Could urinary kidney injury molecule-1 be a good marker in subclinical acute kidney injury in mild to moderate COVID-19 infection?

PURPOSE: To evaluate urinary kidney injury molecule-1 (uKIM-1), which is a proximal tubule injury biomarker in subclinical acute kidney injury (AKI) that may occur in COVID-19 infection. METHODS: The study included proteinuric (n = 30) and non-proteinuric (n = 30) patients diagnosed with mild/moderate COVID-19 infection between March and September 2020 and healthy individuals as a control group (n = 20). The uKIM-1, serum creatinine, cystatin C, spot urine protein, creatinine, and albumin levels of the patients were evaluated again after an average of 21 days. RESULTS: The median (interquartile range) uKIM-1 level at the time of presentation was 246 (141-347) pg/mL in the proteinuric group, 83 (29-217) pg/mL in the non-proteinuric group, and 55 (21-123) pg/mL in the control group and significantly high in the proteinuric group than the others (p < 0.001). Creatinine and cystatin C were significantly higher in the proteinuric group than in the group without proteinuria, but none of the patients met the KDIGO-AKI criteria. uKIM-1 had a positive correlation with PCR, non-albumin proteinuria, creatinine, cystatin C, CRP, fibrinogen, LDH, and ferritin, and a negative correlation with eGFR and albumin (p < 0.05). In the multivariate regression analysis, non-albumin proteinuria (p = 0.048) and BUN (p = 0.034) were identified as independent factors predicting a high uKIM-1 level. After 21 ± 4 days, proteinuria regressed to normal levels in 20 (67%) patients in the proteinuric group. In addition, the uKIM-1 level, albuminuria, non-albumin proteinuria, and CRP significantly decreased. CONCLUSIONS: Our findings support that the kidney is one of the target organs of the COVID-19 and it may cause proximal tubule injury even in patients that do not present with AKI or critical/severe COVID-19 infection.

Evaluation of Urinalysis-Based Screening for Urothelial Carcinoma in Patients With Lynch Syndrome.

BACKGROUND: Approximately 5% to 10% of patients with Lynch syndrome develop urothelial carcinoma. Current screening recommendations vary and are based on expert opinion. Practices need to be evaluated for clinical effectiveness. Our program utilizes urinalysis as a screening test, followed by additional evaluation of microscopic hematuria. OBJECTIVE: This study aimed to determine the clinical utility of a urinalysis-based screening approach for urothelial cancers in patients with Lynch syndrome. DESIGN: This is a retrospective review of a prospectively maintained cohort. SETTING: Patients with Lynch syndrome were managed at a tertiary referral center. PATIENTS: All patients with a Lynch syndrome diagnosis who had a screening urinalysis done as part of our institutional screening protocol (N = 204) were included. MAIN OUTCOME MEASURES: A single-institution hereditary colorectal cancer syndrome registry was queried for patients with Lynch syndrome who had been screened for urothelial carcinomas by urinalysis. Demographics, genotype, family history of urothelial carcinoma, urinalysis results, and subsequent screenings and final diagnosis were gathered for patients between 2008 and 2017. RESULTS: Two hundred four asymptomatic patients underwent screening by urinalysis. Nineteen patients (9.3%) had microscopic hematuria and were further evaluated with urine cytology, imaging, cystoscopy, and/or Urology consultation. None of the 19 patients with microscopic hematuria had urothelial carcinoma. During the same study period, 5 of 204 (2.4%) patients with Lynch syndrome were diagnosed with urothelial cancer, and all presented with symptoms between screening intervals. LIMITATIONS: This is a retrospective study, and not all patients underwent the same secondary evaluation. CONCLUSIONS: No urothelial carcinomas were detected by screening urinalysis in our cohort of asymptomatic patients with Lynch syndrome. False-positive testing led to extensive, mostly uninformative, workups. If urothelial cancer screening is to continue, more effective screening approaches need to be identified. See Video Abstract at http://links.lww.com/DCR/B702. EVALUACIN DEL CRIBADO BASADO EN ANLISIS DE ORINA PARA CARCINOMA UROTELIAL EN PACIENTES CON SNDROME DE LYNCH: ANTECEDENTES:Aproximadamente el 5-10% de los pacientes con síndrome de Lynch desarrollan carcinoma urotelial. Las recomendaciones actuales de detección varían y se basan en la opinión de expertos. Las prácticas deben evaluarse para determinar su eficacia clínica. Nuestro programa utiliza el análisis de orina como prueba de detección, seguido de una evaluación adicional con hematuria microscópica.OBJETIVO:Determinar la utilidad clínica desde un enfoque de cribado basado en análisis de orina, para cánceres uroteliales en pacientes con síndrome de Lynch.DISEÑO:Revisión retrospectiva de una cohorte mantenida prospectivamente.ENTORNO CLINICO:Pacientes con síndrome de Lynch atendidos en un centro de referencia terciario.PACIENTES:Criterios de inclusión fueron todos los pacientes con diagnóstico de síndrome de Lynch realizándoles un análisis de orina de detección como parte de nuestro protocolo de detección institucional (N = 204).PRINCIPALES MEDIDAS DE VALORACION:Solicitando un registro de síndrome de cáncer colorrectal hereditario de una sola institución para pacientes con síndrome de Lynch previamente evaluados para carcinomas uroteliales mediante análisis de orina. Se recopilaron para los pacientes entre 2008 y 2017, datos demográficos, genotipo, antecedentes familiares de carcinoma urotelial, resultados del análisis de orina, posteriores exámenes de detección posteriores y diagnóstico final.RESULTADOS:Doscientos cuatro pacientes asintomáticos fueron sometidos a cribado mediante análisis de orina. Diecinueve pacientes (9,3%) tenían hematuria microscópica y fueron investigados más a fondo con citología de orina, imágenes, cistoscopia y / o consulta de urología. Ninguno de los 19 pacientes con hematuria microscópica tenían carcinoma urotelial. Durante el mismo período de estudio, 5 de 204 (2,4%) pacientes con síndrome de Lynch fueron diagnosticados con cáncer urotelial y todos presentaron presentando síntomas entre los intervalos de detección.LIMITACIONES:Estudio retrospectivo y no todos los pacientes sometidos a la misma evaluación secundaria.CONCLUSIONES:No se detectaron carcinomas uroteliales mediante análisis de orina de detección en nuestra cohorte de pacientes asintomáticos con síndrome de Lynch. Las pruebas de falsos positivos. Condujeron a estudios exhaustivos y en su mayoría poco informativos. Si se desea continuar con la detección del cáncer de urotelio, es necesario identificar enfoques de detección más efectivos. Consulte Video Resumen en http://links.lww.com/DCR/B702.

Associations of kidney tests at medical facilities and health checkups with incidence of end-stage kidney disease: a retrospective cohort study.

No study has assessed the association between no health checkup and end-stage kidney disease (ESKD). This retrospective cohort study, including 69,147 adults aged ≥ 40 years in Japan who were insured by the National Health Insurance and the Late-Stage Medical Care System for the Elderly, assessed the associations of kidney tests at medical facilities and health checkups with incident ESKD. The main exposure was the histories of kidney tests using dipstick urinalysis and/or serum creatinine measurement at medical facilities and checkups in the past year: "checkups," "no kidney test (without checkup)," and "kidney tests (without checkup)" groups. During the median observational period of 5.0 years, ESKD was observed in 246 (0.8%) men and 124 (0.3%) women. The "no kidney test" group was associated with ESKD in men (adjusted subhazard ratio of "no kidney test" vs. "checkups": 1.66 [95% confidence interval, 1.04-2.65], but not in women. Age-specific subgroup analyses identified the "no kidney test" group as a high-risk population of ESKD in elderly men (1.30 [0.70-2.41] and 2.72 [1.39-5.33] in men aged 40-74 and ≥ 75 years, respectively). Elderly men with no kidney test at medical facilities and no health checkup were at higher risk of ESKD.

A Statewide Quality Improvement Collaborative's Adherence to the 2017 American Urological Association Guidelines Regarding Initial Evaluation of Patients With Clinical T1 Renal Masses.

OBJECTIVE: To evaluate MUSIC-KIDNEY's adherence to the American Urological Association (AUA) guidelines regarding the initial evaluation of patient's with clinical T1 (cT1) renal masses. METHODS: We reviewed MUSIC-KIDNEY registry data for patients with newly diagnosed cT1 renal masses to assess for adherence with the 2017 AUA guideline statements regarding recommendations to obtain (1) CMP, (2) CBC, (3) UA, (4) abdominal cross-sectional imaging, and (5) chest imaging. An evaluation consisting of all 5 guideline measures was considered "complete compliance." Variation with guideline adherence was assessed by contributing practice, management strategy, and renal mass size. RESULTS: We identified 1808 patients with cT1 renal masses in the MUSIC-KIDNEY registry, of which 30% met the definition of complete compliance. Most patients received care that was compliant with recommendations to obtain laboratory testing with 1448 (80%), 1545 (85%), and 1472 (81%) patients obtaining a CMP, CBC, and UA respectively. Only 862 (48%) patients underwent chest imaging. Significant variation exists in complete guideline compliance for contributing practices, ranging from 0% to 45% as well as for patients which underwent immediate intervention compared with initial observation (37% vs 23%) and patients with cT1b masses compared with cT1a masses (36% vs 28%). CONCLUSION: Complete guideline compliance in the initial evaluation of patients with cT1 renal masses is poor, which is mainly driven by omission of chest imaging. Significant variation in guideline adherence is seen across practices, as well as patients undergoing an intervention vs observation, and cT1a vs cT1b masses. There are ample quality improvement opportunities to increase adherence and decrease variability with guideline recommendations.

Recurrent Urinary Tract Infection in Women: Primary Care Referral Patterns in a Tertiary Care Center.

OBJECTIVES: With more than 150 million urinary tract infections (UTIs) diagnosed globally per year, the impact on patient care is significant. We sought to examine appropriateness of management of recurrent UTI before referral to a female pelvic medicine and reconstructive surgery practice, as well as the characteristics of patients referred. METHODS: The medical records of 100 consecutive women with a diagnosis of "recurrent UTI" at a single institution between November 2010 and December 2015 were reviewed. The baseline clinical characteristics, laboratory testing, and treatments before and at referral to the female pelvic medicine and reconstructive surgery were examined by descriptive statistics. RESULTS: The evaluation and treatment patterns for recurrent UTI before specialist referral varied widely. Pelvic examination was performed in only 20.8% of patients before referral. Although most women had at least 1 culture performed (65.2%), treatments were variable. Only 42.7% of patients received recommended first-line antibiotic therapy. At symptom recurrence, only 47.2% of patients received a urine culture; most were empirically treated. Approximately 35.0% of patients received the same antibiotic upon their first recurrence. CONCLUSIONS: A large proportion of patients referred for recurrent UTI to a specialty practice had no prior culture, physical examination, or symptom-specific evaluation before referral. Despite existing guidelines, the evaluation, treatment, and referral patterns for recurrent UTI are highly varied and rarely conform to recommendations. Further studies are needed to confirm these trends and determine interventions to improve the efficacy and efficiency of primary care for women with recurrent UTI.

How Reliable Is Automated Urinalysis in Acute Kidney Injury?

OBJECTIVE: Examination of urine sediment is crucial in acute kidney injury (AKI). In such renal injury, tubular epithelial cells, epithelial cell casts, and dysmorphic red cells may provide clues to etiology. The aim of this study was to compare automated urinalysis findings with manual microscopic analysis in AKI. METHODS: Samples from patients diagnosed with AKI and control patients were included in the study. Red blood cells, white blood cells, renal tubular epithelial cells/small round cells, casts, and pathologic (path) cast counts obtained microscopically and by a UF1000i cytometer were compared by Spearman test. Logistic regression analysis was used to assess the ability to predict AKI from parameters obtained from the UF1000i. RESULTS: There was poor correlation between manual and automated analysis in AKI. None of the parameters could predict AKI using logistic regression analysis. However, the increment in the automated path cast count increased the odds of AKI 93 times. CONCLUSION: Automated urinalysis parameters are poor predictors of AKI, and there is no agreement with manual microscopy.

Assessment of Prevalence and Cost of Care Cascades After Routine Testing During the Medicare Annual Wellness Visit.

Importance: For healthy adults, routine testing during annual check-ups is considered low value and may trigger cascades of medical services of unclear benefit. It is unknown how often routine tests are performed during Medicare annual wellness visits (AWVs) or whether they are associated with cascades of care. Objective: To estimate the prevalence of routine electrocardiograms (ECGs), urinalyses, and thyrotropin tests and of cascades (further tests, procedures, visits, hospitalizations, and new diagnoses) that might follow among healthy adults receiving AWVs. Design, Setting, and Participants: Observational cohort study using fee-for-service Medicare claims data from beneficiaries aged 66 years and older who were continuously enrolled in fee-for-service Medicare between January 1, 2013, and March 31, 2015; received an AWV in 2014; had no test-relevant prior conditions; did not receive 1 of the 3 tests in the 6 months before the AWV; and had no test-relevant symptoms or conditions in the AWV testing period. Data were analyzed from February 13, 2019, to June 8, 2020. Exposure: Receipt of a given test within 1 week before or after the AWV. Main Outcomes and Measures: Prevalence of routine tests during AWVs and cascade-attributable event rates and associated spending in the 90 days following the AWV test period. Patient, clinician, and area-level characteristics associated with receiving routine tests were also assessed. Results: Among 75 275 AWV recipients (mean [SD] age, 72.6 [6.1] years; 48 107 [63.9%] women), 18.6% (14 017) received at least 1 low-value test including an ECG (7.2% [5421]), urinalysis (10.0% [7515]), or thyrotropin test (8.7% [6534]). Patients were more likely to receive a low-value test if they were younger (adjusted odds ratio [aOR], 1.69 for ages 66-74 years vs ages ≥85 years [95% CI, 1.53-1.86]), White (aOR, 1.32 compared with Black [95% CI, 1.16-1.49]), lived in urban areas (aOR, 1.29 vs rural [95% CI, 1.15-1.46]), and lived in high-income areas (aOR, 1.26 for >400% of the federal poverty level vs <200% of the federal poverty level [95% CI, 1.16-1.37]). A total of 6.1 (95% CI, 4.8-7.5) cascade-attributable events per 100 beneficiaries occurred in the 90 days following routine ECGs and 5.4 (95% CI, 4.2-6.5) following urinalyses, with cascade-attributable cost per beneficiary of $9.62 (95% CI, $6.43-$12.80) and $7.46 (95% CI, $5.11-$9.81), respectively. No cascade-attributable events or costs were found to be associated with thyrotropin tests. Conclusions and Relevance: In this study, 19% of healthy Medicare beneficiaries received routine low-value ECGs, urinalyses, or thyrotropin tests during their AWVs, more often those who were younger, White, and lived in urban, high-income areas. ECGs and urinalyses were associated with cascades of modest but notable cost.

Analysis of urinary exosomal metabolites identifies cardiovascular risk signatures with added value to urine analysis.

BACKGROUND: Subclinical atherosclerosis may result in fatal cardiovascular (CV) events, but the underlying mechanisms and molecular players leading to disease are not entirely understood. Thus, novel approaches capable of identifying the factors involved in pathological progression and providing a better understanding of the subjacent mechanisms are needed. Extracellular vesicles (EVs) have been shown to have numerous biological functions, and their metabolome has recently generated interest as a source of novel biomarkers. The metabolic content of the exosomes has been so far unexplored in cardiovascular disease (CVD), and here, we developed an analytical strategy aimed at probing urinary exosomal metabolite content and its association to CV risk. RESULTS: Direct analysis of the exosomes without metabolite extraction was evaluated by high-resolution magic angle spinning (1H HR-MAS). Other two methodologies for the analysis of exosomal metabolites by 1H NMR were set up, based on methanol or organic solvents sequential extraction. The three methods were compared in terms of the number of detected signals and signal to noise ratio (S/N). The methanol method was applied to identify altered metabolites in the urinary exosomes of subjects with programmed coronary artery by-pass grafting (CABG) versus a control group. Target mass spectrometry (MS) was also performed for differential analysis. The clinical performance of exosomal metabolites of interest in CVD was investigated, and the added value of the exosomes compared to urine analysis was evaluated. Based on S/N ratio, simplicity, reproducibility, and quality of the spectrum, the methanol method was chosen for the study in CVD. A cardiometabolic signature composed by 4-aminohippuric acid, N-1-methylnicotinamide, and citric acid was identified in urinary exosomes. Directly in urine, 4-aminohippuric acid and citric acid do not show variation between groups and changes in N-1-methylnicotinamide are less pronounced, proving the added value of exosomes. CONCLUSIONS: We set up a novel methodology to analyze metabolic alterations in urinary exosomes and identified a cardiometabolic signature in these microvesicles. This study constitutes the first evidence of a role for the exosomal metabolism in CVD and demonstrates the possibility to evaluate the urinary exosomal metabolic content by NMR and MS.

Point-of-Care Influenza Testing in the Pediatric Emergency Department.

OBJECTIVES: To see what the impact of introducing a rapid polymerase chain reaction-based influenza test has on length of stay (LOS) in emergency department, use of imaging, serum or urine testing, antibiotic use, and antiviral use. METHODS: Audit of electronic medical health records was performed for all emergency department visits from 2014 to 2018 between November and March, which was defined as peak flu season. Patients were included if they were between 3 months and 18 years of age, presented during peak flu season, and were tested for influenza. The pre-point of care (POC) period was defined as November through March of 2014 to 2017 which was compared with the post-POC group which was defined as November through March of 2017 to 2018. RESULTS: Patients tested for influenza in the pre-POC period were more likely to have complete blood count testing (44.7% vs 25.6% P < 0.01), more likely to have blood cultures performed (30% vs 16.3%, P < 0.01), more likely to have urine testing performed (21.5% vs 12.2%, P < 0.01), and more likely to have a chest radiograph completed (47.5% vs 34.4%, P < 0.01). There was no significant difference in rates of antibiotics used. There was increased rates of oseltamivir used in the post-POC period (21.2% vs 13.3%, P < 0.05. The median LOS decreased from 239 minutes in the pre-POC period to 232 minutes in the post-POC period (P < 0.05). CONCLUSIONS: With the introduction of a polymerase chain reaction-based point-of-care influenza test, there were overall decreased rates of invasive blood work, urine studies, and imaging, and median LOS. There was also increased antiviral administration.

The Association Between 24-Hour Urine and Stone Recurrence Among High Risk Kidney Stone Formers: A Population Level Assessment.

OBJECTIVE: To determine if obtaining a 24-hour urine collection (24HU) in stone formers is associated with decreased recurrent stone episodes. METHODS: Using the MarketScan database, adults 17-62 years old with nephrolithiasis were identified between 2007 and 2017 with a minimum of 3-year follow up. High-risk stone formers, those undergoing stone surgery, and those with history of recurrent stones were identified. The exposure was a 24HU within 6 months of primary diagnosis. The outcome was recurrent stone episodes-defined by stone-related emergency room visits, hospitalizations, or stone surgery 90 days to 3 years after diagnosis. Logistic regression was used to estimate recurrence risk by 24HU exposure for the overall cohort and sub-cohorts limited to known recurrent stone formers, high-risk subjects, and those having stone surgery. RESULTS: Of 434,055 subjects analyzed, 30,153 (6.9%) had a 24HU. An annual decline in 24HU utilization was seen (7.5%-5.8%). Regional variation in usage rate was also observed. On multivariate analysis, completing a 24HU was not associated with risk of recurrence in any of the following cohorts: recurrent stone formers (OR 0.98, 95% CI 0.9-1.07), both high risk and recurrent stone formers (OR 0.95 [0.8-1.13]), those undergoing surgery (OR 1.02 [0.97-1.07]); a positive association with 24HU and recurrence was seen in those labeled high-risk (OR 1.08 [1.01-1.16]) and in all-comers (OR 1.15 [1.12-1.19]). CONCLUSION: The 24HU was not associated with decreased recurrence rates in the overall population nor in higher risk sub-cohorts.

[Contamination of urine collected for cytobacteriological examination: situation in a university hospital in Morocco]. / Contamination des urines prélevées pour examen cytobactériologique : situation dans un centre hospitalier universitaire au Maroc.

The pre-analytical step of the cytobacteriological examination of urine (CBEU) is one of the most critical in microbiology. The objectives of our study were to determine the rate of urinary contamination and to analyze the factors that would facilitate this in order to propose solutions to this problem. METHOD: This is a 26-month descriptive study including all CBEU requests to our laboratory. Urine was treated in accordance with the recommendations of the medical microbiology recommendations. Urine was considered contaminated in the case of polymorphic culture with at least three different types of germs with a count from 103 CFU/mL. RESULTS: We collected 16,412 CBEU requests. Urine was contaminated in 4,830 cases (29.43%). Of the contaminated urine, 39.23% (n=1,895) was from emergency departments, 79.44% (n=3,837) was collected in the middle of the stream, 69.83% (n=3,373) was from a female patient and 16.34% (n=789) was from children under the age of 5. DISCUSSION AND CONCLUSION: To reduce urine contamination, quality instructions describing sampling procedures should be available and samples in the middle of the stream and through the collection adhesive bags should be replaced by sus-pubic puncture samples in children, whenever the profit/risk ratio of this method is favourable.

Prevalence, impact, and management strategies for asymptomatic bacteriuria in the acute care elderly patient: a review of the current literature.

Introduction: It is unclear how to prevent the negative impact of inappropriate urine cultures in older acute care patients who have a high rate of asymptomatic bacteriuria.Areas covered: A nonsystematic literature review of the definition, impact, and management of elderly acute care patients with asymptomatic bacteriuria (ASB).Expert opinion: In the elderly, patients with ASB include those with extra-urinary tract diseases (e.g. pneumonia) and those with symptoms/signs that resolve without antibiotic therapy, but the diagnosis of ASB is unclear in febrile patients responding to antibiotics. We consider four management strategies that could decrease the negative impact of culturing the urine including unnecessary antibiotic therapy in those with ASB: (1) Prevent urine testing in patients with extra-urinary tract reasons for their acute care (2) Cancel urine cultures if the urine dipstick is negative. (3) Avoid catheterization in stable patients who cannot provide a urine specimen on demand and (4) Withhold antibiotics in stable non-febrile elderly patients who do not have new local urinary tract symptoms or decompensation on follow-up, and pursue further investigations for another etiology/diagnosis.

Sustained decrease in urine culture utilization after implementing a reflex urine culture intervention: A multicenter quasi-experimental study.

Accurately diagnosing urinary tract infections (UTIs) in hospitalized patients remains challenging, requiring correlation of frequently nonspecific symptoms and laboratory findings. Urine cultures (UCs) are often ordered indiscriminately, especially in patients with urinary catheters, despite the Infectious Diseases Society of America guidelines recommending against routine screening for asymptomatic bacteriuria (ASB).1,2 Positive UCs can be difficult for providers to ignore, leading to unnecessary antibiotic treatment of ASB.2,3 Using diagnostic stewardship to limit UCs to situations with a positive urinalysis (UA) can reduce inappropriate UCs since the absence of pyuria suggests the absence of infection.4-6 We assessed the impact of the implementation of a UA with reflex to UC algorithm ("reflex intervention") on UC ordering practices, diagnostic efficiency, and UTIs using a quasi-experimental design.

Can a semi-quantitative method replace the current quantitative method for the annual screening of microalbuminuria in patients with diabetes? Diagnostic accuracy and cost-saving analysis considering the potential health burden.

OBJECTIVES: Diabetes is a global epidemic, and the high cost of annually and quantitatively measuring urine albumin excretion using the turbidimetric immunoassay is challenging. We aimed to determine whether a semi-quantitative urinary albumin-creatinine ratio test could be used as a screening tool for microalbuminuria in diabetic patients. METHODS: We assessed the diagnostic accuracy of the semi-quantitative method. The costs of false results in the semi-quantitative method were calculated based on the annual probability of disease progression analyzed through a systematic literature review and meta-analysis. The pooled long-term cost-saving effect of the semi-quantitative method compared with the quantitative test was assessed using a Markov model simulating a long-term clinical setting. Diagnostic accuracy and the cost-saving effect were also validated in an independent external cohort. RESULTS: Compared with the quantitative test, the semi-quantitative method had sensitivities of 93.5% and 81.3% and specificities of 61.4% and 63.1% in the overall sample of diabetic patients (n = 1,881) and in diabetic patients with eGFR ≥60 ml/min/1.73 m2 and a negative dipstick test (n = 1,110), respectively. After adjusting for direct and indirect medical costs, including the risk of disease progression, which was adjusted by the meta-analyzed hazard ratio for clinical outcomes, it was determined that using the semi-quantitative method could save 439.4 USD per person for 10 years. Even after adjusting the result to the external validation cohort, 339.6 USD could be saved for one diabetic patient for 10 years. CONCLUSIONS: The semi-quantitative method could be an appropriate screening tool for albuminuria in diabetic patients. Moreover, it can minimize the testing time and inconvenience and significantly reduce national health costs.

Evaluation of statistical techniques to normalize mass spectrometry-based urinary metabolomics data.

Human urine recently became a popular medium for metabolomics biomarker discovery because its collection is non-invasive. Sometimes renal dilution of urine can be problematic in this type of urinary biomarker analysis. Currently, various normalization techniques such as creatinine ratio, osmolality, specific gravity, dry mass, urine volume, and area under the curve are used to account for the renal dilution. However, these normalization techniques have their own drawbacks. In this project, mass spectrometry-based urinary metabolomic data obtained from prostate cancer (n = 56), bladder cancer (n = 57) and control (n = 69) groups were analyzed using statistical normalization techniques. The normalization techniques investigated in this study are Creatinine Ratio, Log Value, Linear Baseline, Cyclic Loess, Quantile, Probabilistic Quotient, Auto Scaling, Pareto Scaling, and Variance Stabilizing Normalization. The appropriate summary statistics for comparison of normalization techniques were created using variances, coefficients of variation, and boxplots. For each normalization technique, a principal component analysis was performed to identify clusters based on cancer type. In addition, hypothesis tests were conducted to determine if the normalized biomarkers could be used to differentiate between the cancer types. The results indicate that the determination of statistical significance can be dependent upon which normalization method is utilized. Therefore, careful consideration should go into choosing an appropriate normalization technique as no method had universally superior performance.