Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Journal of Molecular Sciences  

In peritoneal dialysis (PD) patients, fungi and Pseudomonas aeruginosa are considered important causative microorganisms for peritonitis with poor prognosis. Our objective was to explore expressions of membrane complement (C) regulators (CRegs) and tissue injuries in the peritoneum of patients with PD-related peritonitis, including fungal and Pseudomonas aeruginosa peritonitis. In peritoneal biopsy tissues obtained at PD catheter removal, we investigated the severity of peritonitis-associated peritoneal injuries and the expression of CRegs, CD46, CD55, and CD59 against peritoneal tissues without any episode of peritonitis. In addition, we evaluated peritoneal injuries among fungal and Pseudomonas aeruginosa-peritonitis (P1) and Gram-positive bacterial peritonitis (P2). We also observed deposition of C activation products such as activated C and C5b-9 and measured sC5b-9 in the PD fluid of patients. As a result, the severity of peritoneal injuries correlated inversely with the expression of peritoneal CRegs. Peritoneal CReg expression in peritonitis was significantly reduced compared to no peritonitis. Peritoneal injuries were more severe in P1 than in P2. CReg expression was further decreased and C5b-9 further increased in P1 than in P2. In conclusion, severe peritoneal injuries due to fungal and Pseudomonas aeruginosa-peritonitis decreased CReg expression and increased deposition of activated C3 and C5b-9 in the peritoneum, suggesting that peritonitis, particularly fungal and Pseudomonas aeruginosa-peritonitis, might induce susceptibility to further peritoneal injuries due to excessive C activation.

DOI： 10.3390/ijms24119146

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Scopus

PubMed

Publisher：Renal Replacement Therapy  

Background: Japanese peritoneal dialysis (PD) guidelines do not suggest applying mupirocin/gentamicin ointment to the exit sites of PD patients to prevent exit-site infection (ESI). The guidelines do not mention topical antimicrobials as a treatment for ESI. Methods: We retrospectively investigated the additional use of topical antibiotic ointments on patients receiving oral or intravenous antibiotics for recurrent and/or refractory ESI at Aichi Medical University and Nagoya University Hospitals between 2017 and 2022. Results: A total of 13 patients (11 men, 2 women) were included in this study. Median age was 69.0 years, median duration of PD was 26.0 months, two patients had diabetes as a complication, and ESI incidence was 2.7 episodes per patient-year. Systemic antibacterial treatment had been administered for a median of 27.0 days before application therapy. Mupirocin was used in eight cases and gentamicin in five cases, with complete resolution in all cases. No adverse effects such as skin symptoms, antibiotic resistance, or non-tuberculous mycobacterial infections were observed. Cases were divided into two groups based on the duration of topical antibiotic use: short-term group < 90 days and long-term group ≥ 90 days. All patients in both groups achieved complete resolution, with no significant differences in time to resolution, number of recurrent ESIs, or occurrence of ESIs after discontinuation of application therapy. Conclusion: Additional use of topical antibiotic for recurrent and/or refractory ESI appears safe and effective. This study suggests that future randomized controlled trials are warranted.

DOI： 10.1186/s41100-024-00547-x

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Scopus

Language：English   Publisher：Clinical and Experimental Immunology  

Peritonitis and the resulting peritoneal injuries are common problems that prevent long-term peritoneal dialysis (PD) therapy in patients with end-stage kidney diseases. Previously, we have analyzed the relationship between the complement system and progression of peritoneal injuries associated with PD, particularly focusing on the early activation pathways and effects of the anaphylatoxins. We here utilized a novel mAb 2H2 that blocks assembly of the membrane attack complex (MAC) to investigate roles of the complement terminal pathway in PD-associated peritoneal injury. We intraperitoneally injected mAb 2H2 anti-C5b-7 (2.5 or 5 mg/rat) once or twice over the five-day course of the experiment to investigate the effects of inhibiting formation of MAC in a fungal rat peritonitis model caused by repeated intraperitoneal administration of zymosan after methylglyoxal pretreatment (Zy/MGO model). Rats were sacrificed on day 5 and macroscopic changes in both parietal and visceral peritoneum evaluated. Peritoneal thickness, the abundance of fibrinogen and complement C3 and MAC deposition in tissue and accumulation of inflammatory cells were pathologically assessed. The results showed that mAb 2H2, but not isotype control mAb, reduced peritoneal thickness and accumulation of inflammatory cells in a dose and frequency-dependent manner in the Zy/MGO model. These effects were accompanied by decreased C3, MAC, and fibrinogen deposition in peritoneum. In conclusion, in the rat Zy/MGO model, complement terminal pathway activation and MAC formation substantially contributed to development of peritoneal injuries, suggesting that MAC-targeted therapies might be effective in preventing development of peritoneal injuries in humans.

DOI： 10.1093/cei/uxad088

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PubMed

DOI： 10.1016/j.imbio.2023.152470

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Language：English   Publisher：CEN Case Reports  

Fibrillary glomerulonephritis (FGN), a rare disease is pathologically characterized by glomerular fibril accumulation ranging from 12 to 24 nm in diameter with negative Congo red staining. Recently, the identification of DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sensitive and specific marker for FGN has revolutionized diagnosis of this disease. However, few recent studies have reported DNAJB9-negative glomerulonephritis with fibrillar deposits. As such, it remains unclear whether DNAJB9-negative cases can be considered equivalent to FGN. Here, we report the case of a 70-year-old woman who developed renal impairment and nephrotic-range proteinuria. Renal biopsy and pathological examination revealed focal glomerulonephritis with fibrocellular crescents. Immunofluorescence microscopy showed IgA-dominant deposition of polytypic IgG in the glomerulus. Electron microscopy revealed hump-like subepithelial electron dense deposits with fibrils of 15–25 nm in diameter. These findings were consistent with FGN; thus, Congo red and direct fast scarlet (DFS) staining, and immunohistochemistry for DNAJB9 were performed. In addition to negative Congo red/DFS/DNAJB9 staining, laser microdissection (LMD) and liquid chromatography-tandem mass spectrometry (LC–MS/MS) resulted negative for DNAJB9, which is a highly sensitive and specific marker for FGN. The patient’s renal function further declined, prompting administration of rituximab weekly for 2 weeks, similar to the treatment for FGN. This is a unique case of IgA-dominant glomerulonephritis with DNAJB9-negative fibrillar polytypic immunoglobulin deposits in the subepithelium, unlike previous DNAJB9-negative cases. Thus, DNAJB9-negative cases diagnosed based on accurate electron microscopic evaluation must be gathered, and LMD and LC–MS/MS must be used to analyze the organized fibrillar deposits to reveal the disease entity.

DOI： 10.1007/s13730-022-00759-2

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PubMed

Language：Japanese Book type：Textbook, survey, introduction

Event date： 2021.6

Language：Japanese   Presentation type：Poster presentation  

Venue：神奈川   Country：Japan  

Event date： 2018.9

Language：English   Presentation type：Poster presentation  

Venue：Santa Fe, New Mexico   Country：United States  

Event date： 2017.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福島県   Country：Japan