A Low Prognostic Nutritional Index Is a Risk Factor for High Peritoneal Transport Status in Patients Undergoing Peritoneal Dialysis.

OBJECTIVES: A high peritoneal transport status is a risk factor for mortality and causes technical failure in patients on peritoneal dialysis (PD). High peritoneal transport status is associated with malnutrition and inflammation in patients with PD. The prognostic nutritional index (PNI) is a marker determined by the serum albumin level and lymphocyte count in the peripheral blood. The aim of this study is to investigate the association between PNI and high peritoneal transport status in patients with PD. METHODS: We retrospectively investigated patients with PD from January 1, 2013 to May 31, 2020, in 4 PD centers. Patients with PD were divided into 2 groups according to PNI quartiles: the low PNI group (PNI ≤ 36.6) and the high PNI group (PNI > 36.6). The demographics and clinical and laboratory baseline data of the 2 groups were collected and compared. The association between PNI and high peritoneal transport status was analyzed by multivariate logistic regression analysis. RESULTS: A total of 404 patients with PD were enrolled in our study. A total of 77 (19.06%) patients had high peritoneal transport status. After adjusting for age, sex, body mass index, hypertension, diabetes mellitus, residual urine volume, current smoking status, pre-existing cardiovascular disease, hemoglobin, white blood cell count, triglycerides, and intact parathyroid hormone, low PNI levels were significantly associated with high peritoneal transport status (odds ratio 3.42, 95% confidence interval 1.82-5.18, P = .0056). Subgroup analysis showed that there was no interaction among PNI and age, sex, diabetes, body mass index, pre-existing cardiovascular disease, or current smoking. CONCLUSION: As a marker for malnutrition and inflammation, a low level of PNI is an independent risk factor for high peritoneal transport status in patients with PD.

A Uremic Pig Model for Peritoneal Dialysis.

With increasing interest in home dialysis, there is a need for a translational uremic large animal model to evaluate technical innovations in peritoneal dialysis (PD). To this end, we developed a porcine model with kidney failure. Stable chronic kidney injury was induced by bilateral subtotal renal artery embolization. Before applying PD, temporary aggravation of uremia was induced by administration of gentamicin (10 mg/kg i.v. twice daily for 7 days), to obtain uremic solute levels within the range of those of dialysis patients. Peritoneal transport was assessed using a standard peritoneal permeability assessment (SPA). After embolization, urea and creatinine concentrations transiently increased from 1.6 ± 0.3 to 7.5 ± 1.2 mM and from 103 ± 14 to 338 ± 67 µM, respectively, followed by stabilization within 1-2 weeks to 2.5 ± 1.1 mM and 174 ± 28 µM, respectively. Gentamicin induced temporary acute-on-chronic kidney injury with peak urea and creatinine concentrations of 16.7 ± 5.3 mM and 932 ± 470 µM respectively. PD was successfully applied, although frequently complicated by peritonitis. SPA showed a low transport status (D/P creatinine at 4 h of 0.41 (0.36-0.53)) with a mass transfer area coefficient of 9.6 ± 3.1, 4.6 ± 2.6, 3.4 ± 2.3 mL/min for urea, creatinine, and phosphate respectively. In conclusion, this porcine model with on-demand aggravation of uremia is suitable for PD albeit with peritoneal transport characterized by a low transport status.

Preserved peritoneal function by short-term two-day peritoneal rest in hemodialysis combination therapy patients.

Several reports have demonstrated that peritoneal rest (PR) is considered to preserve the peritoneal function in peritoneal dialysis (PD) patients. However, there has been no report that examines the peritoneal permeability before and after a short-term PR of two days. We examined the effect of the two-day PR on peritoneal permeability. We observed and compared the daily PD ultrafiltration changes in the four PD and hemodialysis (HD) combination patients from the start of dialysis therapy throughout the total observation period of each case. Next, 6 months after the initiation of dialysis therapy we performed a set of peritoneal equilibrium tests (PET) before and after the 2-day PR. D/P creatinine, daily urine volume, daily ultrafiltration volume in PD, weekly residual renal creatinine clearance, and weekly PD creatinine clearance were measured. The daily PD ultrafiltration volume increased significantly after the 2-day PR, and gradually decreased over the last four days throughout the observation period in each patient. In the PET results, D/P creatinine in all patients decreased after the short-term PR, and accordingly the peritoneal ultrafiltration volume increased. However, urine volume, residual renal creatinine clearance, and peritoneal creatinine clearance did not change. The peritoneal permeability clearly decreased after the short-term PR. The repeated improvement in the PD ultrafiltration volume after the short-term PR implies that the peritoneal permeability alteration might be due to a reversible functional change in the initial dialysis period. These results suggest that a short-term PR may preserve the peritoneal function.

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.

The Natural Time Course of Membrane Alterations During Peritoneal Dialysis Is Partly Altered by Peritonitis.

UNLABELLED: ♦ BACKGROUND: The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis-representing the natural course-and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. ♦ METHODS: This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990-2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis ("no-peritonitis group") were compared with the results obtained in patients who experienced 1 or more peritonitis episodes ("peritonitis group") during a follow-up of 4 years. ♦ RESULTS: The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the patients who experienced peritonitis (p < 0.01). No difference was observed in the time-course of the effective lymphatic absorption rate. The time-courses of immunoglobulin G and α2-macroglobulin clearances showed a decrease in both patient groups, with a concomitant increase of the restriction coefficient. Those changes were not evidently influenced by peritonitis. The two groups showed a similar decrease in the mesothelial cell mass marker cancer antigen 125 during follow-up. ♦ CONCLUSIONS: On top of the natural course of peritoneal function, peritonitis episodes to some extent influence the time-course of small-solute and fluid transport-especially the transport of solute-free water. Those modifications increase the risk for overhydration.

The Mutual Relationship Between Peritonitis and Peritoneal Transport.

UNLABELLED: ♦ BACKGROUND: Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport. ♦ METHODS: Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16). ♦ RESULTS: At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport. ♦ CONCLUSIONS: Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD.

Alterations of intercellular junctions in peritoneal mesothelial cells from patients undergoing dialysis: effect of retinoic Acid.

BACKGROUND: Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs. METHODS: Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed. RESULTS: HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT. CONCLUSIONS: Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression.

The first peritonitis episode alters the natural course of peritoneal membrane characteristics in peritoneal dialysis patients.

OBJECTIVE: Little or no evidence is available on the impact of the first peritonitis episode on peritoneal transport characteristics. The objective of this study was to investigate the importance of the very first peritonitis episode and distinguish its effect from the natural course by comparison of peritoneal transport before and after infection. PARTICIPANTS: We analyzed prospectively collected data from 541 incident peritoneal dialysis (PD) patients, aged > 18 years, between 1990 and 2010. Standard Peritoneal Permeability Analyses (SPA) within the year before and within the year after (but not within 30 days) the first peritonitis were compared. In a control group without peritonitis, SPAs within the first and second year of PD were compared. MAIN OUTCOME MEASUREMENTS: SPA data included the mass transfer area coefficient of creatinine, glucose absorption and peritoneal clearances of ß-2-microglobulin (b2m), albumin, IgG and α-2-macroglobulin (a2m). From these clearances, the restriction coefficient to macromolecules (RC) was calculated. Also, parameters of fluid transport were determined: transcapillary ultrafiltration rate (TCUFR), lymphatic absorption (ELAR), and free water transport. Crude and adjusted linear mixed models were used to compare the slopes of peritoneal transport parameters in the peritonitis group to the control group. Adjustments were made for age, sex and diabetes. RESULTS: Of 541 patients, 367 experienced a first peritonitis episode within a median time of 12 months after the start of PD. Of these, 92 peritonitis episodes were preceded and followed by a SPA within one year. Forty-five patients without peritonitis were included in the control group. Logistic reasons (peritonitis group: 48% vs control group: 83%) and switch to hemodialysis (peritonitis group: 22% vs control group: 3%) were the main causes of missing SPA data post-peritonitis and post-control. When comparing the slopes of peritoneal transport parameters in the peritonitis group and the control group, a first peritonitis episode was associated with faster small solute transport (glucose absorption, p = 0.03) and a concomitant lower TCUFR (p = 0.03). In addition, a discreet decrease in macromolecular transport was seen in the peritonitis group: mean difference in post- and pre-peritonitis values: IgG: -8 µL/min (p = 0.01), a2m: -4 µL/min (p = 0.02), albumin: -10 µL/min (p = 0.04). Accordingly, the RC to macromolecules increased after peritonitis: 0.09, p = 0.04. CONCLUSIONS: The very first peritonitis episode alters the natural course of peritoneal membrane characteristics. The most likely explanation might be that cured peritoneal infection later causes long-lasting alterations in peritoneal transport state.

Epithelial-to-mesenchymal transition and slit function of mesothelial cells are regulated by the cross talk between mesothelial cells and endothelial cells.

Peritoneal dysfunction is a major factor leading to treatment failure of peritoneal dialysis (PD). However, the precise mechanism of the peritoneal diffusion changes related to PD remains to be elucidated. To this end, we have established a novel peritoneal diffusion model in vitro, which consists of a three-dimensional culture system using a collagen vitrigel membrane chamber and a fluid-stream generation system. This artificial peritoneal model revealed that high-glucose culture medium and fluid flow stress promoted the epithelial-mesenchymal transition (EMT) process of mesothelial cells and that endothelial cells inhibited this mesothelial EMT process. Mesothelial cells in the EMT state showed high expression of connective tissue growth factor and low expression of bone morphogenic protein-7, while non-EMT mesothelial cells showed the opposite expression pattern of these two proteins. In addition, these protein expressions were dependent on the presence of endothelial cells in the model. Our model revealed that the endothelial slit function was predominantly dependent on the covering surface area, while the mesothelial layer possessed a specific barrier function for small solutes independently of the surface area. Notably, a synergic barrier effect of mesothelial cells and endothelial cells was present with low-glucose pretreatment, but high-glucose pretreatment abolished this synergic effect. These findings suggest that the mesothelial slit function is not only regulated by the high-glucose-induced EMT process but is also affected by an endothelial paracrine effect. This peritoneal diffusion model could be a promising tool for the development of PD.

Longitudinal analysis of peritoneal fluid transport and its determinants in a cohort of incident peritoneal dialysis patients.

BACKGROUND AND OBJECTIVES: There is a paucity of large longitudinal studies on the time course of peritoneal fluid transport. The aim of the present study was to longitudinally analyze changes in fluid transport and relevant solute transport parameters in patients treated with a conventional peritoneal dialysis (PD) fluid and, to mimic clinical reality, not selected for the presence or absence of ultrafiltration (UF) failure. METHODS: This prospective single-center cohort study followed 138 consecutive incident PD patients from July 1994 until censoring in August 2004. The design was longitudinal, with repeated measures over time in each patient. Patients had undergone at least 1 and a maximum of 5 annual standard peritoneal permeability analyses (SPAs) using 3.86% glucose dialysate. A linear mixed model was used to analyze the longitudinal data. RESULTS: No differences in patient characteristics were present at baseline in relation to the number of available SPAs. There were also no differences in patient withdrawal during the years of follow-up. A gradual decline in fluid transport, expressed as free water transport (FWT), small-pore fluid transport (SPFT), and transcapillary UF (TCUF), was observed with duration of PD. The decline was mainly attributable to patients who developed UF failure. The time courses for the determinants of fluid transport, such as the reflection coefficient (σ) and the UF coefficient (LpA), were not different. However, they were associated with an increase in the mass transfer area coefficient of creatinine, reflecting the peritoneal vascular surface area. CONCLUSIONS: Fluid profiles for FWT and SPFT during a dwell can be explained by current knowledge of the three-pore model. Fluid transport declines with the duration of PD because of an increase in the vascular surface area, leading to a rapid dissipation of glucose as the osmotic agent. The absence of a trend in the time course of osmotic conductance and its constituents-that is, LpA and σ-suggests that, in an unselected population, these parameters are affected only late in the time course of PD.

Pathological changes in chronic eosinophilic peritonitis in peritoneal dialysis patient.

We report the pathological findings of the peritoneum in a patient with chronic eosinophilic peritonitis. Peripheral blood eosinophilia was confirmed before insertion of Tenckhoff catheter. Eosinophilic peritonitis continued from the second day after initiation of peritoneal dialysis for 18 months. Pathological findings showed numerous eosinophils in peritoneal blood vessels. Mast cells were also detected in the peritoneum, while neoangiogenesis was not prominent. The highly permeable state of the peritoneal membrane may be due to inflammatory mediators, such as tryptase. Mast cells may be involved in high peritoneal permeability in such patients.

The Suppression of Peritoneal Advanced Glycosylation End Product Formation by Intraperitoneal Aminoguanidine / 대한신장학회잡지

BACKGOUND: The purpose of the study was to evaluate the effect of aminonguanidine on the inhibition of advanced glycosylation end product (AGE) formation and the expression of peritoneal vascular endothelial growth factor (VEGF). Then we analyzed the functional and morphological alterations of peritoneal membrane during long-term PD in rats. METHODS: Male Sprague-Dawley rats were randomly divided into 3 groups:group I (n=6), control rats with PD catheter but not dialyzed; group II (n=9), rats dialyzed with 4.25% glucose solution for all exchanges; group III (n=9), rats dialyzed with 4.25% glucose solution containing aminoguanidine (25 mg/kg) for all changes. Dialysis changes were performed 3 times a day with 25 mL/each exchange for 12 weeks. Immunostaining was performed using a monoclonal anti-AGE antibody and a polyclonal anti-VEGF antibody. One-hour peritoneal equilibration test were performed at every 4-week for the comparison of peritoneal transport characteristics. RESULTS: Expressions of peritoneal AGE and VEGF in dialyzed groups (group IIand III) were higher compared to control group. The level of AGE immunostaining in group III was significantly lower than in the group II. But peritoneal VEGF expression did not differ between the dialyzed groups. In dialyzed groups, D/DO glucose was significantly lower whereas D/P urea was significantly higher than in the control group. On linear regression analysis, peritoneal AGE and VEGF accumulation were directly correlated with D/DO glucose and D/P urea nitrogen. But there was no statistical significance in D/DO glucose and D/P urea nitrogen between the dialyzed groups. CONCLUSION: Peritoneal accumulation of AGE and VEGF increased with time on CAPD in dialyzed groups. Intraperitoneal aminoguanidine was greatly suppressed peritoneal AGE accumulation but no attenuated long-term dialysis related peritoneal hyperpermeability. The VEGF formation may be one of the several mediators resulting the functional deterioration of the peritoneal membrane in long-term peritoneal dialysis.

Altered Expression of Peritoneal Aquaporin-1 and Water Transport during Long-term Peritoneal Dialysis in Rats / 대한신장학회잡지

BACKGROUND: The present work was designed to examine the altered expression of peritoneal AQP-1 and water transport of peritoneal membrane during the long-term peritoneal dialysis with hypertonic glucose solution in rats. METHODS: Eighteen Sprague-Dawley male rats were randomly divided into 2 groups: control rats (n=6) with peritoneal catheter but not dialyzed; rats with peritoneal dialysis (PD) (n=12) were dialyzed with 4.25% glucose dialysate for all exchanges. Before completion of the study, 4 animals in PD group were euthanized owing to nonfunctional catheters or peritonitis, leaving 14 animals for the analysis. Dialysis exchanges were performed 3 times a day with 25 mL/each exchange for 12 weeks. Immunoperoxidase staining was performed using monoclonal anti-AGE antibody and polyclonal anti-AQP-1 antibody. The slides were read by 5 different examiners in a blind fashion. The staining intensity was graded semiquantitively from 0 to 3. The peritoneal membrane function was assessed by performing one-hour peritoneal equilibration tests every 6 week for comparing transport characteristics. Peritoneal membrane transport rate was assessed by D/P of urea nitrogen and D/Do of glucose. Water transport of peritoneal membrane was assessed by D/P of sodium at 12 week. RESULTS: The expression of peritoneal AQP-1 was increased in rats with PD, compared to control rats. Consistent with this, D/P of sodium in rats with PD was significantly decreased compared to control rats (0.58+/-0.04 vs 0.86+/-0.07, p<0.05), indicating high peritoneal water permeability in response to long-term peritoneal dialysis. Moreover, rats with PD were associated with significantly lower D/Do of glucose and higher D/P of urea nitrogen, suggesting high peritoneal membrane transport. CONCLUSION: High expression of peritoneal AQP-1 was associated with an increased peritoneal water permeability in response to long-term peritoneal dialysis with 4.25% glucose for 12 weeks. The underlying mechanisms for the increased AQP-1 expression need to be examined whether it is due to the continuous exposure to the dialysis solution containing high glucose concentration itself or compensatory effects of slowly developed concomitant ultrafiltration failure in chronic peritoneal dialysis.

Pirfenidone Treatment During Peritoneal Dialysis Reduces Peritoneal Fibrosis in Rats / 대한신장학회잡지

BACKGROUND: Peritoneal fibrosis is one of the most serious complications in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In order to determine the effects of pirfenidone treatment for reducing peritoneal fibrosis, we examined the changes of peritoneal permeability (for glucose and urea nitrogen) and peritoneal thickness in a rat model of chronic peritoneal dialysis. METHODS: Thirty male Sprague-Dawley rats were divided into the following three groups: group I (n= 6), control rats with normal chow; group II (n=10), rats dialyzed with standard 4.25% glucose solution maintained on normal chow; group III (n=8), rats dialyzed with standard 4.25% glucose solution and maintained on pirfenidone-mixed chow (pirfenidone 350 mg/kg/day). Dialysis exchanges were performed three times a day with an instillation volume of 25 mL for a period of 12 weeks. Morphometric analysis of the peritoneal membrane were carried out in tissue specimens obtained at the time of sacrifice. One- hour peritoneal equilibration test was done at the beginning and the end of the study to compare the transport characteristics in these groups. RESULTS: The peritoneal permeability of glucose and urea nitrogen was much higher in rats subjected to peritoneal dialysis (both in group II and group III), as compared with control rats (group I). In group II where rats received peritoneal dialysis without pirfenidone treatment, rats had the highest level of peritoneal permeability for glucose and urea nitrogen, suggesting the peritoneal hyperpermeability. In contrast, rats in group III dialyzed with pirfenidone treatment had an improved peritoneal hyperpermeability indicating that pirfenidone treatment may have a protective effect against peritoneal hyperpermeability. Consistent with this, rats subjected to peritoneal dialysis were associated with a marked thickening of peritoneal membrane in both parietal (group I: 13.7+/-3.3 micrometer, group II: 59.5+/-26.2 micrometer, group III: 36.5+/-11.2 micrometer) and visceral (group I: 3.1+/-0.9 micrometer, group II: 10.9+/-5.2 micrometer, group III: 6.1+/-1.7 micrometer) peritoneum. In particular, submesothelial region in peritoneum was significantly thickened by accumulation of collagen, demonstrated by Masson's trichrome staining. Pirfenidone treatment during peritoneal dialysis, however, significantly reduced the accumulation of collagen in mesothelial region of the parietal peritoneum. CONCLUSION: Peritoneal dialysis with high glucose containing dialysate is associated with significant peritoneal collagen accumulation in mesothelial region and an increased peritoneal permeability for glucose and urea nitrogen. In contrast, pirfenidone treatment during peritoneal dialysis significantly reduces peritoneal thickness as well as peritoneal hyperpermeability, suggesting a protective effect against peritoneal fibrosis induced by chronic peritoneal dialysis.