Role of rosiglitazone in lipopolysaccharide-induced peritonitis: A rat peritoneal dialysis model

Aim: The aim of this study was to demonstrate the efficacy of the peroxisome proliferator‐activated receptor (PPAR)‐γ agonist, rosiglitazone, in the amelioration or prevention of inflammation including peritoneal fibrosis secondary to the peritonitis in a peritoneal dialysis (PD) model of non‐uraemic rats. Methods: Thirty male Sprague–Dawley rats were assigned to six groups according to treatment. A 90 min peritoneal equilibrium test, dialysate cellular components, peritoneal thickness and cellularity were assessed on day 21. Additionally, immunohistochemical stains of peritoneal membrane, such as PPAR‐γ, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)‐β1, collagen‐1 and monocyte chemoattractant protein‐1 were performed Results: The dialysate neutrophil count and peritoneal thickness in the high‐dose rosiglitazone group was significantly decreased compared to the lipopolysaccharide (LPS)‐only group. The peritoneal membrane from the LPS‐only group showed marked cellular proliferation in the area of the submesothelial compact zone compared with the PD‐only group, the rosiglitazone‐only group, and the high‐dose rosiglitazone group. The 90 min peritoneal equilibrium test (PET) results showed no statistical difference among the six groups excluding dialysate‐to‐plasma urea ratio. The number of PPAR‐γ expressing cells and the expression of TGF‐β1 were decreased in the high‐dose rosiglitazone group compared to the LPS‐only group. There were no differences in the expression of VEGF and collagen‐1 among the six groups. Interestingly, the number of PPAR‐γ‐positive cells was correlated with expression of VEGF, TGF‐β1, collagen‐1 and monocyte chemoattractant protein‐1 irrespective of the study group. Conclusion: The results of this study showed that rosiglitazone ameliorated peritoneal inflammation induced by LPS and reduced the TGF‐β1 expression in the peritoneal membranes.     

A positive effect of AII inhibitors on peritoneal membrane function in long-term PD patients

Background. Experimental studies showed that inhibition of AIIeffects attenuates the development of peritoneal membrane fibrosisand neoangiogenesis. The latter leads to an increase of peritonealsolute transport and ultrafiltration failure. The results ofa single-centre study showed that use of ACEI/ARB can preventthe increase of small solute transport in long-term PD patients.Our aim was to investigate whether these results would alsobe present in a larger population and influence patient andtechnique survival in long-term PD. Methods. We analysed data from 217 long-term CAPD patients,participating in the Netherlands Cooperative Study on Adequacyof Dialysis (NECOSAD). Included patients underwent CAPD therapyfor at least 2 years; 120 of them were treated with the ACE/AIIinhibitors-ACEI/ARB group. The control group consisted of 87patients who received none of the above drugs and 10 patientswho had them for <25% of their time on PD. Results. A significant difference in the time course of peritonealtransport was found between the two groups. The value of 24-hD/P creatinine was associated with the PD duration (P = 0.01)and its time course was influenced by use of ACEI/ARB (P = 0.05).We found no effect of ACEI/ARB on patient survival, but somebenefit was found for the technique survival: in a multivariatemodel the hazard ratio for the group with the longest use ofACEI/ARB was 0.5 (CI 0.22–1.4), P = 0.19. Conclusions. We conclude that AII inhibition prevents the increasein small solute transport in long-term PD. These drugs may alsohave some positive influence on PD technique survival.     

The Effects of Angiotensin Converting Enzyme Inhibitors on Potassium Homeostasis in Dialysis Patients With and Without Residual Renal Function

Hyperkalemia is exacerbated by angiotensin converting enzyme inhibitors (ACE‐I). Distal potassium (K⁺) secretion is negligible in anuric patients. ACE‐I therapy may reduce renal, peritoneal, and colonic K⁺ losses. We examined the effect of ACE‐I therapy on serum, urinary, and dialysate K⁺ in a cross‐section of peritoneal and hemodialysis patients. Serum, 24‐h urine K⁺, and peritoneal dialysate excretion K⁺ levels were measured and the results were compared in the various dialysis and treatment groups. Eighty‐one hemodialysis (HD) and 32 peritoneal dialysis (PD) patients were included. Serum K⁺ in HD patients with no residual renal function (RRF) was higher in those receiving ACE‐I therapy (P = 0.02). Serum K⁺ levels in HD patients receiving ACE‐I treatments with RRF was similar to that in oligoanuric HD patients not receiving an ACE‐I. Urinary K⁺ excretion was significantly reduced in those on ACE‐I therapy versus those not on an ACE‐I (P < 0.05). Mean serum K⁺ was lower in PD versus HD patients (P < 0.05). PD patients with no RRF on ACE‐I therapy had higher serum K⁺ concentrations (P = 0.002) and dialysate K⁺ excretion was lower (P = 0.05), in comparison with PD patients not on an ACE‐I. PD patients with RRF on ACE‐I therapy had higher serum K⁺ concentrations compared with those not on ACE‐I therapy (P = 0.03). Both urinary and dialysate K⁺ excretion were reduced (P = 0.001 and P = 0.002, respectively). ACE‐I therapy increases serum K⁺ concentration in dialysis patients. PD patients have relatively lower serum K⁺ levels compared with HD patients. In PD patients, ACE‐I therapy reduces dialysate K⁺. These changes may result from reduced peritoneal movement of K⁺.     

Relation of ankle-brachial index to the rate of decline of residual renal function in peritoneal dialysis patients

Aim: The aim of this study was to determine whether ankle‐brachial index (ABI) predicts the rate of decline of residual renal function (RRF) in peritoneal dialysis (PD) patients. Previous studies demonstrated the importance of loss of RRF in predicting all‐cause risk and cardiovascular mortality in PD patients. It is also known that patients with a low ABI value have a greater risk for deteriorating renal function in the general population. The relationship between ABI and the declining rate of RRF in PD patients with an additional dialysis‐specific risk factor is uncertain. Methods: Seventy‐four PD patients with RRF of more than 1 mL/min per 1.73 m² were analyzed. ABI was used as the surrogate measure of pre‐existing cardiovascular disease and atherosclerosis burden to further determine the outcome of RRF in this study. The slope of decline of RRF was used to determine the outcome. Results: Based on the multivariate analysis, only ABI (P < 0.001), diabetes (P = 0.02) and baseline RRF (P = 0.009) independently predicted a faster decline in RRF. A stepwise multiple linear regression analysis demonstrated that ABI was an independent predictor for the slope of decline of RRF (P < 0.001). Conclusion: A low ABI is an independent predictor of not only the known atherosclerotic events, but also of the rate of decline of RRF over time in PD patients.     

Intraperitoneal heparin reduces peritoneal permeability and increases ultrafiltration in peritoneal dialysis patients.

BACKGROUND: Patients on long-term treatment with peritoneal dialysis (PD) suffer from increasing peritoneal permeability and loss of ultrafiltration as a result of persistent inflammation, which may be triggered by bioincompatible dialysis fluids. Heparins have anti-inflammatory and anticoagulant properties. We have examined the effect of intraperitoneal (IP) low-molecular weight heparin (tinzaparin) on peritoneal permeability and ultrafiltration in PD patients. METHODS: By means of a double-blinded cross-over design, 21 PD patients were randomized to receive either placebo or tinzaparin intraperitoneally once a day for two treatment periods of 3 months, separated by a wash-out period. The effect of heparin on peritoneal permeability and ultrafiltration was assessed using the 4 h standard peritoneal equilibration test. RESULTS: IP tinzaparin reduced significantly the dialysate-to-plasma ratios (D/P) of creatinine (P < 0.01), urea (P < 0.01) and albumin (P<0.05). In addition, the ratio of glucose concentration in dialysate at 4 h dwell to that of 0 h dwell (D(4)/D(0)) was increased (P<0.05) along with an increase in ultrafiltration volume (P<0.05). CONCLUSIONS: IP tinzaparin reduces peritoneal permeability to small solutes and increases ultrafiltration in PD patients.     

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.     

Octreotide lessens peritoneal injury in experimental encapsulated peritoneal sclerosis model

Aim: Encapsulated peritoneal sclerosis is characterized by neoangiogenesis and fibrosis. Octreotide, a somatostatin analogue is a well‐known antifibrotic, antiproliferative and anti‐angiogenic agent. The aim of the study is to evaluate the effects of octreotide in encapsulated peritoneal sclerosis‐induced neoangiogenesis and fibrosis and compare the results with resting. Methods: Non‐uraemic Wistar‐Albino male rats (n = 35) were divided into four groups. Group I, control rats, received 2 mL isotonic saline i.p. daily for 3 weeks. Group II, received daily i.p. 2 mL/200 g injection of chlorhexidine gluconate (0.1%) and ethanol (%15) dissolved in saline for 3 weeks. Group III, chlorhexidine gluconate for 3 weeks plus an additional 3 weeks without any treatment (rest), to a total of 6 weeks. Group IV, chlorhexidine gluconate for 3 weeks plus an additional 3 weeks octreotide, 50 mcg/kg bodyweight s.c., for a total of 6 weeks. Results: Octreotide significantly reversed ultrafiltration capacity of peritoneum with decreasing inflammation, neoangiogenesis and fibrosis compared to the resting group. Octreotide also caused inhibition of dialysate transforming growth factor‐β1, vascular endothelial growth factor and monocyte chemotactic protein‐1 activity and improved mesothelial cell cytokeratin expression. Peritoneal resting has no beneficial effects on peritoneum. Conclusion: In conclusion, octreotide may have a therapeutic value in peritoneal dialysis patients who suffer from encapsulated peritoneal sclerosis.     

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.     

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.     

Reduction in Peyronie's‐like plaque size using a vacuum erection device in a rat model of Peyronie's disease via the TGF‐β/SMAD signalling pathway

Peyronie's disease (PD) is a fibrotic disorder of the tunica albuginea (TA). This study aimed to determine the therapeutic effects of a vacuum erection device (VED) in an animal model of PD and explore the possible mechanisms. Twenty‐seven male Sprague‐Dawley rats were used. The sham group (group A) (N = 9) received a 50‐μl‐saline vehicle injection into the TA, while the remaining 18 rats (groups B and C) received a TGF‐β1 injection into the TA. The treatment group (group C) underwent VED therapy for 10 days after the TGF‐β1 injection. Erectile function was then assessed at day 42. Rats injected with TGF‐β1 showed significantly lower intracavernous pressures than those in the sham group (p < 0.0001). After VED therapy, erectile function was significantly better in the treatment group than in the PD group (group B) (p < 0.0147). Masson's trichrome staining confirmed Peyronie's‐like plaques at the TGF‐β1 injection site in the PD group. Furthermore, the treatment group showed markedly smaller fibrotic plaque sizes than the PD group. A significant increase in TGF‐β1, SMAD2, SMAD3 and p‐SMAD2/3 protein expression was observed 6 weeks after the TGF‐β1 injection. However, the expression of the same proteins decreased after VED therapy. Protein expression trends were confirmed using immunohistochemistry analysis. The findings of this study demonstrate that VED therapy can reduce Peyronie's‐like plaque size in a rat model of PD while simultaneously improving erectile function.     

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.     

Compare the effects of intravenous and intraperitoneal mesenchymal stem cell transplantation on ultrafiltration failure in a rat model of chronic peritoneal dialysis

Aim: The purpose of this study was to compare the possible healing effects of intraperitoneal (IP) and intravenous (IV) mesenchymal stem cell (MSC) transplantation on ultrafiltration failure (UFF) in a chronic rat model of peritoneal dialysis (PD). Methods: Rats were initially divided into two groups. The UFF-group received once-daily IP injections of 20?mL of 3.86% glucose PD solution for six weeks to stimulate the development of UFF, and a control group received no injections. The UFF group was sub-divided into four groups: an UFF-C group, a MSC-IP group, a MSC-IV group and a placebo (P) group. Peritoneal equilibration tests (PETs) and peritoneal biopsies were performed in the control and UFF-C groups. MSCs were administered by IP injection in the MSC-IP group and by IV injection in the MSC-IV group. The P group received IP injection of placebo. PETs and peritoneal biopsies were performed in the MSC-IP, MSC-IV and P groups at the three weeks after receiving MSCs or placebo. Results: When compared with the control group, ultrafiltration capacity significantly decreased, and the submesothelial thickness increased in the UFF-C and P group, but there were no differences between the control and MSC-IP and MSC-IV groups. The rate of glucose transport was high in the UFF-C and P group compared with the control group, and D/P_Cr rates in the UFF-C and P group were lower than in the control group. However, D/D0_glucose was higher and D/P_Cr was lower in the MSC-IP group than in the UFF-C and P groups, but D/D0_glucose rate of MSC-IV group similar to UFF-C and P groups and there was no difference between MSC-IV group and the other groups in terms of D/P_Cr rates. The MSC-IP, MSC-IV and P groups had significantly decreased tumor necrosis factor α concentrations compared with the UFF-C group. MSC-IP group had lower levels of TGF-β1 compared with the P group; MSC-IP group had also lower levels of interleukin-6 compared with UFF-C group. Conclusion: The UFF group had a high permeability UFF. These results showed that IV and IP MSC transplantation exerted positive effects on UFF in a chronic rat model of PD. However, healing effect of small solute transport in MSC-IP group was better than MSC-IV group. IP MSC transplantation may be more effective than IV MSC transplantation for the renewal of the peritoneum in chronic PD patients with UFF.     

缬沙坦对持续性不卧床腹膜透析者腹膜功能的影响

目的 探讨血管紧张素受体拮抗剂缬沙坦对长期腹膜透析者腹膜功能的影响.方法 选择在焦作市人民医院接受腹膜透析者51例,采用数字表法随机分为缬沙坦组（n=28）和对照组（n=23）,对照组未服用血管紧张素转化酶抑制剂/血管紧张素受体拮抗剂类药物.观测并比较基线及1年后估计肾小球滤过率,行腹膜平衡实验,检测超滤量、透析液/血清肌酐（4 h）比值、透析液/葡萄糖浓度（4 h）比值.采用ELISA法检测隔夜腹膜透析液中转化生长因子β1以及血管内皮生长因子的含量.采用t检验进行数据统计.结果 基线时,两组患者临床资料差异无统计学意义（P＞0.05）.1年时,缬沙坦组与对照组估计肾小球滤过率均下降,分别为（3.1±1.8）、（2.1±1.9） ml/min,但对照组下降更为明显,与缬沙坦组比较差异有统计学意义（P＜0.05）.两组透析液/血清肌酐比值、透析液葡萄糖浓度比值差异无统计学意义,对照组超滤量增加更为明显,两组比较差异有统计学意义[对照组：基线时（351±210）ml/4 h,1年时（445±209） ml/4 h;缬沙坦组：基线时（336±198）ml/4 h,1年时（391±220）ml/4 h;P＜0.05].干预后,对照组转化生长因子β1和血管内皮生长因子的表达明显增加,与基线比较差异有统计学意义（P＜0.05）,而缬沙坦组干预前后转化生长因子β1和血管内皮生长因子的表达差异无统计学意义.结论 血管紧张素受体拮抗剂缬沙坦对腹膜透析者残余肾功能具有保护作用,可延缓腹膜透析者超滤衰竭的发生,抑制腹透液中腹膜纤维化相关因子的表达,进而抑制、延缓腹膜纤维化的发生和发展,保护腹膜功能.     

The importance of ultrasonographic measurement of peritoneal wall thickness in pediatric chronic peritoneal dialysis patients

Abstract

Loss of peritoneal function due to peritoneal fibrosing syndrome (PFS) is a major factor leading to treatment failure in chronic peritoneal dialysis (PD) patients. Although the precise biologic mechanisms responsible for these changes have not been defined, the general assumption is that alterations in peritoneal function are related to structural changes in the peritoneal membrane. Studies of the peritoneal membrane by non-invasive ultrasonography (US) in chronic PD patients are limited. The aim of the present study is to assess the relationship between functional parameters of peritoneum and peritoneal thickness measured by US in children treated by chronic PD. We recruited two groups of patients: 23 subjects (13 females, 10 males) on chronic PD (patient group) and 26 (7 females, 19 males) on predialysis out-patient follow-up (creatinine clearance: 20–60?mL/min/1.73?m²) (control group). Age, sex, weight, height, body mass index (BMI), chronic PD duration, episodes of peritonitis and the results of peritoneal equilibration test (PET) were recorded. Hemoglobin (Hb), blood pressure (BP), left ventricular mass index (LVMI) and renal osteodystrophy (ROD) parameters were also obtained. The thickness of the parietal peritoneum was measured by trans-abdominal US in all children. Statistical analyses were performed by using Student's t and Pearson's correlation tests. Mean peritoneal thickness in chronic PD patients (1028.26?±?157.26?μm) was significantly higher than control patients (786.52?±?132.33). Mean peritoneal thickness was significantly correlated with mean body height (R²?=?0.93, p?<?0.05), BMI (R²?=?0.25, p?<?0.05), chronic PD duration (R²?=?0.64, p?<?0.05), episodes of peritonitis (R²?=?0.93, p?<?0.05), D/P_creatinine (R²?=?0.76, p?<?0.05) and D4/D0_glucose (R²?=?0.81, p?<?0.05). No correlation was found between peritoneal thickness and Hb, BP, LVMI and ROD parameters. In conclusion, ultrasonographic measurement of peritoneal membrane thickness is a simple and non-invasive method in chronic PD children. This diagnostic tool likely enables to assess peritoneal structure and function in these patients.     

A comparison between residual renal function and peritoneal clearance for Na/H2O and urea removal in peritoneal dialysis patients

Background: To compare the Na/H₂O and urea removal between residual renal function (RRF) and peritoneal clearance (PC) in peritoneal dialysis patients. Try to explore the difference between RRF and PC in prognosis of chronic kidney disease patients who need peritoneal dialysis (PD) treatment. Methods: Weekly Na/H₂O and urea removal by PC and RRF were investigated individually. Independent samples t-test was carried out to compare the efficiency of removal between RRF and PC treatment. Pearson correlated analysis was applied to reveal the relationship between Na/H₂O and urea removal and Kt/V. Results: Although a higher Na/H₂O removal rate by RRF was showed in this investigation, the difference was not statistical significant compared to the one by PC. On the other hand, urea removal by RRF was obviously higher than PC. For every 0.1?Kt/V, Na/H₂O removal by RRF was distinctly higher than PD. The Na and H₂O removal of RRF were 147.88?±?83.72?mmol and 46.54?±?39.11?mmol, respectively; and the ones of PD were 11.40?±?6.08?mmol and 4.47?±?4.79?mmol. By using statistical assay, the correlations relevance between Na/H₂O removal and Kt/V in RRF were showed stronger than in PC. However, the total removal of Na/H₂O showed a poor correlation with Kt/V in both RRF and PC. Conclusions: The removal efficiency of RRF is much higher than PC. This study suggests that it is important to adjust dialysis program when RRF gets declined. Also the correlation between Na/H₂O removal rate and Kt/V is an important monitoring factor for the patients who are receiving peritoneal dialysis.     

Association between residual renal function, inflammation and patient survival in new peritoneal dialysis patients.

BACKGROUND: The recent ADEMEX study (Paniagua R, Amato D, Vonesh E et al. J Am Soc Nephrol 2002; 13: 1307-1320) indicates that peritoneal small solute clearance is not as critical for the survival of peritoneal dialysis (PD) patients as thought previously. On the other hand, low residual renal function (RRF), inflammation and an increased peritoneal transport rate (PTR) as evaluated by the peritoneal equilibration test (PET) are reported to be associated with increased mortality in PD patients, but the relationships between these factors and their separate and combined impact on the survival of PD patients are not clear. In this retrospective analysis, we evaluated possible relationships between RRF, inflammation and initial PTR in patients starting PD and the impact of these factors on patient survival. METHODS: A total of 117 patients with initial assessments for RRF, serum C-reactive protein (CRP) and PET at a mean period of 0.4+/-0.2 months (range 0.1-1.0 months) after start of PD were included in this study. Based on RRF (cut-off point, 4 ml/min/1.73 m(2)), serum CRP (cut-off point, 10 mg/l), and the dialysate to plasma creatinine ratio at 4-h of dwell (mean+1 SD), the patients were divided into different groups: low RRF and high RRF group, high CRP and normal CRP group and high PTR and other PTR group, respectively. RESULTS: Of 117 patients, 54 patients (46%) were in low RRF (<4 ml/min/1.73 m(2)) group, 36 patients (31%) were in high serum CRP (> or = 10 mg/l) group and 17 patients (15%) were in high PTR group. Forty-nine patients (42%) had one of these characteristics, 26 patients (22%) had two of these characteristics, two patients (2%) had three, and 40 patients (34%) had none of these characteristics. Patients with low RRF were older and had a higher prevalence of high CRP, lower normalized protein equivalent of total nitrogen appearance (nPNA), lower total Kt/V(urea) and lower total creatinine clearance (CCr) whereas patients with high CRP were older and had a higher proportion of men, lower serum albumin, lower nPNA, lower RRF and lower total CCr. Patients with high PTR had lower serum albumin, higher RRF and higher total CCr compared with patients with other PTR. Upon logistic multiple regression analysis, age and RRF were identified as factors affecting inflammation. Overall patient survival was significantly lower in the patients with low RRF, with high CRP, and in patients with more than two of the following: low RRF, high CRP and high PTR. In contrast, in patients with none of the discriminators low RRF, high CRP and high PTR, the 5-year survival was 100%. A high PTR was associated with decreased survival during the initial year on PD, but not thereafter. Patients who died during the follow-up period had a higher prevalence of high CRP and lower serum albumin, lower RRF, lower Kt/V(urea) and lower total CCr. Upon Cox proportional hazards multivariate analysis, age and RRF were predictors of mortality. CONCLUSIONS: These results indicate that in patients starting PD, low initial RRF is associated with inflammation, and low RRF and inflammation are both associated with high overall mortality. A high PTR was associated with higher mortality, but only during the initial year on PD, whereas Kt/V(urea) did not predict mortality. These results indicate the importance of RRF and inflammation as predictors of mortality in PD patients whereas the predictive power of PTR as such may lose its significance if these two parameters are taken into consideration.     

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.     

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.