Renal Failure最新文献

Linezolid, an oxazolidinone antibiotic effective against Gram-positive pathogens, may cause nephrotoxicity and lactic acidosis during prolonged therapy. This experimental study investigated the protective effects of adenosine triphosphate (ATP), thiamin, thiamin pyrophosphate (TPP), and their combination (ATTP) on linezolid-induced renal injury and lactic acidosis in rats. Thirty-six male Wistar rats were randomly divided into six groups (n = 6): healthy control (HG), linezolid only (LZD), ATP+linezolid (ATLZD), thiamin + linezolid (TLZD), TPP+linezolid (TPLZD), and ATP+thiamin + TPP+linezolid (ATTPL). Linezolid (125 mg/kg, orally) was administered twice daily, while ATP (4 mg/kg), thiamin (20 mg/kg), and TPP (20 mg/kg) were given intraperitoneally once daily for 28 days. At the end of treatment, kidney tissues were examined for oxidative stress markers [malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT)] and histopathology, and blood samples were analyzed for blood urea nitrogen (BUN), creatinine, and lactate. Linezolid increased oxidative stress, suppressed antioxidants, and elevated BUN, creatinine, and lactate levels. ATP partially improved the oxidative balance in renal tissue but failed to prevent hyperlactatemia and impaired renal function. Thiamin did not produce significant changes. TPP markedly improved oxidative stress markers and reduced renal dysfunction. The triple combination provided the most pronounced protection, restoring antioxidant defenses, kidney function, and lactate levels to near-control values. Histopathological evaluation revealed marked tubular degeneration, interstitial hemorrhage, and mononuclear cell infiltration in the linezolid group, which were markedly improved by TPP and combination therapy. These findings indicate that TPP protects against linezolid-induced nephrotoxicity and lactic acidosis, with its efficacy further enhanced by ATP.

Objectives: ANCA-associated glomerulonephritis (ANCA-GN) is an immune-mediated kidney disease leading to acute or chronic renal failure. This study investigates the role of mitophagy-related genes in ANCA-GN, as mitochondrial dysfunction is closely linked to the pathogenesis of various kidney diseases.

Methods: This study analyzed transcriptomic data from GEO datasets (GSE104948 and GSE108109) to investigate mitophagy-related mechanisms in ANCA-GN. Methods included batch correction, consensus clustering (identifying two subtypes), weighted gene co-expression network analysis (WGCNA), differential expression screening, and machine learning (LASSO, random forest, SVM-RFE). A diagnostic nomogram was constructed and validated, and immune cell infiltration was profiled.

Results: Analyses revealed distinct activation of immune pathways, including complement and phagosome signaling, alongside abnormal infiltration of CD8+ T cells in ANCA-GN. Subtype-specific analysis identified 131 differentially expressed genes (DEGs), while 143 DEGs distinguished ANCA-GN from controls.Intersection analysis and machine learning prioritized two hub genes, PYCARD and IFI30, which exhibited strong diagnostic accuracy (AUC >0.9) and correlated with CD8+ T-cell infiltration. A nomogram model validated their clinical utility (AUC >0.9). Functional enrichment highlighted phagocytosis and immune signaling pathways. Immune profiling revealed significant upregulation of 20 immune cell types in ANCA-GN.

Conclusions: These findings suggest that mitophagy-immune crosstalk drives ANCA-GN progression, with PYCARD and IFI30 as potential diagnostic biomarkers. This study provides mechanistic insights into ANCA-GN pathogenesis and proposes novel targets for clinical intervention.

IgA nephropathy (IgAN) is the most prevalent primary glomerular disease worldwide and a leading cause of end-stage kidney disease (ESKD). Its clinical heterogeneity results in divergent renal outcomes, making early identification of high-risk patients essential. Prognostic models are crucial for stratifying ESKD risk, guiding treatment intensity, optimizing timing of interventions such as immunosuppressive therapy, and informing clinical trial enrollment. Over recent decades, multiple prognostic approaches have emerged, ranging from traditional clinical and histopathological scoring systems to advanced machine learning (ML) and deep learning (DL) models designed to capture complex nonlinear interactions and improve predictive precision. Among them, the International IgA Nephropathy Prediction Tool (IIgAN-PT), endorsed by the 2021 KDIGO guidelines, represents a landmark in globally validated risk assessment and has set the foundation for standardized clinical decision support. However, classical models often rely on static baseline parameters and may not adequately reflect dynamic disease trajectories, limiting their utility in real-time clinical management. To overcome these limitations, ML- and DL-based models increasingly integrate multi-omics data, serial clinical measurements, and digital pathology features, offering enhanced accuracy, dynamic risk tracking, and potential for personalized response prediction. These data-driven approaches are progressively bridging the gap between prognostic research and precision nephrology. This review provides a comprehensive overview of the evolution of IgAN prognostic models, summarizes their strengths and limitations, and discusses considerations for clinical translation. By highlighting emerging trends toward explainable AI, dynamic time-series modeling, and multimodal prognostication, we outline how next-generation prediction tools may enable real-time, AI-driven decision support for individualized IgAN management.

Cardiovascular-kidney-metabolic (CKM) syndrome significantly impacts a large segment of the general population. The risk factors associated with progression of CKM syndrome as well as all-cause mortality warrant further investigations. In this study, we aimed to assess whether nephrolithiasis history would help to identify the high-risk populations among CKM patients. We conducted a multi-center study involving patients with CKM syndrome at stages 2-3 from 28 urban centers across China. We employed multivariable Cox proportional hazards regression analysis to estimate hazard ratios (HRs) along with their corresponding 95% confidence intervals (CIs) for the associations with a history of nephrolithiasis. Subgroup analyses and sensitivity analyses were performed to enhance the robustness of our findings. A total of 344,220 CKM patients at stages 2-3 were included in this study. Among the participants, 28,451 had a history of nephrolithiasis. When compared to individuals without nephrolithiasis history, those with the history demonstrated an increased risk of progression to CKM stage 4 (HR 1.52, 95% CI [1.48-1.56]) and all-cause mortality (HR 1.08, 95% CI [1.03-1.14]). Similar results were obtained in the participants with asymptomatic nephrolithiasis. Consistent findings were observed through subgroup analyses and sensitivity analyses as well. The history of nephrolithiasis is associated with an elevated risk of incident cardiovascular disease and increased all-cause mortality among CKM patients. These findings highlight the significant role of nephrolithiasis in identifying high-risk populations within CKM patients.

Diabetic kidney disease (DKD) is one of the most common microvascular complications among individuals with diabetes and has become a leading cause of end-stage renal disease (ESRD). The mechanisms underlying DKD are complex, and effective therapeutic strategies remain limited. Mitochondrial dysfunction occurs earlier than proteinuria and renal morphological changes, and is considered a key event in the progression of DKD. Mitochondrial dysfunction in diabetic kidneys involves several processes, including excessive production of mitochondrial reactive oxygen species, reduced mitochondrial biogenesis, impaired mitophagy, and disturbances in mitochondrial dynamics. Recently, mitochondria-targeted drugs, including antioxidants, CD38 inhibitors, glucose-linked transport 2 sodium inhibitor (SGLT2i), and compounds derived from traditional Chinese medicine, have shown positive effects in animal experiments or clinical trials. This review aims to highlight the role of mitochondrial quality control and dysfunction in DKD, the specific mitochondrial regulators of different renal cell types, as well as the therapeutic potential of some emerging drugs and the limitations of existing preclinical evidence, thereby identifying promising therapeutic targets and strategies for the disease.

The presence of pretransplant anti-human leukocyte antigen (HLA) donor-specific antibodies (DSAs) is still a significant barrier to successful kidney transplantation, as it increases the risk of rejection and graft failure. Rituximab (anti-CD20 antibody) has been administered in hopes of suppressing DSA production and rejection in those with preformed DSAs. However, existing studies report conflicting outcomes, underscoring the need for more data to guide clinical practice. Thus, we evaluated the efficacy of early posttransplant rituximab administration in a cohort of kidney transplant recipients with pretransplant anti-HLA DSAs. In this retrospective study of 77 patients, we compared 1-year transplant outcomes between patients treated with and without rituximab for pretransplant anti-HLA DSAs. Infectious complications tended to occur more often in the rituximab group (BK polyomavirus DNAemia >10,000 copies/mL, 3 [19%] vs. 8 [13%]; quantifiable cytomegalovirus DNAemia, 8 [50%] vs. 19 [31%]; infection requiring hospitalization, 5 [31%] vs. 11 [18%]), but none of these differences reached statistical significance. The incidence of biopsy-proven rejection (2 [13%] vs. 12 [20%]) and high plasma donor-derived cell-free DNA (2 [18%] vs. 12 [27%]) tended to be more frequent in the no-rituximab group, but none of these reached statistical significance. Preexisting DSA persisted or recurred in 44% of the patients that received rituximab, and in 46% of patients who did not receive rituximab. Similarly, de novo DSA occurred in 31% of those who received rituximab versus in 25% of those who did not. Rituximab administration did not result difference in graft and patient survival or rejection rates or recurrence of preexisting DSA.

This observational cohort study aimed to identify factors influencing long-term renal outcomes in 170 patients with biopsy-proven malignant hypertension (MHT)-associated renal thrombotic microangiopathy (TMA) who were dialysis-independent at baseline, recruited between 2008 and 2023. Over a median follow-up of 23.5 months, 52 patients (30.6%) progressed to end-stage renal disease (ESRD). Those developing ESRD exhibited significantly higher total cholesterol levels, heavier proteinuria, a greater proportion of global glomerulosclerosis, more advanced interstitial fibrosis/tubular atrophy, and lower baseline eGFR, along with lower use of renin-angiotensin-aldosterone system (RAAS) inhibitors. In Cox regression analysis, elevated total cholesterol (HR = 1.48 per 1 mmol/L change; 95% CI: 1.24-1.77, p < 0.001) and a higher percentage of glomerulosclerosis (HR = 1.24, 95% CI: 1.15-1.33, p < 0.001; per 5% increase of glomerulosclerosis) were independent risk factors for ESRD, while RAAS inhibitor use was associated with a significantly reduced risk (HR = 0.45, 95% CI: 0.25-0.82, p = 0.009). These findings underscore the prognostic value of lipid profiles and histologic injury severity in MHT-associated TMA and support the protective role of RAAS blockade in preserving renal function, which may guide risk stratification and therapeutic decisions in this high-risk population.

Patients with end-stage renal disease often require arteriovenous fistula (AVF) creation for hemodialysis. However, nearly 40% of patients develop aneurysmal dilatation of AVF (AVFA) after surgery, which can lead to prolonged bleeding at puncture sites, increased infection risk, and even potential rupture. Despite its high incidence, research on AVFA remains remarkably limited. This study makes an innovative discovery by establishing a link between AVFA formation and alternative splicing of fibronectin (FN), a crucial extracellular matrix component. Specifically, we demonstrate that increased inclusion of the EDA exon in FN within vascular smooth muscle cells triggers phenotypic switching to a synthetic state and extracellular matrix remodeling through the ITGB1/FAK/Src/RUNX2 pathway. These changes ultimately reduce vascular mechanical strength and contribute to AVFA development. Furthermore, we identify the splicing factor SRSF5 as a key regulator of EDA inclusion and characterize its potential binding sites, providing potential therapeutic targets for AVFA prevention.

Peritoneal dialysis (PD) transforms the peritoneum into a dynamic therapeutic interface, with each exchange offering direct access to molecular and cellular signals from the peritoneal cavity. Among these, extracellular vesicles (EVs) have emerged as stable, information-rich messengers reflecting peritoneal health, inflammation, and fibrosis. The review explores the peritoneum as a living therapeutic interface, summarizing current evidence on EV biology, their molecular cargo, and potential roles in monitoring inflammation, fibrosis, and membrane function. It also discusses existing knowledge gaps, technological advances, and opportunities for translating EV research into clinical practice.