Renal Failure最新文献

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.

Chronic kidney disease (CKD) represents a significant global health challenge. Despite the availability of treatments, there remains a considerable residual risk of disease progression with current therapeutic approaches. Glomerular filtration rate (GFR) can increase due to various physiological and pathological stress responses, and the difference between the maximum GFR and the baseline GFR is termed renal functional reserve (RFR). A decline in RFR has been observed to occur well before CKD is clinically diagnosed. In addition, prolonged pathological stimulation of RFR may promote the development of other metabolic, hemodynamic, inflammatory, and fibrotic processes, which can ultimately drive CKD progression. This review consolidates the current evidence on the molecular mechanisms that underlie the initiation and decline of RFR, a phase that remains largely unaddressed as a primary treatment target but is gaining recognition for its critical role in CKD pathophysiology. Additionally, various methods for the safe and effective assessment of RFR are discussed. Recent clinical trial highlight promising new drug therapies and dietary strategies for the management of subclinical stages of CKD.

Aims: To validate the effectiveness of intensive glycemic control in preventing acute kidney injury (AKI) among patients with coronary artery disease (CAD) and prediabetes.

Methods: This investigation employed data from the Prospective Registry of the Current Status of Care for Patients with CAD database. Glycemic control was evaluated using the time-weighted average glucose (TWAG) and the glucose coefficient of variation (CV) for each participant. The primary outcome was AKI occurrence.

Results: A total of 2,454 CAD patients with prediabetes were included between January 2022 and June 2023. The mean age was 62.6 ± 10.3 years, with 27.1% female. In univariate analysis, each 1 mmol/L increase in TWAG was associated with a 1.51-fold (95% confidence interval (CI): 1.36-1.68) higher incidence of AKI. After stepwise adjustment for covariates, the odds ratio (OR) remained significant at 1.50 (95% CI: 1.35-1.67). Similarly, glucose CV showed a positive correlation with AKI risk; a 0.1-unit increase in CV was linked to approximately a 44% higher risk. When both TWAG and CV were included simultaneously in the model, each maintained an independent positive association with AKI. Restricted cubic spline analyses revealed a dose-dependent increase in AKI risk with rising TWAG and CV. Subgroup analyses confirmed the positive relationship between TWAG, glucose variability, and AKI risk.

Conclusions: Our study reveals an association between TWAG or CV of glucose and AKI in individuals with both CAD and prediabetes. These findings highlight the potential value of continuous glucose monitoring and managing glycemic variability to reduce AKI risk in this population.

Background: Traditional Chinese medicine active ingredients have been increasingly recognized for their pivotal role in the treatment of acute kidney injury (AKI).

Methods: This study aimed to investigate the reno-protective effects and underlying mechanisms of 4-Methoxylonchocarpin (4ML), an extract from Abrus precatorius Linne, in a cisplatin-induced AKI model. Kidney injury was assessed through a comprehensive evaluation of renal function indicators and histopathological changes. The impact of 4ML on ferroptosis and AMPK pathways was examined by measuring lipid peroxidation biomarkers and iron ion following low and high dose 4ML treatments in mice. In vitro experiments, using HK-2 cells to assess ferroptosis biomarkers and cell proliferation with or without 4ML treatment, and in the presence of selective inhibitors or activators of ferroptosis and AMPK, to elucidate the potential mechanisms.

Results: 4ML administration significantly attenuated cisplatin-induced AKI in both mice models and HK-2 cells. Mechanistic studies revealed that 4ML treatment markedly reduced ferroptosis and activated the AMPK pathway, as evidenced by altered expression levels of GSH, GPX4, MDA, LPO, and iron ions. The activation of AMPK pathway by 4ML contributed to the amelioration of AKI. Conversely, the induction of ferroptosis and inhibition of AMPK attenuated the protective effects of 4ML.

Conclusion: These findings suggest that 4ML as a promising therapeutic agent for cisplatin-induced AKI, primarily through inhibiting ferroptosis and regulating AMPK. This study provides further evidence supporting the potential of traditional Chinese medicine-derived compounds in the management of AKI.

While nephronophthisis (NPHP) classically manifests as mild tubular proteinuria, emerging evidence reports nephrotic-range proteinuria with edema. This study aims to explore the phenotypes and genotypes of pediatric NPHP patients with different levels of proteinuria. Twenty-one children with NPHP were recruited into this single-center cohort. They were divided into two groups according to proteinuria levels: group A (mild proteinuria, n = 12) and group B (moderate-to-heavy proteinuria, n = 9). The median age at symptom onset was 7.4 years (IQR 2.4-12.8). By the end of follow-up, 20 patients had progressed to ESRD at a median age of 9.8 years (IQR 5.8-12.9). Patients in group B exhibited significantly higher prevalence of family histories, hypertension, edema, and higher urine microalbumin-to-α1-microglobulin (MA/A1M) ratios. Genetic testing identified NPHP1 mutations as the most prevalent (61.9%), followed by TTC21B variants (19.0%). However, TTC21B mutations were more commonly found in group B (3/4, 75.0%) with one homozygous mutation and two compound heterozygous mutations. Five novel mutations of NPHP genes were identified. Further literature review of patients with TTC21B gene mutations revealed that the P209L variant was almost present in all North African/European patients, while the C518R heterozygous mutation occurred in 72.7% of Asian patients. In conclusion, NPHP remains a diagnosis in patients presenting with moderate-to-heavy proteinuria, particularly when accompanied by characteristic features including positive family history, hypertension, and edema, with TTC21B emerging as the predominant pathogenic gene in this clinical subgroup.

Recent studies have closely linked estimated glucose disposal rate (eGDR) to cardiovascular events; however, research on eGDR in chronic kidney disease (CKD) is limited. This study aimed to explore the relationship between eGDR and kidney diseases, including rapid kidney function decline (RKFD) and new-onset CKD (NOCKD), in a non-CKD population. We examined 5,679 non-CKD individuals from the China Health and Retirement Longitudinal Study (2011-2015) with complete eGDR data. Participants were categorized into four groups based on eGDR quartiles. Logistic regression and restricted cubic spline (RCS) were utilized to assess the correlation between eGDR and the incidence of RKFD and NOCKD. Subgroup analyses and optimization of predictive models were conducted based on baseline characteristics of participants. During follow-up, 402 RKFD and 220 NOCKD cases were documented. Higher eGDR was associated with reduced risk of RKFD (OR: 0.87, 95% CI: 0.81-0.94, p < 0.001) and NOCKD (OR: 0.88, 95% CI: 0.80-0.97, p = 0.01) per 1.0-SD increment. Restricted cubic splines models showed a linear relationship (non-linear p > 0.05), with increased RKFD/NOCKD risk when eGDR < 10.405 mg/kg/min. Adding eGDR improved predictive ability for RKFD (AUC: 0.659 vs. 0.672, p = 0.012) and NOCKD (AUC: 0.532 vs. 0.539, p = 0.004). This study demonstrated that lower eGDR levels in Chinese participants aged over 45 years without CKD are associated with an increased risk of developing RKFD and NOCKD.