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Abstract To decrease the number of chronic kidney disease (CKD), early diagnosis of diabetic kidney disease is required. We performed invariant information clustering (IIC)-based clustering on glomerular images obtained from nephrectomized kidneys of patients with and without diabetes. We also used visualizing techniques (gradient-weighted class activation mapping (Grad-CAM) and generative adversarial networks (GAN)) to identify the novel and early pathological changes on light microscopy in diabetic nephropathy. Overall, 13,251 glomerular images (7,799 images from diabetes cases and 5,542 images from non-diabetes cases) obtained from 45 patients in Kanazawa Medical University were clustered into 10 clusters by IIC. Diabetic clusters that mainly contained glomerular images from diabetes cases (Clusters 0, 1, and 2) and non-diabetic clusters that mainly contained glomerular images from non-diabetes cases (Clusters 8 and 9) were distinguished in the t-distributed stochastic neighbor embedding (t-SNE) analysis. Grad-CAM demonstrated that the outer portions of glomerular capillaries in diabetic clusters had characteristic lesions. Cycle-GAN showed that compared to Bowman’s space, smaller glomerular tufts was a characteristic lesion of diabetic clusters. These findings might be the subtle and novel pathological changes on light microscopy in diabetic nephropathy.

Abstract The estimated glomerular filtration rate (eGFR) at 1 year post-transplantation is a well-established predictor of long-term graft survival; however, its predictive accuracy needs improvement. We retrospectively analyzed data from 51 kidney transplant recipients at Kanazawa Medical University Hospital (January 2001–February 2015). Cox regression was used to identify risk factors for death-censored graft loss and create a nomogram to predict graft survival at 15 years post-transplantation. The predictive factors ultimately included in the nomogram included eGFR and serum glucose-regulated protein 78 (GRP78) at 1 year post-transplantation. In terms of discrimination, assessed by area under the receiver operating characteristic curve (AUC-ROC), no significant difference was noted between the eGFR model (AUC 0.84 [0.67–1.00]) and nomogram (AUC 0.92 [0.82–1.00]) (p = 0.38). However, calibration, evaluated by the calibration plot, indicated superiority of the nomogram over the eGFR model, confirmed in the internal validation cohort using the Bootstrap method. Regarding clinical value evaluated by decision curve analysis, the nomogram showed a greater net benefit than the eGFR model, especially at wider diagnostic thresholds (particularly important lower thresholds). Our findings suggest the added predictive value of serum GRP78 at 1 year post-transplantation for long-term graft survival prediction.

Abstract Background Rectus sheath hematoma is a rare presentation often associated with abdominal trauma and anticoagulant therapy. Here, we present a patient with severe rectus sheath hematoma accompanied by nephrotic syndrome who achieved significant clinical improvement without the need for invasive treatment. Case presentation A 72-year-old Japanese woman was referred to our hospital for the treatment of nephrotic syndrome. She was receiving steroid and anticoagulant therapy. Then she had abdominal pain and she was diagnosed with spontaneous rectus sheath hematoma by abdominal computed tomography. She received transfusion and was managed conservatively with bed rest, which led to improvement in abdominal pain. Conclusion Despite the absence of trauma history, rectus sheath hematoma should be considered in patients at risk of vascular failure, including those receiving anticoagulant or steroid therapy, those who are elderly, and those with nephrotic syndrome.

Key Clinical Message The present case indicates that cryoglobulinemia vasculitis should be considered in the differential diagnosis of purpura in patients with adult‐onset Still's disease (AOSD). Abstract The presence of purpura is suggested in adult‐onset Still's disease (AOSD) hematological complications of hemophagocytic syndrome, disseminated intravascular coagulation, or thrombotic microangiopathy. We herein report a case of AOSD complicated by cryoglobulinemia vasculitis presenting with purpura.

Kidney involvement in systemic sclerosis occurs in about 20% of cases, with scleroderma renal crisis as a significant complication. However, cases of glomerular disease with massive proteinuria are rare. We present a unique case of systemic sclerosis with the development of nephrotic syndrome. The report provides clinical details and podocyte pathological findings. A 40-year-old male with prior skin sclerosis was diagnosed with systemic sclerosis. Treatment with oral prednisone led to gradual improvement, but a year later, he experienced a systemic sclerosis renal crisis. Using the angiotensin converting enzyme (ACE) inhibitors improved kidney function. However, 3 months later, nephrotic syndrome was diagnosed. Despite an increased prednisolone dose, proteinuria persisted. A kidney biopsy revealed glomerular sclerosis and characteristic vascular changes. Immunofluorescent studies showed no deposits. Electron microscopy confirmed podocyte abnormalities.

Abstract The use of sutureless securement devices during catheterization might reduce the risk of catheter-related bloodstream infection (CRBSI) by suppressing catheter-exit infection and catheter dislodgement. However, the effectiveness of these devices in reducing CRBSI risk when securing hemodialysis catheters has not been explored. This single-center retrospective observational study examined 211 non-tunneled hemodialysis catheters (NTHCs) from 110 hemodialysis inpatients, of which 121 were secured using conventional skin sutures (Suture group) and 90 with GRIP-LOK (GRIP-LOK group). The stabilized inverse probability of treatment (SIPT)-weighting method was used to generate a new population (SIPT-weighted model) without group differences for each of the 12 predictors of CRBSI development (i.e., age, sex, dialysis history, concomitant acute kidney injury or diabetes, concurrent use of immunosuppressant drugs or aspirin, NTHC insertion site, methicillin-resistant Staphylococcus aureus, carriage, bacteremia event within 3 months before catheterization, hemoglobin level, and serum albumin titer). The effect of GRIP-LOK compared with sutures on CRBSI in the SIPT-weighted model was evaluated using univariate SIPT-weighted Cox proportional regression analysis, which showed a significant CRBSI suppression effect of GRIP-LOK compared with sutures (hazard ratio: 0.17 [95% CI 0.04–0.78], p = 0.023). GRIP-LOK affords a lower risk of CRBSI due to indwelling NTHCs than conventional securement using sutures.

Abstract Collagen type VI (COL6) deposition occurs in various glomerular diseases, causing serious pathological damage like nodular lesions. However, the mechanisms underlying the deposition of COL6 remain unclear. In renal biopsy samples, immunohistochemical analyses revealed that COL6 and phosphorylated histone H2AX (γ-H2AX), a DNA damage marker, were detected mainly in diabetic nodular glomerulosclerosis, in which the γ-H2AX-positive area was identified as the independent factor significantly associated with the COL6-positive area (β: 0.539, t = 2.668). In in vitro studies, COL6 secretion from human renal glomerular endothelial cells (HRGECs) was assessed by measuring the decrease in the cytoplasmic COL6-positive cells and an increase in the amount of COL6 in the culture medium. Mitomycin C (MMc) treatment of HRGECs increased the number of γ-H2AX-positive cells and COL6 secretion, which were suppressed by a specific inhibitor of ataxia telangiectasia and Rad3-related (ATR). MMc-induced COL6 secretion was also suppressed by Annexin A2 (ANXA2) siRNA transfection. Moreover, the inhibition of ATR activity did not induce any extra suppression in the MMc-induced COL6 secretion by ANXA2 siRNA transfected cells. These results confirm that nodular glomerulosclerosis partially results from DNA damage in the glomerulus and that DNA damage-induced COL6 secretion from HRGECs occurs through an ATR and ANXA2-mediated pathway.

DNA methylation is a common method of gene expression regulation, and this form of regulation occurs in the neurodevelopmental disorder Prader-Willi syndrome (PWS). Gene expression regulation via methylation is important for humans, although there is little understanding of the role of methylation in neuronal differentiation. We characterized the cellular differentiation potential of iPS cells derived from a patient with PWS with abnormal methylation (M-iPWS cells). A comparative genomic hybridization (CGH) array revealed that, unlike iPWS cells (deletion genes type), the abnormally methylated M-iPWS cells had no deletion in the15q11.2-q13 chromosome region. In addition, methylation-specific PCR showed that M-iPWS cells had strong methylation in CpG island of the small nuclear ribonucleoprotein polypeptide N (SNRPN) on both alleles. To assess the effect of abnormal methylation on cell differentiation, the M-iPWS and iPWS cells were induced to differentiate into embryoid bodies (EBs). The results suggest that iPWS and M-iPWS cells are defective at differentiation into ectoderm. Neural stem cells (NSCs) and neurons derived from M-iPWS cells had fewer NSCs and mature neurons with low expression of NSCs and neuronal markers. We conclude that expression of the downstream of genes in the PWS region regulated by methylation is involved in neuronal differentiation.

In coronavirus disease 2019 pneumonia, a cytokine storm resulting from an excessive inflammatory response to the viral infection is thought to play a role in the exacerbation of the pneumonia and its prognosis. Favipiravir and ciclesonide are not effective in the inhibition of the cytokine storm. In this case report, we describe the experience of tocilizumab administration and polymyxin B immobilized fiber direct hemoperfusion in severe coronavirus disease 2019 pneumonia patient. A 52-year-old man presented with fever and dyspnea and was diagnosed with coronavirus disease 2019 pneumonia based on a polymerase chain reaction test. Mechanical ventilation and favipiravir administration were started for respiratory failure. However, favipiravir could not be continued due to hepatic dysfunction. Consequently, tocilizumab was administered, and continuous hemodiafiltration and endotoxin adsorption therapy (polymyxin B immobilized fiber direct hemoperfusion) were performed for acute renal failure. C-reactive protein decreased from 44 to 3.52 mg/dL, and the patient’s respiratory status improved over time, enabling mechanical ventilation to be withdrawn. This case indicates that adding polymyxin B immobilized fiber direct hemoperfusion to tocilizumab administration may further increase efficacy in coronavirus disease 2019 treatment; however, more case–control studies are needed.

Automated driving systems are increasingly widespread in the automotive industry. To operate automobiles that are assisted by such systems, drivers must correctly understand their functionality and limitations. Hence, focusing on the rapidly spreading technology of automated braking, this study seeks to clarify the general public's understanding of automatic braking systems. A total of 210 Japanese people responded to a questionnaire regarding how automatic brakes are operated, how they work, when they disengage, and so on. The proportion of those who misunderstood the operation of the system is not especially high, but there were a certain percentage of people who had misconceptions; e.g., some believed that automatic braking could detect pedestrians or bicycles. Moreover, respondents were under the impression that drivers cannot readily disengage automatic braking systems. If they mistakenly use the automatic brake, there is a possibility of posing a risk to the road transportation system. Keywords: Automatic braking, Public understanding, Functionality limitations, Questionnaire

We report a novel missense mutation, p.Ile424Ser, in the PKD2 gene of an autosomal dominant polycystic kidney disease (ADPKD) patient with multiple liver cysts. A 57-year-old woman presented to our university hospital with abdominal fullness, decreasing appetite, and dyspnea for three months. A percutaneous drainage of hepatic cysts was performed with no significant symptomatic relief. A computed tomography (CT) scan revealed a hepatic cyst in the lateral portion of the liver with appreciable compression of the stomach. Prior to this admission, the patient had undergone three drainage procedures with serial CT-based follow-up of the cysts over the past 37 years. With a presumptive diagnosis of extrarenal manifestation of ADPKD, we performed both a hepatic cystectomy and a hepatectomy. Because the patient reported a family history of hepatic cysts, we conducted a postoperative genetic analysis. A novel missense mutation, p.Ile424Ser, was detected in the PKD2 gene. Mutations in either the PKD1 or PKD2 genes account for most cases of ADPKD. To the extent of our knowledge, this point mutation has not been reported in the general population. Our in-silico analysis suggests a hereditary likely pathogenic mutation.