Association of the oral microbiome with cognitive function among older adults: NHANES 2011-2012.

BACKGROUND: An association between the gut microbiome and cognitive function has been demonstrated in prior studies. However, whether the oral microbiome, the second largest microbial habitant in humans, has a role in cognition remains unclear. DESIGN, SETTING, PARTICIPANTS: Using weighted data from the 2011 to 2012 National Health and Nutrition Examination Survey, we examined the association between oral microbial composition and cognitive function in older adults. The oral microbiome was characterized by 16S ribosomal RNA gene sequencing. Cognitive status was assessed using the Consortium to Establish a Registry for Alzheimer's Disease immediate recall and delayed recall, Animal Fluency Test, and Digit Symbol Substitution Test (DSST). Subjective memory changes over 12 months were also assessed. Linear and logistic regression models were conducted to quantify the association of α-diversity with different cognitive measurements controlling for potential confounding variables. Differences in ß-diversity were analyzed using permutational analysis of variance. RESULTS: A total of 605 participants aged 60-69 years were included in the analysis. Oral microbial α-diversity was significantly and positively correlated with DSST (ß, 2.92; 95% CI, 1.01-4.84). Participants with higher oral microbial α-diversity were more likely to have better cognitive performance status based on DSST (adjusted odds ratio, 2.35; 95% CI, 1.28-4.30) and were less likely to experience subjective memory changes (adjusted odds ratio, 0.43; 95% CI, 0.25-0.74). In addition, ß-diversity was statistically significant for the cognitive performance status based on DSST (P = 0.031) and subjective memory changes (P = 0.023). CONCLUSIONS: Oral microbial composition was associated with executive function and subjective memory changes among older adults among older U.S. adults in a nationally representative population sample. Oral dysbiosis is a potential biomarker or therapeutic target for cognitive decline. Further work is needed to elucidate the mechanisms underpinning the association between the oral microbiome and cognitive function.

Diabetes mellitus modifies the association between chronic kidney disease-mineral and bone disorder biomarkers and aortic stiffness in peritoneal dialysis patients.

This study aimed to investigate the relationship of four chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers, including intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), soluble klotho, and fetuin-A, with aortic stiffness in peritoneal dialysis (PD) patients, comparing those with and without diabetes mellitus (DM). A total of 213 patients (mean age 58 ± 14 years; 81 (38.0%) patients with DM) were enrolled. Their aortic pulse wave velocity (PWV) was measured using pressure applanation tonometry, while serum intact PTH, FGF23, α-klotho, and fetuin-A levels were measured using enzyme-linked immunosorbent assay. Overall, patients with DM had higher aortic PWV than those without (9.9 ± 1.8 vs. 8.6 ± 1.4 m/s, p < 0.001). Among the four CKD-MBD biomarkers, FGF23 levels were significantly lower in DM group (462 [127-1790] vs. 1237 [251-3120] pg/mL, p = 0.028) and log-FGF23 independently predicted aortic PWV in DM group (ß: 0.61, 95% confidence interval: 0.06-1.16, p = 0.029 in DM group; ß: 0.10, 95% confidence interval: - 0.24-0.45, p = 0.546 in nonDM group; interaction p = 0.016). In conclusion, the association between FGF23 and aortic PWV was significantly modified by DM status in PD patients.

Association of Frailty With Nutritional Status in Patients With Chronic Kidney Disease.

OBJECTIVES: Frailty is commonly observed in patients with chronic kidney disease (CKD) and is associated with adverse outcomes. Protein-energy wasting (PEW), a state of decreased body stores of protein and energy fuels, may be associated with frailty. However, few data are available on the possible association between frailty and PEW in CKD. METHODS: We examined the association between frailty and nutritional status assessed using anthropometric and body composition measurements, serum albumin, handgrip strength, the Malnutrition Inflammation Score (MIS), and dietary protein and calorie intake in a cross-sectional analysis of nondialysis patients with CKD stages 3-5. Body composition was assessed using multifrequency bioelectrical impedance. Frailty was defined as a Clinical Frailty Scale ≥4. We performed logistic regression with different nutrition assessment tools as the main predictors and age, sex, comorbidity, estimated glomerular filtration rate (eGFR), and hemoglobin as covariates. RESULTS: A total of 157 patients (93 men and 64 women; mean age 64 years; diabetes prevalence 38.9%) with CKD (eGFR 24.4 ± 13.4 mL/min/1.73 m2) were included. Overall, 29.3% of patients were frail. Patients with frailty were older and had a significantly higher fat tissue index and MIS but a significantly lower lean tissue index, eGFR, hemoglobin value, serum albumin value, handgrip strength value, and dietary protein intake. In multivariate logistic regression analyses, a higher body mass index category (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.03-2.31), higher fat tissue index (OR, 1.15; 95% CI, 1.03-1.28), larger waist circumference (OR, 1.05; 95% CI, 1.01-1.09), reduced handgrip strength (OR, 2.70; 95% CI, 1.17-6.21), PEW defined by MIS ≥5 (OR, 3.49; 95% CI, 1.35-9.01), and dietary protein intake ≤0.8 g/kg/day (OR, 2.70; 95% CI, 1.18-6.19) were associated with higher odds of frailty. CONCLUSION: Frailty is associated with nutritional status in patients with CKD. A comprehensive nutrition assessment may allow the implementation of strategies to prevent or reduce frailty.

Associations of Glucometabolic Indices with Aortic Stiffness in Patients Undergoing Peritoneal Dialysis with and without Diabetes Mellitus.

Disruptions in glucose metabolism are frequently observed among patients undergoing peritoneal dialysis (PD) who utilize glucose-containing dialysis solutions. We aimed to investigate the relationship between glucometabolic indices, including fasting glucose, insulin resistance, advanced glycation end products (AGEs), PD-related glucose load, and icodextrin usage, and aortic stiffness in PD patients with and without diabetic mellitus (DM). This study involved 172 PD patients (mean age 58.3 ± 13.5 years), consisting of 110 patients without DM and 62 patients with DM. Aortic stiffness was assessed using the carotid-femoral pulse wave velocity (cfPWV). Impaired fasting glucose was defined as a fasting glucose level ≥ 100 mg/dL. Homeostatic model assessment for insulin resistance (HOMA-IR) scores, serum AGEs, dialysate glucose load, and icodextrin usage were assessed. Patients with DM exhibited the highest cfPWV (9.9 ± 1.9 m/s), followed by those with impaired fasting glucose (9.1 ± 1.4 m/s), whereas patients with normal fasting glucose had the lowest cfPWV (8.3 ± 1.3 m/s), which demonstrated a significant trend. In non-DM patients, impaired fasting glucose (ß = 0.52, 95% confidence interval [CI] = 0.01-1.03, p = 0.046), high HOMA-IR (ß = 0.60, 95% CI = 0.12-1.08, p = 0.015), and a high PD glucose load (ß = 0.58, 95% CI = 0.08-1.08, p = 0.023) were independently associated with increased cfPWV. In contrast, none of the glucometabolic factors contributed to differences in cfPWV in DM patients. In conclusion, among PD patients without DM, impaired fasting glucose, insulin resistance, and PD glucose load were closely associated with aortic stiffness.

Humoral immune response to an mRNA-1273 booster after chAdOx1-nCoV-19-priming among patients undergoing hemodialysis.

Objectives: Patients who are undergoing dialysis due to end-stage kidney disease are susceptible to greater coronavirus disease 2019 (COVID-19) complications. While vaccination is seen as the most effective tactic against COVID-19, the dialysis population usually has impaired immune responses to vaccination. Owing to the global vaccine supply shortage in the early phase of the COVID-19 pandemic, hemodialysis patients in Taiwan were administered homologous ChAdOx1 nCoV-19/ChAdOx1 nCoV-19 at 12-week intervals, with a third booster shot of mRNA-1273 given 12 weeks after the second dose. We assessed the antibody responses of these patients to this extended-interval dosing protocol. Materials and Methods: A total of 168 hemodialysis patients (mean age: 67 ± 13 years) without prior COVID-19 infection were vaccinated between June 16, 2021, and January 5, 2022, and followed until February 10, 2022. The primary outcome was seroconversion with an antispike immunoglobulin G (IgG) antibody level ≥50 arbitrary units (AU)/mL at 4 weeks after the administration of an mRNA-1273 booster shot. The secondary outcome was the level of antispike IgG antibodies. Multivariable linear regression models were used to evaluate the associations between the baseline characteristics and the antispike IgG level. Results: A total of 163 (97.0%) patients reached the primary endpoint, with antibody levels after the third booster dose of mRNA-1273 being significantly higher than those after the second dose of ChAdOx1 nCoV-19 (median IgG titer 12,007 [4394-23,860] vs. 846 [interquartile range 295-2114] AU/mL; P < 0.001). Patients who were male, older, had a higher body mass index, had a lower total lymphocyte count, and used immunosuppressants had lower antibody levels. Conclusion: A third booster dose of mRNA-1273 after two consecutive priming doses of ChAdOx1 nCoV-19 with extended intervals resulted in adequate humoral immune responses among hemodialysis patients.

Dialysis Modality and Incident Stroke Among Patients With End-Stage Kidney Disease: A Registry-Based Cohort Study.

BACKGROUND: Patients with end-stage kidney disease undergoing dialysis are at significant risk of stroke. Whether dialysis modality is associated with cerebrovascular disease is unclear. This study compared the risk of incident stroke in patients undergoing peritoneal dialysis or hemodialysis. METHODS: Thirty-nine thousand five hundred forty-two patients without a history of stroke who initiated dialysis between January 1, 2010, and December 31, 2014 were retrospectively studied using Taiwan's National Health Insurance Research Database. We matched 3809 patients undergoing peritoneal dialysis (mean age 59±13 years; 46.5% women) and 11 427 patients undergoing hemodialysis (mean age 59±13 years; 47.3% women) by propensity score in a 1:3 ratio with follow-up through December 31, 2015. The primary outcome was incident acute ischemic stroke. Secondary outcomes included hemorrhagic stroke, acute coronary syndrome, and all-cause mortality. Cox proportional hazard models were conducted to determine hazard ratios of clinical outcomes according to the dialysis modality. RESULTS: During a median follow-up of 2.59 (interquartile range 1.50-3.93) years, acute ischemic stroke, hemorrhagic stroke, and acute coronary syndrome occurred in 783 (5.1%), 376 (2.5%), and 1350 (8.9%) patients, respectively. In a multivariable Cox model that accounted for the competing risk of death, acute ischemic stroke occurred more frequently in the peritoneal dialysis group than in the hemodialysis group (subdistribution hazard ratio, 1.32 [95% CI, 1.13-1.54]; P=0.0005). There were no significant treatment-related differences in the risk of hemorrhagic stroke (subdistribution hazard ratio, 0.89 [95% CI, 0.70-1.14]; P=0.3571) and acute coronary syndrome (subdistribution hazard ratio, 0.99 [95% CI, 0.88-1.12]; P=0.9080). Patients undergoing peritoneal dialysis were more likely to die from any cause than patients undergoing hemodialysis (adjusted hazard ratio, 1.24 [95% CI, 1.15-1.33]; P<0.0001). CONCLUSIONS: Peritoneal dialysis was associated with a significantly increased risk of acute ischemic stroke compared with hemodialysis. Further studies are needed to clarify whether more aggressive cerebrovascular preventive strategies might mitigate the excess risk for ischemic stroke among patients receiving peritoneal dialysis.

Immunosenescence, gut dysbiosis, and chronic kidney disease: Interplay and implications for clinical management.

Immunosenescence refers to the immune system changes observed in individuals over 50 years old, characterized by diminished immune response and chronic inflammation. Recent investigations have highlighted similar immune alterations in patients with reduced kidney function. The immune system and kidney function have been found to be closely interconnected. Studies have shown that as kidney function declines, both innate and adaptive immunity are affected. Chronic kidney disease (CKD) patients exhibit decreased levels of naive and regular T cells, as well as naive and memory B cells, while memory T cell counts increase. Furthermore, research suggests that CKD and end-stage kidney disease (ESKD) patients experience early thymic dysfunction and heightened homeostatic proliferation of naive T cells. In addition to reduced thymic T cell production, CKD patients display shorter telomeres in both CD4+ and CD8+ T cells. Declining kidney function induces uremic conditions, which alter the intestinal metabolic environment and promote pathogen overgrowth while reducing diversity. This dysbiosis-driven imbalance in the gut microbiota can result in elevated production of uremic toxins, which, in turn, enter the systemic circulation due to compromised gut barrier function under uremic conditions. The accumulation of gut-derived uremic toxins exacerbates local and systemic kidney inflammation. Immune-mediated kidney damage occurs due to the activation of immune cells in the intestine as a consequence of dysbiosis, leading to the production of cytokines and soluble urokinase-type plasminogen activator receptor (suPAR), thereby contributing to kidney inflammation. In this review, we delve into the fundamental mechanisms of immunosenescence in CKD, encompassing alterations in adaptive immunity, gut dysbiosis, and an overview of the clinical findings pertaining to immunosenescence.

Positive Association of Serum Galectin-3 with the Development of Aortic Stiffness of Patients on Peritoneal Dialysis.

A novel cardiovascular stress biomarker known as galectin-3 might be useful for anticipating adverse cardiovascular outcomes. The objective of the current investigation was to assess the association between serum galectin-3 levels and aortic stiffness (AS) in 196 patients on peritoneal dialysis. An enzyme-linked immunosorbent examination and a cuff-based volumetric displacement were employed to determine the levels of serum galectin-3 and the carotid-femoral pulse wave velocity (cfPWV), respectively. The AS group had 48 patients in total (24.5%) with cfPWV greater than 10 m/s. The AS group, when compared with the group without AS, had a significantly higher prevalence of diabetes mellitus and hypertension in addition to greater fasting glucose levels, waist circumference, systolic blood pressure, and serum galectin-3 levels. Multivariate logistic and linear regression analysis demonstrated that serum glactin-3 levels, in addition to gender and age, were significantly and independently associated with cfPWV and AS. Serum galectin-3 levels were linked with AS, according to a receiver operating characteristic curve analysis, with an area under the curve of 0.648 (95% confidence interval, 0.576-0.714; p = 0.0018). In summary, there was a significant correlation between serum galectin-3 levels and cfPWV in patients undergoing peritoneal dialysis therapy for end-stage kidney disease.

Association of diabetic retinopathy with risk of developing cardiovascular diseases in patients undergoing hemodialysis: A population-based cohort study.

BACKGROUND AND AIMS: While patients undergoing dialysis have substantially increased cardiovascular event rates compared with the general population, predicting individual risk remains difficult. Whether diabetic retinopathy (DR) is associated with cardiovascular diseases in this population is unclear. METHODS AND RESULTS: We conducted a nationwide cohort study of 27,686 incident hemodialysis patients with type 2 diabetes who were enrolled in Taiwan's National Health Insurance Research Database between January 1, 2010, and December 31, 2014, and had follow-up data until December 31, 2015. The primary outcome was a composite of macrovascular events, including acute coronary syndrome (ACS), acute ischemic stroke, and peripheral artery disease (PAD). A total of 10,537 (38.1%) patients had DR at baseline. We matched 9164 patients without DR (mean age, 63.7 years; 44.0% women) to 9164 patients with DR (mean age, 63.5 years; 43.8% women) by propensity score. During a median follow-up of 2.4 years, 5204 patients in the matched cohort experienced a primary outcome. The presence of DR was associated with a higher risk of a primary outcome (subdistribution hazard ratio [sHR] 1.07; 95% CI, 1.01-1.13), which reflected a higher risk of acute ischemic stroke (sHR 1.26; 95% CI, 1.14-1.39) and PAD (sHR 1.14; 95% CI, 1.05-1.25) but not ACS (sHR 0.99; 95% CI, 0.92-1.06). CONCLUSIONS: The presence of DR signifies an increased risk of acute ischemic stroke and PAD in hemodialysis patients with type 2 diabetes, independent of the known risk factors. These results highlight the need for more comprehensive cardiovascular assessment and management in hemodialysis patients with DR.

Association of malnutrition with SARS-CoV-2 vaccine response in patients undergoing hemodialysis.

BACKGROUND & AIMS: Patients undergoing dialysis are less likely to develop immune responses to SARS-CoV-2 vaccine. Malnutrition is common in the dialysis population. However, whether malnutrition contributes to the impaired immunogenicity remains unknown. The aim of this study was to assess the association between nutritional status and SARS-CoV-2 vaccine response in patients receiving maintenance hemodialysis. METHODS: A total of 206 hemodialysis patients (mean age, 67 ± 13 years) without prior SARS-CoV-2 infection were examined for the primary outcome of seroconversion, defined as the detection of IgG antibodies (≥50 AU/mL) to the receptor-binding domain of the S1 spike protein of SARS-CoV-2 one month after a priming dose of ChAdOx1 nCoV-19, an adenovirus-vectored vaccine. Nutritional status was assessed by using the Controlling Nutritional Status (CONUT) score, an objective indicator of nutrition incorporating serum albumin, total cholesterol, and total lymphocyte count, as well as the subjective global assessment (SGA). RESULTS: Overall, 16.5% of patients were classified as malnourished, and 64.1% of patients were at risk for malnutrition based on the CONUT score. Anti-SARS-CoV-2 IgG were the highest in patients with normal nutrition. In multivariate logistic regression analyses adjusted for age, sex, comorbidities, and use of immunosuppressants, patients with malnutrition remained less likely to develop an antibody response than those with normal nutrition (odds ratio 0.23, 95% CI, 0.07-0.76). SGA was a significant predictor of anti-SARS-CoV-2 IgG seroconversion in univariate but not multivariate analyses. CONCLUSIONS: Malnutrition according to CONUT score is associated with impaired humoral responses to SARS-CoV-2 vaccination in patients undergoing hemodialysis. Our results highlight the importance of incorporating nutritional assessment into routine dialysis care to identify patients at risk for suboptimal immune responses after SARS-CoV-2 vaccination. Further research is needed to determine whether nutritional intervention can improve immune responses in these vulnerable patients.

Association of secondary prevention medication use after myocardial infarction with mortality in hemodialysis patients.

Background: Mortality after myocardial infarction (MI) among patients undergoing dialysis is high. However, studies investigating the use of secondary prevention medications after MI and clinical outcomes in dialysis patients are lacking. This study aimed to examine the association of the number of guideline-recommended medications (antiplatelets, ß-blockers, statins and renin-angiotensin-aldosterone system inhibitors) with all-cause mortality after MI in hemodialysis (HD) patients. Methods: We conducted a nationwide cohort study of incident HD patients who were admitted for MI between 1 January 2010 and 31 December 2014 and were followed up until 31 December 2015, using Taiwan's national health insurance research database. Results: Of 1471 patients (mean age 68 years, 41.9% women) included in the analysis, 281 (19.1%) were treated with one cardioprotective medication, 406 (27.6%) with two, 490 (33.3%) with three and 294 (20%) with four. During a median follow-up of 1.0 years, 458 (31.1%) patients died. In a multivariable Cox model, each additional use of guideline-recommended therapies was associated with a significant 12% reduction in the risk of mortality {hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.80-0.97]}. Similar results were obtained in the analysis with the inverse probability of treatment weighting [HR 0.84 (95% CI 0.77-0.92)] and in the propensity score-matched subcohort [HR 0.87 (95% CI 0.77-0.98)]. The decreased mortality risk was consistently observed across all subgroups. Conclusions: The use of more evidence-based medications for secondary prevention after MI was associated with a lower risk of all-cause mortality in HD patients.

Using a Short Food Frequency Questionnaire to Evaluate Macronutrients, Fiber, Phosphorus, Potassium, and Calcium in Adults with Stages 3-5 Chronic Kidney Disease.

The progression of chronic kidney disease (CKD) can be directly or indirectly accelerated by a poor diet and the diet's influence on risk factors for this disease. There have been no food frequency questionnaires (FFQs) developed for the assessment of diet in patients with CKD in Taiwan. This study analyzed the validity of a short FFQ (SFFQ) with 42 items for estimating patient intake of macronutrients, fiber, phosphorus, potassium, and calcium against 3-day dietary records (3-day DRs) in Taiwanese patients with stages 3-5 CKD. In an interview, 107 participants with the help of a dietician filled out an SFFQ and reviewed a 3-day DR the patients had filled out prior to the interview. Partial Pearson correlation coefficients between SFFQ and 3-day DR were 0.722, 0.619, 0.593, 0.572, 0.450, 0.611 and 0.410 for protein, fat, carbohydrate, fiber, phosphorus, potassium, and calcium, respectively, after adjusting for energy intake. Cross-classification analysis revealed 63.5-83.2% similarity in cross-tool estimated intakes of macronutrients, fiber, phosphorus, potassium, and calcium in the same quartiles or adjacent ones. Bland-Altman plots revealed good agreement between the two tools along different intake levels. In conclusion, the newly developed SFFQ had moderate relative validity in estimating the usual intake of key nutrients related to nutrition management of patients with late-stage CKD, suggesting it can be used to assess dietary intakes in a population with CKD, especially in those residing in an Asian region.

Association of Reactogenicity with Immunogenicity of the ChAdOx1 nCoV-19 Vaccine in Patients Undergoing Hemodialysis.

The aim of our study was to determine whether local and systemic reactions following SARS-CoV-2 vaccination are predictive of immunogenicity in patients undergoing hemodialysis. We used an established questionnaire to survey 206 hemodialysis patients without prior SARS-CoV-2 infection regarding solicited local (pain, redness, and swelling) and systemic reactions (fatigue, headache, muscle and joint pain, nausea or vomiting, abdominal pain, diarrhea, and fever) within 7 days after receiving 1 dose of the ChAdOx1 nCoV-19 vaccine for SARS-CoV-2. The primary outcome was seroconversion of anti-SARS-CoV-2 IgG (≥50 AU/mL) at 28 days after vaccination. Local and systemic reactions were reported by 80 (38.8%) and 119 (57.8%) patients, respectively. A total of 138 (67.0%) patients developed an antibody response. Responders were younger, had a lower prevalence of coronary artery disease and use of immunosuppressants, and had a higher body mass index and lymphocyte count. In addition, a greater percentage of responders than non-responders reported reactogenicity. In multivariate logistic regression analyses, fever (OR 2.70 [95% CI 1.12-6.50]) and total symptom score (OR 1.33 [95% CI, 1.05-1.68], per one increase) remained strongly associated with a greater humoral response. In conclusion, higher reactogenicity may identify hemodialysis patients who are more responsive to SARS-CoV-2 vaccination.

Aging is associated with slower renal progression in patients with chronic kidney disease.

Objectives: Chronic kidney disease (CKD) is prevalent among the elderly. However, little is known about how the clinical course of CKD vary with age. The purpose of this study was to examine the impact of aging on the risk of end-stage kidney disease (ESKD) in patients with moderate to advanced CKD. Materials and Methods: A total of 454 patients with stages 3-5 CKD were prospectively followed for a median of 5.1 years. The primary outcome was ESKD needing chronic dialysis therapy or preemptive kidney transplantation. The secondary outcome was a composite of ESKD or all-cause mortality. Results: The mean age of the patients was 65 ± 13 years. 65.4% were men, 44.9% had diabetes mellitus, and 22.7% had cardiovascular disease. Overall, 142 participants progressed to ESKD and 63 participants died. Compared with young patients (age <65 years, n = 205), elderly patients (age ≥65 years, n = 249) were associated with a significantly decreased risk of ESKD in Cox proportional hazards models adjusted for sex, smoking history, diabetes mellitus, cardiovascular disease, systolic blood pressure, estimated glomerular filtration rate, urine protein: Creatinine ratio, use of renin-angiotensin-aldosterone blocker, hemoglobin, phosphate, interleukin-6, body mass index, and N-terminal pro-brain natriuretic peptide (hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.45, 0.96; P = 0.028). The results remained statistically significant when death as a competing risk was taken into account (subdistribution HR: 0.65; 95% CI: 0.45, 0.95, P = 0.026). Notably, elderly did not predict a higher risk for the composite outcome (HR: 0.94; 95% CI: 0.67, 1.32; P = 0.723). Conclusion: Elderly confers a decreased risk of ESKD in Taiwanese patients with moderate to advanced CKD. Our findings suggest that age is an important effect modifier for CKD progression.

Malnutrition is Associated with Increased Morbidity and Death in Dialysis Patients Undergoing Endovascular Therapy for Peripheral Artery Disease.

OBJECTIVE: Revascularisation for peripheral artery disease (PAD) is increasingly common in dialysis patients. Patients with PAD who have undergone revascularisation are at high risk of subsequent complications. Malnutrition is an important modifiable risk factor for dialysis patients, yet few data exist on the prognostic impact of malnutrition on post-procedure long term outcomes. The objective was to assess the prevalence and prognostic association of malnutrition using the Controlling Nutritional Status (CONUT) score in a prospective cohort of dialysis patients undergoing endovascular therapy (EVT) for PAD. METHODS: A total of 395 consecutive dialysis patients undergoing endovascular revascularisation for lower extremity PAD between 2005 and 2019 were examined for the primary outcome of all cause death. Secondary outcomes included major adverse limb events (MALEs), defined as acute limb ischaemia, major amputation, and clinically driven revascularisation; and major adverse cardiovascular events (MACEs). Nutritional status was assessed by CONUT score, a screening tool for malnutrition, incorporating albumin, cholesterol, and total lymphocyte count. RESULTS: According to the CONUT score, 40.8% of patients were moderately or severely malnourished. During a median follow up of 2.2 years, 218 (55.2%) patients died; 211 (53.4%) patients had MALEs, and MACEs occurred in 135 (34.2%) patients. Compared with normal nutritional status, severe malnutrition was associated with a significantly increased risk of all cause death (adjusted hazard ration [aHR] 4.83, 95% confidence interval [CI] 2.56 - 9.12) and MALEs (aHR 2.42, 95% CI 1.23 - 4.74) but not MACEs (aHR 1.81, 95% CI 0.74 - 4.40). Similar results were observed when the CONUT score was analysed as a continuous variable. CONCLUSION: Malnutrition is common in dialysis patients with PAD requiring endovascular therapy and is strongly associated with increased death and MALEs. Clinical trials are needed to evaluate whether nutritional interventions improve outcomes for dialysis patients after peripheral revascularisation.

A Comparison of SARC-F, Calf Circumference, and Their Combination for Sarcopenia Screening among Patients Undergoing Peritoneal Dialysis.

Sarcopenia is frequently encountered in patients undergoing peritoneal dialysis (PD). We evaluated and compared the diagnostic performance of a strength, assistance walking, rise from a chair, climb stairs, and falls (SARC-F) questionnaire, SARC-F combined with calf circumference (SARC-CalF), and calf circumference (CC) for screening sarcopenia among patients undergoing PD. We measured the appendicular skeletal muscle mass, evaluated using a multifrequency bioimpedance spectroscopy device, handgrip strength, and 6-m gait speed. SARC-F, SARC-CalF, and CC were obtained in all participants. Sarcopenia was defined using four different diagnostic criteria, including the Asian Working Group for Sarcopenia (AWGS) 2019, revised European Working Group on Sarcopenia in Older People (EWGSOP2), Foundation for the National Institutes of Health (FNIH), and International Working Group on Sarcopenia (IWGS). Among 186 enrolled patients undergoing PD (mean age 57.5 ± 14.1 years), the sarcopenia prevalence was 25.8-38.2% using the four definitions. The discriminative powers of SARC-CalF (range 0.648-0.748) and CC (range 0.652-0.813) against the four definitions were better than those exhibited by SARC-F (range 0.587-0.625), which achieved significant difference, except when adopting the criteria of the FNIH. After stratification by gender, the superiority of SARC-CalF and CC over SARC-F was maintained when AWGS 2019, EWGSOP2, and IWGS were applied. In conclusion, CC and SARC-CalF outperformed SARC-F in the diagnostic accuracy of sarcopenia among patients undergoing PD.

NSC828779 Alleviates Renal Tubulointerstitial Lesions Involving Interleukin-36 Signaling in Mice.

Renal tubulointerstitial lesions (TILs), a common pathologic hallmark of chronic kidney disease that evolves to end-stage renal disease, is characterized by progressive inflammation and pronounced fibrosis of the kidney. However, current therapeutic approaches to treat these lesions remain largely ineffectual. Previously, we demonstrated that elevated IL-36α levels in human renal tissue and urine are implicated in impaired renal function, and IL-36 signaling enhances activation of NLRP3 inflammasome in a mouse model of TILs. Recently, we synthesized NSC828779, a salicylanilide derivative (protected by U.S. patents with US 8975255 B2 and US 9162993 B2), which inhibits activation of NF-κB signaling with high immunomodulatory potency and low IC50, and we hypothesized that it would be a potential drug candidate for renal TILs. The current study validated the therapeutic effects of NSC828779 on TILs using a mouse model of unilateral ureteral obstruction (UUO) and relevant cell models, including renal tubular epithelial cells under mechanically induced constant pressure. Treatment with NSC828779 improved renal lesions, as demonstrated by dramatically reduced severity of renal inflammation and fibrosis and decreased urinary cytokine levels in UUO mice. This small molecule specifically inhibits the IL-36α/NLRP3 inflammasome pathway. Based on these results, the beneficial outcome represents synergistic suppression of both the IL-36α-activated MAPK/NLRP3 inflammasome and STAT3- and Smad2/3-dependent fibrogenic signaling. NSC828779 appears justified as a new drug candidate to treat renal progressive inflammation and fibrosis.

Differences in the Microbial Composition of Hemodialysis Patients Treated with and without ß-Blockers.

ß-blockers are commonly prescribed to treat cardiovascular disease in hemodialysis patients. Beyond the pharmacological effects, ß-blockers have potential impacts on gut microbiota, but no study has investigated the effect in hemodialysis patients. Hence, we aim to investigate the gut microbiota composition difference between ß-blocker users and nonusers in hemodialysis patients. Fecal samples collected from hemodialysis patients (83 ß-blocker users and 110 nonusers) were determined by 16S ribosomal RNA amplification sequencing. Propensity score (PS) matching was performed to control confounders. The microbial composition differences were analyzed by the linear discriminant analysis effect size, random forest, and zero-inflated Gaussian fit model. The α-diversity (Simpson index) was greater in ß-blocker users with a distinct ß-diversity (Bray-Curtis Index) compared to nonusers in both full and PS-matched cohorts. There was a significant enrichment in the genus Flavonifractor in ß-blocker users compared to nonusers in full and PS-matched cohorts. A similar finding was demonstrated in random forest analysis. In conclusion, hemodialysis patients using ß-blockers had a different gut microbiota composition compared to nonusers. In particular, the Flavonifractor genus was increased with ß-blocker treatment. Our findings highlight the impact of ß-blockers on the gut microbiota in hemodialysis patients.