Renal Failure最新文献

In recent years, artificial intelligence (AI) has advanced significantly in the field of pathomics, enabling the transformation of pathological images into high-throughput, machine-readable datasets for quantitative analysis and precise diagnosis in renal pathology. AI-based pathomics has introduced innovative perspectives and sophisticated tools for detecting glomerular injury, evaluating renal interstitial fibrosis, monitoring transplanted kidney pathology longitudinally, and predicting outcomes in renal tumors. Despite its great promise, the application of AI-based pathomics in nephrology still faces several challenges, including complex data annotation, limited model interpretability, lack of comprehensive multi-modal data integration, and insufficient large-scale clinical validation. Future research should prioritize these challenges by enhancing multi-omics integration and promoting interdisciplinary collaboration, thereby advancing AI-based pathomics in nephrology and ultimately improving the precision and efficiency of patient care.

Obstructive sleep apnea (OSA) has been widely associated with DN in observational studies; however, the causal nature and direction of this association remain uncertain. To clarify this, we performed a bidirectional two-sample Mendelian randomization (MR) analysis using large-scale genetic datasets. Genetic instruments for OSA were derived from a genome-wide association study (GWAS) comprising up to 476,853 individuals, while genetic associations for DN were obtained from another GWAS including 452,280 participants. We applied multiple MR methods to ensure robust causal inference, including inverse variance weighting, MR-Egger regression, weighted median, weighted mode, and simple mode. Sensitivity analyses were thoroughly conducted using Cochran's Q test for heterogeneity and the MR-Egger intercept test to assess potential pleiotropy. Furthermore, multivariable MR was employed to evaluate the independent effect of OSA on DN after adjusting for hyperlipidemia and hypertension. The results indicated a significant causal effect of OSA on DN risk, supported by IVW (OR = 1.41, 95% CI: 1.12-1.77, p = 0.003) and weighted median estimates (OR = 1.57, 95% CI: 1.16-2.13, p = 0.003). Reverse MR analysis revealed no evidence of a causal effect of DN on OSA. Importantly, after accounting for hyperlipidemia and hypertension, multivariable MR confirmed that OSA exerts an independent causal influence on DN (OR = 0.90, 95% CI: 0.14-1.67, p = 0.021). These findings suggest that OSA may contribute to the pathogenesis of diabetic nephropathy through specific mechanisms, independent of traditional metabolic risk factors.

Avacopan, a novel C5a receptor inhibitor, offers therapeutic potential for ANCA-associated vasculitis. This study assessed its post-marketing safety using the FDA Adverse Event Reporting System (FAERS) from Q4 2021 to Q4 2024. Disproportionality analyses identified 75 adverse events (AEs) potentially linked to avacopan, with hepatobiliary disorders and infections being most prominent. A total of 62 AEs were classified as having moderate clinical priority, including drug-induced liver injury, renal failure, and deafness. Subgroup analysis revealed age- and sex-based differences in AE patterns. Logistic regression indicated that older age and concomitant use of rituximab or proton-pump inhibitors increased the risk of hepatobiliary AEs. These findings highlight the need for close monitoring of hepatic function and infection risk during avacopan therapy. Further research is warranted to explore the underlying mechanisms and potential drug interactions.

Biopsy-confirmed anticancer drug-induced kidney injury is underreported. This study aimed to characterize its clinicopathological features and outcomes. We retrospectively analyzed 52 patients with biopsy-proven anticancer drug-induced nephrotoxicity (2005-2024). Patients were classified into chemotherapy drugs (CTD, n = 25), molecularly targeted therapies (MTT, n = 22), and immune checkpoint inhibitors (ICI, n = 5; PD-1 inhibitors). The CTD group (e.g. cisplatin, capecitabine, gemcitabine) caused frequent acute kidney injury (AKI, 80%), with acute tubulointerstitial nephritis (ATIN, 32%). Notable glomerular lesions in the CTD group included thrombotic microangiopathy (TMA, 12%), minimal change disease (8%), and focal segmental glomerulosclerosis (8%). The MTT group (e.g. bevacizumab, lenvatinib, sorafenib) had higher proteinuria (0.4 vs. 3.1 vs. 0.7 g/24h; p < 0.05) and TMA incidence (86%). MTT-induced TMA produced distinct subtypes: anti-VEGF(R) therapy (n = 11) caused glomerular capillary ballooning (100%); non-VEGFR-TKIs (n = 4) were associated with segmental glomerulopathy; combined anti-VEGF/VEGFR-TKI (n = 4) resulted in more extensive and severe TMA (>75% of glomeruli). ICI therapy (nivolumab, camrelizumab, sintilimab) led to early AKI, mainly ATIN (80%), with glomerular IgA deposition (80%) and low serum C3 (60%). After a median follow-up of 23.0 months, MTT showed faster AKI recovery than CTD (0.5 vs. 8.0 months; p = 0.002). Anticancer drugs induce distinct nephrotoxic patterns. CTD causes direct cytotoxicity and high irreversible injury risk. MTT drives functional TMA, and new-onset hypertension with proteinuria should raise concern for anti-VEGF-related TMA. ICI triggers immune dysregulation with humoral disturbances, and AKI with low serum C3 can be a safety signal for clinical monitoring.

Diabetic kidney disease (DKD) remains a critical challenge in diabetes management, necessitating a deep understanding of its molecular underpinnings for better diagnosis and treatment strategies. This study was conducted to identify and validate novel biomarkers for DKD by integrating multi-omics analysis and experimental validation. Through weighted gene co-expression network analysis and Mendelian randomization analysis, 11 genes were identified as being causally associated with DKD. ADARB2, GOLPH3L, LRG1, and PEX6 were identified as characteristic genes through machine learning methods, including least absolute shrinkage and selection operator (LASSO) regression and SVM algorithms. Receiver operating characteristic curve analysis demonstrated that the characteristic genes had high predictive accuracy for DKD. Functional enrichment analyses indicated that dysregulation of key genes was associated with inflammatory and immune responses in both peripheral blood mononuclear cells and kidney single-cell populations. Peripheral blood samples from DKD patients and healthy controls were collected to assess the reliability of identified key genes in humans. Kidneys from wild-type and db/db mice were harvested to further validate the reliability of key genes at the tissue level in animal models using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). After RT-qPCR validation, the robustness of LRG1 and PEX6 was confirmed in both human peripheral blood and mouse kidney tissues. The significance of ADARB2 was confirmed in the kidney tissue of DKD mouse models. This study highlights the power of multi-omics analyses in elucidating complex disease pathogenesis and identifying biomarkers, thereby laying a foundation for the development of DKD-targeted therapeutics.

Ischemia reperfusion-induced acute kidney injury (IRI-AKI) is a prevalent clinical complication among hospitalized patients with high morbidity and mortality. Mitochondria, as crucial organelles for maintaining cellular homeostasis, play a pivotal role in IRI-AKI pathogenesis. Currently, no effective and definitive therapeutic targets have been established for IRI-AKI treatment. Previous sequencing data analysis revealed significant upregulation of Arfgef3 following renal ischemia-reperfusion injury, suggesting its potential as a therapeutic target. This study demonstrates that Arfgef3 expression is markedly elevated after ischemia reperfusion injury. Furthermore, Arfgef3 knockout (KO) significantly ameliorated renal injury induced by ischemia-reperfusion in mice. In addition, Arfgef3 knockout effectively attenuates renal inflammation (IL6, MCP1, TNF-α), oxidative stress and apoptosis levels. In addition, Arfgef3 knockout substantially improves ischemia reperfusion-induced mitochondrial abnormalities including mitochondrial biogenesis markers and ATP production capacity. In conclusion, Arfgef3 participates in IRI-AKI pathogenesis by regulating mitochondrial function. Arfgef3 knockout confers renal protection through improving mitochondrial dysfunction, thereby reducing inflammatory response, oxidative stress and apoptosis. These findings provide novel insights into IRI-AKI mechanisms and highlight Arfgef3 as a potential therapeutic target.

The associations between hypoglycemic medications, cordycepin, COVID-19 vaccination, and clinical outcomes of SARS-CoV-2 infection were examined in a retrospective cohort of patients with diabetic kidney disease (DKD) in Ningbo, China, between December 2022 and June 2023. Acute COVID-19 outcomes included fever, pneumonia, hospitalization, and prolonged symptoms. Short-term DKD outcomes at three months post-infection included a serum creatinine increase ≥ 30%, an estimated glomerular filtration rate (eGFR) decrease ≥ 10 mL/min/1.73 m², a urinary albumin-to-creatinine ratio (UACR) increase ≥ 30%, a fasting blood glucose increase ≥ 1.1 mmol/L, and a hemoglobin A1c (HbA1c) increase ≥ 0.3%. Among 642 DKD patients with COVID-19, 66.8% were treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) at baseline, 36.9% with dipeptidyl peptidase-4 inhibitors (DPP4i), 30.8% with metformin, and 36.4% with cordycepin. Logistic regression analysis indicated that SGLT2i use was associated with a reduced risk of hospitalization and less worsening of UACR. Metformin use was linked to a lower incidence of COVID-19 pneumonia but an increased risk of serum creatinine elevation. DPP4i use showed no significant association with adverse outcomes. Cordycepin use was associated with reduced risks of hospitalization and serum creatinine elevation. Compared with unvaccinated patients, multiple-dose COVID-19 vaccination was associated with reduced risks of adverse outcomes, including prolonged COVID-19 symptoms, pneumonia, decreased eGFR, and elevated blood glucose and HbA1c levels. In conclusion, pretreatment with SGLT2i, cordycepin, and multiple-dose COVID-19 vaccination was associated with reduced adverse outcomes among DKD patients with COVID-19.

Uncertainty persists regarding the associations between a body shape index (ABSI) and diabetic kidney disease (DKD), albuminuria, and low estimated glomerular filtration rate (eGFR). Data from 2,770 participants in the 2005-2016 U.S. National Health and Nutrition Examination Survey (NHANES) were analyzed in this study. Multiple logistic regression models and subgroup analyses were utilized to evaluate the relationships between ABSI and DKD, albuminuria, and low eGFR. A restricted cubic spline (RCS) plot was applied to examine trends in these associations. In the fully adjusted model, each unit increase in ABSI was associated with a 33% higher risk of DKD (adjusted OR = 1.33, 95% CI: 1.09-1.61, p = 0.0043) and a 50% higher risk of albuminuria (adjusted OR = 1.50, 95% CI: 1.23-1.84, p < 0.0001). In contrast, no significant relationship was observed with low eGFR (adjusted OR = 1.13, 95% CI: 0.88-1.46, p = 0.3444). These relationships exhibited variation across age, sex, and comorbidity subgroups. Results based on standardized ABSI (z-score) were similar, confirming significant associations with DKD and albuminuria. RCS plots showed that ABSI was significantly and linearly associated with the risks of DKD (P-overall = 0.026, P-nonlinear = 0.577) and albuminuria (P-overall = 0.001, P-nonlinear = 0.658), indicating that the risk of DKD and albuminuria increased with higher ABSI levels. In contrast, no significant association was observed between ABSI and low eGFR (P-overall = 0.298, P-nonlinear = 0.238). Higher ABSI levels are associated with increased risks of DKD and albuminuria, particularly in specific subgroups.

In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising immunotherapeutic strategy beyond oncology, offering new treatment opportunities for immune-mediated kidney diseases. These conditions including systemic lupus erythematosus, ANCA-associated vasculitis, membranous nephropathy, and monoclonal gammopathy-related nephropathies are characterized by dysregulated B cell and plasma cell activity that often proves refractory to standard immunosuppression. CAR-T cells, engineered to target antigens such as CD19 or BCMA, enable potent and durable depletion of pathogenic lymphocyte subsets, with growing evidence of clinical efficacy in autoimmune settings. Recent clinical data suggest that CAR-T therapies can induce profound immunological remission, restore immune tolerance, and improve renal outcomes. Novel platforms such as chimeric autoantibody receptor (CAAR)-T cells and bispecific T-cell engagers (BiTEs) further refine antigen targeting and may offer scalable alternatives. Importantly, early studies also point to the potential use of these therapies in kidney transplantation, particularly desensitization therapy in highly sensitized patients and treatment of post-transplant lymphoproliferative disorders. Despite these advances, challenges remain regarding toxicity, patient selection, cost, and long-term safety. This review critically evaluates the current landscape of CAR-based therapies in nephrology, explores their immunopathological rationale, and outlines future directions for their integration into clinical practice.

Objective: To evaluate the cost-effectiveness of combining finerenone and Sodium-glucose cotransporter-2 inhibitors (SGLT2i) with standard care (SoC) for Chinese patients with chronic kidney disease (CKD) and type 2 diabetes (T2D).

Methods: A validated Markov model (FINE-CKD) was employed to simulate health outcomes and costs from a Chinese healthcare system perspective. Transition probabilities, costs, and utilities were derived from peer-reviewed literature and trial data. The model utilized a 4-month cycle length, consistent with the assessment intervals in the FIDELITY trial, over a ten-year time horizon. The primary economic outcome was the net monetary benefit (NMB). Cost-effectiveness was assessed against China's willingness-to-pay (WTP) threshold, defined as three times the 2023 GDP per capita (268,074 CNY/QALY), following China's pharmacoeconomic evaluation guidelines.

Results: Triple therapy (finerenone + SGLT2i + SoC) demonstrated superior clinical and economic outcomes compared to finerenone therapy (finerenone + SoC) and SGLT2i therapy (SGLT2i + SoC). Specifically, compared to finerenone therapy, triple therapy resulted in cost savings of CNY 102,953.11 and an incremental gain of 0.291 quality-adjusted life years (QALYs), yielding an NMB of CNY 181,032.95. Compared to SGLT2i therapy, triple therapy led to cost savings of CNY 118,628.19 and an additional 0.257 QALYs, corresponding to an NMB of CNY 187,506.53. Sensitivity analyses confirmed the robustness of these findings.

Conclusions: Triple therapy with finerenone, SGLT2i, and SoC is cost-effective for Chinese patients with T2D and CKD, delivering synergistic cardiovascular and renal protective effects while demonstrating robust economic viability within China's healthcare framework.