Urinary Biomarkers Research Articles

Identifying causal relationships between 35 blood and urine biomarkers and urologic cancers: MR-meta combined with Bayesian colocalization Mendelian randomization analysis

BackgroundBlood and urine biomarkers have been associated with urologic tumors, but their causal relationship with urologic tumors is unclear.MethodsWe performed a bidirectional Mendelian randomization (MR) analysis of the association between 35 blood and urine biomarkers and urological tumors in our discovery cohort. A Bayesian weighting approach was used to validate the positive results identified in the discovery cohort, and steiger filtering analysis was used to distinguish causality from reverse causality. Bayesian colocalization analysis was used to analyze which single nucleotide polymorphisms (SNPs) specifically co-located between the positive blood and urine biomarkers and the disease phenotypes were driven, and MR-positive results from the discovery cohort and the validation cohort were combined using the MR-meta method.ResultsSeveral blood and urine biomarkers were found to be significantly and causally associated with urologic cancers. Notably, calcium (OR: 1.34, 95%CI 1.10–1.63, P = 0.0040) and sex hormone-binding globulin (SHBG) (OR: 0.81, 95%CI 0.70–0.95, P = 0.0092) were associated with bladder cancer; gamma glutamyl transferase (GGT) (OR: 0.91, 95%CI 0.83–0.99, P = 0.0209), lipoprotein A (Lp(a)) (OR: 1.12, 95%CI 1.01–1.24, P = 0.0399), and insulinlike growth factor 1 (IGF 1) (OR: 1.10, 95%CI 1.01–1.20, P = 0.0220) were linked to prostate cancer (PCa); non albumin protein (OR: 0.78, 95%CI 0.65–0.93, P = 0.0065) and total protein (OR: 0.80, 95%CI 0.64–0.99, P = 0.0380) were linked to renal cancer; and apolipoprotein A (Apo-A) (OR: 0.56, 95%CI 0.32–0.98, P = 0.0426) and urate (OR:1.89, 95%CI 1.03–3.47, P = 0.0399) were associated with renal pelvis cancer. These associations were validated in an independent cohort, with GGT, IGF 1, and Lp(a) being consistently linked to PCa.ConclusionThis study identified significant biomarkers associated with urological cancers in blood and urine. These include GGT, IGF 1, and Lp(a), which are strong biomarkers for PCa. In addition, the findings of this study provide evidence for a handful of risk and protective factors for the development of urologic cancers.

Discovery of inflammatory response-related proteins as candidate urinary biomarkers of allergic rhinitis

ObjectivesAllergic rhinitis (AR) is a pervasive condition, affecting a significant global population, often with lifelong implications. The objective of this study is to screen for inflammatory-related differential proteins in the urine of AR patients, aiming to analyze the correlation between these identified proteins and the severity of allergic rhinitis. Design and methodsTo diagnose AR, we utilized the sIgE test to measure the allergenic responses. Based on the total IgE levels, patients were segregated into two categories: AR1 (IgE>125IU/mL) and AR2 (IgE≤125IU/mL). The differential proteins related to inflammation in the urine of patients were screened using TMT labeling combined with LC–MS/MS. Subsequently, these proteins were validated through PRM-based proteomics quantification. ResultsWe found significant increases in FCGR3A, A1AT, KRT18, and IL18 in the AR group (P<0.001). PRM-based quantification results highlighted considerable differences in the concentrations of these four proteins across varying degrees of allergic rhinitis severity. A biomarker panel comprising FCGR3A, A1AT, KRT18, and IL18 was identified, with an area under the curve (AUC) value of 0.993 for the detection of AR. ConclusionsThis study provides the first comprehensive report of combined TMT labeling LC–MS/MS quantitative proteomics and PRM analysis for discovering urinary biomarkers related to inflammatory responses in AR. These findings may be instrumental in evaluating the severity of allergic rhinitis and further our understanding of the molecular mechanisms underlying AR.

Identification of Potential Diagnostic Markers for Depressive Disorders using Urinary Biomarkers of N-Methylnicotinamide and Hippuric Acid

Introduction: The diagnostic methodology for depressive disorders, relying on symptom clusters, has inherent limitations in ensuring heterogeneity levels. Consequently, this presents a notable risk of inevitable diagnostic errors in mental health assessments. Therefore, advocating for objective diagnostic approaches through empirical testing in clinical settings becomes crucial for individuals dealing with depressive disorders. This study aims to identify the effectiveness of urine as a diagnostic support for depressive disorders using the N-Methylnicotinamide and Hippuric Acid biomarkers. Methods: This study used 13 urine samples from patients with depressive disorders and 13 normal urine samples. It used ELISA methods with observational analytic and cross-sectional designs. Results: The results showed that the N-methylnicotinamide biomarker had a relationship with depressive disorders with a correlation value of 0.867, while hippuric acid obtained a correlation value of 0.692. Besides, the N-Methylnicotinamide and Hippuric Acid biomarkers showed differences in the urine of depressive disorder and normal patients with significance values of 0.000 and 0.001 for the N-Methylnicotinamide and Hippuric Acid biomarkers, respectively. In addition, the Relative Operating Characteristics curve analysis showed that these two biomarkers had good sensitivity and specificity values in assisting the diagnosis of depressive disorders. N-methylnicotinamide has a sensitivity of 92.3% and a specificity of 100%, while hippuric acid has a sensitivity of 76.9% and a specificity of 84.6%. Conclusions: Significant differences in the biomarkers of N-methylnicotinamide and hippuric acid in the urine of depressed patients compared to normal patients. Therefore, these biomarkers can be the empirical laboratory methods to support the diagnosis of depressive.

In Search of Relevant Urinary Biomarkers for Thyroid Papillary Carcinoma and Benign Thyroid Nodule Differentiation, Targeting Metabolic Profiles and Pathways via UHPLC-QTOF-ESI+-MS Analysis

Background: Identification of specific urine metabolic profiles for patients diagnosed with papillary thyroid carcinoma (TC) vs. benign nodules (B) to identify specific biomarkers and altered pathways compared to those of healthy controls (C). Methods: Patient urine samples were collected, before surgery and after a histological confirmation of TC (n = 30) and B (n = 30), in parallel with sample collection from healthy controls (n = 20). The untargeted and semi-targeted metabolomic protocols were applied using UPLC-QTOF-ESI+-MS analysis, and the statistical analysis was performed using the Metaboanalyst 6.0 platform. The results for the blood biomarkers, previously published, were compared with the data obtained from urine sampling using the Venny algorithm and multivariate statistics. Results: Partial least squares discrimination, including VIP values, random forest graphs, and heatmaps (p &lt; 0.05), together with biomarker analysis (AUROC ranking) and pathway analysis, suggested a specific model for the urinary metabolic profile and pathway alterations in TC and B vs. C, based on 190 identified metabolites in urine that were compared with the serum metabolites. By semi-targeted metabolomics, 10 classes of metabolites, considered putative biomarkers, were found to be responsible for specific alterations in the metabolic pathways, from polar molecules to lipids. Specific biomarkers for discrimination were identified in each class of metabolites that were either upregulated or downregulated when compared to those of the controls. Conclusions: The lipidomic window was the most relevant for identifying biomarkers related to thyroid cancer and benign conditions, since this study detected a stronger involvement of lipids and selenium-related molecules for metabolic discrimination.

Dietary creatine and carcinogenic biomarkers in adult population.

Background: Several reports suggest potential cytotoxic effects of creatine, possibly due to its role in facilitating the formation of food-borne chemical carcinogenic compounds. Aim: This cross-sectional study aims to investigate the relationship between creatine consumption and various carcinogenic biomarkers in blood and urine among individuals aged 18 years and older, utilizing data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). Methods: Daily creatine intake was assessed using the Dietary Data databases, which were compiled from individual in-person 24-h food recall interviews. The concentrations of carcinogenic compounds (heterocyclic amines, acrylamide, and formaldehyde) were extracted from NHANES 2013-2014 Laboratory Data database. Results: The final analysis included 1763 adult respondents, of whom 907 (51.4%) were female. The mean daily creatine intake was 0.83 ± 0.77 grams (95% CI, from 0.80 to 0.87). Regression analysis revealed no significant relationship between daily creatine intake and most carcinogenic biomarkers, except for a significant correlation (Model 1) between creatine intake and acrylamide levels (B = -3.999, ß = -0.088, p = 0.05). Model 2 (demographics) confirmed a significant relationship between daily creatine intake and circulating acrylamide (B = -3.490, ß = -0.077, p = 0.02), as well as for blood levels of glycidamide (B = -2.992, ß = -0.068, p = 0.05) and urinary 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (B = 0.190, ß = 0.088, p = 0.03). However, no correlation between creatine consumption and any carcinogenic biomarkers remained significant after adjusting for nutritional factors (Model 3) (p > 0.05). Conclusion: In conclusion, the consumption of dietary creatine may be considered safe and not associated with increased levels of above carcinogens in the general population.

Modeling a biofluid-derived extracellular vesicle surface signature to differentiate pediatric idiopathic nephrotic syndrome clinical subgroups

Idiopathic Nephrotic Syndrome (INS) is a common childhood glomerular disease requiring intense immunosuppressive drug treatments. Prediction of treatment response and the occurrence of relapses remains challenging. Biofluid-derived extracellular vesicles (EVs) may serve as novel liquid biopsies for INS classification and monitoring. Our cohort was composed of 105 INS children at different clinical time points (onset, relapse, and persistent proteinuria, remission, respectively), and 19 healthy controls. The expression of 37 surface EV surface markers was evaluated by flow cytometry in serum (n = 83) and urine (n = 74) from INS children (mean age = 10.1, 58% males) at different time points. Urine EVs (n = 7) and serum EVs (n = 11) from age-matched healthy children (mean age = 7.8, 94% males) were also analyzed. Tetraspanin expression in urine EVs was enhanced during active disease phase in respect to the remission group and positively correlates with proteinuria levels. Unsupervised clustering analysis identified an INS signature of 8 markers related to immunity and angiogenesis/adhesion processes. The CD41b, CD29, and CD105 showed the best diagnostic scores separating the INS active phase from the healthy condition. Interestingly, combining urinary and serum EV markers from the same patient improved the precision of clinical staging separation. Three urinary biomarkers (CD19, CD44, and CD8) were able to classify INS based on steroid sensitivity. Biofluid EVs offer a non-invasive tool for INS clinical subclassification and “personalized” interventions.

Glutathione s-transferase pi is a marker of loop diuretic resistance in patients with congestive heart failure exacerbation

Abstract Background Loop diuretic resistance (LDR) in patients with heart failure (HF) exacerbation is associated with worse clinical outcomes, greater symptom burden and mortality. Diagnosis and treatment of LDR remains a significant clinical dilemma. Purpose To assess the ability of different urine biomarkers to predict LDR in patients with HF exacerbation. Methods Consecutive patients with congestive HF exacerbation were prospectively included in the study. HF was diagnosed according to ESC 2021 HF Guidelines definition. Congestion was defined as a presence of one or more of the following signs: edema, ascites, pleural effusion. LDR was defined as persistent congestion on the 4th day of hospital stay despite high i.v. loop diuretic dose. Urine biomarkers released from different parts of the nephron (Kidney Injury Molecule-1 - KIM-1, N-acetyl-β-D-glucosaminidase - NAG, uromodulin, glutathione S-transferase Pi - pi-GST, aquaporin-2), transthoracic echo, clinical and biochemical parameters were evaluated on the 1st and 4th day of hospital stay. Results are presented as mean ±standard deviation or median (interquartile range). Results 40 patients were included in the study with median age 84 (72,8; 86) years, median left ventricle ejection fraction (EF) 35.3 (26,5; 49) %, median NT-proBNP 8967.5 (3024; 15241) pg/ml. LDR was found in 14 (35%) patients. Univariate analysis identified the following risk factors for LDR: urine pi-GST concentration on admission and on the 4th day, right ventricle to pulmonary circulation coupling index (TAPSE/PASP ratio), presence of mitral regurgitation, serum creatine concentration, serum urea concentration, serum LDL concentration. Logistic regression analysis identified pi-GST concentration as a significant independent risk factor for LDR in this population: odds ratio (OR) 5.75 [95% confidence interval (CI) 1.271–25.990]. Conclusions Urine pi-GST on admission and after 4 days of treatment might be a marker for a development of LDR in patients with congestive HF exacerbation.

Urinary proteomic signature of mineralocorticoid receptor antagonism by spironolactone: evidence from the HOMAGE trial

Abstract Background Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) detects many sequenced peptides, for &amp;gt;70% derived from collagens. Purpose UPP and serum fibrosis markers were analysed together in patients at risk of HF with as objective to generate insights into the antifibrotic action of spironolactone. Methods In the open-label HOMAGE trial, patients were randomised to usual therapy combined or not with spironolactone 25-50 mg/d and followed for 9 months (n=290; 23.8% women; median age: 73 years). UPP was done by capillary electrophoresis coupled with mass spectrometry; 1498 urinary peptides with detectable signal in ≥30% of patients were analysed. Serum markers of COL1A1 synthesis (PICP and PICP/CITP) were measured. After rank normalisation of the biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted models. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher Z transform. Results Among all the urinary peptides, only the changes in collagen fragments remained significantly different (p&amp;lt;0.05) between randomisation groups after accounting for baseline levels, covariables and multiple testing. Compared to the control group, spironolactone reduced 16 of 27 collagen-derived urinary peptides. From baseline to 9 months, serum PICP and the PICP/CITP ratio decreased from 79.0 to 75.4 µg/L and from 21.3 to 18.3, respectively (p≤0.0129), reflecting decreased COL1A1 synthesis. Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and the serum fibrosis markers. Conclusions Spironolactone downregulated urinary collagen-derived peptides, probably by shrinking the body-wide pool of collagens. Spironolactone did not affect the interaction between urinary and serum fibrosis markers, suggesting that collagen scaffolding is maintained, thereby explaining why some urinary collagen fragments increased. Combining urinary and serum fibrosis biomarkers opens new avenues for discovery of antifibrotic drugs and refines insight in the action of antifibrotic drugs.Figure 1Figure 2

A phase 2, randomized, double-blind, placebo-controlled study to assess the tolerability and pharmacodynamic effects of CRD-740, a PDE9 inhibitor, in participants with chronic heart failure

Abstract Background Natriuretic peptide (NP) receptor activation has a beneficial role in the treatment of heart failure (HF). The enzyme phosphodiesterase (PDE) 9 breaks down cGMP, the second messenger stimulated by natriuretic peptides. PDE9 inhibition may increase intracellular cGMP signaling and, potentially, have beneficial effects in HF. We examined the effects of the selective PDE9 inhibitor CRD-740 on the NP signaling pathway in HF. Purpose The objectives of this early phase 2 trial were to assess the tolerability of CRD-740 and its effects on plasma and urinary cGMP (markers of potential clinical effiacy) in patients with HFrEF, including those receving background treatment with sacubitril/valsartan. Methods Key inclusion criteria were patients with a history of HFrEF of &amp;gt; 6 mos, NYHA II or III, EF &amp;lt; 40% and NT-proBNP ≥600 pg/ml at screening (≥1000 pg/mL if in atrial fibrillation), on treatment with stable guideline-directed therapy for a minimum of 4 weeks. Patients were randomized 2:1 double-blind to CRD-740 (10mg twice daily for 2 weeks, then 25mg twice daily for 10 weeks) or placebo. Tolerability and safety were assessed. The primary pharmacodynamic endpoint was the between-group change from baseline in plasma cGMP at Week 4. Exploratory endpoints included urine cGMP levels, KCCQ and biomarkers. Results 60 patients were randomized to CRD-740 (n=40) or placebo (n=20). Baseline characteristics included age 67+13 yrs, 85% men, EF 28+7%, BMI 30+10, with 73% of patients taking sacubitril/valsartan, and 47% on SGLT2 inhibitors. The primary endpoint was positive, with placebo-corrected change in plasma cGMP significantly increased at all time points at week 4 in those treated with CRD-740 (see Table). cGMP levels were also increased on day 1 (Table) and week 2. A significant increase in urinary cGMP also was observed with CRD-740 vs placebo (Figure) in 6-hour collections at day 1 (p=0.012) and week 2 (p=0.014). In this small study, not powered for exploratory endpoints, directionally favorable placebo-corrected, baseline-adjusted changes also were seen in the KCCQ Clinical (+7.1 [95%CI, -1.6, +15.7], p=0.11) and Overall Summary Scores (+7.4 [-0.8, +15.5], p=0.075) for patients on CRD-740. No significant changes in NT-proBNP were observed between treatment groups. Adverse events (AEs) were observed in 62% and 50% of CRD-740 and placebo-treated patients, with discontinuation in 5% and 10% respectively, with no between-group difference in change in BP. There were no hypotension AEs, and no treatment-related serious adverse events. Conclusions In this early phase 2 trial, PDE9 inhibition with CRD-740 was well-tolerated and resulted in substantial elevations of plasma and urinary cGMP on top of standard care, including sacubitril/valsartan. These results support the potential of PDE9 inhibition to further activate the beneficial effects of the NP receptor-cGMP pathway incrementally to that achieved by existing HF treatments.Changes in Plasma cGMP over Time (ng/mL)Changes in Urinary cGMP over Time

Urinary artificial sweeteners and breast cancer risk in women from the Moli-sani Study

Abstract Background Artificial sweeteners (AS) are chemical substances developed by the food industry to reduce sugar and calories while maintaining sweetness. Cohort studies suggested an increased risk of certain cancers, including breast cancer (BC), associated with AS intake, however evidence exclusively relied on self-reported dietary data rather than objectively measured AS. We examined the association of urinary biomarkers denoting AS intake with BC risk in women from the large Moli-sani Study. Methods Using a case-cohort design, a sample of 987 middle-aged women (mean age 55±12 y) was randomly selected as sub-cohort and compared with 273 women with incident BC (26 of them also belong to the sub-cohort). A total of 6 commonly used AS (i.e. aspartame, acesulfame, saccharine, sucralose, cyclamate, and steviol glycosides) were measured through liquid chromatography-mass spectrometry in urinary samples (creatinine-adjusted concentrations; µg/mg) collected at baseline (2005-2010). The multivariable hazard ratios (HRs) were estimated through Cox regression models using the Prentice method, where each AS was dichotomized as absence/presence, independent of concentrations. Results The main urinary AS was saccharine (E954), contributing to 71% of total AS, followed by steviol glycosides (E960;11%). During a median follow-up of 13.2 y we identified 38 premenopausal and 235 postmenopausal incident BC cases. In multivariable-adjusted Cox analyses, none of the individual AS was associated with overall BC risk, nor was the total urinary AS (HR = 0.93; 95%CI 0.63-1.37 for 1-unit increment). Compared to absence, presence of sucralose (E955) in urine was linked to premenopausal BC (HR = 4.23: 95%CI 1.23-14.51; p = 0.022). Conclusions Urinary artificial sweeteners were not associated with BC risk. However, sucralose presence in urine was linked to a higher risk of premenopausal BC. Prospective, dose-related studies with larger sample size are warranted to possibly confirm our findings. Key messages • The presence in the urine of commonly used artificial sweeteners was not associated with breast cancer risk. • Presence of urinary sucralose was linked to higher risk of premenopausal breast cancer.

Serum uromodulin associates with kidney function and outcome in a cohort of hospitalised COVID-19 patients

This study investigates the prevalence and evaluates the prognostic implications of acute kidney injury (AKI) in COVID-19 patients, with a novel emphasis on the evaluation of serum uromodulin (sUmod) as a potential kidney-specific biomarker. A cohort of hospitalised COVID-19 patients (n = 378) was examined for AKI using standard criteria. In addition to traditional urinary biomarkers, sUmod levels were analysed. Univariable and multivariable regression models were employed to evaluate the association of sUmod and AKI and in-hospital mortality. Levels of sUmod were significantly lower in patients with CKD (91.8 ± 60.7 ng/ml) compared to patients with normal kidney function (204.7 ± 91.7 ng/ml; p < 0.001). 151 patients (40.0%) presented with AKI at the time of hospital admission or developed an AKI during hospitalization. 116 patients (76.8%) had an AKI already at the time of hospital admission. COVID-19 patients with AKI had significantly lower levels of sUmod compared to patients without AKI during hospitalisation (124.8 ± 79.5 ng/ml) vs 214.6 ± 92.3 ng/ml; p < 0.001). The in-hospital mortality rate in this cohort of COVID-19 patients was 15.3%. Patients with AKI had a higher probability for in-hospital death (OR 5.6, CI 1.76 to 17.881, p = 0.004). Patients who died during hospital stay, had significantly lower sUmod levels (129.14 ± 89.56 ng/ml) compared to patients surviving hospitalisation (187.71 ± 96,64 ng/ml; p < 0.001). AKI is frequently associated with COVID-19 in hospitalized patients. Serum uromodulin may emerge as a promising biomarker for AKI in COVID-19 patients. Further research is warranted to explore its clinical application and refine risk stratification in this patient population.

Fluid Overload in Children Following Hematopoietic Cell Transplant: A Comprehensive Review

Fluid overload significantly increases morbidity and mortality in critically ill children. Following hematopoietic cell transplant (HCT), children are at a high risk of fluid accumulation due to essential increased fluid intake for nutrition, blood products, and antimicrobials. In addition, many complications predispose these children to capillary leak and fluid overload (FO), such as sinusoidal obstruction syndrome, engraftment syndrome, sepsis, and acute kidney injury (AKI). FO &gt; 10% occurs in nearly half of children following HCT and is associated with a lower PICU survival rate. In addition, in children with acute respiratory failure post HCT, each 1% increase in cumulative fluid balance on d 3 increases the odds of PICU mortality by 3%. Furthermore, FO worsens AKI. Tools such as the renal angina index and urinary biomarkers such as neutrophil gelatinase-associated lipocalin can help identify patients at risk of AKI and FO. Early detection, prevention, and intervention are crucial to improving outcomes in this population. Management strategies include fluid restriction, diuretics, and continuous kidney replacement therapy (CKRT) when FO exceeds 10% and other measures have failed.

Use of Biomarkers in Nutrition Intervention Studies of Children: A Scoping Review

Obesity in youth is an increasingly prevalent public health concern worldwide. Lifestyle interventions aim to help participants establish healthy habits and reduce obesity-related disease risk by targeting physical activity and dietary habits. Most studies assess weight loss, but biomarkers may enable more rapid and comprehensive assessment of intervention success. This scoping review aims to synthesize the published literature on which biomarkers are assessed during interventions for pediatric obesity to inform future use. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search of five databases conducted in February 2022 returned 1579 unique and relevant articles published between 2006 and 2021. After screening titles, abstracts, and full text, four reviewers determined that 43 studies met eligibility requirements. Quality screening was conducted, and 97.7% of papers were of fair or good quality. Of the 43 studies, 47% reported measures of adipose-related signaling molecules inclusive of adipokines, 74% included insulin-related biomarkers, 63% reported lipid-related biomarkers, 40% reported proinflammatory cytokine biomarkers, 12% reported measures of skin and/or plasma carotenoids, 40% measured blood pressure, and 21% included liver enzymes. Sixty-seven percent of studies measured biomarkers in whole blood, 40% measured biomarkers in plasma, 56% measured biomarkers in serum, and 2% measured biomarkers in urine. This work summarizes the current use of biomarkers in lifestyle intervention studies enrolling children. These biomarkers could be clinically relevant for pediatric weight management interventions.

Does Measuring Urinary Tubular Biomarkers Have Diagnostic Potential for Detecting Early Diabetic Nephropathy in Type-2 Diabetes Mellitus Patients?

Does Measuring Urinary Tubular Biomarkers Have Diagnostic Potential for Detecting Early Diabetic Nephropathy in Type-2 Diabetes Mellitus Patients?

Identification and determination of the urinary metabolite of iodotyrosine invivo

BackgroundCongenital hypothyroidism screening traditionally relies on detecting elevated thyroid-stimulating hormone levels, yet this approach may not detect a specific type of congenital hypothyroidism caused by iodotyrosine dehalogenase-1 (Dehal1) deficiency. The deficiency of this enzyme prevents the deiodination of mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) in the process of iodine recycling. This underscores the potential use of iodotyrosine or its metabolites as non-invasive urinary biomarkers for early diagnosis of congenital hypothyroidism. However, the urinary metabolites of MIT/DIT have not yet been discovered. Thus, this study aimed to identify the urinary metabolites of iodotyrosine in experimental models. MethodGas chromatography mass spectrometry was used to identify the urinary metabolites of iodotyrosine following intraperitoneal injection of MIT in rats. An isotope dilution mass spectrometric assay was developed for assessment of identified metabolites. Urine samples from Dehal1 knockout mice were used to confirm the results. ResultsWe identified novel iodotyrosine metabolites, 3-iodo-4-hydroxyphenylacetic acid (IHPA), and 3,5-diiodo-4-hydroxyphenylacetic acid (Di-IHPA) as the primary urinary metabolites of MIT and DIT respectively. The concentrations of urinary IHPA and Di-IHPA were significantly higher in Dehal1 knockout mice. ConclusionOur findings suggest that IHPA is detected in larger quantities and may hold more clinical significance than previously identified biomarkers like MIT and DIT, making it a promising candidate for diagnosing congenital hypothyroidism or other conditions associated with iodine recycling inhibition.

Fluorescent Determination of Uric Acid Based on Porphyrin and ZnCo2O4 Nanocomposite.

Advances in porphyrin chemistry have provided exciting technologies in the field of optical biosensing. Herein, we have synthesized 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) and porous Zn0.1Co2O4 nanorods using a simple one-pot hydrothermal method. The obtained TCPP- Zn0.1Co2O4 composite was then used for the development of a novel optical sensor for the determination of uric acid (UA), which is an important biomarker in human urine, serum or saliva for the clinical diagnosis of hyperuricemia and hypouricemia, etc. TCPP-Zn0.1Co2O4 composite was characterized using SEM, TEM, EDAX, PXRD, FT-IR, UV-Visible, and NMR spectroscopic techniques. The fluorescence emission spectral analysis of TCPP-Zn0.1Co2O4 was then investigated for potential applications in the detection of uric acid via the fluorescence quenching mechanism. The designed sensor showed a linear response towards the uric acid in the concentration range of 0.99 to 5.2 nM. The optical sensor exhibits a sensitive response to uric acid with a detection limit of 0.015 nM. The sensor was employed to quantify UA in spiked human urine samples and artificial urine with satisfactory results.

Absence of Kidney Tubular Injury in Patients With Acute Heart Failure With Acute Kidney Injury.

Worsening renal function (WRF) is common in hospitalized patients being treated for acute heart failure. However, discriminating clinically significant WRF remains challenging. In patients hospitalized with acute heart failure, we evaluated if blood and urine biomarkers of cardiac and kidney dysfunction were associated with adverse outcomes. We identified 175 of 927 participants in the AKINESIS study (Acute Kidney Neutrophil Gelatinase-Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) who met criteria for stage 1 or 2 Kidney Disease: Improvement Global Outcomes acute kidney injury during the first 3 days of hospitalization. We measured 24 blood and urine biomarkers from specimens collected within 24 hours of meeting acute kidney injury criteria. The primary composite outcome consisted of worsening WRF (higher acute kidney injury stage), need for dialysis, or death at 30 days. Biomarkers' association with the composite outcome was assessed with logistic regression by tertiles and area under the curve (AUC). Of the 175 participants, 32 (18%) developed the primary composite outcome. Only history of chronic kidney disease was significantly different between those with and without the composite outcome. The highest tertile of plasma Gal-3 (galectin-3) and urine epidermal growth factor were associated with increased odds of the composite outcome compared with the lowest tertile in unadjusted analyses. After adjusting for serum creatinine, systolic blood pressure, and blood urea nitrogen, only the highest tertile of Gal-3 was associated with greater odds of the composite outcome (odds ratio, 4.6 [95% CI, 1.4-16.0). Gal-3 had the highest AUC (0.70 [95% CI, 0.58-0.82]), while epidermal growth factor had a lower AUC (0.63 [95% CI, 0.53-0.74]). Notably, urine biomarkers of kidney tubule injury were not associated with the composite outcome. Tubular injury does not occur in most patients with acute heart failure experiencing WRF, consistent with the functional mechanisms of WRF in this patient population. URL: https://www.clinicaltrials.gov/study/NCT01291836?term=NCT01291836&rank=1; Unique identifier: NCT01291836.

FMT intervention decreases urine 5-HIAA levels: a randomized double-blind controlled study.

Autism spectrum disorder (ASD) is often linked to gastrointestinal issues and altered serotonin metabolism. Emerging evidence suggests gut microbiota influence both, with fecal microbiota transplantation (FMT) offering a potential therapeutic approach. However, its impact on serotonin metabolism and ASD symptoms is not well understood. In this study, we aimed to evaluate the clinical effects of FMT and examine changes in specific urinary metabolites in children with ASD. A randomized double-blind controlled trial was performed to evaluate the clinical effects of FMT on GI and ASD-related symptoms. Gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and the ASD-related symptoms were assessed using the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and Social Responsiveness Scale (SRS) scores. Urinary metabolites were analyzed by homogeneous enzyme immunoassay using commercially available kits. Significant improvements in GI and core ASD symptoms were observed following FMT intervention. The average GSRS scores decreased from 30.17 (before) to 19 (after; p < 0.0001), CARS scores decreased from 36.22 to 33.33 (p < 0.0001), SRS scores decreased from 151.17 to 137.5 (p = 0.0002), and the ABC scores decreased 76.39 to 53.17 (p < 0.0001) in the FMT group. However, in the placebo group, GSRS, CARS, and SRS scores showed no significant changes, while ABC scores decreased from 72 to 58.75 (p = 0.034). The FMT group also showed a significant reduction in urinary 5-hydroxyindoleacetic acid (5-HIAA) levels from 8.6 to 7.32 mg/L (p = 0.022), while other metabolites showed no significant changes. FMT is a safe and effective treatment for improving GI and core symptoms in children with ASD, with 5-HIAA showing potential as a urinary biomarker for treatment response.

Plasma and serum volume remain unchanged following a 12-h fast from food and drink despite changes in blood and urinary hydration markers.

The effect of mild dehydration on plasma and serum volume has not been well established. Furthermore, the ability of urinary and blood biomarkers to monitor small hydration changes have not been solidified. There were two objectives of this research: 1. Determine if mild dehydration affects plasma and serum volume; 2. Determine if mild dehydration can be detected better by urinary or blood biomarkers. 47 subjects were recruited; 10 subjects were removed from the study and 37 subjects (27% male) completed the study. This was a crossover study design such that each subject underwent all protocols in a counterbalanced order. Protocols consisted of 12-h dehydration, 12-h hydration, and control. Neither plasma volume (p = 0.914), plasma volume status (p = 0.649), nor serum volume (p = 0.273) were different among protocols. Body mass (p < 0.001) was lower following the dehydration protocol. Urine color (p < 0.001), urine osmolality (p < 0.001), urine specific gravity (p < 0.001), serum osmolality (p < 0.001), and plasma osmolality (p < 0.001) were all lower following the hydration protocol. Hematocrit (p = 0.842) and hemoglobin concentration (p = 0.558) were not different among protocols. Dehydration did not affect plasma or serum volume. Therefore, a 12-h fast from food and water as done in this study will not likely affect laboratory test results of biomarker concentration. All 3 urinary measures were able to detect changes in hydration status, whereas only 2 blood measures were able to detect changes in hydration status. This may indicate that urinary measures are best at detecting small changes in hydration status.

Repeated intravesical injections of platelet-rich plasma are safe and effective in the treatment of interstitial cystitis/bladder pain syndrome

ABSTRACT Objectives: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a challenging chronic inflammatory condition affecting the urinary bladder, with limited treatment options. This study aims to assess the clinical efficacy of repeated intravesical platelet-rich plasma (PRP) injections for promoting urothelial regeneration and reducing inflammation in patients with IC/BPS and investigate its correlation with subjective and objective treatment-related outcomes. Materials and Methods: Four monthly intravesical PRP injections were given to 98 patients with non-Hunner-type IC/BPS. Treatment outcomes were assessed using a global response assessment (GRA) score 3 months posttreatment. In addition, clinical symptom scores, pain severity, voiding diary data, uroflowmetry parameters, and GRA scores were compared before and after treatment and between different treatment outcome groups (satisfactory: GRA≥2 unsatisfactory: GRA&lt;2). Baseline urine biomarkers were analyzed to identify potential treatment outcome predictors. Results: After four PRP injections, 54 (55.1%) patients reported satisfactory outcomes. Lower urinary tract symptoms, bladder pain, urinary frequency, anxiety, and flow rate significantly improved from baseline (P &lt; 0.05) in all patients, regardless of the treatment outcome. All patients experienced improved treatment outcomes and increased maximum bladder capacity with successive PRP treatments, and no major complications were reported. Urine biomarkers indicated elevated inflammation and oxidative stress biomarkers in patients with IC/BPS compared to controls. Conclusion: Repeated PRP injections are safe and effective for reducing symptoms and bladder pain and improving bladder capacity in a majority of IC/BPS patients, with better outcomes observed in patients with a mild form of bladder inflammation. These results support PRP as a promising novel bladder therapy for IC/BPS.