Renal Failure最新文献

Background: Cellular senescence, macrophages infiltration, and vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation participate in the pathophysiology of vascular calcification in chronic kidney disease (CKD). Senescent macrophages are involved in the regulation of inflammation in pathological diseases. In addition, senescent cells spread senescence to neighboring cells via Interferon-induced transmembrane protein3 (IFITM3). However, the role of senescent macrophages and IFITM3 in VSMCs calcification remains unexplored.

Aims: To explore the hypothesis that senescent macrophages contribute to the calcification and senescence of VSMCs via IFITM3.

Methods: Here, the macrophage senescence model was established using Lipopolysaccharides (LPS). The VSMCs were subjected to supernatants from macrophages (MCFS) or LPS-induced macrophages (LPS-MCFS) in the presence or absence of calcifying media (CM). Senescence-associated β-galactosidase (SA-β-gal), Alizarin red (AR), immunofluorescent staining, and western blot were used to identify cell senescence and calcification.

Results: The expression of IFITM3 was significantly increased in LPS-induced macrophages and the supernatants. The VSMCs transdifferentiated into osteogenic phenotype, expressing higher osteogenic differentiation markers (RUNX2) and lower VSMCs constructive makers (SM22α) when cultured with senescent macrophages supernatants. Also, senescence markers (p16 and p21) in VSMCs were significantly increased by senescent macrophages supernatants treated. However, IFITM3 knockdown inhibited this process.

Conclusions: Our study showed that LPS-induced senescence of macrophages accelerated the calcification of VSMCs via IFITM3. These data provide a new perspective linking VC and aging, which may provide clues for diagnosing and treating accelerated vascular aging in patients with CKD.

Background: Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN.

Methods: A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed.

Results: Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value.

Conclusion: Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.

This study aimed to explore the mechanism of Xiaoyu Xiezhuo decoction (XXD) on ischemia-reperfusion-induced acute kidney injury (IRI-AKI) using network pharmacology methods and gut microbiota analysis. A total of 1778 AKI-related targets were obtained, including 140 targets possibly regulated by AKI in XXD, indicating that the core targets were mainly enriched in inflammatory-related pathways, such as the IL-17 signaling pathway and TNF signaling pathway. The unilateral IRI-AKI animal model was established and randomly divided into four groups: the sham group, the AKI group, the sham + XXD group, and the AKI + XXD group. Compared with the rats in the AKI group, XXD improved not only renal function, urinary enzymes, and biomarkers of renal damage such as Kim-1, cystatin C, and serum inflammatory factors such as IL-17, TNF-α, IL-6, and IL 1-β, but also intestinal metabolites including lipopolysaccharides, d-lactic acid, indoxyl sulfate, p-cresyl sulfate, and short-chain fatty acids. XXD ameliorated renal and colonic pathological injury as well as inflammation and chemokine gene abundance, such as IL-17, TNF-α, IL-6, IL-1β, ICAM-1, and MCP-1, in AKI rats via the TLR4/NF-κB/NLRP3 pathway, reducing the AKI score, renal pathological damage, and improving the intestinal mucosa's inflammatory infiltration. It also repaired markers of the mucosal barrier, including claudin-1, occludin, and ZO-1. Compared with the rats in the AKI group, the α diversity was significantly increased, and the Chao1 index was significantly enhanced after XXD treatment in both the sham group and the AKI group. The treatment group significantly reversed this change in microbiota.

Background: This cohort study aimed to explore the relationship between hydration status and the risk of diabetic kidney disease (DKD) as well as all-cause death in DKD patients.

Methods: Weighted univariable and multivariable logistic regression models were used to explore the association between hydration status and DKD risk in diabetic population while weighted univariable and multivariable Cox regression models were used to identify the association between hydration status and all-cause mortality in DKD patients. Kaplan-Meier curve was plotted to present the survival probability of patients with different hydration status. Estimates were presented as odds ratio (OR), and hazard ratio (HR) with 95% confidence interval (CI).

Results: The mean follow-up time was 79.74 (±1.89) months. There were 2041 participants with DKD, and 2889 participants without. At the end of the follow-up, 965 participants were alive. The risk of DKD was increased as the increase of osmolarity level (OR = 1.07, 95%CI: 1.05-1.08). The elevated risk of DKD was observed in patients with impending dehydration (OR = 1.49, 95%CI: 1.19-1.85) or current dehydration (OR = 2.69, 95%CI: 2.09-3.46). The association between increased osmolarty level and elevated risk of all-cause mortality in DKD patients was statistically different (HR = 1.02, 95%CI: 1.01-1.03). Current dehydration was correlated with increased all-cause mortality risk in DKD patients (HR = 1.27, 95%CI: 1.01-1.61). Compared to DKD patients with normal hydration, the survival probability of DKD patients with current dehydration was significant lower (p < 0.001).

Conclusion: Increased osmolarity level was associated with increased risk of DKD and elevated risk of all-cause mortality in DKD patients.

Initiating dialysis therapy in elderly patients with end-stage kidney disease (ESKD) is a challenging decision. We aimed to examine the mortality rates among elderly patients who underwent hemodialysis, peritoneal dialysis, or comprehensive conservative care. This retrospective cohort study included elderly patients (≥70 years) with ESKD who selected their treatment options from January 2008 to December 2018. Patients were categorized into three groups: hemodialysis, peritoneal dialysis, and comprehensive conservative care. The outcome of interest was all-cause mortality analyzed using flexible parametric survival models. Propensity score analysis with inverse probability treatment weighting technique was performed, incorporating age, Charlson Comorbidity Index score, and estimated glomerular filtration rate. The study included 719 elderly ESKD patients with mean age of 78.2 ± 4.9 years, 52.3% were male, and 60.1% died during the median follow-up period of 22.1 months. In a fully adjusted model, patients receiving comprehensive conservative care (n = 50) had higher mortality rates than those receiving hemodialysis (n = 317) (adjusted hazard ratio [HR] 5.60; 95% CI 2.26-13.84, p < 0.001). However, patients who received peritoneal dialysis (n = 352) had a similar mortality rate when compared to those who received hemodialysis (adjusted HR 1.38; 95% CI 0.78-2.44, p = 0.275). The higher mortality rate in the comprehensive conservative care group remained significantly higher than in the hemodialysis group among patients aged ≥80 years (adjusted HR 4.97; 95% CI 1.32-18.80, p = 0.018). Among elderly patients (≥70 years), treatment with dialysis was associated with longer survival rates. This survival advantage persisted in patients aged ≥80 years who chose hemodialysis or peritoneal dialysis over comprehensive conservative care.

5-Fluorouracil (5-FU) is one of the most used anticancer drugs. However, its nephrotoxicity-associated drawback is of clinical concern. Lycopene (LYC) is a red carotenoid with remarkable anti-inflammatory and anti-oxidative properties. In this study, rats were divided randomly into five groups: control, lycopene (10 mg) (10 mg/kg/day; P.O), 5-FU (30 mg/kg/day; i.p.), Lycopene (5 mg) + 5-FU (5 mg/kg + 30 mg/kg/day), and lycopene (10 mg) + 5-FU (10 mg/kg + 30 mg/kg/day). LYC attenuated the loss of renal function induced by 5-FU in a dose-dependent manner. Rats co-treated with LYC had lower serum urea, creatinine, uric acid and KIM-1 levels, and a higher serum albumin level than those receiving 5-FU alone. Furthermore, co-treatment with the high dose of LYC maintained renal oxidant-antioxidant balance by ameliorating/preventing the loss of antioxidants and the elevation of malondialdehyde. Rats treated with 5-FU had markedly lower renal levels of PPAR-gamma, HO-1, Nfr2, and Il-10 and higher levels of NF-kB, TNF-alpha, and IL6 compared to the control rats. Co-treatment with LYC attenuated the reduction in PPAR-gamma, HO-1, Nfr2, and IL-10 levels and moderated the elevated levels of NF-kB, TNF-alpha, and IL-6. The kidneys from rats co-treated with lycopene (10 mg) + 5-FU did not show the degenerative changes in the glomerular tufts and tubules observed for the rats treated with 5-FU alone. In conclusion, LYC is a promising therapeutic strategy for attenuating 5-FU-induced nephrotoxicity through the restoration of antioxidant activities and inhibition of inflammatory responses by modulating PPAR-γ, Nrf2/HO-1, and NF-κB/TNF-α/IL-6, signals.

Background: Adequate delivery of hemodialysis (HD), measured by the spKt/V derived from urea reduction, is an important determinant of clinical outcomes in chronic hemodialysis patients. However, the need for pre- and postdialysis blood samples prevented the assessment of spKt/V in every session.

Methods: This retrospective single-center study was performed on end-stage renal disease (ESKD) patients aged ≥ 18 years who received standard thrice-weekly chronic HD therapy. Eighty-seven variables, including general, intradialytic, and laboratory variables, were collected from the medical records for analysis. Five steps of preprocessing procedure were deployed to select only the most relevant variables. Six binary classification models were developed to predict whether spKt/V was higher than 1.4.

Results: A total of 1869 HD sessions from 373 ESKD patients were included in this study. The Random Forest model showed the best prediction for dialysis adequacy, with AUROC scores of 0.860 in the validation dataset and 0.873 in the testing dataset. Notably, an accessible model that solely relied on noninvasively collected general and dialysis-related variables maintained high prediction accuracy, with AUROC scores of 0.854 and 0.868 in the validation and testing datasets, respectively. The five most significant predictive variables were vascular access, gender, body mass index, ultrafiltration volume, and dialysis duration.

Conclusion: The study results suggest that the development of ML models for accurately predicting dialysis adequacy based on general and intradialytic variables is feasible. These models have the potential to be utilized for noninvasive clinical assessments of dialysis adequacy.

Background: The assessment of left ventricular (LV) remodeling and its association with mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been systematically studied. We aimed to evaluate LV remodeling changes one year after kidney transplantation (KT) and identify their influencing factors.

Methods: Ninety-five KTRs (68 males; ages 40.2 ± 10.8 years) were followed before and one year after KT. Traditional risk factors and bone metabolism indicators were assessed. Left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and left ventricular diastolic dysfunction (LVDD) were measured using two-dimensional transthoracic echocardiography. The relationship between MBD and LV remodeling and the factors influencing LV remodeling were analyzed.

Results: One year after KT, MBD was partially improved, mainly characterized by hypercalcemia, hypophosphatemia, hyperparathyroidism, 25-(OH) vitamin D deficiency, elevated bone turnover markers, and bone loss. LVMI, the prevalence of left ventricular hypertrophy (LVH), and the prevalence of LVDD decreased, while LVEF increased. LVH was positively associated with postoperative intact parathyroid hormone (iPTH) and iPTH nonnormalization. △LVMI was positively associated with preoperative type-I collagen N-terminal peptide and postoperative iPTH. LVEF was negatively associated with postoperative phosphorous. △LVEF was negatively associated with postoperative iPTH. LVDD was positively associated with postoperative lumbar spine osteoporosis. Preoperative LVMI was negatively associated with △LVMI and positively associated with △LVEF. Advanced age, increased BMI, diabetes, longer dialysis time, lower albumin level, and higher total cholesterol and low-density lipoprotein levels were associated with LV remodeling.

Conclusions: LV remodeling partially improved after KT, showing a close relationship with MBD.

Background: Idiopathic membranous nephropathy (IMN) with deposits of phospholipase A2 receptor (PLA2R) antigen in glomerular tissue (GAg+) but no circulating serum PLA2R antibody (SAb-) has been reported. However, little is known about the clinicopathological characteristics and prognosis of this subtype.

Methods: A total of 74 IMN patients with GAg + identified by kidney biopsy were enrolled in this study. We categorized patients into two groups based on the presence or absence of serum PLA2R antibody. Data on clinical features, pathological features, and outcomes were collected. Kaplan-Meier analysis of complete remission (CR) and partial remission (PR) comparing SAb-/GAg + and SAb+/GAg + patients. Cox proportional hazards models was used to examine factors associated with CR and PR.

Results: Among 74 IMN patients, 14 were SAb-/GAg+. Compared with SAb+/GAg + patients, SAb-/GAg + patients presented with higher levels of albumin, lower levels of cholesterol and low density lipoprotein cholesterol (all p < .01), but similar pathological manifestations of kidney biopsy. Multivariate logistic analyses indicated that low albumin (0.79 [95%CI: 0.66-0.95], p = .01) and high cholesterol (1.81 [95%CI: 1.02-3.19], p = .04) were correlated with seropositivity of PLA2R antibody. SAb-/GAg + patients exhibited a significantly higher probability of CR (p = .03) than patients who were SAb+/GAg+. However, no difference was found in the PR rate. Cox regression analyses showed that compared to SAb+/GAg + patients, SAb-/GAg + was more predictive of complete remission (4.28 [95%CI: 1.01-18.17], p = .04).

Conclusion: IMN with PLA2R staining on kidney biopsy but without serum PLA2R antibody has milder clinical manifestations and a better prognosis.