Yasuhiko Ito

Background There have been no clear recommendations regarding the optimal timing, setting, content, and duration for peritoneal dialysis (PD) education. This nationwide survey aimed to examine current PD educational practices across Japanese facilities and explore factors associated with the incidence of PD-related peritonitis. Methods Eligible facilities were institutional members of the Japanese Society for Peritoneal Dialysis. The questionnaire consisted of five sections covering facility characteristics, facility-level peritonitis profiles, PD education, peritonitis prophylaxis, and re-education. Associations between PD practices and the incidence of PD-related peritonitis were examined using linear and logistic regression analyses. Results A total of 194 facilities were included between November 2024 and May 2025. The median peritonitis incidence rates in 2023 and 2024 were 0.18 and 0.20 episodes/patient-year, respectively. Regression analyses showed that an annual training frequency of two or more sessions for education staff, earlier initiation of PD education (before catheter insertion vs. around PD initiation), more frequent visits during the first month after PD initiation (once every 1–2 weeks vs. once every 3–4 weeks), and routine patient re-education were associated with lower incidence of peritonitis or higher achievement of the target incidence rate of < 0.4 episodes/patient-year. Conclusions Regular training for patient educators, early initiation of patient education before catheter insertion, and follow-up with re-education after PD initiation were associated with lower rates of PD-related peritonitis.

Patients undergoing long‐term peritoneal dialysis (PD) frequently develop peritoneal fibrosis and angiogenesis, leading to membrane dysfunction. Transglutaminase 2 (TG2) stabilizes the extracellular matrix against proteases. In an animal model, inhibition of TG2 reduced peritoneal fibrosis, angiogenesis, and inflammation. We investigated the expression of TG2 in 163 human peritoneal membrane tissue samples, including controls, tissues exposed to conventional acidic or low‐glucose degradation product (GDP) pH‐neutral solutions, and those with peritonitis or encapsulating peritoneal sclerosis (EPS), and explored the role of TG2 in high‐glucose–induced pathophysiology in mesothelial cells. TG2 expression was upregulated in association with peritoneal membrane injury and was the highest in peritonitis. TG2 expression was correlated with peritoneal membrane thickness, CD68‐positive macrophages, and myofibroblast expression. TG2 was expressed in mesothelial cells, α‐smooth muscle actin‐positive myofibroblast expression, macrophages, and endothelial cells in the diseased state. In cultured mesothelial cells, high‐glucose–induced upregulation of collagen 1, TGF‐β1, and TG2 was suppressed by a TG2 inhibitor or by TGF‐β1 small interfering RNA. TG2 is involved in the development of peritoneal injury during PD. High‐glucose dialysate is involved in the induction of peritoneal fibrosis through the interactive regulation of TGF‐β and TG2. Targeting TG2 may offer therapeutic potential for managing PD complications and EPS.

The characteristic feature of chronic peritoneal damage in peritoneal dialysis (PD) is a decline in ultrafiltration capacity associated with pathological fibrosis and angiogenesis. The pathogenesis of peritoneal fibrosis is attributed to bioincompatible factors of PD fluid and peritonitis. Uremia is associated with peritoneal membrane inflammation that affects fibrosis, neoangiogenesis, and baseline peritoneal membrane function. Net ultrafiltration volume is affected by capillary surface area, vasculopathy, peritoneal fibrosis, and lymphangiogenesis. Many inflammatory cytokines induce fibrogenic growth factors, with crosstalk between macrophages and fibroblasts. Transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF)-A are the key mediators of fibrosis and angiogenesis, respectively. Bioincompatible factors of PD fluid upregulate TGF-β expression by mesothelial cells that contributes to the development of fibrosis. Angiogenesis and lymphangiogenesis can progress during fibrosis via TGF-β–VEGF-A/C pathways. Complement activation occurs in fungal peritonitis and progresses insidiously during PD. Analyses of the human peritoneal membrane have clarified the mechanisms by which encapsulating peritoneal sclerosis develops. Different effects of dialysates on the peritoneal membrane were also recognized, particularly in terms of vascular damage. Understanding the pathophysiologies of the peritoneal membrane will lead to preservation of peritoneal membrane function and improvements in technical survival, mortality, and quality of life for PD patients.

Background: Peritoneal dialysis (PD)-related peritonitis is a major complication of PD. Wide variations in peritonitis prevention, treatment strategies and consequences are seen between countries. These between-country differences may result from modifiable risk factors and clinical practices. Methods: A total of 1225 Japanese PD patients were included and prospectively followed in the Peritoneal Dialysis Outcomes and Practice Patterns Study phase 1 (2014–2018) and phase 2 (2018–2022). Associations between PD-related peritonitis and various risk factors were assessed by Cox proportional hazards survival models. Results: During follow-up (median 1.52 years), 539 peritonitis episodes were experienced by 364 patients. The country crude peritonitis rate was 0.27 episodes/patient-year. In the fully adjusted model, noticeable patient-level factors associated with experiencing any peritonitis included age {hazard ratio [HR] 1.07 per 5-year increase [95% confidence interval (CI) 1.01–1.14]}, serum albumin level [HR 0.63 per 1 g/dl higher (95% CI 0.48–0.82)] and continuous ambulatory peritoneal dialysis (PD) [HR 1.31 versus automated PD (95% CI 1.05–1.63)]. The adoption of antibiotic prophylaxis practice at the time of PD catheter insertion [HR 0.63 (95% CI 0.51–0.78)] or when having complicated dental procedures [HR 0.74 (95% CI 0.57–0.95)] or lower endoscopy [HR 0.69 (95% CI 0.54–0.89)] were associated with lower hazards of any peritonitis, while a routine facility practice of having more frequent regular medical visits was associated with a higher hazard. Conclusion: Identification of risk factors in Japan may be useful for developing future versions of guidelines and improving clinical practices in Japan. Investigation of country-level risk factors for PD-related peritonitis is useful for developing and implementing local peritonitis prevention and treatment strategies

This review outlines the epidemiology, characteristics, risk factors, and prognosis of peritoneal dialysis (PD)-related peritonitis, PD catheter-related infections, and the effects of assisted PD in elderly patients from the Japanese perspective. Based on the literature, the incidence of peritonitis is likely to be higher in elderly patients than in younger patients. The most frequent causative bacteria in elderly patients are Gram-positive bacteria, as in adult PD patients, most commonly due to transcatheter infection. However, elderly patients may have difficulty recognizing cloudy drainage fluid due to decreased visual acuity. Hypokalemia, the use of gastric acid suppressants, prophylactic antibiotic use before endoscopy, biocompatible fluids and hypoalbuminemia considered modifiable risk factors for peritonitis. However, the mechanism by which treatment of hypokalemia prevents peritonitis is unknown. Currently, the relationship between gastric acid suppression therapy and peritonitis in elderly patients is debatable, with no evidence to strongly recommend uniform discontinuation of gastric acid suppression therapy. Exit-site infection (ESI) is a major risk factor for the development of peritonitis, and appropriate prevention and management of ESI may reduce infection-related hospitalizations in PD patients. Currently, no randomized, controlled trials have verified the effectiveness of antibiotic application for ESI in Japan, but results from other countries are awaited. In assisted PD, it is extremely important that family members, caregivers, and nurses who support the procedure receive sufficient education and training from medical professionals familiar with PD. Early detection and treatment of PD-related infections are required because the risk of death increases in elderly patients.

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.

Peritoneal membrane dysfunction in peritoneal dialysis (PD) is primarily attributed to angiogenesis; however, the integrity of vascular endothelial cells can affect peritoneal permeability. Hyaluronan, a component of the endothelial glycocalyx, is reportedly involved in preventing proteinuria in the normal glomerulus. One hypothesis suggests that development of encapsulating peritoneal sclerosis (EPS) is triggered by protein leakage due to vascular endothelial injury. We therefore investigated the effect of hyaluronan in the glycocalyx on peritoneal permeability and disease conditions. After hyaluronidase-mediated degradation of hyaluronan on the endothelial cells of mice, macromolecules, including albumin and β2 microglobulin, leaked into the dialysate. However, peritoneal transport of small solute molecules was not affected. Pathologically, hyaluronan expression was diminished; however, expression of vascular endothelial cadherin and heparan sulfate, a core protein of the glycocalyx, was preserved. Hyaluronan expression on endothelial cells was studied using 254 human peritoneal membrane samples. Hyaluronan expression decreased in patients undergoing long-term PD treatment and EPS patients treated with conventional solutions. Furthermore, the extent of hyaluronan loss correlated with the severity of vasculopathy. Hyaluronan on endothelial cells is involved in the peritoneal transport of macromolecules. Treatment strategies that preserve hyaluronan in the glycocalyx could prevent the leakage of macromolecules and subsequent related complications.

We present a single-center retrospective analysis of 228 Japanese patients with peritoneal dialysis, in which we examined whether reduced left ventricular ejection fraction (LVEF) is a risk factor for peritonitis development. Time-dependent multivariable-adjusted Cox proportional hazards models revealed that reduced LVEF (LVEF < 50% vs. preserved LVEF ≥ 50%, hazard ratio (HR) 2.10; 95% confidence interval (CI) 1.16–3.82) was associated with peritonitis. Qualitatively, similar associations with reduced LVEF (< 50%) were observed for enteric peritonitis (adjusted HR 7.68; 95% CI 2.51–23.5) but not for non-enteric peritonitis (adjusted HR 1.15; 95% CI 0.54–2.44). Reduced LVEF is associated with a significantly higher risk of subsequent peritonitis, particularly enteric peritonitis. These results indicate that patients with reduced LVEF may be at risk of enteric peritonitis from bowel sources caused by intestinal involvement due to cardiac dysfunction.

Key Points: In a large multinational cohort of PD patients, any GAS use was not associated with an increased risk of all-organism peritonitis. For peritonitis, risks were particularly high among certain classes of organisms particularly for Gram-negative, enteric, and streptococcal peritonitis episodes. The association with enteric peritonitis appeared to be stronger among H2RA users. Background: Peritonitis is a major peritoneal dialysis–related complication. We determined whether gastric acid suppression (GAS) (proton pump inhibitor [PPI] or histamine-2 receptor antagonists [H2RAs]) use was associated with all-cause and organism-specific peritonitis in peritoneal dialysis patients. Methods: In the Peritoneal Dialysis Outcomes and Practice Patterns Study (595 facilities, eight countries, years 2014–2022), associations between GAS use and time to first episode of all-cause peritonitis were examined using Cox proportional hazards models. The primary exposure of interest was GAS and secondarily PPI or H2RA use. Secondary outcomes were organism-specific peritonitis, peritonitis cure rates, and death. Results: Among patients (N=23,797) at study baseline, 6020 (25.3%) used PPIs, and 1382 (5.8%) used H2RAs. Overall risks of GAS use and peritonitis risk (adjusted hazard ratio [AHR]=1.05, 95% confidence interval [CI], 0.98 to 1.13]) and use of PPI (AHR 1.06 [95% CI, 0.99 to 1.14]) or H2RA (AHR 1.02 [95% CI, 0.88 to 1.18]) did not reach statistical significance. In organism-specific analyses, GAS users displayed higher peritonitis risks for Gram-negative (AHR 1.29, 95% CI, 1.05 to 1.57), Gram-positive (AHR 1.15, 95% CI, 1.01 to 1.31), culture-negative (AHR 1.20, 95% CI, 1.01 to 1.42), enteric (AHR 1.23, 95% CI, 1.03 to 1.48), and particularly Streptococcal (AHR 1.47, 95% CI, 1.15 to 1.89) peritonitis episodes. GAS was also associated with higher overall mortality (AHR 1.13 [95% CI, 1.05 to 1.22]). Conclusion: The association between GAS use and peritonitis risk was weaker (hazard ratio [HR] 1.05 [0.98 to 1.13]) than for streptococcal (HR 1.57 [1.15 to 1.89]) and Gram-negative (HR 1.29 [1.05 to 1.57]) peritonitis. A better understanding of mechanisms surrounding the differential effects of GAS subtype on peritonitis risks is needed. Clinicians should be cautious when prescribing GAS. The impact of GAS deprescribing on peritonitis risk requires further evaluation.