Elevated protein catabolism and protein malnutrition are common in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). The underlying etiology includes, but is not limited ...to, metabolic acidosis intestinal dysbiosis; systemic inflammation with activation of complements, endothelin-1 and renin-angiotensin-aldosterone (RAAS) axis; anabolic hormone resistance; energy expenditure elevation; and uremic toxin accumulation. All of these derangements can further worsen kidney function, leading to poor patient outcomes. Many of these CKD-related derangements can be prevented and substantially reversed, representing an area of great potential to improve CKD and ESRD care. This review integrates known information and recent advances in the area of protein nutrition and malnutrition in CKD and ESRD. Management recommendations are summarized. Thorough understanding the pathogenesis and etiology of protein malnutrition in CKD and ESRD patients will undoubtedly facilitate the design and development of more effective strategies to optimize protein nutrition and improve outcomes.
COVID-19 has recently become the most serious threat to public health, and its prevalence has been increasing at an alarming rate. The incubation period for the virus is ~1-14 days and all age groups ...may be susceptible to a fatality rate of about 5.9%. COVID-19 is caused by a novel single-stranded, positive (+) sense RNA beta coronavirus. The development of a vaccine for SARS-CoV-2 is an urgent need worldwide. Immunoinformatics approaches are both cost-effective and convenient, as
predictions can reduce the number of experiments needed. In this study, with the aid of immunoinformatics tools, we tried to design a multi-epitope vaccine that can be used for the prevention and treatment of COVID-19. The epitopes were computed by using B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) base on the proteins of SARS-CoV-2. A vaccine was devised by fusing together the B cell, HTL, and CTL epitopes with linkers. To enhance the immunogenicity, the β-defensin (45 mer) amino acid sequence, and pan-HLA DR binding epitopes (13aa) were adjoined to the N-terminal of the vaccine with the help of the EAAAK linker. To enable the intracellular delivery of the modeled vaccine, a TAT sequence (11aa) was appended to C-terminal. Linkers play vital roles in producing an extended conformation (flexibility), protein folding, and separation of functional domains, and therefore, make the protein structure more stable. The secondary and three-dimensional (3D) structure of the final vaccine was then predicted. Furthermore, the complex between the final vaccine and immune receptors (toll-like receptor-3 (TLR-3), major histocompatibility complex (MHC-I), and MHC-II) were evaluated by molecular docking. Lastly, to confirm the expression of the designed vaccine, the mRNA of the vaccine was enhanced with the aid of the Java Codon Adaptation Tool, and the secondary structure was generated from Mfold. Then we performed
cloning. The final vaccine requires experimental validation to determine its safety and efficacy in controlling SARS-CoV-2 infections.
Processed food has become an indispensable part of the human food chain. It provides rich nutrition for human health and satisfies various other requirements for food consumption. However, ...establishing traceability systems for processed food faces a different set of challenges compared to primary agro-food, because of the variety of raw materials, batch mixing, and resource transformation. In this paper, progress in the traceability of processed food is reviewed. Based on an analysis of the food supply chain and processing stage, the problem of traceability in food processing results from the transformations that the resources go through. Methods to implement traceability in food processing, including physical separation in different lots, defining and associating batches, isotope analysis and DNA tracking, statistical data models, internal traceability system development, artificial intelligence (AI), and blockchain-based approaches are summarized. Traceability is evaluated based on recall effects, TRUs (traceable resource units), and comprehensive granularity. Different methods have different advantages and disadvantages. The combined application of different methods should consider the specific application scenarios in food processing to improve granularity. On the other hand, novel technologies, including batch mixing optimization with AI, quality forecasting with big data, and credible traceability with blockchain, are presented in the context of improving traceability performance in food processing.
Background Recent studies have indicated that phosphorus may play an independent pathogenic role in chronic kidney disease (CKD) progression, but some of those studies were underpowered and yielded ...inconsistent results. Study Design Systematic review and meta-analysis. Setting & Population Non–dialysis-dependent patients with CKD (transplant recipients were excluded). Selection Criteria for Studies Studies assessing the risk ratio of serum phosphorus level on kidney failure and mortality for non–dialysis-dependent patients with CKD published from January 1950 to June 2014 were included following systematic searching of MEDLINE, EMBASE, and the Cochrane Library. Predictor Serum phosphorus level. Outcome Kidney failure, defined as doubled serum creatinine level, 50% decline in estimated glomerular filtration rate, or end-stage kidney disease. Results In 12 cohort studies with 25,546 patients, 1,442 (8.8%) developed kidney failure and 3,089 (13.6%) died. Overall, every 1-mg/dL increase in serum phosphorus level was associated independently with increased risk of kidney failure (hazard ratio, 1.36; 95% CI, 1.20-1.55) and mortality (hazard ratio, 1.20; 95% CI, 1.05-1.37). Limitations Existence of potential residual confounding could not be excluded. Conclusions This meta-analysis suggests an independent association between serum phosphorus level and kidney failure and mortality among non–dialysis-dependent patients with CKD and suggests that large-scale randomized controlled trials should target disordered phosphorus homeostasis in CKD.
Our study aimed to evaluate change in sarcopenia, its defining components over 1 year follow-up and investigate associations with subsequent cognitive decline, incident mild cognitive impairment ...(MCI) and dementia among patients undergoing haemodialysis (HD).
In the multicentre, longitudinal study, 1117 HD patients aged 56.8 ± 14.3 years (654 men; and 463 women) from 17 dialysis centres in Guizhou Province, China, were recruited in 2019 and followed up for 1 year in 2020. Sarcopenia was diagnosed with Asian Working Group for Sarcopenia criteria using appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS). Body composition was measured using body composition monitor; body water, weight, and height were corrected to calculate ASMI. HGS was measured by mechanical handgrip dynamometer. Cognitive function was measured with Mini Mental State Examination. Multivariate linear, logistic regression models and subgroup analyses were employed to examine the associations of changes in sarcopenia, ASMI, and HGS with Mini Mental State Examination score change, and incident MCI, dementia.
Four hundred fourteen (37.1%) patients had sarcopenia at baseline; during 1 year follow-up, 257 (23.0%) developed MCI and 143 (12.8%) developed dementia. According to changes in sarcopenia, patients were stratified into four groups: non-sarcopenia; non-sarcopenia to sarcopenia; sarcopenia; and sarcopenia to non-sarcopenia. HD patients in sarcopenia and non-sarcopenia to sarcopenia groups had higher risk of MCI (34.8%, 32.0%, vs. 17.4%) and dementia (20.6%, 19.8%, vs. 8.7%), compared non-sarcopenia group (P < 0.001). Multivariate linear regression analyses showed that sarcopenia regression coefficients (β) -1.098, 95% confidence interval (CI) -1.872, -0.324, P = 0.005 and non-sarcopenia to sarcopenia (β -1.826, -2.441, -1.212, P < 0.001) were associated with faster cognitive decline compared to non-sarcopenia. HGS decline (β 0.046, 0.027-0.064, P < 0.001) and ASMI decline (β 0.236, 0.109-0.362, P < 0.001) were both positively associated with cognitive decline. Multivariate logistic regression analyses demonstrated that patients with sarcopenia and non-sarcopenia to sarcopenia were both at increased risk of developing MCI odds ratio (OR) 1.788, 95% CI 1.115-2.870, P = 0.016 and OR 1.589, 95% CI 1.087-2.324, P = 0.017, respectively, but only non-sarcopenia to sarcopenia was at increased risk of dementia (OR 1.792, 95% CI 1.108-2.879, P = 0.017). Both greater change of ASMI and HGS had lower risk of MCI with adjusted ORs of 0.857 (0.778-0.945, P = 0.002) and 0.976 (0.963-0.989, P < 0.001). Robust associations were found among female individuals, aged >60 years, and with low educational level.
Longitudinal associations were observed between new-onset, persistent sarcopenia, and cognitive impairment. Early detection and intervention should be implemented to delay the onset of sarcopenia and improve cognitive health among HD patients.
The optimal serum magnesium level of patients undergoing hemodialysis (HD) with cognitive impairment is still unclear. This study aimed to evaluate the association between serum magnesium levels and ...mild cognitive impairment among HD patients.
This was a multicenter observational study. Patients undergoing hemodialysis from 22 dialysis centers in Guizhou Province, China were recruited into the study. HD patients were divided into five groups according to serum magnesium quintile. Cognitive function was measured with Mini Mental State Examination. The outcome was an incident mild cognitive impairment (MCI). Multivariate logistic regression analysis, restricted cubic spline and subgroup analysis were applied to explore the association of serum magnesium level with MCI.
Among 3562 HD patients (mean age 54.3 years, 60.1% male), the prevalence of MCI was 27.2%. After adjusting for confounders, serum magnesium 0.41-0.83 mmol/L odds ratios (OR) 1.55, 95% confidence interval (CI): 1.10-2.18 had a higher risk of MCI compared with serum magnesium of 1.19-1.45 mmol/L. A U-shaped association was identified between the serum magnesium and incident MCI (P for non-linearity = 0.004). The optimal range of magnesium level with the lowest risk of MCI was 1.12-1.24 mmol/L. As the serum magnesium level was lower than 1.12 mmol/L, the risk of MCI decreased by 24% per standard deviation (SD) increase in serum magnesium (OR 0.76, 95%CI: 0.62-0.93); when the serum magnesium level exceeds 1.24 mmol/L, a rise per SD increased the risk of MCI by 21% (OR = 1.20, 95%CI: 1.02-1.43). Subgroup analyses demonstrated that the associations were robust among individuals with low educational level, smoking, living alone, no working, and without hypertension or diabetes.
Serum magnesium has a U-shaped association with MCI among HD patients. Both lower and higher serum magnesium can increase the risk of MCI for this population specifically. The optimal serum magnesium range with the lowest risk of MCI was 1.12-1.24 mmol/L.
The relationship between basal metabolic rate (BMR) and Chronic kidney disease (CKD) remains unclear and controversial. In this study, we investigated the causal role of BMR in renal injury, and ...inversely, whether altered renal function causes changes in BMR.
In this two-sample mendelian randomization (MR) study, Genetic data were accessed from published genome-wide association studies (GWAS) for BMR ((n = 454,874) and indices of renal function, i.e. estimated glomerular filtration rate (eGFR) based on creatinine (n =1, 004, 040), CKD (n=480, 698), and blood urea nitrogen (BUN) (n =852, 678) in European. The inverse variance weighted (IVW) random-effects MR method serves as the main analysis, accompanied by several sensitivity MR analyses. We also performed a reverse MR to explore the causal effects of the above indices of renal function on the BMR.
We found that genetically predicted BMR was negatively related to eGFR, (β= -0.032, P = 4.95*10
). Similar results were obtained using the MR-Egger (β= -0.040, P = 0.002), weighted median (β= -0.04, P= 5.35×10
) and weighted mode method (β= -0.05, P=9.92×10
). Higher BMR had a causal effect on an increased risk of CKD (OR =1.36, 95% CI = 1.11-1.66, P =0.003). In reverse MR, lower eGFR was related to higher BMR (β= -0.64, P = 2.32×10
, IVW analysis). Bidirectional MR supports no causal association was observed between BMR and BUN. Sensitivity analyses confirmed these findings, indicating the robustness of the results.
Genetically predicted high BMR is associated with impaired kidney function. Conversely, genetically predicted decreased eGFR is associated with higher BMR.
Peritoneal dialysis (PD) patients have a high incidence of poor clinical outcomes, which is related to the inflammatory and nutritional status of this population. Platelet-to-albumin ratio (PAR), ...recently identified as a useful biomarker to monitor inflammation and nutrition, can predict a poor prognosis in various diseases. The aim of this study was to investigate the association between PAR and technique failure and mortality in PD patients.
This single-center retrospective study enrolled 405 PD patients from 1 January 2011 to 31 December 2019 and collected complete demographic characteristics, clinical laboratory baseline data. The outcomes were technique failure and mortality. The associations between PAR and technique failure, death were analyzed by Cox proportional hazard models and competing risk regression models with kidney transplantation as a competing event. The areas under the curve (AUC) of receiver-operating characteristic analysis were used to determine the predictive values of PAR for technique failure and mortality.
During a median follow-up period of 24.0 (range, 4.0-91.0) months, 139 (34.3%) PD patients experienced technique failure, 61 (15.1%) PD patients died. The patients with higher PAR levels had increased risk of technique failure and mortality. After adjustment for confounding factors, we found that high PAR levels were risk factor for both technique failure (subdistribution hazard ratio SHR 1.775; 95%CI, 1.157-2.720; p = 0.033 and mortality SHR 3.710; 95%CI, 1.870-7.360; p < 0.001. The predictive ability of PAR was superior to platelet and albumin based on AUC calculations for technique failure and mortality.
PAR was a risk factor associated with technique failure and mortality in PD patients.
Abstract Although decreasing body mass index (BMI) is associated with higher mortality risk in patients undergoing hemodialysis (HD), BMI neither differentiates muscle and fat mass nor provides ...information about the variations of fat distribution. It remains unclear whether changes over time in fat and muscle mass are associated with mortality. We examined the prognostic significance of trajectory in the triceps skinfold (TSF) thickness and mid-upper arm circumference (MUAC). In this multicenter prospective cohort study, 972 outpatients (mean age, 54.5 years; 55.3% men) undergoing maintenance HD at 22 treatment centers were included. We calculated the relative change in TSF and MUAC over a 1-year period. The outcome was all-cause mortality. Kaplan–Meier, Cox proportional hazard analyses, restricted cubic splines, and Fine and Gray sub-distribution hazards models were performed to examine whether TSF and MUAC trajectories were associated with all-cause mortality. During follow-up (median, 48.0 months), 206 (21.2%) HD patients died. Compared with the lowest trajectory group, the highest trajectories of TSF and MUAC were independently associated with lower risk for all-cause mortality (HR = 0.405, 95% CI 0.257–0.640; HR = 0.537; 95% CI 0.345–0.837; respectively), even adjusting for BMI trajectory. Increasing TSF and MUAC over time, measured as continuous variables and expressed per 1-standard deviation decrease, were associated with a 55.7% (HR = 0.443, 95% CI 0.302–0.649), and 97.8% (HR = 0.022, 95% CI 0.005–0.102) decreased risk of all-cause mortality. Reduction of TSF and MUAC are independently associated with lower all-cause mortality, independent of change in BMI. Our study revealed that the trajectory of TSF thickness and MUAC provides additional prognostic information to the BMI trajectory in HD patients.
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