What can urinary exosomes tell us?

Exosomes are involved in a wide variety of biochemical processes in human body homeostasis. Exosomes also provide important information regarding communications among several organ systems. Additionally, they can serve as molecular vehicles to deliver drugs. Therefore, exosomes have received wide attention in current biomedical research for unraveling pathogenic mechanisms of diseases, searching for novel biomarkers, and discovering new drugs. This paper reviews and discusses the significance of urinary exosomes for a better understanding of human disease pathophysiology and their potential use as therapeutic targets. Isolation methods of exosomes and the latest technological advances are also discussed. Furthermore, novel urinary exosomal biomarkers are highlighted with special emphasis on their clinical applicability (particularly sensitivity, specificity, reliability, and other aspects). Finally, future trends for this field are analyzed and our perspectives are provided.

New insights to the potential mechanisms driving coronary flow reserve impairment in Cushing's syndrome: A pilot noninvasive study by transthoracic Doppler echocardiography.

BACKGROUND: The contribution of functional and/or structural remodeling to reduced coronary flow velocity reserve (CFVR), reflecting impaired coronary microcirculation in Cushing's syndrome (CS), has not been clearly elucidated. We aimed to identify the potential mechanisms of coronary microvascular impairment in CS. METHODS: We studied 15 CS patients (11 female, age 50 ±â€¯9 years) without clinical evidence of cardiovascular disease. Coronary flow velocity in the left anterior descending coronary artery was measured by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. Average peak flow velocities, CFVR, and microvascular resistance in baseline (BMR) and hyperemic conditions (HMR) were assessed. CFVR ≤2.5 was considered a marker of microvascular disease (CMD). Diastolic function (E/e'), global longitudinal strain (GLS) and fractional pulse pressure (fPP), an index of arterial stiffness, were also assessed. RESULTS: CMD was present in 5 patients (33.3%). CMD was primarily driven by increased baseline peak flow velocity (29 ±â€¯12 versus 19.6 ±â€¯4.2 cm/s, p = .03) in the presence of decreased BMR (3.62 ±â€¯0.6 versus 5.46 ±â€¯1.4 mm Hg·s/cm, p = .03). Moreover, urinary cortisol and E/e' were higher (p = .001 and p = .001, respectively) and GLS was lower (p = .009) in patients with CMD. fPP was higher in patients with CMD (p = .01). Urinary cortisol correlated to CFVR (p = .008), E/e' (p < .0001) and GLS (p < .0001). fPP directly correlated to average peak flow velocities at rest (p = .01) and inversely to BMR (p = .03). CONCLUSIONS: Functional microvascular regulatory impairment seems to be the potential mechanism of CMD in CS. CMD seems to be related to decreased myocardial contractility and diastolic dysfunction associated with cortisol excess.

Urinary peptidomic biomarkers of renal function in heart transplant recipients.

BACKGROUND: Chronic kidney disease (CKD) is common in patients after heart transplantation (HTx). We assessed whether in HTx recipients the proteomic urinary classifier CKD273 or sequenced urinary peptides revealing the parental proteins correlated with the estimated glomerular filtration rate (eGFR). METHODS: In 368 HTx patients, we measured the urinary peptidome and analysed CKD273 and 48 urinary peptides with a detectable signal in >95% of participants. After 9.1 months (median), eGFR and the urinary biomarkers were reassessed. RESULTS: In multivariable Bonferroni-corrected analyses of the baseline data, a 1-SD increase in CKD273 was associated with a 11.4 [95% confidence interval (CI) 7.25-15.5] mL/min/1.73 m2 lower eGFR and an odds ratio of 2.63 (1.56-4.46) for having eGFR <60 mL/min/1.73 m2. While relating eGFR category at follow-up to baseline urinary biomarkers, CKD273 had higher (P = 0.007) area under the curve (0.75; 95% CI 0.70-0.80) than 24-h proteinuria (0.64; 95% CI 0.58-0.69), but additional adjustment for baseline eGFR removed significance of both biomarkers. In partial least squares analysis, the strongest correlates of the multivariable-adjusted baseline eGFR were fragments of collagen I (positive) and the mucin-1 subunit α (inverse). Associations between the changes in eGFR and the urinary markers were inverse for CKD273 and mucin-1 and positive for urinary collagen I. CONCLUSIONS: With the exception of baseline eGFR, CKD273 was more closer associated with imminent renal dysfunction than 24-h proteinuria. Fragments of collagen I and mucin-1-respectively, positively and inversely associated with eGFR and change in eGFR-are single-peptide markers associated with renal dysfunction.

Unambiguous Characterization of p-Cresyl Sulfate, a Protein-Bound Uremic Toxin, as Biomarker of Heart and Kidney Disease.

p-Cresyl sulfate is one of the bound uremic toxins whose level increases in the sera of patients with the severity of chronic kidney disease and is therefore used as a standard for clinical investigations. Our first attempts to obtain p-cresyl sulfate led exclusively to the product of sulfonation of the aromatic ring instead of sulfation on the OH moiety. Nevertheless, this initial discouraging result allowed us to handle both p-cresyl sulfate and 2-hydroxy-5-methylbenzenesulfonic acid obtained by different synthetic pathways. Interestingly, the comparison between the two isomers pointed out that the two molecules show the same fragmentation pattern and are indistinguishable by mass spectrometry. They cannot be separated on several commercially available columns. The only difference between the two compounds is a 10-fold higher ionization yield under negative ion electrospray ionization. NMR spectral studies definitely confirmed the different molecular structures. We present here an unambiguous biomimetic synthetic route for p-cresyl sulfate and the spectroscopic characterization of both the compounds by nuclear magnetic resonance and mass spectrometry.

Determination of urinary catecholamines and metanephrines in cardiac deaths.

The aim of this study was to measure catecholamines and their O-methylated metabolites in urine and vitreous humor collected in cardiac deaths and noncardiac control cases that underwent medicolegal investigations. Our first goal was to assess whether cardiac events of different types are characterized by different catecholamine/metanephrine urine and/or vitreous profiles. Our second goal was to determine whether noncardiac causes of death with different survival intervals are characterized by different catecholamine/metanephrine urine and/or vitreous profiles. Two study groups were prospectively and retrospectively formed, a cardiac death group (including three subgroups, according to the cause of death) and a noncardiac death group (including two subgroups, according to the length of the agonal period). Postmortem angiography, autopsy, histology, toxicology, and biochemistry were performed in all cases. First results seem to indicate that absolute values measured in urine and vitreous for each of the analyzed markers display no significant differences relating to each of the tested cardiac death subgroups. In the control group, absolute concentrations measured in urine and vitreous for each of the analyzed parameters failed to show significant differences relating to the length of agonal period. Our preliminary findings do not seem to confirm the conclusions of former studies and fail to corroborate the usefulness of urine catecholamine and metanephrine analysis to characterize stress response intensity or length of the dying process in the postmortem setting.

Reduction in cortisol inactivation is part of the adrenal stress response to cardiac and noncardiac pediatric surgery: a prospective study using gas chromatography-mass spectrometry analysis.

We examined the hypothesis that major cardiac surgery triggers a more intense adrenal stress response than less intensive noncardiac surgery, which then alters cortisol inactivation. Urinary excretion rates of glucocorticoid metabolites were determined before and after surgery using gas chromatography-mass spectrometry in 29 children undergoing scheduled major cardiac surgery and 17 control children undergoing conventional noncardiac surgery in a prospective observational study. Excretion rates of glucocorticoid metabolites were summed and corrected for creatinine excretion to calculate cortisol production rates (mg/mmol creatinine/m(2) body surface area). Precursor/product ratios from individual metabolites were calculated to characterize cortisol inactivation (11ß-hydroxysteroid dehydrogenase). Postoperatively, median cortisol production rates increased in both groups ( MCS: from 2.7 to 9.3; controls: from 2.7 to 5.8; p<0.001) with no significant difference between groups (p=0.12). Ratios of cortisol to cortisone metabolites, indicating the overall activity of 11ß-hydroxysteroid dehydrogenase, increased postoperatively in both groups (p<0.001). In conclusion, surgery resulted in a distinct postoperative increase in cortisol production. In contrast to our hypothesis, children undergoing major cardiac surgery did not show an increased adrenal stress response compared to children undergoing conventional surgery. Furthermore, the reduction in cortisol inactivation appears to be an essential part of the stress response to pediatric surgery in general.

[Postoperative complications after orthotopic heart transplantation].

We analysed postoperative complications in 106 patients after orthotopic heart transplantation based on the results of prospective observations during 2 year follow-up. Survival was estimated at 83% (88 patients). Deaths were caused by pyoseptic complications, pulmonary thromboembolism, acute pancreatitis, cardiac arrhythmia or transplant rejection due to non-compliance with the immunotherapeutic regime. The most frequent causes of deaths were pneumonia (28.3%), transplant rejection (11.3%), steroid-induced diabetes (14.6%). It is concluded that heart transplantation should be followed by thorough observation of the patients based at a specialized multi-field clinic to ensure continuous treatment and reduce lethality. Risk factors of unfavourable prognosis of heart transplantation are identified.

Prognostic utility of neutrophil gelatinase associated lipocalin in cardiac ICU: A prospective study.

Our study aims to evaluate the role of neutrophil gelatinase associated lipocalin (NGAL) as an early surrogate marker in predicting acute kidney injury (AKI) and mortality in cardiac ICU patients. The study was conducted at SRN Hospital, excluding those with known renal diseases. Out of 152 patients, 56 developed AKI (cases) and 96 were our controls. Higher NGAL was associated with increased mortality rates (P = 0.0201 and 0.0255 for serum and urinary NGAL respectively). Our study concluded that NGAL measurement at admission may be a boon in improving the outcome of cardiac ICU patients.

Urinary NGAL levels before and after coronary angiography: a complex story.

BACKGROUND: We describe urinary neutrophil gelatinase-associated lipocalin (uNGAL) values in association with clinical characteristics and urinary parameters in adults undergoing coronary angiography. METHODS: This is an observational study of consecutive patients who underwent elective coronary angiography during a 4-month period in a large urban tertiary care hospital. RESULTS: One hundred and thirteen patients were enrolled, and 100 had sufficient data to be included in the analyses. A large range of preprocedural uNGAL levels were observed (range 1-269 ng/mg Cr). Median preprocedural uNGAL was 8 ng/mg Cr. Age (P = 0.009), serum creatinine (P = 0.077) and albumin excretion (P = 0.009) were significant predictors of baseline uNGAL. Half the cohort demonstrated an increase and half a decrease in the absolute values of uNGAL after angiography, irrespective of preprocedural levels. CONCLUSIONS: We observed variable, but relatively low absolute levels of uNGAL prior to angiography in this 'cardiac' cohort. Only age, serum creatinine and albumin excretion could explain some of this variability. When designing studies of at-risk individuals where uNGAL may be used as a marker for acute kidney injury, this variability should be taken into account.

Characterization of NT-proBNP in human urine.

BACKGROUND: Urine amino-terminal probrain natriuretic peptide (NT-proBNP) concentrations may exclude the presence of heart failure and provide insight into renal clearance mechanisms for human NT-proBNP. We characterized the molecular forms of urine NT-proBNP detected by immunoassay. METHODS: Urine from patients with heart failure was subjected to HPLC and analyzed using immunoassays specific toward different epitopes of NT-proBNP. We assessed urine NT-proBNP immunoreactivity in healthy subjects and patients with heart failure. RESULTS: Size-exclusion chromatography of heart failure urine identified no NT-proBNP immunoreactivity coeluting with NT-proBNP(1-76); multiple immunoreactive NT-proBNP fragments were present. The absence of intact urinary NT-proBNP was supported by reversed-phase HPLC. Urine NT-proBNP immunoreactivity was higher in patients with acute [median 192 (interquartile range 108-1445) pg/mg creatinine] and chronic [52 (15-118) pg/mg creatinine] heart failure than in healthy subjects [4.2 (2.6-5.8) pg/mg creatinine] (P < 0.001). In 40 patients with heart failure, urine NT-proBNP immunoreactivity correlated with plasma NT-proBNP (r = 0.72, P < 0.001) and inversely with left ventricular ejection fraction (r = -0.33, P = 0.04). CONCLUSIONS: Our findings clarify previous reported relationships of urine NT-proBNP-like immunoreactivity with plasma NT-proBNP concentrations and the diagnosis of heart failure. As urine NT-proBNP immunoreactivity is not intact NT-proBNP(1-76), but rather reflects assorted metabolites, the diagnostic performance of NT-proBNP assays in urine may be assay specific, necessitating validation of biomarker performance on an assay-by-assay basis.

Comparison of Urine and Plasma Biomarker Concentrations Measured by Aptamer-Based versus Immunoassay Methods in Cardiac Surgery Patients.

BACKGROUND: Protein detection assays are invaluable tools in the field of biomarker discovery. However, only immunoassays are widely used and can measure 10-20 analytes per biosample. The novel SOMAmer-based assay uses nucleotide aptamer technology to measure over 1300 analytes per biosample. We compared the SOMAmer-based platform to traditional approaches to quantify analytes in a clinical setting with paired samples before and after cardiac surgery. METHODS: In a substudy of the Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury cohort, 54 individuals with acute kidney injury after cardiac surgery were identified. Preoperative and postoperative plasma and urine samples that had been previously evaluated for biomarker concentrations via immunoassays were analyzed via SOMAmer-based assay. RESULTS: Spearman correlations were estimated when >50% of biomarker values were within detectable ranges by immunoassay (plasma biomarkers: preoperative, 26/33; postoperative, 31/33; urine biomarkers: preoperative, 13/16; postoperative, 16/16). Overall, 27% of reportable plasma preoperative biomarkers displayed correlations ≥0.75 between immunoassay and SOMAmer measurements; 23% displayed correlations of 0.50-0.75, and 50% displayed correlations <0.50. In urine these values were 15%, 39%, and 46%, respectively. Forty-two percent of reportable plasma postoperative biomarkers displayed correlations ≥0.75, 16% displayed correlations 0.50-0.75, and 42% displayed correlations <0.50. In urine, these values were 19%, 25%, and 56%, respectively. CONCLUSIONS: In cardiac surgery patients, the SOMAmer-based assay detects proteins with moderate to strong correlation to current immunoassay methods. The correlations in urine are weaker than those in plasma. SOMAmer-based assay technology should be further evaluated in multiple settings as a high-throughput screening tool for biomarker discovery.

Diurnal variation of 6beta-hydroxycortisol in cardiac patients.

The 24-hour urinary excretion of 6-beta-hydroxycortisol (6beta-OHC) and the urinary ratio of 6beta- hydroxycortisol/cortisol (6beta-OHC/UFC) have been proposed as noninvasive probes for human cytochrome P450 3A4 isoform (CYP3A4). In this study, we evaluated within- and between-day variability of 6beta-OHC excretion and 6beta-OHC/UFC ratio in nine Caucasian men with cardiac disease. Each study participant was asked to collect 24-hour urine specimens during four consecutive days in five standardized time intervals. Concentrations of UFC and 6beta-OHC were determined by immunoassay and the high-performance liquid chromatographic (HPLC) method, respectively. The HPLC method was accurate and precise, as indicated by the recovery rate of 96.5-103.3 % and less than 5.2 % and 6.3 % of the coefficient of variation for within-run and between-run assay, respectively. In patients, diurnal variations in UFC and 6beta-OHC excretion were parallel. Consequently, 6beta-OHC/UFC ratio remained stable during the day. Both, 6beta-OHC excretion and 6beta-OHC/UFC ratio showed significant relationship between 24-hour value and values measured in corresponding collection periods with best correlations obtained from night interval (22.00-06.00, r = 0.86-0.91). These results indicated that urinary 6beta-OHC excretion and 6beta-OHC/UFC ratio measured in overnight/morning urine could precisely reflect 24-hour values even in severely ill patients. In addition, a simple and sensitive HPLC method was described for determination of 6beta-OHC in urine.

Postoperative Compensatory Ammonium Excretion Subsequent to Systemic Acidosis in Cardiac Patients.

BACKGROUND: Postoperative acid-base imbalances, usually acidosis, frequently occur after cardiac surgery. In most cases, the human body, not suffering from any severe preexisting illnesses regarding lung, liver, and kidney, is capable of transient compensation and final correction. The aim of this study was to correlate the appearance of postoperatively occurring acidosis with renal ammonium excretion. MATERIALS AND METHODS: Between 07/2014 and 10/2014, a total of 25 consecutive patients scheduled for elective isolated coronary artery bypass grafting with cardiopulmonary bypass were enrolled in this prospective observational study. During the operative procedure and the first two postoperative days, blood gas analyses were carried out and urine samples collected. Urine samples were analyzed for the absolute amount of ammonium. RESULTS: Of all patients, thirteen patients developed acidosis as an initial disturbance in the postoperative period: five of respiratory and eight of metabolic origin. Four patients with respiratory acidosis but none of those with metabolic acidosis subsequently developed a base excess > +2 mEq/L. CONCLUSION: Ammonium excretion correlated with the increase in base excess. The acidosis origin seems to have a large influence on renal compensation in terms of ammonium excretion and the possibility of an overcorrection.

[Cardio-Pulmonary-Renal interactions].

Over the past decade, understanding about feedback mechanisms involving the heart, lung and kidney is significantly improved. Each organ injury may trigger hemodynamic, neuro-hormonal and cellular pathway that may damage diverse organs. Recurrent acute on chronic injury may lead to the advanced stage of disease. On the other hand, chronic pathological conditions may decrease functional reserve leading to a high susceptibility to acute injury. Assessment of functional reserve and dosage of novel biomarkers may allow an early diagnosis and treatment. This review summarizes the current state-of-the-art understanding of cardio-pulmonary-renal interactions.

A little "dab" will do ya' in: a case report of neuro-and cardiotoxicity following use of cannabis concentrates.

CONTEXT: The use of marijuana and cannabis concentrates is increasing, especially following decriminalization in several states. Psychosis and cardiotoxicity have been reported following cannabis use; however, myocardial injury from "dabbing" has not yet been reported. We report a case of hyperthermia, tachycardia, hypertension, severe agitation, neuro-, and cardiotoxicity following the use of "dabs" where there is concomitant confirmatory biological and sample testing. CASE DETAILS: A 17-year-old athletic man developed agitation requiring sedation and intubation for safety, with peak systolic blood pressures in the 190s and hyperthermia (to 102 °F). He developed elevated serum troponins with persistent tachycardia despite sedation and no clear non-intoxicant etiology. It was discovered that the patient had recently been "dabbing"; an exhaustive search of his home found a sample of the "dabs" which was analyzed along with a comprehensive urine drug screen by tandem liquid mass spectroscopy (t-LCMS) for confirmation. DISCUSSION: Tetrahydrocannabinol (THC) has been increasingly associated with agitation and cardiotoxicity, while cannabidiol (CBD) has been associated with neuroprotective, inhibitory states. We propose that increasing concentrations of THC as well as THC:CBD ratios seen in cannabis concentrates such as "dabs" may cause agitation and end-organ damage through sympathomimetic and serotonergic pathways.

Isolated right ventricular thrombus in an adult patient with nephrotic syndrome: a case report.

BACKGROUND: Venous thrombosis in nephrotic syndrome is a well-described phenomenon. We report a case of an adult patient with an isolated thrombus in the right ventricle due to nephrotic syndrome, which was initially suspected to be a myxoma. CASE PRESENTATION: A 28-year-old white woman presented to our emergency department with signs of fluid overload. On further evaluation, a right ventricular mass was detected, which was resected and was found to be a thrombus. No other manifestations of venous thrombosis were found. Further evaluation of the patient revealed a nephrotic syndrome, which caused augmented coagulopathy. CONCLUSIONS: We present a case of a patient in whom a right ventricular mass was the first sign of a renally derived coagulopathy. To the best of our knowledge, this is the first report of an isolated thrombus in the right ventricle due to nephrotic syndrome in an adult. In cases of isolated cardiac thrombi in adults, a further search for renal disease might be helpful to reveal the underlying cause.

Phytoestrogen Concentrations in Human Urine as Biomarkers for Dietary Phytoestrogen Intake in Mexican Women.

There has been substantial interest in phytoestrogens, because of their potential effect in reducing cancer and heart disease risk. Measuring concentrations of phytoestrogens in urine is an alternative method for conducting epidemiological studies. Our objective was to evaluate the urinary excretion of phytoestrogens as biomarkers for dietary phytoestrogen intake in Mexican women. Participants were 100 healthy women from 25 to 80 years of age. A food frequency questionnaire (FFQ) and a 24 h recall were used to estimate habitual and recent intakes of isoflavones, lignans, flavonols, coumestrol, resveratrol, naringenin, and luteolin. Urinary concentrations were measured by liquid chromatography (HPLC) coupled to mass spectrometry (MS) using the electrospray ionization interface (ESI) and diode array detector (DAD) (HPLC-DAD-ESI-MS). Spearman correlation coefficients were used to evaluate associations between dietary intake and urine concentrations. The habitual consumption (FFQ) of total phytoestrogens was 37.56 mg/day. In urine, the higher compounds were naringenin (60.1 µg/L) and enterolactone (41.7 µg/L). Recent intakes (24 h recall) of isoflavones (r = 0.460, p < 0.001), lignans (r = 0.550, p < 0.0001), flavonoids (r = 0.240, p < 0.05), and total phytoestrogens (r = 0.410, p < 0.001) were correlated to their urinary levels. Total phytoestrogen intakes estimated by the FFQ showed higher correlations to urinary levels (r = 0.730, p < 0.0001). Urinary phytoestrogens may be useful as biomarkers of phytoestrogen intake, and as a tool for evaluating the relationship of intake and disease risk in Mexican women.

The Pocket-4-Life project, bioavailability and beneficial properties of the bioactive compounds of espresso coffee and cocoa-based confectionery containing coffee: study protocol for a randomized cross-over trial.

BACKGROUND: Coffee is an important source of bioactive compounds, including caffeine, phenolic compounds (mainly chlorogenic acids), trigonelline, and diterpenes. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic diseases, but the impact of coffee dosage on markers of cardiometabolic risk is not well understood. Moreover, the pool of coffee-derived circulating metabolites and the contribution of each metabolite to disease prevention still need to be evaluated in real-life settings. The aim of this study will be to define the bioavailability and beneficial properties of coffee bioactive compounds on the basis of different levels of consumption, by using an innovative experimental design. The contribution of cocoa-based products containing coffee to the pool of circulating metabolites and their putative bioactivity will also be investigated. METHODS: A three-arm, crossover, randomized trial will be conducted. Twenty-one volunteers will be randomly assigned to consume three treatments in a random order for 1 month: 1 cup of espresso coffee/day, 3 cups of espresso coffee/day, and 1 cup of espresso coffee plus 2 cocoa-based products containing coffee twice per day. The last day of each treatment, blood and urine samples will be collected at specific time points, up to 24 hours following the consumption of the first product. At the end of each treatment the same protocol will be repeated, switching the allocation group. Besides the bioavailability of the coffee/cocoa bioactive compounds, the effect of the coffee/cocoa consumption on several cardiometabolic risk factors (anthropometric measures, blood pressure, inflammatory markers, trimethylamine N-oxide, nitric oxide, blood lipids, fasting indices of glucose/insulin metabolism, DNA damage, eicosanoids, and nutri-metabolomics) will be investigated. DISCUSSION: Results will provide information on the bioavailability of the main groups of phytochemicals in coffee and on their modulation by the level of consumption. Findings will also show the circulating metabolites and their bioactivity when coffee consumption is substituted with the intake of cocoa-based products containing coffee. Finally, the effect of different levels of 1-month coffee consumption on cardiometabolic risk factors will be elucidated, likely providing additional insights on the role of coffee in the protection against chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03166540 . Registered on May 21, 2017.

Agreement between laboratory results and on-site pathology testing using Bayer DCA2000+ and Cholestech LDX point-of-care methods in remote Australian Aboriginal communities.

BACKGROUND: Indigenous Australians experience high risk of diabetes and cardiovascular disease. On-site pathology data can help identify those at risk. We sought to evaluate point-of-care (POC) analysers in remote Australian communities. METHODS: Results obtained from population screening (n=76-118) on the DCA2000+ and Cholestech LDX analysers were compared to laboratory measures. Results were compared using parametric and non-parametric statistical analyses, including the use of conventional cut-off values for pathology markers. RESULTS: Agreements (95% CI) between the two methods for categorising results according to the selected cut-off values ranged from 88% (77-94%) for HDL-C to 99% (92-100%) for glucose, and Kappa coefficients ranged from 0.668 for total cholesterol to 0.945 for glucose. Differences in median values were not clinically meaningful but were statistically significant (P<0.05) for urinary albumin (18.8 [inter-quartile range: 7.5-41.7] vs. 18.0 [5.5-43.2] mg/L), creatinine (12.1 [7.9-17.1] vs. 12.4 [8.1-17.0] mmol/L) and albumin:creatinine ratio (ACR; 1.66 [0.70-3.53] vs. 1.27 [0.46-3.03] mg/mmol), HDL cholesterol (HDL-C; 1.05 [0.95-1.25] vs. 1.00 [0.81-1.20] mmol/L), triglycerides (1.65 [1.12-2.19] vs. 1.49 [1.07-2.36] mmol/L) and glucose (5.2 [4.5-6.0] vs. 5.2 [4.7-5.8] mmol/L), respectively, for POC and laboratory methods. Median HbA1c (5.6% [5.3-6.0%] vs. 5.5% [5.3-6.1%]) and total cholesterol (4.4 [3.8-5.0] vs. 4.4 [3.8-5.1] mmol/L) did not differ significantly. Bland-Altman analyses showed statistically significant (but not clinically meaningful) variation in the measurement difference across analyte concentration for all measures except ACR and total cholesterol. CONCLUSION: POC instruments provided a reliable alternative to conventional laboratory methods for screening for chronic disease risk factors in locations remote from urban centres.

Urinary microRNAs as a new class of noninvasive biomarkers in oncology, nephrology, and cardiology.

MicroRNAs (miRNAs) are small noncoding RNAs that posttranscriptionally regulate gene expression. In the last decade, number of evidences showing miRNAs contribution to the regulation of apoptosis, cellular proliferation, differentiation, and other important cellular processes is constantly growing. Specific miRNA expression signatures have been identified in variety of human cancers as well as pathologies of cardiovascular and urinary systems. Our chapter focuses on the potential of urinary miRNAs to serve as biomarkers in uro-oncology, nephrology, and cardiology. We discuss in detail recent knowledge about the origin of urinary miRNAs, their stability, quality control, and their utility as a potential new class of biomarkers in medicine. Finally, we summarize the studies focusing on detection and characterization of urinary miRNAs as potential biomarkers in urologic cancers, nephrology, and cardiology.