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.

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.

Background/Objectives: Kidneys are fatty acid (FA)-consuming organs that use adenosine triphosphate (ATP) for tubular functions, including endocytosis for protein reabsorption to prevent urinary protein loss. Peroxisome proliferator-activated receptor α (PPARα) is a master regulator of FA metabolism and energy production, with high renal expression. Although polyunsaturated fatty acids (PUFAs) are essential nutrients that are natural PPARα ligands, their role in tubular protein reabsorption remains unclear. As clinical PUFA deficiency occurs in humans under various conditions, we used a mouse model that mimics these conditions. Methods: We administered a 2-week intraperitoneal protein-overload (PO) treatment to mice that had been continuously fed a PUFA-deficient diet. We compared the phenotypic changes with those in mice fed a standard diet and those in mice fed a PUFA-deficient diet with PUFA supplementation. Results: In the absence of PO, the PUFA-deficient diet induced increased lysosomal autophagy activation; however, other phenotypic differences were not detected among the diet groups. In the PO experimental condition, the PUFA-deficient diet increased daily urinary protein excretion and tubular lysosomes; suppressed adaptive endocytosis activation, which was probably enhanced by continuous autophagy activation; and worsened FA metabolism and PPARα-mediated responses to PO, which disrupted renal energy homeostasis. However, these changes were attenuated by PUFA supplementation at the physiological intake level. Conclusions: PUFAs are essential nutrients for the tubular adaptive reabsorption response against urinary protein loss. Therefore, active PUFA intake may be important for patients with kidney disease-associated proteinuria, especially those with various PUFA deficiency-inducing conditions.

Background/Objectives: Personalized treatment approaches are increasingly recognized as essential in the management of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), given the substantial heterogeneity in disease severity and patient characteristics. Kidney biopsy has the potential to serve as an effective tool for personalized treatment decision-making in patients with AAV. This study aimed to investigate the association of kidney biopsy with intensive immunosuppressive therapy and clinical outcomes in patients with AAV and kidney impairment. Methods: In this retrospective study, propensity score overlap weighting was applied to compare intensive immunosuppressive therapy and clinical outcomes (ESKD, death, combined ESKD and death, and infectious complications) between patients with AAV who underwent kidney biopsy and those who did not. Results: Out of 74 patients with AAV, 38 underwent kidney biopsy. Overlap weight analysis revealed that kidney biopsy was significantly associated with intensive immunosuppressive therapy (risk difference [RD], 28.9%; 95% confidence interval [CI], 0.017 to 0.562). Kidney biopsy was not associated with combined ESKD and death (RD, −0.2%; 95% CI, −0.302 to 0.298), death (RD, −3.8%; 95% CI, −0.264 to 0.189), ESKD (RD, −7.3%; 95% CI, −0.353 to 0.207), and infectious complications (RD, −25.9%; 95% CI, −0.537 to 0.020). Conclusions: In this observational cohort, kidney biopsy was associated with intensification of immunosuppressive therapy. However, after adjustment using overlap weighting, no statistically significant difference in clinical outcomes was detected, and the reduced effective sample size limited statistical power. These findings should be interpreted cautiously, as causal inference regarding the prognostic impact of kidney biopsy remains limited.