Renal Failure最新文献

Background: Observational studies suggest a correlation between mitochondrial DNA copy number (mtDNA-CN) and renal function; however, the causality remains uncertain. This study employed a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the genetic causal relationship between mtDNA-CN and renal function. Methods: Genome-wide association study (GWAS) data for mtDNA-CN were obtained from the UK Biobank (n = 395,718), with renal function data primarily sourced from the CKDGen consortium and FinnGen studies. Four MR methods were employed, using inverse variance weighting as the primary approach, complemented by weighted median, MR Egger, and MR-PRESSO for sensitivity analyses. Multivariable MR (MVMR) assessed result robustness. Reverse MR treated renal function as the exposure. Validation was performed using additional mtDNA-CN GWAS data from the CHARGE UK Biobank (n = 465,809). Results: Forward MR analysis demonstrated a positive association between genetically predicted mtDNA-CN and estimated glomerular filtration rate (eGFR) [odds ratio (OR) = 1.007, 95% CI 1.003-1.012, p = 0.003]. MVMR suggested weaker evidence after adjusting for neutrophil count. Reverse MR revealed causal associations of urinary albumin-creatinine ratio (OR = 0.958, 0.923-0.994, p = 0.023) and microalbuminuria (OR = 0.981, 0.965-0.997, p = 0.021) with mtDNA-CN, though these effects were non-significant after multiple testing correction. Sensitivity and validation analyses confirmed robust. The findings from validation analyses were consistent. Conclusion: Our study suggests a potential causal association between mtDNA-CN and eGFR. However, the impact of confounding factors and the absence of consistent associations with other renal function markers underscore the necessity for further research to clarify the role of mtDNA-CN in renal function.

Background: Patients with chronic kidney disease (CKD) are at a high risk of cardiovascular disease. This study aims to observe the short-term changes of left ventricular (LV) myocardial work in stage 5 CKD patients with successful kidney transplantation (KT).

Methods: 45 stage 5 CKD patients who are candidates for KT were enrolled. Changes in clinical variables, laboratory data, routine transthoracic echocardiography, and noninvasive myocardial work (NIMW) were analyzed at pre-KT, 10 days, and 3 months post-KT. NIMW parameters include global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE).

Results: 1) Renal function indicators, including blood urea nitrogen, serum creatinine, and estimated glomerular filtration rate improved significantly at 10 days post-KT. At 3 months post-KT, there appears to be a continuing recovery trend; 2) GWE, GWI, and GCW were significantly increased at 3 months post-KT, but GCW and GWI with an early decrease at 10 days post-KT; 3) At the 10 days post-KT, the changes in systolic blood pressure and hemoglobin were positively correlated with the changes in GWI. Meanwhile, the change in systolic blood pressure was also positively correlated with the change in GCW. The change in diastolic blood pressure was positively correlated with the change in GWW.

Conclusion: LV systolic function doesn't improve in parallel with renal function after a successful KT. Steadily controlling blood pressure and correcting anemia is associated with improving myocardial work after KT, especially in the early post-transplant period.

Lycium barbarum polysaccharides (LBP) have shown renal protection effects. However, research on other active components of L. barbarum extract (ELB) for the therapy of chronic kidney disease (CKD) is limited. This study aims to investigate the renoprotective effects and molecular mechanisms of ELB in CKD. ELB was extracted from L. barbarum fruits using 85% ethanol reflux, followed by vacuum concentration and sequential extraction to remove polysaccharides. Chemical components and target genes were identified using TCMSP and UniProt databases, followed by pharmacology network construction and GO/KEGG pathway analysis. A 5/6 nephrectomy model in Sprague-Dawley rats was used to study the renoprotective effects of ELB, with H&E staining and biochemical analyses. Western blot analysis assessed IL-6 and VEGF expression in renal tissues. Chemical analysis of ELB identified 188 components, with 45 meeting screening criteria, and 34 linked to 94 target genes. The intersection with CKD-related genes yielded 39 overlapping genes, with quercetin having the most targets. GO/KEGG pathway analyses highlighted significant biological processes and pathways. A PPI network identified IL-6, VEGFA, CASP3, EGFR, ESR1, and PPARG as hub genes. In a 5/6 nephrectomy rat model, ELB treatment significantly reduced renal damage, serum BUN and SCr levels, as well as IL-6 and VEGF expression in renal tissues, validating its renoprotective effects and supporting bioinformatics predictions. This work identified the intricate components and pharmacological actions of ELB, which is devoid of LBP. The findings preliminarily confirm the potential of ELB as a novel therapeutic agent for preventing and managing CKD.

Purpose: This study aims to investigate the protective effect of baicalin on sepsis-associated acute kidney injury (SA-AKI) and its molecular mechanism.

Materials and methods: An SA-AKI mouse model was established via lipopolysaccharide (LPS) injection. Baicalin's effects on renal function, oxidative stress, and apoptosis were evaluated using histopathology, dihydroethidium, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Bioinformatics, molecular docking, ribonucleic acid (RNA) sequencing, and Western blotting were employed to investigate the role of baicalin in regulating the peroxisome proliferator‑activated receptor‑γ (PPAR-γ)/uncoupling protein 1 (UCP1) pathway. Human kidney-2 cells were used for in vitro validation.

Results: In this study, baicalin significantly ameliorated LPS-induced acute kidney injury by modulating the PPAR-γ/UCP1 signaling pathway. Both in vivo and in vitro experiments revealed that baicalin attenuates inflammation, oxidative stress, and apoptosis while restoring mitochondrial function. RNA sequencing analysis revealed significant upregulation of PPAR-γ/UCP1 in the baicalin-treated group. Further molecular docking and molecular dynamics simulations confirmed a stable interaction between baicalin and UCP1. Validation via small interfering RNA-mediated knockdown of PPAR-γ and UCP1 revealed that inhibition of the PPAR-γ/UCP1 pathway abrogated baicalin's protective effects, highlighting the critical role of this pathway in mediating baicalin's renoprotection.

Conclusion: Baicalin protects against SA-AKI by activating the PPAR-γ/UCP1 signaling pathway. This study provides new insights into the mechanisms through which baicalin mitigates kidney injury in sepsis, suggesting its potential as a therapeutic agent for SA-AKI.

Background: Systematic reviews and meta-analyses play a pivotal role in evidence-based medicine, including nephrology, by consolidating findings from multiple studies. To maximize their utility, rigorous quality assessment during peer review is essential. Challenges such as heterogeneity, bias, and methodological flaws often undermine these studies, necessitating a structured appraisal process.

Methods: This guide outlines a framework for nephrologists on appraising systematic reviews and meta-analyses. Key areas include heterogeneity assessment using the I² statistic, interpretation of forest plots for pooled effect estimates, and the use of funnel plots with Egger's test to identify potential publication bias. Risk of bias is evaluated using RoB 2 for randomized controlled trials and ROBINS-I for non-randomized studies. Subgroup and sensitivity analyses, along with meta-regression, address heterogeneity and examine the robustness of findings.

Results: The I² statistic quantifies heterogeneity by estimating the proportion of variability in a meta-analysis. Funnel plots and Egger's test help detect publication bias. Major biases, such as selection, performance, detection, and publication bias, are identified using structured tools like AMSTAR 2, Cochrane RoB 2, and ROBINS-I. The GRADE framework further assesses the overall certainty of the evidence. Emphasis is placed on PRISMA compliance, protocol pre-registration, and transparent reporting of statistical analyses, subgroup, and sensitivity assessments. The inclusion of grey literature remains optional.

Conclusion: By focusing on key areas such as heterogeneity, risk of bias, and robust statistical methods, this guide enables nephrologists to critically appraise systematic reviews and meta-analyses, fostering better clinical decision-making and improved patient care in nephrology.

The independent and domain-specific associations between physical activity (PA) and chronic kidney disease (CKD) remain underexplored. This study investigates the relationships between leisure-time, occupational, and transportation-related PA, along with sedentary behavior, and CKD prevalence in a nationally representative U.S. adult cohort. We analyzed 24,950 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2012. PA and sedentary behavior were assessed via validated questionnaires. Participants were classified based on adherence to physical activity guidelines (≥150 min/week). Multivariable logistic regression and restricted cubic splines were used to evaluate dose-response and non-linear associations. We found that meeting PA guidelines for total, leisure-time, and occupational PA was independently associated with lower odds of CKD (OR [95% CI]: 0.82 [0.73-0.93], 0.86 [0.76-0.97], and 0.85 [0.76-0.96], respectively). No significant association was observed for transportation-related PA. Sedentary behavior exceeding 6 h/day was associated with higher CKD prevalence. These associations were more pronounced in women, and dose-response patterns were evident across PA domains. This large-scale cross-sectional study identifies robust, domain-specific inverse associations between PA and CKD prevalence, particularly among women. Findings support stratified behavioral interventions targeting leisure and occupational activity domains, alongside sedentary behavior reduction, to mitigate CKD burden. Prospective studies are warranted to confirm causal pathways.

Background: In patients with end-stage renal disease (ESRD), vascular calcification significantly impairs hemodialysis (HD) vascular access functionality, compromising both dialysis efficacy and long-term patency. Early risk prediction of vascular calcification facilitates timely clinical interventions to preserve vascular access integrity.

Methods: A cross-sectional analysis was performed. Risk factors for vascular calcification in CKD patients were identified from the literature and Kidney Disease: Improving Global Outcomes guidelines. All variable selection and model training procedures were conducted on the training set. Univariate logistic regression was performed for all candidate variables. A nomogram was then constructed based on the final multivariate logistic model to facilitate clinical interpretation.

Result: A total of 136 HD patients were included. The predictive model, relying on arteriovenous (AV) access usage time, hip circumference, and diabetes status, is reliable and clinically actionable tool for predicting AV access calcification. Its robust performance across validation and subgroup analyses supports its potential for integration into routine clinical practice.

Conclusion: This study developed a nomogram-based predictive model for calcification, providing a simple, cost-effective, and reliable tool for early risk assessment. Monitoring hip circumference may serve as a practical approach for identifying high-risk patients, allowing for timely intervention and improved vascular access outcomes.

Contrast-induced acute kidney injury (CI-AKI) is the third leading cause of AKI, but there are no effective preventive or therapeutic measures in clinical practice. Glycyrrhizin, a bioactive compound isolated from the Glycyrrhiza glabra L., exhibits anti-inflammatory effects; however, the effects and mechanisms of glycyrrhizin on CI-AKI remain unknown. In present study, the effects of glycyrrhizin on renal dysfunction and tissue damage were evaluated in CI-AKI rats and mice. And the mechanisms were further investigated in iohexol treated renal tubular epithelial cells. Molecular docking and network pharmacology were used to discover the binding targets of glycyrrhizin and identify potential pathogenic pathway. Gene knockout mice and gene silencing cells were used to detect whether glycyrrhizin alleviated CI-AKI through target proteins mediated pathway. Results showed that both pretreatment and co-treatment with glycyrrhizin could alleviate iohexol-induced renal dysfunction and pathological damage in vivo. Similarly, glycyrrhizin could improve iohexol-induced decrease in cell viability of both HK-2 cells and primary mice renal tubular epithelial cells. Mechanistically, glycyrrhizin could directly bind to the active site of HMGB1, then blocking iohexol-induced ferroptosis of renal tubular epithelial cells. HMGB1 silencing was able to inhibit overactivation of AMPK/Beclin-1 axis during CI-AKI, and iohexol-downregulated protein expressions of GPX4 and SLC7A11 were reversed in kidneys of AMPK knockout mice. Comparable results were obtained in vitro with AICAR treatment. Our study is the first to demonstrate that glycyrrhizin exerts both protective and therapeutic effect on CI-AKI by inhibiting tubular epithelial cell ferroptosis via HMGB1/AMPK/Beclin-1 axis, providing a potential choice for treating CI-AKI.

Background: Vascular calcification and autophagy play pivotal roles in the pathogenesis of diabetic nephropathy (DN), though the underlying molecular mechanisms remain unclear. Methods: Differential expression analysis and weighted gene co-expression network analysis were performed on the GSE30529 dataset to identify candidate genes associated with DN. Subsequently, Mendelian randomization analysis was utilized to isolate genes with a causal relationship to DN. DN biomarkers were further validated based on their expression profiles in both the GSE30529 training set and the GSE96804 validation set. Gene set enrichment analysis, immune infiltration analysis, drug prediction, and molecular regulatory network construction were then conducted. Reverse transcription-quantitative PCR (RT-qPCR) was used to assess the expression of biomarkers in clinical DN and normal samples. Results: A total of 286 candidate genes were identified in the GSE30529 dataset, of which seven were linked to DN progression. JCHAIN and IFI44L were highlighted as biomarkers due to their upregulated expression and their association with DN risk. These biomarkers were predominantly enriched in immune-related pathways and were strongly correlated with specific immune cell populations. Expression of IFI44L was found to be potentially regulated by miRNAs and the transcription factor YY1. Furthermore, potential DN therapeutic targets, including JCHAIN and IFI44L, were identified. RT-qPCR confirmed elevated expression levels of JCHAIN (p = 0.0155) and IFI44L (p = 0.0203) in DN samples, consistent with trends observed in the GSE30529 and GSE96804 datasets. Conclusions: The investigation identified VC-CMARGs JCHAIN and IFI44L as promising biomarkers, offering valuable insights for the clinical diagnosis and treatment of DN.