Utility of fractional excretion of urea nitrogen in heart failure patients with chronic kidney disease.

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 m2 ) 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.

Development and validation of a simple equation to evaluate dietary protein intake using the blood urea nitrogen/serum creatinine ratio in patients with stage 3 chronic kidney disease.

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 P30 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 .

The ratio of measured to estimated glomerular filtration rate may be a marker of early mortality and dialysis requirement.

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/1.73m2. 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/1.73m2, 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.

Does daily fasting shielding kidney on hyperglycemia-related inflammatory cytokine via TNF-α, NLRP3, TGF-ß1 and VCAM-1 mRNA expression.

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-ß1 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-ß1 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.

Prognostic Value of Fractional Excretion of Urea Nitrogen at Discharge in Acute Decompensated Heart Failure.

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 m2, 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.

Mean of creatinine clearance and urea clearance examined over 1 h estimates glomerular filtration rate accurately and precisely in children.

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 (CCr ) and urea clearance (CUN ) examined over a 1-h urine collection period (1-h (CCr + CUN )/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 (CIn ) 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 (CCr + CUN )/2, 1-h CCr , 1-h CUN and GFR estimated by Cr-based and cystatin C (CysC)-based formulas for Japanese children were compared with CIn . Bland-Altman plots were used to evaluate correlations. The primary outcome measure was the correlation between 1-h (CCr + CUN )/2 and CIn . RESULTS: Fifty-three children were analysed. Their median age was 10.9 (interquartile range [IQR] 5.3-14.2) years, and median CIn and 1-h (CCr + CUN )/2 were 77.0 (IQR: 51.5-95.1) and 81.0 (IQR: 64.1-97.7) ml/min/1.73 m2 , respectively. Percentage difference of CIn and 1-h (CCr + CUN )/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 (CCr + CUN )/2 was 1.12 times CIn . CONCLUSION: 1 h (CCr + CUN )/2 was almost concordant with CIn . 1-h (CCr + CUN )/2 can estimate GFR accurately and precisely, making it a simple and speedy test for use in clinical practice.

Effect of dietary treatment and fluid intake on the prevention of recurrent calcium stones and changes in urine composition: A meta-analysis and systematic review.

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.

Synthesis, Preclinical Evaluation, and First-in-Human PET Study of Quinoline-Containing PSMA Tracers with Decreased Renal Excretion.

The prostate-specific membrane antigen (PSMA) is considered to be an excellent theranostic target of prostate cancer (PCa). In this study, three 18F-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 [18F]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 [18F]8c, with a Ki value of 4.58 nM, displayed notable low bladder retention and demonstrated good imaging properties in patients with PCa.

pH-modulated aggregation-induced emission of Au/Cu nanoclusters and its application to the determination of urea and dissolved ammonia.

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.

Hyperbaric Oxygen Preconditioning Upregulates Heme OxyGenase-1 and Anti-Apoptotic Bcl-2 Protein Expression in Spontaneously Hypertensive Rats with Induced Postischemic Acute Kidney Injury.

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.

Use of the Urine-to-Plasma Urea Ratio to Predict ADPKD Progression.

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 m2 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 (ß=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_01_27_CJN10470620_final.mp3.

Assessment of Inorganic Phosphate Intake by the Measurement of the Phosphate/Urea Nitrogen Ratio in Urine.

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.

Water-stable perovskite-on-polymer fluorescent microspheres for simultaneous monitoring of pH, urea, and urease.

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, CsPbBr3 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.

Evaluation of Residual Kidney Function during Once-Weekly Incremental Hemodialysis.

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.

Evaluation of a system for sorbent-assisted peritoneal dialysis in a uremic pig model.

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.

Rate of decline in residual kidney function pre and post peritoneal dialysis initiation: A post hoc analysis of the IDEAL study.

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.

Effects of ammonia exposure on antioxidant function, immune response and NF-κB pathway in Chinese Strip-necked Turtle (Mauremys sinensis).

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.

Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank.

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.

Copper nanoclusters@Al3+ complexes with strong and stable aggregation-induced emission for application in enzymatic determination of urea.

The aggregates of glutathione-capped CuNCs induced by Al3+ (named CuNCs@Al3+ 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@Al3+ complexes are a suitable probe to determine urea. The fluorescence of CuNCs@Al3+ 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@Al3+ 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@Al3+ 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.

Signs of Dehydration after Hip Fracture Surgery: An Observational Descriptive Study.

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.