Kidney & blood pressure research最新文献

Introduction: Serum platelet-activating factor (PAF) was proven to be associated with gestational hypertension. However, the predictive value of serum PAF at early pregnancy for the occurrence and outcomes of hypertensive disorders complicating pregnancy (HDCP) remained unclear.

Methods: The demographic and clinical characteristics of patients were compared among the different subgroups. The serum PAF level was determined using an enzyme-linked immunosorbent assay. The predictive value of serum PAF for the occurrence and outcomes of HDCP was evaluated using receiver operating characteristic curve analysis. The correlation of serum PAF with blood pressure was assessed using Spearman analysis.

Results: Both systolic blood pressure and diastolic blood pressure were significantly higher in HDCP patients, as well as the serum levels of TNF-α and IL-1β at diagnosis/enrollment, while serum levels of IL-10 showed the opposite trend. Serum PAF levels were significantly higher in patients with HDCP compared to normal pregnant women. Furthermore, serum PAF levels were higher in HDCP patients with mild preeclampsia compared to those with gestational hypertension and even more elevated in HDCP patients with severe preeclampsia at the early pregnancy stage and at diagnosis. In HDCP patients, increased serum PAF levels at early pregnancy and at diagnosis were associated with poor outcomes. Additionally, serum PAF levels could predict the occurrence of HDCP and poor outcomes.

Conclusion: Serum PAF from HDCP patients at both the early pregnancy and diagnosis stages could effectively predict the occurrence and outcome of HDCP.

Introduction: Regular physical activity is beneficial for health but is often reduced in patients receiving maintenance hemodialysis treatment. Irisin is a muscle-secreted hormone that reportedly improves metabolism and slows down the progression of some chronic diseases. In this study, we aimed to investigate the relationship between physical activity capacity and serum irisin levels in hemodialysis patients.

Methods: Our study included 252 patients undergoing hemodialysis at Xuanwu Hospital Capital Medical University. Enzyme-linked immunosorbent assay was used to measure blood irisin levels. Body composition was analyzed by bioelectrical impedance analysis. The International Physical Activity Questionnaire (IPAQ) was used to score physical activity ability.

Results: Bivariate correlation analysis showed a positive correlation between IPAQ scores and ln irisin (the natural logarithm of irisin; r = 0.326, P < 0.001). Independent determinants of IPAQ scores were ln irisin, age, fasting glucose, and carbon dioxide combining power.

Conclusion: Our findings provide the first clinical evidence that serum irisin levels are positively correlated with physical activity capacity in hemodialysis patients.

Introduction: This study aimed to investigate the potential association between the fatty liver index (FLI), metabolic dysfunction-associated steatotic liver disease (MASLD), and the risk of kidney stones using large-scale population-based data.

Methods: This study employed a cross-sectional design, utilizing data from the 2007-2018 National Health and Nutrition Examination Survey (NHANES) database. A total of 24,342 participants were enrolled in the study, and fatty liver status was assessed by calculating the FLI. MASLD was diagnosed by FLI in conjunction with cardiometabolic criteria. Data on the history of kidney stones were obtained by self-report. We employed logistic regression models to analyze the association between FLI, MASLD, and kidney stone risk and constructed multivariable adjustment models to control for potential confounders. Furthermore, we used restricted cubic spline curve models to investigate the dose-response relationship between FLI and kidney stone risk and conducted subgroup and interaction analyses.

Results: The study's results indicate a strong correlation between increasing FLI quartiles and a notable rise in the prevalence of kidney stones. Specifically, the risk of developing kidney stones was 1.68 times higher among participants in the highest FLI quartile compared to those in the lowest. Furthermore, patients with MASLD exhibited a 1.35-fold increased risk of developing kidney stones compared to those with non-MASLD. Subgroup analyses demonstrated that the correlation between MASLD and kidney stone risk was consistent across multiple subgroups. However, a significant interaction was observed in the subgroups of smoking status, physical activity level, and hypertension (interaction P < 0.05). The restricted cubic spline analysis did not yield a statistically significant nonlinear association between FLI and kidney stone risk. However, the study did identify inflection point values for FLI.

Conclusion: This study demonstrated an association between FLI and MASLD and the risk of kidney stones. This suggests that these conditions may be pivotal risk factors for kidney stones. Further investigation is required to elucidate these associations' underlying mechanisms and develop efficacious interventions to reduce the risk of kidney stones. Also, formulating personalized prevention and treatment strategies for different population subgroups is paramount.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: IRI may induce AKI through RNA methylation to regulate the expression of genes involved in immune cell infiltration.

Introduction: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Introduction: Interstitial cells are crucial to the development of kidney structure and function, although the mechanism underlying their role in it remains unclear to date. Our previous study identified cell clusters in human fetal kidney tissue, and we further analyzed the interstitial cell cluster within this context.

Methods: We extracted the barcoded cDNA from tissue samples and prepared spatial transcriptome libraries. Sequencing data were quality-checked, normalized, and clusters were identified using Seurat. Single-cell and spatial data were integrated using multimodal intersection analysis, and cell types were deconvoluted. DEGs in interstitial cells were identified and functionally annotated using DAVID. CellPhoneDB was used to predict ligand-receptor interactions between cell types.

Results: The results of the present study revealed that this cluster of interstitial cells appeared to be scattered in the junction between the cortical and medullary regions. The subsequent Kyoto Encyclopedia of Genes and Genome pathway analysis revealed that the differentially expressed genes (DEGs) in this cluster of interstitial cells were involved in the WNT signaling pathway. The Gene Ontology (GO) analysis revealed that these DEGs were involved in multiple pathways associated with kidney development, with six of the genes (NKD2, TCF21, WNT5A, WNT4, MDK, and SFRP1) associated with kidney development exhibiting significant upregulation. Accordingly, it was inferred that these interstitial cells might be involved in regulating epithelial cell differentiation, ureteral bud development, and morphogenesis. The subsequent cell-cell communication analysis revealed that the cellular crosstalk was primarily regulated mainly by ligand-receptor pairs. Additionally, 17 genes reported to be associated with kidney disease were focused on, and these genes were found to be predominantly expressed in a single-cell type.

Conclusion: In summary, the present study revealed the characteristics of a previously identified cluster of interstitial cells in the kidney tissue, thereby providing fresh insights into the process of kidney development.

Introduction: Acute kidney injury is characterized by high morbidity and mortality, with renal ischemia/reperfusion (I/R) injury as a critical inducer. Shikonin is the major bioactive compound extracted from the roots of Lithospermum erythrorhizon and possesses diverse pharmacological properties. This study was designed to investigate the biological functions of shikonin in renal I/R injury.

Methods: We established experimental models of renal I/R injury to detect shikonin roles. Renal tissues and blood were collected from mice. Serum levels of creatinine and blood urea nitrogen were evaluated with commercial kits. Kidney damage was detected by measuring KIM-1 protein level and performing hematoxylin and eosin staining and Periodic acid-Schiff staining. Apoptosis in kidney tissues was evaluated by evaluating the expression of apoptosis-related proteins and conducting TUNEL staining. ER stress was determined by measuring ER stress-specific markers. The potential mechanism related to shikonin roles was explored by western blotting and immunofluorescence staining. Cell viability and apoptosis were assayed by CCK-8 and flow cytometry.

Results: For in vivo analysis, renal dysfunctions and tissue structural damage induced by I/R were relieved by shikonin. Additionally, shikonin alleviated ER stress-mediated apoptosis in kidney tissues of I/R mice. Moreover, shikonin activated the SIRT1/Nrf2/HO-1 pathway after I/R, and inhibition of SIRT1 limited the shikonin-mediated protection against ER stress-stimulated apoptosis. For in vitro analysis, shikonin inhibited ER stress-induced apoptosis under H/R conditions. Additionally, inhibition of SIRT1 also attenuated the shikonin-mediated protection against ER stress-induced apoptosis in vitro.

Conclusion: Shikonin can relieve renal I/R injury by activating the SIRT1/Nrf2/HO-1 pathway to inhibit apoptosis caused by ER stress.

Introduction: Urolithiasis is characterized by a high morbidity and recurrence rate, primarily attributed to metabolic disorders. The identification of more metabolic biomarkers would provide valuable insights into the etiology of stone formation and the assessment of disease risk. The present study aimed to seek potential organic acid (OA) biomarkers from morning urine samples and explore new methods based on machine learning (ML) for metabolic risk prediction of urolithiasis.

Methods: Morning urine samples were collected from 117 healthy controls and 156 urolithiasis patients. Gas chromatography-mass spectrometry (GC-MS) was used to obtain metabolic profiles. Principal component analysis (PCA) and ML were carried out to screen robust markers and establish a prediction evaluation model.

Results: There were 25 differential metabolites identified, such as palmitic acid, L-pyroglutamic acid, glyoxylate, and ketoglutarate, mainly involving arginine and proline metabolism, fatty acid degradation, glycine, serine, and threonine metabolism, glyoxylate and dicarboxylic acid metabolism. The urinary organic acid markers significantly improved the performance of the ML model. The sensitivity and specificity were up to 87.50% and 84.38%, respectively. The area under the receiver operating characteristic curve (AUC) was significantly improved (AUC = 0.9248).

Conclusion: The results suggest that OA profiles in morning urine can improve the accuracy of predicting urolithiasis risk, and possibly help to understand the involvement of metabolic perturbations in metabolic pathways of stone formation and to provide new insights.

BACKGROUND 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 twentieth 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. SUMMARY Antihypertensive agents, primarily α-blockers, should be promptly administered for suspected pheochromocytoma. 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 hours. 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. KEY MESSAGES 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 non-selective 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 antihypertensives.