procedures for microscopy are reviewed for diagnostic urine particles, including urine bacteria. Technologies in automated particle counting and visual microscopy are updated with advice how to verify new instruments with the reference microscopy. BACTERIOLOGY: Chromogenic agar is recommended as primary medium in urine cultures. Limits of significant growth are reviewed, with an optimised workflow for routine specimens, using leukocyturia to reduce less important antimicrobial susceptibility testing. Automation in bacteriology is encouraged to shorten turn-around times. Matrix assisted laser desorption ionization time-of-flight mass spectrometry is applicable for rapid identification of uropathogens. Aerococcus urinae, A. sanguinicola and Actinotignum schaalii are taken into the list of uropathogens. A reference examination procedure was developed for urine bacterial cultures.

Urinalysis is predictive for absence of urinary tract infection in men with and without catheters.

OBJECTIVES: To determine accuracy of negative urinalysis (UA) for predicting negative urine culture and the absence of urinary tract infection (UTI), and optimal urine culture growth cutoff for UTI diagnosis in men with and without urinary catheters. SUBJECTS AND METHODS: UAs with urine cultures within 1 week from adult men were identified and evaluated. Predictive values for the absence of UTI (absence of ≥1 of the following criteria: documentation of UTI diagnosis, antibiotic prescription, uropathogen presence on culture) were calculated. RESULTS: In total, 22 883 UAs were included. Negative UA had a high predictive value for negative urine culture (0.95, 95% confidence interval [CI]: 0.94-0.95) and absence of UTI (0.99, CI: 0.99-0.995) in the overall cohort. Negative UA also had a high predictive value for negative urine culture (0.93, CI: 0.90-0.95) and absence of UTI (0.99, CI: 0.98-0.999) in those with indwelling urinary catheters. The traditional threshold of culture growth of 100 000 colony-forming units (CFU)/mL did not capture 22% of UTIs. CONCLUSION: UA exhibits high predictive value for negative urine culture and absence of UTI in men, supporting a protocol wherein culture is only performed in the context of abnormal UA. The traditional 100 000 CFU/mL cut-off may have not captured a subset of UTI in the male population, and warrants further investigation.

Machine learning-assisted image label-free smartphone platform for rapid segmentation and robust multi-urinalysis.

This study presents a groundbreaking approach for the early detection of chronic kidney disease (CKD) and other urological disorders through an image-label-free, multi-dipstick identification method, eliminating the need for complex machinery, label libraries, or preset coordinates. Our research successfully identified reaction pads on 187 multi-dipsticks, each with 11 pads, leveraging machine learning algorithms trained on human urine data. This technique aims to surpass traditional colourimetric methods and concentration-colour curve fitting, offering more robust and precise community screening and home monitoring capabilities. The developed algorithms enhance the generalizability of machine learning models by extracting primary colours and correcting urine colours on each reaction pad. This method's cost-effectiveness and portability are significant, as it requires no additional equipment beyond a standard smartphone. The system's performance rivals professional medical equipment without auxiliary lighting or flash under regular indoor light conditions, effectively managing false positives and negatives across various categories with remarkable accuracy. In a controlled experimental setting, we found that random forest algorithms, based on a Bagging strategy and applied in the HSV colour space, showed optimal results in smartphone-assisted urinalysis. This study also introduces a novel urine colour correction method, significantly improving machine learning model performance. Additionally, ISO parameters were identified as crucial factors influencing the accuracy of smartphone-based urinalysis in the absence of additional lighting or optical configurations, highlighting the potential of this technology in low-resource settings.

Using the Sysmex UF-4000 urine flow cytometer for rapid diagnosis of urinary tract infection in the clinical microbiological laboratory.

BACKGROUND: Urinary tract infections are responsible for a significant worldwide disease burden. Performing urine culture is time consuming and labor intensive. Urine flow cytometry might provide a quick and reliable method to screen for urinary tract infection. METHODS: We analyzed routinely collected urine samples received between 2020 and 2022 from both inpatients and outpatients. The UF-4000 urine flow cytometer was implemented with an optimal threshold for positivity of ≥100 bacteria/µL. We thereafter validated the prognostic value to detect the presence of urinary tract infection (UTI) based on bacterial (BACT), leukocyte (WBC), and yeast-like cell (YLC) counts combined with the bacterial morphology (UF gram-flag). RESULTS: In the first phase, in 2019, the UF-4000 was implemented using 970 urine samples. In the second phase, between 2020 and 2022, the validation was performed in 42,958 midstream urine samples. The UF-4000 screen resulted in a 37% (n = 15,895) decrease in performed urine cultures. Uropathogens were identified in 18,673 (69%) positively flagged urine samples. BACT > 10.000/µL combined with a gram-negative flag had a >90% positive predictive value for the presence of gram-negative uropathogens. The absence of gram-positive flag or YLC had high negative predictive values (99% and >99%, respectively) and are, therefore, best used to rule out the presence of gram-positive bacteria or yeast. WBC counts did not add to the prediction of uropathogens. CONCLUSION: Implementation of the UF-4000 in routine practice decreased the number of cultured urine samples by 37%. Bacterial cell counts were highly predictive for the presence of UTI, especially when combined with the presence of a gram-negative flag.

The interval between the onset of increased blood pressure and proteinuria in preeclampsia and the contributing factors.

PURPOSE: New-onset proteinuria, as a pivotal sign of representative renal lesions in preeclampsia, is still the most common diagnostic tool for this condition and has been proven to be related to a significantly abnormal sFlt-1/VEGF ratio in circulation. At the same time, blood pressure control plays a vital role in the occurrence and evolution of proteinuria. Therefore, it is particularly helpful to investigate their interval, not only for performing urinalysis for protein more accurately but also for evaluating blood pressure as well as the aggravation of illness, as the related research is limited. METHODS: This retrospective study included 515 preeclampsia patients and 358 normotensive pregnant women who labored in the Second Hospital of Tianjin Medical University from January 2016 to January 2020. First, we described the onset circumstance of high blood pressure and proteinuria as well as the interval among the case group and the subgroups. Then, we determined whether there were significant differences in the basic information, laboratory test results, and newborns between the case and normal groups. Finally, multifactor ANOVA was used to determine the factors influencing the interval. RESULTS: 1. The two most common complications in preeclampsia were proteinuria (88.35%) and placental dysfunction (5.05%). Moreover, 72.04% of preeclampsia cases were diagnosed by abnormal blood pressure together with new-onset proteinuria. 2. The average interval between high blood pressure and proteinuria was 22 gestational days (from 0 to 106 days), and this interval was not significantly different between mild and severe PE (26 days vs. 21 days, P > 0.05) but significantly differed between early-onset and late-onset PE (9 days vs. 28 days, P < 0.05). 3. The number of prenatal visits, serum creatinine in the early trimester, gestational time and diastolic blood pressure value when increased blood pressure was initially detected may influence the interval between the onset of increased blood pressure and proteinuria. CONCLUSION: New-onset proteinuria was still the main parameter for identifying preeclampsia. The interval between increased blood pressure and proteinuria was probably related to the imbalance in the sFlt-1/VEGF ratio; therefore, we should pay attention to monitor proteinuria during the prenatal visits, especially for patients with a lower frequency of prenatal visits, higher serum creatinine in the early trimester, earlier onset and higher diastolic blood pressure at the initial onset of increased blood pressure.

Hepatic Biotransformation of Renal Clearable Gold Nanoparticles for Noninvasive Detection of Liver Glutathione Level via Urinalysis.

Renal clearable nanoparticles have been drawing much attention as they can avoid prolonged accumulation in the body by efficiently clearing through the kidneys. While much effort has been made to understand their interactions within the kidneys, it remains unclear whether their transport could be influenced by other organs, such as the liver, which plays a crucial role in metabolizing and eliminating both endogenous and exogenous substances through various biotransformation processes. Here, by utilizing renal clearable IRDye800CW conjugated gold nanocluster (800CW4-GS18-Au25) as a model, we found that although 800CW4-GS18-Au25 strongly resisted serum-protein binding and exhibited minimal accumulation in the liver, its surface was still gradually modified by hepatic glutathione-mediated biotransformation when passing through the liver, resulting in the dissociation of IRDye800CW from Au25 and biotransformation-generated fingerprint message of 800CW4-GS18-Au25 in urine, which allowed us to facilely quantify its urinary biotransformation index (UBI) via urine chromatography analysis. Moreover, we observed the linear correlation between UBI and hepatic glutathione concentration, offering us a noninvasive method for quantitative detection of liver glutathione level through a simple urine test. Our discoveries would broaden the fundamental understanding of in vivo transport of nanoparticles and advance the development of urinary probes for noninvasive biodetection.

Risk of CKD Following Detection of Microscopic Hematuria: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Microscopic hematuria is an uncertain risk factor for chronic kidney disease (CKD). We investigated the association between persistent or single episodes of microscopic hematuria and the development of incident CKD, overall and separately among men and women. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A total of 232,220 Korean adults without CKD at baseline who underwent repeated regular health examinations at Kangbuk Samsung Health Study formed the study cohort. EXPOSURE: Microscopic hematuria was defined by≥5 red blood cells per high-power field. Participants were categorized into 1 of 4 groups according to the presence of hematuria at 2 consecutive examinations: (1) no hematuria at both examinations (reference group); (2) hematuria followed by no hematuria (regressed hematuria group); (3) no hematuria followed by hematuria (developed hematuria group); and (4) hematuria at both examinations (persistent hematuria group). OUTCOME: CKD was defined as an estimated glomerular filtration rate<60mL/min/1.73m2 or proteinuria (1+or more on dipstick examination). ANALYTICAL APPROACH: Semiparametric proportional hazards models were used to estimate hazard ratios. RESULTS: During a 4.8-year median follow-up period, 2,392 participants developed CKD. Multivariable-adjusted hazard ratios for incident CKD, comparing the regressed, developed, and persistent hematuria groups to the no-hematuria group were 1.85 (95% CI, 1.35-2.53), 3.18 (95% CI, 2.54-3.98), and 5.23 (95% CI, 4.15-6.59), respectively. The association between persistent hematuria and incident CKD was stronger in men than women (P for interaction<0.001), although a statistically significant association was observed in both sexes. LIMITATIONS: Lack of albuminuria and inability to consider specific glomerular diseases. CONCLUSIONS: Men and women with microscopic hematuria, especially persistent hematuria, may be at increased risk of CKD.

Major disparities in patient-reported adherence compared to objective assessment of adherence using mass spectrometry: A prospective study in a tertiary-referral hypertension clinic.

AIM: Many challenges exist in determining true rates of adherence to antihypertensive medications among individuals in a clinic setting. For the first time, we aimed to compare patient-reported antihypertensive adherence with objective evidence using mass spectrometry spot urinalysis in a tertiary referral clinic setting. METHODS: A prospective observational single-centre cohort study was performed in a tertiary referral hypertension clinic, encompassing antihypertensive initiation and persistence. Patients were referred with apparent treatment-resistant hypertension or for suspected secondary causes. Participants completed a self-reported assessment of antihypertensive adherence and provided a spot urine sample. The presence of antihypertensive medications and/or their respective metabolites was evaluated using high-performance liquid chromatography tandem mass spectrometry. Patients were determined to be adherent if they demonstrated both self-reported adherence and objective mass spectrometry evidence. RESULTS: Of all 105 eligible participants initially recruited, 73 (69.5%) met the eligibility criteria. Only 27.4% (95% confidence interval 0.2-0.4) of participants demonstrated true adherence to their self-reported antihypertensives, despite 75.3% (0.6-0.8) reporting adherence. Greatest medication adherence was achieved with angiotensin II receptor blockers (61%), with calcium-channel blockers and mineralocorticoid antagonists demonstrating least adherence (38%). CONCLUSION: In patients attending a tertiary hypertension clinic, the combined use of spot urine mass spectrometry and self-reporting identifies higher rates of nonadherence when compared to either modality alone. Both techniques should be combined for more accurate detection of medication adherence.

Calcium salt crystalluria in a captive chimpanzee (Pan troglodytes) population.

BACKGROUND: Urinalysis is a rapid, non-invasive method used to obtain diagnostic information on primates. While several studies have investigated dipstick and specific gravity values in chimpanzees, urine sediment analysis is often excluded. Crystalluria, observed during urine sediment analysis, can be benign or indicate renal pathologies. METHODS: In total, 665 urine samples from sanctuary-housed chimpanzees were analyzed over the course of 17 months for pH, specific gravity, time of collection, and crystalluria. RESULTS AND CONCLUSIONS: Calcium salt crystalluria was seen in 9.0% of the samples from 23.7% of the individuals in the study. Urinary pH and specific gravity were significantly higher in samples with crystalluria than in those lacking crystalluria, while time of collection did not differ between the two groups. While diet is the most likely cause of the crystalluria in this population, several medications could also cause urinary crystallization. Further exploration of the significance of calcium salt crystalluria in chimpanzees is warranted.

Urine transfer devices may impact urinary particle results: a pre-analytical study.

OBJECTIVES: Well-standardized procedures in the pre-analytical phase of urine diagnostics is of utmost importance to obtain reliable results. We investigated the effect of different urine collection methods and the associated urine transfer tubes on urine test strip and particle results. METHODS: In total, 146 selected urine samples were subdivided into three different collection containers and subsequently transferred into its accompanying transfer tube (BD, Greiner, Sarstedt vacuum and Sarstedt aspiration). As reference, the original urine sample was directly measured on the analyser. Both chemical test strip analysis (Sysmex UC-3500) and fluorescence flow cytometry particle analysis (Sysmex UF-5000) were performed on all samples. RESULTS: No statistically significant differences in test strip results were found between the studied transfer methods. On the contrary, transfer of urine samples to the secondary tubes affected their particle counts. Clinically significant reductions in counts of renal tubular epithelial cells and hyaline casts were observed using the BD and Greiner transfer tubes and in counts of pathological casts using the BD, Greiner and Sarstedt vacuum tubes. CONCLUSIONS: The results of this study indicate that the use of urine transfer tubes may impact counts of fragile urine particles. Clinical laboratories need to be aware about the variation that urine collection methods can induce on urine particle counts.

The relationship between abnormal urinalysis findings and appendicitis location.

AIMS: Acute appendicitis is a common cause of acute abdomen in general surgery and early diagnosis is crucial for prognosis. Abnormal urinalysis results have been associated with appendicitis in some studies, with reports of microscopic hematuria or pyuria in laboratory tests. The aim of this article is to evaluate the relationship between laboratory findings of hematuria, pyuria, and the location of acute appendicitis. METHODS: This retrospective study included 577 patients who underwent appendectomy for suspected acute appendicitis between January 1, 2018, and December 31, 2022, at the general surgery clinic of Samsun Training and Research Hospital. RESULTS: Among the 577 patients, 247 were female and 330 were male, with a median age of 34 years. A statistically significant difference was observed between appendicitis location and erythrocyte values (p = 0.009), specifically in paraileal and retrocecal locations. There was a statistically significant difference between appendicitis location and leukocyte values (p < 0.001), with significant differences found in paraileal, promontoric, and retrocecal locations. A statistically significant difference was observed between appendicitis location and leukocyte esterase values (p = 0.002), specifically in paraileal and retrocecal locations. DISCUSSION/CONCLUSION: Abnormal urinalysis findings are not uncommon in patients with acute appendicitis. Our study demonstrated a significant correlation between tit erythrocyte, tit leukocyte, and tit leukocyte esterase positivity with appendicitis locations. Therefore, we believe that pathological findings in urine tests of patients undergoing surgery with a preliminary diagnosis of appendicitis can provide valuable information to surgeons regarding the location of the appendix, ultimately aiding in optimizing the timing and cost of the operation.

Dipping at home: is it better, easier, and more convenient? A feasibility and acceptability study of a novel home urinalysis using a smartphone application.

BACKGROUND: Monitoring proteinuria in patients with kidney disease is of crucial importance given its implications for long-term disease progression and clinical management. Leveraging digital health technology to provide a clinical grade urinalysis result from home holds the potential to greatly enhance the clinical experience and workflows for patients, caregivers, and providers. The goal of this study was to evaluate the acceptability and feasibility of a home-based urinalysis kit using a smartphone application. METHODS: This is a prospective cohort study of children and young adults (5-21 years of age) at a single pediatric center. The study received ethical board approval. Families performed a home urine test using the Healthy.io smartphone app. The app was compared with standard of care of either home dipstick monitoring or urinalysis performed in clinic or a local laboratory. Patient satisfaction was compared between the new app and current practice. RESULTS: A total of 103 children, 63 (61%) male and median age 10.9 years (inter-quartile range 7.8-14.2), were enrolled. Primary diagnosis included 47 (46%) glomerular disease, 48 (47%) non-glomerular kidney disease, and 8 (8%) kidney transplant recipients. One hundred and one (98%) patients reported being satisfied with the smartphone app compared to 41 (40%) patients who were satisfied with the current practice for urine protein monitoring (p < 0.0001). Positive themes identified included ease of use, convenience, and immediacy and accuracy of results. CONCLUSIONS: The Healthy.io home urine testing app received very high rates of satisfaction among patients and caregivers compared to current practice and holds great potential to enhance patient-centered care. A higher resolution version of the Graphical abstract is available as Supplementary information.

Dipstick urinalysis does not predict post-urodynamic study morbidity.

INTRODUCTION AND HYPOTHESIS: Pre-procedure urinalysis may add unnecessary cost and inconvenience for patients undergoing urodynamics. The hypothesis of this study was that urinalysis would perform poorly when predicting complications following urodynamics. METHODS: Case-control study of women aged 18-89 undergoing urodynamics from 01 January2008 to 31 December 2017 at two tertiary medical centers. Data collected included patient demographics, past medical history, lower urinary tract symptoms, urodynamics indication, urodynamics results, urinalysis result, antibiotic administration, and adverse events within 30 days. Wilcoxon rank-sum test was used to compare those with and without an adverse event. Logistic regression was performed using statistically significant variables on pairwise analysis. RESULTS: A total of 601 patients met the criteria; 11 of these experienced an adverse event, of which all were a urinary tract infection. There were no differences in the frequency of adverse events based on any urinalysis result, regardless of whether the patient received antibiotics. On pairwise analysis, variables associated with a higher frequency of adverse events were higher parity (3.5 (2-5) vs 2 (2, 3), p=0.038) and complaint of suprapubic pain (1 (9.1%) vs 4 (0.7%), p=0.002). On logistic regression, significant variables included increasing age (adjusted odds ratio [aOR] 1.03 per year (95% CI 1.03-4.06); p=0.002), any prolapse (aOR 6.45 (95% CI 3.60-11.54); p<0.001), pelvic organ prolapse as the indication for urodynamics (aOR 7.27 (95% CI 2.60-20.36); p<0.001), and a diagnosis of stress urinary incontinence (4.98 (95% CI 1.95-12.67); p<0.001). CONCLUSION: The frequency of adverse events after urodynamics is low, and urinalysis in asymptomatic patients does not seem to be useful in predicting morbidity.

Best methods for urine sample collection for diagnostic accuracy in women with urinary tract infection symptoms: a systematic review.

BACKGROUND: Most guidelines recommend a midstream urine (MSU) or a midstream clean-catch (MSCC) sample for urinalysis. However, whether this sample is better than others is still controversial. OBJECTIVES: To assess the most adequate non-invasive method to collect a urine specimen for diagnosing urinary tract infections (UTI) in symptomatic non-pregnant women. METHODS: This review was conducted according to the Systematic Reviews of Diagnostic Test Accuracy guidelines (PROSPERO CRD42021241758). PubMed was searched paired sample studies and controlled trials. Studies comparing MSCC, MSU without cleaning, first-void urine, and random voiding samples were considered. Studies evaluating invasive methods were excluded. The main outcome was diagnostic accuracy of urine cultures. Contamination rates were evaluated. The risk of bias tool for systematic reviews on diagnostic accuracy (QUADAS-2) was assessed. RESULTS: Six studies including 1,010 patients were evaluated. Only two studies used paired samples. No study was considered as having low risk of bias. There was no difference in contamination for MSU specimens collected with or without cleansing and between random void urine collection and MSCC. In one study comparing first-void urine with MSU samples, the contamination rate was lower in the latter, but the gold standard of urine culture was only used for one sampling collection. CONCLUSIONS: To the best of our knowledge, this systematic review is the first to assess the evidence available from different exclusively non-invasive urine sampling. Despite being widely recommended, our review did not find consistent evidence that asking women to provide midstream samples with or without cleansing is better.

Urine is one type of specimen that can be easily collected from a patient. Urinalysis testing can give the doctor valuable information about the presence of an infection in the urine and the type of microorganism causing this infection. The physician can also use the information from urine testing to diagnose and treat other diseases. The collection of the mid-stream of the urination has always been advocated. However, this recommendation has never been proven with good quality studies, and the results of the studies carried out so far have been controversial. In a systematic review, we recently determined that the use of any specimen during urination is as good as midstream collection when patients are requested to provide a urine sample and in terms of quality even specimens collected without proper cleansing are also comparable to mid-stream collection with cleansing. In the present systematic review, we evaluated the most adequate non-invasive method to collect a urine specimen for diagnosing urinary tract infections in symptomatic non-pregnant women. We identified only six studies comparing different urine sampling techniques and we did not observe any difference regarding the quality of the urine between them.

The impact of urine storage methods on the results of quantitative bacterial culture in dog and cat.

Quantitative bacterial culture (QBC) is the gold standard for determining urinary tract infections. However, the majority of urine samples were sent to a lab for further bacterial culture. Therefore, the storage condition was vital to maintain the quality and accuracy of the urine samples. The main objective of our study was to examine the urine QBC outcomes of (1) immediate culture, (2) culture after urine sample storage at ambient temperature for 24 h, and (3) culture after urine sample storage at 4 °C for 24 hours. There were 49 feline samples and 30 canine samples included in this study. All QBC samples kept at ambient temperature and refrigerator were consistent with immediate QBC in cats. Eight positive results from immediate QBC were in accordance with refrigerated results in dogs. There were ten positive results in the room-temperature sample with two false-positive results. Our study showed that storing conditions at room temperature or refrigeration for 24 h does not impact the results of QBC in cat urine samples. For dog samples, chilled samples have a higher accuracy rate than room temperature samples, although the overall agreement was still satisfactory.

Size-Transformable Superoxide-Triggered Nanoreporters for Crosstalk-Free Dual Fluorescence/Chemiluminescence Imaging and Urinalysis in Living Mice.

Chemiluminescence imaging has been recognized as a valuable tool for ultrasensitive detection of physio-pathological events through elimination of background autofluorescence. However, most chemiluminescent nanoprobes suffer from shallow imaging depths and slow clearance from living bodies, which impede their use in clinical settings. We herein report size-transformable nanoreporters (ADN1 and ADN2) that could be activated at disease site by superoxide anion (O2 ⋅- ) to trigger nanostructure disassembly into renal excretable fluorescent fragments as well as chemiluminescence turn-on for crosstalk-free duplex chemo-fluorescence imaging and in vitro urinalysis. In peritonitis mouse model, we demonstrate that the representative nanoreporter ADN1 spontaneously accumulates at the disrupted peritoneum and is cleaved by upregulated O2 ⋅- to initiate depolymerization and result in red chemiluminescence at 620 nm, enabling sensitive detection of peritonitis at least 19 h earlier than gold standard histological assays. Additionally, the incorporation of a near-infrared (NIR) dye into ADN1 results in ADN2 exhibiting intense and red-shifted chemiluminescence at ≈800 nm, which permits early detection of deeply seated diseases such as drug-induced hepatotoxicity. This study thus showcases a modular design strategy that is not only applicable to developing versatile chemiluminescent nanoprobes with switchable pharmacokinetics for early disease diagnosis, but also promising for future clinical translations.

Artificial Urinary Biomarkers for Early Diagnosis of Acute Renal Allograft Rejection.

Acute renal allograft rejection (ARAR) after kidney transplantation associated with reduced graft survival and eventual graft failure is poorly diagnosed in hospitals. Here, we report the development of Artificial bioMarker Probes (AMPros) for sensitive urinalysis of ARAR in murine models. AMPros spontaneously go to the kidneys after systemic administration, specifically react with the prodromal immune biomarkers to activate their near-infrared fluorescence signals to report cell-mediated rejection, and efficiently undergo renal excretion into urine. Thus, AMPros enable convenient optical urinalysis that detects ARAR prior to histological manifestation of rejection, which is also earlier than current diagnostic methods measuring proinflammatory cytokines and peripheral blood lymphocyte mRNAs. Due to the high kidney specificity, AMPros-based urinalysis discriminates allograft rejection against other non-alloimmune specific diseases, which is unattainable by measurement of serological biomarkers. Such a noninvasive and sensitive urine test holds great promise in continuous monitoring of renal allograft conditions at low resource settings for timely clinical interventions.

Revisiting approaches to and considerations for urinalysis and urine culture reflexive testing.

Urinalysis is considered the world's oldest laboratory test. Today, many laboratories use macroscopic urinalysis as a screening tool to determine when to subject urine samples for a microscopic urinalysis and/or bacterial culture. While reflexive urine microscopy has been practiced for decades, and reflexive urine culture, more recently, evidence-based guidelines regarding optimal reflexive criteria and workflows are lacking. Standard approaches are hindered, in part, by a lack of harmonization of urinalysis and urine culture practices, heterogeneity in patient populations that are studied, and lack of provider adherence to recommended practices. This review summarizes studies that have evaluated the performance of reflexive urine microscopy and reflexive urine culture, particularly in the context of urinary tract infections. It also examines reported clinical outcomes from reflexive urinalysis interventions and their impact on antibiotic stewardship efforts. Finally, it discusses laboratory operational considerations for the implementation of reflexive algorithms.