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Whereas urinary creatinine excretion (UCE) is an established marker of muscle mass, both in critically ill and non-critically ill patients, analysis of urinary urea excretion (UUE) may allow estimation of proteolysis that is associated with critical illness. We evaluated the time courses of plasma urea and creatinine as well UUE and UCE in critically ill patients with a prolonged ICU stay. Our goal was to evaluate changes in plasma urea and creatinine in conjunction with their urinary excretion, to get a better understanding of urea handling in ICU patients. From 2002 to 2021, plasma urea and creatinine, UUE and UCE were determined in routinely obtained 24 h urine samples between ICU admission and day 30, in adult patients with an ICU-stay ≥ 28d. Urea-to-creatinine ratios in plasma and urine were calculated. Patients with stage 3 acute kidney injury (AKI) were excluded. Analyses were performed separately for females and males and for patients with and without acute renal failure to account for respectively differences in muscle mass and impaired renal function. Of 47,120 patients, who were admitted to the ICU between 2002 and 2021, 638 patients met the inclusion criteria. During the first 10 days mean ± SD plasma urea increased from 9.7 ± 6.0 mmol/L at ICU admission to 12.4 ± 7.9 mmol/L (P < 0.001) on day 11 and decreased afterwards with a rate of 0.1 mmol/l/d. UUE peaked at 590 ± 317 mmol/day on day 13 whereas UCE peaked already on day 4. Males had higher plasma urea, plasma creatinine, UUE and UCE than females. Plasma and urinary urea-to-creatinine ratio (UCR) stabilized after day 7, with a gradual increase in plasma UCR and urinary UCR between day 7 and day 30. Similar courses, although less pronounced, were seen in patients without AKI. The course of urea in critically ill patients is characterized by an initial rise of both plasma urea and urinary urea excretion, presumably due to increased catabolism of endogenous and exogenous protein in the first week of ICU admission. Subsequently, UUE and UCE declined steadily in a rate that was comparable to the known loss of muscle mass during ICU admission of approximately 1%/day., (© 2024. The Author(s).)

Healthcare has undergone a revolutionary shift with the advent of smart technologies, and smart toilets (STs) are among the innovative inventions offering non-invasive continuous health monitoring. The present technical challenges toward this development include limited sensitivity of integrated sensors, poor stability, slow response and the requirement external energy supply alongside manual sample collection. In this article, triboelectric nanosensor array (TENSA) is introduced featuring electrodes crafted from laser-induced 3D graphene with functional polymers like polystyrene, polyimide, and polycaprolactone for real-time urine analysis while generating 50 volts output via urine droplet-based triboelectrification. Though modulating interfacial double-layer capacitance, these sensors exhibit exceptional sensitivity and selectivity in detecting a broad spectrum of urinary biomarkers, including ions, glucose, and urea with a classification precision of 95% and concentration identification accuracy of up to 0.97 (R 2 ), supported by artificial neural networks. Upon exposure to urine samples containing elevated levels of Na + , K + , and NH 4 + , a notable decrease (ranging from 32% to 68%) is observed in output voltages. Conversely, urea induces an increase up to 13%. Experimental validation confirms the stability, robustness, reliability, and reproducibility of TENSA, representing a significant advancement in healthcare technology, offering the potential for improved disease management and prevention strategies., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Urine output and urinary urea-N excretion (UUN e ) 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: (1) to compare estimates of UUN e , urine output, and related variables from 3 pre-established measurement protocols (bladder catheterization, external collection cup, and spot sampling) and from dietary salt supplementation, (2) to study temporal variation in UUN e , urine output, and related variables as affected by measurement protocol, and (3) 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 (DM basis) and then assigned to a sequence of 3 protocols (subplot) 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 BW, measured urinary creatinine concentration, and the assumed creatinine excretion of 29 mg/kg BW per day 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 UUN e (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 BW per day) than the value of 29 mg/kg BW per day 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 R 2 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 UUN e , but UUN e 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., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Differentiating between intrinsic and prerenal acute kidney injury (AKI) presents a challenge. Here, we assessed the performance of the fractional excretion of urea (FEUrea) and compared it to the fractional excretion of sodium (FENa) in distinguishing intrinsic from prerenal AKI., Methods: A thorough search was conducted in several databases until January 16, 2024. We included studies evaluating FEUrea, with or without FENa, for differentiating AKI etiologies in adults. We assessed the methodological quality using the QUADAS-2 and QUADAS-C tools. We performed a meta-analysis using the bivariate random effects model, with subgroup analyses to explore the impact of diuretic therapy on FEUrea, and direct statistical comparisons between FEUrea and FENa involving the subgroups with and without diuretics., Results: We included 11 studies with 1108 hospitalized patients. Among eight studies (915 patients) evaluating FEUrea >35% for distinguishing intrinsic from prerenal AKI, the pooled sensitivity and specificity were 66% (95% CI, 49%-79%) and 75% (95% CI, 60%-85%), respectively. In a subset of six studies (302 patients) comparing FEUrea at 35% to FENa at 1% in patients not receiving diuretics, there were no significant differences in sensitivity (77% versus 89%, P = 0.410) or specificity (80% versus 79%, P = 0.956). In four studies, 244 patients on diuretics, FEUrea demonstrated lower sensitivity (52% versus 92%, P < 0.001) but higher specificity (82% versus 44%, P < 0.001) compared to FENa for the diagnosis of intrinsic AKI., Conclusions: FEUrea has limited utility in differentiating intrinsic from prerenal AKI. FEUrea does not provide a superior alternative to FENa, even in patients receiving diuretics., Competing Interests: Declaration of competing interest All authors have nothing to disclose., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Four-dimensional printing (4DP) technologies are revolutionizing the fabrication, functionality, and applicability of stimuli-responsive analytical devices. More practically, 4DP technologies are effective in fabricating devices with complex geometric designs and functions, and the degree of shape programming of 4D-printed stimuli-responsive devices can be optimized to become a reliable analytical strategy. Although shape-programming modes play a critical role in determining the analytical characteristics of 4D-printed stimuli-responsive sensing devices, the effect of shape-programming modes on the analytical performance of 4D-printed stimuli-responsive devices remains an unexplored subject. We employed digital light processing three-dimensional printing (3DP) with acrylate-based photocurable resins and 2-carboxyethyl acrylate (CEA)-incorporated photocurable resins for 4DP of the bending, helixing, and twisting needles. Upon immersion in samples with pH values above the pK a of CEA, the electrostatic repulsion among the dissociated carboxyl groups of polyCEA caused swelling of the CEA-incorporated part and [H + ]-dependent shape programming. When coupling with the derivatization reaction of the urease-mediated hydrolysis of urea, the decline in [H + ] induced shape programming of the needles, offering reliable determination of urea based on the shape-programming angles. After optimizing the experimental conditions, the helixing needles provided the best analytical performance, with the method's detection limit of 0.9 μM. The reliability of this analytical method was validated by determining urea in samples of human urine and sweat, fetal bovine serum, and rat plasma with spike analyses and comparing these results with those obtained from a commercial assay kit. Our demonstration and analytical results suggest the importance of optimizing the shape-programming modes to improve the analytical performance of 4D-printed stimuli-responsive shape-programming sensing devices and emphasize the benefits and applicability of 4DP technologies in advancing the development and fabrication of stimuli-responsive sensing devices for chemical sensing and quantitative chemical analyses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Fractional excretion of urea nitrogen (FEUN), used to differentiate the cause of acute kidney injury, has emerged as a useful fluid index in patients with heart failure (HF). We hypothesized that FEUN could be useful in identifying worsening renal function (WRF) associated with poor outcomes in patients with acute HF (AHF)., Methods and Results: Overall, 1103 patients with AHF (median age, 78 years; male proportion, 60%) were categorized into six groups according to the presence of WRF and FEUN values (low, ≤32.1%; medium, >32.1% and ≤38.0%; and high, >38.0%) at discharge. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level from admission to discharge. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). The cut-off values for low, medium, and high FEUN were based on a previous study. The primary outcome of this study was HF readmission after hospital discharge. During the 1 year follow-up, 170 HF readmissions occurred. Kaplan-Meier analysis revealed significantly higher HF readmission rates in patients with WRF than in those without WRF (log-rank test, P < 0.001). Additionally, among patients with WRF, HF readmission rates were lowest in those with medium FEUN values, followed by those with low FEUN values and those with high FEUN values. On multivariable analysis, the presence of WRF with low or high FEUN values was independently associated with increased HF readmission, as compared with the absence of WRF with medium FEUN values. Notably, no association was noted between WRF with medium FEUN values and HF readmission., Conclusions: The prognostic impact of WRF was significantly mediated by the FEUN values and was associated with worse outcomes only when the FEUN values were either low or high. Our study suggests that FEUN can identify prognostically relevant WRF in patients with AHF., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

We present the development and validation of an impedance-based urine osmometer for accurate and portable measurement of urine osmolality. The urine osmolality of a urine sample can be estimated by determining the concentrations of the conductive solutes and urea, which make up approximately 94% of the urine composition. Our method utilizes impedance measurements to determine the conductive solutes and urea after hydrolysis with urease enzyme. We built an impedance model using sodium chloride (NaCl) and urea at various known concentrations. In this work, we validated the accuracy of the impedance-based urine osmometer by developing a proof-of-concept first prototype and an integrated urine dipstick second prototype, where both prototypes exhibit an average accuracy of 95.5 ± 2.4% and 89.9 ± 9.1%, respectively in comparison to a clinical freezing point osmometer in the hospital laboratory. While the integrated dipstick design exhibited a slightly lower accuracy than the first prototype, it eliminated the need for pre-mixing or manual pipetting. Impedance calibration curves for conductive and non-conductive solutes consistently yielded results for NaCl but underscored challenges in achieving uniform urease enzyme coating on the dipstick. We also investigated the impact of storing urine at room temperature for 24 hours, demonstrating negligible differences in osmolality values. Overall, our impedance-based urine osmometer presents a promising tool for point-of-care urine osmolality measurements, addressing the demand for a portable, accurate, and user-friendly device with potential applications in clinical and home settings.

The human urine metabolome is complex, containing a wide range of organic metabolites that affect treatment of urine collected in resource-oriented sanitation systems. In this study, an advanced oxidation process involving heat-activated peroxydisulphate was used to selectively oxidise organic metabolites in urine over urea and chloride. Initial experiments evaluated optimal conditions (peroxydisulphate dose, temperature, time, pH) for activation of peroxydisulphate in unconcentrated, non-hydrolysed synthetic urine and real urine acidified to pH 3.0. Subsequent experiments determined the fate of 268 endogenous organic metabolites (OMs) and removal of COD from unconcentrated and concentrated real urine (80-90% mass reduced by evaporation). The results revealed >90% activation of 60 mM peroxydisulphate in real unconcentrated urine heated to 90 °C for 1 h, resulting in 43% ΣOMs degradation, 22% COD removal and 56% total organic carbon removal, while >94% of total nitrogen and >97% of urea in real unconcentrated urine were recovered. The mechanism of urea degradation was identified to be chemical hydrolysis to ammonia, with the rate constant for this reaction determined to be 1.9 × 10 -6 s -1 at pH 3.0 and 90 °C. Treating concentrated real urine resulted in similar removal of COD, ΣOMs degradation and total nitrogen loss as observed for unconcentrated urine, but with significantly higher chloride oxidation and chemical hydrolysis of urea. Targeted metabolomic analysis revealed that peroxydisulphate treatment degraded 157 organic metabolites in urine, of which 67 metabolites were degraded by >80%. The rate constant for the reaction of sulphate radicals with oxidisable endogenous organic metabolites in urine was estimated to exceed 10 8 M -1 s -1 . These metabolites were preferentially oxidised over chloride and urea in acidified, non-hydrolysed urine treated with peroxydisulphate. Overall, the findings support the development of emerging urine recycling technologies, including alkaline/acid dehydration and reverse osmosis, where the presence of endogenous organic urine metabolites significantly influences treatment parameters such as energy demand and product purity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prithvi Simha reports financial support was provided by Stiftelsen Lantbruksforskning. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Maintenance of euvolaemia with diuretics is critical in heart failure (HF) patients with chronic kidney disease (CKD); however, it is challenging because no reliable marker of volume status exists. Fractional excretion of urea nitrogen (FEUN) is a useful index of volume status in patients with renal failure. We aimed to examine whether FEUN is a surrogate marker of volume status for risk stratification in HF patients with CKD., Methods and Results: We examined 516 HF patients with CKD (defined as discharge estimated glomerular filtration rate < 60 mL/min/1.73 m 2 ) whose FEUN was measured at discharge (median age, 80 years; 58% male). The patients were divided into four groups according to quartile FEUN value at discharge: low-FEUN, FEUN ≤ 32.1; medium-FEUN, 32.1 < FEUN ≤ 38.0; high-FEUN, 38.0 < FEUN ≤ 43.7; and extremely-high-FEUN, FEUN > 43.7. FEUN was calculated by the following formula: (urinary urea × serum creatinine) × 100/(serum urea × urinary creatinine). During the 3 year follow-up, 131 HF readmissions occurred. Kaplan-Meier analysis showed that the HF readmission rate was significantly lower in the medium-FEUN group than in the other three groups (log-rank test, P = 0.029). Multivariate Cox regression analysis identified the low-FEUN, high-FEUN, and extremely-high-FEUN values as independent factors associated with post-discharge HF readmission. In the analysis of 130 patients who underwent right heart catheterization during hospitalization, a significant correlation between FEUN value and right atrial pressure was observed (R = 0.243, P = 0.005). Multivariate linear regression analysis revealed that FEUN value at discharge decreased in a dose-dependent manner with loop diuretics., Conclusions: In HF patients with CKD, FEUN is a potential marker of volume status for risk stratification of post-discharge HF readmission. Low FEUN value (FEUN ≤ 32.1) may represent intravascular dehydration, whereas high FEUN value (FEUN > 38.0) may represent residual congestion; both of them were independent risk factors for HF readmission. FEUN may be useful to determine euvolaemia and guide fluid management in HF patients with CKD., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: The aim of this research was to develop a simple equation to evaluate dietary protein intake (DPI) in patients with stage 3 chronic kidney disease (CKD) using the blood urea nitrogen (BUN)/serum creatinine (SCr) ratio (BUN/SCr)., Methods: In a prospective cohort of 136 inpatients with stage 3 CKD from 2 centres, the estimated dietary protein intake (DPI) was calculated using Maroni's formula after the patients implemented a 7 day protein-restricted diet. We developed estimation equations based on BUN/SCr and the spot urinary urea nitrogen (UUN)/urinary creatinine (UCr) ratio (UUN/UCr) in combination with sex and body mass index (BMI). These equations were then internally and externally validated., Results: The following candidate parameters were derived from univariate regression analysis for 5 established models: sex, BMI, BUN/SCr, UUN and UUN/UCr. Sex and BMI were included in all models after variable evaluation using multiple regression analysis. UUN, UUN/UCr and BUN/SCr were included in model 3, model 4 and model 5, respectively. Both internal and external validation indicated that model 5 resulted in the lowest values for bias and root mean square error and the highest P 30 compared with model 3 and model 4. Therefore, the model 5 equation, DPI =  - 5.18 (- 14.49 if the patient is female) + 1.89 × BMI + 1.38 × BUN/SCr, was selected because of the higher correlation (r = 0.498) between the estimated DPI and predicted DPI., Conclusion: The DPI equation developed using BUN/SCr, sex and BMI may be used to estimate protein intake for patients with stage 3 CKD., Trial Registration: Chinese Clinical Trial Registry Center (ChiCTR-ROC-17011363). Registered on 11 May 2017, Retrospectively registered, http://www.chictr.org.cn/index.aspx ., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: It has been suggested that, in patients with CKD stage 5, measured GFR (mGFR), defined as the mean of urea and creatinine clearance, as measured by a 24-h urine collection, is a better measure of renal function than estimated GFR (eGFR), based on the CKD-EPI formula. This could be due to reduced muscle mass in this group. Its use is recommended in the ERBP guidelines. Unplanned dialysis initiation (DI) is associated with increased morbidity, mortality, and reduced modality choice and is generally considered undesirable. We hypothesized that the ratio mGFR/eGFR (M/E) aids prediction of death and DI., Methods: All 24-h measurements of urea and creatinine excretion were extracted from the clinical biochemistry databases in Zealand. Data concerning renal diagnosis, comorbidity, biochemistry, medical treatment, mortality and date of DI, were extracted from patient notes, the National Patient Registry and the Danish Nephrology Registry. Patients were included if their eGFR was < 30 ml/min/1.73m 2 . The last available value for each patient was included. Follow-up was 12 months., Results: One thousand two hundred sixty-five patients were included. M/E was median 0.91 ± 0.43. It was highly correlated to previous determinations. It was negatively correlated to eGFR, comorbidity, high age and female sex. It was positively related to albumin and negatively to C-reactive protein. M/E was higher in patients treated with ACE inhibitors and diuretics but no other treatment groups. On a multivariate analysis, M/E was negatively correlated with mortality and combined mortality/DI, but not DI. A post hoc analysis showed a negative correlation to DI at 3 months. For patients with an eGFR 10-15 ml/min/1.73m 2 , combined mortality and DI at 3 months was for low M/E (< 0.75) 36%, medium (0.75-1.25) 20%, high (> 1.25) 8%. A low M/E predicted increased need for unplanned DI. A supplementary analysis in 519 patients where body surface area values were available, allowing BSA-corrected M/E to be analyzed, revealed similar results., Conclusion: A low mGFR/eGFR ratio is associated with comorbidity, malnutrition, and inflammation. It is a marker of early DI, mortality, and unplanned dialysis initiation, independently of eGFR, age and comorbidity. Particular attention paid to patients with a low M/E may lower the incidence of unplanned dialysis requirement., (© 2021. The Author(s).)

This study aimed to investigate the effects of blood glucose control and the kidneys' functions, depending on fasting, in the streptozotocin-induced diabetes model in rats via TNF-α, NLRP-3, TGF-β1 and VCAM-1 mRNA expression in the present study. 32 Wistar albino rats were allocated randomly into four main groups; H (Healthy, n = 6), HF (Healthy fasting, n = 6), D (Diabetes, n = 10), DF (Diabetes and fasting, n = 10). Blood glucose and HbA1c levels significantly increased in the D group compared to the healthy ones (p < 0.05). However, the fasting period significantly improved blood glucose and HbA1c levels 14 days after STZ induced diabetes in rats compared to the D group. Similar findings we obtained for serum (BUN-creatinine) and urine samples (creatinine and urea levels). STZ induced high glucose levels significantly up-regulated TNF-α, NLRP-3, TGF-β1 and VCAM-1 mRNA expression and fasting significantly decreased these parameters when compared to diabetic rats. Histopathological staining also demonstrated the protective effects of fasting on diabetic kidney tissue. In conclusion, intermittent fasting regulated blood glucose level as well as decreasing harmful effects of diabetes on kidney tissue. The fasting period significantly decreased the hyperglycemia-related inflammatory cytokine damage on kidneys and also reduced apoptosis in favor of living organisms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: Accurate and precise estimation of glomerular filtration rate (GFR) is essential in kidney disease. We evaluated the usefulness of the mean of creatinine clearance (C Cr ) and urea clearance (C UN ) examined over a 1-h urine collection period (1-h (C Cr  + C UN )/2) in a retrospective, cross-sectional study across two centres, as a relatively simple method for estimating GFR in children., Methods: Children aged ≤18 years who underwent inulin clearance (C In ) tests were eligible. Two clearance values were obtained during a 2-h test consisting of two periods of 1 h each. The mean clearance in two periods was defined as 1-h clearance. 1-h (C Cr  + C UN )/2, 1-h C Cr , 1-h C UN and GFR estimated by Cr-based and cystatin C (CysC)-based formulas for Japanese children were compared with C In . Bland-Altman plots were used to evaluate correlations. The primary outcome measure was the correlation between 1-h (C Cr  + C UN )/2 and C In ., Results: Fifty-three children were analysed. Their median age was 10.9 (interquartile range [IQR] 5.3-14.2) years, and median C In and 1-h (C Cr  + C UN )/2 were 77.0 (IQR: 51.5-95.1) and 81.0 (IQR: 64.1-97.7) ml/min/1.73 m 2 , respectively. Percentage difference of C In and 1-h (C Cr  + C UN )/2 in the Bland-Altman plot was -11.2% (95% confidence interval - 15.3% - -7.1%), with 95% lower and upper limits of agreement of -40.3% and 18.0%, respectively. Thus, 1-h (C Cr  + C UN )/2 was 1.12 times C In ., Conclusion: 1 h (C Cr  + C UN )/2 was almost concordant with C In . 1-h (C Cr  + C UN )/2 can estimate GFR accurately and precisely, making it a simple and speedy test for use in clinical practice., (© 2021 Asian Pacific Society of Nephrology.)

Background Maintaining euvolemia is crucial for improving prognosis in acute decompensated heart failure (ADHF). Although fractional excretion of urea nitrogen (FEUN) is used as a body fluid volume index in patients with acute kidney injury, the clinical impact of FEUN in patients with ADHF remains unclear. This study aimed to investigate whether FEUN can determine the long-term prognosis in patients with ADHF. Methods and Results We retrospectively identified 466 patients with ADHF who had FEUN measured at discharge between April 2011 and December 2018. The primary endpoint was post-discharge all-cause death. Patients were divided into two groups according to a FEUN cut-off value of 35%, commonly used in pre-renal failure. The FEUN <35% (low-FEUN) group included 224 patients (48.1%), and the all-cause mortality rate for the total cohort was 37.1%. The log-rank test revealed that the low-FEUN group had a significantly higher rate of all-cause death compared to the FEUN equal to or greater than 35% (high-FEUN) group ( P <0.001). Multivariate Cox proportional hazards model analysis revealed that low-FEUN was associated with post-discharge all-cause death, independently of other heart failure risk factors (hazard ratio, 1.467; 95% CI, 1.030-2.088, P =0.033). The risk of low-FEUN compared to high-FEUN in post-discharge all-cause death was consistent across all subgroups; however, the effects tended to be modified by renal function (threshold: 60 mL/min/1.73 m 2 , interaction P =0.069). Conclusions Our study suggests that FEUN may be a novel surrogate marker of volume status in patients with ADHF requiring diuretics.

To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) for investigating the effect of dietary treatment and fluid intake on the prevention of recurrent calcium stones and changes in urine composition. PubMed, Web of Science, Embase, EBSCO, and Cochrane Library databases (updated November 2020) were searched for studies with the following keywords: diet, fluid, recurrent, prevention, randomized controlled trials, and nephrolithiasis. The search strategy and study selection process was conducted by following the PRISMA statement. Six RCTs were identified for satisfying the inclusion criteria and enrolled in this meta-analysis. Our result showed that low protein with or without high fiber diet intervention does not decrease the recurrence of stone upon comparing with control groups (RR = 2.32, 95% CI = 0.42-12.85; P = 0.34) with significant heterogeneity among the studies (I2 = 81%, P = 0.02). But normal-calcium, low protein, low-salt diet had recurrences did reduced the recurrence compared to normal-calcium diet. And the fluid intake has a positive effect on prevention of recurrent stone formation (RR = 0.39, 95% CI = 0.19-0.80; P = 0.01) with insignificant heterogeneity among the studies (I2 = 9%, P = 0.30). The different components of urine at baseline were reported in four studies. Upon reviewing the low protein with or without high fiber dietary therapy groups, it was found that there were no obvious changes in the 24-hour urine sodium, calcium, citrate, urea, and sulfate. In conclusion, our study shows that the only low protein with or without fiber does not affect recurrence, but low Na, normal Ca diet has a marked effect on reducing recurrence of calcium stone. And fluid intake shows a significant reduction in the recurrence of calcium stone., Competing Interests: No authors have competing interests.

The prostate-specific membrane antigen (PSMA) is considered to be an excellent theranostic target of prostate cancer (PCa). In this study, three 18 F-labeled PSMA tracers with a more lipophilic quinoline functional spacer were designed, synthesized, and evaluated based on the Glu-Ureido-Lys binding motif. The effect of structure-related lipophilic difference on distribution and excretion of these tracers in vitro and in vivo (cells, rodent, primate, and human) was investigated by comparing with [ 18 F]DCFPyL. There is no significant correlation between the renal elimination and the lipophilicity of the tracers in all species. However, the higher the lipophilicity of tracer, the higher the radioactivity accumulation in the liver of primate and human, and the less radioactivity is to excrete to the bladder with urine. The screened tracer [ 18 F] 8c , with a K i value of 4.58 nM, displayed notable low bladder retention and demonstrated good imaging properties in patients with PCa.

A fluorescence platform is designed based on aggregation-induced emission of Au/Cu nanoclusters (Au/Cu NCs) driven by pH value. When pH increases from 6.0 to 7.0, Au/Cu NCs change from aggregation to dispersion, accompanied by the oxidation of Cu cores. Under the catalysis of urease, urea is hydrolysed to release ammonia, which further undergoes a hydrolysis reaction to produce OH - , causing the pH to increase. The fluorescence of Au/Cu NCs quenches linearly at 590 nm with the excitation wavelength at 320 nm when the concentration of urea varies from 5.0 to 100 μM. The limit of detection (LOD) and limit of quantification (LOQ) of urea are 2.23 and 7.45 μM, respectively. Combined with headspace single-drop microextraction technology, Au/Cu NCs are employed to monitor dissolved ammonia with low-cost and simple operation. The linear range of dissolved ammonia is from 20 to 300 μM. The LOD and LOQ of dissolved ammonia are 7.04 and 23.4 μM, respectively. The relative standard deviation (RSD) values of the intra-day and inter-day precision of urea are 2.4-3.0% and 3.0-3.7%, respectively, and those of dissolved ammonia are in the range 3.4-5.1% (intra-day precision) and 4.2-5.8% (inter-day precision). No interferences have been indentified in the determination of urea and dissolved ammonia. Finally, the proposed method has been applied to determine urea in human urine samples and dissolved ammonia in water samples with satisfactory results.Graphical abstract The pH increase produces the dispersion and decomposition of Au/Cu NCs, leading to the fluorescence quenching. Both urea and dissolved ammonia are detected successfully because they cause the pH change to alkaline.

Perovskite materials have attracted attention due to their excellent optical and electrical properties; however, their unsatisfactory stability limits their application in biochemical detection. In this paper, CsPbBr 3 perovskite quantum dots were successfully encapsulated in poly(styrene/acrylamide) microspheres, using a swelling-shrinking method. The manufactured perovskite microspheres (PDPS composites) not only maintained strong photoluminescence (PL) stability but also demonstrated great water solubility. Additionally, a real-time pH monitoring platform was constructed based on the prepared PDPS composites and dopamine, and the system showed a good linear relationship in a pH range of 4-12. Furthermore, urea could be hydrolyzed to produce hydroxyl groups, thereby increasing the pH of the solution. Therefore, this system was then extended for urea and urease detection. As a result, the detection limits of urea and urease were recorded as 1.67 μM and 2.1 mU/mL, respectively. This development provides an interesting demonstration of the expanding list of applications of perovskite materials.

Background and Objectives: Predicting disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) poses a challenge, especially in early-stage disease when kidney function is not yet affected. Ongoing growth of cysts causes maximal urine-concentrating capacity to decrease from early on. We therefore hypothesized that the urine-to-plasma urea ratio, as a reflection of the urine-concentrating capacity, can be used as a marker to predict ADPKD progression., Design: The urine-to-plasma urea ratio was calculated by dividing concentrations of early morning fasting spot urine urea by plasma urea. First, this ratio was validated as surrogate marker in 30 patients with ADPKD who underwent a prolonged water deprivation test. Thereafter, association with kidney outcome was evaluated in 583 patients with ADPKD with a broad range of kidney function. Multivariable mixed-model regression was used to assess association with eGFR slope, and logarithmic regression to identify patients with rapidly progressive disease, using a cutoff of -3.0 ml/min per 1.73 m 2 per year. The urine-to-plasma urea ratio was compared with established predictors, namely, sex, age, baseline eGFR, Mayo Clinic height-adjusted total kidney volume class, and PKD gene mutation., Results: The maximal urine-concentrating capacity and urine-to-plasma urea ratio correlated strongly ( R =0.90; P <0.001). Next, the urine-to-plasma urea ratio was significantly associated with rate of eGFR decline during a median follow-up of 4.0 (interquartile range, 2.6-5.0) years, both crude and after correction for established predictors ( β =0.58; P =0.02). The odds ratio of rapidly progressive disease was 1.35 (95% confidence interval, 1.19 to 1.52; P <0.001) for every 10 units decrease in urine-to-plasma urea ratio, with adjustment for predictors. A combined risk score of the urine-to-plasma urea ratio, Mayo Clinic height-adjusted total kidney volume class, and PKD mutation predicted rapidly progressive disease better than each of the predictors separately., Conclusions: The urine-to-plasma urea ratio, which is calculated from routine laboratory measurements, predicts disease progression in ADPKD in addition to other risk markers., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021&#95;01&#95;27&#95;CJN10470620&#95;final.mp3., (Copyright © 2021 by the American Society of Nephrology.)

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.

In chronic kidney disease (CKD) patients, it would be desirable to reduce the intake of inorganic phosphate (P) rather than limit the intake of P contained in proteins. Urinary excretion of P should reflect intestinal absorption of P(inorganic plus protein-derived). The aim of the present study is to determine whether the ratio of urinary P to urinary urea nitrogen (P/UUN ratio) helps identify patients with a high intake of inorganic P.A cross-sectional study was performed in 71 patients affected by metabolic syndrome with CKD (stages 2-3) with normal serum P concentration. A 3-day dietary survey was performed to estimate the average daily amount and the source of P ingested. The daily intake ofPwas1086.5 ± 361.3mg/day; 64% contained in animal proteins, 22% in vegetable proteins, and 14% as inorganic P. The total amount of P ingested did not correlate with daily phosphaturia, but it did correlate with the P/UUN ratio ( p < 0.018). Patients with the highest tertile of the P/UUN ratio >71.1 mg/g presented more abundant inorganic P intake ( p < 0.038).The P/UUN ratio is suggested to be a marker of inorganic P intake. This finding might be useful in clinical practices to identify the source of dietary P and to make personalized dietary recommendations directed to reduce inorganic P intake.

Background: The initial once-weekly administration of incremental hemodialysis to patients with residual kidney function (RKF) has recently attracted considerable interest., Methods: The aim of our study was to assess the performance of a series of different methods in measuring serum urea nitrogen and serum Cr (sCr) RKF in patients on once-weekly hemodialysis (1WHD). Evaluations were carried out by means of 24-h predialysis urine collection (Kr-24H) or 6-day inter-dialysis collection (Kr-IDI) and estimation of glomerular filtration rate based on (KrSUN + KrsCr)/2 for the purpose of identifying a simple reference calculation to be used in assessing RKF in patients on 1WHD dialysis. Ninety-five urine samples were collected from 12 1WHD patients. A solute solver urea and Cr kinetic modeling program was used to calculate residual urea and Cr clearances. Mann-Whitney U test, Pearson's correlation coefficient (R), and linear determination coefficient (R2) were used for statistical analysis., Results: 1WHD patients displayed a mean KrSUN-IDI of 4.5 ± 1.2 mL/min, while KrSUN-24H corresponded to 4.1 ± 0.9 mL/min, mean KrsCr-IDI to 9.1 ± 4.0 mL/min, and KrsCr 24H to 8.9 ± 4.2 mL/min, with a high regression between IDI and 24-h clearances (for IDI had R2 = 0.9149 and for 24H had R2 = 0.9595). A good correlation was also observed between KrSUN-24H and (KrSUN + KrsCR/2) (R2 = 0.7466, p < 0.01., Discussion: Urine collection over a 24-h predialysis period yielded similar results for both KrSUN and KrsCr compared to collection over a longer interdialytic interval (KrSUN + KrsCr)/2 could be applied to reliably assess RKF in patients on 1WHD., Conclusion: The parameters evaluated are suitable for use as a routine daily method indicating the commencement and continued use of the 1WHD Incremental Program., (© 2020 S. Karger AG, Basel.)

As one of the main toxic substances in aquaculture water, ammonia causes seriously physiological harm to aquatic animals. In order to investigate the effects of ammonia exposure on the antioxidant defense, immune response, and NF-κB signaling pathway in Chinese Strip-necked Turtle (Mauremys sinensis), we designed two experimental groups (control and 6.45 mM ammonia), and sampled at 6 h, 24 h, 48 h, re 24 h (recover 24 h), and re 48 h. The results showed that the blood ammonia (BA) content was significantly increased when the turtles were subjected to ammonia, and the activities of cholinesterase (CHE) and aspartate aminotransferase (AST) in the serum also showed a significant upward trend. The malondialdehyde (MDA) content continuously increased during ammonia exposure, and more than doubled at 48 h compared with the control group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and their corresponding relative mRNA expression levels in the liver during ammonia exposure were obviously increased when compared to the control group, but most decreased to the normal levels at re 48 h. In addition, the relative mRNA and protein expression levels of NF-E2 related factor 2 (Nrf2) showed similar up-regulation patterns to antioxidase during ammonia exposed periods; whereas kelch-like ECH-binding protein 1 (Keap1), as Nrf2 negative regulator, showed opposite patterns. Moreover, the relative mRNA expression levels of heat shock proteins (HSP70, HSP90) significantly elevated upon the exposure of ammonia. Furthermore, ammonia increased the relative mRNA and protein expression levels of p50 and p65 at different exposed times. The reative mRNA expression levels of immune cytokines (BAFF and IL-6) were upregulated during ammonia exposured time, while there was a decline but did not return to normal levels, in the recovery periods. Taken together, these results indicated that antioxidation, immunity, and NF-κB signaling played a certain protective role for Mauremys sinensis under ammonia exposure. Our results will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in turtles., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A system for sorbent-assisted peritoneal dialysis (SAPD) has been developed that continuously recirculates dialysate via a tidal mode using a single-lumen peritoneal catheter with the regeneration of spent dialysate by means of sorbents. SAPD treatment may improve plasma clearance by the maintenance of a high plasma-to-dialysate concentration gradient and by increasing the mass transfer area coefficient (MTAC) of solutes. The system is designed for daily 8-hr treatment (12 kg, nighttime system). A wearable system (2.3 kg, daytime system) may further enhance the clearance of phosphate and organic waste solutes during the day. Uremic pigs (n = 3) were treated with the day- (n = 3) and nighttime system (n = 15) for 4-8 hr per treatment. Plasma clearance (Cl), MTAC, and total mass transport (MT) of urea, creatinine, phosphate, and potassium were compared with a static dwell (n = 28). Cl, MTAC, and MT of urea, creatinine, phosphate, and potassium were low in the pig as compared to humans due to the pig's low peritoneal transport status and could be enhanced only to a limited extent by SAPD treatment compared with a static dwell (nighttime system: Cl urea: ×1.5 (p = .029), Cl creatinine: ×1.7 (p = .054), Cl phosphate: ×1.5 (p = .158), Cl potassium: ×1.6 (p = .011); daytime system: Cl creatinine: ×2.7 (p = .040), Cl phosphate: ×2.2 (p = .039)). Sorbent-assisted peritoneal dialysis treatment in a uremic pig model is safe and enhances small solute clearance as compared to a static dwell. Future studies in humans or animal species with higher peritoneal transport should elucidate whether our SAPD system enhances clearance to a clinically relevant extent as compared to conventional PD., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank., Methods: A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure., Results: After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death., Conclusion: We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.

Background: Residual kidney function (RKF) is associated with improved survival and quality of life in dialysis patients. Previous studies have suggested that initiation of peritoneal dialysis (PD) may slow RKF decline compared to the pre-dialysis period. We sought to evaluate the association between PD initiation and RKF decline in the Initiating Dialysis Early And Late (IDEAL) trial., Methods: In this post hoc analysis of the IDEAL randomized controlled trial, PD participants were included if results from 24-hour urine collections had been recorded within 30 days of dialysis initiation, and at least one value pre- and one value post-dialysis commencement were available. The primary outcome was slope of RKF decline, calculated as mean of urinary creatinine and urea clearances. Secondary outcomes included slope of urine volume decline and time from PD initiation to anuria., Results: The study included 151 participants (79 early start, 72 late start). The slope of RKF decline was slower after PD initiation (-2.69±0.18mL/min/1.73m2/yr) compared to before PD (-4.09±0.33mL/min/1.73m2/yr; change in slope +1.19 mL/min/1.73m2/yr, 95%CI 0.48-1.90, p<0.001). In contrast, urine volume decline was faster after PD commencement (-0.74±0.05 L/yr) compared to beforehand (-0.57±0.06L/yr; change in slope -0.18L/yr, 95%CI -0.34--0.01, p = 0.04). No differences were observed between the early- and late-start groups with respect to RKF decline, urine volume decline or time to anuria., Conclusions: Initiation of PD was associated with a slower decline of RKF compared to the pre-dialysis period., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: YC reports personal fees from Baxter, outside the submitted work. CH reports personal fees from Janssen, GlaxoSmithKline and Osuka, and grant support from Baxter, Fresenius, Shire, PKD Aus and NHMRC, outside the submitted work. MGW has received honorarium for scientific lectures from AstraZeneca, Retrophin, Amgen and Baxter, outside the submitted work. His employer, the George Institute for Global Health, holds research contracts for trials in cardiovascular and/or kidney disease with a range of commercial organizations. DJ reports personal fees from AWAK, Astra-Zeneca, Baxter Healthcare and Fresenius Medical Care, and grant support from Baxter Extramural Grant and Baxter CEC Grant, outside the submitted work. The other authors declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To assess the predictive abilities of serum and urinary cystatin C levels for glomerular lesions in pregnant women with pre-eclampsia., Methods: In this study, kidney function markers were compared between38 pregnant women with pre-eclampsia and 22 healthy pregnant women., Results: The serum and urine levels of cystatin C and urea were significantly higher in the pre-eclampsia group than in the control group. Receiver operating characteristic curve analysis demonstrated that the serum cystatin C level (91.7%) had a superior diagnostic accuracy for pre-eclampsia than the other markers., Conclusion: Serum cystatin C level maybe a significant marker of pre-eclampsia.

The aggregates of glutathione-capped CuNCs induced by Al 3+ (named CuNCs@Al 3+ complexes) show a stable aggregation-induced emission (AIE) for about 1 month. Their fluorescence maintains a high level in the pH range 4.0 to 7.0, while it quenches as pH increases from 7.0 to 7.7 or decreases from 4.0 to 3.0. Under urease-catalyzed hydrolysis, urea produces ammonia, which can be further hydrolyzed to yield OH - . This leads to a pH increase of the immediate environment. Hence, the CuNCs@Al 3+ complexes are a suitable probe to determine urea. The fluorescence of CuNCs@Al 3+ complexes quenches linearly at 585 nm with the excitation wavelength at 340 nm when the concentration of urea increases from 20 to 150 μM. The limit of detection (LOD) of urea is 5.86 μM. This sensitivity is superior to other reported works due to the narrow pH response range of CuNCs@Al 3+ complexes. This method has been successfully applied for measuring urea in human urine samples with satisfactory recoveries. Graphic abstract Schematic representation of urea determination based on pH-responsive property of copper nanoclusters@Al 3+ complexes. Ammonia is produced in the hydrolysis of urea by urease, and it is further hydrolyzed to yield OH - , leading to increasing pH of the environment.

Background and Objectives: Dehydration might be an issue after hip fracture surgery, but the optimal tools to identify the dehydrated condition have not been determined. The aim of the present study was to compare the characteristics of elderly postoperative patients who were classified as dehydrated according to the methods used in the clinic. Materials and Methods: Thirty-eight patients aged between 65 and 97 (mean, 82) years were studied after being admitted to a geriatric department for rehabilitation after hip fracture surgery. Each patient underwent blood analyses, urine sampling, and clinical examinations. Results: Patients ingested a mean of 1,008 mL (standard deviation, 309 mL) of fluid during their first day at the clinic. Serum osmolality increased significantly with the plasma concentrations of sodium, creatinine, and urea. Seven patients had high serum osmolality (≥300 mosmol/kg) that correlated with the presence of tongue furrows ( p < 0.04), poor skin turgor ( p < 0.03), and pronounced albuminuria ( p < 0.03). Eight patients had concentrated urine (urine-specific gravity ≥ 1.025) that correlated with a low intake of liquid and with a decrease in body weight during the past month of -3.0 kg (25-75 th percentiles, -5.1 to -0.9) versus +0.2 (-1.9 to +2.7) kg ( p < 0.04). Conclusions: Renal fluid conservation of water, either in the form of hyperosmolality or concentrated urine, was found in 40% of the patients after hip fracture surgery. Hyperosmolality might not indicate a more severe fluid deficit than is indicated by concentrated urine but suggests an impaired ability to concentrate the urine.

Datura metel is traditionally used as a remedy for renal toxicity. However, the nephroprotection has not been scientifically validated yet. To evaluate the nephroprotective like effect of methanolic extract of D. metel in gentamicin induced mice model, mice of either sex were divided into groups. One group received normal saline as negative control. The 2nd group received gentamicin 100mg/kg for 8 days as positive control, 3rd group received 50mg/kg silymarin as standard, while the reaming groups received 100, 200 and 300 mg/kg of MEDM and gentamicin 100mg/kg, for 8 days. The blood and urine samples were collected on 9th day, animals were then dissected and whole kidneys were removed and preserved in formalin for later histological examinations. The level of serum creatinine, blood urea nitrogen, urine creatinine and urine urea were significantly (P&lt;0.05) elevated and the renal MDA level was also elevated significantly (P&lt;0.05) by gentamicin in mice. After the treatment of test animals with MEDM, the elevated level of serum and urine biomarkers by gentamicin were reversed by MEDM. The nephroprotective effect was found in dose dependent manner. As the MEDM significantly protected the nephrotoxicity via its antioxidant effect. The findings of our study thus proved the scientific background for the nephroprotective effect of MEDM.

In this study, we hypothesized that spot urine can be used to predict protein intake at both group and individual levels. Participants (n = 369) of this study were recruited from all 47 prefectures in Japan. Sex-specific formulas were developed based on the ratio of urea nitrogen to creatinine concentration obtained from 3 spot urine samples. Validity of the formulas was examined against two 24-hour urine collections for 7 combinations of spot urine (single and means of 2 or 3 samples) using t test (mean estimation), Spearman correlation, and Bland-Altman plot (individual bias). Means of measured protein intake based on 24-hour urinary excretions were 87.3 g/d (standard deviation 19.7) for men and 70.5 g/d (standard deviation 14.7) for women. Irrespective of sex, the predicted intakes were not significantly different (within 2.7% of differences) from those measured by urinary excretions. Predicted intakes were moderately correlated with measured intakes (men, 0.45-0.60; women, 0.35-0.53). Even after using the mean of 3 samples, Bland-Altman plots showed a considerably wide limit of agreement (men, -30 to 33 g/d; women, -27 to 24 g/d). Except for using single spot urine samples in women, the formula tended to overestimate intake at a lower and underestimate at a higher level of protein intake (slope: men, -0.47 [P < .0001]; women, -0.38 [P = .002]). In conclusion, predictive formulas developed in this study can be used to predict protein intake at group level or to rank individuals' intake but not to predict absolute intake at individual level., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The current study was aimed at exploring the protective efficacy of spirulina against the hemato-biochemical alterations and nephrotoxicity induced by lead (Pb). Female rats aged 12 weeks were treated for 4 weeks with Pb (0.344 g kg -1 bw) associated or not with spirulina (5.3 g kg -1 bw). Renal damage induced by Pb was related to a severe anemia, increases of oxidative stress-related parameters (thiobarbituric acid reactive substances (TBARS) (+29%), protein carbonyl (PCO) (+66.3%), and advanced oxidation protein product (AOPP) (+110%)), plasma lactate dehydrogenase (LDH) (+80%), creatinine and urea levels in plasma, and uric acid concentration in urine, as well as genotoxic changes (+89.3% and +60% for DNA and mRNA levels, respectively). Conversely, LDH and antioxidant enzyme activities in kidney were decreased, as well as the levels of plasma uric acid, and urinary creatinine and urea levels. Spirulina-supplemented rats exhibited normal peripheral blood and renal parameters and renal histology. It can be suggested that Arthrospira platensis alleviates damages induced by Pb, thanks to its high phenolic content and antioxidant capacity.

Do kidney osmolytes counteract the deleterious effects of urea on kidney proteins? To answer this question, we measured guanidinium chloride (GdmCl)-induced denaturation of triose phosphate isomerase-β-globin subunit complex (TIM-β-globin) from sheep kidney in the presence of various concentrations of urea and each of kidney osmolytes (glycine betaine, myo-inositol and sorbitol) alone and in combination at pH 7.5 and 25 °C. Analysis of GdmCl-induced denaturation curve at a given osmolyte (or urea) concentration gave ΔG D 0 (Gibbs free energy change in the absence of GdmCl). For a co-solute (CO), a linear plot of ΔΔG D 0 (difference between values of ΔG D 0 in the presence and absence of CO) against [CO] (molar concentration of CO) yielded m-value (=δΔΔG D 0 /δ[CO]). m-value for urea (m urea ) and that for the osmolyte (m osm ) were used to determine [urea]:[osmolyte], the molar ratio for the perfect counteraction of the denaturing effect of urea on the protein stability by an osmolyte. For each osmolyte, we tested this ratio for the perfect counteraction. It was observed that glycine betaine and myo-inositol provide perfect counteraction at the predicted molar ratio whereas sorbitol fails to do so. Furthermore, urea and GdmCl induced a two-state denaturation, and both TIM and β-globin have identical thermodynamic stability., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Objectives: Residual kidney function is important to the health and wellbeing of patients with ESKD. We tested whether the kidney clearances of proximal tubular secretory solutes are associated with burden of uremic and heart failure symptoms among patients on peritoneal dialysis with residual kidney function., Design, Setting, Participants, & Measurements: We enrolled 29 patients on incident peritoneal dialysis with residual urine output >250 ml daily. We used targeted liquid chromatography-mass spectrometry to quantify plasma, 24-hour urine, and peritoneal dialysate concentrations of ten tubular secretory solutes. We calculated the kidney and peritoneal dialysis clearances of each secretory solute, creatinine, and urea, and we estimated a composite kidney and peritoneal secretion score. We assessed for uremic symptoms using the Dialysis Symptom Index and heart failure-related symptoms using the Kansas City Cardiomyopathy Questionnaire. We used linear regression to determine associations of composite secretory solute clearances and GFR urea+Cr with Dialysis Symptom Index symptom score and Kansas City Cardiomyopathy Questionnaire summary score., Results: Mean residual kidney clearances of creatinine and urea were 8±5 and 9±6 ml/min per 1.73 m 2 , respectively, and mean GFR urea+Cr was 8±5 ml/min per 1.73 m 2 . The residual kidney clearances of most secretory solutes were considerably higher than creatinine and urea clearance, and also, they were higher than their respective peritoneal dialysis clearances. After adjustments for age and sex, each SD higher composite kidney secretion score was associated with an 11-point lower Dialysis Symptom Index score (95% confidence interval, -20 to -1; P =0.03) and a 12-point higher Kansas City Cardiomyopathy Questionnaire score (95% confidence interval, 0.5- to 23-point higher score; P =0.04). Composite peritoneal dialysis secretion score was not associated with either symptom assessment., Conclusions: Residual kidney clearances of secretory solutes are higher than peritoneal dialysis clearances. Kidney clearances of secretory solutes are associated with patient-reported uremic and heart failure-related symptoms., (Copyright © 2020 by the American Society of Nephrology.)

Background: Residual kidney function (RKF) provides substantial volume and solute clearance even after dialysis initiation. Preservation of RKF is associated with improved outcomes including mortality in patients on both peritoneal and haemodialysis (HD). Factors predicting RKF loss are unclear, including HD modality. Nocturnal haemodialysis (NHD) may result in less aggressive fluid and solute shifts, however, retrospective data suggests frequent NHD may accelerate RKF decline. The aim of the study was to determine if decline in RKF differs between patients undergoing conventional haemodialysis (CHD) versus NHD., Methods: A prospective observational study of incident HD patients was undertaken comparing patients undertaking CHD (4-5 h, 3 days/week) and NHD (8 h, 3-5 nights/week). Change in RKF was measured by urea and creatinine clearance (48-h interdialytic urine collection) and glomerular filtration rate (GFR) (Cr51-EDTA nuclear scan) at initiation of dialysis (baseline) and 12 months., Results: A total of 18 incident HD patients were recruited (8 CHD, 10 NHD). Three patients withdrew after baseline (n = 15). Baseline RKF was similar between groups with mean nuclear GFR of 13.3 ± 4.1 mL/min in the CHD cohort vs 13.5 ± 4.6 mL/min in the NHD group (p = 0.89). Baseline urine volume was 2399 ± 950 mLs and 2794 ± 1662 mLs in the CHD and NHD, respectively (p = 0.57). Nuclear GFR declined from time 0 to 12 months to 9.3 ± 2.5 mL/min and 10.4 ± 4.3 mL/min in the CHD and NHD, respectively (p = 0.52). There was a significant decline in 48-h urine volume over 12 months with a mean volume of 1943 ± 1087.0 mLs in the CHD compared to 601.7 ± 315.3 mLs in the NHD (p = 0.01). No significant difference was found in other measures of RKF between groups over 12 months., Conclusion: This small prospective cohort study found that the loss of residual urine volume was greater in the NHD vs the CHD cohort but there was no difference in other measures of RKF.

Background: Two consecutive trials were carried out to study the effects of dietary supplementation of rumen-protected methionine (RPM) on nutrient digestibility, nitrogen (N) metabolism (Trial 1), and consequently the nitrous oxide (N 2 O) emissions from urine in beef cattle (Trial 2). Eight 24-month-old castrated Simmental bulls with liveweights of 494 ± 28 kg, and four levels of dietary supplementation of RPM at 0, 10, 20, and 30 g head -1 d -1 , were allocated in a replicated 4 × 4 Latin square for Trial 1 and the N 2 O emissions from the urine samples collected in Trial 1 were measured using a static incubation technique in Trial 2., Results: Supplementation of RPM at 0, 10, 20, and 30 g head -1 d -1 to a basal ration deficient in methionine (Met) did not affect the apparent digestibility of dry matter, organic matter, neutral detergent fiber, or acid detergent fiber (P > 0.05), but decreased the urinary excretions of total N (P < 0.05) and urea (P < 0.001), increased the ratio of N retention / digested N (P < 0.05) in beef cattle, and decreased the estimated cattle urine N 2 O-N emissions by 19.5%, 23.4%, and 32.6%, respectively (P < 0.001)., Conclusion: Supplementation of RPM to Met-deficient rations was effective in improving the utilization rate of dietary N and decreasing the N 2 O emissions from urine in beef cattle. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Hypernatremia is a common electrolyte problem at the intensive care setting, with a prevalence that can reach up to 25%. It is associated with a longer hospital stay and is an independent risk factor for mortality. We report a case of hypernatremia of multifactorial origin in the intensive care setting, emphasizing the role of osmotic diuresis due to excessive urea generation, an underdiagnosed and a not well-known cause of hypernatremia. This scenario may occur in patients using high doses of corticosteroids, with gastrointestinal bleeding, under diets and hyperprotein supplements, and with hypercatabolism, especially during the recovery phase of renal injury. Through the present teaching case, we discuss a clinical approach to the diagnosis of urea-induced osmotic diuresis and hypernatremia, highlighting the utility of the electrolyte-free water clearance concept in understanding the development of hypernatremia.

Background: Dietary protein supports resistance exercise-induced anabolism primarily via the stimulation of protein synthesis rates. The indicator amino acid oxidation (IAAO) technique provides a noninvasive estimate of the protein intake that maximizes whole-body protein synthesis rates and net protein balance., Objective: We utilized IAAO to determine the maximal anabolic response to postexercise protein ingestion in resistance-trained men., Methods: Seven resistance-trained men (mean ± SD age 24 ± 3 y; weight 80 ± 9 kg; 11 ± 5% body fat; habitual protein intake 2.3 ± 0.6 g·kg-1·d-1) performed a bout of whole-body resistance exercise prior to ingesting hourly mixed meals, which provided a variable amount of protein (0.20-3.00 g·kg-1·d-1) as crystalline amino acids modeled after egg protein. Steady-state protein kinetics were modeled with oral l-[1-13C]-phenylalanine. Breath and urine samples were taken at isotopic steady state to determine phenylalanine flux (PheRa), phenylalanine excretion (F13CO2; reciprocal of protein synthesis), and net balance (protein synthesis - PheRa). Total amino acid oxidation was estimated from the ratio of urinary urea and creatinine., Results: Mixed model biphasic linear regression revealed a plateau in F13CO2 (mean: 2.00; 95% CI: 1.62, 2.38 g protein·kg-1·d-1) (r2 = 0.64; P ˂ 0.01) and in net balance (mean: 2.01; 95% CI: 1.44, 2.57 g protein·kg-1·d-1) (r2 = 0.63; P ˂ 0.01). Ratios of urinary urea and creatinine concentrations increased linearly (r = 0.84; P ˂ 0.01) across the range of protein intakes., Conclusions: A breakpoint protein intake of ∼2.0 g·kg-1·d-1, which maximized whole-body anabolism in resistance-trained men after exercise, is greater than previous IAAO-derived estimates for nonexercising men and is at the upper range of current general protein recommendations for athletes. The capacity to enhance whole-body net balance may be greater than previously suggested to maximize muscle protein synthesis in resistance-trained athletes accustomed to a high habitual protein intake. This trial was registered at clinicaltrials.gov as NCT03696264., (Copyright © The Author(s) 2019.)

Growing evidence suggests that increased arginase activity affects vital bioprocesses in various systems and universally mediates the pathogenesis of numerous metabolic diseases. The adverse effects of arginase are associated with a severe decline in L-arginine bioavailability, which leads to nitric oxide synthase substrate insufficiency, uncoupling, and, eventually, superoxide anion generation and substantial reduction of nitric oxide (NO) synthesis. In cooperation, it contributes to chronic oxidative stress and endothelial dysfunction, which might lead to hypertension and atherosclerosis. Recent preclinical investigations point arginase as a promising therapeutic target in ameliorating metabolic and vascular dysfunctions. In the present study, adult rats with inherited stress-induced arterial hypertension (ISIAH) were used as a model of hypertension. Wistar rats served as normotensive controls. Experimental animals were intraperitoneally administered for seven days with nonproteinogenic amino acid L-norvaline (30 mg/kg/day), which is a potent arginase inhibitor, or with the vehicle. Blood pressure (BP), body weight, and diuresis were monitored. The changes in blood and urine levels of creatinine, urea, and NO metabolites were analyzed. We observed a significant decline in BP and induced diuresis in ISIAH rats following the treatment. The same procedure did not affect the BP of control animals. Remarkably, the treatment had no influence upon glomerular filtration rate in two experimental groups, just like the daily excretion of creatinine and urea. Conversely, NO metabolite levels were amplified in normotonic but not in hypertensive rats following the treatment. The data indicate that L-norvaline is a potential antihypertensive agent and deserves to be clinically investigated. Moreover, we suggest that changes in blood and urine are causally related to the effect of L-norvaline upon BP regulation., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Michael A. Gilinsky et al.)

Purpose: Tolvaptan, a vasopressin V2 receptor antagonist, slows the decline in renal function in autosomal dominant polycystic kidney disease (ADPKD). However, it increases urine output such that patient adherence could be compromised. In a cohort of patients with ADPKD on tolvaptan, we aimed to identify the contribution of sodium and urea excretion rate to daily urine output, and to evaluate the effectiveness of dietary counseling on sodium and urea excretion rates., Methods: Retrospective analysis of 30 ADPKD patients who underwent a single session of personalized dietary counseling to reduce sodium and protein intake before initiation of tolvaptan. Creatinine and 24-h urine were obtained regularly on treatment. Generalized estimation equations were used., Results: Mean age and median eGFR were 44 ± 11 years and 52 (43-74) ml/min/1.73 m 2 . Tolvaptan increased diuresis from 2.5 to 5.2 l/day. After adjusting for the dose of tolvaptan, an increase in sodium and urea excretion rate by 50 mmol/day was associated with an estimated additional urine volume of 0.6 l/day (95% CI 0.4-0.8 l/day; P < 0.001) and 0.25 l/day (95% CI 0.11-0.39 l/day; P < 0.001), respectively. Dietary counseling resulted in a transient reduction of sodium excretion by 19 mmol/day during the first 4 months (P = 0.016) but resulted in a more sustained reduction in urea excretion by 69 mmol/day (P = 0.008)., Conclusion: Both sodium and urea excretion rates contribute significantly to daily urine volume in patients treated with tolvaptan, and a single session of dietary counseling was transiently effective in reducing sodium intake but achieved a more sustained reduction in protein intake. Dietary counseling should be considered in the management of ADPKD patients treated by tolvaptan.

Objectives: To evaluate the use of multifrequency bioelectrical impedance analysis to predict creatinine/urea clearance based on 24 hours urine collection. A practical formula was developed, and its performance was compared with that of established formulas such as Cockcroft-Gault, Modification of Diet in Renal Disease, and Jelliffe's., Design: An open-label prospective observational cohort study., Setting: A 12-bed ICU at a nonuniversity major teaching hospital (Gelre ziekenhuizen Apeldoorn/Zutphen, The Netherlands)., Patients: Adult critical care patients with an expected ICU length of stay at admission of at least 48 hours., Interventions: Each patient's body composition was assessed using a validated Quadscan 4000 analyzer (Bodystat, Isle of Man, British Isles). Twenty-four hours urine was collected, and laboratory variables in serum including creatinine, urea, and albumin were obtained at the beginning and end of the collection period., Measurements and Main Results: A total of 151 patients, stratified to an acute and nonacute ICU-group, were enrolled in the study over a 2-year period. A formula to predict creatinine/urea clearance based on 24 hours urine collection was developed using stepwise linear regression using a training data set of 75 patients. This formula was subsequently tested and compared with other relevant predictive equations using a validation data set of 76 patients. Serum creatinine values ranged from 40 to 446 µmol/L. With the predictive model based on estimated body cell mass and a "prediction marker" more than 71% of the observed variance in creatinine/urea clearance based on 24 hours urine collection could be explained. Predictive performance was superior to the other eight evaluated models (R = 0.39-0.55) and demonstrated to be constant over the whole range of creatinine/urea clearance based on 24 hours urine collection values., Conclusions: Multifrequency bioelectrical impedance analysis measurements can be used to predict creatinine/urea clearance based on 24 hours urine collection with superior performance than currently established prediction models. This rapid, noninvasive method enables correction for influences of a patient's actual body composition and may prove valuable in daily clinical practice.