International braz j urol : official journal of the Brazilian Society of UrologyMarcos Tobias-Machado, Ricardo C Brianson, John Eder Gamarra Bravo, Alcedir Raiser, Eliney Faria
INTRODUCTION: Horseshoe kidney is an uncommon congenital fusion anomaly that can make renal tumor surgery especially challenging because of altered rotation, limited mobility, variable vascular supply, and an unpredictable collecting system (1-7). This video presents a robot-assisted partial nephrectomy for a high-complexity renal tumor in this setting. CASE PRESENTATION: A 33-year-old man, with ECOG 0 and no relevant comorbidities, was diagnosed with a 7.5-cm solid renal mass in the central posterior portion of the left moiety of a horseshoe kidney. The lesion had a RENAL score of 10p. Contrast-enhanced computed tomography and three-dimensional reconstruction were used to understand the relationship between the tumor, aberrant vessels, renal hilum, and collecting system, supporting the decision to attempt nephron-sparing surgery (5, 8). Surgical technique and results: The procedure was performed through a transperitoneal robotic approach with the patient in right lateral decubitus using the Da Vinci Si platform. Port placement followed a standard renal robotic configuration, with a paramedian supraumbilical camera port, three robotic working ports along a craniocaudal lateral axis, a caudal fourth-arm port, and two medial assistant ports for suction, exposure, and support during renorrhaphy. After exposure of the horseshoe kidney and left hilar dissection, two arterial branches and one renal vein were identified. Tumor excision was performed under vascular control, with 20 minutes of warm ischemia and no collecting system opening, followed by two-layer absorbable renorrhaphy with adjunctive hemostatic agents. The operative time was 150 minutes. No transfusion, conversion, drain placement, or relevant immediate complication occurred. The urinary catheter was removed after 24 hours, and the patient was discharged 72 hours after surgery. Pathology showed clear cell renal cell carcinoma, Fuhrman grade 3, pT2N0M0, with negative surgical margins. During 12 months of oncologic follow-up, renal function remained stable and semiannual imaging showed no evidence of recurrence. Contemporary video reports have also emphasized the feasibility of advanced robotic renal surgery and complex partial nephrectomy strategies in selected patients (9, 10). CONCLUSION: In a carefully selected patient, robot-assisted partial nephrectomy supported by three-dimensional planning was feasible for a complex renal tumor in a horseshoe kidney, with negative surgical margins, preserved renal function, and no recurrence during 12 months of follow-up.
Renal tubular epithelial cells are among the earliest renal parenchymal cells to be injured in the context of acute kidney injury (AKI). Numerous studies have confirmed that fibrinogen-like protein 2 (FGL2) can regulate the occurrence and development of inflammation during disease progression. We found that FGL2 expression is elevated under AKI conditions. However, the role of FGL2 in AKI remains unclear. To elucidate the role of FGL2 in AKI, we employed lentiviral and adeno-associated virus for transfection in cellular and murine models. Furthermore, by leveraging datasets from the gene expression omnibus and gene set enrichment analysis databases, we identified the inflammation-related genes in AKI and predicted their interaction with FGL2. Both in vivo and in vitro studies showed that overexpression of FGL2 markedly increased complement C3a (C3a) levels and exacerbated inflammation and injury. In contrast, knockdown of FGL2 resulted in a marked decline in C3a levels, which not only conferred a substantial protective effect against hypoxia/reoxygenation-induced injury in tubular cells but also effectively alleviated kidney injury in mice. At the molecular level, FGL2 interacts with complement C3, leading to elevated C3a production. This stimulates the inflammatory response of renal tubular epithelial cells, thereby inducing tubular damage. Targeting FGL2 may hold potential prevention and treatment strategy for tubular injury in AKI.
Renal failureSheng-Han Yueh, Jochen Raimann, Bernard Canaud, Meijiao Zhou, Xiaoling Ye, Ariella Mermelstein, Jeroen Kooman, Frank van der Sande, Len Usvyat, Peter Kotanko, …
BACKGROUND: Optimized fluid management is crucial in dialysis care because extracellular volume overload drives adverse cardiovascular outcomes. At the same time, comorbidities such as inflammation and protein energy wasting lead to decreased muscle mass and intracellular water. Accurate assessment of total body water (TBW) and its extracellular water (ECW) and intracellular water (ICW) compartments is therefore essential to guide ultrafiltration, evaluate dialysis adequacy, and monitor patient risk. METHOD: Using adult patients from the MONitoring Dialysis Outcomes (MONDO) 2012 cohort, we developed predictive models to estimate fluid volume compartments based on demographic data, laboratory values, treatment parameters, and multi-frequency whole-body bioimpedance spectroscopy (BIS) measurements. Clinical features were aggregated over an up-to-90-day look-back window, yielding 18,600 patients and 162,479 dialysis treatments. eXtreme Gradient Boosting (XGBoost) models were trained and tested using patient-level splits, with parallel models built either incorporating or excluding prior BIS measurements. RESULTS: Models including BIS data showed excellent accuracy (R2 > 0.85), models excluding BIS features achieved inferior performance (R2 = 0.73-0.81). In models using BIS inputs, recent bioimpedance changes dominated feature importance. Models without BIS data relied primarily on urea distribution volume, age, and height. CONCLUSION: These findings indicate that fluid volume compartments can be reliably estimated from routinely collected clinical data and history BIS measurements, offering valuable support for interim assessment of fluid status between scheduled BIS measurements.
Renal failureJialing Rao, Yin Li, Wang Qian, Yunfang Zhang, Xianrui Dou, Huimin Cao, Zengchun Ye, Hui Peng
Protein-energy wasting (PEW) is common in incident hemodialysis patients and linked to poor outcomes. The uric acid/HDL-cholesterol ratio (UHR) and intact parathyroid hormone (iPTH) relate to metabolic, inflammatory, and nutritional disturbances, but their value for predicting PEW in incident hemodialysis is unclear. This retrospective multicenter study included 863 incident hemodialysis patients. PEW was defined according to the International Society of Renal Nutrition and Metabolism criteria. UHR and iPTH were evaluated using ROC analysis, multivariable logistic regression, and ten machine learning models. Restricted cubic spline, mediation, and trajectory analyses were performed, with SHAP for interpretability. PEW was identified in 59.2% of patients. Feature selection across four machine learning approaches consistently identified UHR, iPTH, and eGFR as key predictors. Higher baseline and cumulative UHR were independently associated with a lower risk of PEW. Trajectory analysis showed that both rapidly increasing and decreasing UHR patterns with higher mean levels were linked to the lowest PEW risk. Nonlinear associations were observed, with an inverted U-shaped relationship between UHR and PEW and an S-shaped relationship between iPTH and PEW. Mediation analysis indicated that iPTH accounted for approximately 10-13% of the association between UHR and PEW. Among all models, XGBoost achieved the best performance (AUC = 0.801). A web-based Shiny tool was developed for individualized PEW risk assessment. UHR and iPTH were associated with PEW risk within specific ranges. Machine learning models integrating these markers showed favorable predictive performance and may assist individualized risk assessment in clinical practice.
Annals of medicineRuichao Feng, Yang Shao, Yuxin Zhao, Xiangfei Cui, Congcong Jiao, Hua Zhou
BACKGROUND: Given the established association between chronic kidney disease (CKD) and systemic inflammation, this study examined the relationships between complete blood count (CBC)-derived inflammatory markers and prevalent CKD. METHODS: Two data sets (Chinese clinical data, n = 4,518; NHANES 2017-2020, n = 7,724) are analyzed. Seven CBC‑derived inflammatory indices were calculated: SII, SIRI, NLR, dNLR, NMLR, MLR, and PLR. Each index was categorized into quartiles (Q1-Q4). Weighted logistic regression (for NHANES) and unweighted logistic regression (for the Chinese clinical data) were applied to estimate associations with CKD, with sequential adjustment for demographics, body mass index, and comorbidities. To control for multiple comparisons, false discovery rate (FDR) correction was applied. Furthermore, subgroup analysis, restricted cubic spline analysis and sensitivity analysis were also performed in this study. RESULTS: In the two fully adjusted models, the highest quartile (Q4) of SIRI, NLR, and NMLR was significantly associated with higher odds of prevalent CKD compared with Q1. After FDR correction, these associations remained significant in both cohorts: in the Chinese cohort, all padj < 0.001; in NHANES, padj = 0.028 for SIRI, 0.040 for NLR, and 0.041 for NMLR. Sensitivity analyses consistently supported the primary findings: excluding outliers, log2 transformation, and the alternative CKD definition yielded similar effect directions and significance levels. Heterogeneity was observed across subgroups, and restricted cubic splines revealed nonlinear dose‑response relationships (p for nonlinearity <0.05). CONCLUSIONS: Elevated SIRI, NLR, and NMLR are associated with prevalent CKD, suggesting systemic inflammation may play a role, yet prospective studies are required to establish temporality and causality.
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia GroupMichał Kazanowski, Paweł Lesiak, Jędrzej Wierzbicki, Bartosz Kapturkiewicz, Paweł Maciejewski, Marcin Pawłowski, Krzysztof Szewczyk, Tomasz Jastrzębski, Marek …
INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is used for selected peritoneal malignancies but carries substantial perioperative physiological stress. Acute kidney injury (AKI) is clinically relevant, yet data on its incidence and postoperative timing remain heterogeneous. METHODS: We performed a retrospective single-center cohort study of consecutive adults undergoing CRS-HIPEC between 2014 and 2024. AKI was defined using KDIGO serum creatinine criteria assessed from postoperative day (POD) 1 to POD 5. Baseline, oncologic and treatment related variables were compared according to AKI status. Exploratory multivariable logistic regression assessed associations between routinely available variables and postoperative AKI. Secondary outcomes included length of stay and exploratory overall survival. RESULTS: Among 308 cases, AKI occurred in 70 cases (22.7%). Stage 1 AKI occurred in 45 cases (14.6%), stage 2 in 18 cases (5.8%) and stage 3 in 7 cases (2.3%). Renal replacement therapy was required in 2 cases (0.6%). Peak serum creatinine occurred on POD 1 to POD 2 in 64.3% of cases, while 35.7% peaked on POD 3 to POD 5. Median length of stay was 7.5 days [IQR 6.5 to 9.6] in the AKI group and 7.4 days [IQR 6.5 to 8.8] in the non-AKI group (p = 0.0998). In exploratory multivariable analysis, no included variable was significantly associated with AKI; PCI showed a non-significant association (OR 1.04 per point, p = 0.11). CONCLUSIONS: AKI was frequent after CRS-HIPEC, and more than one third of cases peaked beyond the first 48 h. These findings support postoperative renal surveillance through POD 5.
Renal failureKyle Backston, Benjamin Buehrer, Defne Ezgü, Pranav Sivaram, Shay Tanna, Riddhima Koka, Sidharth Kumar Sethi, Michael Moritz, Rupesh Raina
Acute Kidney Injury (AKI) is currently diagnosed in pediatric patients by measuring rises in serum creatinine. The objective of this systematic review is to determine the diagnostic accuracy of novel biomarkers for early detection or prediction of pediatric AKI across a variety of high-risk pediatric populations. Relevant studies were searched in PubMed, Cochrane Library, and Web of Science databases. Observational studies and randomized trials assessing diagnostic biomarkers for AKI in high-risk pediatric populations were included, while studies limited to traditional biomarkers, adult populations, or non-original research were excluded. Risk of bias was assessed using the QUADAS-2 tool. The review was prospectively registered in PROSPERO (CRD420261293432). Diagnostic accuracy outcomes included AUC, sensitivity, specificity, and other performance measures. 53 total studies were included and grouped into 1 of 5 categories based on the specific population of pediatric patients studied and the general etiology of their AKI. Of note, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and cystatin-C were among the most studied biomarkers and showed significant promise as reliable indicators of kidney injury. The product of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein-7, interleukin-18, and others showed some evidence of being predictive, early markers of AKI and warrant additional investigation. The review further discusses the integration of novel biomarkers within existing clinical detection frameworks, including validated risk stratification tools and emerging FDA-approved biomarker assays, to contextualize their translational potential in high-risk pediatric populations. Future advances in precision medicine may lead to earlier diagnosis and better prognosis for pediatric patients suffering from AKI.
Renal failureShuo Li, Yan Huang, Meiran Cao, Jingfu Wang
Background: The tubular atrophy/interstitial fibrosis (T) lesions of the Oxford Classification is a key prognostic determinant in IgA nephropathy (IgAN). The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is an emerging lipid marker, but its link with renal histologic damage in IgAN is unknown.Methods: This cross-sectional and retrospective study investigated the relationship between NHHR and T lesions in 400 biopsy-proven IgAN patients. Participants were divided into NHHR quartiles. The association between NHHR and T lesions was assessed using Spearman's rank correlation analysis, binary logistic regression analysis, restricted cubic spline (RCS) analysis, receiver operating characteristic (ROC) curve analysis, and subgroup analysis.Results: Compared to the lowest quartile (Q1), the highest NHHR quartile (Q4) showed significantly adverse clinical profiles and a higher prevalence of T1/T2 lesions (p < 0.05). NHHR was positively correlated with T lesions (r = 0.229, p < 0.001). Multivariate logistic regression analysis identified elevated NHHR and reduced estimated glomerular filtration rate (eGFR) as independent risk factors for T1/T2 lesions. RCS analysis demonstrated a linear association between NHHR and the risk of T1/T2 lesions (p for nonlinearity = 0.343). The ROC curve analysis yielded an area under the curve (AUC) of 0.635 for NHHR alone (optimal cutoff value = 3.54, sensitivity = 58.2%, specificity = 63.6%), and the composite NHHR+eGFR model achieved an AUC of 0.814. Subgroup analysis showed a consistent association between NHHR and the risk of T1/T2 lesions across all subgroups, with no significant interaction effects.Conclusion: Elevated NHHR is an independent risk factor for the progression of T lesions in patients with IgAN.
Although cardiovascular complications are the most common cause of morbidity and mortality in chronic kidney disease (CKD), the detection of subclinical cardiorenal remodeling is still limited. This is a single-center, exploratory observational study of 127 patients with CKD of various etiologies (hypertensive nephropathy, diabetic nephropathy and chronic glomerulonephritis) and 30 healthy controls. In addition to transthoracic echocardiography at rest and after exercise, biomarkers of podocyte injury (urinary nephrin), fibrosis (urinary type IV collagen and serum galectin-3), cardiac wall stress (serum NT-proBNP) and renal filtration/cardiovascular risk integration (serum cystatin C) were assessed. Biomarker abnormalities were consistent across all CKD groups, even in the absence of overt heart-failure symptoms and preserved ejection fraction. Urinary nephrin and type IV collagen were significantly increased, as were galectin-3 and NT-proBNP concentrations. All CKD groups had resting E/e' values above the normal range and these values were further elevated following exercise. Nephrin showed a strong positive correlation with E/e' and post-exercise echocardiography was associated with greater discrimination of an operationally defined subclinical cardiorenal phenotype than resting imaging. These exploratory findings indicate that a combined biomarker and echocardiographic profile is associated with an early cardiorenal phenotype and may assist in risk stratification of patients with CKD exhibiting early cardiorenal remodeling prior to the development of overt heart failure; they are hypothesis-generating and not intended to set diagnostic criteria. Prior to implementing this multimarker strategy clinically, larger, multicenter prospective studies with multivariable adjustment and external validation should be performed.
Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) reduces thrombotic risk in acute coronary syndrome (ACS) but may increase bleeding, especially in chronic kidney disease (CKD). This study evaluated the impact of different DAPT durations on cardiovascular and bleeding outcomes in ACS patients with and without CKD. Using the Taiwan National Health Insurance Research Database (2001-2018), patients ≥20 years with ACS who underwent PCI and received clopidogrel plus aspirin for ≥1 month were analyzed. Primary outcomes were cardiovascular events and bleeding events. Subgroup analysis was conducted by CKD status, which was defined using claims-based International Classification of Diseases, Ninth and Tenth Revision (ICD-9/ICD-10) diagnostic codes. Among 4,800 patients with ACS identified (median age: 62 years; 77% male), there were no significant differences in cardiovascular events across DAPT duration groups. No associations between DAPT duration and cardiovascular outcomes were identified in patients with or without CKD. However, DAPT duration ≥7 months was associated with a higher incidence of other major bleeding in patients with CKD (adjusted odds ratio [aOR] = 29.7, 95% confidence interval [CI]: 1.80-491.05, p = 0.018). In patients undergoing PCI for ACS, no clear association was observed between longer DAPT duration and reduced cardiovascular events. In prespecified subgroup analyses, prolonged DAPT was associated with a higher incidence of bleeding events among patients with claims-defined CKD; however, this finding should be interpreted as exploratory given the observational design and low event rates. These results highlight the importance of individualized decision-making regarding DAPT duration, particularly in patients with increased bleeding susceptibility.
Gut microbesBerengère Benoit, Pierre Letourneau, Vincent Verdier, Angélique Viney, Cécile Barnel, Karim Chikh, Oriane Vitalis, Audrey Jalabert, Sandra Wagner, Manolo Laiol…
Low-protein diets (LPD) are recommended in chronic kidney disease (CKD) to reduce disease progression. However, their clinical efficacy and safety are debated due to the risk of protein-energy wasting. A deeper mechanistic understanding is therefore required. Herein, the metabolic effects of LPD in both murine models and a randomized controlled trial in nondiabetic CKD patients were investigated, focusing on glucose homeostasis, plasmatic uremic toxin (UTs) levels, gut microbiota remodeling, and endocrine adaptations. In both experimental and clinical settings, LPD improved glucose tolerance and significantly decreased circulating levels of gut-derived UTs while reducing body weight (-33% weight gain in mice and a decrease in body mass index of ~-0.5 kg/m2 in humans). These metabolic improvements were associated with alterations in gut microbiota composition and function, including the downregulation of microbial pathways involved in aromatic amino acid biosynthesis. In both mice and patients, LPD triggered a significant hepatic induction of fibroblast growth factor 21 (FGF21), an endocrine regulator of amino acid deficiency (+2.9-fold in human and 28-fold in mice) FGF21 levels correlated negatively with lean mass and positively with fat mass and glycemic control, supporting a dual role in metabolic adaptation and catabolic signaling. To mitigate the adverse nutritional effects of LPD, we administered Lactiplantibacillus plantarum WJL (LpWJL), a probiotic previously found to enhance growth of under nutritional stress in CKD mice. LpWJL restored circulating amino acid levels, suppressed FGF21 induction (-26%) and stress-related biosynthetic responses, and preserved body weight (+247% weight gain) and composition, without impairing the benefits of LPD on kidney and metabolic parameters. The present findings identify UTs and FGF21 as crucial factors of the metabolic response to LPD, and support microbiota-targeted strategies, such as LpWJL supplementation, to enhance LPD efficacy. Clinical trials are, however, required to confirm their relevance in CKD management.
BACKGROUND: Patients undergoing dialysis are at an elevated risk of cardiovascular events. This study aimed to develop machine learning (ML) prediction models to identify risk factors for major adverse cardiovascular events (MACE) in dialysis patients. MATERIALS AND METHODS: This retrospective study included 203 patients undergoing dialysis with a median age of 45.0 years and 64.0% male. The participants were divided into training and test sets in a 7:3 ratio. LASSO regression selected characteristic variables from patients'general information, laboratory tests, and echocardiographic parameters (including global longitudinal strain [GLS]). Eight ML models were constructed,and SHAP analysis evaluated feature importance. RESULTS: The incidence of MACE (including myocardial infarction, unstable angina, heart failure, and cardiovascular death) in dialysis patients was 38.92%. The average follow-up period was 18 months. LASSO regression identified eight feature variables. Among the ML models, AdaBoost demonstrated superior performance, with an AUC of 0.883 (95% CI: 0.830-0.937), accuracy of 0.804, sensitivity of 0.864 and specificity of 0.762 in the training set, and an AUC of 0.809 (95% CI: 0.706-0.912), accuracy of 0.750, sensitivity of 0.90 and specificity of 0.675 in the test set. The SHAP analysis identified N-terminal pro-brain natriuretic peptide (NT-proBNP) level, estimated glomerular filtration rate (eGFR), GLS and age as the four most important features for predicting MACE in patients undergoing dialysis (mean absolute SHAP values: 0.199, 0.176, 0.096 and 0.091, respectively). CONCLUSION: Elevated NT-proBNP, advanced age, reduced eGFR and impaired GLS were independently associated with an increased risk of MACE in patients undergoing dialysis.
Renal failureRenzhong Ding, Yan Yang, Shiyi Xiang, Wenjun Wu, Ye Yuan, Tingting Li, Yi Song
BACKGROUND: Compartment syndrome (CS) is a severe complication after revascularisation for lower extremity arterial occlusive disease (LEAOD), but its association with systemic complications remains unclear. METHODS: This single-center retrospective cohort study included 153 patients with LEAOD who underwent revascularisation between January 2020 and December 2025. Postoperative CS was the primary exposure, and patients were classified into CS and non-CS groups. Clinical outcomes, including final amputation and acute kidney injury (AKI), were compared using multivariable logistic regression. RESULTS: CS occurred in 29 patients (19.0%). Patients with CS showed more severe ischemia and metabolic disturbance. The CS group had a higher crude final amputation rate than the non-CS group, but CS was not independently associated with final amputation after adjustment (OR 1.56; 95% CI 0.27-8.97; p = 0.618). AKI occurred more frequently in the CS group (69.0 vs. 12.1%, p < 0.001), and CS remained strongly associated with AKI after adjustment (OR 20.94; 95% CI 5.62-78.10; p < 0.001), with consistent findings in sensitivity analyses. Among patients with both CS and AKI, CS preceded AKI in all cases. CONCLUSIONS: Postoperative CS may represent a clinically recognizable marker of severe ischemia-reperfusion injury and systemic injury burden associated with AKI, rather than a definitive causal determinant of AKI or limb loss.
Renal failureYanyan Zhang, Mingli Zhang, Shan Liu, Xingrui Li
Chronic kidney disease (CKD) is a global health concern characterized by high prevalence and mortality rates, yet its underlying pathogenesis remains inadequately understood. This study aimed to investigate microbial biomarkers associated with CKD progression across various stages by employing 16S rDNA sequencing, complemented by machine learning techniques including Lasso regression, the Boruta algorithm, and K-fold cross-validation, alongside microbial network analysis. Fecal samples were collected from a cohort consisting of six patients with stage II CKD, five with stage III CKD, seven with stage IV CKD, and nine healthy controls. Following quality control of the sequencing data, we analyzed microbial composition, richness, and diversity, revealing significant differences among the groups. Ten differential microbial taxa were identified, with Actinobacteriota and Bifidobacterium showing the highest relative abundances. Machine learning methods highlighted six microbial biomarkers, including Eubacterium eligens and Lactococcus, all exhibiting AUC values exceeding 0.7, indicating their potential in distinguishing CKD patients from healthy individuals. Furthermore, species driving force analysis uncovered 26, 27, and 39 microbial interaction relationships between stages II, III, IV CKD, and controls, respectively. In conclusion, our integrative analysis elucidates stage-specific gut microbial biomarkers and functional pathways that are implicated in CKD progression, thereby supporting the mechanistic role of the gut-kidney axis and underscoring the potential for microbiota-based interventions and early diagnostic approaches in CKD.
Renal failureRuitong Liao, Xuemei Zhang, Lian Lin, Zhiyun Ning, Xiyan He, Yifan Lin, Yiqiang Zhan, Xiaoqing Ye
This study examined the associations of anxiety, insomnia, and psychological resilience with health-related quality of life (HRQoL) among maintenance dialysis patients and explored potential mediating roles. In this cross-sectional study, 207 adult patients undergoing maintenance dialysis were recruited. HRQoL was assessed using the Short Form-36 Health Survey (SF-36), generating Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Anxiety, insomnia, and psychological resilience were measured using the Generalized Anxiety Disorder-7 (GAD-7), Athens Insomnia Scale (AIS), and 25-item Connor-Davidson Resilience Scale (CD-RISC-25), respectively. Multivariable linear regression and bootstrap-based mediation analyses were conducted. Furthermore, subgroup analyses were conducted to examine the robustness of the results.Higher anxiety and insomnia scores were independently associated with lower PCS and MCS, whereas resilience was positively associated with both components. Each one-point increase in anxiety score was associated with a 1.61-point decrease in PCS and a 1.15-point decrease in MCS; corresponding decreases for insomnia were 1.01 and 0.91 points. Psychological resilience partially mediated the association between anxiety and HRQoL (23.46% for PCS; 30.37% for MCS), but no significant mediation was observed for insomnia. Subgroup analyses showed consistent associations for insomnia, while the anxiety-HRQoL relationship was modified by smoking status and diabetes. Anxiety and insomnia are independently associated with impaired HRQoL in dialysis patients. Psychological resilience partially explains the adverse impact of anxiety, but not insomnia, suggesting distinct patterns of association and potential targets for tailored psychosocial interventions.
This study aims to utilize summary-data-based Mendelian randomization (SMR) to explore the potential associations linking mitochondrial-related genes with acute kidney injury (AKI) and chronic kidney disease CKD. This study utilized mitochondrial-related genes from the MitoCarta3.0 database, alongside DNA methylation (mQTLs), gene expression (eQTLs), and protein expression (pQTLs) quantitative trait loci data. We obtained summary statistics from genome-wide association studies for AKI and CKD from the United States Million Veteran Program, with subsequent validation in the UK Biobank. The SMR method, complemented by colocalization analysis, was used to assess associations. We further performed validation using kidney cortex-specific eQTL data from Genotype-Tissue Expression project and single-cell transcriptome data from the KPMP database. In the discovery datasets, SMR analysis identified 174 mQTLs, 64 eQTLs, and 20 pQTL associated with AKI risk, and 253 mQTLs, 80 eQTLs, and 23 pQTLs associated with CKD risk. A total of 32 mQTLs, 16 eQTLs and 9 pQTLs were identified as common signals associated with both AKI and CKD risks. Specifically, FASN, DELE1, SARS2, NDUFB2, and ATP23 were significantly associated with both AKI and CKD risks, while ATAD3B and GCDH were CKD-specific signals. Notably, the shared gene ATP23 was identified as a risk factor for both AKI and CKD in kidney cortex tissue. Furthermore, ATAD3B was validated as a potentially protective factor for CKD, although the effect size was modest (OR 0.95, 95% CI 0.90-1.00). This study utilized the SMR method to identify potential risk and protective genes for AKI and CKD, revealing a molecular link between mitochondrial-related genes and renal failure.
Kidney renal clear cell carcinoma (KIRC) features an immunosuppressive tumor microenvironment (TME). We investigated the role of transcription factor POU2F2 in KIRC oncogenesis and macrophage polarization. Single-cell and spatial transcriptomics showed that POU2F2 is upregulated in KIRC and associated with metastasis and poor prognosis. POU2F2 knockdown inhibited KIRC cell proliferation, migration, and invasion in vitro. POU2F2 expression correlated with macrophage infiltration and JAK-STAT signaling. Co-culture assays showed that POU2F2 silencing reduced macrophage recruitment and shifted M2 polarization toward an anti-tumor M1 phenotype. Overall, POU2F2 acts as an oncogenic driver and prognostic biomarker in KIRC, promoting an immunosuppressive TME and representing a potential therapeutic target.
Renal failureYueguo Wang, Xin Wang, Xiancong Wang, Jian Sun, Yulan Wang, Xiongfeng Zhu, Huadong Meng, Shusheng Zhou, Kui Jin
Acute kidney injury (AKI) is a common and serious complication in critically ill patients receiving extracorporeal membrane oxygenation (ECMO), significantly affecting mortality and long-term renal function. However, risk factors and clinical course of AKI across different ECMO modalities remain poorly understood. Herein, our study identified independent risk factors for AKI in ECMO patients and evaluated the effect of AKI severity on 30-day mortality. This multicenter retrospective cohort study enrolled patients from three ECMO centers (September 2019-June 2024). AKI was defined and staged according to KDIGO serum creatinine criteria within 7 days after ECMO initiation. Multivariate stepwise logistic regression identified predictors of moderate-to-severe AKI (stages 2-3). Cox proportional-hazards models assessed the association between AKI stage and 30-day mortality. Among 210 patients, 110 (52.4%) developed AKI stages 2-3 within 7 days. Serial monitoring showed a progressive increase in stage 2, while stage 3 plateaued. Moderate-to-severe AKI was independently associated with 30-day mortality. In the overall cohort, VA-ECMO modality and norepinephrine use were independent risk factors for AKI stages 2-3, while high fibrinogen (FIB) level and a history of cardiovascular disease (CVD) were protective. In the VV-ECMO subgroup, elevated lactate, bicarbonate, FIB, procalcitonin, and blood urea nitrogen levels, along with decreased total bilirubin and white blood cell counts were significantly associated with increased moderate-to-severe AKI risk. Herein, our study indicated that severe AKI independently predicts 30-day mortality in ECMO patients. VA-ECMO modality and NE use increase moderate-to-severe AKI risk, while high FIB level and CVD provide protection.
OncoimmunologyChang Gon Kim, Junkyu Kim, In-Ho Kim, Eun Hee Jung, Hyeon-Su Im, Byung Woog Kang, Ji Hyun Park, Joo-Hwan Park, Jungmin Jo, Eo Jin Kim, Seung Hoon Beom, Sun You…
Non-clear cell renal cell carcinoma (nccRCC) represents a biologically heterogeneous group of tumors for which optimal systemic treatment strategies remain poorly defined despite recent therapeutic advances. To address this gap, we evaluated the clinical activity and safety of cabozantinib plus nivolumab in patients with advanced nccRCC. In this nationwide, multicenter retrospective cohort study conducted in the Republic of Korea, 62 patients received the combination across multiple lines of therapy, with most treated in the first-line setting. Papillary RCC was the most common histologic subtype (50.0%), followed by FH-deficient (22.6%), TFE3-rearranged (9.7%), chromophobe (6.5%), collecting duct (6.5%), and unclassified tumors (4.8%). With a median follow-up of 22.2 months (95% confidence interval [CI], 15.4-29.1), the objective response rate (ORR) was 45.2% (95% CI, 32.4-57.9) and the disease control rate (DCR) was 93.6% (95% CI, 87.3-99.8). Responses were seen across histologic subtypes (ORR = 48.4% in papillary, 50.0% in FH-deficient, 50.0% in TFE3-rearranged, 25.0% in chromophobe, 25.0% in collecting duct, and 33.3% in unclassified tumors; P = 0.876). Median progression-free and overall survival were 9.7 months (95% CI, 7.7-11.6) and 22.0 months (95% CI, 15.2-28.7), respectively. Grade 3-4 treatment-emergent adverse events occurred in 46.8% of patients, and treatment discontinuation due to toxicity was reported in 6.5%. These findings demonstrate that cabozantinib plus nivolumab provides clinically meaningful and durable antitumor activity with manageable toxicity across diverse histologic subtypes in advanced nccRCC, supporting further prospective evaluation of cabozantinib plus nivolumab in advanced nccRCC.
OncoimmunologyFanny Méjean, Thi Tran, Maya Merabet, Alain Gey, Andyara Munoz, Benjamin Morin, Ali Bal, Morgane Bourhis, Nesrine Mabrouk, Magali Terme, Eric Tartour, Corinne …
Despite significant progress achieved by combining VEGFR tyrosine-kinase inhibitors (TKIs) with immune checkpoint inhibitors (ICIs), complete responses remain rare in metastatic renal cell carcinoma (mRCC), highlighting the need for strategies that optimize therapeutic synergy. Here, we show that the efficacy of VEGFR blockade, vaccination, and PD-1 inhibition critically depends on treatment sequence. Using an orthotopic RENCA model, we show that short-term VEGFR inhibition with axitinib transiently remodels tumor vasculature, alleviates hypoxia, and limits suppressive myeloid subsets, thereby generating an immune-permissive window. Administering a survivin-based long-peptide vaccine (SVX) during this preconditioning phase elicits strong Th1-polarized CD4⁺ and cytotoxic CD8⁺ T-cell infiltration, which exhibit a polyfunctional cytokine and chemokine profile. When PD-1 blockade is introduced concomitantly with vaccination, after, rather than during, axitinib treatment, the triple regimen (axitinib + [SVX + anti-PD-1]) achieves durable tumor control with a high rate of complete responses, outperforming all other treatment schedules. Mechanistically, this sequence aligns vascular reprogramming, antigen-specific priming, and checkpoint release, converting an immune-excluded tumor into a T-cell-dominated, cytotoxic niche. Collectively, these findings identify temporal coordination as a critical determinant of therapeutic success and establish a mechanistically grounded framework for integrating vascular preconditionning, tumor-antigen vaccination, and PD-1 blockade as a curative immunotherapy strategy in renal carcinoma.