Catabolic Rate Research Articles

Factors Associated With Withdrawal From Dialysis Therapy in Incident Hemodialysis Patients Aged 80 Years or Older

ObjectivesAmong kidney disease patients ≥80 years progressing to end-stage renal disease, there is growing interest in conservative nondialytic management approaches. However, among those who have initiated hemodialysis, little is known about the impact of withdrawal from dialysis on mortality, nor the patient characteristics associated with withdrawal from dialysis. Study designHistorical cohort study. Setting and participantsWe examined 133,162 incident hemodialysis patients receiving care within a large national dialysis organization from 2007 to 2011. MeasuresWe identified patients who withdrew from dialysis, either as a listed cause of death or censor reason. Incidence rates and subdistribution hazard ratios for withdrawal from dialysis as well as 4 other censoring reasons were examined across age groups. In addition, demographic and clinical characteristics associated with withdrawal from dialysis therapy among patients ≥80 years old was assessed using logistic regression analysis. ResultsAmong 17,296 patients aged ≥80 years, 10% of patients withdrew from dialysis. Duration from the last hemodialysis treatment to death was 10 [interquartile range 6-16] days in patients with available data. Withdrawal from dialysis was the second and third most common cause of death among patients aged ≥80 years and <80 years, respectively. Among patients ≥80 years, minorities were much less likely than non-Hispanic whites to stop dialysis. Other factors associated with higher odds of dialysis withdrawal included having a central venous catheter compared to an arteriovenous fistula at dialysis start, dementia, living in mid-west regions, and less favorable markers associated with malnutrition-inflammation-cachexia syndrome such as higher white blood cell counts and lower body mass index, albumin, and normalized protein catabolic rate. Conclusion/ImplicationsAmong very-elderly incident hemodialysis patients, dialysis therapy withdrawal exhibits wide variations across age, race and ethnicity, regions, cognitive status, dialysis vascular access, and nutritional status. Further studies examining implications of withdrawal from dialysis in older patients are warranted

One-Year Historical Cohort Study of the Phosphate Binder Sucroferric Oxyhydroxide in Patients on Maintenance Hemodialysis

Objective:The high pill burden of many phosphate binders (PBs) may contribute to increased prevalence of hyperphosphatemia and poor nutritional status observed among patients undergoing maintenance hemodialysis therapy. We examined the real-world effectiveness of sucroferric oxyhydroxide (SO), a PB with low pill burden, in managing serum phosphorus in patients with prevalent hemodialysis over a 1-year period.Design:Historical cohort analyses of de-identified electronic medical records.Subjects:In-center hemodialysis patients switched from another PB to SO therapy as part of routine care with 12 months of uninterrupted SO prescriptions recorded, and documented serum phosphorus levels were eligible for inclusion. Clinical data were extracted from a pharmacy service, FreseniusRx, database and Fresenius Kidney Care clinical data warehouse.Main outcome measures:Comparisons were made between the 91-day period before SO initiation (i.e., baseline) and the 4 consecutive 91-day intervals of SO treatment (Q1-Q4). Clinical measures included achievement of target phosphorus levels (#5.5 mg/dL) and mean number of PB pills/day.Results:Among 530 analyzed patients, the proportion achieving target serum phosphorus levels increased by >100% 1 year after switching to SO therapy, that is, from 17.7% at baseline to 24.5%, 30.5%, 36.4%, and 36.0% at Q1 through Q4, respectively (P < .0001 for all). Reductions in serum phosphorus were observed at all follow-up timepoints (P <.0001), irrespective of baseline PB. From a mean baseline PB pill burden of 8.5 pills/day, patients experienced an average 50% pill burden reduction during SO treatment (P <. 0001). Phosphorus-attuned albumin and phosphorus-attuned protein intake (normalized protein catabolic rate) improved significantly after transition to SO (P < .0001). The effectiveness of SO was evident in prespecified subgroups of interest (i.e., black/African-American patients, Hispanic/Latino patients, and women).Conclusion:Among patients on hemodialysis, switching to SO resulted in a 2-fold greater likelihood of achieving target phosphorus levels while halving daily PB pill burden. Increases in phosphorus-attuned albumin and protein intake suggest improved nutritional status.

Carbohydrate and Lipid Prescription, Administration, and Oxidation in Critically Ill Patients With Acute Kidney Injury: A Post Hoc Analysis

In a prospective multicenter study on adult patients with acute kidney injury (AKI) receiving enteral and/or parenteral nutrition, administered carbohydrates and lipids were compared to the prescribed amounts, as well as to substrate utilization data derived from indirect calorimetry measurements. Resting energy expenditure (REE) was measured by indirect calorimetry. Nitrogen excretion was obtained from the protein catabolic rate calculated from urinary urea nitrogen when available and by urea kinetic-based methods in patients on renal replacement therapy. Fat and carbohydrate oxidations were derived from Frayn formulas. Ninety-two REE measurements were available in 35 critically ill patients with AKI (16 on renal replacement therapy). The mean lipid oxidation rate was 101g/24 h (standard deviation [SD] 73.8), whereas prescribed lipids were 67g/24 h (SD 32; P<.001). Carbohydrate utilization was derived from the same REE measurements yielding a mean carbohydrate oxidation of 105.8g/24 h (SD 131.8), thus, much lower than the prescribed carbohydrates (186.7g/24 h; SD 74.3; P<.001). The amount of fat and carbohydrates administered correlated to the prescribed amount (r=0.896 and r=0.829, respectively). Further analysis showed that this nutritional pattern was independent from the presence of sepsis. Our study suggests that critically ill patients with AKI do not receive an amount of carbohydrate and lipids adequate to support their needs on the basis of measured substrate utilization data. Thus, current nutritional approach in these patients, based on commercial formulas, should be challenged with measured substrate utilization-guided nutritional support.

Examination of the Catabolic Rates of 13C-Labeled Fatty Acids Bound to the α and β Positions of Triacylglycerol Using 13CO2 Expired from Mice.

Fatty acids in triacylglycerol (TAG) are catabolized after digestion. However, the catabolic rates of several fatty acids bound to the α (sn-1, 3) or β (sn-2) position of TAG have not been thoroughly compared. In this study, the catabolic rates of 13C-labeled palmitic acid, oleic acid, linoleic acid, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) bound to the α and β position of TAG were compared using isotope ratio mass spectrometry. The catabolic rates of the studied fatty acids were evaluated using the ratio of 13C and 12C in carbon dioxide expired from mice. The results indicated that palmitic acid, oleic acid, or α-linolenic acid bound to the β position was slowly catabolized for a long duration compared to that when bound to the α position. In contrast, EPA bound to the β position was quickly catabolized, and EPA bound to the α position was slowly catabolized for a long time. For linoleic acid or DHA, no difference in the catabolic rates was detected between the binding positions in TAG. Furthermore, EPA and DHA were less catabolized than the other fatty acids. These results indicate that the catabolic rates of fatty acids are influenced by their binding positions in TAG and that this influence on the catabolic rate differed depending on the fatty acid species.

Correlation between Aortic Calcification Score and Biochemical Parameters in Hemodialysis Patients.

The purpose of this study was to determine the correlation between aortic calcification and demographic and biochemical parameters in hemodialysis patients. Calcification scores of the aortic arch and abdominal aorta were determined from multi-slice computed tomography scans and evaluated according to the Agatston score. The associations between demographic and biochemical parameters and aortic calcification score were determined. In total, 190 patients were included in the study. There was a significant positive correlation between aortic calcification scores and age, duration of hemodialysis, cardiothoracic ratio, normalized protein catabolic rate, brachial-ankle pulse wave velocity (baPWV), serum markers of mineral metabolism, and inflammation. A significant negative correlation was found between aortic calcification scores and platelet count. Multivariate analysis showed that age, duration of hemodialysis, baPWV, phosphate, calcium and phosphate (Ca×P) product, parathyroid hormone, and C-reactive protein levels were independent risk factors for calcification of the aortic arch, while baPWV and Ca×P product were independent risk factors for calcification of the abdominal aorta. Key Messages: Aortic calcification scores correlate with age, duration of hemodialysis, and several biochemical parameters of inflammation and mineral metabolism.

Relationship of Plasma-Free Amino Acids and Aminotransferase Expression in Nile Tilapia Oreochromis niloticus (Cichlidae)

There is a relationship between concentrations of free amino acids in blood plasma in Nile tilapia and expression levels of hepatic enzymes involved in protein catabolism. It was established that expression levels of alanine aminotransferase and aspartate aminotransferase hepatic transcripts correlated with clearances of amino acids under deamination. Alanine aminotransferase activity had its maximum at the beginning of absorption, while aspartate aminotransferase had prolonged activity and mainly contributed to metabolism maintenance but did not determine amino acid catabolism rate.

Effect of Calcium Treatment on Catabolic Rates of 13C-Labeled Fatty Acids Bound to the α and β Positions of Triacylglycerol.

The absorption efficacies and catabolic rates of fatty acids are affected by their binding position on triacylglycerol (TAG). However, the kind of effect calcium treatment has on the catabolism of fatty acids is unclear. In this study, the catabolic rates of 13C-labeled palmitic acid, oleic acid, and linoleic acid bound to sn-1, 3 (α) and sn-2 (β) position of TAG in the presence of calcium were compared using isotope ratio mass spectrometry. The catabolic rates of 13C-labeled fatty acids were evaluated using the ratio of 13C to 12C in the carbon dioxide expired by mice. The catabolic rate of palmitic acid bound to the α position was significantly lower than that of palmitic acid bound to the β position of TAG. The rates of 13CO2 formation from palmitic acid at the β position remained higher for a long time. In contrast, oleic and linoleic acids at the α position were as well catabolized as those at the β position. These results indicate that in the presence of calcium, the saturated fatty acid bound to the β position is highly catabolized, whereas that bound to the α position is not well catabolized. Saturated fatty acid at the α position is hydrolyzed by pancreatic lipase to promptly form insoluble complexes with calcium, which are excreted from the body, and thereby reducing the catabolic rate of these fatty acids.

Lipoprotein (a) and Low-density lipoprotein apolipoprotein B metabolism following apheresis in patients with elevated lipoprotein(a) and coronary artery disease.

Lipoprotein apheresis effectively lowers lipoprotein(a) [Lp(a)] and low-density lipoprotein (LDL) by approximately 60%-70%. The rebound of LDL and Lp(a) particle concentrations following lipoprotein apheresis allows the determination of fractional catabolic rate (FCR) and hence production rate (PR) during non-steady state conditions. We aimed to investigate the kinetics of Lp(a) and LDL apolipoprotein B-100 (apoB) particles in patients with elevated Lp(a) and coronary artery disease undergoing regular apheresis. A cross-sectional study was carried out in 13 patients with elevated Lp(a) concentration (>500mg/L) and coronary artery disease. Lp(a) and LDL-apoB metabolic parameters, including FCR and PR were derived by the fit of a compartment model to the Lp(a) and LDL-apoB concentration data following lipoprotein apheresis. The FCR of Lp(a) was significantly lower than that of LDL-apoB (0.39 [0.31, 0.49] vs 0.57 [0.46, 0.71] pools/day, P=0.03) with no significant differences in the corresponding PR (14.80 [11.34, 19.32] vs 15.73 [11.93, 20.75] mg/kg/day, P=0.80). No significant associations were observed between the FCR and PR of Lp(a) and LDL-apoB. In patients with elevated Lp(a), the fractional catabolism of Lp(a) is slower than that of LDL-apoB particles, implying that different metabolic pathways are involved in the catabolism of these lipoproteins. These findings have implications for new therapies for lowering apolipoprotein(a) and apoB to prevent atherosclerotic cardiovascular disease.

The state of nutrition care in outpatient hemodialysis settings in Malaysia: a nationwide survey

BackgroundThis study aimed to assess the situational capacity for nutrition care delivery in the outpatient hemodialysis (HD) setting in Malaysia by evaluating dietitian accessibility, nutrition practices and patients’ outcomes.MethodsA 17-item questionnaire was developed to assess nutrition practices and administered to dialysis managers of 150 HD centers, identified through the National Renal Registry. Nutritional outcomes of 4362 patients enabled crosscutting comparisons as per dietitian accessibility and center sector.ResultsDedicated dietitian (18%) and visiting/shared dietitian (14.7%) service availability was limited, with greatest accessibility at government centers (82.4%) > non-governmental organization (NGO) centers (26.7%) > private centers (15.1%). Nutritional monitoring varied across HD centers as per albumin (100%) > normalized protein catabolic rate (32.7%) > body mass index (BMI, 30.7%) > dietary intake (6.0%). Both sector and dietitian accessibility was not associated with achieving albumin ≥40 g/L. However, NGO centers were 36% more likely (p = 0.030) to achieve pre-dialysis serum creatinine ≥884 μmol/L compared to government centers, whilst centers with dedicated dietitian service were 29% less likely (p = 0.017) to achieve pre-dialysis serum creatinine ≥884 μmol/L. In terms of BMI, private centers were 32% more likely (p = 0.022) to achieve BMI ≥ 25.0 kg/m2 compared to government centers. Private centers were 62% less likely (p < 0.001) while NGO centers were 56% less likely (p < 0.001) to achieve serum phosphorus control compared to government centers. Patients from centers with a shared/visiting dietitian had 35% lower probability (p < 0.001) to achieve serum phosphorus levels below 1.78 mmol/L compared to centers without access to a dietitian.ConclusionsThere were clear discrepancies in nutritional care in Malaysian HD centers. Changes in stakeholder policy are required to ensure that dietitian service is available in Malaysian HD centers.

Effects of mipomersen, an apolipoprotein B100 antisense, on lipoprotein (a) metabolism in healthy subjects

Elevated lipoprotein (a) [Lp(a)] levels increase the risk for CVD. Novel treatments that decrease LDL cholesterol (LDL-C) have also shown promise for reducing Lp(a) levels. Mipomersen, an antisense oligonucleotide that inhibits apoB synthesis, is approved for the treatment of homozygous familial hypercholesterolemia. It decreases plasma levels of LDL-C by 25% to 39% and lowers levels of Lp(a) by 21% to 39%. We examined the mechanisms for Lp(a) lowering during mipomersen treatment. We enrolled 14 healthy volunteers who received weekly placebo injections for 3 weeks followed by weekly injections of mipomersen for 7 weeks. Stable isotope kinetic studies were performed using deuterated leucine at the end of the placebo and mipomersen treatment periods. The fractional catabolic rate (FCR) of Lp(a) was determined from the enrichment of a leucine-containing peptide specific to apo(a) by LC/MS. The production rate (PR) of Lp(a) was calculated from the product of Lp(a) FCR and Lp(a) concentration (converted to pool size). In a diverse population, mipomersen reduced plasma Lp(a) levels by 21%. In the overall study group, mipomersen treatment resulted in a 27% increase in the FCR of Lp(a) with no significant change in PR. However, there was heterogeneity in the response to mipomersen therapy, and changes in both FCRs and PRs affected the degree of change in Lp(a) concentrations. Mipomersen treatment decreases Lp(a) plasma levels mainly by increasing the FCR of Lp(a), although changes in Lp(a) PR were significant predictors of reductions in Lp(a) levels in some subjects.

Association of serum angiopoietin-2 with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients: a prospective cohort study

BackgroundTo examine serum angiopoietin-2 (Angpt-2) in relation to malnutrition, inflammation, atherosclerosis and cardiac valvular calcification, so-called MIAC syndrome and its predictive role in outcomes of peritoneal dialysis (PD) patients.MethodsA prospective observational study was conducted in 324 chronic PD patients. Biochemical analysis was performed at baseline for serum angiopoietins, albumin and high sensitive C-reactive protein (hs-CRP) and echocardiography was done to detect cardiac valvular calcification. Primary study end points were fatal or nonfatal cardiovascular events and mortality.ResultsThe median of serum Angpt-2 levels was 5.44 ng/mL (interquartile range, 3.41–7.85). Across the three tertiles of serum Angpt-2, a significant trend effect was observed for body mass index, normalized protein catabolic rate, calcium × phosphorus product, hs-CRP, brain natriuretic peptide, lower-density lipoprotein cholesterol, left ventricular ejection fraction, total weekly urea clearance and residual renal function (all p < 0.05). Serum Angpt-2 showed a significant increase across the four groups of patients with increasing components of MIAC syndrome (p < 0.001). There were 77 deaths and 57 cardiovascular events. High serum Angpt-2 was an independent predictor of fatal and nonfatal cardiovascular events in PD patients (p = 0.02), however serum Angpt-2 was not an independent predictor of all-cause mortality (p = 0.3).ConclusionsSerum Angpt-2 showed close association with valvular calcification, atherosclerosis, inflammation and malnutrition, having significant independent prognostic value and is useful for cardiovascular event stratification in chronic PD patients. Angpt-2 might be a potential mediator of increased cardiovascular risk in patients undergoing PD treatment.

Serum levels of the adipokine zinc-alpha2-glycoprotein (ZAG) predict mortality in hemodialysis patients

Wasting has been associated with increased cardiovascular and all-cause mortality in chronic kidney disease (CKD). We investigated whether serum zinc-alpha2-glycoprotein (ZAG), a potent cachectic and lipid-mobilizing factor that is increased in patients with CKD, predicts clinical outcomes in patients on chronic hemodialysis. We quantified serum ZAG at baseline in a prospective cohort of 252 patients undergoing maintenance hemodialysis. Serum ZAG concentrations were inversely associated with serum albumin, creatinine, and triglycerides and, conversely, positively associated with age. Although ZAG is strongly linked to protein energy wasting (PEW) in patients with cancer, higher ZAG concentrations were not associated with PEW in our cohort. During a mean study follow-up of 954 days, 49 patients died and 62 patients experienced a cardiovascular event. Kaplan-Meier analysis revealed a significant correlation between serum ZAG concentrations and all-cause mortality and cardiovascular events. In separate multivariable Cox regression models, serum ZAG concentrations remained significantly associated with all-cause mortality and cardiovascular events after adjustment for demographic factors (age, sex, and dialysis vintage), metabolic parameters (serum albumin, prealbumin, triglycerides, cholesterol, normalized protein catabolic rate, and body mass index), and cardiovascular risk factors (diabetes, dyslipidemia, history of cardiovascular disease, smoking, and diuretic use as a proxy of residual renal function). Thus, serum ZAG appears to be a strong and independent predictor of mortality and cardiovascular events in patients with end-stage renal disease. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms.

Eliminating the need for routine monthly postdialysis serum urea nitrogen measurement: A method for monitoring Kt/V and normalized protein catabolic rate using conductivity determined dialyzer clearance.

Many dialysis machines can compute dialyzer sodium clearances at multiple time points during a dialysis treatment using conductivity. For a given treatment, the average dialyzer sodium clearance (K), when combined with treatment time (t), and the estimated urea distribution volume (V, usually based on either anthropometry or bioimpedance), can be used to estimate Kt/V, an important measure of hemodialysis adequacy. While this conductivity-derived value for Kt/V correlates moderately with Kt/V calculated from predialysis and postdialysis serum urea nitrogen (SUN) values (urea reduction ratio, URR), the ultrafiltration volume, and session length it is, unfortunately, not sufficiently accurate to replace URR-based Kt/V. Here we underline the potential utility of an alternative method to estimate Kt/V (a variant of a technique originally proposed by Gotch and Levin and their colleagues) using conductivity-derived sodium clearance (K) that does not require routine measurement of the postdialysis SUN but which should closely track Kt/V computed in the usual fashion. The increased accuracy with the new method is explained by the use of a patient-specific value of V, which is an average value calculated from several dialysis sessions where both conductivity dialyzer clearance and predialysis and postdialysis SUN have been measured. Once this patient-specific conductivity/URR-based value for V has been determined, it can be used to calculate Kt/V for subsequent treatments in which conductivity-based dialyzer clearances are measured, but around which predialysis and postdialysis SUN values have not been obtained. (If the predialysis SUN values for such a subsequent treatment are also measured, then a normalized protein catabolic rate that closely tracks the value from conventional urea modeling, can also be determined.) By reducing the number of postdialysis SUN measurements needed to monitor hemodialysis adequacy this new method of estimating Kt/V by conductivity should save staff time and laboratory costs, increase patient and staff safety, and decrease error rates associated with improper postdialysis blood sampling technique.

Nitrogen excretion during marsupial development in the terrestrial isopod Armadillidium vulgare

Marsupial embryos of Armadillidium vulgare (Isopoda: Oniscidea) were collected at different stages of development and assayed for products of nitrogen excretion. Stages were classified as early stage one, late stage one (clear embryo and somite differentiation), early stage two (chorion shed, prior to blastokinesis), late stage two (following blastokinesis), and mancae (vitelline membrane shed; second embryonic molt). Stage one and stage two embryos were primarily ammonotelic. Mancae showed a significant increase in stored uric acid and decrease in ammonia production, in most cases to undetectable levels. The increased metabolic rate of mancae, and the fact that they imbibe marsupial fluid prior to exiting the marsupium, may have favored a switch from ammonotely to uricotely to avoid ammonia toxicity. Protein metabolism, estimated from ammonia production, accounted for 7% of the measured catabolic rate in Stage 2 embryos. Newly emerged juveniles showed a >2-fold increase in metabolism relative to mancae, accompanying the transition from aquatic to aerial respiration. Following 48 h post-emergence, juveniles resumed ammonia excretion, volatilizing the base (NH3) as in later instars. Elevated ammonia excretion in early juveniles may derive from the catabolism of remaining yolk protein. A sharp increase in whole-animal glutamine in juveniles is consistent with its role as an intermediary nitrogen store during periodic ammonia excretion. Total ammonia concentration in the marsupial fluid fluctuated but did not increase significantly over time and ammonia was not volatilized across the oostegites, indicating that embryo ammonia is transported into the maternal hemolymph for excretion.

101. Lipoprotein turnover and possible remnant accumulation in preeclampsia: Insights from the Freiburg preeclampsia H.E.L.P.-Apheresis Study

Introduction Preeclampsia is a potentially life threatening disease occurring in pregnancy. The only causative cure consists in delivery with all the risks for a premature fetus. In preeclampsia, the lipid metabolism is substantially altered and lipid apheresis is being explored as a possible therapeutic approach to prolong preeclamptic pregnancies and allow further maturation of the fetus. In the Freiburg H.E.L.P.-Apheresis Study, 6 early onset preeclamptic patients were treated with H.E.L.P. apheresis. Objective/hypothesis Detailed analysis of apheresis-induced dynamics in serum lipid parameters. Methods 6 early onset preeclamptic patients underwent repeated apheresis treatments (n = 23). We evaluated parameters of the lipoprotein metabolism in 6 preeclamptic patients in detail. Results Reduction of lipoproteins by apheresis was lower than theoretically expected. Lipids reached previous pre-apheresis levels before the next apheresis even though apheresis was repeated within 2.9 ± 1.2 days. Fractional catabolic rates and synthetic rates were found to be substantially elevated, with fractional catabolic rates for ApoB/ LDL-cholesterol being 0.7 ± 0.3/ 0.4 ± 0.2 [day−1] and synthetic rates being 26 ± 8/ 17 ± 8 [mg*kg−1*day−1]. The distribution of LDL-subclasses after apheresis shifted to larger buoyant LDL, while IDL levels remained unaffected. Discussion Apheresis induced changes in lipoprotein profiles point to an underlying remnant removal disease like imbalance in plasma lipid conversion during preeclamptic conditions.

Liraglutide Reduces Postprandial Hyperlipidemia by Increasing ApoB48 (Apolipoprotein B48) Catabolism and by Reducing ApoB48 Production in Patients With Type 2 Diabetes Mellitus

Objective- Treatment with liraglutide, a GLP-1 (glucagon-like peptide-1) agonist, has been shown to reduce postprandial lipidemia, an important feature of diabetic dyslipidemia. However, the underlying mechanisms for this effect remain unknown. This prompted us to study the effect of liraglutide on the metabolism of ApoB48 (apolipoprotein B48). Approach and Results- We performed an in vivo kinetic study with stable isotopes (D8-valine) in the fed state in 10 patients with type 2 diabetes mellitus before treatment and 6 months after the initiation of treatment with liraglutide (1.2 mg/d). We also evaluated, in mice, the effect of a 1-week liraglutide treatment on postload triglycerides and analysed in vitro on jejunum, the direct effect of liraglutide on the expression of genes involved in the biosynthesis of chylomicron. In diabetic patients, liraglutide treatment induced a dramatic reduction of ApoB48 pool (65±38 versus 162±87 mg; P=0.005) because of a significant decrease in ApoB48 production rate (3.02±1.33 versus 6.14±4.27 mg kg-1 d-1; P=0.009) and a significant increase in ApoB48 fractional catabolic rate (5.12±1.35 versus 3.69±0.75 pool d-1; P=0.005). One-week treatment with liraglutide significantly reduced postload plasma triglycerides in mice and liraglutide, in vitro, reduced the expression of ApoB48, DGAT1 (diacylglycerol O-acyltransferase 1), and MTP (microsomal transfer protein) genes. Conclusions- We show that treatment with liraglutide induces a significant reduction of the ApoB48 pool because of both a reduction of ApoB48 production and an increase in ApoB48 catabolism. In vitro, liraglutide reduces the expression of genes involved in chylomicron synthesis. These effects might benefit cardiovascular health. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02721888.

Gibbs Energy Dynamic Yield Method (GEDYM): Predicting microbial growth yields under energy-limiting conditions

Biomass-explicit biogeochemical models assign microbial growth yields (Y) using values measured in the laboratory or predicted using thermodynamics-based methods. However, Y values are rarely measured under the low energy delivery conditions that often prevail in the subsurface, and existing predictive methods for calculating Y values when the catabolic energy supply rate is limited remain poorly tested. Here, we derive and validate a new semi-theoretical method for calculating Y values: the Gibbs Energy Dynamic Yield Method (GEDYM). Method validation relies on a compilation of 132 geochemically relevant literature Y values comprising predominantly (60%) low energy (> −25 kJ (mol e−)−1) metabolisms. GEDYM is based on estimating the Gibbs energy change of the metabolic reaction (ΔGmet), which links the Gibbs energy changes of the catabolic (ΔGcat) and anabolic (ΔGan) reactions of a microorganism through its growth yield. Given that the values of ΔGmet,ΔGcat and ΔGan all depend on their respective reaction quotients, the resulting Y values account for changes in the chemical environment surrounding the cells. GEDYM incorporates an empirical relationship that accurately estimates the extent to which ΔGmet deviates from its standard state value from the relative difference between ΔGcat and its corresponding standard state value. GEDYM yields Y values with lower relative errors and statistical bias than the existing Gibbs energy dissipation method (GEDM). Using dissimilatory iron reduction, sulfate reduction and methanogenesis as examples, we illustrate the importance of considering variations in ΔGcat and ΔGan when predicting Y values for individual metabolisms. Because of its ability to dynamically adjust the values of ΔGmet and Y to variable geochemical conditions, GEDYM yields a more realistic representation of geomicrobial activity in predictive reactive transport models.

Total weight loss obtained after 2 weeks of very low caloric diet is strongly associated with baseline (net) protein catabolic and glutamine production rates

Rationale: Obesity is a major healthcare problem and the need for management is well established. Very Low-Calorie Diet (VLCD) is often used for weight reduction, but large individual changes in weight loss between subjects have been observed. We studied whether the variation in weight loss after a VLCD among (morbidly) obese participants can be explained by individual differences in baseline protein and amino acid metabolism (so-called “metabolic phenotyping”).

The impact of residual renal function on quality of life in patients with peritoneal dialysis .

Residual renal function (RRF) is a crucial factor that plays an important role in peritoneal dialysis (PD) patients, but whether RRF influences the quality of life (QOL) of PD patients is still controversial. The aims of this study were to explore the effects of RRF on QOL in patients with continuous ambulatory peritoneal dialysis (CAPD) and analyze the related factors that might affect patients' QOL. All 120 adult patients in this study received regular CAPD treatment for at least 3 months. Patients were divided into two groups: an RRF group (residual glomerular filtration (rGFR) ≥ 1 mL×min-1×(1.73m2)-1) and a non-RRF group (rGFR ≥ 1 mL×min-1×(1.73m2)-1). The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was used as a reference to calculate the scores of CAPD patients for assessing their QOL. Multiple- and single-linear regression analysis was performed to analyze correlation degree of several SF-36-related indexes. The indexes of age, gender, cause of disease, complication, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), hemoglobin (HB), cholesterol, triglycerides, high- and low-density lipoprotein, normalized protein catabolic rate (nPCR), and cardiothoracic ratio (CTR) showed no difference between the two groups (RRF and non-RRF). Comparing with RRF group, the patients without RRF showed a significant difference on indexes of PD duration, urine volume, ultrafiltration volume, dialysis dose, serum albumin, potassium, Kt/V (urea reduction ratio), creatinine, calcium, phosphate, C-reactive protein (CRP), and parathyroid hormone (PTH). Single-linear regression analysis that achieved total score of SF-36 showed no correlation with rGFR, but there was a correlation of SF-36 score with CRP, creatinine, CTR, albumin, and ultrafiltration volume. These results suggested that there was no correlation between RRF and QOL in CAPD patients, but chronic inflammation, fluid overload, and malnutrition were considered as the main factors that affect patients' QOL. .

Plasma PCSK9 correlates with apoB-48-containing triglyceride-rich lipoprotein production in men with insulin resistance

Intestinal triglyceride (TG)-rich lipoproteins (TRLs) are important in the pathogenesis of atherosclerosis in insulin resistance (IR). We investigated the association of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations with apoB-48-containing TRL metabolism in 148 men displaying various degrees of IR by measuring in vivo kinetics of TRL apoB-48 during a constant-fed state after a primed-constant infusion of L-[5,5,5-D3]leucine. Plasma PCSK9 concentrations positively correlated with TRL apoB-48 pool size (r = 0.31, P = 0.0002) and production rate (r = 0.24, P = 0.008) but not the fractional catabolic rate (r = -0.04, P = 0.6). Backward stepwise multiple linear regression analysis identified PCSK9 concentrations as a positive predictor of TRL apoB-48 production rate (standard β = +0.20, P = 0.007) independent of BMI, age, T2D/metformin use, dietary fat intake during the kinetic study, and fasting concentrations of TGs, insulin, glucose, LDL cholesterol, or C-reactive protein. We also assessed intestinal expression of key genes involved in chylomicron processing from duodenal samples of 71 men. Expression of PCSK9 and HMG-CoAR genes was positively associated (r = 0.43, P = 0.002). These results support PCSK9 association with intestinal secretion and plasma overaccumulation of TRL apoB-48 in men with IR.