Risk factors for encapsulating peritoneal sclerosis in patients who have experienced peritoneal dialysis treatment

Background The present study was conducted to clarify the clinical risk factors related to the development of encapsulating peritoneal sclerosis (EPS), which is one of the most serious complications in patients undergoing peritoneal dialysis (PD).Methods The records of 78 patients with a history of PD treatment, including 18 with EPS, were retrospectively analyzed (male/female, 51:27; age, 51.8 ± 11.0 years; PD treatment, 94.1 ± 42.7 months). The inclusion criteria were: duration of PD more than 24 months; 36-month follow up after discontinuation of PD; available data for dialysate-to-plasma creatinine ratio (D/P Cr), by fast peritoneal equilibration test within 3 months before PD discontinuation; and absence of EPS at PD discontinuation. Analytical parameters included age, sex, underlying renal disease, duration of PD, membrane transport state (higher transporter or lower transporter: D/P cr ratio more than or less than 0.75), number of episodes of peritonitis during PD treatment, performance of peritoneal lavage after PD discontinuation, and reasons for PD withdrawal (ultrafiltration failure, acute peritonitis, social matters).Results Significant differences were noted regarding the PD duration, D/P cr, higher membrane transport state, and number of peritonitis episodes during PD. On receiver operating characteristic curves, the cutoff points for EPS were: D/P cr ratio, 0.74; number of peritonitis episodes, 2; and PD duration (months), 115.2. Multivariate analysis, employing the factors age, PD duration, higher membrane transport state, and number of peritonitis episodes, which were selected by stepwise analysis, identified the latter two factors as significant for the development of EPS (odds ratio [OR], 4.0; P = 0.046 and OR, 12.0; P = 0.049, respectively).Conclusions A higher transporter membrane state and the number of peritonitis episodes are factors contributing to the occurrence of EPS in patients who have experienced PD treatment.     

La péritonite sclérosante et encapsulante

Encapsulating peritoneal sclerosis is a rare but devastating complication of long-term peritoneal dialysis with a high mortality rate. The incidence is between 0.5 and 2.5%, decreasing with time. PSE is defined as a clinical syndrome with signs of gastrointestinal obstruction, inflammation parameters, radiological and macroscopic changes. The duration of treatment and the cessation of peritoneal dialysis are the main risks. About 75% occured in patients on hemodialysis or after kidney transplantation. Morphological alterations are disappearance of mesothelial layer, submesothelial fibrosis, interstitial sclerosis and vasculopathy. Ultrafiltration failure, fast transport status of the peritoneal membrane and loss of sodium sieving, the most powerful predictor, are the functional abnormalities. Biomarkers in peritoneal effluent include cancer antigen 125, interleukin-6. The pathophysiology is probably a consequence of a multiple-hit process in which expression of growth factors and cytokines play a central role. Medical strategies (corticosteroids, tamoxifen) in association with parenteral nutrition and/or surgery (enterolysis) are discussed. Prevention is the use of physiological peritoneal dialysis solutions, icodextrine instead of high glucose concentration solutions and peritoneal lavage after peritoneal dialysis stopping.     

Risks of peritoneal membrane failure in children undergoing long-term peritoneal dialysis

Children undergoing long-term peritoneal dialysis are at risk for membrane injury, necessitating conversion to hemodialysis. We analyzed the incidence and risk factors for membrane failure (inadequate ultrafiltration with or without peritoneal adhesions and decreased peritoneal surface area) in 68 children maintained with peritoneal dialysis for more than 3 months at our institution. The overall incidence of membrane failure was 16.2% (11/68). Kaplan-Meier estimates of peritoneal membrane survival were 88% at 24 months, 72% at 36 months, 65% at 48 months, and 52% at 60 months. Logistic regression analysis demonstrated that the risk of membrane failure increased with the number of episodes of peritonitis (odds ratio 1.61). The rate of peritonitis was 1 per 7.02 patient months in children who developed membrane failure compared with 1 per 9.18 patient months in children without membrane failures but the rate of peritonitis was not predictive of membrane failure (P=0.09). Multiple logistic regression analysis demonstrated that peritonitis caused byPseudomonas aeruginosa or alpha streptococcal organisms were independent predictors of membrane failure. We conclude that peritoneal membrane survival declines substantially with time on peritoneal dialysis and that membrane failure is associated with peritonitis, particularly peritonitis caused byPseudomonas aeruginosa and alpha streptococcal organisms. The mechanism(s) of membrane injury are unknown but may be related to the inflammatory response initiated during peritonitis.     

Restoration of peritoneal integrity after withdrawal of peritoneal dialysis: characteristic features of the patients at risk of encapsulating peritoneal sclerosis

Background The epidemiological characteristics of encapsulating peritoneal sclerosis (EPS), such as its high incidence in patients with long-term peritoneal dialysis (PD) treatment, and the onset of EPS after patients are switched to hemodialysis (HD) may indicate an activated pathological process after PD withdrawal, especially in long-term PD patients. Accordingly, we aimed to observe changes in peritoneal function after the stoppage of PD, and to clarify the characteristic features of the patients at risk of EPS. Methods Thirty-three patients who were switched from continuous ambulatory peritoneal dialysis (CAPD) to HD were enrolled in this trial. Changes in the dialysate/plasma creatinine (D/P Cr) and CA125 levels in the effluent of the peritoneal equilibration test were observed for 6 months. Furthermore, each patient was followed-up for 36 months after PD withdrawal to monitor for the development of EPS. Results D/P Cr decreased significantly, while CA125 levels tended to increase. Nine patients developed EPS during the follow-up period and they specifically showed significant increases of D/P Cr levels and significantly lower levels of CA125 at PD withdrawal. The accumulation of high transporters in the EPS group at 0 and 6 months after PD withdrawal was significant. Conclusions Peritoneal recovery may take place after withdrawal from PD treatment and such recover indicated by improvement of transport states and a rise of the CA125 level. The present study revealed that a high-transport state and lack of increase of CA125 in the effluent were associated with EPS development after PD withdrawal. This may suggest that the lack of peritoneal recovery after PD withdrawal is predictive for EPS development.     

水孔蛋白1在人腹膜组织的表达及腹膜透析对其表达的影响

目的 观察水孔蛋白1（aquaporin-1,AQP1)在人腹膜组织的表达以及腹膜透析（腹透）对其表达的影响。以期探讨长期腹透后腹膜超滤功能下降的可能机制。方法 采用Western blot，免疫组织化学（组化）以及RT-PCR等技术观察正常对照者，尿毒症非透析患者以及腹透患者的腹膜活检标本AQP1在蛋白质和基因水平表达。结果 各组腹膜均有AQP1表达。除了毛细血管和小静脉内皮细胞外，腹膜间皮细胞也表达AQP1。半定量分析表明各组AQP1蛋白和mRAN的表达量差异均没有显著性意义。结论 本研究支持AQP1是腹膜转运超小孔的分子结构。研究结果提示腹膜间皮细胞可能也参与了腹膜跨细胞的水转运。腹透对腹膜AQP1的表达量没有明显影响。因此进一步深入研究AQP1结构或分布的改变，以及与超滤衰竭的关系可能对探讨腹膜超滤衰竭的发生机制具有一定意义。     

改良腹膜平衡试验在腹膜透析患者中的应用

目的 观察改良腹膜平衡试验(改良PET)在腹膜透析(腹透)患者中的应用,初 步建立改良PET转运参数的参考值,探讨其评估腹膜溶质转运特性的准确性及临床意义。方法 97例腹透患者用高渗腹透液(4．25％葡萄糖)进行改良PET,分别测定4 h透析液肌酐与血肌酐 比值(4h D／Pcr)、计算物质转运面积系数(MTAC)、1 h透析液钠与血钠比值(1h D／PNa+)及记录 净超率量(nUF)。其中有14例患者在1个月内曾行标准腹膜平衡试验(标准PET),其结果与改 良PET进行自身比较。所有患者在研究时及研究前1个月内均无腹膜炎。结果 97例腹透患 者中有90例nUF大于400 ml,这些患者的转运参数经正态分布校正后建立了改良PET的参考 值。改良PET的4 hD／Pcr为0．70±0．15,标准PET4 hD／Pcr为0．68±0．13,两者非常接近,差异 无统计学意义。两种PET对患者腹膜转运特性分型结果相似。7例nUF小于400 ml的患者中有 5例有效腹膜表面积增大;2例存在水通道介导的水转运障碍,其中1例同时存在有效腹膜表面 积增大,还有1例患者改良PET转运参数在正常范围内。结论 与标准PET相比,用高渗腹透 液进行改良PET能够准确地评估腹膜小分子溶质转运特性,此外还能提供更多更敏感的液体转 运信息,为临床诊断超滤衰竭,以及进一步鉴别其原因提供了有力的手段。     

腹膜透析对人腹膜形态结构的影响

目的 探讨腹膜透析（腹透）对人腹膜，重点在间皮层形态结构的影响及其意义。方法 采用光镜，扫描电镜和透射电镜对10例正常对照者，12例尿毒症非透析患者以及10例腹透患者的腹膜活检标本进行形态学观察。结果 尿毒症非透析患者腹膜的结构与正常对照者相似，而腹透患者的腹膜形态结构随着透析时间而呈进行性改变。主要表现为间质细胞表面微绒毛减少，消失，间皮细胞从基底膜脱落直至完全消失，最后只剩下裸露的纤维结缔组织。结论 腹膜透析可引起腹膜的形态学明显改变，这可能是长期腹膜透析引起腹膜衰竭的原因之一。进一步深入研究腹膜结构与功能间关系能为人们了解长期腹透对腹膜影响的病理生理机制并进而寻找保护腹膜的手段提供理论依据。     

Peritoneal thickening is not inevitable in long-term peritoneal dialysis and is associated with peritoneal transport characteristics: a two-centre sonographic study.

BACKGROUND: The peritoneum is subject to alterations in the life-long course of peritoneal dialysis (PD). Studies of the parietal peritoneum by non-invasive ultrasonography in PD patients are limited. We hypothesize that a prolonged PD duration is associated with a thicker peritoneum on ultrasonography and alterations in Doppler indexes of mesenteric vessels. METHODS: We recruited two groups of patients, 18 who had >7 years of PD and 18 who had <12 months of PD. We excluded patients with active peritonitis, history of major abdominal surgery, cirrhosis or malignancy. We measured the sonographic thickness of the parietal peritoneum and Doppler indexes of mesenteric vessels by trans-abdominal ultrasonography at two PD units in Taiwan. RESULTS: We found no significant difference between two groups of PD patients in peritoneal thickness and in Doppler indexes. However, our univariate and multivariate analysis indicated that peritoneal thickness is associated with peritoneal transport characteristics (dialysate/plasma creatinine) but not with age, duration of dialysis, body height, body weight or Doppler index. The peritoneum is significantly thicker in rapid transporters than in slow transporters (RUQ: 0.59 +/- 0.40 mm versus 0.27 +/- 0.29 mm, P = 0.01; LUQ: 0.60 +/- 0.40 mm versus 0.27 +/- 0.32 mm, P = 0.016; LQ: 1.07 +/- 0.85 mm versus 0.48 +/- 0.53 mm, P = 0.026). In addition, rapid transporters have a marginally lower Doppler resistive index of the superior mesenteric artery (0.87 +/- 0.08 versus 0.90 +/- 0.10, P = 0.028). CONCLUSIONS: Our data showed that peritoneal thickening is not inevitable in long-term PD patients. Sonographic thickness in the parietal peritoneum is associated with transport characteristics. Rapid transporters have a significantly thicker peritoneum. The Doppler index of mesenteric vessels had no association with PD duration or transport characteristics. Trans-abdominal ultrasonography is non-invasive and useful in evaluating peritoneal characteristics of PD patients.     

Multidirectional approach to study peritoneal dialysis fluid biocompatibility in a chronic peritoneal dialysis model in the rat.

BACKGROUND: Peritoneal dialysis causes the functional and morphological changes in the peritoneum that result from the bioincompatibility of dialysis solutions. We present a model of chronic peritoneal dialysis in the rat that can be used for testing the biocompatibility of dialysis fluids. Methods and Results. Long-term exposure of the peritoneum to dialysis solutions can be performed in rats with implanted peritoneal catheters. Sampling of the dialysate allows the evaluation of intraperitoneal inflammation by examining cell differential and dialysate cytokine levels. Peritoneal permeability can be evaluated at designed time intervals with the peritoneal equilibration test (PET). At the end of dialysis, peritoneal histology is studied with light and electron microscopy. CONCLUSIONS: Such a multidirectional approach is an effective way to test biocompatibility of dialysis solutions.     

Ultrafiltration capacity and peritoneal fluid kinetics in continuous ambulatory peritoneal dialysis patients

Abstract:  Volume control is critical for peritoneal dialysis. Although peritoneal equilibration test (PET) has been used to clarify the peritoneal membrane characteristics, it is not able to adequately predict peritoneal fluid removal and optimize appropriately the dwell time. In the present study, we applied computer simulation and performed a more detailed evaluation of the fluid kinetics in patients with different ultrafiltration (UF) capacity. Patients who used three to four exchanges of 2.27% glucose dialysate per day (poor UF capacity group), and patients who used three to four exchanges of 1.36% glucose dialysate per day (good UF capacity group) to achieve adequate amount of peritoneal fluid removal were included in the present analysis. All included patients were asked to record appropriately their dialysis exchanges for the assessment of their peritoneal fluid transport characteristics. Seventeen continuous ambulatory peritoneal dialysis patients were selected in the present study, nine in poor UF capacity group and eight in good UF capacity group. Patients in poor UF capacity group had significantly higher daily glucose exposure, higher dialysate-to-plasma ratio of creatinine (D/P creatinine) values, and higher peritoneal fluid absorption rate, K _e, as compared to patients with good UF capacity. Our results suggest that patients with poor UF capacity have significant higher peritoneal small solute transport rate, and more importantly, higher peritoneal fluid absorption rate as compared to patients with good UF capacity.     

腹膜溶质转运特性与蛋白质和氨基酸经透析液丢失

目的　探讨腹膜透析（ＰＤ）时腹膜溶质转运特性与蛋白质和氨基酸经ＰＤ液丢失的关系。方法　比较了２５ 名腹膜溶质转运特性为高转运或低转运的ＰＤ 患者每日经ＰＤ 液丢失总蛋白质、白蛋白和２１ 种氨基酸量的差别。结果　高转运组患者每日经透析液丢失的总蛋白、白蛋白和总氨基酸量均明显高于低转运组［分别为（６－９±２－４０） 比（４－９６±１－５０）ｇ／２４ｈ、（４－９±２－０） 比（３－２±１－４）ｇ／２４ ｈ 和（１５－２４±３－７０）比（９－８９±３－７０）ｍｍｏｌ／２４ ｈ,Ｐ值均＜０－０５］;高转运组患者血浆白蛋白水平明显低于低转运组（３４－９±１－０）比（３８－８±１－９）ｇ／Ｌ,两组有显著性差异（ Ｐ＜０－０５）。根据腹膜平衡试验确定的Ｄ／Ｐ４Ｃｒ 值与透析液中白蛋白和总氨基酸的丢失量呈显著正相关,与血浆白蛋白水平呈显著负相关。结论　高转运ＰＤ患者较低转运者丢失更大量的蛋白质和氨基酸,导致血浆白蛋白水平下降,营养不良。应高度重视慢性ＰＤ的高转运患者的营养管理问题。     

Pathogenesis and treatment of peritoneal membrane failure

Peritoneal dialysis (PD) is a viable treatment option for end stage renal disease (ESRD) patients worldwide. PD may provide a survival advantages over hemodialysis (HD) in the early years of treatment. However, the benefits of PD are short-lived, as peritoneal membrane failure ensues in many patients, owing mainly to structural and functional changes in the peritoneal membrane from the use of conventional bio-incompatible PD solutions, which are hyperosmolar, acidic, have lactate buffer and contain high concentrations of glucose and glucose degradation products (GDPs). Current data suggest that chronic exposure of the peritoneum to contemporary PD fluids provokes activation of various inflammatory, fibrogenic and angiogenic cytokines, interplay of which leads to progressive peritoneal fibrosis, vasculopathy and neoangiogenesis. There is emerging evidence that peritoneal vascular changes are mainly responsible for increased solute transport and ultrafiltration failure in long-term PD. However, the precise pathophysiologic mechanisms initiating and propagating peritoneal fibrosis and angiogenesis remain elusive. The protection of the peritoneal membrane from long-term toxic and metabolic effects of high GDP-containing, conventional, glucose-based solutions is a prime objective to improve PD outcome. Recent development of new, more biocompatible, PD solutions should help to preserve peritoneal membrane function, promote ultrafiltration, improve nutritional status and, hopefully, preserve peritoneal membrane and improve overall PD outcomes. Elucidation of molecular mechanisms involved in the cellular responses leading to peritoneal fibrosis and angiogenesis spurs new therapeutic strategies that might protect the peritoneal membrane against the consequences of longstanding PD.     

Longitudinal changes in peritoneal equilibration test with or without peritonitis in children

This study was conducted to evaluate longitudinal changes in the peritoneal equilibration test (PET) in children treated with continuous peritoneal dialysis (CPD). The effects of prolonged CPD and episodes of peritonitis on the PET were examined. PET was repeated up to five times in 12 paediatric patients who were subdivided into groups with and without peritonitis. In the peritonitis group (n=6), the dialysate/plasma (D/P) creatinine ratio at a 4-h dwell time decreased progressively with time on CPD in five of six patients. In a comparison of the initial and final PETs performed at a mean interval of 22.8±11.6 months, the D/P creatinine ratio in the final PET was significantly lower than in the initial PET (P<0.01). In contrast, in the non-peritonitis group (n=6), the D/P creatinine ratio in the final PET was unchanged for 28.2±12.3 months from the initial PET. The D/Do glucose ratio at a 4-h dwell time was unchanged over time in each group. Thus, repeated PET measurements revealed that membrane permeability for creatinine was not affected by prolonged CPD itself, but decreased with time after episodes of peritonitis. Although the protocol for PET is not standardised in children, PET was useful for determining the sequential changes in peritoneal function in such patients on CPD.     

Factors influencing peritoneal transport parameters during the first year on peritoneal dialysis: peritonitis is the main factor.

BACKGROUND: Studies on the evolution of peritoneal transport during the first year of peritoneal dialysis (PD) are scarce and their results are contradictory. The aim of the present study was to analyse the evolution of peritoneal transport and residual renal function during the first year on PD, and to determine the factors that may influence them. METHODS: We studied 249 patients on continuous ambulatory PD with glucose exchange solutions (117 men, 132 women, mean age 51.9+/-16 years) 59 of whom had diabetes (25 type I). At baseline and after 1 year, we determined the mass transfer coefficients of urea (U-MTAC) and creatinine (Cr-MTAC), net ultrafiltration and residual renal function. RESULTS: Residual renal function decreased significantly during the first year (from 3.9+/-2.8 to 2.4+/-2.2 ml/min, P<0.001). Both U-MTAC and Cr-MTAC decreased after 1 year [U-MTAC from 22.7+/-7.8 to 20.7+/-6.6 ml/min (P<0.001), Cr-MTAC from 10.5+/-5.3 to 10.1+/-4.6 ml/min (NS)]. The ultrafiltration capacity increased significantly (from 923+/-359 to 987 U 341 ml/4 h, P<0.001). The evolution of MTAC values was independent of age, sex, diabetes and amount of hypertonic glucose used. When patients were grouped according to their initial Cr-MTAC, we observed a tendency toward normalization of the parameters of peritoneal function. Patients with peritonitis (n = 88) showed a first year increase in Cr-MTAC, which was significantly higher than in patients without peritonitis (11.1+/-5 vs 9.5+/-4.2, P<0.01). Ultrafiltration decreased in patients with more than four accumulated days of peritonitis (from 1062+/-447 to 1024+/-340 ml/4 h, NS); it increased in patients without peritonitis. CONCLUSIONS: The peritoneal transport parameters tended toward normalization during the first year on PD, mainly with a decrease of small solute transport and an increase of ultrafiltration capacity. This evolution is independent of age, gender, diabetes and higher exposure to glucose in PD solutions. Peritonitis was the only independent factor that affected peritoneal function during the first year on peritoneal dialysis.     

Vitamin status of infants receiving long-term peritoneal dialysis

The oral vitamin intakes and blood vitamin concentrations of seven infants receiving long-term peritoneal dialysis were measured. The serum concentrations of vitamin A, vitamin B₁₂, vitamin C and folic acid were determined. Thiamine and riboflavin were assessed by the activation of erythrocyte transketolase and erythrocyte glutathione reductase, respectively. Vitamin B₆ was measured as plasma pyridoxal phosphate. All patients received a daily vitamin supplement devoid of vitamin A. Dietary vitamin intake was derived from infant formula. In all cases, the patients' blood concentrations of the water-soluble vitamins were equal to or greater than normal infant values. Serum vitamin A levels were elevated despite the lack of supplementation. The combined dietary/supplemental water-soluble vitamin intake of the patients exceeded the recommended daily allowance in all but one patient. These preliminary data emphasize the need to further evaluate the vitamin requirements of infants receiving long-term peritoneal dialysis.     

Natural changes in peritoneal equilibration test results in continuous ambulatory peritoneal dialysis patients: a retrospective, seven year cohort survey

We conducted a retrospective, 7 year cohort survey to examine the natural changes in peritoneal equilibration test (PET) results in patients with long-term uneventful continuous ambulatory peritoneal dialysis (CAPD). Thirty-two (17 males, 15 females) patients on CAPD with two or more standard PETs performed more than 6 months apart, in the absence of peritoneal insult, were included. Changes and pattern of PET results were evaluated by the dialysate to plasma ratio of creatinine (D:P-cre), the fourth h dialysate to instilled glucose ratio (D4:Do) and ultrafiltration volume (UF, ml). The subgroups included high (H), high-average (HA), low-average (LA), or low (L) transporters with the dividing ratios (D:P-cre) of >0.81, >0. 65 to 0.81, >0.5 to 0.65, and <0.5, respectively. The median D:P-cre significantly decreased (p = 0.04), but neither the D4:Do nor the final median UF significantly decreased. The change in D:P-cre was strongly and inversely correlated with the initial D:P-cre value (r = -0.68; p < 0.05). A similar relationship was found between the change in the final D4:Do and the initial D4:Do (r = -0.752; p < 0. 01) and between the change in the final UF and the initial UF (r = -0.875; p < 0.01). No correlation was found between the change in D:P-cre and the age of the patient, the time interval between PETs, monthly dialysate glucose exposure, or underlying diabetes/non-diabetes. The final peritoneal transport pattern was altered with 5 (15.6%) patients remaining in the extreme subgroups (H or L) and, by contrast, 84.4% (27/32) of the patients now in the averaged (HA or LA) groups (p < 0.01, chi2 test). We demonstrated a natural "centralization" migration of PET results after long-term uneventful CAPD, which may help to explain why patients with extreme PET characteristics, that is, H or L, continued to do well on CAPD.     

低分子肝素对腹膜透析患者腹膜功能影响的观察

目的探讨低分子肝素对腹膜透析患者腹膜通透性、腹膜超滤量的影响。方法选择病情稳定的腹膜透析患者22例,采用双盲交叉对照设计,将患者随机分成2组,分别于腹膜透析液中加入低分子肝素和生理盐水,治疗3个月,再经1个月的洗脱期后交换处理因素,分别观察患者的腹膜通透性、超滤量及各凝血指标的变化。结果低分子肝素处理期,透析液肌酐／血肌酐和透析液尿素／血尿素比值较处理前和生理盐水处理期均明显降低,差异均有统计学意义（P〈0．05）。低分子肝素处理期透析液白蛋白／血白蛋白比率较处理前和生理盐水处理期明显降低,差异均有统计学意义（P〈0．05）。低分子肝素处理期4h、0h透析液葡萄糖比率及24h超滤量均较处理前和生理盐水处理期明显升高,差异均有统计学意义（P〈0．05）。所有患者观察期间均未出现腹腔出血并发症。结论腹膜透析患者腹膜透析液中加入低分子肝素可降低腹膜小分子的通透性,增加腹膜超滤量,而不增加出血的风险。     

In vitro buffering capacity of residual peritoneal dialysate fluid: implications for peritoneal dialysis therapy

The buffering capacity of the residual peritoneal dialysate fluid from each of 5 patients undergoing continuous ambulatory peritoneal dialysis was assessed by titrating with fresh, conventional, acidic, and lactate-containing peritoneal dialysis solutions. It was found that residual fluids had considerable buffering capacity.