24-h Urea Research Articles

MO435: The Prognostic Implication of 24-h Urine Urea Excretion With Renal Progression: Analysis of KNOW-CKD Study

Abstract BACKGROUND AND AIMS Urea excretion is the basic function of the nephron. However, its prognostic implication has been not extensively studied in a specific subpopulation of chronic kidney diseases (CKD). METHOD Total of 2232 patients in KNOW-CKD cohort were analyzed. Baseline characteristics were used as a prognosticator in the Cox regression model. For categorical comparison, tertiles of 24-h urea excretion were used as high, low and moderate excretion of urea. Linear modelling and nonlinear modelling based on restricted cubic splines were used to study the impact of 24-h urea excretion on renal survival. RESULTS Mean daily urea excretion was 8.2 ± 3.6 g/day. Mean daily urea excretion was 12.1 ± 3.1 g/day versus 4.8 ± 1.3 g/day in the high urea excretion group (HUG) and low urea excretion group (LUG) (P < 0.001). Mean eGFR of LUG was 47.0 ± 30.9 mL/min/1.73m2 and mean eGFR of HUG was 60.6 ± 29.9 mL/min/1.73m2 (P < 0.001). Serum albumin level was higher in HUG with 4.3 ± 0.4 g/dL versus 4.1 ± 0.5 g/dL of LUG (P < 0.001). Compared with HUG, LUG showed a hazard ratio of end-stage renal disease (ESRD) with 1.407 [95% confidence interval (CI) 1.115–1.774, P = 0.004] in the linear multiple regression model, which was adjusted by eGFR, age, gender, body mass index, type of CKD, proteinuria amount, systolic blood pressure, hemoglobin, blood urea nitrogen, serum albumin, serum cholesterol, serum uric acid, hsCRP, statin usage, renin-angiotensin-aldosterone system blocker usage. In the non-linear modeling, daily urea excretion showed a two-step change in log hazard ratio to ESRD. Threshold points of log hazard ratio among the whole study population were observed at 5 g/day and 15 g/day, respectively. The reduction of log hazard ratio in the HUG was more clear in the eGFR 30–60 mL/min/1.73m2 subpopulation (Figure 1C). Similarly, a reduction in log hazard ratio in the HUG was observed in glomerulonephritis, polycystic kidney disease subpopulations, but not in the diabetes mellitus nephropathy subpopulation (Figure 1D–F). CONCLUSION Daily urea urine excretion showed prognostic implications in the CKD stage 3 subgroups, glomerulonephritis subgroups and polycystic kidney disease subgroups. In the following researches, studies focusing on interventional targets in the context of daily urea excretion in those subgroups should be warranted.

MO422: Strong Positive Association Between GFR and the Urine-To-Plasma Urea Concentration Ratio in Patients With Sickle Cell Disease. Possible Functional Meaning

Abstract BACKGROUND AND AIMS Sickle cell disease (SCD) induces a decline in urine concentration and progressive deterioration of kidney (K) function. Hyperfiltration is often observed before this decline, and plasma urea is low. Oral urea or hydroxyurea improves the condition of these patients (pts). These observations draw the attention to renal urea handling in SCD. Studies suggest that addition of urea into the loop of Henle may indirectly modify NaCl concentration at the macula densa and induce a rise in glomerular filtration rate (GFR) by depressing the tubule-glomerular feedback (TGF) [1]. The urine-to-plasma urea concentration ratio (U/P urea) is a novel marker associated with GFR and the progression of disease in ADPKD [2]. The present study addresses the relationship of U/P urea with GFR in SCD pts. METHOD A total of 184 homozygous SCD pts referred to our department were included. They underwent extensive evaluation including measured GFR (mGFR) (51Cr EDTA clearance) and plasma and 24-h urine chemistries. The association between mGFR and U/P urea was tested using univariate, and multivariate stepwise regression analyses. RESULTS Mean age was 35.6 ± 2.8 years (mean ± SD) and body mass index (BMI) 22.2 ± 0.3 kg/m2. Mean mGFR was 107 ± 3 ml/min x 1.73m2. Hyperfiltration was observed in 37% of pts. Urine volume (UV) 1.71 ± 0.75 L/24h. Urea excretion 267 ± 151 mmol/24h. In 13% of pts fractional excretion of urea (FEurea) exceeded 50%. U/P urea (42 ± 20) varied from 6 to 112. It was not associated with 24-h urea excretion but showed a negative association with UV (P < 0.007). mGFR was strongly and positively associated with U/P urea (r = 0.58, P < 0.0001) but not with U/P osmolarity (see Figure and Table). mGFR was also associated with U/P creatinine although more weakly (r = 0.266, p < 0.0001) and with BMI and negatively associated with age, MAP and serum creatinine (creat). After adjustment for U/P creat, the association between mGFR and U/P urea remained highly significant, whereas, after adjustment for U/P urea, the association between mGFR and U/P creat disappeared. In multivariate regression, mGFR remained strongly associated with U/P urea. CONCLUSION Our data show a strong association between mGFR and U/P urea that remains highly significant after multivariate analysis. i) This suggests that a specific estimated GFR equation for SCD patients including the U/P urea ratio could be clinically more relevant than CKD-EPI equations. ii) A specific mechanism may link GFR and intrarenal urea handling, as U/P urea but not U/P osmolarity appears to be involved. Urea could play a role, indirectly, in the regulation of GFR [1]. In SCD, the longer transit time of the blood in vasa recta may favour countercurrent exchanges and lead to a greater addition of urea in loops of Henle (increasing the U/P urea ratio) and thus increasing GFR by reducing TGF. Sickled red cells and resulting in slower blood flow in the medulla may selectively influence urea handling, participating in high FEurea and GFR often observed in SCD pts. iii) As is the case in ADPKD, more attention should be given to longitudinal studies to the relationship between U/P urea and kidney disease progression in SCD pts.

MiR-93 inhibits the vascular calcification of chronic renal failure by suppression of Wnt/β-catenin pathway.

To explore the effect of miR-93-mediated Wnt/β-catenin pathway on the vascular calcification (VC) of chronic renal failure (CRF). SD rats were utilized to construct CRF models and divided into Control, CRF, CRF + LV (lentiviral vector)-miR-93 and CRF + LV-Con groups. Renal tissues collected from rats were performed hematoxylin and eosin (HE) staining and Masson staining, while the abdominal aorta was dissected for alizarin red staining and Von Kossa staining. VC-related genes were determined by qRT-PCR while Wnt/β-catenin pathway-related proteins were examined by Western blotting. As compared to Control group, the serum levels of blood urea nitrogen (BUN), serum creatinine (Scr), phosphorus (P), cystatin C (Cys-C) and 24-h urea protein (24h Upro), and the scores of renal interstitial lesion and fibrotic area in rats from CRF group were elevated, with the increased calcified area of aorta as well as the enhanced calcium content and ALP. Meanwhile, rats in the CRF group had up-regulated expression of OPN, OCN, RUNX2 and BMP-2 and down-regulated expression of miR-93. As for the expression of Wnt/β-catenin pathway, rats in the CRF group had sharp increases in the protein expression of TCF4 and β-catenin, while α-SMA was down-regulated. However, changes of the above were reversed in rats from CRF + LV-miR-93 group, and TCF4 was confirmed to be a target gene of miR-93. MiR-93, via inhibiting the activity of Wnt/β-catenin pathway by targeting TCF4, can improve the renal function of CRF rats, thereby mitigating the vascular calcification of CRF.

Fibroblast growth factor 21 and protein energy wasting in hemodialysis patients

Protein energy wasting (PEW) is the most important risk factor for morbidity and mortality in hemodialysis patients. Inadequate dietary protein intake is a frequent cause of PEW. Recent studies have identified fibroblast growth factor 21 (FGF21) as an endocrine protein sensor. This study aims to investigate the potential of FGF21 as a biomarker for protein intake and PEW and to investigate intradialytic FGF21 changes. Plasma FGF21 was measured using an enzyme-linked immunoassay. Complete intradialytic dialysate and interdialytic urinary collections were used to calculate 24-h urea excretion and protein intake. Muscle mass was assessed using the creatinine excretion rate and fatigue was assessed using the Short Form 36 and the Checklist Individual Strength. Out of 59 hemodialysis patients (65±15 years, 63% male), 39 patients had a low protein intake, defined as a protein intake less than 0.9g/kg/24-h. Patients with a low protein intake had nearly twofold higher plasma FGF21 compared to those with an adequate protein intake (FGF21 1370 [795-4034] pg/mL versus 709 [405-1077] pg/mL;P<0.001). Higher plasma FGF21 was associated with higher odds of low protein intake (Odds Ratio: 3.18 [1.62-7.95] per doubling of FGF21; P=0.004), independent of potential confounders. Higher plasma FGF21 was also associated with lower muscle mass (std β:-0.34 [-0.59;-0.09];P=0.009), lower vitality (std β:-0.30 [-0.55;-0.05];P=0.02), and more fatigue (std β: 0.32 [0.07;0.57];P=0.01). During hemodialysis plasma FGF21 increased by 354 [71-570] pg/mL, corresponding to a 29% increase. Higher plasma FGF21 is associated with higher odds of low protein intake in hemodialysis patients. Secondarily, plasma FGF21 is also associated with lower muscle mass, less vitality, and more fatigue. Lastly, there is an intradialytic increase in plasma FGF21. FGF21 could be a valuable marker allowing for objective assessment of PEW.

Association of protein intake with the outcomes of critically ill patients: a post hoc analysis of the PermiT trial

The optimal amount of protein intake in critically ill patients is uncertain. In this post hoc analysis of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we tested the hypothesis that higher total protein intake was associated with lower 90-d mortality and improved protein biomarkers in critically ill patients. In this post hoc analysis of the PermiT trial, we included patients who received enteral feeding for ≥3 consecutive days. Using the median protein intake of the cohort as a cutoff, patients were categorized into 2 groups: a higher-protein group (>0.80 g · kg-1 · d-1) and a lower-protein group (≤0.80 g · kg-1 · d-1). We developed a propensity score for receiving higher protein. Primary outcome was 90-d mortality. We also compared serial values of prealbumin, transferrin, 24-h urinary nitrogen, and 24-h nitrogen balance on days 1, 7, and 14. Among the 729 patients included in this analysis, the average protein intake was 0.8±0.3 g · kg-1 · d-1 [1.0±0.2 g · kg-1 · d-1 in the higher-protein group (n=365) and 0.6±0.2 g · kg-1 · d-1 in the lower-protein group (n=364); P<0.0001]. There was no difference in 90-d mortality between the 2 groups [88/364 (24.2%) compared with 94/363 (25.9%), propensity score-adjusted OR: 0.80; 95% CI: 0.56, 1.16; P=0.24]. Higher protein intake was associated with an increase in 24-h urea nitrogen excretion compared with lower protein intake, but without a significant change in prealbumin, transferrin, or 24-h nitrogen balance. In the PermiT trial, a moderate difference in protein intake was not associated with lower mortality. Higher protein intake was associated with increased nitrogen excretion in the urine without a corresponding change in prealbumin, transferrin, or nitrogen balance. Protein intake needs to be tested in adequately powered randomized controlled trials targeting larger differences in protein intake in high-risk populations.

Effect of early enteral nutrition on elderly patients with gastric cancer after total gastrectomy

Objective To explore the effect of early enteral nutrition(EEN) on elderly patients with gastric cancer after total gastrectomy(TG). Methods A total of 76 cases of elderly patients with gastric cancer accepted TG in our hospital from April 2012 to January 2014 were selected, according to different ways for postoperative nutritional support, patients were divided into EEN group with 38, patients received EEN support, and parenteral nutrition(PN) group with 38 patients treated with conventional deep vein PN.Statistics postoperative bowel function recovery time hospital stay and complications in patients, as well as nutritional indicators(serum protein ALB, transferrin and 24h urea nitrogen(24hUP)) and immune function index(CD3, CD4, CD8, CD4/CD8 and NK cell activity) at 10d after surgery were recorded and compared. Results Time of anal exhaust, time of anal defecation and hospital stay in the EEN group were(53.5±10.2) h, (78.7±15.4) h and(13.6±3.4) d, and were(66.7±11.5) h, (114.2±13.6) h and(21.5±3.5) d in PN group, the differences were statistically significant(P<0.05); complications in EEN group was 13.2%(5/38), and was 34.2%(13/38) in the PN group, the difference was statistically significant(P<0.05); nutrition indicators and immune function indicators 7 d after surgery in EN group were significantly better than those in the PN group, the difference was statistically significance(P<0.05). Conclusions Given EEN nutritional support to elderly patients with gastric cancer after surgery is safe and effective, and is benefit to immune function recovery and clinical signs improvement, thus worthy of further promotion in clinical practice. Key words: EEN; Elderly gastric cancer; PN; Immune function

Parallel assessment of nutrition and activity in athletes: Validation against doubly labelled water, 24-h urea excretion, and indirect calorimetry

The assessment of nutrition and activity in athletes requires accurate and precise methods. The aim of this study was to validate a protocol for parallel assessment of diet and exercise against doubly labelled water, 24-h urea excretion, and respiratory gas exchange. The participants were 14 male triathletes under normal training conditions. Energy intake and doubly labelled water were weakly associated with each other (r = 0.69, standard error of estimate [SEE] = 304 kcal · day−1). Protein intake was strongly correlated with 24-h urea (r = 0.89) but showed considerable individual variation (SEE = 0.34 g · kg−1 · day−1). Total energy expenditure based on recorded activities was highly correlated with doubly labelled water (r = 0.95, SEE = 195 kcal · day−1) but was proportionally biased. During running and cycling, estimated exercise energy expenditure was highly correlated with gas exchange (running: r = 0.89, SEE = 1.6 kcal · min−1; cycling: r = 0.95, SEE = 1.4 kcal · min−1). High exercise energy expenditure was slightly underestimated during running. For nutrition data, variations appear too large for precise measurements in individual athletes, which is a common problem of dietary assessment methods. Despite the high correlations of total energy expenditure and exercise energy expenditure with reference methods, a correction for systematic errors is necessary for the valid estimation of energetic requirements in individual athletes.

Urea Nitrogen Concentrations in Spot Urine, Estimated Protein Intake and Blood Pressure Levels in a Japanese General Population

An inverse association between total protein intake and blood pressure has been reported in Western countries. Such evidence is limited in the Japanese population, however, whose major protein sources are plants and seafood. We conducted a population-based cross-sectional study of 986 men and 1,636 women, aged 40-74 years, in a Japanese rural community to examine the association between blood pressure levels and urea nitrogen concentrations in spot urine. The concentration of urea nitrogen in spot urine, an indicator of total protein intake that was validated by 24-h urea nitrogen excretion and 24-h dietary research, was inversely associated with systolic blood pressure levels for men: a 238 mg/dl increase in urea nitrogen concentration was associated with a 2.1 mm Hg lower mean systolic blood pressure. For women, a weaker and nonsignificant inverse association was observed. There was no association between urea nitrogen concentrations and diastolic blood pressure levels in either sex. Total protein intake estimated from spot urine was also inversely associated with systolic blood pressure levels for men: a 19.2 g/day increase in estimated protein intake was associated with a 1.5 mm Hg lower mean systolic blood pressure. A urinary biomarker for total protein intake was inversely associated with systolic blood pressure levels for men in a Japanese general population.

Artificial neural networks for assessing the risk factors for urinary calcium stones according to gender and family history of stone

In a previous work, we evidenced that artificial neural networks (ANNs) were more informative than classical statistical analyses for assessing the risk of idiopathic calcium nephrolithiasis in male stone-formers. We compared risk factors for idiopathic calcium nephrolithiasis (age, body mass index, calcemia, calcium oxalate supersaturation, and 24-h calciuria, oxaluria, uricosuria, citraturia, urea, and sodium) in four populations: men and women with and without a family history of stone (FHS). A total of 119 males (58 with an FHS, 61 without) and 59 females (30 with an FHS, 29 without) were compared to healthy controls. For each variable, receiver operating characteristic (ROC) curve indices were calculated by means of ANNs. In men without an FHS, the most discriminant variables were 24-h urea (ROC curve index 0.76), supersaturation (ROC curve index 0.72), 24-h calciuria (ROC curve index 0.68), 24-h uricosuria (ROC curve index 0.64), 24-h oxaluria (ROC curve index 0.63), 24-h sodium (ROC curve index 0.62), and calcemia (ROC curve index 0.60). In men with an FHS, only supersaturation (ROC curve index 0.67) was discriminant. In women without FHS, calcemia (ROC curve index 0.67), 24-h calciuria (ROC curve index 0.64), and 24-h uricosuria (ROC curve index 0.62) were discriminant. In women with an FHS, supersaturation (ROC curve index 0.70), 24-h uricosuria (ROC curve index 0.69), 24-h urea (ROC curve index 0.68), and 24-h calciuria (ROC curve index 0.67) were discriminant. Risk factors for idiopathic calcium nephrolithiasis were roughly the same in men with or without an FHS, and in women with an FHS. In these patients, calcium oxalate supersaturation and 24-h urea were the most discriminant factors. Conversely, in women without an FHS, calcium abnormalities (calcemia, 24-h calciuria) were discriminant and should prompt a search for infraclinical primary hyperparathyroidism or sarcoidosis.

The relation between nutrition indices and age in patients on continuous ambulatory peritoneal dialysis receiving similar small solute clearances.

To analyze the effect of age on nutrition indices in subjects on the same continuous ambulatory peritoneal dialysis (CAPD) schedule. We analyzed 613 sets of clearance values and nutrition indices in 302 CAPD patients. Small solute clearances included urea clearance (Kt/Vurea) and creatinine clearance (Ccr). Nutrition indices included body mass index (BMI), serum albumin, urea and creatinine, 24-h urea nitrogen and creatinine excretion in urine plus dialysate, protein nitrogen appearance (PNA), PNA normalized by standard weight (nPNA), lean body mass (LBM) computed by creatinine kinetics, and LBM/Weight. CAPD subjects were classified in 4 age quartiles (Q): Group Q1, age 33.7 +/- 7.6 years, N = 149; group Q2, age 49.5 +/- 3.8 years, N = 158; group Q3, age 61.5 +/- 2.6 years, N = 154; and group Q4, age 72.1 +/- 5.4 years, N = 152. Group comparison was done by one-way ANOVA or chi-square. Predictors of low nutritional parameters were identified by logistic regression. Selected variables were compared by linear regression. Mean Kt/Vurea and Ccr were above the current adequacy standards and did not differ between the age quartiles. In contrast, older quartiles had, in general, lower nutrition indices than younger quartiles. However, the youngest quartile had the lowest BMI. By logistic regression, young age was a predictor of low BMI, while advanced age was a predictor of low creatinine and urea nitrogen excretion, low nPNA, and low LBM/Weight. The regressions of nPNA on Kt/Vurea differed between the age quartiles. By these regressions, the youngest quartile had higher nPNA values for the same Kt/Vurea than the oldest quartile in the clinically relevant range of Kt/Vurea and nPNA values. Nutrition indices are worse in older than in younger CAPD patients with the same small solute clearances. Nutrition of CAPD patients is adversely affected by age and requires special attention in the older age group.

Inhibition of NaCl-induced heat shock protein 72 expression renders MDCK cells susceptible to high urea concentrations.

Exposure of Madin-Darby canine kidney (MDCK) cells to elevated extracellular NaCl concentrations is associated with increased heat shock protein 72 (HSP72) expression and improved survival of these pretreated cells upon exposure to an additional 600 mM urea in the medium. To establish a causal relationship between HSP72 expression and cell protection against high urea concentrations, two approaches to inhibit NaCl-induced HSP72 synthesis prior to exposure to 600 mM urea were employed. First, the highly specific p38 kinase inhibitor SB203580 was added (100 microM) to the hypertonic medium (600 mosm/kg H2O by NaCl addition, 2 days of exposure), which significantly reduced HSP72 mRNA abundance and HSP72 content. Survival of these cells after a 24-h urea treatment (600 mM) was markedly curtailed compared with appropriate controls. Second, a pcDNA3-based construct, containing 322 bases of the HSP72 open reading frame in antisense orientation and the geneticine resistance gene, was transfected into MDCK cells. Clones with strong inhibition of HSP72 synthesis and others which express the protein at normal levels (comparable to nontransfected MDCK cells) after heat shock treatment or hypertonic stress were established. When these transformants were subjected to hypertonic stress for 2 days prior to exposure to an additional 600 mM urea for 24 h, cell survival was significantly reduced in those clones in which HSP72 expression was strongly inhibited. These results provide further evidence for the protective function of HSP72 against high urea concentrations in renal epithelial cells.

Protein Intake and 24-h Urea Excretion

Protein Intake and 24-h Urea Excretion