Renal Failure最新文献

Background: Arteriovenous fistula (AVF) is currently the preferred vascular access for hemodialysis patients. However, the low maturation rate of AVF severely affects its use in patients. A more comprehensive understanding and study of the mechanisms of AVF maturation is urgently needed.

Methods and results: In this study, we downloaded the publicly available datasets (GSE119296 and GSE220796) from the Gene Expression Omnibus (GEO) and merged them for subsequent analysis. We screened 84 differentially expressed genes (DEGs) and performed the functional enrichment analysis. Next, we integrated the results obtained from the degree algorithm provided by the Cytohubba plug-in, Molecular complex detection (MCODE) plug-in, weighted gene correlation network analysis (WGCNA), and Least absolute shrinkage and selection operator (LASSO) logistic regression. This integration allowed us to identify CTSG as a hub gene associated with AVF maturation. Through the literature search and Pearson's correlation analysis, the genes matrix metalloproteinase 2 (MMP2) and MMP9 were identified as potential downstream effectors of CTSG. We then collected three immature clinical AVF vein samples and three mature samples and validated the expression of CTSG using immunohistochemistry (IHC) and double-immunofluorescence staining. The IHC results demonstrated a significant decrease in CTSG expression levels in the immature AVF vein samples compared to the mature samples. The results of double-immunofluorescence staining revealed that CTSG was expressed in both the intima and media of AVF veins. Moreover, the expression of CTSG in vascular smooth muscle cells (VSMCs) was significantly higher in the mature samples compared to the immature samples. The results of Masson's trichrome and collagen I IHC staining demonstrated a higher extent of collagen deposition in the media of immature AVF veins compared to the mature. By constructing an in vitro CTSG overexpression model in VSMCs, we found that CTSG upregulated the expression of MMP2 and MMP9 while downregulating the expression of collagen I and collagen III. Furthermore, CTSG was found to inhibit VSMC migration.

Conclusions: CTSG may promote AVF maturation by stimulating the secretion of MMP2 and MMP9 from VSMCs and reducing the extent of medial fibrosis in AVF veins by inhibiting the secretion of collagen I and collagen III.

Background: Plasma volume (PV) calculated from hematocrit and body weight has applications in cardiovascular disease. The current study investigated the validity of the calculated PV for predicting volume overload and its prognostic utility in patients undergoing hemodialysis (HD).

Patients and methods: Fifty-four HD patients were prospectively enrolled, and their actual PV (aPV) and relative PV status (PVS) were calculated. Bioelectrical impedance analysis (BIA) with assessment of and total body water (TBW), intracellular water (ICW), extracellular water (ECW), and overhydration (OH) and routine blood examinations were performed before dialysis. A second cohort of 164 HD patients was retrospectively enrolled to evaluate the relationship between the calculated PVS and the outcome, with an endpoint of all-cause mortality.

Results: aPV was significantly associated with TBW, ICW, ECW, OH, and ECW/TBW (all p < 0.001), and most strongly with ECW (r = 0.83). aPV predicted the extent of volume overload with an AUC of 0.770 (p < 0.001), but PVS did not (AUC = 0.617, p = 0.091). Median follow-up time was 53 months, during the course of which 60 (36.58%) patients died. Values for PVS (12.94 ± 10.87% vs. 7.45 ± 5.90%, p = 0.024) and time-averaged PVS (12.83 ± 11.20 vs. 6.78 ± 6.22%, p < 0.001) were significantly increased in patients who died relative to those who survived. A value of time-averaged PVS >8.72% was significantly associated with an increased incidence of all-cause mortality (HR = 2.48, p = 0.0023).

Conclusions: aPV was most strongly associated with ECW measured using BIA. HD patients with higher time-averaged PVS had a higher rate of all-cause mortality.

Background: The severity and course of sepsis-associated acute kidney injury (SA-AKI) are correlated with the mortality rate. Early detection of SA-AKI subphenotypes might facilitate the rapid provision of individualized care.

Patients and methods: In this post-hoc analysis of a multicenter prospective study, we combined conventional kidney function variables with serial measurements of urine (tissue inhibitor of metalloproteinase-2 [TIMP-2])* (insulin-like growth factor-binding protein [IGFBP7]) at 0, 6, 12, and 24 h) and then using an unsupervised hierarchical clustering of principal components (HCPC) approach to identify different phenotypes of SA-AKI. We then compared the subphenotypes with regard to a composite outcome of in-hospital death or the initiation of renal replacement therapy (RRT).

Results: We included 184 patients presenting SA-AKI within 6 h of the initiation of catecholamines. Three distinct subphenotypes were identified: subphenotype A (99 patients) was characterized by a normal urine output (UO), a low SCr and a low [TIMP-2]*[IGFBP7] level; subphenotype B (74 patients) was characterized by existing chronic kidney disease (CKD), a higher SCr, a low UO, and an intermediate [TIMP-2]*[IGFBP7] level; and subphenotype C was characterized by very low UO, a very high [TIMP-2]*[IGFBP7] level, and an intermediate SCr level. With subphenotype A as the reference, the adjusted hazard ratio (aHR) [95%CI] for the composite outcome was 3.77 [1.92-7.42] (p < 0.001) for subphenotype B and 4.80 [1.67-13.82] (p = 0.004) for subphenotype C.

Conclusions: Combining conventional kidney function variables with urine measurements of [TIMP-2]*[IGFBP7] might help to identify distinct SA-AKI subphenotypes with different short-term courses and survival rates.

Purpose: This study aimed to investigate the inhibitory effect of chrysophanol on renal fibrosis and its molecular mechanism.

Methods: Initially, potential targets of chrysophanol were predicted through network pharmacology analysis, and a protein-protein interaction network of these targets was constructed using Venn diagrams and the STRING database. GO enrichment analysis predicted the biological process of chrysophanol in treating renal fibrosis. Subsequently, both in vivo and in vitro experiments were conducted using unilateral ureteral obstruction (UUO) induced CKD mouse model and HK-2 cell model, respectively. In the mouse model, different doses of chrysophanol were administered to assess its renal protective effects through biochemical indicators, histological examination, and immunofluorescence staining. In the cell model, the regulatory effect of chrysophanol on the Trx-1/JNK/Cx43 pathway was evaluated using western blotting and flow cytometry.

Results: Chrysophanol treatment significantly ameliorated renal dysfunction and histopathological damage in the UUO mouse model, accompanied by a reduction in serum oxidative stress markers. Furthermore, chrysophanol markedly upregulated the expression of Trx-1 in renal tissues and inhibited the activation of the JNK/Cx43 signaling pathway. At the cellular level, chrysophanol enhanced the activity of Trx-1 and downregulated the JNK/Cx43 signaling pathway, thereby inhibiting TGF-β induced oxidative stress and cell apoptosis.

Conclusion: This study demonstrated a significant inhibitory effect of chrysophanol on renal fibrosis, mediated by the activation of Trx-1 to inhibit the JNK/Cx43 pathway. These findings provide experimental support for the potential use of chrysophanol as a therapeutic agent for renal fibrosis.

Objective: The purpose of this study was to investigate the correlation between different subtypes of acute kidney injury (AKI) and clinical outcomes following lung transplantation (LTx) and to identify a reliable indicator for predicting poor prognosis in the LTx population.

Methods: We retrospectively analyzed the clinical data of 279 LTx patients from August 2016 to March 2023. The AKI subtypes included AKI, persistent AKI on Day 7 (P7-AKI) and Day 14 (P14-AKI) after LTx, and AKI stages. The correlations of these factors with respiratory outcomes, mortality at 90 days, mortality at 1 year and data finalization were assessed, and the risk factors for the selected AKI subtypes were evaluated.

Results: AKI occurred in 215 patients (77.1%), with 129 (46.2%) experiencing P7-AKI and 95 (34.1%) experiencing P14-AKI. P7-AKI was associated with more respiratory and mortality outcomes than were AKI and AKI stages, and P7-AKI surpassed P14-AKI in terms of a shorter diagnostic time. After adjusting for age, sex, BMI, type of transplant, transplant diagnosis and comorbidities, P7-AKI independently correlated with increased mortality risk at 90 days [HR 12.312 (95% CI: 2.839-53.402)], 1 year [HR 3.847 (95% CI: 1.840-8.044)], and data finalization [HR 2.010 (95% CI: 1.331-3.033)]. Five variables were identified as independent predictors for P7-AKI, including preoperative body mass index, prothrombin activity, hemoglobin and serum creatinine, and intraoperative colloid administration.

Conclusion: P7-AKI has been identified as a reliable indicator for predicting adverse outcomes in LTx patients, which may assist healthcare professionals in identifying high-risk individuals.

Background: Tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) as a noninvasively measured index of right ventricular-pulmonary artery uncoupling is associated with poor outcomes in heart failure patients. However, the relationship by which the TAPSE/PASP is linked to atrial fibrillation (AF) in peritoneal dialysis (PD) patients is not clear. We aimed to investigate the relationship between the TAPSE/PASP and AF in PD patients.

Methods: This study was divided into two parts. First, we included 329 PD patients. All the subjects provided detailed a medical history, laboratory analysis and transthoracic echocardiography on admission. We evaluated the differences in the TASPE/PASP ratios between the AF and non-AF groups. Second, a total of 121 patients were followed up to compare mortality between the AF and non-AF groups.

Results: Age, BNP, RDW, LA, and septal E/e' were significantly higher, and TAPSE/PASP was significantly lower in patients with AF than in those without AF (p < 0.05). Moreover, the TAPSE/PASP was more pronounced in persistent AF patients. PD patients with AF had a greater risk of mortality (7.2%) than did those without AF (3.8%) after an average follow-up of 12 months. Kaplan-Meier analysis revealed that patients with TAPSE/PASP ratios ≤ 0.715 had a greater risk of mortality than did those with TAPSE/PASP ratios > 0.715.

Conclusions: The results suggested that the TAPSE/PASP was lower in AF patients than in non-AF patients. The TAPSE/PASP may be a useful factor for predicting mortality in AF patients with PD, but large-scale prospective studies are needed for verification.

Background: Body mass index (BMI) is associated with diabetic nephropathy (DN). However, the mediator factors in the BMI-DN effects remain unclear.

Methods: Univariate and multivariate Mendelian randomization (MR) analysis were performed to estimate the association between six lifestyles (moderate to vigorous physical activity levels, years of schooling, BMI, nap during day, number of treatments/medications taken and coffee intake) and DN. MR Egger, Weighted median, Simple mode, and Weighted mode was supplemental methods to Inverse variance weighted. Sensitivity analysis included heterogeneity test, horizontal pleiotropy test, and Leave-One-Out. Additionally, mediation MR was conducted to evaluate the mediating role of lifestyles between BMI and DN. Finally, functional enrichment analysis based on the mediation MR results was performed.

Results: univariate and multivariate Mendelian randomization (MR) analysis were performed to estimate the association between six lifestyles (moderate to vigorous physical activity levels, years of schooling, BMI, nap during day, number of treatments/medications taken and coffee intake) and DN. MR Egger, Weighted median, Simple mode, and Weighted mode was supplemental methods to Inverse variance weighted. Sensitivity analysis included heterogeneity test, horizontal pleiotropy test, and Leave-One-Out. Additionally, mediation MR was conducted to evaluate the mediating role of lifestyles between BMI and DN. Finally, functional enrichment analysis based on the mediation MR results was performed.

Conclusion: our results supported mediation role of vigorous physical activity level and number of treatments/medications in BMI-DN effects.

Objectives: To investigate glymphatic function in nondialysis-dependent ESRD (ND-ESRD) patients with diabetic kidney disease (DKD) or non-DKD using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and choroid plexus (CP) volume to explore the associations among DTI-ALPS index, CP volume, clinical characteristics, and cognitive function.

Methods: 25 DKD patients, 25 non-DKD patients, and 25 healthy control (HC) were included in this study. All participants underwent cerebral MRI and cognitive assessments. Bilateral DTI-ALPS index and CP volume were calculated and were compared among three groups. Correlations among the DTI-ALPS index, CP volume, clinical characteristics, and cognitive function were analyzed.

Results: DKD patients had significantly lower left DTI-ALPS index (p = 0.001) and mean DTI-ALPS index (p = 0.003) than non-DKD patients. In ND-ESRD patients, there was a significant positive correlation between the left DTI-ALPS index and phosphorus (r = 0.377, p = 0.007) and attention score (r = 0.434, p = 0.002). In DKD group, the mean DTI-ALPS was positively correlated with total cholesterol (r = 0.631, p = 0.001). In non-DKD group, there was a significant positive correlation between the left DTI-ALPS index and phosphorus (r = 0.696, p < 0.001). Both DKD and non-DKD patients exhibited significant higher CP volume than HC group. In non-DKD group, CP volume was negatively correlated with mean DTI-ALPS (r = -0.535, p = 0.006) and attention score of MoCA (r = -0.538, p = 0.006).

Conclusions: Glymphatic system dysfunction may contribute to the pathogenesis of clinical and cognitive impairment in ND-ESRD patients especially with DKD.

Anti-human thymocyte globulin-Fresenius (ATG-F) is frequently utilized to achieve successful induction for kidney transplantation recipients. This study aimed to examine the association between the ATG-F dose-to-recipient-weight ratio (ADR) and the risk of developing urinary tract infections (UTIs) following kidney transplantation. Data of kidney transplant recipients who underwent ATG-F-induction peri-operatively in a medical center were retrospectively collected, and the incidence of UTIs during the first postoperative year was also recorded. The risk of UTI associated with ADR was analyzed, and receiver operating characteristic curves were drawn to determine the optimal ADR, followed by Cox regression models. In total, 131 recipients were included, with an UTI incidence of 19.08% and a mean interval of 3.08 months. The optimal ADR was 6.34, involving 41 and 90 patients in the low ADR and high ADR groups, respectively. The UTI-free rate in the low ADR group was significantly higher than that in the high ADR group (p = 0.007). Cox regression analysis indicated that a high ADR independently increased the risk of UTI following kidney transplantation (hazard ratio: 5.306, 95% confidence interval: 1.243-22.660, p = 0.024). There was no significant difference in rejection rate between the high ADR and low ADR groups. In conclusion, a high ADR increased the incidence of early postoperative UTI among kidney transplant recipients.

Chronic disease progression models are available for several highly prevalent conditions. For chronic kidney disease (CKD), the scope of existing progression models is limited to the risk of kidney failure and major cardiovascular (CV) events. The aim of this project was to develop a comprehensive CKD progression model (CKD-PM) that simulates the risk of CKD progression and a broad range of complications in patients with CKD. A series of literature reviews informed the selection of risk factors and identified existing risk equations/algorithms for kidney replacement therapy (KRT), CV events, other CKD-related complications, and mortality. Risk equations and transition probabilities were primarily sourced from publications produced by large US and international CKD registries. A patient-level, state-transition model was developed with health states defined by the Kidney Disease Improving Global Outcomes categories. Model validation was performed by comparing predicted outcomes with observed outcomes in the source cohorts used in model development (internal validation) and other cohorts (external validation). The CKD-PM demonstrated satisfactory modeling properties. Accurate prediction of all-cause and CV mortality was achieved without calibration, while prediction of CV events through CKD-specific equations required implementation of a calibration factor to balance time-dependent versus baseline risk. Predicted annual changes in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio were acceptable in comparison to external values. A flexible eGFR threshold for KRT equations enabled accurate prediction of these events. This CKD-PM demonstrated reliable modeling properties. Both internal and external validation revealed robust outcomes.