Transient paper-based electrochemical biosensor Fabricated by superadditive Cu-TCPP(Fe)/Mxene for Multipathway non-invasive, highly sensitive detection of Bodily metabolites.

Current advances in non-invasive fluid diagnostics highlight unique benefits for monitoring metabolic diseases. However, the low concentrations and complex compositions of biomarkers in fluids such as sweat, urine, and saliva impose stringent demands on the sensitivity and stability of detection technologies. Here, we developed a high-sensitivity, low-cost instantaneous electrochemical sensor based on the superadditive effect mechanism of Cu-TCPP(Fe)/Mxene (MMs Paper-ECL Sensor), which has been successfully applied for the simultaneous real-time detection of glucose and uric acid. Strong interfacial interactions between Mxene and Cu-TCPP(Fe) were revealed through precise simulation calculations and multi-dimensional characterization analysis, significantly enhancing the sensor's electrocatalytic performance and reaction kinetics. Experimentally, this exceptional electrocatalytic activity was demonstrated in its unprecedented high sensitivity and wide linear detection range for glucose and uric acid, with a non-invasive linear range from 0.001 nM to 5 mM, 0.025 nM-5 mM, detection limits as low as 1.88 aM and 5.80 pM, and stability extending up to 100 days. This represents not only a breakthrough in sensitivity and stability but also provides an effective, low-cost solution that overcomes the limitations of existing electronic devices, enabling multi-channel simultaneous detection. The universality of this sensor holds vast potential for application in the field of non-invasive fluid diagnostics.

A Novel Electrochemical Sensor Based on Pd Confined Mesoporous Carbon Hollow Nanospheres for the Sensitive Detection of Ascorbic Acid, Dopamine, and Uric Acid.

In this study, we designed a novel electrochemical sensor by modifying a glass carbon electrode (GCE) with Pd confined mesoporous carbon hollow nanospheres (Pd/MCHS) for the simultaneous detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA). The structure and morphological characteristics of the Pd/MCHS nanocomposite and the Pd/MCHS/GCE sensor are comprehensively examined using SEM, TEM, XRD and EDX. The electrochemical properties of the prepared sensor are investigated through CV and DPV, which reveal three resolved oxidation peaks for AA, DA, and UA, thereby verifying the simultaneous detection of the three analytes. Benefiting from its tailorable properties, the Pd/MCHS nanocomposite provides a large surface area, rapid electron transfer ability, good catalytic activity, and high conductivity with good electrochemical behavior for the determination of AA, DA, and UA. Under optimized conditions, the Pd/MCHS/GCE sensor exhibited a linear response in the concentration ranges of 300-9000, 2-50, and 20-500 µM for AA, DA, and UA, respectively. The corresponding limit of detection (LOD) values were determined to be 51.03, 0.14, and 4.96 µM, respectively. Moreover, the Pd/MCHS/GCE sensor demonstrated outstanding selectivity, reproducibility, and stability. The recovery percentages of AA, DA, and UA in real samples, including a vitamin C tablet, DA injection, and human urine, range from 99.8-110.9%, 99.04-100.45%, and 98.80-100.49%, respectively. Overall, the proposed sensor can serve as a useful reference for the construction of a high-performance electrochemical sensing platform.

Urine multi-index intelligent detection based on polymer/paper hybrid microfluidic biochip for hyperuricemia monitoring.

Hyperuricemia (HUA) has gradually become a public health burden as an independent risk factor for a variety of chronic diseases. Herein, a user-friendly point-of-care (POC) detection system (namely "Smart-HUA-Monitor") based on smartphone-assisted paper-based microfluidic is proposed for colorimetric quantification of HUA urinary markers, including uric acid (UA), creatinine (CR) and pH. The detection limits of UA and CR were 0.0178 and 0.5983 mM, respectively, and the sensitivity of pH were 0.1. The method was successfully validated in artificial urine samples and 100 clinical samples. Bland-Altman plots showed a high consistency between µPAD and the testing instruments (HITACHI 7600 Automatic Analyzer, URIT-500B Urine Analyzer and AU5800B automatic biochemical analyzer) in hospital. Smart-HUA-Monitor provides an accurate quantitative, rapid, low-cost and reliable tool for the monitoring and early diagnosis of HUA urine indicators.

Urinary stone analysis and clinical characteristics of 496 patients in Taiwan.

Evaluate urinary stone components' epidemiological features in urolithiasis individuals and explore potential correlations between stone components and patients' clinical characteristics. A retrospective analysis of urinary stone compositions in 496 patients from a northern Taiwan medical center (February 2006 to October 2021) was conducted. We investigated associations between sex, age, body mass index (BMI), hypertension, diabetes mellitus (DM), hyperlipidemia (HLP), gout, coronary artery disease (CAD), cerebral vascular accident (CVA), chronic kidney disease (CKD), habits, urine pH, and three main stone groups: calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid (UA). Males accounted for 66.5% of cases, with a male-to-female ratio of 1.99:1. Males were negatively associated with CaP stones (OR 0.313, p < 0.001) and positively with UA stones (OR 2.456, p = 0.009). Age showed a negative correlation with CaOx stones (OR 0.987, p = 0.040) and a positive correlation with UA stones (OR 1.023, p < 0.001). DM had a protective effect against CaP stones (OR 0.316, p = 0.004). Gout had a positive association with UA stones (OR 2.085, p = 0.035). Smoking was adversely associated with UA stones (OR 0.350, p = 0.018). Higher urine pH was a risk factor for CaP stones (OR 1.641, p = 0.001) and a protective factor against UA stones (OR 0.296, p < 0.001). These results may provide insights into the pathogenesis of urinary stones and the development of preventative strategies for high-risk populations. Further research is required to confirm and expand upon these findings.

Association of urinary excretion rates of uric acid with biomarkers of kidney injury in patients with advanced chronic kidney disease.

BACKGROUND: The potential influence of hyperuricemia on the genesis and progression of chronic kidney disease (CKD) remains controversial. In general, the correlation between blood levels of uric acid (UA) and the rate of progression of CKD is considered to be modest, if any, and the results of relevant trials oriented to disclose the effect of urate-lowering therapies on this outcome have been disappointing. Urinary excretion rates of UA could reflect more accurately the potential consequences of urate-related kidney injury. METHOD: Using a cross-sectional design, we investigated the correlation between different estimators of the rates of urinary excretion of UA (total 24-hour excretion, mean urinary concentration, renal clearance and fractional excretion)(main study variables), on one side, and urinary levels of selected biomarkers of kidney injury and CKD progression (DKK3, KIM1, NGAL, interleukin 1b and MCP)(main outcome variables), in 120 patients with advanced CKD (mean glomerular filtration rate 21.5 mL/minute). We took into consideration essential demographic, clinical and analytic variables with a potential confounding effect on the explored correlations (control variables). Spearman's rho correlation and nonlinear generalized additive regression models (GAM) with p-splines smoothers were used for statistical analysis. MAIN RESULTS: Multivariate analysis disclosed independent correlations between urinary UA concentrations, clearances and fractional excretion rates (but not plasma UA or total 24-hour excretion rates of UA), on one side, and the scrutinized markers. These correlations were more consistent for DKK3 and NGAL than for the other biomarkers. Glomerular filtration rate, proteinuria and treatment with statins or RAA axis antagonists were other independent correlates of the main outcome variables. CONCLUSIONS: Our results support the hypothesis that urinary excretion rates of UA may represent a more accurate marker of UA-related kidney injury than plasma levels of this metabolite, in patients with advanced stages of CKD. Further, longitudinal studies will be necessary, to disclose the clinical significance of these findings.

Development of a paper-based transcription aptasensor for convenient urinary uric acid self-testing.

The abnormal uric acid (UA) level in urine can serve as warning signals of many diseases, such as gout and metabolic cardiovascular diseases. The current methods for detecting UA face limitations of instrument dependence and the requirement for non-invasiveness, making it challenging to fulfill the need for home-based application. In this study, we designed an aptasensor that combined UA-specific transcriptional regulation and a fluorescent RNA aptamer for convenient urinary UA testing. The concentration of UA can be translated into the intensity of fluorescent signals. The aptasensor showed higher sensitivity and more robust anti-interference performance. UA levels in the urine of different volunteers could be accurately tested using this method. In addition, a paper-based aptasensor for UA self-testing was manufactured, in which the urinary UA levels could be determined using a smartphone-based colorimetric approach. This work not only demonstrates a new approach for the design of disease-associated aptasensor, but also offers promising ideas for home-based detection of UA.

Association between caffeine metabolites in urine and muscle strength in young and older adults: A cross-sectional study from NHANES 2011-2012.

BACKGROUND: Elevated levels of reactive oxygen species may contribute to the gradual decline in muscle strength over time. Although caffeine and its metabolites have antioxidant properties that can mitigate oxidative stress, the association of caffeine and its metabolites with muscle strength remains unknown. AIM: To investigate whether caffeine metabolites in urine are associated with muscle strength in young and older adults. METHODS: A cross-sectional study was conducted with 1145 individuals aged over 20 years (n = 801 < 60 years and n = 344 ≥ 60 years) from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Muscle strength was assessed using a handgrip dynamometer, and combined grip strength was determined by summing the highest value from each hand. Caffeine and its metabolites in urine were quantified using ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (1-methyluric acid, 3-methyluric acid, 7-methyluric acid, 1,3-dimethyluric acid, 1,7-dimethyluric acid, 3,7-dimethyluric acid, 1,3,7-trimethyluric acid, 1-methylxanthine, 3-methylxanthine, 7-methylxanthine, 1,3-dimethylxanthine, 1,7-dimethylxanthine, 3,7-dimethylxanthine, 1,3,7-trimethylxanthine, 5-acetylamino-6-amino-3-methyluracil). Linear regression analyses were performed to determine the association of caffeine and its metabolites with muscle strength in young and older adults, adjusting for confounders. RESULTS: Positive associations between muscle strength and levels of 7-methyluric acid (ß = 0.029; p = 0.021), 1,3-dimethyluric acid (ß = 0.008; p = 0.004), 3,7-dimethyluric acid (ß = 0.645; p = 0.012), 3-methylxanthine (ß = 0.020; p = 0.002), 7-methylxanthine (ß = 0.020; p = 0.006), 1,3-dimethylxanthine (theophylline) (ß = 0.030; p = 0.004) and 3,7-dimethylxanthine (theobromine) (ß = 0.035; p = 0.029) were observed in older adults. In contrast, no such associations were noted in young adults. CONCLUSION: Our study indicates a positive association between certain caffeine metabolites in urine and muscle strength in older adults, but not in younger individuals. These findings indicate that specific caffeine metabolites may contribute to an antioxidant role especially in older adults.

The key role of major and trace elements in the formation of five common urinary stones.

BACKGROUND: Urolithiasis has emerged as a global affliction, recognized as one of the most excruciating medical issues. The elemental composition of stones provides crucial information, aiding in understanding the causes, mechanisms, and individual variations in stone formation. By understanding the interactions between elements in various types of stones and exploring the key role of elements in stone formation, insights are provided for the prevention and treatment of urinary stone disease. METHODS: This study collected urinary stone samples from 80 patients in Beijing. The chemical compositions of urinary stones were identified using an infrared spectrometer. The concentrations of major and trace elements in the urinary stones were determined using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS), respectively. The data were processed using correlation analysis and Principal Component Analysis (PCA) methods. RESULTS: Urinary stones are categorized into five types: the calcium oxalate (CO) stone, carbonate apatite (CA) stone, uric acid (UA) stone, mixed CO and CA stone, and mixed CO and UA stone. Ca is the predominant element, with an average content ranging from 2.64 to 27.68% across the five stone groups. Based on geochemical analysis, the high-content elements follow this order: Ca > Mg > Na > K > Zn > Sr. Correlation analysis and PCA suggested significant variations in the interactions between elements for different types of urinary stones. Trace elements with charges and ionic structures similar to Ca may substitute for Ca during the process of stone formation, such as Sr and Pb affecting the Ca in most stone types except mixed stone types. Moreover, the Mg, Zn and Ba can substitute for Ca in the mixed stone types, showing element behavior dependents on the stone types. CONCLUSION: This study primarily reveals distinct elemental features associated with five types of urinary stones. Additionally, the analysis of these elements indicates that substitutions of trace elements with charges and ion structures similar to Ca (such as Sr and Pb) impact most stone types. This suggests a dependence of stone composition on elemental behavior. The findings of this study will enhance our ability to address the challenges posed by urinary stones to global health and improve the precision of interventions for individuals with different stone compositions.

Machine learning-enhanced drug testing for simultaneous morphine and methadone detection in urinary biofluids.

The simultaneous identification of drugs has considerable difficulties due to the intricate interplay of analytes and the interference present in biological matrices. In this study, we introduce an innovative electrochemical sensor that overcomes these hurdles, enabling the precise and simultaneous determination of morphine (MOR), methadone (MET), and uric acid (UA) in urine samples. The sensor harnesses the strategically adapted carbon nanotubes (CNT) modified with graphitic carbon nitride (g-C3N4) nanosheets to ensure exceptional precision and sensitivity for the targeted analytes. Through systematic optimization of pivotal parameters, we attained accurate and quantitative measurements of the analytes within intricate matrices employing the fast Fourier transform (FFT) voltammetry technique. The sensor's performance was validated using 17 training and 12 test solutions, employing the widely acclaimed machine learning method, partial least squares (PLS), for predictive modeling. The root mean square error of cross-validation (RMSECV) values for morphine, methadone, and uric acid were significantly low, measuring 0.1827 µM, 0.1951 µM, and 0.1584 µM, respectively, with corresponding root mean square error of prediction (RMSEP) values of 0.1925 µM, 0.2035 µM, and 0.1659 µM. These results showcased the robust resiliency and reliability of our predictive model. Our sensor's efficacy in real urine samples was demonstrated by the narrow range of relative standard deviation (RSD) values, ranging from 3.71 to 5.26%, and recovery percentages from 96 to 106%. This performance underscores the potential of the sensor for practical and clinical applications, offering precise measurements even in complex and variable biological matrices. The successful integration of g-C3N4-CNT nanocomposites and the robust PLS method has driven the evolution of sophisticated electrochemical sensors, initiating a transformative era in drug analysis.

Iron-carbon dots embedded in molybdenum single-atom nanoflowers as multifunctional nanozyme for dual-mode detection of hydrogen peroxide and uric acid.

Single-atom catalysts (SACs) have attracted extensive attention in the field of catalysis due to their excellent catalytic ability and enhanced atomic utilization, but the multi-mode single-atom nanozymes for biosensors remain a challenging issue. In this work, iron-doped carbon dots (Fe CDs) were loaded onto the edges and pores of Mo SACs with nanoflower morphology; accordingly, a composite material Fe CDs/Mo SACs was prepared successfully, which improves the catalytic performance and develops a fluorescence mode without changing the original morphology. The steady-state kinetic data indicates that the material prepared have better affinity for substrates and faster reaction rates under optimized conditions. The specific kinetic parameters Km and Vmax were calculated as 0.39 mM and 7.502×10-7 M·s-1 respectively. The excellent peroxidase-like activity of Fe CDs/Mo SACs allows H2O2 to decompose into •OH, which in turn oxidizes colorless o-phenylenediamine (OPD) to yellow 2,3-diaminophenazine (DAP). At the same time, the fluorescence signal of Fe CDs/Mo SACs quenches obviously by DAP at 460 nm through internal filtration effect (IFE), while the characteristic fluorescence response of DAP gradually increases at 590 nm. Based on this sensing mechanism, a sensitive and accurate dual-mode (colorimetric and ratiometric fluorescent) sensor was constructed to detect H2O2 and uric acid, and the rate of recovery and linearity were acceptable for the detection of UA in human serum and urine samples. This method provides a new strategy for rapid and sensitive detection of UA, and also broadens the development of SACs in the field of biosensors.

Association between urinary uric acid excretion and kidney outcome in patients with CKD.

Inhibiting tubular urate reabsorption may protect the kidney from urate-induced tubular injury. However, this approach may promote intratubular uric acid crystallization, especially in acidified urine, which could be toxic to the kidney. To assess how tubular urate handling affects kidney outcomes, we conducted a retrospective cohort study including 1042 patients with estimated glomerular filtration rates (eGFR) of 15-60 mL/min/1.73 m2. The exposures were fractional excretion of uric acid (FEUA) and urinary uric acid-to-creatinine ratio (UUCR). The kidney outcome was defined as a halving of eGFR from baseline or initiating kidney replacement therapy. The median FEUA and UUCR were 7.2% and 0.33 g/gCre, respectively. During a median follow-up of 1.9 years, 314 kidney outcomes occurred. In a multivariate Cox model, the lowest FEUA quartile exhibited a 1.68-fold higher rate of kidney outcome than the highest FEUA quartile (95% confidence interval, 1.13-2.50; P = 0.01). Similarly, lower UUCR was associated with a higher rate of kidney outcome. Notably, patients in the highest quartile of FEUA and UUCR were at the lowest risk of kidney outcome even among those with aciduria. In conclusion, lower FEUA and UUCR were associated with a higher risk of kidney failure, suggesting that increased urate reabsorption is harmful to the kidney.

Correlation research demonstrates that an inflammatory diet is a risk factor for calcium oxalate renal stone formation.

BACKGROUND AND AIMS: Previous studies have demonstrated associations between the Dietary Inflammatory Index (DII®), an analytical tool which evaluates the inflammatory potential of the diet according to the pro- and anti-inflammatory properties of its components, and renal stone formation. However, these have not comprehensively addressed important parameters such as stone type, gender, DII scores in stone formers (SFs) and healthy controls (Cs) and associations of DII with urine and blood chemistries. These were adopted as the survey parameters for the present study, the purpose of which was to test whether the contributory role of an inflammatory diet on stone formation could be further confirmed. METHODS: 97 calcium oxalate (CaOx) SFs and 63 Cs, matched for age and gender each completed a semi-quantitative food frequency questionnaire from which nutrient composition was computed. These data were used to calculate the DII® score. To control the effect of energy intake, energy-adjusted DII scores were calculated per 1000 kcal consumed (E-DII™). A single blood sample and two consecutive overnight (8h) urine samples were collected from a subset (n = 59 SFs and n = 54 Cs) of the overall number of particpants (n = 160). These were analysed for renal stone risk factors. Data were analysed using regression models fit in R software. RESULTS: E-DII scores were found to fit the data better than DII, so they were used throughout. E-DII scores were significantly more positive (more pro-inflammatory) in SFs than in controls in the combined gender group (-0.34 vs. -1.73, p < 0.0001) and separately in males (-0.43 vs. -1.78, p = 0.01) and females (-0.26 vs. - 1.61, p = 0.05). In blood, a significant negative correlation was seen between E-DII and HDL cholesterol. In urine significant positive correlations were seen between E-DII and each of calcium (ρ = 0.25, p = 0.02), phosphate (ρ = 0.48, p < 0.001), magnesium (ρ = 0.33, p < 0.0001) and uric acid (ρ = 0.27, p = 0.004) concentrations. A significant negative correlation was seen between E-DII and urinary volume ρ = -0.27, p = 0.003). There was no correlation between E-DII scores and the relative supersaturations of urinary CaOx, calcium phosphate (brushite) and uric acid. CONCLUSIONS: Our findings provide hitherto unreported quantitative evidence in support of the notion that the diet of calcium oxalate renal stone patients is significantly more pro-inflammatory than that of healthy controls.

Advancements in Uric Acid Stone Detection: Integrating Deep Learning with CT Imaging and Clinical Assessments in the Upper Urinary Tract.

INTRODUCTION: Among upper urinary tract stones, a significant proportion comprises uric acid stones. The aim of this study was to use machine learning techniques to analyze CT scans and blood and urine test data, with the aim of establishing multiple predictive models that can accurately identify uric acid stones. METHODS: We divided 276 patients with upper urinary tract stones into two groups: 48 with uric acid stones and 228 with other types, identified using Fourier-transform infrared spectroscopy. To distinguish the stone types, we created three types of deep learning models and extensively compared their classification performance. RESULTS: Among the three major types of models, considering accuracy, sensitivity, and recall, CLNC-LR, IMG-support vector machine (SVM), and FUS-SVM perform the best. The accuracy and F1 score for the three models were as follows: CLNC-LR (82.14%, 0.7813), IMG-SVM (89.29%, 0.89), and FUS-SVM (29.29%, 0.8818). The area under the curves for classes CLNC-LR, IMG-SVM, and FUS-SVM were 0.97, 0.96, and 0.99, respectively. CONCLUSION: This study shows the feasibility of utilizing deep learning to assess whether urinary tract stones are uric acid stones through CT scans, blood, and urine tests. It can serve as a supplementary tool for traditional stone composition analysis, offering decision support for urologists and enhancing the effectiveness of diagnosis and treatment.

Genetic Determinants of Thiazide-Induced Hyperuricemia, Hyperglycemia, and Urinary Electrolyte Disturbances - A Genome-Wide Evaluation of the UK Biobank.

Thiazide diuretics, widely used in hypertension, cause a variety of adverse reactions, including hyperglycemia, hyperuricemia, and electrolyte abnormalities. In this study, we aimed to identify genetic variants that interact with thiazide-use to increase the risk of these adverse reactions. Using UK Biobank data, we first performed genomewide variance quantitative trait locus (vQTL) analysis of ~ 6.2 million SNPs on 95,493 unrelated hypertensive White British participants (24,313 on self-reported bendroflumethiazide treatment at recruitment) for 2 blood (glucose and urate) and 2 urine (potassium and sodium) biomarkers. Second, we conducted direct gene-environment interaction (GEI) tests on the significant (P < 2.5 × 10-9) vQTLs, included a second UK Biobank cohort comprising 13,647 unrelated hypertensive White British participants (3,478 on thiazides other than bendroflumethiazide) and set significance at P = 0.05 divided by the number of vQTL SNPs tested for GEIs. The vQTL analysis identified eight statistically significant SNPs for blood glucose (5 SNPs) and serum urate (3 SNPs), with none being identified for the urinary biomarkers. Two of the SNPs (1 glucose SNP: CDKAL1 intron rs35612982, GEI P = 6.24 × 10-3; and 1 serum urate SNP: SLC2A9 intron rs938564, GEI P = 4.51 × 10-4) demonstrated significant GEI effects in the first, but not the second, cohort. Both genes are biologically plausible candidates, with the SLC2A9-mediated interaction having been previously reported. In conclusion, we used a two-stage approach to detect two biologically plausible genetic loci that can interact with thiazides to increase the risk of thiazide-associated biochemical abnormalities. Understanding how environmental exposures (including medications such as thiazides) and genetics interact, is an important step toward precision medicine and improved patient outcomes.

Reliable quantitative detection of uric acid in urine by surface-enhanced Raman spectroscopy with endogenous internal standard.

Abnormal levels of uric acid (UA) in urine serve as warning signs for gout and metabolic cardiovascular diseases, necessitating the monitoring of UA levels for early prevention. However, the current analytical methods employed suffer from limitations in terms of inadequate suitability for home-based applications and the requirement of non-invasive procedures. In this approach, creatinine, a metabolite with a constant excretion rate, was incorporated as an endogenous internal standard (e-IS) for calibration, presenting a rapid, pretreatment-free, and accurate strategy for quantitative determination of UA concentrations. By utilizing urine creatinine as an internal reference value to calibrate the signal fluctuation of surface-enhanced Raman spectroscopy (SERS) of UA, the quantitative accuracy can be significantly improved without the need for an external internal standard. Due to the influence of the medium, UA, which carries a negative charge, is selectively adsorbed by Au@Ag nanoparticles functionalized with hexadecyltrimethylammonium chloride (CTAC) in this system. Furthermore, a highly convenient detection method was developed, which eliminates the need for pre-processing and minimizes matrix interference by simple dilution. The method was applied to the urine detection of different volunteers, and the results were highly consistent with those obtained using the UA colorimetric kit (UACK). The detection time of SERS was only 30 s, which is 50 times faster than UACK. This quantitative strategy of using urinary creatinine as an internal standard to correct the SERS intensity of uric acid is also expected to be extended to the quantitative detection needs of other biomarkers in urine.

Preventive Pharmacological Therapy and Risk of Recurrent Urinary Stone Disease.

BACKGROUND: Urinary stone disease is a prevalent condition associated with a high recurrence risk. Preventive pharmacological therapy has been proposed to reduce recurrent stone episodes. However, limited evidence exists regarding its effectiveness, contributing to its underutilization by physicians. This study aimed to evaluate the association between preventive pharmacological therapy (thiazide diuretics, alkali therapy, and uric acid-lowering medications) and clinically significant urinary stone disease recurrence. METHODS: Using data from the Veterans Health Administration, adults with an index episode of urinary stone disease from 2012 through 2019 and at least one urinary abnormality (hypercalciuria, hypocitraturia, or hyperuricosuria) on 24-hour urine collection were included. The primary outcome was a composite variable representing recurrent stone events that resulted in emergency department visits, hospitalizations, or surgery for urinary stone disease. Cox proportional hazards regression was performed to estimate the association between preventive pharmacological therapy use and recurrent urinary stone disease while adjusting for relevant baseline patient characteristics. RESULTS: Among the cohort of patients with urinary abnormalities ( n =5637), treatment with preventive pharmacological therapy was associated with a significant 19% lower risk of recurrent urinary stone disease during the 12-36-month period after the initial urine collection (hazard ratio, 0.81; 95% confidence interval, 0.65 to 1.00; P = 0.0496). However, the effectiveness of preventive pharmacological therapy diminished over longer follow-up periods (12-48 and 12-60 months after the urine collection) and did not reach statistical significance. When examining specific urinary abnormalities, only alkali therapy for hypocitraturia was associated with a significant 26% lower recurrence risk within the 12-36-month timeframe (hazard ratio, 0.74; 95% confidence interval, 0.56 to 0.97; P = 0.03). CONCLUSIONS: When considering all urinary abnormalities together, this study demonstrates that the use of preventive pharmacological therapy is associated with a lower risk of clinically significant recurrent episodes of urinary stone disease in the 12-36 month timeframe after urine collection, although only the association with the use of alkali therapy for hypocitraturia was significant when individual abnormalities were examined.

Urinary excretion of calcium, phosphate, magnesium, and uric acid in healthy infants and young children. Influence of feeding practices in early infancy.

BACKGROUND: Reference values for urinary calcium (Ca) and other solutes/creatinine (Cr) ratios in infants and young children are scarce. Its variation with type of lactation administered, breastfed (BF) or formula (F), is incompletely known. METHODS: A total of 511 spot urine samples from 136 children, aged 6 days to < 5 years, was collected. Urine was collected no fasting in infants < 18 months and first morning fasting in children aged 2.5-4 years. Urinary osmolality, Cr, urea, Ca, phosphate (P), magnesium (Mg), and uric acid (UA) were determined. Values are expressed as solute-to-Cr ratio. RESULTS: Urinary values were grouped according to the child's age: 6-17 days (G1), 1-5 months (G2), 6-12 months (G3), 13-18 months (G4), and 2.5-4 years (G5). G1 was excluded; Ca/Cr and UA/Cr (95th percentile) decreased with age (G2 vs. G5) from 1.64 to 0.39 and 2.33 to 0.83 mg/mg, respectively. The P/Cr median rises significantly with age from 0.31 (G2) to 1.66 mg/mg (G5). Mg/Cr was similar in all groups (median 0.20, 95th percentile 0.37 mg/mg). Ca/Cr (95th percentile) of BF infants was 1.80 mg/mg (< 3 months) and 1.63 mg/mg (3-5 months), much higher than F infants (0.93 and 0.90 mg/mg, respectively). P/Cr and P/Ca were lower in BF infants. CONCLUSIONS: Values for urinary Ca/Cr, P/Cr, Mg/Cr, and UA/Cr in infants and children < 5 years were updated. BF infants < 6 months showed higher Ca/Cr and lower P/Cr than F infants. New cutoff values to diagnose hypercalciuria in infants < 6 months, according to the type of lactation, are proposed.

The Efficacy and Safety of Dotinurad on Uric Acid and Renal Function in Patients with Hyperuricemia and Advanced Chronic Kidney Disease: A Single Center, Retrospective Analysis.

Objective: We investigated the efficacy and safety of dotinurad, a selective urate reabsorption inhibitor, in hyperuricemic patients with advanced chronic kidney disease (CKD) (stage G3-5). Patients and Methods: We retrospectively analyzed the cases of 34 patients (mean age, 68.6 ± 13.3 years; 17 men and 17 women) after 12 months of dotinurad treatment based on the changes in uric acid (UA) and the urine protein-to-creatinine ratio (UPCR) plus the annual change in estimated glomerular filtration rate (eGFR). Hyperuricemia (UA ≥6.0 mg/dL) and advanced CKD (mean eGFR: 32.0 ± 13.3 mL/min/1.73m2; stage G3, n=17; G4, n=13; G5, n=4) were present in all of the patients. The cases of 34 matched individuals with similar propensity scores (who were not taking dotinurad) were analyzed as a control group. Results: UA values decreased significantly in the dotinurad group (7.1 ± 0.8 mg/dL to 5.9 ± 1.0 mg/dL, p<0.05) but those did not change in the control group. UPCR did not change in either group. Low-density lipoprotein cholesterol also decreased significantly in the dotinurad group (98.8 ± 43.4 mg/dL to 82.9 ± 33.1 mg/dL, p<0.05). With the 12-month dotinurad treatment, the annual change in the patients' eGFR was significantly improved from -6.0 ± 12.9 mL/min/1.73 m2/year to -0.9 ± 4.6 mL/min/1.73 m2/year (p<0.05), but there was no change in the control group. Conclusion: Dotinurad can decrease UA levels and might attenuate renal function decline in individuals with hyperuricemia and advanced CKD.

Simultaneous recognition of dopamine and uric acid in real samples through highly sensitive new electrode fabricated using ZnO/carbon quantum dots: bio-imaging and theoretical studies.

Dopamine (DA) and uric acid (UA), which are vital components in human metabolism, cause several health problems if they are present in altered concentrations; thus, the determination of DA and UA is essential in real samples using selective sensors. In the present study, graphite carbon paste electrodes (CPE) were fabricated using ZnO/carbon quantum dots (ZnO/CQDs) and employed as electrochemical sensors for the detection of DA and UA. These electrodes were fully characterized via different analytical techniques (XRD, SEM, TEM, XPS, and EDS). The electrochemical responses from the modified electrodes were evaluated using cyclic voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy. The results showed that the present electrode has exhibited high sensitivity towards DA, recognizing even at low concentrations (0.12 µM), and no inference was observed in the presence of UA. The ZnO/CQD electrode was applied for the simultaneous detection of co-existing DA and UA in real human urine samples and the peak potential separation between DA and UA was found to be greatly associated with the synergistic effect originated from ZnO and CQDs. The limit of detection (LOD) of the electrode was analyzed, and compared with other commercially available electrodes. Thus, the ZnO/CQD electrode was used to detect DA and UA in real samples, such as Saccharomyces cerevisiae cells.