Exploring the nexus between fatigue, body composition, and muscle strength in hemodialysis patients.

BACKGROUND: Fatigue is a relatively prevalent condition among hemodialysis patients, resulting in diminished health-related quality of life and decreased survival rates. The purpose of this study was to investigate the relationship between fatigue and body composition in hemodialysis patients. METHODS: This cross-sectional study included 92 patients in total. Fatigue was measured by Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (cut-off ≤ 34). Body composition was measured based on quantitative computed tomography (QCT), parameters including skeletal muscle index (SMI), intermuscular adipose tissue (IMAT), and bone mineral density (BMD). Handgrip strength was also collected. To explore the relationship between fatigue and body composition parameters, we conducted correlation analyses and binary logistic regression. RESULTS: The prevalence of fatigue was 37% (n = 34), abnormal bone density was 43.4% (n = 40). There was a positive correlation between handgrip strength and FACIT-F score (r = 0.448, p < 0.001). Age (r = - 0.411, p < 0.001), IMAT % (r = - 0.424, p < 0.001), negatively associated with FACIT-F score. Multivariate logistic regression analysis shows that older age, lower serum phosphorus, higher IMAT% are associated with a high risk of fatigue. CONCLUSION: The significantly increased incidence and degree of fatigue in hemodialysis patients is associated with more intermuscular adipose tissue in paraspinal muscle.

Diosmin ameliorates renal fibrosis through inhibition of inflammation by regulating SIRT3-mediated NF-κB p65 nuclear translocation.

BACKGROUND: Renal fibrosis is considered an irreversible pathological process and the ultimate common pathway for the development of all types of chronic kidney diseases and renal failure. Diosmin is a natural flavonoid glycoside that has antioxidant, anti-inflammatory, and antifibrotic activities. However, whether Diosmin protects kidneys by inhibiting renal fibrosis is unknown. We aimed to investigate the role of Diosmin in renal interstitial fibrosis and to explore the underlying mechanisms. METHODS: The UUO mouse model was established and gavaged with Diosmin (50 mg/kg·d and 100 mg/kg·d) for 14 days. HE staining, Masson staining, immunohistochemistry, western blotting and PCR were used to assess renal tissue injury and fibrosis. Elisa kits were used to detect the expression levels of IL-1ß, IL-6, and TNF-α and the activity of SIRT3 in renal tissues. In addition, enrichment maps of RNA sequencing analyzed changes in signaling pathways. In vitro, human renal tubular epithelial cells (HK-2) were stimulated with TGF-ß1 and then treated with diosmin (75 µM). The protein and mRNA expression levels of SIRT3 were detected in the cells. In addition, 3-TYP (selective inhibitor of SIRT3) and SIRT3 small interfering RNA (siRNA) were used to reduce SIRT3 levels in HK-2. RESULTS: Diosmin attenuated UUO-induced renal fibrosis and TGF-ß1-induced HK-2 fibrosis. In addition, Diosmin reduced IL-1ß, IL-6, and TNF-α levels in kidney tissues and supernatants of HK-2 medium. Interestingly, Diosmin administration increased the enzymatic activity of SIRT3 in UUO kidneys. In addition, Diosmin significantly increased mRNA and protein expression of SIRT3 in vitro and in vivo. Inhibition of SIRT3 expression using 3-TYP or SIRT3 siRNA abolished the anti-inflammatory effects of diosmin in HK-2 cells. Enrichment map analysis by RNA sequencing indicates that the nuclear factor-kappa B (NF-κB) signaling pathway was inhibited in the Diosmin intervention group. Furthermore, we found that TGF-ß1 increased the nuclear expression of nuclear NF-κB p65 but had little significant effect on the total intracellular expression of NF-κB p65. Additionally, Diosmin reduced TGF-ß1-caused NF-κB p65 nuclear translocation. Knockdown of SIRT3 expression by SIRT3 siRNA increased the nuclear expression of NF-κB p65 and abolished the inhibition effect of Diosmin in NF-κB p65 expression. CONCLUSIONS: Diosmin reduces renal inflammation and fibrosis, which is contributed by inhibiting nuclear translocation of NF-κB P65 through activating SIRT3.

Global, Regional, and National Burden of CKD in Children and Adolescents from 1990 to 2019.

BACKGROUND AND AIMS: CKD is one of the most prevalent non-communicable health concerns in children and adolescents worldwide; however, data on its incidence, prevalence, disability-adjusted life years (DALYs), and trends in the population are limited. We aimed to assess the global, regional, and national trends in CKD burden in children and adolescents. METHODS: In this trend analysis based on the 2019 Global Diseases, Injuries, and Risk Factors Study, CKD incidence, prevalence, and DALYs rates per 100,000 population for children and adolescents were reported at the global, regional, and national levels, as well as the average annual percentage change (AAPC). These global trends were analyzed by age, sex, region, and socio-demographic index (SDI). RESULTS: Globally, the overall incidence of CKD (all stages including KRT) in children and adolescents showed an increasing trend (AAPC 0.44 [95% CI 0.36-0.52]) between 1990 and 2019. Similarly, the overall prevalence of CKD also showed an upward trend (AAPC 0.46 [95% CI 0.42-0.51]). However, the DALYs of CKD showed a continuous decreasing trend (AAPC -1.18[-1.37- -0.99]). The population aged 15-19 years had the largest CKD incidence increase during this period. The largest increase in age-standardized incidence rate (ASIR) was in middle SDI countries (AAPC 0.56 [0.45-0.67]). The relationship between the ASIR and SDI showed an inverse U-shaped correlation while the relationship between the age-standardized DALYs rate (ASDR) and SDI showed an inverse trend with SDI. Among adolescents (15-19 years), the ASIR continued to increase for five causes of CKD, owing to type 2 diabetes mellitus and hypertension. Most of the disease burden was concentrated in countries with a lower SDI. Andean Latin America and Central Latin America showed the largest increases in CKD ASIR between 1990 and 2019. CONCLUSION: The burden of CKD in children and adolescents has increased worldwide, especially in regions and countries with a lower SDI.

Identification of basement membrane markers in diabetic kidney disease and immune infiltration by using bioinformatics analysis and experimental verification.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease worldwide. Basement membranes (BMs) are ubiquitous extracellular matrices which are affected in many diseases including DKD. Here, the authors aimed to identify BM-related markers in DKD and explored the immune cell infiltration in this process. The expression profiles of three datasets were downloaded from the Gene Expression Omnibus database. BM-related differentially expression genes (DEGs) were identified and Kyoto encyclopaedia of genes and genomes pathway enrichment analysis were applied to biological functions. Immune cell infiltration and immune function in the kidneys of patients with DKD and healthy controls were evaluated and compared using the ssGSEA algorithm. The association of hub genes and immune cells and immune function were explored. A total of 30 BM-related DEGs were identified. The functional analysis showed that BM-related DEGs were notably associated with basement membrane alterations. Crucially, BM-related hub genes in DKD were finally identified, which were able to distinguish patients with DKD from controls. Moreover, the authors observed that laminin subunit gamma 1(LAMC1) expression was significantly high in HK2 cells treated with high glucose. Immunohistochemistry results showed that, compared with those in db/m mouse kidneys, the levels of LAMC1 in db/db mouse kidneys were significantly increased. The biomarkers genes may prove crucial for DKD treatment as they could be targeted in future DKD treatment protocols.

Analysis of the potential biological mechanisms of diosmin against renal fibrosis based on network pharmacology and molecular docking approach.

BACKGROUND: Interstitial fibrosis is involved in the progression of various chronic kidney diseases and renal failure. Diosmin is a naturally occurring flavonoid glycoside that has antioxidant, anti-inflammatory, and antifibrotic activities. However, whether diosmin protects kidneys by inhibiting renal fibrosis is unknown. METHODS: The molecular formula of diosmin was obtained, targets related to diosmin and renal fibrosis were screened, and interactions among overlapping genes were analyzed. Overlapping genes were used for gene function and KEGG pathway enrichment analysis. TGF-ß1 was used to induce fibrosis in HK-2 cells, and diosmin treatment was administered. The expression levels of relevant mRNA were then detected. RESULTS: Network analysis identified 295 potential target genes for diosmin, 6828 for renal fibrosis, and 150 hub genes. Protein-protein interaction network results showed that CASP3, SRC, ANXA5, MMP9, HSP90AA1, IGF1, RHOA, ESR1, EGFR, and CDC42 were identified as key therapeutic targets. GO analysis revealed that these key targets may be involved in the negative regulation of apoptosis and protein phosphorylation. KEGG indicated that pathways in cancer, MAPK signaling pathway, Ras signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway were key pathways for renal fibrosis treatment. Molecular docking results showed that CASP3, ANXA5, MMP9, and HSP90AA1 stably bind to diosmin. Diosmin treatment inhibited the protein and mRNA levels of CASP3, MMP9, ANXA5, and HSP90AA1. Network pharmacology analysis and experimental results suggest that diosmin ameliorates renal fibrosis by decreasing the expression of CASP3, ANXA5, MMP9, and HSP90AA1. CONCLUSIONS: Diosmin has a potential multi-component, multi-target, and multi-pathway molecular mechanism of action in the treatment of renal fibrosis. CASP3, MMP9, ANXA5, and HSP90AA1 might be the most important direct targets of diosmin.

Environmental factors influencing the risk of ANCA-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of diseases characterized by inflammation and destruction of small and medium-sized blood vessels. Clinical disease phenotypes include microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The incidence of AAV has been on the rise in recent years with advances in ANCA testing. The etiology and pathogenesis of AAV are multifactorial and influenced by both genetic and environmental factors, as well as innate and adaptive immune system responses. Multiple case reports have shown that sustained exposure to silica in an occupational environment resulted in a significantly increased risk of ANCA positivity. A meta-analysis involving six case-control studies showed that silica exposure was positively associated with AAV incidence. Additionally, exposure to air pollutants, such as carbon monoxide (CO), is a risk factor for AAV. AAV has seasonal trends. Studies have shown that various environmental factors stimulate the body to activate neutrophils and expose their own antigens, resulting in the release of proteases and neutrophil extracellular traps, which damage vascular endothelial cells. Additionally, the activation of complement replacement pathways may exacerbate vascular inflammation. However, the role of environmental factors in the etiology of AAV remains unclear and has received little attention. In this review, we summarized the recent literature on the study of environmental factors, such as seasons, air pollution, latitude, silica, and microbial infection, in AAV with the aim of exploring the relationship between environmental factors and AAV and possible mechanisms of action to provide a scientific basis for the prevention and treatment of AAV.

Early Humoral Responses of Hemodialysis Patients After Inactivated SARS-CoV-2 Vaccination.

Purpose: To detect antibody responses to inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis and to investigate vaccine-related adverse events. Patients and Methods: A total of 120 hemodialysis (HD) patients and 24 healthy controls (HCs) who had not been previously infected with SARS-CoV-2 and had received their first dose of the inactivated vaccine (CoronaVac; Sinovac Biotech Ltd) were recruited for this study. All participants were scheduled to receive a second dose of inactivated SARS-CoV-2 vaccine. Serum-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against the SARS-CoV-2 were detected at least 14 days after the second dose of vaccine using a commercial kit. Positive and negative results were defined as a sample/cutoff (S/CO) ratio≥1.00 and <1.00, respectively. Vaccination-related adverse events were assessed using a standardized questionnaire. Results: There were no significant differences regarding the seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and the self-reported vaccination-related adverse events between HD patients and HCs. The analysis results for HD patients suggest that 82 (68.3%) and 27 (22.5%) tested positive for IgG and IgM, respectively. The levels of IgG were higher than IgM levels (P<0.0001). In addition, the IgG-positive group had significantly higher serum albumin levels than the IgG-negative group (P<0.05). Only mild vaccine-related adverse events were observed in two patients (1.66%) and in one healthy individual (4.2%). Conclusion: The seroprevalences of IgG and IgM antibodies against SARS-CoV-2 and vaccination-related adverse effects are similar between HD and HCs. The inactivated SARS-CoV-2 vaccine is effective and safe in inducing near-term immunity in hemodialysis patients.

Neutrophil-to-lymphocyte ratio in relation to the risk of all-cause mortality and cardiovascular events in patients with chronic kidney disease: a systematic review and meta-analysis.

AIM: To systematically evaluate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the risk of all-cause mortality or cardiovascular events in patients with chronic kidney disease (CKD). METHODS: PubMed, Embase, and Web of Science databases were searched for cohort studies that were published since the databases were launched, until 1 April 2020. We selected papers according to specific inclusion and exclusion criteria, extracted data, and evaluated the quality of the citations. Data from eligible studies were used to calculate the combined hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS: The search identified 1048 potentially eligible records, and 10 studies (n = 1442) were selected. Eight studies reported all-cause mortality, and two studies reported cardiovascular events. The combined HR of all-cause mortality was 1.45 (95% CI 1.20-1.75) and the HR of cardiovascular events was 1.52 (95% CI 1.33-1.72) when NLR was considered as a categorical variable. Similarly, the association between NLR and all-cause mortality was confirmed (HR 1.35; 95% CI 1.23-1.48) when NLR was used as a continuous variable. CONCLUSION: NLR is a predictor of all-cause mortality and cardiovascular events in patients with chronic kidney disease.