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.

Percutaneous renal biopsy is essential for diagnosing kidney disease. It is invasive and requires technical training to ensure patient safety. Simulation-based education is increasingly used to teach invasive procedures and minimize patient risk. However, most renal biopsy simulation studies focus on residents rather than undergraduate medical students. We evaluated the educational effectiveness of a renal biopsy simulation workshop during a nephrology clinical clerkship. This prospective educational study enrolled fifth-year medical students (n = 113) who participated in a nephrology clinical clerkship at Okayama University between January 2023 and January 2024. The students attended a renal biopsy simulation workshop that included a short lecture, peer ultrasound practice, and hands-on workshop with a renal biopsy simulator. We assessed educational outcomes using anonymous pre- and post-workshop questionnaires that evaluated knowledge, confidence, and educational satisfaction. Before the workshop, only 4.5

Despite the increasing number of patients diagnosed with postprandial reactive hypoglycemia (PRH), standardized diagnostic criteria and evaluation methods have not been established. We report three cases of PRH in young adult Japanese women with a normal body weight, identified through oral glucose tolerance testing and continuous glucose monitoring. In these patients, PRH was likely driven by disproportionately increased insulin secretion, possibly related to residual insulin resistance stemming from a history of childhood obesity. As PRH can occur in individuals with various known and yet-to-be-defined predispositions, careful assessment of the underlying contributing factors is essential.

IntroductionTumor cells use immune checkpoint proteins such as programmed cell death 1 to escape immunological defenses. Immune checkpoint inhibitors (ICIs) that target these proteins have been used to treat several malignancies. ICI-induced diabetes is a rare but life-threatening adverse event. Our previous study evaluated pancreatic β-cell activity using the homeostasis model assessment of β-cell (HOMA-β) function before ICI treatment and demonstrated its association with treatment outcomes. In addition, DRB1*04:05 and DRB1*09:01 reportedly increase the risk of type 1 diabetes in Japanese patients, whereas DRB1*15:01 protected against type 1 diabetes. However, the association between human leukocyte antigen (HLA) class II alleles and treatment outcomes of ICI therapy remains unclear.MethodsWe included 96 patients who were diagnosed with advanced cancer. The HLA genotypes that cause type 1 diabetes in patients with ICI-treated cancers were evaluated to determine their association with the cancer prognosis.ResultsThe median progression-free survival (PFS) in the DRB1*04:05-positive group (2 months, 95% confidence interval [CI]: 1.214–2.786; 31 events; 1 censored event) was significantly shorter than that in the DRB1*04:05-negative group (3 months; 95% CI: 1.933–4.067; 56 events; 8 censored events) (log rank p=0.045). Additionally, a multivariable Cox proportional hazards regression revealed that DRB1*04:05 was independently associated with shorter PFS for patients treated with ICIs.ConclusionsHLA class II alleles were associated with shorter PFS in patients treated with ICIs. In particular, DRB1*04:05 positivity was associated with worse survival outcomes, suggesting a potential immunogenetic contribution to treatment outcomes.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotizing vasculitis characterized by eosinophilic infiltration and granuloma formation, affecting multiple organs. Gastrointestinal (GI) involvement is relatively uncommon and it typically presents with nonspecific symptoms, such as abdominal pain or diarrhea; in contrast, ulceration and intestinal perforation are rare, but potentially life-threatening complications that often require surgical intervention. The standard treatment for severe GI EGPA includes high-dose glucocorticoids combined with cyclophosphamide or rituximab (RTX). However, the perioperative escalation of glucocorticoids is generally avoided owing to the increased risk of postoperative complications. We report a case with a 5-year follow-up of EGPA resistant to multiple immunosuppressive agents with severe GI involvement, including intestinal perforation and multiple jejunal ulcers, which was successfully treated with RTX for postoperative remission induction and long-term maintenance therapy without any prednisolone escalation. The prednisolone dose was gradually reduced from 17.5 mg/day to 1 mg/day over two years without any escalation, and a sustained remission was achieved throughout the course. This case suggests that RTX may represent a viable therapeutic option for severe or treatment-resistant EGPA in cases with GI involvement when glucocorticoid escalation is undesirable or unsafe, such as in the perioperative setting.

Background: Lower urine pH has been associated with reduced kidney function and an increased risk of kidney disease; however, its prognostic and pathological significance in biopsy-proven kidney disease remains unclear. A recent study demonstrated that medullary cast formation is independently associated with adverse renal outcomes beyond established predictors such as interstitial fibrosis and tubular atrophy (IFTA), yet its clinical determinants are not fully elucidated. Urine pH reflects the intratubular acid-base microenvironment and may contribute to tubular obstruction through cast formation. In this study, we examined kidney outcomes in patients undergoing native kidney biopsy, and the associations of urine pH with medullary cast formation. Methods: Among 1167 adults who underwent native kidney biopsy between 2011 and 2024, 503 patients with evaluable medullary tissue were included in this retrospective observational cohort study. Urine pH was analyzed in relation to clinical and histological variables and kidney outcomes. The primary outcome was a 40% decline in estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Results: The mean baseline eGFR was 54.3 mL/min/1.73 m2, the mean urine pH was 6.15, and the median urinary protein excretion was 1.1 g/gCr. During a median follow-up of 2.11 years, 113 patients (22.5%) reached the kidney outcome. Kaplan-Meier analysis showed that lower urine pH was associated with a higher risk of kidney outcomes. In Cox proportional hazards models adjusted for proteinuria, baseline eGFR, and IFTA score, urine pH remained independently associated with kidney outcomes (hazard ratio, 0.69; 95% confidence interval, 0.51-0.91). Inclusion of urine pH improved prognostic discrimination beyond established risk factors (Harrell C-index, 0.642 to 0.654). Lower urine pH was also associated with greater medullary cast formation. Conclusion: In patients undergoing native kidney biopsy, lower urine pH was independently associated with adverse kidney outcomes and greater medullary cast formation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Japanese Society for the Promotion of Science (JSPS)/Grant-in-Aid for Scientific Research (C) (grant no. 24K11411). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Background B-cell acute lymphoblastic leukemia (B-ALL) is an uncommon malignancy in adults. Polymyalgia rheumatica-like syndromes are rare and present features that can lead to a diagnostic delay. Magnetic resonance imaging (MRI) may reveal diffuse bone-marrow abnormalities. However, these findings are often nonspecific. Case Presentation A Japanese woman in her 40s presented with persistent pain in the bilateral shoulders, upper arms, and thighs. Initial laboratory tests showed anemia and elevated C-reactive protein levels, but no blasts were detected in the peripheral blood. Polymyalgia rheumatica was suspected; however, her age, absence of morning stiffness, and symmetrical diaphyseal pain were atypical for this condition. MRI revealed diffuse T2-short tau inversion recovery hyperintensity and patchy enhancement in the femoral and humeral shafts and adjacent muscles, without the dominant bursitis or synovitis typical of polymyalgia rheumatica. Bone marrow biopsy revealed hypercellularity with numerous CD19-positive lymphoblasts, leading to a diagnosis of B-ALL. Induction chemotherapy resulted in rapid pain relief and normalization of the clinical findings. Conclusion This case highlights that hematologic malignancies, including B-ALL, can present with polymyalgia rheumatica-like symptoms in adults. MRI is useful for detecting bone marrow infiltration and should prompt early bone marrow examination. Recognizing atypical features in presumed polymyalgia rheumatica and avoiding premature glucocorticoid therapy may prevent delays in the diagnosis of life-threatening conditions such as leukemia.

AIMS/INTRODUCTION:Sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent cardiovascular events in patients with diabetic kidney disease (DKD). However, limited data exist regarding the change in B-type natriuretic peptide (BNP) after treatment. This study investigated whether SGLT2i are associated with a greater BNP reduction than other antidiabetic drugs and identified the predictors of BNP reduction following SGLT2i. MATERIALS AND METHODS:Using the Japanese nationwide database, we compared BNP levels before and 30-365 days after initiation of antidiabetic medication in 1818 patients with DKD (71 ± 12 years, 68% men, BNP 71 [27-190] pg/mL, estimated glomerular filtration rate (eGFR) 51 ± 22 mL/min/1.73 m2). RESULTS:BNP reduction, defined as a reduction of >10%, occurred in 474 (50.5%) of 939 patients treated with SGLT2i and 339 (38.6%) of 879 treated with other antidiabetic drugs. SGLT2i was associated with BNP level reduction in a multivariable logistic regression analysis (odds ratio, 1.497 [1.206-1.859]; p < 0.001). This association was consistent across eGFR, proteinuria, and multiple BNP endpoints. Concomitant use of loop diuretics was associated with a lower rate of BNP reduction after SGLT2i. CONCLUSIONS:Compared with other antidiabetic drugs, SGLT2i was substantially associated with BNP reduction in a broad spectrum of DKD.

Background: Renal biopsy provides important prognostic information for patients with chronic kidney disease (CKD), primarily through evaluation of cortical histopathological lesions, including interstitial fibrosis and tubular atrophy (IFTA). However, the prognostic significance of renal medullary lesions remains poorly understood. We investigated whether medullary pathological findings are independently associated with renal outcomes and whether they improve prognostic discrimination beyond conventional cortical assessments. Methods: This single-center retrospective cohort study screened 1,136 adult patients who underwent native kidney biopsy between 2011 and 2023. After applying predefined inclusion and exclusion criteria, 488 patients with adequate medullary tissue were included in the final analysis. Medullary fibrosis, inflammatory cell infiltration, and cast formation were semi-quantitatively graded and evaluated as predictors of renal outcomes. The primary outcome was a composite of 40% decline in estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Associations were assessed using Cox proportional hazards models with sequential adjustment for demographic factors, baseline eGFR, proteinuria, and cortical IFTA. Model discrimination was evaluated using Harrell's concordance-index (C-index). Results: During a median follow-up of 2.3 years, 112 patients (23.0%) reached the composite renal outcome. In multivariable analysis adjusted for age, sex, baseline eGFR, and proteinuria, medullary cast formation was significantly associated with adverse renal outcomes (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.28-2.24). This association remained significant after additional adjustment for IFTA (HR 1.64, 95% CI 1.21-2.21), whereas medullary fibrosis lost significance after IFTA adjustment. Addition of medullary cast formation improved C-index by 0.016, indicating incremental prognostic value beyond conventional predictors. Conclusion: Medullary cast formation is independently associated with renal outcomes and improves prognostic discrimination beyond established cortical parameters. Systematic evaluation of medullary lesions during routine kidney biopsy may enhance risk stratification in CKD. Prospective studies are warranted to clarify the causal role of medullary pathology in CKD progression. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Japanese Society for the Promotion of Science (JSPS)/Grant-in-Aid for Scientific Research (C) (grant no. 24K11411). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the institutional review board of Okayama University (Approval Nos. 1908-022 and 2407-038). The requirement for written informed consent was waived because of the retrospective design. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available from the corresponding author upon reasonable request.