The association between soluble intercellular adhesion molecule-1 levels in drained dialysate and peritoneal injury in peritoneal dialysis

Background: Chronic inflammation of the peritoneum causes peritoneal injury in patients on peritoneal dialysis. Intercellular adhesion molecule-1 and its circulating form, soluble intercellular adhesion molecule-1, play pivotal roles in inflammation. However, their role in peritoneal injury is unclear.

Methods: We measured changes in intercellular adhesion molecule-1 expression in the peritoneum of a peritoneal injury model in rats. The associations between soluble intercellular adhesion molecule-1 levels in drained dialysate and the solute transport rate (D/P-Cr and D/D0-glucose) determined by the peritoneal equilibration test, and matrix metalloproteinase-2 levels in drained dialysate were investigated in 94 peritoneal drained dialysate samples.

Results: Intercellular adhesion molecule-1 expression was increased in the peritoneum of rats with peritoneal injury. Soluble intercellular adhesion molecule-1 levels in drained dialysate were significantly positively correlated with D/P-Cr (r?=?.51, p?r?=??.44, p?r?=?.86, p?Conclusions: Intercellular adhesion molecule-1expression is increased in the peritoneum of a peritoneal injury model in the rat, and soluble intercellular adhesion molecule-1 levels in drained dialysate are associated with peritoneal injury in patients on peritoneal dialysis. These results suggest that soluble intercellular adhesion molecule-1 could be a novel biomarker of peritoneal injury in patients on peritoneal dialysis.     

Effect of peritoneal dialysis on expression of vascular endothelial growth factor, basic fibroblast growth factor and endostatin of the peritoneum in peritoneal dialysis patients

Aim: The aim of this study is to investigate the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin (ES) in human peritoneum and investigate the relationship between them and peritoneum neoangiogensis in the patients with uraemia and peritoneal dialysis (PD). Methods: Peritoneal biopsies were obtained from normal subjects (n = 8), uraemic predialysis patients (n = 12) and PD patients (n = 10). The mRNA expression of VEGF, bFGF and ES in peritoneal tissues were measured through real‐time polymerase chain reaction. The protein expression of VEGF, bFGF and ES in peritoneal tissues were determined through western blot. Microvessel density (MVD) of peritoneal tissue was assessed using immunohistochemistry with CD34 monoclonal antibody. Results: The mRNA and protein of VEGF, bFGF and ES were expressed in all peritoneal samples. Compared with the normal control group, the mRNA and protein expression of VEGF and bFGF in peritoneal tissues were all significantly upregulated in the uraemic predialysis and PD group (all P < 0.05). Compared with the normal control group, the protein expression of ES were significantly upregulated in the uraemic predialysis and PD group (all (P < 0.05), but the mRNA expression of ES did not have obvious differences in the uraemic predialysis and PD group as compared to the normal control group (P > 0.05). MVD of peritoneal tissue were increased in the uraemic predialysis and PD group compared with the normal group (all P < 0.05). A significant positive correlation was found between VEGF mRNA expression and MVD, bFGF mRNA expression and MVD. Conclusion: The mRNA expression of VEGF and bFGF, the protein expression of VEGF, bFGF, and ES and microvessel density (MVD) are increased both in the uraemic predialysis and PD patients. These results show that uraemia circumstances and non‐physiological compatibility of peritoneal dialysis solution might increase VEGF, bFGF and ES expression and MVD, which might participate in the increment of the peritoneum neoangiogensis and ultrafiltration failure in PD patients.     

Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis

Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.     

参芎注射液对大鼠腹膜间皮细胞紧密连接的影响

目的:观察高糖腹膜透析液和添加参芎注射液的腹膜透析液对腹膜间皮细胞(PMC)紧密连接形态结构和紧密连接相关蛋白封闭蛋白-1(ZO-1)表达的影响。方法:SD大鼠随机分为4组,空白组、模型组和参芎注射液低剂量、高剂量干预组,4周后检测4组SD大鼠的腹透超滤量、腹膜转运功能。并应用光镜、透射电镜和免疫组织化学染色法观察各组的腹膜厚度,紧密连接结构的改变和ZO-1蛋白水平表达的变化。结果:各组之间比较超滤量、D/Pcr、D4/D0、腹膜厚度及ZO-1表达率差异均有统计学意义(P<0.05),腹透液中添加参芎注射液能改善大鼠的腹透超滤量,减轻腹膜的增厚,改善腹膜的转运功能,且高剂量干预组优于低剂量干预组(P<0.05)。结论:高糖腹膜透析液可引起PMC的损伤,影响紧密连接和ZO-1的表达,参芎对PMC及其紧密连接等结构有一定的保护作用。     

Fas Expression on Peritoneal Macrophages during Continuous Ambulatory Peritoneal Dialysis Peritonitis

Background. Peritonitis is a common complication of end stage renal failure (ESRF) patients receiving continuous ambulatory peritoneal dialysis (CAPD). Peritoneal macrophage may participate in the activation of specific T cells and in the generation of local cell-mediated immunity to various pathogens. The purpose of this study is to investigate the possible role of macrophage in CAPD patients with peritonitis. Methods. We evaluated the expression of Fas receptor (CD95), ICAM-1 (CD54), CD25, and CD69 by two-color flow cytometry on extravasted macrophages from 16 ESRF patients on CAPD with peritonitis (peritonitis-positive) and compared them to 11 ESRF patients on CAPD without peritonitis (peritonitis-negative) and normal controls. Results. We found an increased expression of CD95, CD54, and CD25 on macrophage in peritonitis-positive group compared to controls (all p < 0.001). In the peritonitis-positive group, the CD95 expression was significantly higher than that of the peritonitis-negative group (p < 0.001). The expression of CD54, CD25, and CD69, however, was not significantly different between the peritonitis-positive and peritonitis-negative CAPD subgroups. Conclusion. We found an abnormally increased percentage of macrophage-expressing Fas receptor and ICAM-1, and the percentage of CD95+ macrophage, but not those of other markers, were increased among the subset of CAPD patients with peritonitis. The later finding suggests that this macrophage phenotype is associated with peritonitis occurring in CAPD.     

The Effect of Colchicine on the Peritoneal Membrane

Peritoneal dialysis (PD) is a treatment modality for patients with renal failure. Peritoneal fibrosis is one of the most serious complications after long-term continuous ambulatory peritoneal dialysis (CAPD). Histological studies in both humans and animals show that chronic peritoneal dialysis results in fibrosis of the peritoneal membrane. In our study, we investigated the effect of colchicine on peritoneal alterations induced by hypertonic PD solution in rats. Sprague-Dawley rats intraperitoneally received saline (control group) once daily, for 28 days, or 3.86% glucose (PDF group), or 3.86% glucose plus colchicine (colchicine group). Animals from each group were sacrificed after 28 days with anesthetized ketamine (60 mg/kg BW). For the PD fluid assessment, 1 h before the sacrifice of animals, 10 mL PD fluid of 2.27% glucose was given, and this fluid was obtained after the sacrifice. The levels of transforming endothelial growth factor β (TGF-β), tumor necrosis factor α (TNF-α) and albumin were investigated both in the peritoneal dialysate and blood, and the levels of malondialdehyde (MDA) were investigated only in peritoneal dialysate. The peritoneal membrane was evaluated histologically by light microscopy. When groups were compared in terms of body weight change, the colchicine group significantly lost weight compared to controls and PDF group (?4.7% ± 4.5, 3.5% ± 7.2, 3.0% ± 1.3, respectively, p = 0.018). Also, the blood albumin level was significantly lower for these in the colchicine group compared to those in the PDF group (2.7 ± 0.35 versus 3.2 ± 0.3 g/dL, respectively, p = 0.048). The blood TGF-β level was significantly lower in the control group, and no difference was observed between the PDF and colchicine groups (294.4 ± 67.5 versus 787.4 ± 237.4 versus 615.3 ± 235.1 pg/mL, respectively, p = 0.004). The mesothelial thickness found in groups was as follows: control group 102 ± 18.9 µm, PDF group 128.33 ± 33.1 µm, colchicine group 117 ± 35.6 µm (p = 0.34). In conclusion, a rat model for peritoneal dialysis associated peritoneal derangement without fibrosis could be induced. Colchicine could not prevent peritoneal derangement in this model.     

The potential of matrix metalloproteinase-2 as a marker of peritoneal injury, increased solute transport, or progression to encapsulating peritoneal sclerosis during peritoneal dialysis--a multicentre study in Japan.

BACKGROUND: Long-term peritoneal dialysis (PD) leads to peritoneal injury. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis (EPS), which is a serious complication of PD. The mortality rate of EPS is extremely high. To perform PD safely, monitoring of peritoneal injury that leads to EPS is a necessity. METHODS: A total of 444 PD patients with end-stage renal disease at 60 centres in Japan were analysed (sex, 54% males; median age, 56 years; median PD duration, 55 months). Matrix metalloproteinase (MMP)-2 and MMP-9 in the peritoneal effluents were analysed with gelatin zymography or enzyme-linked immunosorbent assay. Cells expressing MMP-2 in the peritoneal tissue were investigated immunohistologically with anti-MMP-2 antibodies. Peritoneal solute transport was assessed with the peritoneal equilibration test (PET). RESULTS: The MMP-2 levels in peritoneal effluents obtained with the PET were significantly correlated with the D/P Cr ratio (R = 0.69, P < 0.001) and the D/D0 glucose ratio (R = -0.59, P < 0.001). The MMP-2 levels in patients with mild peritoneal injury, moderate peritoneal injury, severe peritoneal injury (EPS) and infectious peritonitis were significantly higher than those in control patients (P < 0.001, P < 0.001, P < 0.01 and P < 0.05, respectively). MMP-2 was produced by myofibroblast-like mesenchymal cells and macrophages in the peritoneum. The peritoneal effluents from patients with infectious peritonitis showed strong MMP-9 signals. CONCLUSIONS: From these results, MMP-2 levels in peritoneal effluents reflect peritoneal solute transport and changes in MMP-2 levels are associated with peritoneal injury that leads to EPS. MMP-2 may be a useful marker of peritoneal injury, increased solute transport or progression to EPS.     

Increases in peritoneal small solute transport in the first month of peritoneal dialysis predict technique survival

BACKGROUND: Peritoneal transport of small solutes generally increases during the first month of peritoneal dialysis (PD). The aim of this study was to prospectively evaluate the ability of the peritoneal equilibration test (PET), carried out 1 and 4 weeks after the commencement of PD, to predict subsequent technique survival. METHODS: Fifty consecutive patients commencing PD at the Princess Alexandra Hospital between 1 February 2001 and 31 May 2003 participated in the study. Paired 1 week and 1 month PET data were collated and correlated with subsequent technique survival. RESULTS: A significant increase was observed in the dialysate : plasma creatinine ratio at 4 h (D/P Cr) between 1 and 4 weeks after the onset of PD (0.55 +/- 0.12 vs 0.66 +/- 0.11, P <0.001). Mean death-censored technique survival was superior in patients who experienced > or =20% rise in D/P Cr during the first month of PD compared with those who did not (2.3 +/- 0.2 vs 1.6 +/- 0.2 years, P <0.05). Using a multivariate Cox proportional hazards model analysis, the significant independent predictors of death-censored technique survival were an increase in D/P Cr of greater than 20% during the first month (adjusted hazard ratio [HR] 0.20, 95% CI 0.05-0.75), the absence of diabetes mellitus, the absence of ischaemic heart disease, body mass index and baseline peritoneal creatinine clearance. CONCLUSIONS: A 20% or greater rise in D/P Cr during the first month of commencing PD is independently predictive of PD technique survival. Further investigations of the mechanisms underlying this phenomenon are warranted.     

腹膜透析患者癌症相关抗原125水平与腹膜转运功能关系的研究

目的:检测腹膜透析患者腹透液中癌症相关抗原125(CA125)水平及腹膜转运功能,并探讨二者之间关系及其临床意义.方法:电化学发光法测定过夜腹透液中CA125浓度,行腹膜平衡试验检测腹膜转运功能.结果:腹透短期组、腹透中期组、腹透长期组三者的腹透液中CA125水平及4 h D/PCr相比较皆有统计学差异(P<0.05或P<0.01);腹透腹膜炎中、低发组观察前后两指标皆无统计学差异,也无明显的相关性,而腹透腹膜炎高发组观察前后两指标有统计学差异;观察各组两指标皆呈非显著性负相关.结论:腹膜透析患者癌症相关抗原125水平与腹膜转运功能关系不大.     

High mobility group box 1 and tumor growth factor β: useful biomarkers in pediatric patients receiving peritoneal dialysis

Background: Peritonitis, the most important limitation of peritoneal dialysis (PD), could be detected by biomarkers in dialysate effluent, representing a noninvasive method to indirectly assess the peritoneum status. The aim of our study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating its role as precocious marker of peritoneum damage during peritonitis. Transforming growth factor (TGF)-β was correlated with peritoneal transport characteristics.

Methods: Six patients, treated by ambulatory PD, were enrolled. Samples were collected at the onset of peritonitis (T1) and every day until its resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was also evaluated. Peritoneal Equilibration Test evaluated the filter activity of peritoneum.

Results: In patients with acute peritonitis, the highest serum and peritoneal HMGB1 values (64?±?3.6 and 70?±?5.3?ng/mL, respectively) were assessed, with a progressive decrease of their levels at the resolution time (T-end: sHMGB1:36?±?2.5; pHMGB1:30.5?±?7.0?ng/mL). While no differences of sWBC and pWBC were observed between baseline and T-end values, pHMGB1 levels remained higher at T-end than those observed at T0 (pHMGB1:30.5?±?7.0 versus 6.9?±?3.6; p?p?=?0.01). An inverse correlation was found between TGF-β levels and dialysate/plasmatic creatinine values (r = ?0.83; p?=?0.03).

Conclusion: HMGB1 represents a useful biomarker for peritoneum evaluation in PD patients. A prognostic role of this alarmin, as a marker of response to therapy, could be hypothesized. TGF-β could predict the peritoneal transport status and dialysis technique adequacy.     

Inhibition of Rho-kinase alleviates peritoneal fibrosis and angiogenesis in a rat model of peritoneal dialysis

Abstract

Background/Aims: The present study investigated whether Rho-kinase inhibition had a therapeutic role on the pathogenesis of peritoneal fibrosis and angiogenesis. Methods: A rat model of peritoneal dialysis was induced by a daily intraperitoneal infusion of 4.25% Dianeal. Those rats were treated with Rho-kinase inhibitor, fasudil. Immunofluorescence, Western blot and RT-PCR were used to detect the expression of TGF-β1, Collagen I, αSMA and VEGF in each group. Microvessel density (MVD) was measured by immunohistochemistry. Rho-kinase activity was determined by western immunoblotting. Results: Rho-kinase was activated in the peritoneum of the PD group, which was inhibited by fasudil. Compared with PD group, the mRNA and protein expressions of TGF-β1, αSMA and Collagen I were significantly downregulated in fasudil treatment groups in a dose-dependent manner, and the expression of VEGF and peritoneal MVD was also significantly downregulated in fasudil treatment groups in a dose-dependent manner. Conclusion: The Rho-kinase was activated in the peritoneum of the peritoneal dialysis rats, and the inhibition of Rho-kinase by fasudil can remarkably decrease peritoneal fibrosis and angiogenesis.     

不同腹膜转运特性对血钙、血磷及PTH的影响

目的研究无尿持续非卧床腹膜透析（CAPD）患者腹膜转运功能对骨矿物质代谢的影响。方法选择159例无尿CAPD患者,根据腹膜平衡试验将患者分为2组：低转运特性组87例,高转运特性组72例。检测两组患者血钙、血磷、甲状旁腺激素等生化指标,测定腹膜尿素清除指数（KT／V）及肌酐清除率（CCr）。结果与低转运特性患者相比,高转运特性患者血钙、血磷和甲状旁腺激素水平明显偏低,而KT／V、CCr偏高,差异有统计学意义（P〈0．05）。多元逐步回归分析显示,CCr与血钙、血磷呈负相关（P〈0．05）,Kt／V与血钙呈负相关关系（P〈0．05）,而D／Pcr与血钙、血磷、甲状旁腺激素无明显相关性。结论低腹膜转运特性患者易出现高磷血症和高甲状旁腺激素;腹摸转运特性能影响血钙、血磷、甲状旁腺激素水平,但之间未见显著相关性。     

CD4/CD8 T‐Cell Ratio in Peritoneal Dialysis Effluents Predicts the Outcome of Peritonitis in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

This study aimed to clarify the role of peritoneal T‐lymphocytes in peritoneal immune defense mechanisms. This study was designed to examine the changes in T‐cell subpopulations during peritonitis in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Our observations were correlated to responses to treatment and with outcomes. The present study was carried out in 20 patients (8 males, 12 females) under CAPD. Peritonitis was diagnosed according to the criteria defined by the Ad Hoc Advisory Committee on Peritonitis Management. Peritoneal dialysate effluent (PDE) samples were collected from our patients, and lymphocyte subsets (CD2+, CD3+, CD3+/4+, CD3+/8+, CD3?/16+56+, CD4/CD8 ratio) were quantitated by using monoclonal antibodies. CD4/CD8 ratio was measured every day during peritonitis until the patients had completely recovered. The serial measurements of the CD4/CD8 ratio made in the PDE during peritonitis followed two patterns: the first pattern was characterized by a progressive increase in the CD4/CD8 ratio. The CD4/CD8 ratios on days 5, 6, and 7 were significantly higher than those on day 1 (P < 0.05). Overall, the patients who exhibited pattern 1 had favorable clinical courses. The second pattern was characterized by high initial CD4/CD8 ratios, which progressively decreased significantly (P < 0.05). This second pattern was associated with a delayed clinical response to treatment. Symptoms and signs of peritonitis persisted beyond 72 h. The pattern of the CD4/CD8 ratio in PDE may determine the outcome of peritonitis in CAPD patients.     

Prevention of Postoperative Peritoneal Adhesions by Administration of Estrogen

Aim: Postoperative abdominal adhesions represent one of the most common causes of intestinal obstruction in surgical patients. In this study, the effects of intraperitoneal administration of estrogen on the development of postoperative intraabdominal adhesions and peritoneal leucocytes in a rat adhesion model were investigated. Methods: Sixty Wistar albino rats were divided into three groups. Group 1 (control group) had their abdomen closed after surgery without administration of any material or drug. Group 2 (saline group) received 2 ml of 0.9% NaCl, and group 3 (estrogen group) animals received a single intraperitoneal dose of 2 cc (1 mg) estrogen (Estradiol propionate, 50.000U, Akrofilline®, Biofarma, Turkey). All the groups were exposed to the same adhesion-creating procedure (Swolin K. Experimental studies on the prevention of intra-abdominal adhesions. Studies on rats with an emulsion of lipid and prednisolone. Acta Obstet Gynecol Scand. 1966;45:473–498.). After 7–42 days, all animals were sacrificed. Adhesions were scored and peritoneal leucocytes were counted. Results: The adhesion formation and peritoneal leucocyte count of the estrogen group were significantly less than the control and saline groups and a statistically significant difference was determined in comparison of those groups (p <. 05). Conclusion: We concluded that intraperitoneal estrogen decreases the incidence of postoperative intraabdominal adhesion formation in rat adhesion model.     

The effects of Panax notoginseng saponins on the cytokines and peritoneal function in rats with peritoneal fibrosis

Abstract

Background: Due to the long-term and chronic exposure to the peritoneal dialysis fluid, patients could develop peritoneal fibrosis and ultrafiltration failure which compromises treatment efficacy and outcome, and fibrosis is the major cause of peritoneal dialysis (PD) withdraw among patients. Methods: Twenty-one male WISTAR rats were randomly assigned to three groups, namely saline group, standard peritoneal dialysis fluid (PDF) group, and panax notoginseng saponins (PNS) group. Peritoneal fibrosis was induced by daily injection of PDF for 4 weeks. After execution, multiple histological techniques including HE and Masson's trichrome staining and transmission electron microscopy (TEM) were applied to observe the pathological changes and concentrations of multiple cytokines may involve in the process of fibrosis were determined by enzyme-linked immune sorbent assay (ELISA). Biochemistry parameters were determined by automated chemistry analyzer. Results: PNS can significantly inhibit the expression of transforming growth factor beta (TGF-β1), connective tissue growth factor (CTGF), and monocyte chemoattractant protein (MCP-1) in the peritoneum of rats. Furthermore, pathological damages, including extracellular matrix deposition, vascularization, and fibroblast, were ameliorated in PNS group when being compared with standard PDF group. Peritoneal functions were improved by regular PNS treatment with significantly elevated ultrafiltration. Conclusion: PNS is capable of improving peritoneal function in subjects with PDF exposure and can possibly applied in patients with PD after further verification.     

腹膜平衡试验在临床中应用及护理

随着腹膜透析（ＰＤ）装置的不断改进，ＰＤ合并感染虽明显减少，但透析不充分、营养不良等问题却日益突出。腹膜平衡试验（ＰＥＴ）提供了秀好的解决办法。它使ＰＤ剂量和方式个体化。通过临床应用２８例，其中高转运３例占１０．６％，后改行间隙透析（ＩＰＤ）；高于平均转运１９例占６７．９％；低于平均转运５例占１７．９％；低转运１例占３．６％，后改行ＨＤ。在ＰＥＴ过程中，护士应准确无误的采集标本，教会患者正确配合；     

Association between inflammation and changes in residual renal function and peritoneal transport rate during the first year of dialysis.

BACKGROUND: Peritoneal transport rate, a major determinant of peritoneal dialysis (PD) patient survival, increases in most patients starting on PD, while in other patients peritoneal transport rate may decline. Although several factors may contribute to changes in peritoneal transport rate, inflammation is known to be associated with a high peritoneal transport rate, and residual renal function (RRF), which often declines after start of PD, may also be related to inflammation. Therefore, we hypothesized that changes in peritoneal transport rate during patients' first year on PD and declining RRF may be linked with inflammation. METHODS: A total of 76 PD patients (40 males, mean age 56.8+/-14.1 years), who underwent two peritoneal equilibration tests at a mean of 0.4 months and 1 year after beginning PD, were included in the study. Based on the change in dialysate to plasma creatinine concentration ratio at 4-h dwell (D/P Cr) during first year on PD, the patients were divided into decreased or unchanged (group DUC; n=22) and increased (group I; n=54) groups. RESULTS: Initially, group I had a lower proportion of high transporters and more often high serum C-reactive protein (sCRP, > or =10 mg/l) and lower RRF compared with the DUC group. In group I, serum albumin and RRF decreased significantly and dialysate protein loss and glucose absorption increased significantly during the first year on PD. When patients were divided into two groups based on median change in RRF (1.9 ml/min), patients with a decrease in RRF >1.9 ml/min during first year on PD had a higher proportion of high sCRP, higher D/P Cr, and higher changes in D/P Cr compared to patients with a decrease in RRF < or =1.9 ml/min. Patients with elevated sCRP at one year included a higher proportion of patients who had high sCRP at the start of PD, higher increase in D/P Cr, lower serum albumin, lower RRF, and more decrease in RRF during first year on PD compared with patients having normal sCRP. RRF was inversely correlated with changes in D/P Cr during the first year on PD (r=-0.28, P=0.02). Multiple regression analysis revealed that the only factors affecting changes in D/P Cr were high sCRP and a low RRF. CONCLUSIONS: Our preliminary short-term study suggests that changes in peritoneal transport rate during patients' first year on PD may be linked with inflammation and declining residual renal function. Inflammation and residual renal function were identified as the only independent factors determining peritoneal transport rate during the first year on PD. It is possible that inflammation may cause both an increase in peritoneal transport rate and a decline in residual renal function, or that the decline in residual renal function and the increase in peritoneal transport rate may induce or aggravate inflammation. Further studies are needed to confirm these findings.     

血管内皮生长因子和内皮抑素在人腹膜组织的表达及其与腹膜毛细血管新生的关系

目的 检测血管内皮生长因子（VEGF）和血管内皮抑素（ES）在人腹膜组织表达,探讨两者与腹膜血管新生之间的关系。 方法 取健康对照者、尿毒症非透析患者以及腹透患者的腹膜标本,用反转录聚合酶链反应（RT-PCR）检测VEGF和ES mRNA的表达;组织免疫组化染色检测VEGF和ES蛋白质水平的表达;CD34染色计数腹膜组织毛细血管密度（MVD）。 结果 各组腹膜均有VEGF及ES表达;健康对照组、尿毒症非透析组、腹透组VEGF mRNA的相对表达量依次为0.47±0.01、0.62±0.02、0.74±0.02。VEGF免疫组化染色阳性区平均灰度值依次为95.673±2.01、117.126±2.07、140.184±2.25。ES免疫组化染色阳性区平均灰度值依次为94.902±2.38、113.380±2.33、145.489±3.05。尿毒症非透析组、腹透组VEGF mRNA和蛋白表达水平及ES蛋白表达水平表达均高于健康对照组,且腹透组升高更为明显,差异均具有统计学意义（均P < 0.05）。3组ES在mRNA水平表达量依次为0.42±0.02、0.43±0.03、0.43±0.02,各组表达差异无统计学意义（P > 0.05）。3组腹膜MVD依次为3.05±0.45、5.98±0.47、9.62±0.49,尿毒症非透析组、腹透组均高于健康对照组,且腹透组增高更为明显,差异均具有统计学意义（均P < 0.05）。 结论 腹膜透析患者腹膜组织VEGF mRNA和蛋白表达水平升高,ES蛋白表达水平也升高,这可能在长期透析所致腹膜组织新生毛细血管形成过程中发挥一定作用。     

Effects of atorvastatin on development of peritoneal fibrosis in rats on peritoneal dialysis

Rational: Peritoneal sclerosis is one of the important complications of long-term peritoneal dialysis (PD). In this study, efficacy of atorvastatin on peritoneal histology and functions in non-uremic rats on PD was tested. Objectives: Twenty-two non-uremic Wistar albino rats were randomized into three groups: Sham (intraperitoneal saline), peritoneal dialysis (PD, intraperitoneal 3.86% dextrose containing PD solution), and treatment (TX, intraperitoneal 3.86% dextrose containing PD solution plus atorvastatin added into drinking water). At the end of a 4-week period, 1 h peritoneal equilibration test was performed. Serum lipids and certain cytokines, mediators, markers, and antioxidant enzyme activities in serum and dialysate were studied. Peritoneal thickness was measured and peritoneal inflammation, fibrosis, and vascular proliferation were scored in histological sections. Main findings: In histological examinations, inflammation, fibrosis, and vascular proliferation were significantly more frequent in PD group than Sham group and it seemed to decrease significantly when atorvastatin was used in conjunction with PD. Additionally, peritoneum was significantly thicker in PD group when compared to that of Sham and TX groups. Serum parameters did not significantly differ between groups. On the other hand, dialysate glutathione reductase (GR) activity and TGF-β were significantly lower in TX group than that of the PD group, whereas dialysate IL-6 level was higher in TX group. Principal conclusions: In our study, atorvastatin use appeared to diminish structural changes in peritoneum. Decreased expression of TGF-β in dialysate may be one of the possible underlying mechanisms.