Pathophysiology of encapsulating peritoneal sclerosis: lessons from findings of the past three decades in Japan.

Encapsulating peritoneal sclerosis (EPS), a condition with a high mortality rate, is a serious complication of peritoneal dialysis (PD). In Japan, EPS became a central issue in the clinical setting during the mid-90s and the beginning of this century. However, following the introduction of biocompatible neutral PD solutions containing lower levels of glucose degradation products, the incidence and clinical severity of EPS has been greatly lessened. During the past three decades, the etiology of EPS has been elucidated by findings obtained by peritoneal biopsy, laparoscopy, and surgical intervention. Accumulating findings suggest the need for a paradigm change on the nature of EPS pathophysiology; notably, EPS appears not to reflect peritoneal sclerosis per se, but rather the formation of a neo-membrane as a biological reaction to peritoneal injury. This narrative review looks back on the history of EPS in Japan, and discusses EPS pathophysiology, the impact of neutral PD solution on peritoneal protection, and a future novel diagnostic approach, ultra-fine endoscope, for the identification of patients at high risk of EPS.

Pitavastatin Compared with Differential Intervention Trial by Standard Therapy on Cardiovascular Events in Patients with Dyslipidemia on Chronic Hemodialysis (DIALYSIS): A Randomized Controlled Trial.

INTRODUCTION: Statin has been reported to reduce cardiovascular events. However, the comparative efficacy of statin with standard therapy on cardiovascular events has not been sufficiently reported in patients on chronic hemodialysis. Thus, this study aimed to compare the effects of pitavastatin and standard therapy on mortality and cardiovascular events in chronic hemodialysis patients with dyslipidemia in Japan. METHODS: Patients on chronic hemodialysis with dyslipidemia were randomized into pitavastatin-administered (pitavastatin group) or dietary therapy as standard therapy (control) group. Primary outcomes are all-cause mortality and myocardial infarction; secondary outcomes are cardiac arrest and fatal myocardial infarction. The composite outcomes included the incidence of coronary intervention, stroke, fracture, and hospitalization due to heart failure and unstable angina. The clinical outcome analyses used a logistic regression model to categorize the variables. A p value of <0.05 was considered statistically significant. RESULTS: This study included 848 patients (422 in the control group and 426 in the pitavastatin group) from 79 health facilities. The mean age of the patients was 60.1±10.3 years, and the dialysis period was 7.2±7.6 years. The mean observation period was 36.5 months. The low-density lipoprotein cholesterol level was significantly lower than the baseline value in the pitavastatin group after 12 months of trial (79.8±26.1 vs. 107.8±25.5 mg/dL, p < 0.001). Moreover, the total number of deaths was 85, of which 50 occurred in the control group and 35 in the pitavastatin group. In an analysis adjusted for confounding factors due to participant attributes, there was a significant difference between the control group and the pitavastatin group in the primary and composite endpoints (p = 0.007 and p = 0.022, respectively). CONCLUSION: Our study has demonstrated that aggressive intervention with pitavastatin is more effective than the standard (dietary) therapy for improving the clinical outcomes in patients with dyslipidemia on chronic hemodialysis.

Relationship between laparoscopic and microscopic findings of peritoneum in peritoneal dialysis patients.

Long-term exposure to the peritoneal dialysis solution (PDS) causes functional and morphological alterations that diminish the efficacy of peritoneal dialysis (PD). Macroscopic and microscopic findings, submesothelial compact zone (SMC) thickness and vascular patency, were associated with PD duration. The relationship between microscopic and laparoscopic morphological findings in PD patients was determined. A total of 78 laparoscopic intraperitoneal findings were recorded during PD catheter removal and 45 peritoneal tissues were obtained from the anterior parietal peritoneum. We examined macroscopic morphological findings in both parietal and visceral peritoneums and bowel movement and assessed the score semiquantitatively. SMC thickness and vascular patency were examined as microscopic findings. Total laparoscopic finding's score (LFS) and microscopic findings, SMC thickness and vascular patency, were associated with PD duration. Total LFS was related to SMC thickness in both visceral and parietal peritoneum, whereas it was related to vascular patency in parietal but not in visceral peritoneum. There was no relationship between microscopic findings and peritoneal surface color, properties, vasculopathy, and adhesion. Total LFS in patients with newly formed membrane and omentum atrophy was higher than in those without. There was a significant relationship between microscopic and laparoscopic findings in PD patients. It is important to evaluate laparoscopic findings in more PD patients to find the predictive findings of encapsulating peritoneal sclerosis development.

The Influence of an Unexpected Switch of Hemodialysis Facilities on the Quality of Life (QOL) in Hemodialysis Patients.

Background: We experienced a sudden breakdown of hemodialysis system during a clinical study of dermal itch and serum BNP concentrations. Patients and Methods: Forty-eight hemodialysis patients were enrolled in the itch-related study. It was intended to improve itch by lowering BNP with supportive communication between the patients and the dialysis staff. We planned to collect data, including visual analogue scale (VAS), dermatology life quality index (DLQI), blood samples and QOL score (KDQOL-SF), four times over a four week interval. The first data was obtained just prior to switching facilities due to a breakdown. The patients underwent hemodialysis in other facilities for two weeks and underwent determination of their clinical data, including QOL scores, three times. Results: While mean blood pressure showed no significant differences, serum albumin, iron and phosphate levels were worsened significantly between pre- and post-relocation. Serum BNP and DLQI showed no significant changes. VAS was significantly worsened. The mean values of the cognitive function in the KDQOL-SF and sleep and the role-physical, role-emotional, social function, dialysis staff's encouragement in SF-36 analysis were identified as statistically significant items by MANOVA. Both SF-12 physical and mental composites were also statistically significant. Although SF-12 physical composites were significant among the patients under 66 yrs of age (median), eight factors were significant among those over 66 yrs. Independent analyses revealed every item that was detected worsened significantly after the switch of facilities. Conclusion: Unexpected switching of hemodialysis facilities severely impacts the QOL for a long duration as well as the patients' symptom and laboratory data.

An association between subcutaneous fat mass accumulation and hypertension.

Evidence to assess relationships between subcutaneous fat area (SFA) and lifestyle-related diseases, including hypertension, remains limited. The aim of this study was to investigate the relationship between SFA and hypertension. This study was a single-institution, cross-sectional study of 1,899 eligible Japanese participants who underwent health checkups between December 2016 and December 2018. All patients were measured for SFA and visceral fat area (VFA) by abdominal computed tomography (CT). SFA was divided into quartiles by gender, and multivariate logistic regression analysis was performed to estimate associations between SFA quartiles (Q) and hypertension. Mean age and SFA were 60.9 9 (standard devastation [SD]:12.0) years and 123.0 (56.9) cm2 in men, and 60.6 (12.8) years and 146.6 (79.0) cm2 in women, respectively. Risk of hypertension from multivariate regression modeling compared with the lowest quartile (Q) in both sexes was as follows: for men Q2 [odds ratio (OR), 1; 95% confidence interval (CI), 0.55-1.51 ], Q3 (OR, 1.73; 95%CI, 1.17-2.56), and Q4 (OR, 1.96; 95%CI, 1.31-2.94); for women Q2 (OR, 0.87; 95%CI, 0.48-1.58), Q3 (OR, 1.73; 95%CI, 1.02-2.95), and Q4 (OR, 2.54; 95%CI, 1.51-4.28). The optimal SFA cutoff value at risk of hypertension was 114.7 cm2 in men and 169.3 cm2 in women. The prevalence of hypertension was positively associated with SFA quartiles in both genders. The present results may indicate the necessity of considering not only VFA, but also SFA for the primary and secondary prevention of hypertension.

An association between visceral or subcutaneous fat accumulation and diabetes mellitus among Japanese subjects.

BACKGROUND: The impact of subcutaneous fat accumulation remains controversial. This study assessed the association between visceral or subcutaneous fat area (VFA and SFA, respectively) and diabetes mellitus (DM) among Japanese subjects. METHODS: This was a cross-sectional study involving 1907 eligible participants (men, 1050; women, 857) who participated in a voluntary health check-up conducted at Juntendo University Hospital from January 2017 to December 2018, in Tokyo, Japan. Associations between VFA or SFA quartiles and DM were identified using adjusted odds ratios (AORs) and 95% confidence intervals (CIs) with multivariable logistic regression analysis adjusted for confounders. Receiver operating characteristic (ROC) curve analysis was used to assess appropriate cut-off values of VFA or SFA. RESULTS: Multivariate analyses showed that Q4 (≥ 125 cm2) of VFA was significantly positively associated with DM compared to Q1 (< 65 cm2) (AOR = 1.94, 95% CI 1.02-3.71), whereas there was no association between SFA and DM in men. Among women, Q4 (≥ 85 cm2) of VFA was significantly positively associated with DM compared to Q1 (< 30 cm2) (Q4, AOR = 6.15, 95% CI 1.65-22.99). Also, Q3 and Q4 (≥ 135 cm2) of SFA were significantly positively associated with DM compared to Q1 (< 90 cm2) (Q3, AOR = 5.64, 95% CI 1.21-26.25; Q4, AOR = 7.81, 95% CI 1.71-35.65). The appropriate cut-off value of VFA in men was 101.5 cm2. Those of VFA and SFA in women were 72.5 cm2 and 165.3 cm2, respectively. CONCLUSIONS: Our results suggest the importance of considering SFA as well as VFA, especially in women, for primary and secondary prevention of DM.

Recent Understanding of Peritoneal Pathology in Peritoneal Dialysis Patients in Japan.

The thin peritoneum covering the peritoneal cavity has been used as a dialysis membrane for peritoneal dialysis (PD) because it is highly vascularized and has a large body surface area. However, it has been reported that peritoneal membranes affected by peritonitis, as well as those exposed to the nonphysiological high glucose levels containing PD dialysate, may undergo histological and functional changes. Patients undergoing PD may experience encapsulating peritoneal sclerosis (EPS), which is a life-threatening serious complication of PD that can significantly impair activities of daily living. The incidence of EPS was 1.4-7.3% of maintenance PD patients in the 1980s. The incidence has improved to 1.0% after a neutral dialysate became the standard PD treatment in Japan. Furthermore, the pathogenesis of EPS is uncertain although its onset may be explained by the "two-hit theory," in which some factors leading to impairment had an additive effect on simple peritoneal sclerosis. The evaluation of histopathological findings has shown the impact of the neutral dialysate on peritoneal deterioration as well as its role in the development of functional changes. In the present report, we discuss the advances in the understanding of peritoneal deterioration based on histological and macroscopic evaluations of the peritoneum of patients undergoing PD. We also discuss the recent treatment for PD patients.

A disposable, ultra-fine endoscope for non-invasive, close examination of the intraluminal surface of the peritoneal dialysis catheter and peritoneal cavity.

The ability to visualize intraluminal surface of peritoneal dialysis (PD) catheter and peritoneal cavity could allow elucidation of the cases of outflow problems, and provide information on changes to the peritoneal membrane leading to encapsulating peritoneal sclerosis. A non-invasive examination that allows those monitoring in need is desirable. We have developed a disposable ultra-fine endoscope that can be inserted into the lumen of the existing PD catheter, allowing observation of the luminal side of the catheter and peritoneal cavity from the tip of the PD catheter, with minimum invasion in practice. In a pre-clinical study in pigs and a clinical study in 10 PD patients, the device provided detailed images, enabling safe, easy observation of the intraluminal side of the entire catheter, and of the morphology and status of the peritoneal surface in the abdominal cavity under dwelling PD solution. Since this device can be used repeatedly during PD therapy, clinical application of this device could contribute to improved management of clinical issues in current PD therapy, positioning PD as a safer, more reliable treatment modality for end-stage renal disease.

A nationwide observational study of locomotive syndrome in Japan using the ResearchKit: The Locomonitor study.

BACKGROUND: We developed the Locomonitor application (app), the world's first iOS app to study locomotive syndrome, using the ResearchKit and examined the prevalence and risk factors for locomotive syndrome in Japanese general individuals 20-69 years old in a nationwide cross-sectional observational study. METHODS: The participants were recruited from February to August 2016. The outcome measures for the locomotive function were evaluated by locomotive syndrome risk tests (LSRTs) using the Locomonitor app. The chi-squared test, a linear-by-linear association trend analysis, and Spearman's correlation test were performed as statistical analyses. RESULTS: A total of 2177 subjects from all prefectures in Japan were included (average 42.2 years old). The Locomo25 and Stand-Up test scores in female participants and the Two-Step test scores in male participants showed age-dependent deterioration. In the overall population, the incidence of Locomo stage 1 and 2, as evaluated by the Locomo25, Stand-Up test or Two-Step test, was 30.2% and 29.2%, respectively. In subjects without locomotive syndrome (40.5%), LSRT scores showed age-dependent deterioration in both sexes. Locomotive syndrome in participants with a body mass index (BMI) of ≥25 kg/m2 was more frequent than in those with a BMI of <25 kg/m2 (age- and gender-adjusted odds ratio [OR] 1.344 [95% confidence interval {CI} 1.03-1.75, p = 0.027]). Locomotive syndrome in participants with an exercise habit was less frequent than in those without an exercise habit (age- and gender-adjusted OR 0.499 [95% CI 0.33-0.755, p < 0.0001]). CONCLUSIONS: The Locomonitor app, a newly developed remote platform, revealed that approximately 20%-30% of Japanese individuals 20-69 years old in the general population met the definition of locomotive syndrome. Locomotive syndrome in participants with obesity was more frequent than those without obesity, while locomotive syndrome in participants with an exercise habit was less frequent than those without an exercise habit.

Effects of long-term treatment with low-GDP, pH-neutral solutions on peritoneal membranes in peritoneal dialysis patients.

BACKGROUND: The morphological changes induced by bio-incompatible peritoneal dialysis (PD) solutions are well known. However, the morphological damage induced by long-term low-glucose degradation product (GDP), pH-neutral solutions has not been reported in detail. The aim of this study was to investigate the long-term effects of pH-neutral PD solutions on morphological and functional changes in the peritoneal membrane. METHODS: We assessed peritoneal membrane biopsy samples from PD patients treated with acidic (Conventional group) or pH-neutral solutions (pH-neutral group) using pathology and immunopathology techniques. RESULTS: Analyses of 54 Conventional and 73 pH-neutral group samples showed that the peritoneal membrane was thicker (P < 0.001), the ratio of luminal diameter to vessel diameter (L/V ratio) was significantly smaller (P < 0.001), and advanced glycation end-product (AGE) accumulation was higher in the Conventional than in the pH-neutral group (P < 0.001). Comparison of samples from patients in the Conventional (n = 33) and pH-neutral groups (n = 33) who were treated for 4-10 years also showed significant differences in peritoneal thickness, L/V ratio and AGE score. Furthermore, the L/V ratio in the Conventional group significantly decreased over time (P < 0.01); however, no such change was seen in the pH-neutral group. Peritoneal membrane thickness was not associated with PD duration in both groups. Dialysate-to-plasma ratio of creatinine and L/V ratio negatively correlated with PD treatment duration in the Conventional group, but not in the pH-neutral group. CONCLUSIONS: These findings suggest that pH-neutral solutions prevent the morphological and functional peritoneal changes induced by long-term PD treatment.

Morphologic characteristics of macroscopic peritoneal finding in patients with peritoneal dialysis.

Peritoneal dialysis (PD) has been an attractive treatment for end-stage kidney disease. Long-term exposure to the PD solution creates functional and morphological alterations, and these alterations diminish the efficacy of PD. It is important to establish an evaluation of the changes in PD patients and strategies for the prevention of PD damage and encapsulating peritoneal sclerosis (EPS). We determined the relationship between clinical findings and macroscopic morphological findings by laparoscopy in patients receiving PD. Macroscopic intraperitoneal findings were recorded at the PD catheter removal in 23 PD patients. We examined macroscopic morphological findings such as fibrin deposition, peritoneal turbidity, vasculopathy, adhesion and calcification in both parietal and visceral peritoneum of upper and lower peritoneal cavities, and assessed the score semi-quantitatively. We then evaluated the relationship between the morphological score and clinical findings, especially observational parts and findings in EPS patients. The total macroscopic score increased with PD duration. Peritoneal turbidity, fibrin deposition, and calcification were observed in the whole peritoneal cavity. Scores of fibrin deposition, turbidity, and calcification increased with PD duration. Vasculopathy in the parietal peritoneum was more serious compared with that in the visceral peritoneum, but there was no difference in the vasculopathy between the upper and lower areas. A characteristic of the macroscopic findings in EPS patients was peritoneal calcification in this study. It appears that macroscopic findings using laparoscopy is significant in evaluating the degree of the peritoneum damage and predicting EPS development.

Hydroxyhomocitrulline Is a Collagen-Specific Carbamylation Mark that Affects Cross-link Formation.

Carbamylation is a non-enzymatic post-translational modification that physiologically occurs during aging and is a risk factor for various diseases. The most common product of carbamylation is homocitrulline (HCit), where a lysine (Lys) amino group has reacted with urea-derived cyanate. HCit has recently been detected in collagen; however, given that 15%-90% of total Lys in collagen is hydroxylated, it is unclear how hydroxylation affects collagen carbamylation. Here, we identified a collagen-specific carbamylation product, hydroxyhomocitrulline (HHCit), and showed that high levels of HHCit are correlated with age in rat tissue collagen and in vivo carbamylation in mice, as well as with the decline of kidney function in the serum of dialysis patients. Proteomic analysis of the carbamylated collagens identified α2(I) Lys933, a major cross-linking site, as a preferential HHCit site. Furthermore, our results suggest that hydroxylysine carbamylation affects the mechanical properties of connective tissue by competitively inhibiting collagen cross-link formation.

Scavenging of reactive oxygen species by astaxanthin inhibits epithelial-mesenchymal transition in high glucose-stimulated mesothelial cells.

BACKGROUND: High glucose concentrations influence the functional and structural development of the peritoneal membrane. We previously reported that the oral administration of astaxanthin (AST) suppressed peritoneal fibrosis (PF) as well as inhibited oxidative stress, inflammation, and epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) in a chlorhexidine-induced PF rat model. This suggests that oxidative stress induction of EMT is a key event during peritoneal damage. The present study evaluated the therapeutic effect of AST in suppressing EMT, in response to glucose-induced oxidative stress. METHODS: Temperature-sensitive mesothelial cells (TSMCs) were cultured in the presence or absence of AST and then treated with 140 mM glucose for 3 or 12 hours. Expression levels of TNF-α, TGF-ß, and VEGF were determined at the mRNA and protein levels, and nuclear factor kappa B (NF-κB) activity was evaluated. We measured NO2-/NO3- concentrations in cellular supernatants and determined 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in mitochondrial and nuclear DNA. The expressions of E-cadherin and alpha-smooth muscle actin (α-SMA) were evaluated by double immunofluorescence and protein levels. RESULTS: High glucose concentrations induced overproduction of reactive oxidative species (ROS), increasing 8-OHdG mitochondrial DNA and cytokine levels. The NF-κB pathway was activated in response to high glucose concentrations, whereas de novo α-SMA expression was observed with decreased E-cadherin expression. AST treatment attenuated ROS production, inflammatory cytokine production, NF-κB activation, and EMT. CONCLUSION: The findings of the present study indicate that AST may have an anti-EMT effect due to anti-oxidative and anti-inflammatory activities by scavenging glucose-induced ROS from mitochondria in PMCs. AST may be an efficacious treatment for PF.

Recommendations for pathological diagnosis on biopsy samples from peritoneal dialysis patients.

Peritoneal dialysis (PD) has been established as an essential renal replacement therapy for patients with end stage renal disease during the past half century. Histological evaluation of the peritoneal membrane has contributed to the pathophysiological understanding of PD-related peritoneal injury such as peritonitis, fibrosis, and encapsulating peritoneal sclerosis (EPS). Hyalinizing peritoneal sclerosis (HPS), also known as simple sclerosis, is observed in almost all of PD patients. HPS is morphologically characterized by fibrosis of the submesothelial interstitium and hyalinizing vascular wall, particularly of the post-capillary venule (PCV). Two histological factors, the thickness of submesothelial compact zone (SMC) and the lumen/vessel ratio (L/V) at the PCV, have been used for the quantitative evaluation of HPS. The measuring system on SMC thickness and L/V ratio is easy and useful for evaluating the severity of HPS. On the other hand, EPS is characterized by unique encapsulation of the intestines by an "encapsulating membrane". This newly formed membranous structure covers the visceral peritoneum of the intestines, which contains fibrin deposition, angiogenesis, and proliferation of fibroblast-like cells and other inflammatory cells. This review will cover the common understandings of PD-related peritoneal alterations and provide a basic platform for clinical applications and future studies in this field.

Pancreatic lipase activity in overnight effluent predicts high transport status in peritoneal dialysis patients.

BACKGROUND: Long-term peritoneal dialysis (PD) causes peritoneal morphological and functional changes, resulting in high transport status featuring increased peritoneal permeability. High transport status is diagnosed by peritoneal equilibration test (PET), a reliable but time-consuming method. We identifed a reliable biomarker in peritoneal effluent to predict high transport status in PD patients. METHODS: We collected peritoneal effluent and serum from 33 PD patients and measured common laboratory test parameters. High transport status was determined by PET if the dialysate/plasma ratio of creatinine at 4h dwell (D/P Cr 4h) was ≥0.81. RESULTS: There were significant correlations between D/P Cr 4h and some laboratory parameters in overnight effluent (pancreatic lipase activity, r=0.65, p<0.001; ß2-microglobulin concentration, r=0.59, p<0.001; IL-6 concentration, r=0.53, p<0.001; and CA125 concentration, r=0.29, p=0.027). In a multivariate logistic regression analysis, the pancreatic lipase activity in overnight effluent was identified as an independent predictor of high transport status even after adjusting for age, PD duration, and glomerular filtration rate [OR=1.43 (95% CI: 1.11-1.83), p=0.005]. CONCLUSIONS: The pancreatic lipase activity in overnight effluent is an independent predictor of high transport status in PD patients.

Vascular Endothelial Cell Injury Is an Important Factor in the Development of Encapsulating Peritoneal Sclerosis in Long-Term Peritoneal Dialysis Patients.

BACKGROUND AND OBJECTIVES: Encapsulating peritoneal sclerosis (EPS) is a rare but serious and life-threatening complication of peritoneal dialysis (PD). However, the precise pathogenesis remains unclear; in addition, predictors and early diagnostic biomarkers for EPS have not yet to be established. METHODS: Eighty-three peritoneal membrane samples taken at catheter removal were examined to identify pathological characteristics of chronic peritoneal deterioration, which promotes EPS in patients undergoing long-term PD treatment with low occurrence of peritonitis. RESULTS: According to univariable logistic regression analysis of the pathological findings, thickness of the peritoneal membrane (P = 0.045), new membrane formation score (P = 0.006), ratio of luminal diameter to vessel diameter (L/V ratio, P<0.001), presence of CD31-negative vessels (P = 0.021), fibrin deposition (P<0.001), and collagen volume fraction (P = 0.018) were associated with EPS development. In analyses of samples with and without EPS matched for PD treatment period, non-diabetes, and PD solution, univariable analysis identified L/V ratio (per 0.1 increase: odds ratio (OR) 0.44, P = 0.003) and fibrin deposition (OR 6.35, P = 0.027) as the factors associated with EPS. L/V ratio was lower in patients with fibrin exudation than in patients without fibrin exudation. CONCLUSIONS: These findings suggest that damage to vascular endothelial cells, as represented by low L/V ratio, could be a predictive finding for the development of EPS, particularly in long-term PD patients unaffected by peritonitis.

Determinants of coronary artery calcification in maintenance hemodialysis patients.

In addition to the well-known traditional risk factors, uremia-related so-called novel risk factors and medications appear to affect coronary artery calcification in hemodialysis patients. This study was performed to evaluate coronary artery calcification score (CACS) in maintenance hemodialysis (MHD) patients, and to identify significantly related factors. We assessed CACS using Agatston Score by MDCT, sex, age, dialysis vintage, presence of diabetes mellitus, smoking history, presence of ≥100 ml urine volume/day, normalized protein catabolic rate, geriatric nutritional risk index, administration of active vitamin D3, cinacalcet, phosphate binders or antihypertensive agents, and circulation parameters including creatinine, albumin, corrected calcium and phosphate in 207 MHD patients. Coronary artery calcifications were observed in 192 patients (92.8%). In multivariate analysis, CACS showed direct associations with age (p < 0.001), dialysis vintage (p < 0.001) and presence of diabetes mellitus (p < 0.01), and an inverse association only with active vitamin D3 administration (p < 0.001) in MHD patients. Patients with active vitamin D3 showed significantly lower CACS than in those without it (1349.6 ± 1635.0 vs. 2475.6 ± 2646.6 H, p < 0.05). Older age, longer duration of dialysis and diabetes mellitus are risk factors and administration of active vitamin D3 is protective factor for coronary artery calcification in MHD patients.

Morphological characteristics in peritoneum in patients with neutral peritoneal dialysis solution.

Peritoneal dialysis solution (PDS) plays a role in functional and morphological damage to the peritoneum. This study aimed to clarify the effect of neutral PDS in preventing morphological changes by assessing peritoneal damage and comparing morphological alterations between PD patients treated with neutral PDS and acidic PDS. Sixty-one patients participated from seven hospitals. All patients were treated with neutral PDS excluding icodextrin, during their entire PD treatment, and experienced no episode of peritonitis. The thickness of submesothelial compact (SMC) zone and the presence of vasculopathy in the anterior parietal abdominal peritoneum were assessed. The impact of icodextrin, hybrid therapy, and peritoneal rest and lavage in morphological alterations were determined. There was no significant difference in the average SMC thickness between neutral and acidic PDS. The vessel patency in patients using neutral PDS was significantly higher compared to that in acidic PDS at any time during PD. There were no significant suppressive effects from interventions or use of icodextrin with respect to peritoneal morphological injury. A monolayer of mesothelial cell was observed in approximately half the patients, especially in their receiving lavage patients. Neutral PDS, accompanied by other preventive approaches against peritoneal injury, might suppress the development of peritoneal morphological alterations.

Long-term outcome of encapsulating peritoneal sclerosis (EPS) patients in a single center.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is the most serious complication of peritoneal dialysis (PD) with a high mortality rate. The objective of the present study was to determine the clinical characteristics, the incidence rate, and the long-term outcome of EPS patients compared with control patients. METHODS: Two hundred and seventy patients with end-stage kidney disease were started on PD from 1987 to 2013 in the Juntendo University Hospital. EPS was diagnosed by clinical findings, radiological findings, and macroscopic inspection at the time of laparoscopy or surgical operation. Patient medical records were analyzed retrospectively, including clinical characteristics, laboratory findings, treatment modality, and outcomes. Using a Kaplan-Meier analysis, we compared the survival rate between EPS patients and control PD patients, matched for age, gender, diabetes, and duration of PD. RESULTS: Among 270 PD patients, 13 patients (4.8 %) developed EPS. The mean duration of PD was 120.5 ± 42.8 months. There were no significant difference in demographic findings between EPS and control PD patients. Among the EPS patients, seven patients died, of which four deaths were directly attributed to EPS. All four patients that had had surgical enterolysis were doing well and had no recurrences. No significant difference in the survival rate between EPS and control PD patients was observed in the Kaplan-Meier analysis. CONCLUSIONS: There was no significant difference in the survival rate between EPS patients and control PD patients. It appears that an early diagnosis by laparoscopy and accurate treatment, including surgical enterolysis, might improve mortality.

Oral Astaxanthin Supplementation Prevents Peritoneal Fibrosis in Rats.

BACKGROUND: Preventing peritoneal damage during peritoneal dialysis is critical. Reactive oxygen species (ROS) have an important role in peritoneal damage; however, few studies have investigated this. We aimed to determine the effects of oral astaxanthin (AST) supplementation in a peritoneal fibrosis (PF) rat model. METHODS: Thirty-seven Sprague-Dawley rats were divided into 5 groups: Control 1 (fed a normal diet without stimulation), Control 2 (fed an AST-supplemented diet without stimulation), Group 1 (fed a normal diet with 8% chlorhexidine gluconate [CG] stimulation for 3 weeks), Group 2 (fed a 0.06% AST-supplemented diet with CG stimulation), and Group 3 (fed a 0.06% AST-supplemented diet that was initiated 4 weeks before CG stimulation). Peritoneal fibrosis, vascular proliferation, and fibrosis-related factor expression were examined. RESULTS: Peritoneal thickness was significantly suppressed by AST supplementation. Astaxanthin diminished the number of CD68-, 8-hydroxy-2'-deoxyguanosine (8-OHdG)-, and monocyte chemoattractant protein-1 (MCP-1)-positive cells. Type 3 collagen, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and MCP-1 mRNA expression was significantly lower in Group 3 than in Group 1. Increased transforming growth factor-ß (TGF-ß) and Snail mRNA expression, vascular density, and the number of α-smooth muscle actin (α-SMA)-positive cells were also decreased in Group 3. CONCLUSION: Astaxanthin suppressed PF development through the inhibition of inflammation and oxidation in PF rats. It appears that the anti-oxidative agent AST may be useful for the prevention of peritoneal damage.