Kidney & blood pressure research最新文献

Backgrounds: The overall screening rate for complication of diabetes kidney disease is improving; however, regional variations are increasing. It is necessary to select regions vulnerable to change and understand their characteristics.

Methods: Group-based trajectory analysis was performed to derive change patterns in the complication of diabetes kidney disease screening rate in 244 regions using Community Health Survey data between 2015 and 2019. ANOVA test was conducted to examine the differences in regional characteristics and CVD in each change pattern.

Results: The change patterns in complication of diabetes kidney disease screening rate were classified into four groups: high and rapidly increasing (Group 1, 5.2%), steady high (Group 2, 8.2%), moderate and increasing (Group 3, 52.9%), and low and slightly increasing (Group 4, 23.8%). Group 4 had many rural areas and worse socioeconomic status, healthcare systems, health behaviors, and diabetes management, and these regions had higher CVD mortality rates.

Conclusions: Regions where the screening for complication of diabetes kidney disease rate did not improve compared to other regions were vulnerable not only in socioeconomic status, healthcare system, and health behavior, but also in disease management. This suggests the need for local and environmental support, as well as aggressive health service interventions in relatively vulnerable areas.

Introduction: Vitexin is a natural flavonoid compound extracted from Vitex leaves or seeds, exhibiting various pharmacological activities including anticancer, antihypertensive, anti-inflammatory, and spasmolytic effects. However, its protective effects on hypertensive nephropathy (HN) and the underlying mechanisms remain unclear.

Methods: Spontaneous hypertension rats were fed a high-sugar and high-fat diet for 8 weeks to induce the disease HN model. From the 5th week, the rats were administered vitexin via gavage. Blood pressure was measured biweekly using the tail-cuff method. Histopathological changes were assessed using HE staining, and biochemical analyses were performed to evaluate the effects of vitexin on HN rats. The underlying mechanisms of vitexin treatment were investigated through western blotting.

Results: The data demonstrated that vitexin significantly lowered systolic, diastolic, and mean arterial pressures and ameliorated histopathological changes in HN rats. Biochemical analyses revealed that vitexin reduced the levels of creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), total protein (TP), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and advanced glycation end products (AGEs), while increasing the levels of albumin (ALB) and superoxide dismutase (SOD). Western blotting results indicated that vitexin treatment decreased the expression of TNF-α, IL-6, and nuclear factor kappa-B (NF-κB), while increasing the expression of SOD.

Conclusion: The findings of this study suggest that vitexin exerts protective effects against HN, providing pharmacological evidence for its potential use in HN treatment.

Introduction: Individuals with chronic kidney disease (CKD) are at increased risk of thrombotic events and bleeding. Acetylsalicylic acid (ASA), an effective antiplatelet agent, is one of the most frequently used medications for both primary and secondary prevention of cardiovascular disease (CVD). However, it can also contribute to bleeding events due to its inherent antiplatelet effect. The objective of this study was to determine the characteristics of CKD patients at increased risk of bleeding under ASA therapy.

Methods: This retrospective analysis included patients with non-dialysis-dependent CKD who were treated with ASA for primary prevention of CVD for at least 3 consecutive months and did not receive anti-coagulants or anti-platelets. Data were collected from electronic medical records from January 2014 to December 2018. CKD diagnosis was based on an estimated glomerular filtration rate of <60 mL/min/1.73 m2. CKD patients who experienced major bleeding events during ASA therapy (bleeding group) versus all others (control group) were compared. Additional outcomes included first documented nonfatal cardiovascular event and all-cause mortality.

Results: Of the 900 adult CKD patients included in this analysis, 82 (9.1%) had a major bleeding event during 31.6 ± 25.9 months of follow-up. The most common bleeding site was gastrointestinal (52 cases, 63.4% of major bleeding events). Patients who had a major bleeding event were older (76.5 ± 10 vs. 74 ± 10.3 years, p = 0.038). On multivariate analysis, age was the most important predictor of major bleeding event (odds ratio: 1.029, 95% confidence interval: 1.004-1.056).

Conclusions: Given its controversial efficacy in primary prevention of CVD in CKD patients, characterizing those at increased risk of bleeding under ASA therapy is important in the era of tailored medicine. Age, CKD stage, and cardiovascular risk are key factors to consider regarding the safety and effectiveness of ASA for CKD patients.

Introduction: Maternal undernutrition (MUN)-induced low birth weight (LBW) neonates are susceptible to the development of high blood pressure and kidney disease later in life, although the underlying pathological causes remain unclear. The study here investigated the role of renal oxidative stress, impairment of vascular function, and altered sensitivity to angiotensin II (Ang II) as factors that contribute to these pathologies in aged LBW mice.

Methods: LBW offspring were generated using a combined protein and caloric restricted MUN mouse model. The resulting LBW offspring were examined 1 year after birth for mean arterial blood pressure (MABP) (carotid artery catheterization), renal blood flow (RBF) (laser Doppler flowmetry), glomerular filtration rate (GFR) (sinistrin clearance), vasoreactivity (myograph), renal vascular density (CD31 staining), and reactive oxygen species (ROS) (ROS probes). Immunoblotting examined Ang II type 1 receptor (AT1R), soluble guanylate cyclase (sGC), and antioxidant systems. Pharmacological agents delivered to animals included the sGC stimulator δ-aminolevulinic acid (ALA), the AT1R inhibitor losartan, the antioxidant ethyl pyruvate (EP), and the toll-like receptor 4 inhibitor TAK242.

Results: After 1 year, MABP was increased, while RBF, GFR, vascular reactivity, renal vascular density, and sGC were all reduced in the LBW aged adult. All four pharmacological agents improved MABP, RBF, GFR, vascular density, and vascular reactivity. Renal ROS was increased in the LBW adult but was reduced by ALA, EP, and TAK242 treatment. AT1R was upregulated in the LBW adult, while sGC was decreased, an effect reversed by ALA treatment. Endogenous antioxidant systems, including SOD1, catalase, and glutathione were downregulated in the LBW adult.

Conclusion: MUN-induced LBW mice experience increased Ang II sensitivity and oxidative stress. The increased Ang II sensitivity and ROS generation influences vascular density and reactivity, which drive an increase in MABP, and a concomitantly decrease in RBF and glomerular filtration. Pharmacological intervention that inhibits AT1R, enhances levels of sGC, reduces ROS, or inhibits toll-like receptor 4 improves vascular and renal function in the LBW adult.

Introduction: The coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus is alleged to enable a proinflammatory state that leads to the activation of the coagulation and the complement cascade. In this study, we aimed to establish the impact of the COVID-19 pandemic on patients with new onset of cTMA/aHUS in the Vienna TMA cohort and whether COVID-19 or SARS-CoV-2 vaccinations would pose a greater risk of initial manifestation of cTMA/aHUS.

Methods: We used the Vienna TMA cohort database to examine the prevalence of COVID-19-related and of SARS-CoV-2 vaccination-related aHUS/cTMA during the first 3 years of the COVID-19 pandemic in a large single-centre cohort.

Results: Between March 2020 and May 2023, a total of 7 patients experienced their first aHUS/cTMA episode. No patient experienced a TMA relapse or more than one episode during the follow-up period. Three TMA episodes were attributable to either COVID-19 (n = 1; 33%) or SARS-CoV-2 vaccination (n = 2; 66%), respectively. All 3 patients had systemic signs of TMA, and TMA was confirmed by kidney biopsy in all cases. Among the 7 patients, we recorded five infections that triggered one TMA episode (20%) and 19 vaccinations triggered two TMA episodes (10%; p = 0.52, odds ratio 0.47; 95% CI: 0.04-8.39).

Conclusion: We speculate that both SARS-CoV-2 vaccinations and COVID-19 episodes can represent a triggering factor for aHUS/cTMA episodes in (genetically) vulnerable individuals. However, COVID-19 might have a stronger association and might be a stronger trigger than the SARS-CoV-2 vaccines. The incidence of new aHUS cases did not differ from the pre-pandemic era in a large tertiary care centre cohort.

Introduction: Biomarkers are urgently required to identify peritoneal dialysis (PD) patients at risk of cardiovascular (CV) events. This study aimed to investigate the predictive value of soluble suppression of tumorigenicity-2 (sST2) for CV events in patients undergoing incident PD.

Methods: In this prospective cohort study, incident PD patients were enrolled. Blood samples to measure sST2 levels were obtained before PD catheter implantation. The patients underwent a standard peritoneal equilibration test (PET) after initiation of PD for 4-6 weeks. The sST2 levels in both serum and dialysate were determined using enzyme-linked immunosorbent assay. CV events were recorded during the follow-up period.

Results: A total of 137 patients were enrolled. During the follow-up period of 17.3 months, 49 (35.76%) patients experienced CV events. When patients were dichotomized based on the median values and the calculated cutoff values of sST2, the higher sST2 group had 2.980- and 3.048-fold increased risks of CV events, respectively, when compared with the lower sST2 group. Moreover, the prognostic value of sST2 remained significant as a continuous variable (per 1 standard deviation increase, hazard ratio [HR] = 1.037, 95% confidence interval [CI] 1.010-1.066, p = 0.008). N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were found to indicate a higher risk only when dichotomized based on the calculated cutoff values. Furthermore, serum sST2 and NT-proBNP levels simultaneously above the calculated cutoff values were associated with a higher risk of CV events (HR = 3.398, 95% CI 1.813-6.367, p < 0.001).

Conclusion: Baseline serum sST2 level is an independent predictor of the risk of CV events in patients receiving incident PD, and in combination with NT-proBNP level, it can provide a more accurate predictive value.

Background: The potential applications of nanotechnology in the medical field have become increasingly recognized in recent years. Nanocarriers have emerged as a versatile tool, offering a wide range of applications due to their unique properties. In addition to the targeted drugs delivery, nanocarriers have also proven to be extremely effective in imaging and diagnostics. Continuous advances in nanotechnology have paved the way for innovative solutions to complex challenges in human health, shaping the future of nanotechnology and its applications.

Summary: By exploring different types of nanoparticles, this review delves into the different characteristics that can be tailored to enhance their kidney access. Although the structural complexity of the kidney may prevent nanocarriers passage, optimization of nanocarrier characteristics such as shape, size, charge, and surface modifications may overcome these barriers, allowing for targeted delivery. By harnessing the potential of nanoparticles, researchers aim to develop targeted and efficient therapies that can address various kidney-related disorders.

Key messages: This review highlights the promising advancements in nanotechnology and their potential impact on improving the therapeutic outcomes for several kidney diseases.

Background: To improve the clinical evaluation of the prognosis of papillary renal cell carcinoma (PRCC), we screened a model to predict the survival of patients with mutations in related genes.

Methods: We downloaded RNA sequencing information from all patients with PRCC in TCGA. We first analyzed the differences in genes and the enrichment of these differences. Then, by selecting mutant genes, constructing a protein-protein interaction network, least absolute shrinkage and selection operator regression, and multivariable Cox regression, a prognosis model was constructed. Additionally, the model was validated using external data sets. We analyzed the immune infiltration of PRCC and the correlation between the model and popular targets. Finally, we performed tissue microarray analysis and immunohistochemistry to verify the expression levels of the three genes.

Results: We constructed a three-gene (never in mitosis gene A-related kinase 2 [NEK2], centromere protein A [CENPA], and GINS complex subunit 2 [GINS2]) model. The verification results indicated that the model had a good prediction effect. We also developed a visual nomogram. Enrichment analysis revealed the major pathways involved in muscle system processes. Immunoassays showed that the expression level of CENPA was positively correlated with PD-1 and CTLA4 expression levels. Immunohistochemical and tissue microarray results showed that these three genes were highly expressed in PRCC, which was consistent with the predicted results in the database.

Conclusion: We constructed and verified a three-gene model to predict the patient survival. The results show that the model has a good prediction effect.

Background: Chronic kidney disease (CKD) is a progressive systemic condition characterized by numerous complications. Among these, alterations in skeletal muscle physiology, such as sarcopenia, are particularly significant, as they are associated with poor outcomes and reduced quality of life.

Summary: Various interventions, including pharmacological approaches and lifestyle modifications have been investigated to slow CKD progression and prevent or treat its complications. Physical exercise, in particular, has emerged as a promising intervention with multiple beneficial effects. These include improvements in physical functioning, increased muscle mass, modulation of metabolic abnormalities, and reduced cardiovascular risk. However, the pathophysiology of physical exercise in patients with kidney disease is complex and remains only partially understood. A crucial advancement in understanding this phenomenon has been the identification of myokines - molecules expressed and released by skeletal muscle in response to physical activity. These myokines can exert both paracrine and systemic effects, influencing not only skeletal muscle physiology but also other processes such as energy metabolism and lipid regulation.

Key messages: The interplay among skeletal muscle, physical activity, and myokines may act as a pivotal regulator in various physiological processes, including aging, as well as in pathological conditions like cachexia and sarcopenia, frequently observed in CKD patients at different stages, including patients on dialysis. Despite the potential importance of this relationship, only a limited number of studies have explored the relationship between exercise and myokine, and the effect of this interaction on experimental models or individuals with kidney disease. In the following sections, we review and discuss this topic.

Introduction: Hypertension (HTN) is a major cardiovascular disease that can cause and be worsened by renal damage and inflammation. We previously reported that renal lymphatic endothelial cells (LECs) increase in response to HTN and that augmenting lymphangiogenesis in the kidneys reduces blood pressure and renal pro-inflammatory immune cells in mice with various forms of HTN. Our aim was to evaluate the specific changes that renal LECs undergo in HTN.

Methods: We performed single-cell RNA sequencing. Using the angiotensin II-induced and salt-sensitive mouse models of HTN, we isolated renal CD31+ and podoplanin+ cells.

Results: Sequencing of these cells revealed three distinct cell types with unique expression profiles, including LECs. The number and transcriptional diversity of LECs increased in samples from mice with HTN, as demonstrated by 597 differentially expressed genes (p < 0.01), 274 significantly enriched pathways (p < 0.01), and 331 regulons with specific enrichment in HTN LECs. These changes demonstrate a profound inflammatory response in renal LECs in HTN, leading to an increase in genes and pathways associated with inflammation-driven growth and immune checkpoint activity in LECs.

Conclusion: These results reinforce and help to further explain the benefits of renal LECs and lymphangiogenesis in HTN.