Associations between serum 25-hydroxyvitamin D and prognosis of chronic kidney disease: a prospective cohort study.

BACKGROUND AND OBJECTIVES: 25-hydroxyvitamin D [25(OH)D] deficiency is prevalent in patients with chronic kidney disease (CKD), the associations between serum 25(OH)D levels and mortality in patients with CKD remain unclear, and this study aimed to explore these associations further. METHODS: 4989 participants with CKD were enrolled in the study, and the Cox regression model was used to assess the effects of serum 25(OH)D concentrations on mortality risk. A restricted cubic spline model was used to explore the dose-response relationships, and threshold effect analysis was performed based on inflection points identified by a two-piecewise linear regression model. In addition, subgroup and sensitivity analyses were employed. RESULTS: 1255 participants died during a mean follow-up period of 70 months. Compared with the 25(OH)D-deficient group, the fully adjusted hazard ratios and 95% confidence intervals for the 25(OH)D-adequate group were 0.631 (0.545, 0.730) for all-cause mortality, 0.569 (0.435, 0.743) for cardiovascular mortality, 0.637 (0.461, 0.878) for hypertension mortality, and cancer mortality was 0.596 (0.426, 0.834). The inflection points of serum 25(OH)D concentration affecting all-cause and cardiovascular mortality were 89 nmol/L, and 107 nmol/L, respectively. Subgroup analyses and interaction tests suggested that the effects varied across populations. The results of sensitivity analyses indicated a reliable correlation. CONCLUSION: We found an association between serum 25(OH)D concentrations and the prognosis of patients with CKD as a reliable predictor of early intervention and intensive care.

Association of systemic immune-inflammation index and systemic inflammation response index with chronic kidney disease: observational study of 40,937 adults.

BACKGROUND: Chronic kidney disease (CKD) is linked to immunity and inflammation. Systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) are novel measures for gauging an individual's systemic inflammatory activity. We aim to investigate the potential associations between them. METHODS: This study encompassed a cohort of 40,937 adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. SII and SIRI were log2-transformed before conducting regression analysis, considering that these inflammatory markers were right skewed distributed. Weighted logistic regression models assessed the association of log2-SII and log2-SIRI levels with CKD prevalence. Weighted Cox regression models were utilized to estimate the risk of death. Subgroup analyses were performed to further clarify the effects of other covariates on the associations. Sensitivity analyses were performed to assess the robustness of our results. RESULTS: 6986 participants with CKD were recorded, and 2818 patients died during a mean follow-up time of 100 months. After adjusting for all covariates, the highest level of log2-SII increased the CKD incidence (odds ratio [OR]: 1.47, 95% confidence intervals [CI]: 1.32-1.65, P < 0.001), as well as log2-SIRI (OR: 1.79, 95% CI 1.60-2.01, P < 0.001) when compared with the lowest level reference group. The highest level of log2-SII significantly increased all-cause mortality (hazard risk [HR]: 1.29; 95% CI 1.13-1.48, P < 0.001), cardiovascular mortality (HR: 1.61, 95% CI 1.25-2.09, P < 0.001), and hypertension mortality (HR: 1.73, 95% CI 1.23-2.42, P = 0.001) in CKD patients. Additionally, the positive associations were also found between log2-SIRI and all cause (HR: 1.54, 95% CI 1.35-1.76, P < 0.001), cardiovascular (HR: 1.90, 95% CI 1.38-2.60, P < 0.001), and hypertension mortality (HR: 2.15, 95% CI 1.56-2.94, P < 0.001). Subgroup analyses unveiled variations in these effects among different populations. CONCLUSION: There existed a substantial association of SII and SIRI levels with CKD prevalence, as well as mortality in patients with CKD in the U.S.

A Single-Chain Variable Fragment Antibody Inhibits Aggregation of Phosphorylated Tau and Ameliorates Tau Toxicity in vitro and in vivo.

BACKGROUND: Alzheimer's disease (AD) is a common cause of dementia among elderly people. Hyperphosphorylation and aggregation of tau correlates with the clinical progression of AD; therefore, therapies targeting the aggregation of tau may have potential applications for anti-AD drug development. Several inhibitors of tau aggregation, including small molecules and antibodies, have been found to decrease the aggregation of tau and the corresponding pathology. OBJECTIVE: To screen one kind of single-chain variable fragment (scFv) antibody which could inhibit the aggregation of tau and ameliorate its cytotoxicity. METHODS/RESULTS: Using phosphorylated tau (pTau) as an antigen, we obtained a scFv antibody via the screening of a high-capacity phage antibody library. Biochemical analysis revealed that this scFv antibody (scFv T1) had a strong ability to inhibit pTau aggregation both in dilute solutions and under conditions of macromolecular crowding. ScFv T1 could also depolymerize preformed pTau aggregates in vitro. Furthermore, scFv T1 was found to be able to inhibit the cytotoxicity of extracellular pTau aggregates and ameliorate tau-mediated toxicity when coexpressed with a hTauR406W mutant in the eye of transgenic Drosophila flies. CONCLUSION: This scFv T1 antibody may be a potential new therapeutic agent against AD. Our methods can be used to develop novel strategies against protein aggregation for the treatment of neurodegenerative diseases.