The Ratio of Plasma Amyloid-ß 1-42 over Serum Albumin Can Be a Novel Biomarker Signature for Diagnosing End-Stage Renal Disease-Associated Cognitive Impairment.

BACKGROUND: Cognitive impairment (CI) is one of the major complications in chronic kidney disease patients, especially those with end-stage renal disease (ESRD). Limited biomarkers have been found that can significantly predict ESRD-associated cognitive decline. OBJECTIVE: This cohort study aimed to investigate de novo biomarkers for diagnosis of the ESRD-associated CI. METHODS: In this cohort study, qualified samples were divided into control (with an estimated glomerular filtration rate (eGFR) of≥60 mL/min and a Mini-Mental State Examination (MMSE) score of > 27), ESRD without CI (eGFR < 15 and MMSE > 27), and ESRD with CI (eGFR < 15 and MMSE < 27) groups. Levels of plasma amyloid-ß (Aß)1 - 42, serum indoxyl sulfate, and hematologic and biochemical parameters were measured. RESULTS: Compared to the control group, levels of blood urea nitrogen, creatinine, and indoxyl sulfate were elevated in ESRD patients both without and with CI. Interestingly, ESRD patients with CI had the lowest levels of serum albumin. In contrast, levels of plasma Aß1 - 42 were significantly higher in the ESRD with CI group than in the control and ESRD without CI groups. In addition, the ratio of plasma Aß1 - 42 over serum albumin was significantly higher in the ESRD with CI group than in the control or ESRD without CI groups. Importantly, the area under the receiver operating characteristic curve (AUROC) for CI in the total population by the ratio of Aß1 - 42 over albumin was 0.785 and significant (p < 0.05). CONCLUSIONS: This cohort study has shown that the ratio of plasma Aß1 - 42 over serum albumin can be a de novo biomarker for the diagnosis and prognosis of ESRD-associated cognitive decline.

Resveratrol triggers the ER stress-mediated intrinsic apoptosis of neuroblastoma cells coupled with suppression of Rho-dependent migration and consequently prolongs mouse survival.

Neuroblastoma, the most common childhood tumor, are highly malignant and fatal because neuroblastoma cells extremely defend against apoptotic targeting. Traditional treatments for neuroblastomas are usually ineffective and lead to serious side effects and poor prognoses. In this study, we investigated the molecular mechanisms of resveratrol-induced insults to neuroblastoma cells and survival extension of nude mice with neuroblastomas, especially in the endoplasmic reticular (ER) stress-intracellular reactive oxygen species (iROS) axis-mediated signals. Resveratrol specifically killed neuroblastoma cells mainly via apoptosis and autophagy rather than necrosis. As to the mechanisms, resveratrol time-dependently triggered productions of Grp78 protein and iROS in neuroblastoma cells. Attenuating the ER stress-iROS signaling axis significantly suppressed resveratrol-induced autophagy, DNA damage, and cell apoptosis. Successively, resveratrol decreased phosphorylation of retinoblastoma protein and induced cell cycle arrest at the S phase, translocation of Bak protein to mitochondria, a reduction in the mitochondrial membrane potential, cascade activation of caspases-9, -3, and -6, and DNA fragmentation. Moreover, weakening the ER stress-iROS axis concomitantly overcome resveratrol-induced decreases in translocation of Rho protein to membranes and succeeding cell migration. Interestingly, administration of resveratrol did not cause significant side effects but could protect the neuroblastoma-bearing nude mice from body weight loss and consequently extended the animal survival. In parallel, resveratrol elevated levels of Grp78 and then induced cell apoptosis in neuroblastoma tissues. This study has shown that resveratrol could kill neuroblastoma cells and extend survival of animals with neuroblastomas by triggering the ER stress-iROS-involved intrinsic apoptosis and suppression of Rho-dependent cell migration. Our results imply the potential of resveratrol as a drug candidate for chemotherapy of neuroblastoma patients.

Exploring the Relevance between Gut Microbiota-Metabolites Profile and Chronic Kidney Disease with Distinct Pathogenic Factor.

The intimate correlation of chronic kidney disease (CKD) with structural alteration in gut microbiota or metabolite profile has been documented in a growing body of studies. Nevertheless, a paucity of demonstrated knowledge regarding the impact and underlying mechanism of gut microbiota or metabolite on occurrence or progression of CKD is unclarified thus far. In this study, a liquid chromatography coupled-mass spectrometry and long-read sequencing were applied to identify gut metabolites and microbiome with statistically-discriminative abundance in diabetic CKD patients (n = 39), hypertensive CKD patients (n = 26), or CKD patients without comorbidity (n = 40) compared to those of healthy participants (n = 60). The association between CKD-related species and metabolite was evaluated by using zero-inflated negative binomial (ZINB) regression. The predictive utility of identified operational taxonomic units (OTUs), metabolite, or species-metabolite association toward the diagnosis of incident chronic kidney disease with distinct pathogenic factor was assessed using the random forest regression model and the receiver operating characteristic (ROC) curve. The results of statistical analyses indicated alterations in the relative abundances of 26 OTUs and 41 metabolites that were specifically relevant to each CKD-patient group. The random forest regression model with only species, metabolites, or its association differentially distinguished the hypertensive, diabetic CKD patients, or enrolled CKD patients without comorbidity from the healthy participants. IMPORTANCE Gut dysbiosis-altered metabolite association exhibits specific and convincing utility to differentiate CKD associated with distinct pathogenic factor. These results present the validity of pathogenesis-associated markers across healthy participants and high-risk population toward the early screening, prevention, diagnosis, or personalized treatment of CKD.

Effect of Different Nutritional Education Based on Healthy Eating Index for HemoDialysis Patients on Dietary Quality and Muscle Mass.

BACKGROUND: Hemodialysis patients are at high risk of muscle loss as a result of aging and disease, and combined with inadequate dietary intake. The Healthy Eating Index for HemoDialysis patients (HEI-HD) was developed to assess the dietary quality of hemodialysis patients. The purposes of this study were to examine the effects of different nutritional education models using HEI-HD-based education on dietary quality and muscle mass in hemodialysis patients. METHODS: A quasi-experimental study was conducted from May 2019 to April 2021, with four groups, including no course for patients and nurses (Non-C), course for nurses (CN), course for patients (CP), and course for patients and nurses (CPN). The courses were delivered by registered dietitians. The data of 94 patients were collected and analyzed at baseline, after 2 months of intervention, and 2 months follow-up, including demographics, body composition, 3-day dietary records, and hemodialysis dietary knowledge. The HEI-HD index score was calculated. RESULTS: Patients aged 58.3 ± 10.1 years. The dietary quality change in the CPN group was improved as compared with the Non-C group (-3.4 ± 9.5 vs. 3.0 ± 5.5, 0.04). The skeletal muscle mass of the Non-C group at intervention was also significantly lower than baseline, but the CPN group was not. CONCLUSIONS: The HEI-HD-based nutritional education for both patients and nurses showed a positive effect on improving the dietary quality and maintaining muscle mass in hemodialysis patients.

Enzalutamide Induces Apoptotic Insults to Human Drug-Resistant and -Sensitive Glioblastoma Cells via an Intrinsic Bax-Mitochondrion-Cytochrome C Caspase Cascade Activation Pathway.

Glioblastoma multiforme (GBM) is the most common and malignant brain tumor. Temozolomide (TMZ) is the first-line chemotherapeutic drug for treating GBM. However, drug resistance is still a challenging issue in GBM therapy. Our preliminary results showed upregulation of androgen receptor (AR) gene expression in human GBM tissues. This study was designed to evaluate the effects of enzalutamide, a specific inhibitor of the AR, on killing drug-resistant and -sensitive glioblastoma cells and the possible mechanisms. Data mining from The Cancer Genome Atlas (TCGA) database revealed upregulation of AR messenger (m)RNA and protein expressions in human GBM tissues, especially in male patients, compared to normal human brains. In addition, expressions of AR mRNA and protein in human TMZ-sensitive U87 MG and -resistant U87 MG-R glioblastoma cells were elevated compared to normal human astrocytes. Exposure of human U87 MG and U87 MG-R cells to enzalutamide concentration- and time-dependently decreased cell viability. As to the mechanism, enzalutamide killed these two types of glioblastoma cells via an apoptotic mechanism. Specifically, exposure to enzalutamide augmented enzyme activities of caspase-9 rather than those of caspase-8. Moreover, enzalutamide successively triggered an elevation in levels of the proapoptotic Bax protein, a reduction in the mitochondrial membrane potential, release of cytochrome c, cascade activation of caspases-3 and -6, DNA fragmentation, and cell apoptosis in human TMZ-sensitive and -resistant glioblastoma cells. Pretreatment with Z-VEID-FMK, an inhibitor of caspase-6, caused significant attenuations in enzalutamide-induced morphological shrinkage, DNA damage, and apoptotic death. Taken together, this study showed that enzalutamide could significantly induce apoptotic insults to human drug-resistant and -sensitive glioblastoma cells via an intrinsic Bax-mitochondrion-cytochrome c-caspase cascade activation pathway. Enzalutamide has the potential to be a drug candidate for treating GBM by targeting the AR signaling axis.

Luminal pressure gradient and risk of arteriovenous fistula nonmaturation.

While arteriovenous fistula (AVF) nonmaturation is a major issue of hemodialysis care, an effective treatment to improve AVF maturation remains lacking. AVF introduces pulsatile arterial blood flow into its venous limb and produces high luminal pressure gradient, which may have adverse effect on vascular remodeling. As such, the aim of the present study is to investigate effect of luminal pressure gradient on AVF nonmaturation. This single-center, prospective observational study includes patients receiving autologous AVF creation. Participants received early postoperative ultrasound 5-7 days after surgery to collect parameters including diameters, flow rates, and volume at inflow and outflow sites. Luminal pressure gradient was estimated by using modified Bernoulli equation. The outcome was spontaneous AVF maturation within 8 weeks after surgery without intervention. Thirty patients were included, of which the mean age was 66.9 years and 70% were male. At the end of study, 13 (43.3%) patients had spontaneous AVF maturation. All demographic and laboratory characteristics were similar between patients with mature and nonmature AVF. Regarding ultrasonographic parameters, nonmature AVF showed significantly higher inflow/outflow diameter ratio, inflow velocity, and luminal pressure gradient. While these 3 parameters were significantly correlated, multivariate logistic regression showed their significant association with AVF nonmaturation. Receiver operating characteristic curve exhibited their high predictive value for AVF nonmaturation. Our findings showed that higher inflow/outflow ratio, inflow velocity, and AVF luminal pressure gradient in early postoperative ultrasound predicted risk of AVF nonmaturation. Reducing inflow/outflow diameter ratio or inflow rate may be an approach to improve AVF maturation. The predictive value of this early assessment might have impact on the clinical practice of AVF care.

The Effect of Different Nutritional Education Models on Reducing Cardiovascular Disease Risk Factors by Improving Dietary Fat Quality in Hemodialysis Patients.

Cardiovascular disease (CVD) is the most common complication in hemodialysis patients. Nutritional education provided by dietitians could improve overall dietary quality and dietary fat quality to reduce the risk of CVD. However, no studies have investigated the relationship between dietary fat quality (using the hypocholesterolemic/hypercholesterolemic ratio, or the h/H) and CVD risk factors in hemodialysis patients. The aim of this study was to examine the association between the h/H and CVD risk factors, and further explore how nutritional education intervention models could improve dietary fat quality and CVD risk factors in hemodialysis patients. A quasi-experimental design was conducted from May 2019 to April 2021 on four groups, including 'no course for patients and nurses' as the non-C group, a "course for nurses" as the CN group, a "course for patients" as the CP group, and a "course for patients and nurses" as the CPN group. Nutritional education booklets based on a healthy eating index for hemodialysis patients were developed and provided to patients and nurses. Data of 119 patients were collected at baseline, intervention, and follow-up periods, including patients' basic information, blood biochemical data, dietary content, and calculated h/H. The results showed that the h/H was negatively correlated with body mass index (BMI) and positively correlated with high-density lipoprotein cholesterol (HDL-C). Compared with the non-C group, the CPN group was significantly higher in the h/H as well as HDL-C, and significantly lower in serum total cholesterol. In conclusion, the h/H was found to predict CVD risk factors, which helps in improving dyslipidemia. Nutritional education for both patients and nurses showed a beneficial impact on reducing CVD risks in hemodialysis patients.

The Humoral Immune Response of the ChAdOx1 nCoV-19 Vaccine in Maintenance Dialysis Patients without Prior COVID-19 Infection.

BACKGROUND: Chronic kidney disease (CKD) patients tend to have a reduced immune response to infection and vaccination. The efficacy of current available COVID-19 vaccines in CKD patients has not been widely evaluated. METHODS: In the present study, three hundred and eight chronic dialysis patients received ChAdOx1 nCoV-19 (Oxford-AstraZeneca, AZ). Blood tests using an antibody against the receptor-binding domain (RBD) of the S1 subunit of the SARS-CoV-2 spike protein had performed at four designed time points before and after the first and second vaccine. RESULTS: The mean age of patients was 65.5 ± 12.38 years, and the male/female ratio was 61.4%:38.6% (189/119). Two weeks after the first vaccination, only 37.66% of patients had a positive antibody response (>50 AU/mL). However, 65.58% of the participants showed a delayed antibody response ten weeks after the first vaccine. Four weeks after the second vaccine, 94.16% of participants had positive antibody levels. Age was the most significant factor associated with antibody response. Flow cytometry analysis revealed that immune-naïve patients had significantly lower early active B cells and proliferative B cells than the age- and sex-matched immune responders. CONCLUSION: Despite a delayed response, 94.16% of chronic dialysis patients achieved a positive antibody response after two doses of the AZ vaccine. Age is the most significant factor associated with antibody response.

Oligosaccharides Ameliorate Acute Kidney Injury by Alleviating Cluster of Differentiation 44-Mediated Immune Responses in Renal Tubular Cells.

Acute kidney injury (AKI) is a sudden episode of kidney damage that commonly occurs in patients admitted to hospitals. To date, no ideal treatment has been developed to reduce AKI severity. Oligo-fucoidan (FC) interferes with renal tubular cell surface protein cluster of differentiation 44 (CD44) to prevent renal interstitial fibrosis; however, the influence of oligosaccharides on AKI remains unknown. In this study, FC, galacto-oligosaccharide (GOS), and fructo-oligosaccharide (FOS) were selected to investigate the influence of oligosaccharides on AKI. All three oligosaccharides have been proven to be partially absorbed by the intestine. We found that the oligosaccharides dose-dependently reduced CD44 antigenicity and suppressed the hypoxia-induced expression of CD44, phospho-JNK, MCP-1, IL-1ß, and TNF-α in NRK-52E renal tubular cells. Meanwhile, CD44 siRNA transfection and JNK inhibitor SP600125 reduced the hypoxia-induced expression of phospho-JNK and cytokines. The ligand of CD44, hyaluronan, counteracted the influence of oligosaccharides on CD44 and phospho-JNK. At 2 days post-surgery for ischemia-reperfusion injury, oligosaccharides reduced kidney inflammation, serum creatine, MCP-1, IL-1ß, and TNF-α in AKI mice. At 7 days post-surgery, kidney recovery was promoted. These results indicate that FC, GOS, and FOS inhibit the hypoxia-induced CD44/JNK cascade and cytokines in renal tubular cells, thereby ameliorating AKI and kidney inflammation in AKI mice. Therefore, oligosaccharide supplementation is a potential healthcare strategy for patients with AKI.

Inhibition of ß-catenin signaling attenuates arteriovenous fistula thickening in mice by suppressing myofibroblasts.

BACKGROUND: Arteriovenous fistula (AVF) is the most important vascular access for hemodialysis; however, preventive treatment to maintain the patency of AVFs has not been developed. In endothelium, ß-catenin functions in both the intercellular adherens complex and signaling pathways that induce the transition of endothelial cells to myofibroblasts in response to mechanical stimuli. We hypothesize that mechanical disturbances in the AVF activate ß-catenin signaling leading to the transition of endothelial cells to myofibroblasts, which cause AVF thickening. The present study aimed to test this hypothesis. METHODS: Chronic kidney disease in mice was induced by a 0.2% adenine diet. AVFs were created by aortocaval puncture. Human umbilical vein endothelial cells (HUVECs) were used in the cell experiments. A pressure-culture system was used to simulate mechanical disturbances of the AVF. RESULTS: Co-expression of CD31 and smooth muscle alpha-actin (αSMA), loss of cell-cell adhesions, and the expression of the myofibroblast marker, integrin subunit ß6 (ITGB6), indicated transition to myofibroblasts in mouse AVF. Nuclear translocation of ß-catenin, decreased axin2, and increased c-myc expression were also observed in the AVF, indicating activated ß-catenin signaling. To confirm that ß-catenin signaling contributes to AVF lesions, ß-catenin signaling was inhibited with pyrvinium pamoate; ß-catenin inhibition significantly attenuated AVF thickening and decreased myofibroblasts. In HUVECs, barometric pressure-induced nuclear localization of ß-catenin and increased expression of the myofibroblast markers, αSMA and ITGB6. These changes were attenuated via pretreatment with ß-catenin inhibition. CONCLUSIONS: The results of this study indicate that mechanical disturbance in AVF activates ß-catenin signaling to induce the transition of endothelial cells to myofibroblasts. This signaling cascade can be targeted to maintain AVF patency.

Characteristics and Outcomes in Primary Aldosteronism Patients Harboring Glucocorticoid-Remediable Aldosteronism.

The clinical characteristics and surgical prognosis of glucocorticoid-remediable aldosteronism (GRA, also known as familial hyperaldosteronism type 1, FH-I) have not been widely studied. Using data from the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry retrospectively, we describe the associated clinical factors for GRA and clinical predictors of surgical outcomes among identified GRA patients. We found 79 GRA-positive (51.2 ± 13.8 years; women 39 (49.4%)) and 114 GRA-negative primary aldosteronism (PA) patients matched with age, gender, and body mass index. Lower plasma aldosterone concentrations (PACs) and aldosterone-renin ratios were found among GRA-positive individuals. Multivariable logistic regression demonstrated that a PAC ≤ 40 ng/dL could predict concealed GRA individuals (OR 0.523, p = 0.037). Low serum potassium (OR 0.285, p = 0.008), but not the presence of GRA, was associated with hypertension-remission. Of note, PRA (OR 11.645, p = 0.045) and hypokalemia (OR 0.133, p = 0.048) were associated with hypertension-remission in GRA patients. Unilateral primary aldosteronism patients harboring concomitant GRA were not associated with inferior hypertension-remission after an adrenalectomy. Low serum potassium and high PRA were positively associated with hypertension-remission in GRA patients.

Gut Microbiota Composition and Its Metabolites in Different Stages of Chronic Kidney Disease.

A growing body of study have documented the association of gut dysbiosis or fecal metabolites with chronic kidney disease (CKD). However, it is not clear whether the phenomenon simply reflects the microenvironment changes correlated with the CKD severity or contributes to the progression of CKD. In this study, we identified the gut microbiota and metabolite in feces samples correlated with CKD severity using the Nanopore long-read sequencing platform and UPLC-coupled MS/MS approach. A cross-sectional cohort study was performed from 1 June 2020 to 31 December 2020. One hundred and fifty-six clinical participants, including 60 healthy enrollees and 96 Stage 1-5 CKD patients, were enrolled in this study. The ROC curve generated with the relative abundance of Klebsiella pneumonia or S-Adenosylhomocysteine showed a gradual increase with the CKD severity. Our results further revealed the positive correlation of increased K. pneumonia and S-Adenosylhomocysteine in gut environment, which may be of etiological importance to the deterioration of a CKD patient. In that sense, the microbiota or metabolite changes constitute potential candidates for evaluating the progression of CKD.

Involvement of microRNA in Solid Cancer: Role and Regulatory Mechanisms.

MicroRNAs (miRNAs) function as the post-transcriptional factor that finetunes the gene expression by targeting to the specific candidate. Mis-regulated expression of miRNAs consequently disturbs gene expression profile, which serves as the pivotal mechanism involved in initiation or progression of human malignancy. Cancer-relevant miRNA is potentially considered the therapeutic target or biomarker toward the precise treatment of cancer. Nevertheless, the regulatory mechanism underlying the altered expression of miRNA in cancer is largely uncovered. Detailed knowledge regarding the influence of miRNAs on solid cancer is critical for exploring its potential of clinical application. Herein, we elucidate the regulatory mechanism regarding how miRNA expression is manipulated and its impact on the pathogenesis of distinct solid cancer.

Combined protective effects of oligo-fucoidan, fucoxanthin, and L-carnitine on the kidneys of chronic kidney disease mice.

Chronic kidney disease (CKD) is a common global progressive disease, but there are no ideal drugs for the treatment. Fucoidan and fucoxanthin, and L-carnitine are one of the very few natural products that have a therapeutic effect on CKD in animal experiments. However, the combined effects of these compounds on CKD are unknown. We established a mouse CKD model by right nephrectomy with transient ischemic injury to the left kidney. Oligo-fucoidan and fucoidan were extracted from Laminaria japonica. We fed CKD mice with the two compounds and L-carnitine to evaluate the combined effects on CKD. Oligo-fucoidan and fucoidan inhibited renal fibrosis and reduced serum creatine in CKD mice to a greater extent than any single compound. L-carnitine had no measurable effect on renal fibrosis but promoted the protective effect of the mixture of oligo-fucoidan and fucoidan on renal function in CKD mice. In the two-month safety test, the combined mixture further improved renal function and did not elevate serum aspartate aminotransferase and alanine aminotransferase levels in CKD mice. Furthermore, the weights of CKD mice treated with the combination increased to the normal level. We also found that all oligo-fucoidan, fucoxanthin, and L-carnitine inhibit H2O2-induced apoptosis and activated Akt in rat renal tubular cells. Our results confirm that oligo-fucoidan, fucoxanthin, and L-carnitine have a combined protective effect on the kidneys. The combined mixture may be beneficial for CKD patients.

Energy Requirement of Patients Undergoing Hemodialysis: A Cross-Sectional Study in Multiple Centers.

BACKGROUND: Energy requirements must be estimated before nutritional care can be provided for patients undergoing hemodialysis (HD). However, the recommended caloric intake for patients has not been conclusively determined because of insufficiently large sample sizes. METHOD: This cross-sectional observational study recruited patients undergoing long-term HD from multiple centers as well as people in the general population without chronic kidney disease. People from both groups were matched by sex and age. Resting energy expenditure (REE) was estimated using an indirect calorimeter. Two commonly used equations for estimating REE and daily energy requirement recommended by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) were chosen. RESULTS: This study had 154 HD patients and 33 matched HD-control group pairs. Age (r = -0.36, p < 0.01) and dry body weight after dialysis (r = -0.36, p < 0.01) and dry body weight after dialysis (. CONCLUSIONS: Age and dry body weight are the main factors affecting the energy expenditure of HD patients. Furthermore, predicting the energy expenditure of HD patients by measuring the energy expenditure of their sedentary counterparts in the general population with the same sex, age range, and weight may yield better results than using traditional equations for predicting TEE. In East Asian populations, the TEE values were 32 and 30 kcal/kg dry weight for those aged <65 and ≥65 years, respectively. Future prospective cohort studies with larger sample sizes are needed.

Insulin Resistance and Cardiovascular Risks in Different Groups of Hemodialysis Patients: A Multicenter Study.

BACKGROUND: To investigate the association between insulin resistance (IR) and cardiovascular disease (CVD) risks among hemodialysis patients. METHODS: We conducted a cross-sectional study between 2013 and 2017, on 384 hemodialysis patients from seven hospital-based-dialysis centers. HOMA-IR is classified according to median value. The CVD risks were defined by the K/DOQI Guidelines. Logistic regression analysis was used. RESULTS: Patients' age was 60.9 ± 11.8, 58.1% men, and 40.3% overweight/obese. The median of HOMA-IR was 5.4, 82.8% high systolic blood pressure, and 85.7% hyperhomocysteinemia. In multivariate analysis, IR was significantly associated with higher odds of low high-density lipoprotein cholesterol, high triglyceride, and impaired fasting glucose in groups of normal weight, overweight/obese, nondiabetes, diabetes, and overall sample. IR linked with elevated high-sensitive C-reactive protein in normal weight patients (odd ratio, OR=2.21, 95% confidence interval, 1.16-4.22, p < .05), with hypoalbuminemia in normal weight patients (OR=8.31, 95% CI, 2.35-29.37, p < .01), in nondiabetes patients (OR=6.59, 95% CI, 1.81-23.95, p < .01), and overall sample (OR=3.07, 1.51-6.23, p < .01). CONCLUSIONS: The level of IR and prevalence of CVD risks were high in hemodialysis patients. IR was independently associated with CVD risks.

Hyperhomocysteinemia Associated with Low Muscle Mass, Muscle Function in Elderly Hemodialysis Patients: An Analysis of Multiple Dialysis Centers.

BACKGROUND: The hyperhomocysteinemia was with high prevalence and has been considered as a risk factor for cardiovascular disease in hemodialysis patients. These patients also experienced a high risk of muscle wasting caused by the comorbidity, malnutrition, and low physical activity. We investigated the associations of homocysteinemia with muscle mass, muscle function in elderly hemodialysis patients. METHODS: A clinical cross-sectional study was conducted on 138 hemodialysis patients aged 65 years and above in seven hospital-based hemodialysis centers in Taiwan. The data on anthropometry, laboratory, and 3-day dietary intake was examined. The skeletal muscle mass (SMM) was measured by the bioelectrical impedance analysis; the SMM was adjusted by height or weight as SMMHt2 (kg/m2) and SMMWt (%). Muscle function was defined as handgrip strength (HGS) (kg) measured by handgrip dynamometer. Statistical analyses were conducted using simple regression and multivariable stepwise regression analysis. RESULTS: In the total sample, 74.6 % of hemodialysis patients were hyperhomocysteinemia (≥ 15 µmol/L). The means of SMMHt2, SMMWt, arm lean mass, hand grip strength, and muscle quality were 8.7 ± 1.2, 37.7 ± 5.6, 1.7 ± 0.5, 21.1 ± 7.4, and 10.0 ± 3.0, respectively. The multivariable stepwise regression analysis showed that homocysteinemia level was significantly inversely associated with SMMWt (B-coeff. = -0.03, p = 0.02) in hemodialysis patients above 65 years old, but not with muscle function. CONCLUSIONS: Hyperhomocysteinemia is common and associated with decreased muscle mass in the elderly hemodialysis patients. Future studies are suggested to explore the impact of the homocysteine-lowering therapy on muscle decline.

Adaptation and Validation of Alternative Healthy Eating Index in Hemodialysis Patients (AHEI-HD) and Its Association with all-Cause Mortality: A Multi-Center Follow-Up Study.

A valid diet quality assessment scale has not been investigated in hemodialysis patients. We aimed to adapt and validate the alternative healthy eating index in hemodialysis patients (AHEI-HD), and investigate its associations with all-cause mortality. A prospective study was conducted on 370 hemodialysis patients from seven hospital-based dialysis centers. Dietary data (using three independent 24-hour dietary records), clinical and laboratory parameters were collected. The construct and criterion validity of original AHEI-2010 with 11 items and the AHEI-HD with 16 items were examined. Both scales showed reasonable item-scale correlations and satisfactory discriminant validity. The AHEI-HD demonstrated a weaker correlation with energy intake compared with AHEI-2010. Principle component analysis yielded the plateau scree plot line in AHEI-HD but not in AHEI-2010. In comparison with patients in lowest diet quality (tertile 1), those in highest diet quality (tertile 3) had significantly lower risk for death, with a hazard ratio (HR) and 95% confidence intervals (95%CI) of HR: 0.40; 95%CI: 0.18 - 0.90; p = 0.028, as measured by AHEI-2010, and HR: 0.37; 95%CI: 0.17-0.82; p = 0.014 as measured by AHEI-HD, respectively. In conclusion, AHEI-HD was shown to have greater advantages than AHEI-2010. AHEI-HD was suggested for assessments of diet quality in hemodialysis patients.

Point of Care eGFR and the Prediction of Outcomes in Pneumonia.

Pneumonia is a leading cause of mortality. Severity-assessment scores in pneumonia guide treatment crucially, but the ones currently in existence are limited in their use. Community-based studies demonstrated the association between pre-existing low estimated glomerular filtration rate (eGFR) and outcomes in pneumonia. However, whether a single emergency department-eGFR measurement could predict outcomes in pneumonia remains unclear. This retrospective cohort study included 1554 patients hospitalized with pneumonia. The predictor was the first eGFR measurement. Outcomes included mortality, intensive care unit (ICU) admission, durations of hospital and ICU stay, and ventilator use. Receiver operating characteristic curves was used to determine optimal cutoff values to predict mortality. Of 1554 patients, 263 had chronic kidney disease, demonstrated higher C-reactive protein and SMART-COP scores, and had more multilobar pneumonia, acute kidney injury, ICU admission, and mortality. Patients with higher pneumonia severity scores tended to have lower eGFR. For predicting in-hospital mortality, the optimal eGFR cutoff value was 56 mL/min/1.73 m2. eGFR < 56 mL/min/1.73 m2 had an odds ratio of 2.5 (95% confidence interval, 1.6-4.0) for mortality by multivariate logistic regression. In Conclusion, eGFR < 56 mL/min/1.73 m2 is an independent predictor of mortality, indicating that even mild renal impairment affects the outcome of pneumonia adversely.