Urinary Creatinine Concentration Research Articles

#2983 Correlation of microRNA expression with IgA nephropathy progression: preliminary results

Abstract Background and Aims IgA nephropathy (IgAN) is the most common cause of glomerulonephritis worldwide. IgAN is diagnosed based on the result of histopathological examination. The risk factors for disease progression primarily include the level of impairment of renal function at the time of diagnosis (GFR < 60 ml/min/1.73 m2), the presence of hypertension, daily administration of more than 1.0 g, and the occurrence of hematuria. MicroRNAs (miRNAs) are important regulators of gene expression. Their role has a significant impact on the proper functioning of the body, and disorders related to their expression can lead to the development of many pathological processes in the body. The study aimed to assess the dependence of microRNA expression on the stage of the disease in patients with IgA nephropathy. Method A study was conducted involving patients newly diagnosed with IgA nephropathy based on histopathological examination results. The expression of microRNA molecules (miR-146a, miR-155, miR-200b, miR-429) was determined in urine sediment and blood. The analysis focused on examining the relationship between microRNA expression and the stage of disease progression (proteinuria, renal parameters). Blood and urine tests were performed before the start of immunosuppressive treatment with glucocorticosteroids according to the Pozzi regimen. Results Twenty-seven patients were included in the study group- 14 women (51.9%) and 13 men (48.1%). Nephrotic-range proteinuria (>3000 mg/24 h) was observed in 5 patients (18.5%), while subnephrotic proteinuria was present in 22 patients (77.8%). Reserved kidney function (eGFR > 90) was found in 17 patients (63%). The exact distribution of results according to the stage of renal failure is given in the Table 1. Statistically significant positive correlation was found between serum creatinine concentration and miR-200b expression in urine (R = 0,398, p = 0,049). Initially, no statistically significant correlation was found between the expression of selected miRNA molecules and the degree of 24-hour proteinuria. Conclusion MiRNA molecules may be promising, non-invasive biomarkers widely used in clinical practice. Determining the viability of clinical use of microRNA molecules will require a panel of miRNAs or miRNAs used in combination with other biomarkers and clinical outcomes to improve diagnostic utility.

#2715 Towards precise prediction of prognosis in ADPKD: a comprehensive biomarker analysis

Abstract Background and Aims Determining prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD) heavily relies on the height-adjusted total kidney volume (HtTKV) Mayo classification. This classification predicts kidney outcomes on a group level but lacks precision in individual patients. Recently, several urine and blood biomarkers have demonstrated prognostic value in ADPKD, independent of HtTKV and baseline eGFR. This study compares the prognostic value of various biomarkers to aid selection when developing novel risk stratification tools. Method Included were participants of the DIPAK studies with a follow-up duration of >1 year and ≥3 eGFR measurements. We excluded patients with diabetes mellitus and patients using tolvaptan or somatostatin analogues. At baseline, urine samples were analyzed for albumin, urea, creatinine, β2-microglobulin (β2-MG), monocyte chemotactic protein-1 (MCP-1), TmP/GFR (tubular maximum reabsorption rate of phosphate to GFR), and blood was drawn to measure creatinine, urea (for assessment of urinary-to-plasma urea ratio; UP urea), glucagon, fibroblast growth factor 23 (FGF-23) and copeptin. Albumin, β2-MG and MCP-1 were divided by urinary creatinine concentration to account for concentration effects. The cross-sectional and longitudinal association with baseline eGFR and eGFR decline over time was analyzed using multivariate linear regression and repeated measures linear mixed model regression. Furthermore, logistic regression models were tested to identify patients with rapidly-progressive disease (eGFR slope ≤ −3.0 ml/min/1.73 m2/year). Lastly, multivariate Cox regression analysis was conducted to evaluate the time to the combined endpoint of 30% decline in eGFR, reaching an eGFR ≤ 15 ml/min/1.73 m2, initiation of dialysis or receiving a kidney transplant. Results 565 patients were included with a mean age of 47 ± 11 years, eGFR of 64 ± 27 ml/min/1.73 m2 and HtTKV of 858 [IQR: 540, 1305] ml/m. During a mean follow-up of 5.2 ± 2.2 years, the mean eGFR decline was −3.38 ± 2.37 mL/min/1.73 m2/year. Of these patients, 283 (50.1%) had rapidly progressive disease and 267 (47.3%) reached the combined kidney endpoint. All biomarkers except glucagon were associated with baseline eGFR and eGFR decline over time after adjustment for established clinical risk factors for disease progression (sex, PKD mutation and baseline age and eGFR). After adjustment for the same covariates, albumin/creatinine, MCP-1/creatinine, FGF-23, UP-urea and copeptin were predictive of rapid disease progression. The area under the curve (AUC) value for predicting rapidly progressive disease for the Mayo HtTKV classification alone was 0.694, which could be improved to 0.766 (P < .001) by a risk prediction model that also included the aforementioned predictive clinical risk factors. The introduction of several biomarkers further improved this clinical model, including albumin/creatinine (AUC 0.794, p = 0.03), MCP-1/creatinine (AUC 0.804, p = 0.04) and copeptin (AUC 0.789, p = 0.05). Similar results were seen in multivariate Cox regression models after adjustment for covariates, with independent predictors of the combined endpoint being again albumin/creatinine (P < .001), MCP-1 creatinine (P < .001), copeptin (p = 0.012), but now also UP-urea (p = 0.008) and FGF-23 (P < .001). These findings appeared robust in subgroup analyses of 200 patients with Mayo HtTKV class 1C and 122 patients with early disease (age ≤ 40 years and eGFR ≥ 60 ml/min/1.73 m2 at baseline), in whom predicting prognosis is most challenging. Conclusion In patients with ADPKD, albumin/creatinine, MCP-1/creatinine, FGF-23 and copeptin are consistent predictors of kidney outcomes after adjustment for established clinical risk factors. Our data suggest that these biomarkers should be prioritized when developing novel multimarker models to enhance precision of risk prediction in ADPKD.

Iodine Status and Its Influencing Factors in Hospitalized and Healthy Preschool-Age Children.

Iodine is a trace element necessary for synthesizing thyroid hormones. It is especially crucial for the neurodevelopment and intellectual development of children. Preschool-age children admitted to the hospital tend to have more fragile physical and mental health, but few studies demonstrate their iodine status. Our study aimed to investigate the iodine status of hospitalized and healthy preschool-age children and to explore the factors influencing them. From January to December 2021, 426 children aged 3-6 years were admitted to the respiratory department for pneumonia, bronchopneumonia, or bronchiectasis, but they could eat normally and were recruited as hospitalized children. Six hundred ten healthy children aged 3-6 years were included. We collected anthropometric measurements and urine samples from hospitalized and healthy preschool-age children, and iodine status was assessed through urinary iodine concentration (UIC) and urinary iodine/creatinine ratio (UI/Cr). UIC was 40.1 and 166.1µg/L for hospitalized and healthy preschool-age children, respectively (P < 0.001). Urinary creatinine concentration (UCr) was 0.2 and 0.8g/L for hospitalized and healthy preschool-age children, respectively (P < 0.001). UIC decreased with increasing height z-scores in hospitalized children (Spearman's rho = -0.11, P = 0.022). A significantly increased risk of UIC < 100µg/L was found in hospitalized children (OR = 9.1 (6.8, 12.2), P < 0.001) when compared to healthy children. In conclusion, hospitalized preschool-age children are likelier to have iodine insufficiency than healthy preschool-age children, especially those with good linear growth. Measures should be implemented to ensure adequate iodine intake of preschool-age children during hospitalization to avoid affecting their intellectual and physical development. Due to lower UCr in hospitalized children, creatinine is not appropriate for assessing iodine status in hospitalized children.

11 The effect of increased standardized ileal digestible lysine through increased soybean meal during late gestation on lactating sow and litter performance

Abstract A total of 87 sows (Line 241, DNA) and their offspring were used to evaluate the effect of increasing standardized ileal digestible (SID) lysine through increasing soybean meal (SBM) concentration in late gestation diets on lactating sow and litter performance. Sows were blocked by parity and body weight (BW) on approximately d 90 of gestation and allotted to 1 of 3 treatments with 29 replications per treatment. Diets included increasing SID lysine (0.60, 0.80, or 1.00%) through increased SBM (14, 21, or 29% of the diet). Sows received approximately 2.04 kg/d of their treatment diet for an average SID Lys intake of 11.9, 15.8, or 19.9 g/d, respectively. Diets were fed from d 90 of gestation until farrowing. After farrowing, all females were fed a common lactation diet containing 1.10% SID Lys until weaning (19 d post-farrow). Sow BW, caliper score, and backfat and loin depth were collected on d 90, upon entry into the farrowing house (d 110), and at weaning. Urine samples were collected on d 90 and 110 of gestation to ascertain urinary creatinine concentrations. Litters were cross-fostered within sow treatment by 48 h after farrowing to equalize litter size. Parity was included in the statistical model as a fixed effect with females being classified as either a primiparous (n = 35) or multiparous (n = 52) sow. Body weight gain from d 90 to 110 of gestation increased as SID Lys increased (linear, P &amp;lt; 0.001; Table). There were no differences in starting litter size or piglet birth weight with increasing SID Lys in late gestation (linear, P &amp;gt; 0.10). Change in urinary creatinine level from d 90 to 110 of gestation tended to decrease as SID Lys increased in the diet (linear, P = 0.063) suggesting that less muscle catabolism occurred with increasing SID Lys. Piglet average daily gain (ADG) from d 2 to 10 of lactation linearly increased as SID Lys increased (P = 0.017), but not from d 2 to weaning. From d 2 until weaning, litters from sows fed the 0.80% SID Lys gestation diet had the greatest litter gain (quadratic, P = 0.044). Pre-weaning mortality from birth until d 2 of lactation was greatest for sows fed 0.80% SID Lys (quadratic, P = 0.025). There was a parity × gestation diet interaction for pre-weaning mortality from d 2 to weaning (P = 0.049) where mortality increased as SID Lys increased in primiparous sows but decreased in multiparous sows. In conclusion, increased SID Lys through increased SBM linearly increased late gestation sow BW gain and piglet ADG during the first portion of lactation. However, litters from sows on the 0.80% SID Lys treatment exhibited the highest litter ADG during late lactation and overall.

Evaluation of protocols to determine urine output and urinary urea nitrogen excretion in dairy cows with and without dietary salt supplementation

Urine output and urinary urea-N excretion (UUNe) excretion are critical measures to accurately evaluate N metabolism in lactating dairy cows and environmental concerns related to manure N. The objectives of this study were: (a) to compare estimates of UUNe, urine output, and related variables from 3 pre-established measurement protocols (bladder catheterization, external collection cup, and spot sampling) and from dietary salt supplementation, (b) to study temporal variation in UUNe, urine output, and related variables as affected by measurement protocol, and (c) to evaluate urine specific gravity as a predictor of urine output. Twelve multiparous Holstein cows were used in a split-plot, Latin square design. Cows were randomly assigned to a diet (main plot) containing either 0.7 or 1.6% NaCl (dry matter basis) and then assigned to a sequence of 3 protocols (sub-plot) in a balanced 3 × 3 Latin square with 14-d period. For each protocol, measurements were conducted every 4 h for 3 consecutive days. Urine output was determined gravimetrically for bladder catheterization and external collection cup or based on measured cow body weight, measured urinary creatinine concentration, and the assumed creatinine excretion of 29 mg/kg body weight per d for spot sampling. Urine specific gravity was measured by refractometry. When averaged over a 3-d measurement period and compared with bladder catheterization, spot sampling underestimated urine output (6.8 kg/d; 20%) and UUNe (26 g/d; 13%) but exhibited greater concentration of urinary urea-N (+58 mg/dL; 10%). There were no differences in any measurements determined via bladder catheterization or external cup device protocols, except for urine output that tended to be 3.7 kg/d lower for collection cup compared with bladder catheterization. The 2 gravimetric protocols yielded lower urinary creatinine concentration than spot sampling (64.7 vs. 88.1 mg/dL) and lower creatinine excretion (25.3 mg/kg of body weight per d) than the value of 29 mg/kg of body weight per d generally assumed in the spot sampling protocol. Salt supplementation tended to increase urine output (+5.2 kg/d) and decrease urinary urea-N concentration (-93 mg/dL), urinary creatinine concentration (-9.5 mg/dL), milk protein concentration (-0.19 percentage unit) and milk protein yield (-70 g/d). There was greater temporal variation of urine output when measured via the collection cup compared with bladder catheterization in the first 2 d but not the third day of sampling, suggesting that an extended period of adaptation might have improved data quality of the collection cup protocol. The R2 of the linear regression to predict urine output with urine specific gravity was 67, 73, and 32% for bladder catheterization, collection cup, and spot sampling, respectively. In this study, spot sampling underestimated both urine output and UUNe, but UUNe determination did not differ between external collection cup and bladder catheterization. However, our data suggested the need to investigate the adaptation protocol, required days of measurements and the conversion of urine mass to urine volume to improve accuracy and precision of urine collection protocols.

Urinary haloacetic acid concentrations in relation to sex and thyroid hormones among reproductive-aged men

Sex and thyroid hormones are critical for male reproductive health. However, the relationship between haloacetic acid (HAA) exposure – a known endocrine disruptor – and sex and thyroid hormones in humans remains unclear. We thus recruited 502 male participants seeking fertility evaluation from a reproductive center. We measured concentrations of sex and thyroid hormones in a single blood sample and dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in repeated urine samples. Multivariable linear regression models were constructed to evaluate the association between HAA concentrations and hormone measurements. After adjusting for potential confounders and urinary creatinine concentrations, urinary concentrations of TCAA were inversely associated with serum levels of sex hormone-binding globulin (SHBG), testosterone (T), T/luteinizing hormone ratio (T/LH), and thyroid stimulating hormone (TSH) (all P for trend < 0.10). Compared with participants in the lowest quartile of TCAA concentrations, those in the highest quartile had reduced serum levels of SHGB by 14.2 % (−26.7, −3.0 %), T by 11.1 % (−21.7, −1.3 %), T/LH by 21.0 % (−36.7, −7.1 %), and TSH by 19.1 % (−39.7, −1.5 %). Additionally, we observed inverse associations between continuous measurements of urinary HAAs and serum levels of free T, bioactive T, and estradiol. Our findings suggest that male HAA exposure may be associated with disrupted sex and thyroid function.

Diagnostic value of stimulated urine luteinizing hormone after triptorelin stimulation test in girls with CPP.

To investigate the diagnostic value of urine luteinizing hormone (ULH) after triptorelin stimulation test detected by immunochemiluminometric assay (ICMA) in girls with central precocious puberty (CPP). The girls with precocious puberty were involved. The triptorelin stimulation test at 8:30 a.m.were performed. Two consecutive 12-hour urine samples were collected after the test, defined as first 12-hour and second 12-hour urine, respectively. ICMA measured ULH. Urine creatinine (Cr) concentration was measured. CPP and peripheral precocious puberty (PPP) were diagnosed by the same pediatric endocrinologist based on clinical symptoms, signs, and progression of clinical development. A total of 97 cases (CPP n=69; PPP n=28) were included, with 12 cases not meeting the receiver operating characteristic analysis criteria. The first and second 12-hour ULH/Cr in CPP group were higher than those in PPP group. When first 12-hour ULH/Cr was ≥ 287.252 IU/mol, the sensitivity and specificity for diagnosing CPP were 87.3% and 90.9%, respectively. When second 12-hour ULH/Cr was ≥ 152.769 IU/mol, the sensitivity and specificity for diagnosing CPP were 92.1% and 90.9%, respectively. The area under the curve of first and second 12-hour ULH/Cr were 0.933 and 0.954, respectively. The ULH detection method after the triptorelin stimulation test has clinical significance for diagnosing CPP in girls. When the compliance of blood sampling in girls with precocious puberty is poor, first 12-hour ULH/Cr ≥ 288 IU/mol (or second 12-hour ≥ 153 IU/mol) after the triptorelin stimulation test can serve as a laboratory indicator for diagnosis of CPP.

An Eco-Friendly alternative for voltammetric determination of creatinine in urine sample using copper(II) immobilized on biochar

Creatinine (CRE) is the final product of creatine and phosphocreatine metabolism in mammals. CRE is primarily excreted by the kidneys, and a decrease in urinary creatinine content can be an indicator of kidney failure. Therefore, monitoring this biomarker in urine samples is crucial. For this purpose, an electrochemical sensor had been proposed for indirect determination of the target based on the immobilization of copper ions on biochar, an eco-friendly material. First, copper ions (Cu2+) were spontaneously preconcentrated at the surface of a biochar-modified carbon paste electrode. Next, CRE was spontaneously accumulated over this surface, resulting in the suppression of the copper voltammetric signal. This suppression was attributed to the formation of a creatinine-copper complex, and used as the analytical response. A linear dynamic range (LDR) of 300–700 µmol L−1 in the presence of a synthetic urine matrix was achieved, along with limits of detection (LOD) and quantification (LOQ) of 91.0 µmol L−1 and 300 µmol L−1, respectively. Selectivity was suitable for the most common metallic species found in urine and equimolar uric acid concentration. The standard addition method was adopted for CRE determinations in synthetic urine samples, and the recoveries values were 101 ± 7 % for the method's limit of quantification (LOQ) concentration (300 µmol L−1), and 100 ± 7 % for the usual creatinine concentration in urine after a dilution step, 500 µmol L−1. Therefore, an approach based on metal immobilization, using an eco-friendly material, was proposed for indirect creatinine determination, and successfully applied to biomarker analysis in a synthetic urine matrix.

Biomonitoring and health risk assessment of exposure to phthalate esters in waste management workers

Humans are at risk of exposure to phthalates due to the widespread use of plasticized plastics, and one of the major concerns is occupational exposure. The present study investigated occupational exposure to phthalates at one of the greatest solid waste management sites in the second-largest country in the Middle East. Carcinogenic and non-carcinogenic health risks were assessed by human biomonitoring (HBM). The concentration of phthalate esters was determined using gas chromatography-mass spectrometry (GC–MS), and the daily intake (DI) of phthalate was calculated based on the adjusted urinary creatinine concentrations. Moreover, carcinogenic and non-carcinogenic risks were assessed. Monte Carlo simulations were performed for uncertainty and sensitivity analysis. The highest concentration recorded was 130.80 µg/g creatinine for mono-ethyl phthalate (MEP) among the composting group, while the lowest concentration was 0.49 µg/g creatinine for Monobenzyl phthalate (MBzP) among the office group. All estimates of daily intake were below the reference concentration, and differences between the DI at site sections were statistically significant (p < 0.05). The non-carcinogenic risk level was negligible. The excess lifetime cancer risk (ELCR) values corresponding to di-(2-ethylhexyl) phthalate (DEHP) exposure were 2.07E-04 among the composting group and 2.07E−04 among the processing group, posing a definite risk. The carcinogenic risk value among the office group was in a possible risk category with ELCR values of 9.75 E−05. The on-site workers of waste management sites can be highly exposed to phthalates, and their health risk is considerable. Appropriate measures and interventions should be considered to reduce occupational exposure to phthalates.

Effect of sodium-glucose cotransporter 2 inhibitor canagliflozin on interstitial glucose concentration in insulin-treated diabetic dogs.

The utility of sodium-glucose cotransporter 2 inhibitors (SGLT2i) has not been reported in insulin-treated diabetic dogs. Canagliflozin, a PO-administered SGLT2i, decreases interstitial glucose concentration (IG) in insulin-treated diabetic dogs. Five insulin-treated diabetic dogs. Uncontrolled open label longitudinal study. Canagliflozin (2-4 mg/kg/day PO) was added to an unchanged insulin dose for 7 days. Fractional excretion of glucose was calculated by dividing the product of urine glucose and serum creatinine concentrations by the product of serum glucose and urine creatinine concentrations. Hypoglycemia was defined as IG <60 mg/dL. Median IG in 2869 measurements obtained while dogs were treated with insulin and canagliflozin was 87 mg/dL (range, 40-500 mg/dL) and was significantly lower than median IG in 1426 measurements obtained while dogs were treated with insulin alone (212 mg/dL; range, 41-500 mg/dL; P < .001). Median fractional excretion of glucose when dogs were treated with insulin and canagliflozin was 1.1% (range, 0.9%-2.0%), significantly higher than when dogs were treated with insulin alone (0.3%; range, 0.01%-1.0%; P = .04). The frequency of hypoglycemia was higher in dogs treated with insulin and canagliflozin (544 of 2869 IG measurements, 19%) compared with the frequency of hypoglycemia in dogs treated with insulin alone (52 of 1426 IG measurements, 4%; P < .001). Canagliflozin may have a role in improving glycemic control in insulin-treated diabetic dogs, but the dose of insulin should be decreased when adding canagliflozin to insulin treatment.

Low serum concentrations of bevacizumab and nivolumab owing to excessive urinary loss in patients with proteinuria: a case series.

Proteinuria can cause interindividual variability in the pharmacokinetics of therapeutic antibodies and may affect therapeutic efficacy. Here, we measured the serum and urinary concentrations of bevacizumab (BV) and nivolumab (NIVO) in patients with proteinuria and reported a case series of these patients. Thirty-two cancer patients who received BV every 3 weeks or NIVO every 2 weeks between November 2020 and September 2021 at Kyoto University Hospital were enrolled in this study. The serum and urinary concentrations of BV and NIVO were measured using liquid chromatography-tandem mass spectrometry. We divided the BV-treated patients and the NIVO-treated patients into two groups based on the urine protein-creatinine ratio (UPCR): UPCR 1g/g or higher (BV, n = 9; NIVO, n = 3) and UPCR less than 1g/g (BV, n = 14; NIVO, n = 6). Serum concentrations of the therapeutic antibodies adjusted by their doses were significantly lower in both BV- and NIVO-treated patients with UPCR 1g/g or higher compared to those with less than 1g/g. In patients with UPCR 1g/g or higher, urinary concentrations of the therapeutic antibodies adjusted by their serum concentrations and urinary creatinine concentrations tended to increase. This case-series study suggests a possibility of reduction in serum concentrations of BV and NIVO in patients with proteinuria by urinary excretion of these drugs.

Associations of concentrations of eight urinary phthalate metabolites with the frequency of use of common adult consumer and personal-care products

This study analyzed the relationship between urine concentrations of phthalate metabolites (UCOM) and personal care products (PCPs) used in adults and examined the change in UCOM according to the usage frequency of PCPs based on raw data from the 3rd Korean National Environmental Health Survey conducted between 2015 and 2017. The relationship between PCP use frequency and UCOM was analyzed using multiple regression analysis, adjusting for baseline factors. The regression model consisted of a Crude Model with log-transformed UCOM before and after adjustment for urine creatinine concentrations. Model 1 was additionally adjusted for age, sex, and obesity, while Model 2 was additionally adjusted for smoking, alcohol consumption, pregnancy history, average monthly income of the household, and PCP exposure within the past 2 days. PCP usage frequency was significantly associated with the UCOM without adjustment for urine creatinine and correlated with demographic characteristics, urine creatinine concentration, and PCP exposure within the past 2 days. This study on exposure to urinary phthalates will play a crucial role in Korean public health by aligning with the fundamentals of research priorities and providing representative data on phthalate exposure for conducting population-level studies.

Urinary Sphingosine-1-Phosphate as a Biomarker for Bladder Pain Syndrome.

Sphingosine-1-phosphate (S1P) is a signaling molecule involved in inflammation and bladder contraction. The aims of this case-control pilot study were to compare urinary S1P concentrations in bladder pain syndrome (BPS) participants to controls and determine whether these concentrations correlate with disease severity and duration. Adult females with BPS and controls were enrolled. Bladder pain syndrome participants completed an O'Leary-Sant questionnaire. Information on duration of symptoms and treatment history was obtained. Urinary S1P and creatinine concentrations were determined. Mann-Whitney U tests were used to compare groups, and Spearman correlation was used to test for associations between concentrations and duration and severity of symptoms. Twenty-five participants were in each group. Median S1P concentration was 1,225 ng/dL in the BPS group and 2,183 ng/dL in the control group, which was significantly different (P < 0.0001). This difference did not persist when normalized to urinary creatinine (P = 0.58). No differences were noted in urinary S1P concentrations between treated and untreated participants (P = 0.53) or with symptom scores of 13 or greater and less than 13 (P = 0.69). Sphingosine-1-phosphate levels did not correlate with O'Leary-Sant scores (P = 0.08) or duration of symptoms (P = 0.67). Results did not change when using S1P concentrations normalized to creatinine. This study demonstrated successful quantification of human urinary S1P concentrations. A difference in urinary S1P was found between BPS participants and controls but not when normalized to creatinine. While this is the first study to investigate urinary S1P as a biomarker for BPS, results suggest that it may have a potential role as a biomarker requiring further research.

Correlation between urine anion gap and urine ammonia-creatinine ratio in healthy cats and cats with kidney disease.

Ammonium excretion decreases as kidney function decreases in several species, including cats, and may have predictive or prognostic value in patients with chronic kidney disease (CKD). Urine ammonia measurement is not readily available in clinical practice, and urine anion gap (UAG) has been proposed as a surrogate test. Evaluate the correlation between urine ammonia-to-creatinine ratio (UACR) and UAG in healthy cats and those with CKD and determine if a significant difference exists between UAG of healthy cats and cats with CKD. Urine samples collected from healthy client-owned cats (n = 59) and those with stable CKD (n = 17). Urine electrolyte concentrations were measured using a commercial chemistry analyzer and UAG was calculated as ([sodium] + [potassium]) - [chloride]. Urine ammonia and creatinine concentrations had been measured previously using commercially available enzymatic assays and used to calculate UACR. Spearman's rank correlation coefficient between UAG and UACR was calculated for both groups. The UAG values of healthy cats and cats with CKD were assessed using the Mann-Whitney test (P < .05). The UAG was inversely correlated with UACR in healthy cats (P < .002, r0 = -0.40) but not in cats with CKD (P = .55; r0 = -0.15). A significant difference was found between UAG in healthy cats and those with CKD (P < .001). The UAG calculation cannot be used as a substitute for UACR in cats. The clinical relevance of UAG differences between healthy cats and those with CKD remains unknown.

Prostaglandin E-major urinary metabolites as a new biomarker for acute mesenteric ischemia.

Acute mesenteric ischemia (AMI) is an emergent vascular disease caused by cessation of the blood supply to the small intestine. Despite advances in the diagnosis, intervention, and surgical procedures, AMI remains a life-threatening condition. Prostaglandin E2 major urinary metabolite (PGE-MUM), the urinary metabolite of prostaglandin E2, is known to be stable in urine and has been suggested to be a valuable biomarker for intestinal mucosal inflammation, such as ulcerative colitis. We therefore investigated whether or not PGE-MUM levels reflect the degree of ischemia in an intestinal ischemia-reperfusion model. Male rats were used to establish a superior mesenteric artery occlusion (SMAO) group, in which the superior mesenteric artery was clamped, and a sham group. The clamping times in the SMAO group were either 30 minutes or 60 minutes, and reperfusion times were either 3 hours or 6 hours, after which PGE-MUM values were measured. The histological injury score of the SMAO (30-minute ischemia and 6-hour reperfusion group, 1.8 ± 0.4; 60-minute ischemia and 6-hour reperfusion group, 4.7 ± 0.5) and were significantly greater than that of the sham group (0.4 ± 0.7, p < 0.05). The PGE-MUM levels in the SMAO group (30-minutes ischemia and 6-hour reperfusion group, 483 ± 256; 60-minutes ischemia and 6-hour reperfusion group, 889 ± 402 ng/mL) were significantly higher than in the sham group (30-minute and 6-hour observation group, 51 ± 20; 60-minute and 6-hour observation group, 73 ± 32 ng/mL; p < 0.05). Furthermore, the PGE-MUM value was corrected by the concentration of urinary creatinine (Cr). The PGE-MUM/urinary Cr levels in the SMAO group were also significantly higher than in the sham group ( p < 0.05). We found that intestinal ischemia-reperfusion increased urinary PGE-MUM levels depending on the ischemic time. This suggests the potential utility of PGE-MUM as a noninvasive marker of intestinal ischemia.

Spot urine sodium as a marker of urine dilution and decongestive abilities in acute heart failure

The decongestion ability in response to diuretic treatment plays a crucial role in the treatment of acute heart failure. This effectiveness is evaluated through the assessment of sodium concentration and urine volume, which are also treatment goals themselves. However, the bidirectional interconnection between these factors remains not fully understood. The objective of this study is to provide mechanistic insights into the correlation between spot urine sodium concentrations (UNa+) and urine dilution. This aims to better understand of the decongestive abilities in acute heart failure (AHF). The study was single-center, prospective, conducted on a group of 50 AHF patients. Each participant received a standardized furosemide dose of 1 mg per kg of body weight. Hourly diuresis was measured in the first 6 h of the study, and urine composition was assessed at predefined timepoints. The study group presented the exponential (rather than linear) pattern of relationship between UNa+ and 6-h urine volume, whereas relationship between eGFR and 6-h urine volume was linear (r = 0.61, p < 0.001). The relationship between UNa+ and all other analyzed indices of urine dilution, including the change from baseline in urine creatinine concentration, urine osmolarity, and urine osmolarity corrected for urine sodium, also exhibited an exponential relationship. Patients who were chronically exposed to furosemide demonstrated a significantly lower urine dilution (1.78 [1.18–3.54] vs 11.58 [3.9–17.88]; p < 0.001) in comparison to naïve individuals. In conclusion, it should be noted that in AHF higher UNa+ is associated with disproportionally higher urine dilution, and patients naïve to furosemide have significantly greater ability to dilute urine when compare to chronic furosemide users.

Effect and Mechanism of Rhein-praseodymium Complex on Intestinal Uric Acid Excretion in Rats with Renal Injury and Hyperuricemia.

Hyperuricemia (HUA) is a disease characterized by excessive uric acid production and/or insufficient uric acid excretion caused by abnormal purine metabolism in the human body. Uric acid deposition caused by hyperuricemia can cause complications, such as kidney damage. The current therapeutic drugs for HUA are not very targeted and usually have specific toxic side effects. This study aimed to synthesize a compound using rhein and praseodymium, which can effectively help hyperuricemia patients with kidney injury to excrete uric acid through the intestine and preliminarily explore its intestinal excretion mechanism. The natural active ingredient rhein and rare earth metal praseodymium were used to synthesize Rh-Pr. The possible chemical structure of Rh-Pr was deduced by UV, IR, 1H-NMR, conductivity method, and thermogravity analysis. Adenine (100 mg/kg) and ethambutol hydrochloride (250 mg/kg) were administered by gavage for three weeks to establish the hyperuricemia rat model of renal injury. Serum uric acid (UA), creatinine (Cr), urea nitrogen (BUN), and uric acid concentration in urine and feces were detected by biochemical methods. The protein expression levels of GLUT9, ABCG2, and MRP4 in the jejunum, ileum, and colon of rats were detected by Western Blotting. According to the characterization, the chemical composition formula of the complex is Pr(C15H7O6)3·2H2O. In vivo, activity tests showed that Rh-Pr could enhance the intestinal uric acid excretion level of rats, upregulate the expression of ABCG2 protein in the jejunum and ileum, down-regulate the expression of GLUT9 protein in the ileum and colon, and also had a good recovery effect on serum uric acid, creatinine, and urea nitrogen levels. Rh-Pr is different from other drugs in that it promotes intestinal uric acid excretion and has a renal recovery effect. It reduces the patient's kidney burden and is significant for hyperuricemia patients with kidney injury.

Increased urinary creatinine during hibernation and day roosting in the Eastern bent-winged bat (Miniopterus fuliginosus) in Korea

Torpor and arousal cycles, both daily and seasonal (e.g. hibernation), are crucial for small mammals, including bats, to maintain the energy and water balance. The alternation between torpor and arousal leads to metabolic changes, leaving traceable evidence of metabolic wastes in urine. In this study we investigated urinary creatinine and acetoacetate (a ketone body) in the Eastern bent-wing bat (Miniopterus fuliginosus) in Mungyeong, South Korea. We found an increase in urinary creatinine during torpor in summer, indicating changes in renal water reabsorption rates during the active season. Although we could not confirm ketonuria in hibernating bats due to a methodological limitation caused by the small amount of urine, we verified an increase in urinary creatinine concentration during hibernation. This finding suggests that managing water stress resulting from evaporative water loss is one of key reasons for arousal during hibernation in Eastern bent-wing bats.

Rapid electrodeposition of Cu nanoparticle film on Ni foam as an integrated 3D free-standing electrode for non-invasive and non-enzymatic creatinine sensing.

High cost, inherent destabilization, and intricate fixing of enzyme molecules are the main drawbacks of enzyme-based creatinine sensors. The design of a low-cost, stabilizable, and enzyme-free creatinine sensing probe is essential to address these limitations. In this work, an integrated three-dimensional (3D) free-standing electrode was designed to serve as a non-enzymatic creatinine sensing platform and was fabricated by rapid electrodeposition of a dense copper nanoparticle film on nickel foam (Cu NP film/NF). This low-cost, stable, easy-to-fabricate, and binder-free Cu NP film/NF electrode has abundant active sites and excellent electrochemical performance. Cyclic voltammetry measurements show a wide linear range (0.25-24 mM), low detection limit (0.17 mM), and high sensitivity (306 μA mM-1 cm-2). The developed sensor shows high recovery of creatinine concentration in real urine. Besides, it has better specificity, reproducibility, and robustness in detecting creatinine. These excellent results suggest that a non-enzymatic creatinine sensor based on an integrated 3D free-standing Cu NP film/NF electrode has good potential for non-invasive detection of urinary creatinine.

Water Intake and Hydration Status among Pregnant Women in the Second Trimester in China: A Three-Day Metabolic Trial.

Adequate water intake and optimal hydration status during pregnancy are crucial for maternal and infant health. However, research on water intake by pregnant women in China is very limited. This study mainly aimed to observe the daily total water intake (TWI) of pregnant women and its different sources and to investigate the relationship between their water intake and hydration biomarkers. From October to November 2020, a convenience sample of pregnant women in the second trimester (n = 21) was recruited. Under conditions close to daily life, they undertook a 3-day metabolic trial. Each participant was provided with sufficient bottled water, and the weight of what they drank each time was measured. The intake of other beverages and foods was measured using a combination of weighing and duplicate portion method. Fasting venous blood and 24 h urine samples were collected and analyzed for the hydration biomarkers, including the serum/urine osmolality, urine pH, urine specific gravity, and the concentrations of major electrolytes in urine and serum. The results showed that the mean daily TWI was 3151 mL, of which water from beverages and foods accounted for 60.1% and 39.9%, respectively. The mean total fluid intake (TFI) was 1970 mL, with plain water being the primary contributor (68.7%, r = 0.896). Among the participants, 66.7% (n = 14, Group 1) met the TWI recommendation set by the Chinese Nutrition Society. Further analysis revealed that the TFI, water from beverages and foods, plain water, and milk and milk derivatives (MMDs) were significantly higher in Group 1 than those who did not reach the adequate intake value (Group 2) (p < 0.05). The results of hydration biomarkers showed that the mean 24 h urine volume in Group 1 was significantly higher than that in Group 2 (p < 0.05), while the 24 h urine osmolality, sodium, magnesium, phosphorus, chloride, and creatinine concentrations in Group 1 were significantly lower than those in Group 2 (p < 0.05). However, no significant differences were observed in serum biomarkers. Partial correlation analysis showed that TWI was moderately positively correlated with 24 h urine volume (r = 0.675) and negatively correlated with urine osmolality, sodium, potassium, magnesium, calcium, phosphorus, and chloride concentrations (r = from-0.505 to -0.769), but it was not significantly correlated with serum biomarkers. Therefore, under free-living conditions, increasing the daily intake of plain water and MMDs is beneficial for pregnant women to maintain optimal hydration. The hydration biomarkers in urine are more accurate indicators of water intake and exhibit greater sensitivity compared to serum biomarkers. These findings provide a scientific basis for establishing appropriate water intake and hydration status for pregnant women in China.