As classical agonists for peroxisomal proliferator-activated receptor alpha (PPARα), fibrates activate renal fatty acid metabolism (FAM) and provide renoprotection. However, fibrate prescription is limited in patients with kidney disease, since impaired urinary excretion of the drug causes serious adverse effects. Pemafibrate (PEM), a novel selective PPARα modulator, is mainly excreted in bile, and, thus, may be safe and effective in kidney disease patients. It remains unclear, however, whether PEM actually exhibits renoprotective properties. We investigated this issue using mice with fatty acid overload nephropathy (FAON). PEM (0.5 mg/kg body weight/day) or a vehicle was administered for 20 days to 13-week-old wild-type male mice, which were simultaneously injected with free fatty acid (FFA)-binding bovine serum albumin from day 7 to day 20 to induce FAON. All mice were sacrificed on day 20 for assessment of the renoprotective effect of PEM against FAON. PEM significantly attenuated the histological findings of tubular injury caused by FAON, increased the renal expressions of mRNA and proteins related to FAM, and decreased renal FFA content and oxidative stress. Taken together, PEM exhibits renoprotective effects through the activation and maintenance of renal FAM and represents a promising drug for kidney disease.

Sulfatides are glycosphingolipids that are associated with coagulation and platelet aggregation. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) activates platelet function and often leads to thrombotic complications. These facts suggest an association between serum sulfatides and AAV. We aimed to clarify the significance of serum sulfatide levels in patients with AAV. We conducted a retrospective, single-center, observational pilot study that included 35 patients who developed AAV and 10 control patients who were candidates for living-donor kidney transplantation. We compared serum sulfatide levels between the control and AAV patients. We analyzed the differences in serum sulfatide levels among four classes (focal, crescentic, mixed, and sclerotic class) of glomerular lesions that were categorized by histopathologic classification of ANCA-associated glomerulonephritis. Serum sulfatide levels in patients with AAV were significantly lower than those in the controls. Serum sulfatide levels were significantly different between the four classes. Additionally, serum sulfatide levels in the crescentic class were significantly lower than those in the other classes. Serum sulfatide levels were significantly correlated with albumin, cholesterol, C-reactive protein, and pentraxin 3. In conclusion, serum sulfatide levels are significantly correlated with inflammation, reflecting crescentic glomerulonephritis, which is an active glomerular lesion in AAV patients.

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) can occasionally trigger thrombotic microangiopathy (TMA). Cytomegalovirus (CMV) may be reactivated during intensive immunosuppressive therapy for AAV and cause TMA. Therefore, we aimed to evaluate the clinical features of and the association between vascular endothelial injury markers and TMA due to CMV in patients with AAV. A 61-year-old female was diagnosed with AAV and severe kidney injury. Immunosuppressive therapy gradually improved her symptoms and laboratory findings. However, 2 weeks after induction therapy initiation, she exhibited altered consciousness, a significant decrease in platelet count, and hemolytic anemia, resulting in a TMA diagnosis. Plasma exchange did not improve TMA findings and routine screening test revealed CMV infection. Ganciclovir injection improved the infection and TMA findings. Consequently, we diagnosed her with CMV-induced TMA. Both AAV and CMV may induce severe vascular endothelial injury, potentially leading to TMA development. CMV-induced TMA should be considered when TMA develops during induction therapy against AAV. Moreover, of the three serum markers of vascular injury—serum sulfatides, soluble thrombomodulin, and pentraxin 3—serum sulfatides may be associated with the development of TMA, and a high level of soluble thrombomodulin may be associated with the development of CMV viremia during the clinical course of AAV.

We aim to elucidate factors to aid in the prediction of cytomegalovirus viremia during the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We conducted a single-center, retrospective, observational study of 35 patients with newly diagnosed AAV. Factors associated with the development of CMV viremia were investigated via a logistic regression analysis. The CMV antigenemia test was performed in 25 patients (71%), of whom 15 (60%) were diagnosed with CMV viremia. Of these 15 patients, 5 developed a CMV infection. The total protein, hemoglobin, platelet count and lymphocyte counts at the time of the CMV antigenemia test were significantly lower in patients who developed CMV viremia. In addition, total protein, hemoglobin, platelet count and lymphocyte count also presented significantly decreasing trends in the following order: patients who did not develop CMV viremia, patients who developed CMV viremia without any symptoms, and patients who developed CMV infection. All patients with CMV recovered. In conclusion, the total protein, hemoglobin, platelet count and lymphocyte count may be useful markers for the prediction of CMV viremia and infection after the start of induction of immunosuppressive therapy for patients with AAV.

Background and Aims: Hepatitis C virus (HCV) infection remains a global public health concern, with many carriers remaining undiagnosed because of its asymptomatic nature. Although Japan was previously considered to be on track for national HCV elimination by 2030, recent global modeling studies and updated elimination dashboards indicate that Japan is currently not on track. This underscores the importance of locally coordinated efforts to detect residual cases. Micro‐elimination has recently emerged as a pragmatic and scalable approach by targeting defined populations or geographic areas. The Nagawa Project sought to identify HCV positive individuals through community‐wide screening and directing viremic cases to appropriate direct‐acting antiviral (DAA) therapy. The present study describes the implementation and outcomes of this cohort‐based HCV micro‐elimination strategy. Methods: All 5027 adult residents of Nagawa town, Japan, aged ≥ 20 years were prospectively targeted for HCV antibody testing through routine health check‐ups, outpatient visits, and mailed invitations between June 2021 and March 2024. HCV Antibody positive individuals underwent additional HCV core antigen testing to confirm viremia. Results: A total of 3121 residents (62.1%) underwent HCV antibody testing. Testing rates were significantly higher in early‐stage elderly (65–74 years; 73.7%) residents than in both adult (20–64 years; 54.5%) ( p < 0.001) and late‐stage elderly (≥ 75 years; 66.7%) ( p < 0.001) residents. Twenty‐eight individuals (0.897%) were HCV antibody positive, with three cases (0.096%) confirmed as viremic. Antibody positivity was significantly higher in late‐stage elderly residents (1.91%; p < 0.001 vs. adult and p = 0.031 vs. early‐stage elderly residents). Two viremic individuals received DAA therapy and achieved a sustained virological response. After adjusting for age and sex by propensity score matching, no significant difference in overall survival was observed between HCV antibody positive and negative individuals. Conclusion: The Nagawa Project illustrates the success of a locally coordinated HCV micro‐elimination approach. It offers a practical framework for identifying and managing residual HCV infections, contributing to progress toward Japan's alignment with the World Health Organization's 2030 HCV elimination goals.

A 93‐year‐old hemodialysis patient became hospitalized for thiamine deficiency‐induced appetite loss and ultimately experienced consciousness disorder diagnosed as Wernicke's encephalopathy (WE). Since brain MRI on admission was retrospectively found to display faint WE findings, careful brain MRI assessment is recommended in hemodialysis patients with appetite loss alone.