Kidney & blood pressure research最新文献

Introduction Diabetic kidney disease (DKD) is a common cause of chronic kidney disease with around 25-40% of patients with diabetes being affected. The course of DKD is variable and estimated glomerular filtration rate (eGFR) and albuminuria, the currently used clinical markers, are not able to accurately predict the individual disease trajectory, in particular in early stages of the disease. The aim of this study was to assess the association of urine levels of selected protein biomarkers with the progression of DKD at an early stage of disease. Methods We measured 22 protein biomarkers using the Mesoscale Discovery platform in 461 urine samples of the PROVALID cohort, an observational study of patients with type 2 diabetes mellitus followed at the primary health care level for a minimum of four years. Odds ratios (OR) were estimated for the effect of marker values above median on fast progression using unadjusted and adjusted logistic regression models. RNA expression at the single cell level in kidney biopsy samples obtained from a cohort of young persons with type 2 diabetes mellitus was in addition determined for markers showing significant associations with disease progression. Results Increased urinary levels of epidermal growth factor (EGF) were linked to lower odds of fast progression (defined as annual eGFR decline greater than 2.58 ml/min per 1.73 m2) with an odds ratio (OR) of 0.60 (95% CI 0.46, 0.78). The association with outcome was even stronger when adjusting for a set of 14 baseline clinical parameters including age, biological sex, eGFR, body mass index, albuminuria, and HbA1c. Elevated urinary levels of fatty acid binding protein 3 (FABP3) and vascular cell adhesion molecule 1 (VCAM1) were each significantly associated with fast progression with an OR of 1.44 (95% CI 1.11, 1.87) and an OR of 1.41 (95% CI 1.08, 1.83), respectively. Enriched expression of EGF and FABP3 was observed in distal convoluted tubular cells and VCAM1 in parietal epithelial cells at single cell level from biopsies of patients with early DKD. Conclusion In summary we show that lower urinary levels of EGF and higher urinary levels of FABP3 and VCAM1 are significantly associated with DKD progression in early-stage disease.

BACKGROUNDː Physical performance is poorly addressed in dialysis patients, due to several clinical and organizational barriers. In this study we investigated the physical functional status of a cohort of dialysis patients, using a multidimensional assessment. METHODSː Four hundred and forty-six individuals from 8 hemodialysis centers (176 females), mean age 67.5±14.1 years, and dialysis vintage 62 ± 72.1 months, were assessed by a multidimensional battery including Short Form Health Survey (SF12), Elderly Falls Screening Test (EFST), Short Physical Performance Battery (SPPB), and handgrip strength test (HST). Individuals were stratified into 3 groups (poor, moderate and good performers) according to the SPPB score. Functional assessments were performed by staff nurses, with the support of physiotherapists and nephrologists. RESULTSː According to SPPB 53,4% of dialysis patients showed a severe physical impairment. A significant difference emerged among the 3 SPPB groups for age, HST, EFST and SF12. The main predictors of the SPPB score group were age (p=0,0001) EFST (p=0,028 moderate performers and p=0,0001 poor performers) dominant HST(p=0,04 moderate performers) and SF12 physical (p=0,003 moderate performers and p=0,0001 poor performers) . Each age groups showed physical performance comparable to healthy general population of ten years older. CONCLUSIONSː Our results confirmed the severe impairment of physical function in ESKD population. The multidimensional assessment showed that SPPB test is an effective tool to stratify dialysis population. Moreover, EFST, HST and SF12 may contribute to the definition of a tailored physical activity program based on patient characteristics.

TThe literature lacks whether metabolic alkalemia occurs in outpatients with hypercalciuric nephrolithiasis. Thus, we aim to investigate it because these patients are often treated with thiazides to reduce urinary calcium excretion. However, thiazides induce chloride losses due to the inhibition of Na-Cl cotransporter expressed in the renal distal tubule cells. Besides thiazide prescription, many of these patients are also supplemented with potassium citrate, which is an addition of alkali source in their bodies.

Methods: We collected clinical, demographic characteristics, and laboratory data from electronical medical charts of outpatients with calcium-kidney stones followed in our institution from January 2013 to July 2021. We diagnosed as metabolic alkalemia those cases in which the venous blood gas tests showed pH≥7.46 and bicarbonate concentration>26 mEq/L. Then, we applied statistical analysis to compare distinct categories between patients with and without metabolic alkalemia.

Results: We diagnosed metabolic alkalemia in 4.3% of hypercalciuric nephrolithiasis outpatients, and we verified that thiazides had been used in all of them except in one case. Furthermore, we observed that the amount of thiazide taken daily was higher in patients with metabolic alkalemia than those without this imbalance. Additionally, hypokalemia was present in 37% of patients that developed metabolic alkalemia. We also found lower chloride, magnesium and ionic calcium serum concentrations in patients with metabolic alkalemia than in those without an acid-base disequilibrium.

Conclusion: Despite the low prevalence of metabolic alkalemia in hypercalciuric kidney stone formers, it is important to monitor these patients due to high incidence of hypokalemia and the potential presence of other electrolyte disorders.

Background: Tumor Lysis syndrome (TLS) is a well-recognized medical emergency in patients with cancer diagnosis. The diagnostic criteria of TLS have been revised many times since it was recognized, but still have many drawbacks limit diagnosis accuracy.

Summary: Autopsy studies in patients with perimortem diagnoses of TLS have shown that they may not have actually had TLS. Therefore, many cancer patients who are at risk for TLS, clinical and laboratory criteria may be fulfilled due to other causes of acute kidney injury. In this review, we aim to cast a spotlight on the shortcomings and pitfalls of the current diagnostic criteria for TLS, and propose a roadmap for developing a more rigorous criteria that improve on the diagnostic accuracy.

Key messages: Causes of AKI in patients with cancer other than TLS should be considered. Because current diagnostic criteria may miss those differential diagnosis, specific biomarkers that can tell when TLS is the underlying process is an important need, besides appropriate criteria that can jump over the pitfalls in the current criteria and enhance the recognition of TLS among other causes.

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.

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.

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.

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.