Catabolic Rate Research Articles

Validation of formulas calculating normalized protein catabolic rate in patients undergoing home hemodialysis.

Depner and Daugirdas developed a simplified formula to estimate the normalized protein catabolic rate in patients on twice- or thrice-weekly hemodialysis (JASN, 1996). The aim of our work was to establish formulas in more frequent schedules and validate them in home-based hemodialysis patients. We realized that the structure of Depner and Daugirdas' normalized protein catabolic rate formulas has a general meaning and can be expressed as PCRn = C0/[a + b*(Kt/V) + c/(Kt/V)] + d, where C0 is pre-dialysis blood urea nitrogen, Kt/V is dialysis dose,a, b, c, dare the specific coefficients for each combination of home-based hemodialysis schedules and the day of blood sampling. The same applies to the formula that adjusts C0 (C'0) for residual kidney clearance of blood water urea (Kru) and urea distribution volume (V): C'0 = C0*[1 + (a1 + b1/(Kt/V))*Kru/V]. On this basis, we computed the six coefficients (a, b, c, d, a1, b1) for each of the 50 possible combinations and simulated a total of 24,000 weekly dialysis cycles using the Daugirdas Solute Solver software recommended by the KDOQI 2015 guidelines. From the associated statistical analyses we obtained 50 sets of coefficient values, which were validated comparing the paired normalized protein catabolic rate values (i.e., those estimated with our formulas with those modeled with Solute Solver) in 210 datasets of27patients on home-based hemodialysis. The mean values ± SD were 1.06 ± 0.262 and 1.07 ± 0.283g/kg/day, respectively, with a mean difference of 0.004 ± 0.034g/kg/day (p = 0.11). The paired values were highly correlated (R2 = 0.99). In conclusion, even if the coefficient values were validated in a relatively small sample of patients, they allow an accurate estimation of normalized protein catabolic rate in home-based hemodialysis patients.

#5941 SERUM LEPTIN AND MALNUTRITION IN PERITONEAL DIALYSIS PATIENTS: A CONNECTION YET TO BE FOUND

Abstract Background and Aims Leptin is a hormone responsible for the modulation of the satiety signals and that it is known for being increased in patients undergoing Peritoneal Dialysis (PD) treatment. Nevertheless, conclusions about its role in the malnutrition associated with this technique remains to be done. Our study aimed to characterize the nutritional state of a Portuguese program of PD and to establish the impact that leptin levels had on it. Method A cross-sectional study was performed involving 28 patients of a PD program. To characterize the patients’ nutritional status we collected the following data: anthropometric measurements (weight, body mass index (BMI), fat tissue index and lean tissue index using Fresenius ® Body Composition Monitor), analytical values (albumin, total proteins, total cholesterol, high-density lipoprotein cholesterol, low-density cholesterol, triglycerides, leptin serum levels), protein metabolism (normalized protein catabolic rate (nPCR), normalized dialysate protein loss (nEPL), normalized urine protein loss (nUPL), normalized total protein loss (nTPL) and normalized dietary protein requirement (nDPR)) and peritoneal dialysis adequacy (total, renal and peritoneal kT/v; total, renal and peritoneal creatinine clearance). The collected data were statistically analyzed and correlations were made using Mann-Whitney U test and Spearman test, depending on the variable type. Results 7 (25%) patients were females, and the mean age was 59.5 years old (± 14.31). The mean dialysis vintage was 27.04 months (± 20.14) and the majority (n=23, 82,1%) preformed automated peritoneal dialysis (APD). Regarding the nutritional status, the mean BMI, FTI and LTI was 26.64 kg/m2 (±4.39), 14.24 kg/m2 (±5.47) and 11.62 kg/m2 (±2.52) respectively. 57.1% (n=16) had serum albumin below 3.5 mg/dL, with a mean phosphorus of 5.01mg/dl (±0.72) and a mean leptin of 28.58ng/mL (±28.44). The serum leptin was 5.4 times higher than the adjusted value for BMI in the population without kidney disease. The adjusted serum leptin for BMI was different between sex (U=15, P = .001) and it was positively correlated with total (ρ=0.47, P = .012) and high-density lipoprotein (HDL) cholesterol (ρ=0.535, P = .003). It was not associated with the protein metabolism (nPCR, nEPL, nUPL, nTOL and nDPR), albumin or total proteins and PD adequacy. Conclusion Leptin values independent of BMI are significantly higher amongst patients on PD. Alike the healthy population, women on PD are also prone to have higher serum leptin values. Although studies are still controversial about the association between this hormone and cholesterol, in this population there is a positive correlation. As so, hyperleptinaemia cannot yet be associated with the malnutrition that is generally present amongst PD patients, but it must be considered as a contribute to the already known increased cardiovascular risk.

#4971 IMPACT OF RAMADAN FASTING ON NUTRITION, INFLAMMATION AND DIALYSIS ADEQUACY AMONG HEMODIALYSIS PATIENTS

Abstract Background and Aims There is a paucity of data concerning safety of fasting in Ramadan in End stage kidney disease patients (ESKD) on haemodialysis (HD). The aim of the present study was to assess the possible effect of fasting on nutritional status (clinical, biochemical variables), inflammatory status and adequacy of haemodialysis. This observational study was carried out during 2022 when fasting duration was around 14 hours. Method Sixty-five patients suffered from ESKD who received regular HD for more than six months in dialysis unit, urology and nephrology center Mansoura university were included in this prospective observational study. Patients were categorized into three groups. 21 patients fasted all days of Ramadan,25 patients fasted days other than session days and 19 patients never. We did not oblige our patient to fast. nutritional status was assessed clinically by Anthropometric measurements including body weight, BMI, triceps skin fold thickness (TSF) and estimation of protein catabolic rate (PCR) were measured, and laboratory by serum Albumin, cholesterol and fasting blood glucose. Neutrophils to lymphocytes ratio (NLR), Soluble receptor of advanced glycation end product(SRAGE) and human B-cell lymphoma/leukemia2 (BCL2) was measured as inflammatory markers, also dialysis adequacy was determined with urea reduction ratio (URR) and KT/V. Assessment of all patients were carried out before and after Ramadan month and was repeated 3 months after Ramadan in all patients. Results In 30 days fasting group: there was significant reductions (all P < .02), serum albumin, triceps skin fold thickness, Subjective global assessment score (SGA) for nutritional assessment also in inflammatory markers as neutrophils to lymphocytes ratio (NLR) and human Bcell lymphoma/leukemia2 (BCL2). But these were not accompanied by any significant change (all P >0.05) in body mass index, serum cholesterol, fasting blood sugar (FBS), urea reduction ratio (URR), intradialytic weight gains (IDWG), Kt/V and human soluble receptor for advanced glycation end products (sRAGEs). In the group Who was reported fasting in days other than HD session days: fasting led to significant reductions (all P < .02) only in serum albumin and triceps skin fold thickness. There were no significant changes in BMI, URR, Cholesterol, FBS, KT/V, IDWG, SGA score, NLR, sRAGEs and BCL2. In patients Who never fast at all: there was significant reduction (all P<0.02) in triceps skin fold thickness, significant change in SGA score and also in sRAGEs and BCL2. Conclusion There was no harmful effect for Muslim patients receiving regular HD who want to fast Ramadan in days other than HD session days. In the current study the fasting group has the benefit of both being fasting and non-significant changes in mostly all nutritional assessment points, inflammatory markers and the adequacy of HD.

Complement protein C1q stimulates hyaluronic acid degradation via gC1qR/HABP1/p32 in malignant pleural mesothelioma.

Complement component C1q can act as a pro-tumorigenic factor in the tumor microenvironment (TME). The TME in malignant pleural mesothelioma (MPM) is rich in C1q and hyaluronic acid (HA), whose interaction enhances adhesion, migration and proliferation of malignant cells. HA-bound C1q is also capable of modulating HA synthesis. Thus, we investigated whether HA-C1q interaction would affect HA degradation, analyzing the main degradation enzymes, hyaluronidase (HYAL)1 and HYAL2, and a C1q receptor candidate. We first proceeded with the characterization of HYALs in MPM cells, especially HYAL2, since bioinformatics survival analysis revealed that higher HYAL2 mRNA levels have an unfavorable prognostic index in MPM patients. Interestingly, Real-Time quantitative PCR, flow cytometry and Western blot highlighted an upregulation of HYAL2 after seeding of primary MPM cells onto HA-bound C1q. In an attempt to unveil the receptors potentially involved in HA-C1q signaling, a striking co-localization between HYAL2 and globular C1q receptor/HABP1/p32 (gC1qR) was found by immunofluorescence, surface biotinylation and proximity ligation assays. RNA interference experiments revealed a potentially regulatory function exerted by gC1qR on HYAL2 expression, since C1QBP (gene for gC1qR) silencing unexpectedly caused HYAL2 downregulation. In addition, the functional blockage of gC1qR by a specific antibody hindered HA-C1q signaling and prevented HYAL2 upregulation. Thus, C1q-HA interplay is responsible for enhanced HYAL2 expression, suggesting an increased rate of HA catabolism and the release of pro-inflammatory and pro-tumorigenic HA fragments in the MPM TME. Our data support the notion of an overall tumor-promoting property of C1q. Moreover, the overlapping localization and physical interaction between HYAL2 and gC1qR suggests a potential regulatory effect of gC1qR within a putative HA-C1q macromolecular complex.

Factors affecting presenteeism in workers with nocturnal hemodialysis: A two-center cross-sectional study.

Presenteeism and work dysfunction in dialysis patients should be assessed to improve disease management and work productivity. Therefore, this study aimed to investigate the prevalence and factors surrounding presenteeism and work dysfunction in workers with nocturnal hemodialysis. This multicenter cross-sectional study included 42 workers with nocturnal hemodialysis. Presenteeism was measured in patients using the Work Functioning Impairment Scale (WFun), employment status, exercise habit, and exercise self-efficacy (SE). The WFun score was 12.5 ± 6.3 points, and patients with mild presenteeism were 12 (28.6%), moderate was 2 (4.8%), and severe was 1 (2.4%). Multiple regression analysis, which was adjusted for few confounding factors, showed that WFun had a significant relationship with lower exercise SE (r = -0.32) and normalized protein catabolism rate (r = 0.31). Working patients with nocturnal hemodialysis had presenteeism and a significant correlation with exercise SE and nPCR. This study provides a framework to prevent work dysfunction in nocturnal hemodialysis patients.

Correlation of Serum Asprosin Levels With Normalized Protein Catabolic Rate in Patients Receiving Peritoneal Dialysis Treatment.

Background Peritoneal dialysis patients are malnourished due to loss of protein in the dialysate and inadequate dialysis, although they take additional calories every day during treatment. Many parameters are used to assess nutritional status, with normalized protein catabolic rate (nPCR) being one of the most common. Asprosin, a novel adipokine secreted by adipose tissue, peaks during fasting and induces hepatic glucose release through the activation of the G-protein-cAMP-PKA pathway, which has been indicated to have a curative effect on chronic inflammation. In this study, we aimed to investigate the relationship between asprosin levels and nutritional parameters in patients receiving peritoneal dialysis treatment as well as to investigate the applicability of more practical tests. Methodology A total of 70 peritoneal dialysis patients, 35 female (59%) and 24 male (41%), were included in the study. The mean age of the patients was 53 ± 14 years (range = 18-80 years), and the median peritoneal dialysis duration was 31.5 months (range = 20-56.2 months). The most common etiologic cause was hypertension(37%). Patients over 18 years of age who had been receiving peritoneal dialysis treatment for at least 24 months were included in the study. The correlation between patients' nPCR levels and serum asprosin, body mass index, and lipids was evaluated. Results The correlation between the level of nPCR and the serum asprosin level, body mass index, and lipids was evaluated. Patients with nPCR <0.815 were considered malnourished, and factors affecting malnutrition were determined by univariate analysis. Among the factors affecting malnutrition according to univariate analysis, those with p-value <0.05 were analyzed by multivariate analysis. Low asprosin level was one of the independent factors affecting malnutrition in patients (Exp(B) = 0.944, 95% confidence interval (CI) = 0.896-0.994). Other independent factors affecting malnutrition were Kt/V (Exp(B) = 0.018, 95% CI = 0.001-0.550) and residual renal function (Exp(B) = -0.004, 95% CI = 0.993-0.999). Conclusions There is a need for more accessible tests and reliable parameters to evaluate dialysis and nutritional deficiency in peritoneal dialysis patients. One possible hormone that could serve as a guide is asprosin.

Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control

Considerable evidence confirms the importance of Cyp26a1 to all-trans-retinoic acid (RA) homeostasis during embryogenesis. In contrast, despite its presence in postnatal liver as a potential major RA catabolizing enzyme and its acute sensitivity to induction by RA, some data suggested that Cyp26a1 contributes only marginally to endogenous RA homeostasis postnatally. We report reevaluation of a conditional Cyp26a1 knockdown in the postnatal mouse. The current results show that Cyp26a1 mRNA in WT mouse liver increases 16-fold upon refeeding after a fast, accompanied by an increased rate of RA elimination and a 41% decrease in the RA concentration. In contrast, Cyp26a1 mRNA in the refed homozygotic knockdown reached only 2% of its extent in WT during refeeding, accompanied by a slower rate of RA catabolism and no decrease in liver RA, relative to fasting. Refed homozygous knockdown mice also had decreased Akt1 and 2 phosphorylation and pyruvate dehydrogenase kinase 4 (Pdk4) mRNA and increased glucokinase (Gck) mRNA, glycogen phosphorylase (Pygl) phosphorylation, and serum glucose, relative to WT. Fasted homozygous knockdown mice had increased glucagon/insulin relative to WT. These data indicate that Cyp26a1 participates prominently in moderating the postnatal liver concentration of endogenous RA and contributes essentially to glucoregulatory control.

MP16-18 ASSOCIATION BETWEEN SOCIAL DETERMINANTS OF HEALTH AND 24-HOUR URINE COMPOSITION IN PATIENTS WITH NEPHROLITHIASIS

You have accessJournal of UrologyCME1 Apr 2023MP16-18 ASSOCIATION BETWEEN SOCIAL DETERMINANTS OF HEALTH AND 24-HOUR URINE COMPOSITION IN PATIENTS WITH NEPHROLITHIASIS Max Abramson, Kevin Labagnara, Rutul D Patel, Alexander C Small, and Dima Raskolnikov Max AbramsonMax Abramson More articles by this author , Kevin LabagnaraKevin Labagnara More articles by this author , Rutul D PatelRutul D Patel More articles by this author , Alexander C SmallAlexander C Small More articles by this author , and Dima RaskolnikovDima Raskolnikov More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003236.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Social determinants of health (SDH) are economic and environmental conditions that influence patients’ health. While dietary and environmental factors are known to influence kidney stone disease (KSD) risk, the effects of SDH have not been well explored. We used a validated 10-item social needs screener (SNS) to assess the relationship between SDH and 24-hour urine composition in patients with nephrolithiasis. METHODS: Between 04/2018 and 06/2022, the SNS tool was implemented as a population health initiative in the primary care clinic of our institution, which acts as a safety-net hospital in a low-resource, urban setting. We retrospectively identified the patients who were referred to urology and underwent 24-hour urine collection for KSD evaluation. The SNS included questions on housing, utilities, finances, transportation, healthcare costs, and other SDH needs. Patient demographics, comorbidities, and 24-hour urine parameters were compared between those with and without self-reported unmet SDH needs. RESULTS: Of the 5,403 patients referred to urology who previously completed the SNS, 1,456 had a diagnosis of nephrolithiasis and 124 completed a 24-hour urine analysis. Respondents were mostly female (64%) and Hispanic (56%). Consistent with the larger cohort of non-stone formers, 18 patients (15%) with recurrent nephrolithiasis expressed 1+ unmet SDH need. Those with SDH needs were more likely to be enrolled in Medicare/Medicaid than private insurance (94% vs 62%, p=0.007) and to have diabetes (72% vs 39%, p=0.008) when compared to those without social needs. On 24-hour urine analysis, those with 1+ SDH need had less urinary uric acid (0.44 vs 0.60, p=0.019), sulfate (25 vs 31, p=0.014), and urea nitrogen (7.55 vs 8.77, p=0.044), and a lower protein catabolic rate (0.75 vs 0.88; p=0.026). There were no differences in other 24-hour urinary parameters or stone composition. CONCLUSIONS: Patients with nephrolithiasis and unmet SDH needs have unique findings on 24-hour urinary testing. The use of a validated SDH screening tool may help to identify patients with KSD and unique risk factors for recurrence. Further prospective study is needed to explore this relationship and identify opportunities for improved nephrolithiasis treatment in patients with social and economic barriers to care. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e209 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Max Abramson More articles by this author Kevin Labagnara More articles by this author Rutul D Patel More articles by this author Alexander C Small More articles by this author Dima Raskolnikov More articles by this author Expand All Advertisement PDF downloadLoading ...

Folate Catabolism is Related to Growth Rate in Weanling Rats

The relationship between growth rate and folate catabolism was determined using a catch-up growth model in weanling rats. A recently developed HPLC method was employed to compare the urinary excretion of the major end product of folate catabolism, acetamidobenzoylglutamate (apABGlu), in normally growing (n = 8) and age-matched growth-restricted (n = 8) weanling animals, during and after food restriction. During the 12-d period of food restriction in which restricted rats were fed (per gram of body weight) at a level of 50% of the required dietary intake for normal growth, apABGlu excretion was significantly higher in normally growing rats compared with growth-restricted rats. In the latter group after restriction, apABGlu concentrations increased markedly, tending to exceed those of normally growing rats of comparable age. Thus growth retardation resulted in a decreased rate of folate catabolism, whereas accelerated growth following dietary restriction was associated with an increase in catabolism. Because early growth in rats is predominantly hyperplastic, these results suggest that the rate of folate catabolism is related to folate utilization in cell division.

Folate Catabolism Is Increased during Pregnancy in Rats

The hypothesis examined in the present study is that pregnancy results in a greater rate of folate catabolism. Mammalian folate catabolism proceeds by cleavage of the vitamin at the C9-N10 position to yield p-aminobenzoylglutamate, which is quantitatively excreted in the urine after its acetylation. A recently developed HPLC method for the determination of endogenous levels of this catabolite, acetamidobenzoylglutamate, in rat urine was used to investigate folate catabolism in three groups of female rats (n = 6/group), one nonpregnant and two pregnant groups. One of the pregnant groups was allowed to feed freely whereas the other was pair-fed to the nonpregnant control group. The daily excretion of acetamidobenzoylglutamate was stable in the nonpregnant group over the experimental period but increased significantly with progression of gestation in both pregnant groups, in which values peaked at d 18 to concentrations of up to three times those of the nonpregnant animals. In both pregnant groups the values fell significantly before parturition, demonstrating that increased catabolism of folate is a feature of pregnancy per se and not simply due to increased weight. These results suggest that increased catabolism may make an important contribution to the folate deficiency associated with pregnancy.

High Protein Whole Food Snack and Albumin Outcomes in Patients With Dialysis-Dependent Chronic Kidney Disease

Protein-energy wasting is common among patients on hemodialysis (HD). This study sought to define effects that a novel, post-HD, high-calorie, high-protein whole food snack had on patients' serum albumin (serum alb), serum phosphorus and equilibrated normalized protein catabolic rate (enPCR). A 12-month (6months intervention, 6months pre/post data collection), single-center, unblinded study was conducted. Participants (n=67) consumed, ad libitum, a whole food snack post-HD for 6 treatments each month. Upon analysis, regression models identified relationships between serum alb and whole food snack consumption across follow up. Predefined effect size anticipated was + 0.2g/dL. Patients were stratified by high (≥4g/dL) or low (<4g/dL) mean serum alb during a 3-month baseline period. Paired t-tests compared mean per patient difference in serum alb, enPCR and serum phosphorus from baseline to each month of follow up, stratified by high (≥640 g) or low (<640 g) consumption of the whole food snack (a priori caloric estimation). Linear regression models showed positive associations between higher serum alb and enPCR with higher whole food snack consumption across follow up (all P<.05). Assessments from baseline to each follow-up month show some increases in serum alb, yet t test comparisons were not significant. No significant changes were seen in serum phosphorus levels during follow-up. Albeit the catabolic effects of HD are well-known, effective nutritional interventions are scarce. Results showed that providing a whole food snack post-HD to individuals with serum alb <4.0g/dL may be beneficial but further studies are recommended.

Tracking fungal species-level responses in soil environments exposed to long-term warming and associated drying.

Climate change is affecting fungal communities and their function in terrestrial ecosystems. Despite making progress in the understanding of how the fungal community responds to global change drivers in natural ecosystems, little is known on how fungi respond at the species level. Understanding how fungal species respond to global change drivers, such as warming, is critical, as it could reveal adaptation pathways to help us to better understand ecosystem functioning in response to global change. Here, we present a model study to track species-level responses of fungi to warming-and associated drying-in a decade-long global change field experiment; we focused on two free-living saprotrophic fungi which were found in high abundance in our site, Mortierella and Penicillium. Using microbiological isolation techniques, combined with whole genome sequencing of fungal isolates, and community level metatranscriptomics, we investigated transcription-level differences of functional categories and specific genes involved in catabolic processes, cell homeostasis, cell morphogenesis, DNA regulation and organization, and protein biosynthesis. We found that transcription-level responses were mostly species-specific but that under warming, both fungi consistently invested in the transcription of critical genes involved in catabolic processes, cell morphogenesis, and protein biosynthesis, likely allowing them to withstand a decade of chronic stress. Overall, our work supports the idea that fungi that invest in maintaining their catabolic rates and processes while growing and protecting their cells may survive under global climate change.

PS-C18-6: THE IMPACT OF ANTIHYPERTENSIVE DRUG USE ON INTRADIALYTIC BLOOD PRESSURE DECLINE CONSIDERING SEASONAL VARIATION: A RETROSPECTIVE COHORT STUDY

Objective: Risk factors of intradialytic systolic blood pressure decline remain less understood. We aimed to identify clinical and laboratory predictors of intradialytic systolic blood pressure decline, considering its seasonal variation. Design and method: In a retrospective cohort of 47,219 hemodialysis sessions from 307 patients undergoing hemodialysis for 1 year in three dialysis clinics, seasonal variation and intradialytic systolic blood pressure decline predictors (predialysis systolic blood pressure - nadir intradialytic systolic blood pressure) were assessed using cosinor analysis and linear mixed models adjusted for baseline/monthly hemodialysis-related variables, respectively. Results: Intradialytic systolic blood pressure decline was highest and lowest in the winter and summer, respectively, following a clear seasonal pattern. In both models adjusted for baseline and monthly hemodialysis-related parameters, calcium channel blocker use was associated with a smaller decline (-4.58 [95% confidence interval (CI), -5.84 to -3.34], P &lt; 0.001; -3.66 [95% CI, -5.69 to -1.64], P &lt; 0.001) and alfa blocker use, with a greater decline (3.25 [95% CI, 1.53–4.97], P &lt; 0.001; 3.57 [95% CI, 1.08–6.06], P = 0.005). Baseline and monthly serum phosphorus levels were positively correlated with a decline (1.55 [95% CI, 0.30–2.80], P = 0.02; 0.59 [95% CI, 0.16–1.00], P = 0.007) and baseline and monthly normalized protein catabolic rate, inversely correlated (-22.41 [95% CI, -33.53 to -11.28], P &lt; 0.001; 9.65 [95% CI, 4.60–14.70], P &lt; 0.001) Conclusions: Calcium channel blocker use, alfa blocker avoidance, and serum phosphorus-lowering therapy may attenuate intradialytic systolic blood pressure decline and should be investigated in prospective trials.

327: NUTRITION IN NEONATAL AND PEDIATRIC EXTRACORPOREAL LIFE SUPPORT: A SURVEY OF CURRENT PRACTICES

Introduction: Adequate nutritional support is essential for children in the ICU. Malnourishment during critical illness is associated with increased morbidity and mortality, and improved enteral nutrition (EN) and protein intake are associated with decreased 60-day mortality. ICU patients with cardiac and/or respiratory failure who require ECMO are at increased risk due to high rates of protein catabolism and challenges in estimating energy requirements. These patients also have unclear metabolic needs and safety risks with both parenteral nutrition (PN) and EN. Assessing current national practices is crucial for standardized guideline development and recommendations. We aim to provide an update on current practices since a 2015 survey and hypothesized more respondents would report utilizing EN during ECMO with few differences between ICU physicians (MD/DOs) and registered dieticians (RDs). Methods: We distributed a survey via Qualtrics to 100 ECMO medical directors who had previously participated in survey-based research and those who requested participation during PediECMO presentations of this study. We also requested they forward the survey to their center RDs. Results: In total, 36 MD/DOs and 19 RDs responded. Respondents utilize PN more than EN (59%; 49%) at least half of the time. Respondents were more likely to start PN than EN during the first 24 hours (32%; 23%) but were equally likely to start PN and EN during the 24–48-hour window (34%; 32%). Respondents considered volume, calories, and protein to be the most critical nutritional goals with some variance in order between groups. Continuous feeds were preferred to bolus EN (70%; 17%). EN was preferred in respiratory distress syndrome and heart disease with biventricular physiology whereas PN was preferred for single ventricle physiology, ileus, and diaphragmatic hernia. Conclusions: Nutrition is a key component of reduction in morbidity and mortality; however, there is great variability in its delivery. Compared to 2015, EN is more commonly utilized than previously reported (49%; 24%) despite less protocol use (14%; 38%). These data support the need for development of a universal stepwise nutrition support algorithm to determine the safety of early EN versus PN as recommended by the ELSO Nutrition Guidelines published July 2022.

Lysosome signaling in cell survival and programmed cell death for cellular homeostasis.

Recent developments in lysosome biology have transformed our view of lysosomes from static garbage disposals that can also act as suicide bags to decidedly dynamic multirole adaptive operators of cellular homeostasis. Lysosome-governed signaling pathways, proteins, and transcription factors equilibrate the rate of catabolism and anabolism (autophagy to lysosomal biogenesis and metabolite pool maintenance) by sensing cellular metabolic status. Lysosomes also interact with other organelles by establishing contact sites through which they exchange cellular contents. Lysosomal function is critically assessed by lysosomal positioning and motility for cellular adaptation. In this setting, mechanistic target of rapamycin kinase (MTOR) is the chief architect of lysosomal signaling to control cellular homeostasis. Notably, lysosomes can orchestrate explicit cell death mechanisms, such as autophagic cell death and lysosomal membrane permeabilization-associated regulated necrotic cell death, to maintain cellular homeostasis. These lines of evidence emphasize that the lysosomes serve as a central signaling hub for cellular homeostasis.

The Relationship of Uremic Toxin Indoxyl Sulfate and Intestinal Elimination Mechanisms in Hemodialysis Patients

Introduction: High indoxyl sulfate (IS) concentration is a serious problem for patients with CKD increasing the risk of cardiovascular diseases and CKD progression. Thus, the methods of decreasing the toxin concentrations are highly desired. The study aimed to discover the role of selected intestine-related factors on IS concentration. Methods: We evaluated the impact of ABCG2 and ABCC2 polymorphisms influencing activity and protein intake by normalized protein catabolic rate. Additionally, we examined the relation of IS and uric acid (UA) that can share common elimination transporters. A monocentric, prospective, open cohort pilot study was performed on 108 patients undergoing dialysis treatment. Results: The positive effect of residual diuresis on the reduction of IS levels was confirmed (p = 0.005). Also, an increase in IS depending on the dietary protein intake was confirmed (p = 0.040). No significant correlation between ABC gene polymorphisms was observed either, suggesting the negligible role of ABCG2 and ABCC2 in the elimination of IS in small bowel. The significant difference was observed for UA where ABCG2 421C>A (rs72552713) gene polymorphism was higher (505.3 μmol/L) in comparison with a wild-type genotype (360.5 μmol/L). Conclusion: No evidence of bowel elimination pathway via ABCC2 and ABCG2 transporters was found in renal replacement therapy patients.

Показники прооксидантно-антиоксидантної системи і білкового обміну у щурів, після впливу слабких електромагнітних полів

The purpose of the work was to study the state of the components of the prooxidant-antioxidant system and indicators of protein metabolism in animals after a long period after exposure to weak electromagnetic fields. Materials and methods. The experiment was carried out on three-month-old white outbred rats. The animals were exposed to low-intensity electromagnetic radiation in the centimeter range for 2 months, 4 hours daily. The study of biochemical parameters of blood serum was carried out 3 months after the end of the experimental exposure. When conducting the research, an emitter in the form of a rectangular horn with a base area of 875 cm was used. Energy radiation was expressed in the power flow density in the area where the experimental animals were located. In the comparison group (n=10), animals were placed in a similar chamber every day, but were not exposed to electromagnetic radiation. Research was conducted in the first half of the day, taking into account circadian rhythms. The analysis of biochemical parameters of blood serum was carried out 3 months after the end of exposure, that is, for rats aged 8 months. Results and discussion. It was revealed that in animals exposed to weak electromagnetic radiation, after a long period after the cancellation of the action, there is an imbalance in the prooxidant-antioxidant system; activation of the non-enzymatic link of antioxidant protection is observed – an increase in the level of s-nitrosothiols against the background of a decrease in the level of lipid peroxidation, which, in addition to a destructive effect on the cell membrane, is a necessary element in maintaining the system of renewal of functionally important component of the lipid layer of cell membranes. The experimentally established dysproteinemia (decrease in the α1 fraction and increase in the α2 fraction of globulins) in animals of the main group may indicate a specific change in the enzymatic spectrum of the synthesis of these proteins in the liver. The activation of antioxidant defense components that we discovered is probably a protective measure aimed at maintaining homeostasis after prolonged exposure to electromagnetic radiation. Conclusion. A decrease in the level of final products of protein metabolism was revealed: creatinine and urea, which suggests a decrease in the rate of protein catabolism. It is concluded that in animals, after a long period after exposure to weak electromagnetic fields of the centimeter range, the level of lipid peroxidation is reduced, specific changes in the indicators of protein metabolism are noted, indicating a decrease in the level of their catabolism. It is suggested that this may be related to a decrease in total muscle mass

Tau kinetics in Alzheimer's disease.

The cytoskeletal protein tau is implicated in the pathogenesis of Alzheimer's disease which is characterized by intra-neuronal neurofibrillary tangles containing abnormally phosphorylated insoluble tau. Levels of soluble tau are elevated in the brain, the CSF, and the plasma of patients with Alzheimer's disease. To better understand the causes of these elevated levels of tau, we propose a three-compartment kinetic model (brain, CSF, and plasma). The model assumes that the synthesis of tau follows zero-order kinetics (uncorrelated with compartmental tau levels) and that the release, absorption, and clearance of tau is governed by first-order kinetics (linearly related to compartmental tau levels). Tau that is synthesized in the brain compartment can be released into the interstitial fluid, catabolized, or retained in neurofibrillary tangles. Tau released into the interstitial fluid can mix with the CSF and eventually drain to the plasma compartment. However, losses of tau in the drainage pathways may be significant. The kinetic model estimates half-life of tau in each compartment (552 h in the brain, 9.9 h in the CSF, and 10 h in the plasma). The kinetic model predicts that an increase in the neuronal tau synthesis rate or a decrease in tau catabolism rate best accounts for observed increases in tau levels in the brain, CSF, and plasma found in Alzheimer's disease. Furthermore, the model predicts that increases in brain half-life of tau in Alzheimer's disease should be attributed to decreased tau catabolism and not to increased tau synthesis. Most clearance of tau in the neuron occurs through catabolism rather than release to the CSF compartment. Additional experimental data would make ascertainment of the model parameters more precise.

Long-term body composition changes in patients undergoing hemodialysis: a single-center retrospective study

BackgroundPatients undergoing dialysis experience substantial decreases in muscle mass and functional muscle weakness. Muscle mass loss in patients undergoing hemodialysis is an independent predictor of survival, so muscle mass maintenance is essential for continued hemodialysis. This study examined longitudinal changes in the body composition of patients undergoing hemodialysis in different dialysis periods.MethodsWe retrospectively analyzed body composition measurements obtained by bioelectrical impedance analysis (BIA) using the same measuring instrument. The dialysis periods were 1–10 years from the start of hemodialysis for group A (n = 25), 10–20 years for group B (n = 22), and 20–30 years for group C (n = 9). The initial and final measurements of each group were compared. Furthermore, the nutritional status based on the inflammation and nutritional indicators obtained during the measurement period of each group was examined.ResultsMuscle mass did not significantly decrease in groups A and B but did decrease in group C (P < 0.05). In all groups, the extracellular water-to-total body water ratio (ECW/TBW) significantly increased (P < 0.001). C-reactive protein in groups A and B increased; however, the median initial and final values were < 0.2 mg/dL, and no changes were observed in group C. Furthermore, the median normalized protein catabolic rate was 0.86–1.05 g/kg/day, and there was no difference in the initial or final rates. The mean energy and protein daily intakes were 30–32 kcal/ideal body weight (IBW) kg/day and 1.1 g/IBW kg/day, respectively.ConclusionsIn patients undergoing hemodialysis, even if the muscle mass values are maintained, the possibility of a substantial decrease in muscle mass cannot be ruled out when ECW/TBW increases. Control of inflammation and nutritional intake may help minimize muscle mass loss caused by continued hemodialysis in patients.

Severe hyperparathyroidism is associated with nutritional impairment in maintenance hemodialysis patients.

Severe hyperparathyroidism predicts poor outcomes in patients with kidney failure. Mechanisms underlying the relationship between high parathyroid hormone (PTH) and decreased survival other than bone loss are largely unexplored. Recent evidence suggests the role of excess PTH in adipose tissue browning resulting in protein-energy wasting. The present retrospective observational study examined nutritional status among patients receiving maintenance hemodialysis with different degree of hyperparathyroidism. Seven hundred forty-five patients were categorized into four groups according to PTH levels: group 0, < 200; group 1, 200–599; group 2, 600–1,499; and group 3, ≥1,500 pg/ml. Group 0 was excluded because of the relationship between low PTH with aging and malnutrition. Patients in groups 1 and 2 were matched to group 3 by propensity score yielding 410 patients in the final analysis. Nutritional parameters at baseline and the preceding 1 and 2 years were examined. At baseline, lower serum albumin, creatinine/body surface area (Cr/BSA), height in female and higher percentage of patients with serum albumin < 38 g/L were observed in group 3 compared to groups 1 and 2. Higher PTH level was independently associated with serum albumin < 38 g/L and Cr/BSA < 380 μmol/L/m2. The longitudinal decline in serum albumin and Cr/BSA and the increase in the frequency of patients with serum albumin < 38 g/L were observed among patients in group 3. Between group comparisons confirmed a significant decline in serum albumin and Cr/BSA in association with an increase in the proportion of patients with serum albumin < 38 g/L and Cr/BSA < 380 μmol/L/m2 in group 3 compared to groups 1 and 2. Weight loss was more significant and was of greater magnitude among patients in group 3 compared to groups 1 and 2. Normalized protein catabolic rate in 3 groups were comparable. There was no significant difference in any of the nutritional parameters between groups 1 and 2. In conclusion, patients receiving maintenance hemodialysis with severe hyperparathyroidism showed deterioration of nutritional status compared to patients with moderate hyperparathyroidism and patients with PTH level in the recommended range. These findings support the role of extreme PTH level in protein-energy wasting emphasizing the importance of early management of hyperparathyroidism.