Renal Failure最新文献

Radial-artery to cephalic-vein end-to-side arteriovenous fistulae (RCAVF) are the first-line vascular access for hemodialysis, yet early stenosis or thrombosis reduces its long-term patency. Indoxyl sulfate (IS), a protein-bound uremic toxin with diverse vascular effects, may impede fistula maturation. We conducted a single-center prospective cohort study enrolling 113 stage 5 chronic kidney disease patients who underwent RCAVF creation between February 2023 and August 2024. Patients were stratified by IS tertiles to assess fistula outcomes. Multivariable Cox regression, Kaplan-Meier analyses, and nomogram construction were used to identify risk factors and patency. Additionally, multiplex tyramide signal amplification immunofluorescence was applied to 40 samples of cephalic vein to quantify aryl hydrocarbon receptor (AHR) and tissue factor (TF) expression. After a median follow-up of 12 months, serum IS was higher in the dysfunction group (p = 0.005). Elevated IS (p = 0.013) and diabetes mellitus (p = 0.006) were independent risk factors for RCAVF dysfunction. Restricted cubic spline analysis showed a linear relationship between IS and risk. Kaplan-Meier curves revealed decreasing primary patency with increasing IS tertiles (p < 0.05), consistent in diabetic patients. The 1-year patency nomogram had good predictive performance (AUC = 0.87). Histopathology showed upregulated AHR and TF expression in veins from dysfunctional fistulas, with correlated fluorescence intensities (r = 0.60, p < 0.05), though neither correlated directly with serum IS (p > 0.05). In conclusion, elevated serum IS independently predicts RCAVF dysfunction, and the aberrant IS-AHR-TF signaling axis may contribute to its pathogenesis.

To investigate the long-term efficacy and safety of rituximab (RTX) in treating patients with primary membranous nephropathy (pMN), a total of 154 patients with pMN receiving RTX treatment were retrospectively enrolled in this study. The study included 92 patients who received RTX as an initial therapy, and 62 patients who received it as an alternative therapy. Over a median follow-up of 30.0 (24.0, 47.0) months after RTX treatment, 102/121 (84.3%) patients achieved immunological remission. And 128/154 (83.1%) patients achieved clinical remission (including 37.7% of CR and 45.5% of PR), accompanied by significant reduction in proteinuria and increase in serum albumin levels. Clinical response rates were comparable between the initial and alternative therapy groups (87.0 vs. 77.4%, p = 0.131), though patients in the alternative therapy group required a longer time to achieve remission. Among the 21 patients with eGFR < 60 mL·min^-1·(1.73 m²)^-1, 12 (57.1%) responded to RTX. Though two patients progressed to end-stage renal disease (ESRD) during follow-up, the remaining 19 patients showed an improvement in eGFR from 48.0 (38.0, 55.0) to 62.0 (36.0, 73.0) mL·min^-1·(1.73 m²)^-1. The clinical response in the RTX monotherapy group did not differ significantly from that in patients who received RTX in combination with glucocorticoids or other immunosuppressive agents. Twenty-eight patients experienced adverse events, most of which were mild and manageable. RTX, utilized as either an initial or alternative therapy, induced a significant clinical response in patients with pMN, including those with compromised renal function. These findings support RTX as an effective and well-tolerated option across various pMN patient profiles.

The clinical presentation and prognosis of immunoglobulin A nephropathy (IgAN) in older adults are poorly defined. We evaluated kidney and patient outcomes and predictors of progression in patients aged ≥60 years with biopsy-proven IgAN. We conducted a retrospective observational study in elderly patients diagnosed with primary IgAN between 2010 and 2024 at a tertiary center. Baseline clinical, laboratory, and histopathologic data were collected, and kidney biopsies were scored using the Oxford MEST-C (Mesangial hypercellularity, Endocapillary hypercellularity, Segmental glomerulosclerosis, Tubular atrophy/interstitial fibrosis, Crescents) classification. The primary outcome was a composite of end-stage kidney disease (ESKD) or death. Predictors of progression were assessed using Kaplan-Meier's analysis and Cox proportional hazards models. A total of 102 patients were included (median age 65 years; 73% male). Comorbidity burden was high (median Charlson Comorbidity Index 4), hypertension was prevalent (88%), and baseline kidney function was reduced (median estimated glomerular filtration rate (eGFR) 29.5 mL/min/1.73 m²). Chronic nephritic syndrome was the most frequent presentation (55%), and chronic histologic lesions predominated (T1/T2 in 52%, S1 in 32%). Over a median follow-up of 5 years, 49 patients (48%) reached the composite outcome, including 32 (31%) who progressed to ESKD. Older age, higher comorbidity burden, and greater proteinuria independently predicted progression, whereas baseline eGFR and individual MEST-C lesions did not. Renin-angiotensin system inhibitor use was associated with better outcomes, while no independent benefit of immunosuppression was observed after adjustment. Elderly patients with IgAN present with advanced chronic kidney disease and substantial comorbidity. Progression is driven mainly by age, comorbidity burden, and proteinuria, supporting optimized supportive care as the cornerstone of management.

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.

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.

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.

Our study seeks to access the impact of ultrafiltration volume (UFV) variability on clinical outcomes in patients undergoing maintenance hemodialysis (HD) using a population-based cohort. This study employed a retrospective design using data derived from the national HD quality assessment initiative in Republic of Korea, which was combined with health insurance claims records (n = 50,583). To assess UFV variability, a linear regression model was fitted for each individual across the six measurements, and the residual standard deviation from this model was calculated. Based on this metric, patients were stratified into four quartiles representing increasing levels of UFV variability (Q1 to Q4). The 5-year survival rates for patients in Q1, Q2, Q3, and Q4 were 68.3%, 67.9%, 66.4%, and 65.8%, respectively. Multivariable analysis revealed that the hazard ratio (HR) for all-cause mortality was the highest in the Q4 group. Additionally, a spline curve using the multivariable model indicated that an increase in UFV variability, based on a median of 0.44 L/session, was linked to all-cause mortality. Multivariable Cox regression indicated that the Q4 group had a higher HR for cardiovascular events or atrial fibrillation compared to the Q1 and Q2 groups. Additionally, the Q1 group had the lowest HR for dementia among the four groups. Our study demonstrated an association between high UFV variability and various clinical outcomes, particularly all-cause mortality and dementia. These findings suggest that UFV variability could serve as a useful supplementary indicator for predicting prognosis, in addition to UFV or ultrafiltration rate.

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.