Kidney & blood pressure research最新文献

{"title":"Monotherapy Blood Pressure Response and Control Rates in Treatment-Naïve Patients with Arterial Hypertension: A Randomized Comparison of Four Different Antihypertensive Drug Classes.","authors":"Annina Salome Vischer, Maria Bertsch, Vera Van der Velpen, Franziska Küng, Thenral Socrates, Michael Mayr, Manuel Haschke, Thilo Burkard","doi":"10.1159/000545908","DOIUrl":"10.1159/000545908","url":null,"abstract":"<p><strong>Introduction: </strong>Four different antihypertensive drug classes are equivalently recommended in the previous guidelines for first-line treatment of arterial hypertension (HTN). However, it is unclear, whether one of these drugs is more capable than the others to reach blood pressure (BP) control. We sought to compare response rates and BP control in these 4 classes.</p><p><strong>Methods: </strong>Patients with newly diagnosed mild to moderate HTN on 24-h BP measurements (ABPM) were randomized in a 1:1:1:1 fashion to either perindopril, olmesartan, amlodipine, or hydrochlorothiazide (HCT). ABPM was completed at baseline (BL) and after 4 weeks of half dose (treatment period 1 [TP1]). If BP control was not reached after TP1, drug dose was doubled and another ABPM completed after 4 weeks (treatment period 2 [TP2]). Patients were classified as controlled if 24-h mean BP was <130/80 mm Hg, awake BP <135/85 mm Hg, and night BP <120/70 mm Hg, and as optimal if 24-h mean BP was 115-124/65-74 mm Hg.</p><p><strong>Results: </strong>88 patients were randomized: 20 (23%) to perindopril, 23 (26%) to olmesartan, 24 (27%) to amlodipine, and 21 (24%) to HCT. Median 24-h mean BP reduction from BL to TP1 was -11/-6 mm Hg and from TP1 to TP2 -4/-2 mm Hg. The highest BP reduction was reached with olmesartan (-15/-10 mm Hg), particularly for diastolic values, the lowest with HCT (-8/-1 mm Hg). 27% of patients reached systo-diastolic BP control, with the best control rate with perindopril and olmesartan (40 and 39%), the lowest with HCT (5%), and 21%/18% reached an optimal treatment goal for systolic/diastolic 24-h mean values, respectively, after TP1. Three additional participants (4%) reached BP control after TP2.</p><p><strong>Conclusion: </strong>Initial antihypertensive monotherapy failed in most patients (73% uncontrolled, 21%/18% reached optimal treatment goal at TP1) even in low-risk patients, with efficacy varying by drug class (inhibitors of the renin-angiotensin-aldosterone system best, HCT least). These findings support guideline-recommended combination therapy.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"325-340"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis of RNA Methylation-Regulated Gene Signature and Immune Infiltration in Ischemia/Reperfusion-Induced Acute Kidney Injury.","authors":"Wei-Hua Liu, Fang Cao, Miao Lin, Fu-Yuan Hong","doi":"10.1159/000542787","DOIUrl":"10.1159/000542787","url":null,"abstract":"<p><strong>Introduction: </strong>The morbidity and mortality of acute kidney injury (AKI) are increasing. Epigenetic regulation and immune cell infiltration are thought to be involved in AKI. However, the relationship between epigenetic regulation and immune cell infiltration in AKI has not been elucidated. This study was conducted to identify the differentially expressed genes (DEGs), differentially expressed RNA methylation genes (DEMGs), and infiltrated immune cells in the kidneys of ischemia-reperfusion induced-acute kidney injury (IRI-AKI) models and further explore their relationships in IRI-AKI.</p><p><strong>Methods: </strong>This is a bioinformatic analysis using R programming language in 3 selected IRI-AKI datasets from the Gene Expression Omnibus (GEO) database, including 16 IRI-AKI kidney tissues and 10 normal kidney tissues. The DEGs were screened, and enrichment pathways were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The DEMGs and core DEMGs were identified using the R package. The ROC curve was plotted to predict disease occurrence of 7 core DEMGs. The correlation of 7 core DEMGs and other genes was analyzed using Pearson's correlation test. The gene set enrichment analysis (GSEA) of each DEMG was conducted using the R package. The upstream miRNAs and transcript factors of 7 core DEMGs were predicted based on the RegNetwork database and Cytoscape software. The STITCH database was used to predict the possible binding compounds of the 7 core DEMGs. Immune cell infiltration in kidney tissues between the IRI-AKI group and control group was evaluated using the R package.</p><p><strong>Results: </strong>A total of 2,367 DEGs were obtained, including 1,180 upregulated and 1,187 downregulated genes in IRI-AKI kidney associated with the cell structure, proliferation, molecule binding/interaction, and signaling pathways such as the leukocyte migration and chemokine signaling pathways. Ten DEMGs were identified, with Ythdf1, Rbm15, Trmt6, Hnrnpc, and Dnmt1 being significantly upregulated, while Lrpprc, Cyfip2, Mettl3, Ncbp2, and Nudt7 were significantly downregulated in IRI-AKI tissues. The molecules interacting with 7 core DEMGs were identified. Significant changes in the infiltration of 8 types of immune cells were observed in IRI-AKI kidneys compared to normal controls. The significant correlation between 6 core DEMGs and the infiltration of immune cells was observed.</p><p><strong>Conclusion: </strong>IRI may induce AKI through RNA methylation to regulate the expression of genes involved in immune cell infiltration.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"14-32"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe Coronary Artery Calcifications in Chronic Kidney Disease Patients, Coupled with Inflammation and Bone Mineral Disease Derangement, Promote Major Adverse Cardiovascular Events through Vascular Remodeling.","authors":"Marion Morena-Carrere, Isabelle Jaussent, Leila Chenine, Anne-Marie Dupuy, Anne-Sophie Bargnoux, Hélène Leray-Moragues, Kada Klouche, Hélène Vernhet, Bernard Canaud, Jean-Paul Cristol","doi":"10.1159/000542418","DOIUrl":"10.1159/000542418","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiovascular (CV) diseases persist as the foremost cause of morbidity/mortality among chronic kidney disease (CKD) patients. This paper examines the values of coronary artery calcification (CAC) and biomarkers of CV on major adverse CV events (MACE)/CV death in a sample of 425 non-dialysis CKD patients.</p><p><strong>Methods: </strong>At inclusion, patients underwent chest multidetector computed tomography for CAC scoring and biomarkers of CV risk including CRP, mineral metabolism markers, fibroblast growth factor-23 (FGF-23), α-Klotho, osteoprotegerin, tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin, matrix gla protein (both dephosphorylated uncarboxylated [dp-ucMGP] and total uncarboxylated), and growth differentiation factor-15 (GDF-15) were measured. Patients were followed for a median of 3.61 years (25th-75th percentiles = 1.92-6.70).</p><p><strong>Results: </strong>Our results reported that CAC was a major independent factor of MACE/CV mortality showing a hazard ratio of 1.71 95% (confidence interval = 1.00-2.93) after adjustment for age, gender, diabetes, and history of CV events for patients with CAC >300. Interestingly, CAC effect was further enhanced in the presence of low levels of 25(OH) vitamin D3 or α-Klotho and high levels of intact parathyroid hormone (PTH), high-sensitive C reactive protein, FGF-23, osteoprotegerin, sclerostin, dp-ucMGP, or GDF-15.</p><p><strong>Conclusion: </strong>CAC constitutes a significant CV risk, further exacerbated by inflammation, hyperparathyroidism, and regulation of bone molecules implicated in calcification progression. This finding aligns with the original concept of multiple hits. Consequently, addressing the detrimental environment that fosters plaque vulnerability, reducing chronic low-grade inflammation, and normalizing mineral metabolism markers (such as vitamin D and PTH) and bone-regulating molecules may emerge as a viable therapeutic strategy.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"33-45"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intercellular Communication Network of CellChat Uncovers Mechanisms of Kidney Fibrosis Based on Single-Cell RNA Sequencing.","authors":"Lei Lei, Yun-Xiu Xiang, Mao-Lin Luo, Ze-Yu Zhang, Hong-Wei Wu, Chun Tang, Tian-Jiao Cui, Xue-Mei Zhang, Xiao-Hua Wang, Denis Delic, Thomas Klein, Yvonne Liu, Bernhard K Krämer, Zhi-Hua Zheng, Yong-Ping Lu, Berthold Hocher, Ting Zhu","doi":"10.1159/000545209","DOIUrl":"10.1159/000545209","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) is a global health concern, with renal fibrosis being a major pathological feature. Empagliflozin (Empa), a sodium-glucose co-transporter-2 inhibitor, has shown promise in protecting the kidney. This study aimed to investigate the effects of Empa on renal fibrosis in a nondiabetic CKD model and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>We established a CKD model using 5/6 nephrectomy (5/6 Nx) rats and divided them into three groups: placebo-treated sham surgery rats, placebo-treated 5/6 Nx rats, and Empa-treated 5/6 Nx rats. Kidney function was assessed by measuring blood urea nitrogen, serum creatinine, and urinary albumin-to-creatinine ratio. Renal fibrosis was evaluated histologically. Single-cell RNA sequencing (scRNA-seq) was performed to analyze intercellular communication networks and identify alterations in ligand-receptor pairs and signaling pathways involved in fibrosis.</p><p><strong>Results: </strong>Empa treatment significantly improved kidney function and reduced renal interstitial fibrosis in 5/6 Nx rats. scRNA-seq revealed that Empa modulated the TGF-β signaling pathway, inhibited intercellular communication, and reduced the expression of fibrotic genes such as COLLAGEN, FN1, THBS, and LAMININ. Furthermore, Empa downregulated GRN gene expression, weakened signal transmission in the MIF pathway, consequently reduced the interaction between M2 macrophages and other cell types, such as endothelial cells, fibroblasts, and mesangial cells.</p><p><strong>Conclusion: </strong>This study elucidates the potential mechanisms by which Empa slows the progression of renal fibrosis in nondiabetic CKD. By reducing the number of M2 macrophages and inhibiting signal transduction in both pro-inflammatory and fibrotic pathways, Empa modulates the intercellular communication network in renal cells, offering a promising therapeutic strategy for CKD management.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"276-299"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Diagnosis of Malnutrition in Patients with Chronic Kidney Disease: Evaluating the Value of NRS2002 and SGA Scores.","authors":"Lihua Zhao, Shuai Chen, Liqing Ren, Lizhuang Zhang, Yicun Xu, Lina Yuan, Caixia Liu, Baoli Zhao, Jing Xue","doi":"10.1159/000546832","DOIUrl":"10.1159/000546832","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to explore the value of Nutritional Risk Screening 2002 (NRS2002) and Subjective Global Assessment (SGA) scores in diagnosing malnutrition in patients with chronic kidney disease (CKD).</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 87 patients with CKD admitted to our hospital from July 2023 to July 2024. Patient demographics were collected, and patients were grouped based on age, using 60 years as the cut-off. Clinical data were collected, and the number of cases with malnutrition and normal nutrition assessed by NRS2002 and SGA scores was calculated for different age and gender groups of CKD patients. Spearman's rank correlation analysis was used to assess the correlation between NRS2002 scores, SGA scores, and clinical data among CKD patients of different genders. Binary multivariable logistic regression analysis was performed to analyze the influencing factors of malnutrition in CKD patients evaluated by NRS2002 scores and SGA scores.</p><p><strong>Results: </strong>Among the CKD patients, 47.13% were classified as malnourished based on BMI, 65.52% based on NRS2002 scores, and 59.77% based on SGA scores. Correlation analysis showed a significant positive correlation between NRS2002 and SGA scores. Furthermore, NRS2002 scores and SGA scores exhibited a significant positive correlation with age (p < 0.001). Binary multivariable logistic regression analysis identified stage IV, age, BMI, RBC, Tp, PA, ALB, and GFR as significant factors associated with malnutrition in CKD patients.</p><p><strong>Conclusion: </strong>The NRS2002 and SGA scores are valuable tools for diagnosing malnutrition in CKD patients. Early detection and management of malnutrition can improve patient outcomes in this population.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"513-522"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of a PANoptosis-Related Gene Signature for Diabetic Nephropathy.","authors":"Li Geng, Yingying Liu, Yunwei Sun, Yan Chen","doi":"10.1159/000546764","DOIUrl":"10.1159/000546764","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic nephropathy (DN) is a serious complication of diabetes. In this study, we aimed to develop a diagnostic model for DN based on PANoptosis-related genes.</p><p><strong>Methods: </strong>PANoptosis-related differentially expressed gene (DEGs) associated with DN were identified in the GSE96804 and GSE142025 datasets. Pairwise correlations among these genes were assessed via Pearson correlation analysis. Immune cell abundance in DN patients versus controls was compared in GSE96804. Feature genes for DN prediction were selected with machine learning, and a diagnostic model was constructed using LASSO regression. High-risk and low-risk groups were established based on risk scores, with GSEA used to explore enriched biological processes and pathways. The association between risk scores and immune cell infiltration was examined using CIBERSORT. Potential therapeutic drugs were investigated via the DGIdb database.</p><p><strong>Results: </strong>Six PANoptosis-related DEGs were found. Immune cell analysis showed significant differences in dendritic cells, macrophages, mast cells, and neutrophils between DN patients and controls. A diagnostic model using three genes (PDK4, YWHAH, PRKX) achieved high accuracy (area under the curve = 0.8-1.0) across datasets, with a reliable nomogram for DN prediction. Risk stratification linked higher risk scores to distinct immune infiltration patterns and enriched cellular transport and metabolic pathways in high-risk DN patients. Protein-protein interaction network and correlation analyses revealed complex gene interactions. Potential therapeutic targets (PRKX, PDK4) and drugs were identified, and quantitative PCR validated YWHAH upregulation in patient plasma samples.</p><p><strong>Conclusion: </strong>The integration of PANoptosis-related genes PDK4, YWHAH, and PRKX offers a promising diagnostic model for DN, with YWHAH potentially involved in the pathological progression of DN.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"496-512"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological Analysis of Podocyte Injury and Death in Primary IgA Nephropathy.","authors":"Maria Luíza Gonçalves Dos Reis Monteiro, Laura Penna Rocha, Luísa Almeida Sarti Vasconcellos, Lucas Fernandes Pinheiro, Rosiane Nascimento Alves, Aline Cristina Souza da Silva, Liliane Silvano Araújo, Crislaine Aparecida Silva, Marlene Antônia Reis, Juliana Reis Machado","doi":"10.1159/000545841","DOIUrl":"10.1159/000545841","url":null,"abstract":"<p><strong>Introduction: </strong>IgA nephropathy (IgAN) is characterized by hematuria but can present with different clinical presentations. Proteinuria has been reported as the most important risk factor for the progression of IgAN and it may be related to podocyte injury.</p><p><strong>Methods: </strong>The kidney biopsy samples from patients with IgAN were analyzed using immunohistochemistry for WT1 to determine podocyte density and transmission electron microscopy to assess ultrastructural changes in podocytes and adjacent structures. A comparative group of patients diagnosed with minimal change disease (MCD) and a control group of autopsy samples without kidney disease were included.</p><p><strong>Results: </strong>Slit diaphragm density was lower in IgAN cases compared to controls but higher than in MCD cases. Podocyte density was significantly lower in the IgAN and MCD groups compared to controls, with the MCD group showing even lower density than the IgAN group. Podocyte density was lower in cases with nephrotic proteinuria both in MCD and IgAN. A significant negative correlation was detected between podocyte density and proteinuria in both conditions. A significantly lower proportion of detached podocytes was observed in cases with isolated autophagy and cases with autophagy showed a lower frequency of hematuria and a higher percentage of T0.</p><p><strong>Conclusion: </strong>We demonstrated that podocyte alterations in IgAN correlate with clinical parameters, including nephrotic proteinuria, hematuria, and interstitial fibrosis. Podocyte loss was associated with necrosis and mitotic catastrophe, while autophagy was prevalent but not apoptosis. Autophagy appears to protect against podocyte detachment. These findings highlight pathophysiological mechanisms relevant to diagnostic and clinical practice.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"351-365"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Investigations and Therapeutic Perspectives on Metabolic Syndrome following Kidney Transplantation.","authors":"Kejing Zhu, Yuji Jin, Weijian Liu, Cheng Wen, Xinrui Zheng, Zhixiong Li, Yunjian Chen, Yulin Niu, Wei Pan, Yong Jiang, Yingji Jin","doi":"10.1159/000545032","DOIUrl":"10.1159/000545032","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplantation was an effective method for treating chronic kidney failure via transplanting a healthy kidney from a donor to a patient with the loss of kidney function. However, clinical studies revealed that the posttransplantation status of patients was associated with a substantial aggregation of risk factors contributing to metabolic syndrome.</p><p><strong>Summary: </strong>This article provided a comprehensive review of the current researches on metabolic syndrome after kidney transplantation, and the latest advances in the interaction between metabolism and immune cells were also covered.</p><p><strong>Key messages: </strong>Our aim was to identify and intervene high-risk recipients in time and thus improving the prognosis of recipients.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"232-239"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACOT4 and ACOT6 Activate Akt-mTOR Pathway and Inhibit Calcium Oxalate-Induced Renal Tubular Cell Injury.","authors":"Shenghan Wang, Zhentao Lei, Wei Liu, Yuqiang Shi, Sherryn Sherryn, Qiang Gao, Bao Zhang","doi":"10.1159/000546897","DOIUrl":"10.1159/000546897","url":null,"abstract":"<p><strong>Introduction: </strong>Kidney stone caused by calcium oxalate (CaOx) is a chronic kidney disease. Acyl-coenzyme A thioesterases (ACOTs) serve as the key regulators of fatty acid metabolism. However, ACOTs' effect on CaOx kidney stone formation remains to be explored. Here, we aimed to investigate the effect of ACOTs on CaOx kidney stone formation.</p><p><strong>Methods: </strong>HK-2 and M-1 cells were cultured in DMEM/F12 medium supplemented with 10% FBS. Cells were treated with varying concentrations of calcium oxalate (CaOx) and transfected with siRNA or plasmid vectors targeting ACOT4 and ACOT6 using Lipofectamine RNAiMAX or Lipofectamine 3000. RT-qPCR and Western blotting were used to analyze gene and protein expression. Cell viability was assessed with CCK-8, and cell apoptosis was measured by flow cytometry. Crystal adhesion was visualized under a microscope. Lactate dehydrogenase (LDH) release was measured using a cytotoxicity assay kit. A kidney stone mouse model was established by injecting glyoxylic acid to induce kidney stones, and tissues were analyzed by Western blotting.</p><p><strong>Results: </strong>The mRNA and protein levels of several ACOT family members were upregulated in HK-2 cells treated with CaOx (inducing cell injury). Knockdown of ACOT4 and ACOT6 significantly suppressed the activity of CaOx-pretreated HK-2 and M-1 cells, and promoted the crystal formation and LDH release, whereas overexpression of ACOT4 and ACOT6 reduced CaOx crystal-induced kidney cell injury. Furthermore, the levels of p-AKT and p-S6 decreased after ACOT4 and ACOT6 knockdown and increased following ACOT4 and ACOT6 overexpression, suggesting that both ACOT4 and ACOT6 activated Akt/mTOR signaling pathway in HK-2 cells. We also observed that knockdown of ACOT4 and ACOT6 induced the apoptosis of HK-2 cells after CaOx treatment. Inhibition of apoptosis using Z-VAD-FMK reversed the enhanced cell injury caused by CaOx treatment and ACOT4/6 knockdown, suggesting that knockdown of ACOT4 and ACOT6 promoted cell injury via inducing cell apoptosis.</p><p><strong>Conclusions: </strong>ACOT4 and ACOT6 could be protecting factors for kidney cell injury induced by CaOx via reducing apoptosis and activating Akt/mTOR signaling pathway. The study of the role of ACOT4 and ACOT6 in kidney cell injury provides a new insight into the cause of CaOx kidney stone formation. Its in-depth study may provide new targets for stone treatment.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"533-544"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12503452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative Blood Pressure Management Recommendations in Pediatric Pheochromocytoma: A 10-Year Narrative Review.","authors":"Cahyani Gita Ambarsari, Nadhifah Nadhifah, Hertanti Indah Lestari","doi":"10.1159/000542897","DOIUrl":"10.1159/000542897","url":null,"abstract":"<p><strong>Background: </strong>Pheochromocytomas and paragangliomas are rare chromaffin cell-derived tumors characterized by catecholamine-secreting activity. Pheochromocytomas account for 1.7% of pediatric hypertension cases. Surgical resection, the definitive pheochromocytoma treatment, carries risks of hemodynamic instability and cardiovascular complications. Nevertheless, mortality rates decreased significantly in the latter half of the 20th century due to effective perioperative blood pressure (BP) management. The literature on BP management tailored to pediatric pheochromocytoma is limited, while the sustained hypertension rate in this population is high (up to 90%) and related to a high risk of intraoperative complications. In this narrative review, we provide up-to-date recommendations regarding BP management to minimize perioperative comorbidities in children with pheochromocytoma.</p><p><strong>Summary: </strong>Antihypertensive agents, primarily alpha (α)-blockers, should be promptly administered for suspected pheochromocytoma. Beta (β)-blockers may be introduced thereafter to counteract reflex tachycardia. The patient must be salt- and water-replete preoperation. Intraoperatively, stable hemodynamics should be ensured during anesthesia and surgery, and short-acting intravenous medications and resuscitation fluid should be supplied. Postoperatively, patients should be admitted to the pediatric intensive care unit for close monitoring for at least 24-48 h. Genetic testing is recommended for all pheochromocytoma patients. Identifying underlying mutations, like in succinate dehydrogenase subunit B, which is linked to a higher risk of multifocality and metastasis, is imperative for tailoring treatment strategies and prognostication.</p><p><strong>Key messages: </strong>Achieving optimal outcomes in pediatric pheochromocytoma relies on preoperative BP optimization with appropriate antihypertensive agents, intraoperative hemodynamic stability, and postoperative routine long-term follow-up to monitor for complications, recurrence, and metastasis. Future research should prioritize well-designed prospective multicenter studies with adequate sample sizes and, where feasible, randomized controlled trials with standardized protocols and appropriate endpoints. These studies should focus on the efficacy and safety of preoperative nonselective versus selective α-blockers, whether as monotherapy or combined with other medications (e.g., calcium channel blockers and/or β-blockers), or treatment without preoperative anti-hypertensives.</p>","PeriodicalId":17813,"journal":{"name":"Kidney & blood pressure research","volume":" ","pages":"61-82"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}