Kidney & blood pressure research最新文献

Introduction: Cisplatin-induced acute kidney injury (Cis-AKI) is a significant cause of renal damage, characterized by tubular injury, ferroptosis, and oxidative stress. While therapeutic options for Cis-AKI remain limited, identifying novel targets to prevent kidney injury is critical. This study focuses on GALNT14, a gene associated with ferroptosis, and its potential role in mitigating Cis-AKI.

Methods: The Limma package was used to analyze differentially expressed genes (DEGs) between the saline and cisplatin groups. The weighted correlation network analysis (WGCNA) was performed to discover the co-expressed modules and hub genes linked with Cis-AKI. The hub genes were then put into String database to create a network of protein-protein interactions. The FerrDb database was used to acquire genes related to ferroptosis, which were then screened for their association with CiS-AKI. The role of GALNT14 was examined in vitro using HK-2 renal tubular cells and in vivo in a Cis-AKI murine model.

Results: Totally, 1,201 DEGs in intravenous (iv) administration group were retrieved. The 806 genes were obtained from intersection WGCNA and DEGs. Ultimately, we identified 4 genes (ALOX5, CD44, GALNT14, and ASNS) that may play important roles in the regulation of ferroptosis in Cis-AKI. The mRNA expression level of GALNT14 exhibited the most notable difference between Cis-AKI and the control group. In vitro, GALNT14 overexpression in HK-2 cells reduced renal injury and ferroptosis markers, including KIM1, NGAL, and FSP1, while increasing GPX4 expression. Conversely, silencing GALNT14 exacerbated Cis-AKI-induced injury. In vivo, GALNT14 overexpression in Cis-AKI mice attenuated kidney injury, reduced ferroptosis markers, and reversed pathological alterations such as tubular dilatation and loss of brush border.

Conclusion: GALNT14 inhibits Cis-AKI by regulating tubular ferroptosis, demonstrating its potential as a therapeutic target for kidney injury. Our findings suggest that GALNT14 could be an effective strategy for preventing Cis-AKI and improving renal function in kidney injury-related diseases.

Introduction: Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease and mortality. However, data on the prediction of long-term adverse outcomes in advanced predialysis CKD patients are lacking.

Methods: We studied the factors associated with mortality and major adverse cardiovascular and cerebrovascular events (MACCEs, including cardiovascular death, myocardial infarction, stroke, and coronary revascularization) in a cohort of 210 patients with non-dialysis CKD stages 4-5 during a 5-year follow-up. The participants underwent stress ergometry testing to study maximal exercise capacity (Wmax%), a plain lateral abdominal radiograph to study abdominal aortic calcification score (AAC) and laboratory tests including cardiac troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (ProBNP). Furthermore, a dichotomous composite covariate was created and explored by combining ProBNP and Wmax% using the cut-offs determined with the Youden index. The associations between covariates of interest and study outcomes were explored using multivariable Cox proportional hazards models adjusted with age, sex, coronary artery disease (CAD), and incident kidney transplantation (KTx).

Results: Median age at baseline was 65 (52-73) years and eGFR 12 (10-15) mL/min/1.73 m2, 34.8% were female, and 44.8% had diabetes. Altogether 67 (31.9%) patients died during follow-up, and 65 (31.0%) were observed with a MACCE. In separate multivariable Cox proportional hazards models adjusted for age, gender, CAD, and KTx, Wmax% (HR 0.983 [95% CI: 0.968-0.999], p = 0.019), TnT (HR 1.004 [95% CI: 1.002-1.005], p < 0.001), and ProBNP (HR 1.036 per 1,000 ng/L [95% CI: 1.014-1.059], p = 0.002) were independently associated with mortality. In similarly adjusted multivariable Cox models, Wmax% (HR 0.977 [95% CI: 0.962-0.992], p = 0.003), TnT (HR 1.004 [95% CI: 1.002-1.005], p < 0.001), and ProBNP (HR 1.034 per 1,000 ng/L [95% CI: 1.010-1.058], p = 0.006) were independently associated with the occurrence of MACCE during follow-up. AAC was associated with the risk of an incident MACCE (HR 1.080 [95% CI: 1.028-1.135], p = 0.002) but, surprisingly, not with mortality (HR 1.046 [95% CI: 0.994-1.101], p = 0.083). Finally, in participants with Wmax ≤50% and ProBNP ≥1,270 ng/L, the risk of mortality (HR 8.760 [95% CI: 4.730-16.222], p < 0.001) and MACCE (HR 3.293 [95% CI: 1.850-5.862], p < 0.001) was significantly greater than those with Wmax >50% and/or ProBNP <1,270 ng/L.

Conclusion: Wmax% and ProBNP separately and together as a composite risk factor may serve as important predictors of long-term all-cause mortality and MACCE in patients with CKD stages 4-5 not undergoing dialysis at baseline.

Introduction: Urine samples could partially reflect the renal condition and could provide possible mechanism of high-risk factor for the long-term development of chronic kidney disease (CKD) caused by prematurity.

Methods: Urine samples were collected from preterm infants (gestational age <28 weeks) when their corrected gestational weeks reached ≥37 weeks. In addition, urine samples were collected from full-term infants beyond 3 days after birth as the control group. The urine proteome was investigated by using liquid chromatography-tandem mass spectrometry analysis, and subsequent bioinformatics analysis was performed. Differentially expressed proteins were validated using ELISA.

Results: A total of 2,634 proteins were identified, 366 proteins were highly expressed in the preterm group, while 102 proteins were enriched in the full-term group. Based on functional analysis, proteins enriched in preterm group were implicated in structure organization, cell adhesion, and extracellular part, while proteins enriched in urine of the full-term group were implicated in the immune response. Kidney inherent cells accelerated into urine have been examined in preterm infants group. Each of the top 20 differentially expressed proteins enriched in the urine of preterm infants was used as a keyword for literature retrieval, ultimately leading to the selection and validation of CDH6 and CDH11 through ELISA. Both proteins were found to be more abundant in the urine of preterm infants than in that of full-term infants.

Conclusion: The present study provides differences in urine protein profiles between preterm and full-term infants and a new potential explanation for the high risk of CKD development caused by preterm birth.

Introduction: Diabetic nephropathy (DN) is a common complication in diabetic patients, and the pathological mechanism has not been fully understood. PIAS2, as a counter-regulator of the JAK2/STAT3 signaling pathway, may play a crucial role in DN. This study aimed to investigate the expression of PIAS2 in high glucose-induced podocytes and the protective effect against podocyte cell injury.

Methods: Human kidney podocytes were cultured under normal glucose (5.5 mm) and high glucose (30 mm) conditions. The expression of PIAS2 was detected by RT-qPCR and Western blotting. Subsequently, the effects of PIAS2 overexpression in high glucose-induced human podocytes were evaluated through the determination of cell viability, apoptosis, and secretion of inflammatory cytokines. Recombinant human IL-6 was used as an agonist of the JAK2/STAT3 signaling pathway to further validate the mechanism of the effects of PIAS2 in high glucose-induced human podocytes.

Results: High glucose treatment significantly increased the expression levels of PIAS2 in human podocytes. Overexpression of PIAS2 significantly reversed high glucose-induced human podocyte injury, evidenced by increased cell viability, reduced cell apoptosis, decreased expression of pro-apoptotic proteins Bax and cleaved caspase-3, increased expression of the antiapoptotic protein Bcl-2, and reduced secretion of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Additionally, IL-6 significantly reversed the protective effects of PIAS2 on high glucose-induced human podocytes.

Conclusion: PIAS2 plays a protective role in DN by inhibiting JAK2/STAT3 signaling pathway to alleviate high glucose-induced podocyte injury. PIAS2 may be a potential new target in the treatment of DN.

Introduction: High sodium and low potassium intake are associated with cardiovascular disease. This meta-analysis investigates the combined effect of dietary sodium and potassium intake (Na+/K+-ratio), on cardiovascular outcome.

Methods: We systematically searched MEDLINE and Embase databases (1946-2024) for randomized controlled trials and cohort studies reporting the association between estimated diet Na+/K+-ratio and cardiovascular events or mortality in adults. Two authors screened articles, extracted data, and assessed risk of bias (ROBINS-E tool). We pooled results using random-effects models and compared outcomes across the general population, patients with chronic kidney disease, and those with a history of cardiovascular disease. The study was registered in PROSPERO (ID: CRD42024450279).

Results: Twenty-four studies were included. Participants were 59 ± 11 years old, 49 ± 22% were men and the estimated dietary Na+/K+-ratio was 2.0 ± 0.6 mmol/mmol. The risk of bias was low in 9% of the studies, high in 39% of the studies and 52% of the studies were appraised as some concerns. Higher estimated diet Na+/K+-ratio was associated with a higher risk for cardiovascular events and mortality (hazard ratio 1.10 [95% confidence interval: 1.06-1.16]), which was apparent in the general population and subjects with a history of cardiovascular disease. In patients with chronic kidney disease, only limited data were available.

Conclusion: Higher estimated diet Na+/K+-ratio is associated with a higher incidence of cardiovascular events and mortality in both the general population and patients with a cardiovascular disease history.

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.

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.