Peritoneal Transport Function Research Articles

#6690 THE ASSOCIATION BETWEEN SERUM CHEMERIN AND PERITONEAL MEMBRANE TRANSPORT FUNCTION IN INCIDENT PERITONEAL DIALYSIS PATIENTS: A PROSPECTIVE COHORT STUDY

Abstract Background and Aims Some biomarkers in drained dialysate or peritoneal membrane have been found related to the dialysate/plasma ratio of creatinine at 4 h (D/P Cr) in patients undergoing peritoneal dialysis (PD). But so far, there is no report on serum markers. Some biomarkers are associated with cardiovascular diseases (CVDs). Chemerin is a multifunctional chemoattractant adipokine which plays roles in inflammation, adipogenesis and metabolism. In this study, we intended to investigate the role of chemerin in the peritoneal membrane transport function and CVDs in incident PD patients. Method This prospective cohort study was conducted in our PD center. The patients underwent initial standardized peritoneal equilibration test (PET) after PD for 4–6 weeks. Level of serum chemerin was determined via enzyme-linked immunosorbent assay (ELISA). The patients’ CVDs were recorded during the follow-up period. Results 151 eligible patients with a mean age of 46.59±13.52 years were enrolled. And the median duration of PD was 25.0 months. The median concentration of serum chemerin was 29.09 ng/mL. Baseline D/P Cr was found to be positively correlated with serum chemerin (r = 0.244, p = 0.003). The multivariate analyses revealed that serum chemerin (p = 0.002), age (p = 0.041), albumin (p = 0.000), and high-density lipoprotein (HDL) (p = 0.022) were independent factors of D/P Cr. The serum chemerin level was significantly higher in diabetes mellitus (DM) patients than that of patients without DM (36.45 vs 27.37 ng/mL, p = 0.000). And there was a significant statistical difference in CVDs between the high chemerin group (≥29.09 ng/mL) and low chemerin group (<29.09 ng/mL) (42% vs 21%, p = 0.009). Conclusion Serum chemerin has a positive correlation with baseline D/P Cr in incident PD patients. It may be a biomarker that can predict the baseline transport function of peritoneal membrane. And serum chemerin may be a risk factor of CVDs for incident PD patients. Multicenter studies with a larger sample size are warranted in the future.

The Association between Serum Chemerin and Peritoneal Membrane Transport Function in Patients Undergoing Incident Peritoneal Dialysis: A Prospective Cohort Study

Introduction: Some biomarkers in drained dialyzate or peritoneal membrane have been found related to the dialyzate/plasma ratio of creatinine at 4 h (D/P Cr) in patients undergoing peritoneal dialysis (PD). But so far, there is no report on serum markers. Some biomarkers are associated with cardiovascular diseases (CVDs). Chemerin is a multifunctional chemoattractant adipokine which plays important roles in inflammation, adipogenesis, and metabolism. We intended to investigate the role of chemerin in the peritoneal membrane transport function and CVDs in incident PD patients. Methods: This prospective cohort study was conducted in our PD center. The patients underwent initial standardized peritoneal equilibration test after PD for 4–6 weeks. Level of serum chemerin was determined via enzyme-linked immunosorbent assay. The patients’ CVDs were recorded during the follow-up period. Results: 151 eligible patients with a mean age of 46.59 ± 13.52 years were enrolled, and the median duration of PD was 25.0 months. The median concentration of serum chemerin was 29.09 ng/mL. Baseline D/P Cr was positively correlated with serum chemerin (r = 0.244, p = 0.003). The multivariate analyses revealed that serum chemerin (p = 0.002), age (p = 0.041), albumin (p = 0.000), and high-density lipoprotein (p = 0.022) were independent factors of D/P Cr. The serum chemerin level was significantly higher in diabetes mellitus (DM) patients than that of patients without DM (36.45 ng/mL vs. 27.37 ng/mL, p = 0.000), and there was a significant statistical difference in CVDs between the high chemerin group (≥29.09 ng/mL) and low chemerin group (<29.09 ng/mL) (42 vs. 21%, p = 0.009). Conclusions: Serum chemerin has a positive correlation with baseline D/P Cr in incident PD patients. It may be a biomarker that can predict the baseline transport function of the peritoneal membrane, and serum chemerin may be a risk factor of CVDs for incident PD patients. Multicenter studies with a larger sample size are warranted in the future.

Influence of dietary protein on serum phosphorous levels in peritoneal dialysis patients with different initial transport function

Introduction This cross-sectional study investigated the influence of dietary protein intake (DPI) on serum phosphate levels in peritoneal dialysis (PD) patients and determined the DPI cutoff required to prevent hyperphosphatemia. Methods A total of 504 PD patients were categorized into fast (4 h dialysate/plasma [D/P] creatinine clearance ≥0.65) or slow (<0.65) peritoneal transporters. Serum phosphorus and peritoneal solute clearance were compared between the groups with different DPI. Results The fast peritoneal transporters (n = 233) were older, had lower serum albumin and phosphorus levels, and had higher peritoneal phosphorus clearance (all p < 0.001). Among the slow transporters (n = 271), serum phosphorus levels were significantly higher among patients with DPI > 1.0 g/kg/d (p < 0.001). High DPI only increased the hyperphosphatemia risk in slow transporters (not in high transporters). DPI ≥1.026 g increased the hyperphosphatemia risk in those patients (area under the curve: 0.66, p = 0.001). Conclusion High DPI increases the hyperphosphatemia risk in PD patients with slower peritoneal transport function.

MO720: Elevated Dialysate IL-6 Concentrations are Prospectively Associated with Impaired TLR-Stimulated Cytokine Release from Peritoneal Cells—a Longitudinal Cohort Study

Abstract BACKGROUND AND AIMS Infectious complications and peritoneal inflammation occurring in a significant proportion of PD patients lead to progressive peritoneal membrane injury and account for most peritoneal dialysis (PD) technique failures. Reduced peritoneal immune-competence, caused by the continuous exposure to PD fluids, has been described as a therapy-related pathomechanism. We therefore hypothesized a relationship between dialysate interleukin 6 (IL-6) concentrations and peritoneal host defense. We established an ex vivo stimulation assay to test host defense mechanisms in only 9 mL of PD effluent. The aim of this study was to analyse basal inflammation and immune-competence in the PD population at routine conditions to evaluate the assay as surrogate parameter of immune competence and linking it to PD vintage and clinical outcome parameters. METHOD We prospectively analysed 195 serial routine peritoneal equilibration tests (PETs) of 123 stable PD patients treated exclusively with low-GDP, multi-chamber PD fluids during the glucose dwells and compared the data to routine follow-up clinical data. The cohort represents 76% of all eligible PD patients treated between April 2013 and September 2020 at the local Department of Nephrology. The study was approved by the local ethics committee and was conducted in accordance with the Declaration of Helsinki. All participants underwent a standardized 4-h PET with 3.86% glucose PDF as routine follow-up to test peritoneal membrane transport function, with an additional ex vivo cell stimulation protocol. PD effluent samples were obtained at the 1- and 4-h PET timepoints and immediately processed. Effluent samples were collected directly from the drainage bags into standard 9 mL additive-free sample tubes. For ex vivo stimulation, 100 ng/mL toll-like receptor (TLR) 4 agonist LPS and TLR2 agonist Pam3Cys were added to the effluent in the 9 mL collection tubes in duplicates and incubated at 37°C for 24 h. Unstimulated samples kept in parallel were used as controls. IL-6 concentrations were measured with ELISA in the supernatants. RESULTS Patients were stratified into two cohorts (incident and prevalent) at 120 days of continuous PD therapy. The cohorts were statistically indistinguishable except for stratification-specific variables. During a total follow-up period of 2499 patient-months, 55 patients underwent repeated PETs. Ex vivo stimulation of peritoneal cells significantly increased the IL-6 release 20-fold compared to unstimulated controls and resulted in a dwell-time dependent increase, with a significant lower cytokine released at the 1 h PET timepoint. To assess local inflammation, IL-6 concentrations in PD effluent of the 4 h PET were analysed. PD effluent IL-6 concentrations from the entire study cohort or from incident and prevalent patient subcohorts correlated neither with patient characteristics, RRF, disease background (including prior peritonitis) nor with time on PD. Effluent IL-6 concentrations correlated significantly with markers of systemic inflammation, serum CRP and albumin, with PSTR and with peritoneal protein loss. Interestingly, effluent IL-6 concentrations also had predictive value for risk of a subsequent peritonitis episode during follow-up. Effluent IL-6 levels were, in contrast, negatively correlated with ex vivo–stimulated IL-6 release from PD effluent cells, most remarkably in PD patients with history of prior peritonitis. CONCLUSION This longitudinal study provides the first direct evidence in PD patients of a correlation between peritoneal inflammation and impaired peritoneal immune cell function, likely driving infectious complications. Our study results suggest a mechanistic link between peritoneal inflammation and host defense that may foster innovative therapeutic approaches to improve clinical outcomes of chronic PD.

Are USPD patients suitable for incremental peritoneal dialysis: Yes or no?

Incremental peritoneal dialysis (IPD) is the practice of initiating PD exchange less than 4 times a day in consideration of residual renal function (RRF). This study determined whether IPD could be used for urgent-start peritoneal dialysis (USPD) patients when starting dialysis, and when compared to full-dose PD, could IPD affect the RRF in USPD patients. 169 USPD patients with eGFR between 4 and 6 mL/min/1.73m2 were retrospectively analyzed. The duration of follow-up was 1 year. Patients were divided into an incremental PD (i-PD) group (dialysis dose ≤ 6,000 mL) and a full-dose PD (f-PD) group (dialysis dose ≥ 8,000 mL). The demographics, clinical indices, peritoneal transport function, dialysis adequacy, and complications of peritoneal dialysis were compared between both groups. (1) 111 patients (average age 45.01 ± 12.84 years) were included in the i-PD group and 58 patients (average age 43.5 ± 15.62 years) in the f-PD group. The demographics and clinical indices of both groups before PD were similar (p < 0.05). (2) During the follow-up period, the dialysis dose in the f-PD group exceeded that of the i-PD group (p < 0.05). The dialysis adequacy of both groups was as expected. (3) During the follow-up period, peritoneal transport function, the RRF, the blood pressure control, correction of anemia, and correction of calcium and phosphorus abnormalities were similar in both groups. (4) The peritoneal dialysis-related infection, mechanical complications, and technical survival rate were similar between groups. Incremental PD did not cause a rapid decline of RRF in USPD patients. The dialysis effect and complications from it, were similar to full-dose peritoneal dialysis. Thus, USPD patients can be treated by IPD.

The effects of peritoneal dialysis on QT interval in ESRD patients

BackgroundPatients with chronic kidney disease (CKD) are at a high risk of fatal arrhythmias. The extended corrected QT (QTc) interval is a hallmark of ventricular arrhythmias and sudden cardiac death. Previous studies have shown that QT interval and QTc are prolonged with the decline in renal function. However, there were no available results for patients with peritoneal dialysis (PD). In this study, we examined changes in QT interval and QTc in patients with end-stage renal disease (ESRD) who underwent peritoneal dialysis.MethodsA total of 66 ESRD patients who received PD, including 50 males and 16 females, with an average age of 43.56 ± 15.15 years, were enrolled. The follow-up lasted 1 year. The demographics and the etiology of patients were recorded. QTc and clinical/biochemical indexes before dialysis and at 6 and 12 months were determined and analyzed. Dialysis adequacy and peritoneal transport function were assessed in each patient. Analysis of variance (ANOVA), least significant difference (LSD) or Tamhane’s T2, Paired T-test, Chi-square test, multiple linear regression analysis, and Pearson correlation coefficient were used to analyze the data. P < 0.05 was considered as statistically significant.ResultsWith reference to etiology, 37 patients (56.06%) had chronic nephritis, and 11 (16.67%) had diabetic nephropathy. Most of the peritoneal transport functions were low average transport (25, 37.88%), while the least were high transport (2, 3.03%).During the follow-up period, all patients had adequate peritoneal dialysis. Compared with a baseline before dialysis, anemia, low albumin, blood pressure, blood urea nitrogen, creatinine, uric acid, potassium, calcium, phosphorus, and parathyroid hormone improved after 6 and 12 months, while the residual renal function gradually decreased during the follow-up. The mean QTc of all patients was stable during the follow-up period. According to gender, the QTc in males and female patients were similar. Before PD, diastolic blood pressure, calcium concentration, and hemoglobin level were negatively correlated with QTc in end-stage renal disease patients; After PD, the observed clinical indexes were no longer relevant to QTc.ConclusionUnlike hemodialysis-induced QTc prolongation, PD did not increase the patient’s QT interval and QTc interval, which suggested that myocardial electrical activity might be more stable in patients with adequate peritoneal dialysis.

Vascular endothelial growth factor-mediated peritoneal neoangiogenesis in peritoneal dialysis.

Peritoneal dialysis (PD) is an important renal replacement therapy for patients with end-stage renal diseases, which is limited by peritoneal neoangiogenesis leading to ultrafiltration failure (UFF). Vascular endothelial growth factor (VEGF) and its receptors are key angiogenic factors involved in almost every step of peritoneal neoangiogenesis. Impaired mesothelial cells are the major sources of VEGF in the peritoneum. The expression of VEGF will be up-regulated in specific pathological conditions in PD patients, such as with non-biocompatible peritoneal dialysate, uremia and inflammation, and so on. Other working cells (i.e. vascular endothelial cells, macrophages and adipocytes) can also stimulate the secretion of VEGF. Meanwhile, hypoxia and activation of complement system further aggravate peritoneal injury and contribute to neoangiogenesis. There are several signalling pathways participating in VEGF-mediated peritoneal neoangiogenesis including tumour growth factor-β, Wnt/β-catenin, Notch and interleukin-6/signal transducer and activator of transcription 3. Moreover, VEGF is highly expressed in dialysate effluent of long-term PD patients and is associated with peritoneal transport function, which supports its role in the alteration of peritoneal structure and function. In this review, we systematically summarize the angiogenic effect of VEGF and evaluate it as a potential target for the prevention of peritoneal neoangiogenesis and UFF. Preservation of the peritoneal membrane using targeted therapy of VEGF-mediated peritoneal neoangiogenesis may increase the longevity of the PD modality for those who require life-long dialysis.

Lipid microsphere-coated PGE1 improves peritoneal transport and reduces inflammation in peritoneal dialysis: A randomized clinical pilot trial.

To evaluate the effects of lipid microspheres coated with prostaglandin E1 (lipo-PGE1) on peritoneal transport function and inflammation in patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD). In total, 89 patients were randomly allocated to the lipo-PGE1 and control groups. All the patients received conventional treatment, and those in the lipo-PGE1 group received lipo-PGE1 intravenously for 2weeks. The levels of β2-microglobulin (β2-MG), cystatin C, albumin, urea, creatinine, interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2), and high-sensitivity C-reactive protein (hs-CRP) were measured before and at 1 and 2weeks after treatment. In the lipo-PGE1 group, the peritoneal clearance rates of β2-MG, cystatin C, and albumin were significantly increased comparing with pre-treatment values, and the IL-6 appearance rate (AR) in the peritoneal dialysate and the serum levels of IL-6 and hs-CRP were markedly decreased (p<0.05). The lipo-PGE1 group had significantly higher peritoneal clearance rates of β2-MG and cystatin C and lower IL-6 AR in the peritoneal dialysate than the control group (p<0.05). Lipid microspheres coated with prostaglandin E1 may increase the peritoneal clearance of moderately sized molecules and macromolecules with insignificant effect on the clearance of small molecules. The reduction in IL-6 level following treatment with lipo-PGE1 may alleviate inflammation.

Excessive salt intake increases peritoneal solute transport rate via local tonicity-responsive enhancer binding protein in subtotal nephrectomized mice.

High peritoneal transport is associated with high mortality and technical failure in peritoneal dialysis (PD). Baseline peritoneal solute transport rate (PSTR) as measured by the peritoneal equilibration test (PET) within 6 months after PD initiation varies between patients. Sodium is reported to be stored in the skin or muscle of dialysis patients. This study investigated whether excessive salt intake in uremic mice caused peritoneal alterations without exposure to PD fluid. Sham-operated (Sham) and subtotal nephrectomized (Nx) mice were randomly given tap water or 1% sodium chloride (NaCl)-containing water for 8 weeks. PET was then performed to evaluate peritoneal function. Human mesothelial cell line Met-5A was used for in vitro studies. We observed higher PSTR in Nx mice with 1% NaCl-containing drinking water (Nx + salt) compared with those with tap water (Nx + water), along with enhanced angiogenesis and inflammation in the peritoneum. Blockade of interleukin (IL)-6 signaling rescued peritoneal transport function in Nx + salt mice. In cultured Met-5A, additional NaCl in the medium upregulated IL-6 as well as vascular endothelial growth factor-A, associated with increased expression and nuclear translocation of tonicity-responsive enhancer binding protein (TonEBP). Knockdown of TonEBP lowered the induction caused by high tonicity. Peritoneal TonEBP expression was higher in Nx + salt mice, while removal of high-salt diet lowered TonEBP level and improved peritoneal transport function. Excessive dietary salt intake caused peritoneal membrane functional and structural changes under uremic status. TonEBP regulated hypertonicity-related inflammatory changes and might play a crucial role in high baseline peritoneal transport.

Ultrafiltration Failure Is a Reflection of Peritoneal Alterations in Patients Treated With Peritoneal Dialysis.

Ultrafiltration (UF) failure is a common and important complication of peritoneal dialysis (PD), especially in long-term patients without residual urine production, because it often causes overhydration, which is an important cause of death in this population. The current review provides an overview of the pathways of peritoneal fluid transport, followed by the mechanisms and causes of UF failure. The egression of circulating fluid to the tissue compartment and its subsequent re-uptake by the colloid osmotic pressure are markedly influenced by PD, because the dialysis solutions contain glucose as a low molecular weight agent causing removal of fluid from the circulation by crystalloid osmosis. Pores involved in transcapillary UF consist of inter-endothelial small pores and the intra-endothelial water channel aquaporin-1. The former allows transport of plasma fluid with dissolved low molecular weight solutes and accounts for 60% of the filtered volume, the latter transports 40% as pure water. This free water transport (FWT) is driven by the crystalloid pressure gradient, while small pore fluid transport (SPFT) is dependent on both hydrostatic and crystalloid osmotic pressure. The number of perfused peritoneal microvessels as assessed by small solute transport parameters, is differently associated with UF: a positive relationship is present with SPFT, but a negative one with FWT, because the effect of more vessels is counteracted by a faster disappearance rate of glucose. Ultrafiltration failure can be present shortly after the start of PD, for instance due to mesothelial-to-mesenchymal transition. Late UF failure develops in 21% of long-term patients. Both FWT and SPFT can be affected. Patients with encapsulating peritoneal sclerosis have severely impaired FWT, probably due to interference of interstitial collagen-1 with the crystalloid osmotic gradient. This mechanism may also apply to other patients with reduced FWT. Those with mainly impaired SPFT likely have a reduced hydrostatic filtration pressure due to vasculopathy. Deposition of advanced glycosylation end products is probably important in the development of this vasculopathy. It can be concluded that long-term UF failure may affect both SPFT and FWT. Vasculopathy is important in the former, interstitial fibrosis in the latter. Measurements of peritoneal transport function should include separate assessments of small pore-and FWT.

Neutral pH and low–glucose degradation product dialysis fluids induce major early alterations of the peritoneal membrane in children on peritoneal dialysis

The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low-glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function.

Pharmacological inhibition of heparin-binding EGF-like growth factor promotes peritoneal angiogenesis in a peritoneal dialysis rat model.

Molecular mechanisms of peritoneal dialysis (PD) ultrafiltration failure, peritoneal neo-angiogenesis, and fibrosis remain to be determined. We aimed to determine the role of heparin-binding EGF-like growth factor (HB-EGF) inhibition on angiogenesis of peritoneal membrane in a PD rat model. 32 male Wistar rats were assigned into (1) control group; (2) uremic non-PD group: subtotal nephrectomy-induced uremic rats without PD; (3) uremic rats subjected to PD: uremic rats that were dialyzed with Dianeal® for 4weeks; (4) CRM 197 group: dialyzed uremic rats were supplemented with CRM197, a specific HB-EGF inhibitor. Peritoneal transport function was examined by peritoneal equilibration test. Expression of HB-EGF and EGFR in peritoneal samples were examined by real-time PCR, immunohistochemical staining, and western blot. Progressive angiogenesis and fibrosis were observed in uremic PD rats, and there were associated with decreased net ultrafiltration (nUF), increased permeability of peritoneal membrane, and reduced expression of HB-EGF and EGFR protein and mRNA in uremic PD rats compared to uremic non-PD or control groups (both p<0.05). CRM197 significantly induced peritoneal membrane permeability, decreased nUF, increased higher vessel density, and reduced pericyte count compared to that of uremic PD rats. The levels of HB-EGF and EGFR expression negatively correlated with vessel density in peritoneal membrane (both p<0.001). PD therapy was associated with peritoneal angiogenesis, functional deterioration, and downregulation of HB-EGF/EGFR. Pharmacological inhibition of HB-EGF promoted PD-induced peritoneal angiogenesis and fibrosis and ultrafiltration decline, suggesting that HB-EGF downregulation contributes to peritoneal functional deterioration in the uremic PD rat model.

Clinical characteristics and the factors relevant to peritoneal transport function in patients with continuous ambulatory peritoneal dialysis

To observe the clinical characteristics with different peritoneal transport type in patients with continuous ambulatory peritoneal dialysis (CAPD), and to investigate the factors associated with peritoneal transport function. Methods: The clinical data of 158 CAPD patients were analyzed retrospectively. According to peritoneal equilibration test, a method for evaluation of the peritoneal transport function, the patients were divided into 2 groups: a high average and high peritoneal transport group (Group A, n=84) and a low average and low peritoneal transport group (Group B, n=74). The demographics, clinical biochemical indexes and the incidence of cardiovascular complications were compared between the 2 groups. Logistic regression analysis was used to find the factors relevant to peritoneal transport function. Results: The level of serum albumin (ALB) in the Group B was significantly higher than that in the Group A (P<0.05). The 4 h dialysate/plasma creatinine (D/Pcr), high-sensitivity C-reactive protein (hs-CRP), body mass index (BMI), and the rates of cardiovascular complications in the Group A were significantly higher than those in the Group B (P<0.05). Correlation analysis showed that the D/Pcr was positively correlated with the BMI, serum hs-CRP and cardiovascular complications (r=0.179, 0.373 and 0.426, respectively, P<0.05), while it was negatively correlated with ALB (r=-0.393, P<0.01). Logistic regression analysis showed that the high BMI (OR=1.178, P<0.05), cardiovascular complications (OR=5.035, P<0.01), and the low serum ALB (OR=0.852, P<0.01) were the risk factors for high peritoneal transport. Conclusion: The serum ALB level, BMI and the cardiovascular complications are associated with high peritoneal transport, which are useful markers for predicting the peritoneal transport function before peritoneal dialysis.

Effects of extraction of Angelicae sinensis and Astragalus mongholicus on the peritoneal structure, functions and TGF-β1 expression in the chronic peritoneal failure rats

To study the effects of extraction of Angelicae sinensis and Astragalus mongholicus (EAA) on the peritoneal structure, functions and transforming growth factor-β1(TGF-β1) expression in the chronic peritoneal failure rats. Fifty SD rats were randomly divided into normal control group, model control group, positive control group, high-dose and low-dose EAA group(n=10). The modeling rats were established by intraperitoneal injection(ip) 4.25% high-glucose peritoneal dialysate 100 ml/kg, lasted 40 d, and ip lipopolysaccharides (LPS) 5 mg/kg at 8thd, 10thd and 12thd. At the same time, the rats were treated with the corresponding drugs. The body weight and general states, the levels of ultrafiltration volume, the parameters of peritoneal transport function, the changes of peritoneal morphology and the TGF-β1 expression in parietal peritoneum of rats were observed. EAA could increase the levels of ultrafiltration volume and improve the parameters of peritoneal transport function. The peritoneal thickness were decreased, and the TGF-β1 expression in parietal peritoneum were also lowered significantly. EAA has some protective effects on the peritoneal structure and functions, and can inhibit TGF-β1 expression.

The Fast Peritoneal Equilibration Test First and Second Hour Results

Abstract Introduction. The Peritoneal Equilibration Test (PET) is employed to assess peritoneal membrane transport function. The purpose of the test is to determine the optimal peritoneal dialysis regimen. The performance of the test, which is conducted over 4 hours, is time consuming both for the nurses and the patient. There have been studies to validate an approved short version of the original PET protocol, and all have yielded different results. We evaluated the concordance between the 1-hour, 2-hour and 4-hour (classical) test results of the fast PET. Methods. The study included 32 patients (20 males and 12 females). The patients underwent the 4-hour fast PET test, and the dialysate-to-plasma ratio of creatinine concentration (D/Pcrea) was determined. The standard deviation was added to or subtracted from the mean D/Pcrea ratios at hours 1, 2, and 4 to determine transport groups. Results. The mean age of the patients was 51.4±16.7 years. Mean D/Pcrea ratios at hours 1, 2, and 4 were 0.41±0.07, 0.54±0.10, and 0.69+0.12, respectively. There was a strong correlation between the 4-hour D/Pcrea ratio and 1-hour (r=0.756, p&lt;0.001) and 2-hour (r=0.867, p&lt;0.001) D/Pcrea ratios. Seventeen patients (53%) were in the same transport group at hours 1, 2, and 4. Eighteen patients (56%) at 1 hour and 24 patients (75%) at 2 hours fell into the same transport group at 4 hours. The patients that fell into different transport groups at different time points showed a shift to a lower or higher transport group. Conclusions. Two-hour fast PET gives promising results for clinical assessment purposes.

Adipokines and parameters of peritoneal membrane transport in newly started peritoneal dialysis patients.

Adiponectin and leptin are two adipokines playing important roles in the regulation of body weight, appetite, carbohydrate and lipid metabolism. In patients with chronic kidney disease (CKD) adipokines accumulate in serum due to reduced renal clearance. Since adipokines have pleiotropic actions, the adipokine balance may have an impact on peritoneal membrane transport. The aim of this study was to assess whether serum adiponectin and leptin levels were related to peritoneal transport and residual renal function (RRF) in newly started peritoneal dialysis patients. 25 clinically stable patients, 4 to 6 weeks after the onset of PD, were included in the study. For each patient clinical and laboratory data were reviewed and standard PET test was performed. Serum adiponectin and leptin concentrations were determined and leptin/adiponectin (L/A) ratio was calculated. Serum adiponectin correlated negatively with weight, BMI and glucose concentration. Serum leptin and L/A ratio correlated positively with BMI. Serum adiponectin correlated positively with dialysate to plasma (D/P) creatinine ratio and ultrafiltration in PET test. Serum leptin level and L/A ratio correlated strongly negatively with peritoneal creatinine clearance. Serum adiponectin concentration is positively associated with baseline solute transport. Leptin concentration and L/A ratio are negatively associated with dialysis adequacy in newly started PD patients.

Impact of Rapamycin on Peritoneal Fibrosis and Transport Function

Objectives: To observe the impact of rapamycin on peritoneal fibrosis and peritoneal transport function in a rat model of peritoneal fibrosis. Methods: A total of 40 male SD rats were randomly divided into five groups, with 8 rats in each group. Group N was the normal control. In group NS, the rats were injected daily with 20 ml of saline intraperitoneally. In groups GLU, L-RAPA and H-RAPA, rats were injected daily with 20 ml of 4.25% peritoneal dialysis solution intraperitoneally, together with 150 µg of lipopolysaccharide on days 1, 3, 5 and 7. Rapamycin was administered to groups L-RAPA (250 µg/day) and H-RAPA (500 µg/day) intragastrically. On days 21 and 35, 4 rats from each group were selected to evaluate their peritoneal transport function (ultrafiltration volume, D₂/D₀ ratio). The parietal peritoneal membrane from the rats was used for pathological study. Light microscopy (HE staining and VG staining) was used to assess the morphological changes. The expression levels of Col I, α-SMA, TGF-β₁, Reca and Ki67 in the parietal peritoneal membrane were observed by immunohistochemistry. Results: The ultrafiltration volume and D₂/D₀ ratio decreased in group GLU compared with group N on day 21 (p < 0.05) and further decreased on day 35 (p < 0.01), whereas such a significant change was not observed in group L-RAPA or H-RAPA. Furthermore, severe loss of the peritoneal mesothelial cells, exposure of the collagen matrix under the mesothelial cells, and infiltration of fibroblasts and various inflammatory cells were detected in group GLU on days 21 and 35. The thickness of the submesothelial compact zone significantly increased in group GLU compared with group N (p < 0.01). However, in groups L-RAPA and H-RAPA, the morphological changes were clearly alleviated, and the submesothelial compact zone was thinner than in group GLU (p < 0.01). The expression levels of Col I, α-SMA, TGF-β₁, Ki67 and Reca in the peritoneal membrane were significantly increased in group GLU compared with group N on days 21 and 35 (p < 0.01), whereas these changes were significantly attenuated in groups L-RAPA and H-RAPA compared with group GLU (p < 0.01). Conclusions: Rapamycin had an obvious effect in inhibiting peritoneal fibrosis and improving peritoneal membrane transport function.

Development of Encapsulating Peritoneal Sclerosis Following Bacterial Peritonitis in a Peritoneal Dialysis Patient

Encapsulating peritoneal sclerosis (EPS) isan uncommon and often fatal complication inpatients on peritoneal dialysis (PD) therapy. EPSis a clinical syndrome characterized by symp-toms of impaired intestinal motility, such asanorexia, nausea, vomiting, abdominal fullness,abdominalpain,absentbowelsounds,andconsti-pation.

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

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. 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. 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. 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.

Hypoproteinemia in Patients with Diabetes Undergoing Continuous Ambulatory Peritoneal Dialysis is Attributable to High Permeability of Peritoneal Membrane

The present study used the newly developed personal dialysis capacity (PDC) peritoneal function test to investigate differences in individual peritoneal membrane transport function and nutritional status in non diabetic (non DM) and diabetic (DM) patients on continuous ambulatory peritoneal dialysis (CAPD). To clarify the differences in peritoneal function that determine plasma protein levels, we carried out PDC tests in non DM and DM patients. Between May 1995 and May 1999, in multicenter study in Japan, we carried out 232 PDC tests on 232 non DM patients and 47 PDC tests on 47 DM patients who had been on CAPD for 1 - 210 months. Plasma levels of total protein and albumin in DM patients were significantly lower than those in non DM patients (total protein: 6.5 +/- 0.1 g/dL non DM vs. 5.9 +/- 0.1 g/dL DM, p < 0.0001; albumin: 3.5 +/- 0.1 g/dL non DM vs. 2.9 +/- 0.1 g/dL DM, p < 0.0001). The mean membrane area in the DM group was significantly larger than that in the non DM group (21 943 +/- 608 cm/1.73 m(2) non DM vs. 26 304 +/- 1699 cm/1.73 m(2) DM, p = 0.0076). The mean plasma loss through the large pores in the DM group was significantly greater than that in the non DM group (0.095 +/- 0.004 mL/min/1.73 m(2) non DM vs. 0.119 +/- 0.008 mL/min/1.73 m(2) DM, p = 0.0113). Protein loss into dialysate in DM patients was significantly greater than that in non DM patients. We observed a significant correlation between total protein or albumin and plasma loss from dialysis solution in non DM and DM patients on CAPD. The study demonstrated that peritoneal function, including peritoneal membrane transport and peritoneal permeability to protein was significantly higher in DM patients than in non DM patients. Hypoproteinemia in DM patients might be associated with high permeability of peritoneal membrane in CAPD.