Minimal change nephrotic syndrome (MCNS) is characterized by podocyte injury leading to severe proteinuria, mainly mediated by T-cell activation and cytokine imbalance. Relapses are often triggered by immunological stimuli such as infections, vaccinations, or drugs; however, relapse following administration of sulfamethoxazole–trimethoprim (ST) combination therapy has not been reported previously. We report an extremely rare case of MCNS relapse triggered by ST combination therapy.A 55-year-old woman with a history of breast cancer treated with tamoxifen developed nephrotic syndrome and was diagnosed with MCNS by renal biopsy. After remission was achieved with prednisolone 50 mg/day, ST therapy was initiated for prophylaxis of Pneumocystis jirovecii pneumonia. Approximately 12 days after starting ST, she developed generalized erythema accompanied by relapse of nephrotic syndrome. Discontinuation of ST, atorvastatin, and esomeprazole while continuing prednisolone 40 mg/day led to a second remission. Drug-induced lymphocyte stimulation tests for all agents were negative, possibly due to concurrent corticosteroid therapy.Metabolites of sulfamethoxazole have been shown to activate CD4+ T cells and induce multiple cytokines including interleukin-13, interferon-γ, interleukin-22, and granzyme B. Such immune activation could explain the simultaneous occurrence of cutaneous manifestations (drug eruption) and renal relapse (MCNS).Relapse of drug-induced MCNS may occur through either direct podocyte injury or immune-mediated allergic mechanisms. Given the concurrent drug eruption, the latter mechanism appears most consistent with this case.When introducing new medications under immunosuppressive conditions, clinicians should consider the possibility of drug-induced relapse if proteinuria reappears.

Background: In pancreatic ductal adenocarcinoma (PDAC), desmoplastic stroma limits drug delivery and contributes to therapeutic resistance. First-line gemcitabine plus nab-paclitaxel (GnP) has historically achieved an objective response rate (ORR) of about 23%, and no stromal-targeting approach has yet altered the first-line standard of care. Tamibarotene (AM80), a retinoid, induces tumour-restraining cancer-associated fibroblasts (rCAFs) in preclinical models, a reprogramming effect associated with improved intratumoural chemotherapy delivery. We evaluated tamibarotene plus GnP in patients with unresectable PDAC. Methods: MIKE-1 was an investigator-initiated, open-label, single-arm phase 1/2 trial in previously untreated unresectable PDAC. Phase 1, conducted at Nagoya University Hospital, used a 3+3 dose escalation design; phase 2 was undertaken at Nagoya University Hospital and University of Tokyo Hospital. Primary endpoints were determination of the recommended phase 2 dose in phase 1 and investigator-assessed confirmed ORR per RECIST version 1·1 in phase 2. Findings: Between March 2022 and April 2025, 60 patients were enrolled and 59 started treatment. At data cutoff (2 October 2025; median follow-up 12·7 months), the confirmed ORR in phase 2 (n=42; tamibarotene 8 mg/day on days 1–14 plus GnP) was 50·0% (21/42; 90% CI 36·5–63·5; p<0·001 vs the prespecified historical 23% threshold), and the disease control rate was 85·7% (36/42). Median progression-free survival was 11·3 months, median overall survival was not reached, and 12-month overall survival was 86·9% (95% CI 71·0–94·4). Interstitial lung disease (ILD) occurred in seven (16·7%) of 42 patients; all improved or resolved, and no grade 5 treatment-related adverse events occurred. In 12 phase 1/2 paired-biopsy patients, Xenium spatial transcriptomics showed an on-treatment shift away from myofibroblastic CAFs (myCAFs) towards rCAFs. Interpretation: Tamibarotene plus GnP exceeded the prespecified ORR threshold, with paired-biopsy increases in stromal Meflin and a myCAF-to-rCAF shift consistent with stromal reprogramming. A randomised trial versus GnP alone, with prospective ILD monitoring, is warranted.

Chronic kidney disease (CKD) affects approximately 10% of the global population and exhibits substantial heterogeneity in disease progression and clinical outcomes. Despite ongoing efforts to develop new therapeutic strategies, the number of patients progressing to end-stage kidney disease (ESKD) and the incidence of cardiovascular disease (CVD) continue to rise. Although severity classification systems for CKD are well established and refined, they remain insufficient to capture prognostically relevant patient subtypes. In this study, we developed an outcome-aware and interpretable clustering framework for CKD subtyping using data from the FROM-J cohort with prognostic follow-up. A supervised XGBoost model was first trained to predict a ≥ 30% decline in estimated glomerular filtration rate (eGFR), a surrogate marker of CKD progression. SHAP (SHapley Additive exPlanations) values derived from this model were then used to quantify outcome-relevant feature contributions. Based on these feature attributions, a similarity graph was constructed, and spectral clustering was performed to identify patient subtypes driven by prognostic relevance. The proposed framework identified four CKD subtypes with distinct baseline clinical characteristics and significantly different risks of renal replacement therapy (RRT) and cardiovascular disease (CVD) events. Serum albumin, blood urea nitrogen (BUN), and smoking status consistently emerged as key features defining subtype structure and prognosis. Robust risk stratification was preserved even when clustering was restricted to these three routinely measured variables. Overall, our findings demonstrate that integrating outcome-driven feature attribution into clustering enables interpretable and clinically relevant CKD subtyping, providing a practical approach for characterizing disease heterogeneity and supporting risk stratification and personalized management.

Background:Current guidelines for hyponatremia recommend slow sodium correction; however, recent large-scale observational studies have associated slow correction with increased mortality. The association between correction rate and mortality can be influenced by numerous factors, including comorbidities, overall condition, and treatment interventions, but this complex interplay remains unclear. We aimed to clarify this association by developing interpretable machine-learning models using detailed clinical features. Methods:We included 546 patients with serum sodium ≤120 mEq/l, collected clinical features through chart review, and developed four machine-learning models to predict in-hospital mortality. The best-performing model, selected by the area under the receiver operating characteristic curve (ROC-AUC), was interpreted using SHapley Additive exPlanations (SHAP) to quantify each feature's contribution to mortality prediction. Results:In-hospital mortality was 18%. The random forest model demonstrated the best predictive performance (ROC-AUC = 0.907; 95% confidence interval, 0.832-0.965). SHAP analysis revealed that the most influential predictors were baseline characteristics reflecting underlying illness severity: serum albumin, C-reactive protein, Charlson comorbidity index, and metastatic malignancy; their predictive effects were consistent across correction rates. Among treatment-related features, intravenous fluid choice and sodium monitoring frequency had a greater predictive impact than correction rate. Although slower correction was associated with higher mortality, the correction rate ranked 14th among all 59 features in predictive importance. Conclusions:In profound hyponatremia, multiple key predictors of mortality exist beyond the correction rate. These findings suggest that the observed association between slow correction and higher mortality may not be causal but rather an epiphenomenon driven by underlying illness severity and treatment intensity.

OBJECTIVE:Malnutrition and altered body composition are major determinants of mortality in patients undergoing maintenance hemodialysis (HD). We aimed to evaluate the association between subcutaneous adipose tissue radiodensity (SAT-HU) measured on noncontrast abdominal computed tomography (CT) and 5-year all-cause mortality. METHODS:We conducted a retrospective cohort study of 444 maintenance HD patients within the Kaikoukai Healthcare Group who underwent noncontrast CT between 2011 and 2021. The primary exposure was mean SAT-HU at the third lumbar vertebra, categorized into sex-specific tertiles; visceral adipose tissue radiodensity was assessed secondarily. The primary end point was 5-year all-cause mortality. Cox proportional hazards models with multiple imputation were used to estimate adjusted hazard ratios, adjusting for nutritional indices (e.g., body mass index and serum albumin) and other covariates. RESULTS:During a median follow-up of 3.1 years, 87 deaths (19.6%) occurred. Patients in the highest SAT-HU tertile had lower body mass index, serum albumin and triglyceride levels, and subcutaneous fat area than those in the other tertiles (P < .001). Survival was poorest in the highest SAT-HU tertile (log-rank P < .001). In the fully adjusted model, the highest SAT-HU tertile had higher mortality risk than the lowest tertile (hazard ratio 2.44; 95% confidence interval 1.24-4.80), with a stronger association among patients aged ≥ 75 years (P for interaction = .004). Higher visceral adipose tissue radiodensity was not significantly associated with mortality after adjustment. CONCLUSIONS:Higher SAT-HU independently predicts all-cause mortality in HD, particularly in older patients, and may provide a practical CT-based biomarker for risk stratification beyond conventional nutritional indices.

Mesenchymal stem cells (MSCs) possess immunomodulatory and tissue repair properties, and their therapeutic efficacy has been reported in models of glomerulonephritis. However, the clinical application of bone marrow-derived MSCs (BMSCs) is limited due to the invasive nature of bone marrow harvesting. In this study, we focused on amnion-derived MSCs (AMSCs), which can be obtained non-invasively after delivery, and investigated their therapeutic effects in a rat model of anti-glomerular basement membrane (GBM) nephritis. In a rat model of anti-GBM nephritis, human AMSCs, BMSCs, or vehicle were intravenously administered. Evaluations included renal function, histology, intravital imaging of glomerular neutrophils, and flow cytometric analysis of leukocytes. In addition, we used an anti-CD44 neutralizing antibody in vivo to examine the therapeutic relevance of CD44 blockade, including its impact on neutrophil. The renoprotective effects observed in the AMSC-treated group were comparable to or greater than those in the BMSC-treated group. Furthermore, neutrophils exposed to AMSCs exhibited shorter dwell time in the glomeruli, and specifically in renal neutrophils, the expression of the adhesion molecule CD44 was reduced. In addition, administration of an anti-CD44 antibody produced similar renoprotective effects and reductions in neutrophil infiltration, suggesting that modulation of CD44 signaling contributes to the renoprotective effects of AMSCs. Collectively, these findings indicate that AMSCs exert renoprotective effects comparable to or greater than those of BMSCs, and may represent a novel therapeutic approach for anti-GBM nephritis by specifically suppressing CD44 expression in neutrophils at sites of inflammation.

Pregnancy induces vascular, coagulation, and immune alterations that predispose to thrombotic microangiopathy (TMA). Within this spectrum—preeclampsia/ hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP) and complement-mediated TMA (CM-TMA)—overlapping features complicate diagnosis, whereas management and prognosis diverge. A 39-year-old woman developed severe hypertension at 35 weeks’ gestation, underwent emergency cesarean section for preeclampsia, and subsequently became anuric. She had schistocytic hemolysis, thrombocytopenia, elevated lactate dehydrogenase (LDH), and transaminitis. One plasma exchange, hemodialysis, and supportive care were provided; urine output recovered and dialysis ceased. Atypical complement tests results persisted for 1 month (undetectable serum CH50 with elevated C3/C4), with normal functional assays and no pathogenic variants in complement-regulatory genes. On subsequent testing with Ethylenediaminetetraacetic acid (EDTA) plasma, preserved at − 80 °C, showed a normal CH50, suggesting that ex vivo complement activation may have contributed to the low serum CH50. In the acute setting, HELLP versus CM-TMA remained indeterminate, so management was guided by the clinical trajectory: brief plasma exchange during TTP evaluation, close monitoring, and deferral of complement inhibition as platelets, LDH, and urine output improved. This case supports a “trend-first” approach to peripartum TMA, and underscores ex vivo complement activation as a key pitfall when interpreting complement assays in the peripartum setting.

Although depression is common among patients with chronic kidney disease (CKD), its impact on the incidence of end-stage kidney disease (ESKD) and all-cause mortality remains unclear. This retrospective cohort study used Cox proportional hazards (CPH) models and CPH models with penalized splines to assess the association between depression severity and the incidence of ESKD and mortality in patients with CKD, drawing on data from the Chronic Kidney Disease Japan Cohort (CKD-JAC) Study. This study included 1,694 patients with CKD (median age 61 years; mean eGFR 29.0 ± 12.2 mL/min/1.73 m2; median Beck Depression Inventory-II (BDI-II) score 8). Depression severity was classified into four categories: normal (0–13), mild (14–19), moderate (20–28), and severe (≥ 29). In Multivariable CPH models, ESKD risk showed a stepwise elevation in hazard ratios (HRs) without reaching statistical significance, whereas, mortality risk increased significantly in the moderate and severe group: HR 3.11 (95

Key Points. We evaluated the association between the four categories of left ventricular geometry and all-cause mortality in patients undergoing hemodialysis. Concentric hypertrophy was the most prevalent, followed by concentric remodeling, and these were associated with a high risk of mortality. Echocardiography screening for evaluating the four categories of left ventricular geometry may be useful for risk prediction in patients undergoing hemodialysis. Background. Left ventricular (LV) geometry, which is classified into four categories on the basis of left ventricular mass index and relative wall thickness, can predict mortality more accurately than the presence of LV hypertrophy alone in patients with hypertension. However, this association remains inconclusive in patients undergoing maintenance hemodialysis. Methods. We conducted a retrospective multicenter cohort study involving patients undergoing maintenance hemodialysis in Japan who underwent echocardiography between October 2006 and December 2021. The exposure of interest was LV geometry abnormalities (concentric remodeling, eccentric hypertrophy, and concentric hypertrophy). The primary outcome of this study was all-cause death. Results. Among the 2228 patients included in the analysis (mean age, 67 years; 67% male individuals; median dialysis vintage, 1.5 years), 476 (21%) had normal geometry, 592 (27%) had concentric remodeling, 493 (22%) had eccentric hypertrophy, and 667 (30%) had concentric hypertrophy. During a median follow-up period of 3.8 years, 825 patients (37%) died. Compared with patients with normal geometry, those with concentric hypertrophy (adjusted hazard ratio [aHR], 1.32; 95% confidence interval [CI], 1.06 to 1.63) and concentric remodeling (aHR, 1.27; 95% CI, 1.02 to 1.58) had a higher risk of mortality. Eccentric hypertrophy was associated with a similar risk of mortality (aHR, 1.03; 95% CI, 0.81 to 1.30) compared with normal geometry. Conclusions. Approximately 80% of patients undergoing maintenance hemodialysis exhibited abnormal LV geometry, with concentric hypertrophy being the most common pattern, followed by concentric remodeling. These abnormalities were associated with a higher risk of all-cause mortality compared with normal geometry. Risk prediction on the basis of the presence or absence of LV hypertrophy cannot consider concentric remodeling; therefore, echocardiography screening for evaluating the four categories of LV geometry may be beneficial in patients undergoing hemodialysis.

Fracture risk associated with sleep drugs is of great concern in patients with chronic kidney disease (CKD). However, the fracture risk among sleep drugs with different mechanisms of action remains controversial. This study aimed to examine how fracture risk differs between the use of benzodiazepine receptor agonists (BDZRA) and dual orexin receptor antagonists (DORA) in patients with CKD. A large-scale Japanese medical claims database of patient data collected between April 2008 and August 2021 was analysed. The association between composite hip and vertebral body fracture risk and continuous prescription of DORA or BDZRA was examined using a Cox proportional hazards model. Propensity score matching was employed to reduce confounding. DORA and BDZRA were prescribed to 4,504 and 22,080 patients, respectively. The BDZRA group showed a lower cumulative incidence rate of composite hip and vertebral body fractures than the DORA group (hazard ratio [HR]: 0.67, p = 0.06 in the unmatched cohort and HR: 0.64, p = 0.129 in the matched cohort). The risk of hip fracture alone was comparable for both the unmatched cohort (HR: 0.83, p = 0.507) and matched cohort (HR: 0.94, p = 0.869). The risk of vertebral body fracture alone was significantly lower in both the unmatched and matched cohorts (HR: 0.45, p = 0.021 for the unmatched cohort and HR: 0.23, p = 0.023 for the matched cohort). The results suggest a possible association between DORA prescription and bone metabolism in patients with CKD. DORA should be used with caution in these patients. Not applicable.

Atherosclerosis, which leads to cardiovascular disease (CVD), can progress without any symptoms. To prevent CVD, it is important to detect atherosclerotic lesions early and assess their severity. Atherosclerosis evaluation for primary prevention is a preferable non-invasive diagnostic tool. In this study, a new device was developed to measure arterial stiffness. This new device measures the pressure-volume relationship during avascularization and the upper arm release process, similar to an automatic blood pressure monitor. The proportionality coefficient between pressure and volume was calculated from this curve; the larger the proportionality coefficient, the greater the arterial stiffness. Using this device, the arterial stiffness index (ASI), standard arteriosclerosis indices, cardio-ankle vascular index (CAVI), ankle-brachial pressure index (ABI), and pulse wave velocity (PWV) were measured in 97 patients with chronic kidney disease and investigated the associations between ASI and these arteriosclerosis indices, as well as CVD history. A positive correlation was observed between ASI and PWV (P = 0.04); however, ABI and CAVI showed no correlation with ASI when analyzed using multiple regression, adjusting for age, sex, smoking, diastolic pressure, and serum creatinine. Furthermore, ASI was related to CVD history by an odds ratio of 1.03 (95% CI, 1.01-1.06) using logistic regression analysis adjusted for age, sex, smoking, and diastolic pressure, whereas CAVI, PWV, and ABI showed no relation to CVD history. ASI measured by our device is easier to measure than indices by devices in everyday use and was the only index to identify actual atherosclerotic disease events.

Abstract Background Renal dysfunction is a common complication in patients supported with left ventricular assist devices (LVADs), and a subset requires long-term renal replacement therapy (RRT). The coexistence of right heart failure (RHF), venous congestion, and hemodynamic instability complicates dialysis management. However, evidence guiding dialysis modality and vascular access selection in this population remains limited, leaving key clinical decisions unsupported. Methods We conducted a scoping review in accordance with the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. PubMed, Scopus, and the Cochrane Library were searched for studies published between January 2015 and October 2025. We included studies involving adult LVAD recipients requiring maintenance dialysis after LVAD implantation, focusing on dialysis modality, vascular access, clinical outcomes, and RHF. Two reviewers independently screened studies and extracted data. A structured descriptive analysis was performed across predefined domains. Results A total of 31 studies were included, comprising 17 cohort studies, 8 case reports or case series (20 patients), and 6 narrative reviews. All reported LVADs were continuous-flow devices. Hemodialysis was the predominant modality, whereas peritoneal dialysis was suggested as a potential alternative in patients with hemodynamic instability or RHF. Cohort studies rarely reported dialysis modality or vascular access in detail, and no comparative analyses were identified. Vascular access strategies and the impact of RHF on dialysis outcomes were also insufficiently evaluated. Most studies originated from the USA, indicating limited geographic diversity. Conclusions Current evidence does not adequately support clinical decision-making regarding dialysis modality or vascular access in LVAD-supported patients. Despite increasing clinical complexity, key determinants, such as RHF, are not systematically evaluated. Prospective and comparative studies are urgently needed to establish evidence-based dialysis strategies in this population.