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Concept: Urea

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BACKGROUND: The aim of this study was to determine the effects of creatine supplementation on kidney function in resistance-trained individuals ingesting a high-protein diet. METHODS: A randomized, double-blind, placebo-controlled trial was performed. The participants were randomly allocated to receive either creatine (20 g/d for 5 d followed by 5 g/d throughout the trial) or placebo for 12 weeks. All of the participants were engaged in resistance training and consumed a high-protein diet (i.e., >= 1.2 g/Kg/d). Subjects were assessed at baseline (Pre) and after 12 weeks (Post). Glomerular filtration rate was measured by 51Cr-EDTA clearance. Additionally, blood samples and a 24-h urine collection were obtained for other kidney function assessments. RESULTS: No significant differences were observed for 51Cr-EDTA clearance throughout the trial (Creatine: Pre 101.42 +/- 13.11, Post 108.78 +/- 14.41 mL/min/1.73m2; Placebo: Pre 103.29 +/- 17.64, Post 106.68 +/- 16.05 mL/min/1.73m2; group x time interaction: F = 0.21, p = 0.64). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria remained virtually unchanged. CONCLUSIONS: A 12-week creatine supplementation protocol did not affect kidney function in resistance-trained healthy individuals consuming a high-protein diet; thus reinforcing the safety of this dietary supplement.Trial registration: ClinicalTrials.gov NCT01817673.

Concepts: Renal failure, Kidney, Nephrology, Renal physiology, Renal function, Blood urea nitrogen, Electrolyte, Urea

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Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake. We observed that the renal concentration mechanism couples natriuresis with correspondent renal water reabsorption, limits natriuretic osmotic diuresis, and results in concurrent extracellular volume conservation and concentration of salt excreted into urine. This water-conserving mechanism of dietary salt excretion relies on urea transporter-driven urea recycling by the kidneys and on urea production by liver and skeletal muscle. The energy-intense nature of hepatic and extrahepatic urea osmolyte production for renal water conservation requires reprioritization of energy and substrate metabolism in liver and skeletal muscle, resulting in hepatic ketogenesis and glucocorticoid-driven muscle catabolism, which are prevented by increasing food intake. This natriuretic-ureotelic, water-conserving principle relies on metabolism-driven extracellular volume control and is regulated by concerted liver, muscle, and renal actions.

Concepts: Kidney, Ammonia, Metabolism, Glucose, Urine, Glycogen, Sodium, Urea

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Experimental evidence suggests that higher levels of urea may increase insulin resistance and suppress insulin secretion. However, whether higher levels of blood urea nitrogen (BUN) are associated with increased risk of incident diabetes mellitus in humans is not known. To study this, we built a national cohort of 1,337,452 United States Veterans without diabetes to characterize the association of BUN and risk of incident diabetes. Over a median follow-up of 4.93 years, there were 172,913 cases of incident diabetes. In joint risk models of estimated glomerular filtration rate (eGFR) and BUN. there was no association between eGFR and the risk of incident diabetes in those with a BUN of 25 mg/dl or less. However, the risk was significantly increased in those with a BUN over 25 mg/dl at all eGFR levels, even in those with an eGFR of 60 ml/min/1.73m2 or more (hazard ratio 1.27; confidence interval 1.24-1.31). The risk of incident diabetes was highest in those with BUN over 25 mg/dL and an eGFR under 15 ml/min/1.73m2 (1.68; 1.51-1.87). Spline analyses of the relationship between BUN and risk of incident diabetes showed that risk was progressively higher as BUN increased. In models where eGFR was included as a continuous covariate, compared to a BUN of 25 mg/dl or less, a BUN over 25 mg/dl was associated with increased risk of incident diabetes (1.23; 1.21-1.25). Every 10 ml/min/1.73m2 decrease in eGFR was not associated with risk of incident diabetes (1.00; 1.00-1.01). Two-stage residual inclusion analyses showed that, independent of the impact of eGFR, every 10 mg/dL increase in BUN concentration was associated with increased risk of incident diabetes (1.15; 1.14-1.16). Thus, higher levels of BUN are associated with increased risk of incident diabetes mellitus.

Concepts: Nephrology, Insulin, Diabetes mellitus, Obesity, Renal function, Blood urea nitrogen, Insulin resistance, Urea

154

The contamination of the environment with microplastic, defined as particles smaller than 5 mm, has emerged as a global challenge because it may pose risks to biota and public health. Current research focuses predominantly on aquatic systems, whereas comparatively little is known regarding the sources, pathways, and possible accumulation of plastic particles in terrestrial ecosystems. We investigated the potential of organic fertilizers from biowaste fermentation and composting as an entry path for microplastic particles into the environment. Particles were classified by size and identified by attenuated total reflection-Fourier transform infrared spectroscopy. All fertilizer samples from plants converting biowaste contained plastic particles, but amounts differed significantly with substrate pretreatment, plant, and waste (for example, household versus commerce) type. In contrast, digestates from agricultural energy crop digesters tested for comparison contained only isolated particles, if any. Among the most abundant synthetic polymers observed were those used for common consumer products. Our results indicate that depending on pretreatment, organic fertilizers from biowaste fermentation and composting, as applied in agriculture and gardening worldwide, are a neglected source of microplastic in the environment.

Concepts: Agriculture, Fertilizer, Urea, Compost, Organic fertilizer, Manure, Green manure, Vermicompost

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Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA. In vivo infusion of (15)N-glutamine in obese mouse models of PDA demonstrates enhanced nitrogen flux into the urea cycle and infusion of (15)N-arginine shows that Arg2 loss causes significant ammonia accumulation that results from the shunting of arginine catabolism into alternative nitrogen repositories. Furthermore, analysis of PDA patient tumors indicates that ARG2 levels correlate with body mass index (BMI). The specific dependency of PDA on ARG2 rather than the principal hepatic enzyme ARG1 opens a therapeutic window for obesity-associated pancreatic cancer.Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Here the authors show that obesity induces the expression of the mitochondrial form of arginase ARG2 in PDA and that ARG2 silencing or loss results in ammonia accumulation and suppression of obesity-driven PDA tumor growth.

Concepts: Cancer, Ammonia, Metabolism, Body mass index, Nitrogen, Urea, Urea cycle, Ornithine

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PURPOSE: Few studies have focused on the metabolic changes induced by creatine supplementation. This study investigated the effects of creatine supplementation on plasma and urinary metabolite changes of athletes after endurance and sprint running. METHODS: Twelve male athletes (20.3 ± 1.4 y) performed two identical (65-70 % maximum heart rate reserved) 60 min running exercises (endurance trial) before and after creatine supplementation (12 g creatine monohydrate/day for 15 days), followed by a 5-day washout period. Subsequently, they performed two identical 100 m sprint running exercises (power trial) before and after 15 days of creatine supplementation in accordance with the supplementary protocol of the endurance trial. Body composition measurements were performed during the entire study. Plasma samples were examined for the concentrations of glucose, lactate, branched-chain amino acids (BCAAs), free-tryptophan (f-TRP), glutamine, alanine, hypoxanthine, and uric acid. Urinary samples were examined for the concentrations of hydroxyproline, 3-methylhistidine, urea nitrogen, and creatinine. RESULTS: Creatine supplementation significantly increased body weights of the athletes of endurance trial. Plasma lactate concentration and ratio of f-TRP/BCAAs after recovery from endurance running were significantly decreased with creatine supplementation. Plasma purine metabolites (the sum of hypoxanthine and uric acid), glutamine, urinary 3-methylhistidine, and urea nitrogen concentrations tended to decrease before running in trials with creatine supplements. After running, urinary hydroxyproline concentration significantly increased in the power trial with creatine supplements. CONCLUSIONS: The findings suggest that creatine supplementation tended to decrease muscle glycogen and protein degradation, especially after endurance exercise. However, creatine supplementation might induce collagen proteolysis in athletes after sprint running.

Concepts: Protein, Amino acid, Ammonia, Metabolism, Urine, Nitrogen, Urea, Uric acid

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Background: Experience with hydroxyethyl starch (HES) in children is limited. This study was conducted to observe the effects of HES or Ringer’s lactate (RL) usage as the priming solution on renal functions in children undergoing cardiac surgery. Methods: After ethical committee approval and parent informed consent, 24 patients were included in this prospective, randomized study. During cardiopulmonary bypass (CPB), Group I received RL and Group II received HES (130/0.4) as priming solution. Serum creatinine, blood urea nitrogen (BUN), β2-microglobulin, cystatin C, and urinary albumin and creatinine, serum, and urine electrolytes were analyzed after the induction (T1), before CPB (T2), during CPB (T3), after CPB (T4), at the end of the operation (T5), on 24th hour (T6), and on 48th hour postoperatively (T7). Fractional sodium excretion (FENa), urinary albumin/creatinine ratio, and creatinine clearance were calculated. Drainage, urine output, inotropes, diuretics, and blood requirements were recorded. Results: In both the groups, β2-microglobulin was decreased during CPB and cystatin C was decreased at T3,T4, and T5 periods (p < 0.05) and the levels remained within the normal range. Creatinine clearance did not differ in the HES group, but increased in the RL group (p < 0.05). Urine albumin/creatinine ratio was increased (p < 0.05) after CPB in the HES group, and it increased at T3, T4, and T5 in the RL group (p < 0.05). There were no differences in cystatin C, β2-microglobulin, FENa, urine albumin/creatinine ratio, creatinine clearance, total fluid amount, urine output, drainage, and inotropic and diuretic requirements between the groups. Conclusion: We conclude that usage of HES (130/0.4) did not have negative effects on renal function, and it can be used as a priming solution in pediatric patients undergoing cardiac surgery.

Concepts: Nephrology, Renal physiology, Renal function, Blood urea nitrogen, Creatinine, Electrolyte, Urea, Cystatin C

27

End-product from 16 public mixed latrine style composting toilets (CTs) at 12 sites between 50 and 2100 m.a.s.l. in Western North America was tested in order to evaluate the effect of composting variables (TS%, NH(3)-N, temperature, and material age) on compost quality and hygiene (VS%, Escherichia coli, [Formula: see text] -N, and pH). Principal component analysis indicated that TS%, temperature, and material age equally contributed to reduction in VS%. NH(3)-N had the greatest effect on [Formula: see text] -N, E. coli, and pH. Nitrification was significantly inhibited above 386 mg/kg NH(3)-N, but no such limit was found for E. coli, despite a significant (p = 0.016) but weak (r(2) = 0.11) negative relationship. It may be possible to amplify the sanitizing effect of ammonia and overcome pathogen resistance due to low temperatures and re-contamination (caused by poor design) with generous dosing of urea and ash. However, even sanitized, the fertilization effect of discharged material on the natural environment may not be desired or permitted in parks or protected areas where many CTs were found. To this end, operators of CTs need to evaluate their primary management objectives and ensure congruency with proven system capabilities.

Concepts: Ammonia, Urine, Thermodynamics, Principal component analysis, Urea, Sanitation, Toilet, Composting toilet

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BACKGROUND: Chronic drug interactions that exist between symptomatic congestive heart failure (CHF) therapy and pharmacologic agents used for hyperuricemia and gout are a challenging problem in clinical practice. Recent observational studies showed that prednisone can induce a potent diuresis and lower serum uric acid concentration (SUA) in CHF. We therefore designed a randomized study to compare the effect of prednisone with allopurinol on SUA in symptomatic CHF patients with hyperuricemia. METHODS: Thirty-four symptomatic CHF participants with hyperuricemia (≥ 565 μmol/L) were randomized to receive prednisone (1 mg/kg/d, orally) or allopurinol (100 mg, thrice daily, orally) for 4 weeks. The primary outcome measure was change from baseline in SUA. The secondary outcome measures were change from baseline in serum creatinine levels, estimated glomerular filtration rate, daily urine output, body weight, N-terminal pro-B-type natriuretic peptide levels, physician-assessed global clinical status, and New York Heart Association functional class. RESULTS: Both prednisone and allopurinol greatly lowered SUA rapidly. The overall SUA-lowering effect did not differ between treatment groups during the study period (P = 0.48, 2-way repeated measures analysis of variance). However, prednisone increased estimated glomerular filtration rate and daily urine output, and lowered body weights and N-terminal pro-B-type natriuretic peptide. Consequently, participants treated with prednisone had an improvement in clinical status. CONCLUSIONS: The study showed that the SUA-lowering effect of prednisone and allopurinol is similar in symptomatic CHF patients. Prednisone might be useful for short-term SUA-lowering in CHF patients with hyperuricemia.

Concepts: Heart failure, Blood urea nitrogen, Creatinine, Gout, Urea, Uric acid, Hyperuricemia, Hyperuricosuria