Biocompatible Dialysis Solutions Research Articles

Survival of Peritoneal Membrane Function on Biocompatible Dialysis Solutions in a Peritoneal Dialysis Cohort Assessed by a Novel Test.

Background: Longitudinal surveillance of peritoneal membrane function is crucial in defining patients with a risk of ultrafiltration failure. Long PD is associated with increased low molecular weight solute transport and decreased ultrafiltration and free water transport. Classic PET test only provides information about low molecular solute transport, and the vast majority of longitudinal studies are based on this test and include patients using conventional dialysates. Our aim was to prospectively analyze longitudinal data on peritoneal function in patients on biocompatible solutions using a novel test. Methods: Membrane function data were collected based on uni-PET (a combination of modified and mini PET). A total of 85 patients (age 61.1 ± 15.1 years) with at least one test/year were included. Results: The median follow up was 36 months (21.3, 67.2). A total of 219 PETs were performed. One-way repeated measures ANOVA showed that there were no statistically significant differences over time in ultrafiltration, free water transport, ultrafiltration through small pores, sodium removal, D/D0 and D/PCre in repeated PET-tests. Twenty-three tests revealed ultrafiltration failure in 16 (18.8%) patients. Those patients were longer on PD, had higher D/P creatinine ratios, lower ultrafiltration at one hour with lower free water transport and higher urine volume at baseline. Multivariate analysis revealed that the variation of ultrafiltration over repeated PET-tests independently correlated only with D/Pcreatinine, free water transport and ultrafiltration through small pores. Conclusions. Uni-PET is a combination of two tests that provides more information on the function of the membrane compared with PET. Our study on a PD cohort using only biocompatible solutions revealed that function membrane parameters remained stable over a long time. Ultrafiltration failure was correlated with increased D/P creatinine and decreased free water transport and ultrafiltration through small pores.

FC 101PROTEOMIC PROFILE OF MESOTHELIAL EXOSOMES ISOLATED FROM PERITONEAL DIALYSIS EFFLUENT OF CHILDREN WITH FOCAL SEGMENTAL GLOMERULOSCLEROSIS

Abstract Background and Aims Peritoneal dialysis (PD) is the worldwide preferred dialysis treatment for children affected by end stage kidney disease. However, due to the unphysiological composition of PD fluids, the peritoneal mesothelium of these patients may undergo structural and functional alterations, which may cause fibrosis. Several factors may accelerate this process and primary kidney disease may have a causative role. In particular, patients affected by corticosteroid resistant focal segmental glomerulosclerosis (FSGS), a rare glomerular disease leading to nephrotic syndrome, seems more prone to develop peritoneal fibrosis. The mechanism causing this predisposition is still unrecognized. To better define this condition, we carried out, for the first time, a new comprehensive comparative proteomic mass spectrometry analysis of mesothelial exosomes from peritoneal dialysis effluent (PDE). Method We enrolled 12 paediatric patients on PD. Half of them affected by FSGS and the others affected by other disorders (NO FSGS). Exosomes from mesothelial peritoneal cells were isolated by centrifugation and, using a biotinylated antibody and streptavidin magnetic beads. Exosome size was determined by dynamic light scattering, and antigen profile of exosomes was assayed by western blot. Mass spectrometry data were analyzed by unsupervised hierarchical clustering using multidimensional scaling, in order to identify outliers and dissimilarity between samples. The normalized data were used to construct a co-expression network using the weighted gene co-expression network analysis (WGCNA). A weighted adjacency matrix was constructed, and transformed into a topological overlap matrix, which measures the network connectivity of all proteins. To identify the relationship between each module and each clinical trait, we used module eigengenes (MEs) and calculated the correlation between MEs and the clinical traits. To identify the hub proteins of modules that maximize the discrimination between FSGS and NO FSGS samples, we applied T-test, and non-linear support vector machine (SVM) learning. Finally, gene set enrichment analysis was done to build a functional proteins network based on their Gene Ontology (GO) annotations extracted from the Gene Ontology Consortium. Results Our omic study demonstrated that SVM allowed a complete distinction of the whole proteomic exosome mesothelial content of FSGS versus NO FSGS (100% accuracy). Out of the 2490 identified proteins, 40% (995) were involved in endothelial to mesenchymal transition /fibrosis and in the TGF-B pathway. The WGCNA analysis highlighted a total of 40 proteins were that maximize the discrimination between FSGS and NO FSGS patients (Figure 1A). Their expression profile is reported in a heatmap diagram (Figure 1B). Additionally, we performed GO enrichment analysis (Figure 2) and the algorithm identified that some of the discriminative proteins (TIMP1, CTHRC1, SPARC, CHMP4B, COL5A2, ANXA13, FNC2 and CENP-E) were also highly correlated to the peritoneal dialysis vintage, fibrosis, EMT and PM disease. Conclusion Our data demonstrated, for the first time, that mesothelial cells of FSGS are more prone to activate a pro-fibrotic machinery with exosomes having a primary role in this process. Moreover, they indicated that identified FSGS-associated element in mesothelial exosome protein could be employed as potential new biomarkers of mesothelial integrity. Finally, results highlighted that FSGS should be treated with more biocompatible dialysis solution, reduce the length of time on PD and personalize type and regimens of PD to minimize the risk of rapid loss of peritoneal membrane.

Comparison of Longitudinal Membrane Function in Peritoneal Dialysis Patients According to Dialysis Fluid Biocompatibility

IntroductionPreservation of peritoneal function is essential in long-term peritoneal dialysis. Biocompatible dialysis solutions might prevent or postpone the membrane alteration resulting in ultrafiltration failure and consecutive morbidity and mortality.MethodsWe conducted an observational cohort study in which we made a longitudinal comparison between the course of peritoneal solute and fluid transport during treatment with conventional and biocompatible solutions. Therefore, prospectively collected peritoneal transport data from the yearly standard peritoneal permeability analysis were analyzed in 251 incident patients treated between 1994 and censoring in 2016. Fluid transport included small pore and free water transport. Solute transport was assessed by creatinine mass transfer area coefficient and glucose absorption. Linear mixed models including change point analyses were performed. Interaction with peritonitis was examined.ResultsOne hundred thirty-five patients received conventional and 116 biocompatible solutions. Sixty-seven percent (conventional) and 64% (biocompatible) of these underwent minimally three transport measurements. Initially, biocompatible fluids showed higher small solute transport and lower ultrafiltration than conventional fluids up to 3 years. Thereafter, conventional fluids showed an increase in small solute transport (+2.7 ml/min per year; 95% confidence interval [CI]: 0.9 to 4.5) and a decrease of free water transport (−28.0 ml/min per year; 95% CI: −60.4 to 4.4). These were minor or absent in biocompatible treatment. Peritonitis induced a decrease of transcapillary ultrafiltration after 2 years on dialysis with conventional solutions (−291 ml/min per year; 95% CI: −550 to −32) while this was absent in biocompatible treatment.ConclusionDespite a higher initial solute transport with biocompatible solutions, these have less influence on functional long-term peritoneal alterations than conventional solutions.

Economic Evaluation of Neutral-pH, Low–Glucose Degradation Product Peritoneal Dialysis Solutions Compared With Standard Solutions: A Secondary Analysis of the balANZ Trial

Biocompatible solutions may lower peritonitis rates, but are more costly than conventional solutions. The aim of the present study was to assess the additional costs and health outcomes of biocompatible over conventional solutions in incident peritoneal dialysis patients to guide practice decisions. Secondary economic evaluation of a randomized controlled trial. 185 participants in the balANZ trial. Cost-effectiveness of biocompatible compared to standard solution over the 2 years using an Australian health care funder perspective. Intervention group received biocompatible solutions and control group received standard solutions over 2 years. Costs included dialysis charges, costs of treating peritonitis, non-peritonitis-related hospital stays, and medication. Peritonitis was the health outcome of interest; incremental cost-effectiveness ratios were reported in terms of the additional cost per additional patient avoiding peritonitis at 2 years. Mean total per-patient costs were A$57,451 and A$53,930 for the biocompatible and standard-solution groups, respectively. The base-case analysis indicated an incremental cost of A$17,804 per additional patient avoiding peritonitis at 2 years for biocompatible compared to standard solution. In a sensitivity analysis excluding extreme outliers for non-peritonitis-related hospitalizations, mean per-patient costs were A$49,159 and A$52,009 for the biocompatible and standard-solution groups, respectively. Consequently, the incremental cost-effectiveness ratio also was reduced significantly: biocompatible solution became both less costly and more effective than standard solution and, in economic terms, was dominant over standard solution. Peritonitis was a secondary outcome of the balANZ trial. Health outcomes measured only in terms of patients avoiding peritonitis over 2 years may underestimate the longer term benefits (eg, prolonged technique survival). Biocompatible dialysis solutions may offer a cost-effective alternative to standard solutions for peritoneal dialysis patients. Reductions in peritonitis-related hospital costs may offset the higher costs of biocompatible solution.

Operative Techniques for Placement of Peritoneal Catheters

As a renal replacement therapy, peritoneal dialy- sis has been applied in the clinic since the 1970s. Com- pared with hemodialysis, it has a unique superior- ity since it requires only simple equipment and sur- gery and it is more effective at protecting residual re- nal function. In recent years, with significant improve- ment of the peritoneal dialysis connecting system and peritoneal dialysis solution biocompatibility, as well as increasing standartization of patients` training has be- come the best method of early renal replacement ther- apy for patients with end-stage renal disease. We present you a review of different techniques, the cost effectiveness and comparison of the most frequent complications and we share our ten years` experience in peritoneal catheter placement in our clinic.

32 Years' Experience of Peritoneal Dialysis-Related Peritonitis in a University Hospital

Peritonitis in peritoneal dialysis (PD) patients can lead to technique failure and contributes to infection-related mortality. Peritonitis prevention and optimization of treatment are therefore important in the care for PD patients. In the present study, we analyzed the incidence of peritonitis, causative pathogens, clinical outcomes, and trends in relation to three major treatment changes that occurred from 1979 onward: use of a disconnect system since 1988, daily mupirocin at the exit-site since 2001, and exclusive use of biocompatible dialysis solutions since 2004. In this analysis of prospectively collected data, we included peritonitis episodes from the start of PD at our center in August 1979 to July 2010. Incident PD patients were allocated to one of four groups: Group 1 - 182 patients experiencing 148 first peritonitis episodes between 1979 and 1987, before the introduction of the disconnect system; Group 2 - 352 patients experiencing 239 first episodes of peritonitis between 1988 and 2000, before implementation of daily mupirocin application at the catheter exit-site; Group 3 - 79 patients experiencing 50 first peritonitis episodes between 2001 and 2003, before the switch to biocompatible solutions; and Group 4-118 patients experiencing 91 first peritonitis episodes after 2004. Cephradine was used as initial antibiotic treatment. In 32 years, 731 adult patients started PD, and 2234 episodes of peritonitis in total were diagnosed and treated. Of those episodes, 88% were cured with medical treatment only, and 10% resulted in catheter removal. In 3% of the episodes, the patient died during peritonitis. Median time to a first peritonitis episode increased from 40 days for group 1 to 150 for group 2, 269 for group 3, and 274 for group 4. The overall peritonitis rate and the gram-positive and gram-negative peritonitis rates showed a time-trend of decline. However, the duration of antibiotic treatment increased over time, with groups 3 and 4 having the longest duration of treatment, accompanied by a higher percentage of antibiotic switch. Increased resistance to cephradine was found for coagulase-negative Staphylococcus. Peritonitis rates declined significantly over the years because of several changes in PD treatment. However, the need to change the initial antibiotic increased because of diminished antibiotic susceptibility rates over time. Nevertheless, the cure rate was high and remained stable during the entire period analyzed, and the death rate remained low. Consequently, peritonitis is a manageable complication of PD that cannot be considered a contraindication to this mode of renal replacement therapy.

3,4-DGE is cytotoxic and decreases HSP27/HSPB1 in podocytes

Hyperglycemia is the key driver of diabetic complications and increased concentrations of glucose degradation products. The study of peritoneal dialysis solution biocompatibility has highlighted the adverse biological effects of glucose degradation products. Recently, 3,4-dideoxyglucosone-3-ene (3,4-DGE) was identified as the most toxic glucose degradation product in peritoneal dialysis fluids. In addition, 3,4-DGE is present in high-fructose corn syrup, and its precursor 3-deoxyglucosone is increased in diabetes. The role of 3,4-DGE in glomerular injury had not been addressed. We studied the effects of 3,4-DGE on cultured human podocytes and in vivo in mice. 3,4-DGE induced apoptosis in podocytes in a dose- and time-dependent manner. 3,4-DGE promoted the release of cytochrome c from mitochondria and activation of caspase-3. While high glucose concentrations increased the levels of the podocyte intracellular antiapoptotic protein HSP27/HSPB1, 3,4-DGE decreased the expression of podocyte HSP27/HSPB1. Apoptosis induced by 3,4-DGE was caspase-dependent and could be prevented by the broad-spectrum caspase inhibitor zVAD-fmk. Antagonism of Bax by a Ku-70-derived peptide also prevented apoptosis. Intravenous administration of 3,4-DGE to healthy mice resulted in a decreased expression of HSP27/HSPB1 and caspase-3 activation in whole kidney and in podocytes in vivo. In conclusion, 3,4-DGE induces apoptotic cell death in cultured human podocytes, suggesting a potential role in glomerular injury resulting from metabolic disorders.

Can Effluent Matrix Metalloproteinase 2 and Plasminogen Activator Inhibitor 1 be Used as Biomarkers of Peritoneal Membrane Alterations in Peritoneal Dialysis Patients?

Peritoneal effluent contains clinically relevant substances derived from intraperitoneal production or transperitoneal transport, or both. The glycoproteinase matrix metalloproteinase 2 (MMP-2) cleaves denatured collagen and complements other collagenases in the degradation of fibrillar collagens. Elevated intraperitoneal levels of plasminogen activator inhibitor 1 (PAI-1) have been demonstrated to be present in patients with intra-abdominal adhesions. The aim of the present study was therefore to investigate the potential for effluent MMP-2 and PAI-1 to be used as markers of the development of peritoneal alterations. In addition, MMP-2 was analyzed in previously frozen effluent samples from a uremic rat model, in which data concerning the severity of peritoneal fibrosis were available. This prospective, single-center cohort study included 86 incident peritoneal dialysis (PD) patients. All patients were treated solely with biocompatible dialysis solutions and underwent a standard peritoneal permeability analysis (SPA). The presence of local MMP-2 and PAI-1 production and the relationships between those markers and peritoneal transport parameters were analyzed. Furthermore, effluent interleukin 6 was analyzed as a marker of local inflammation. Median effluent levels of 21.4 ng/mL for MMP-2 and 0.9 ng/mL for PAI-1 were found. The median dialysate appearance rates were 218.8 ng/min for MMP-2 and 9.6 ng/min for PAI-1. Local peritoneal production averaged 90% of effluent MMP-2 concentration and 74% of effluent PAI-1 concentration. Furthermore, correlations between peritoneal transport parameters and MMP-2 and PAI-1 were observed. Longitudinal follow-up showed no change for MMP-2 (p = 0.37), but a tendency for PAI-1 to increase with the duration of PD (p < 0.001). In rats, a significant relationship was present between the extent of peritoneal fibrosis and the appearance rate of MMP-2 (r = 0.64, p = 0.03). The foregoing data illustrate the potential of effluent MMP-2 and PAI-1 as biomarkers of peritoneal modifications, especially fibrosis; however, the components of peritoneal transport and local production should be clearly distinguished in every patient.

Dialysate cancer antigen 125 in long-term peritoneal dialysis patients

Structural and functional peritoneal membrane changes are associated with long-term peritoneal dialysis. These changes can lead to ultrafiltration failure and peritoneal fibrosis, reducing the efficacy of the peritoneal membrane to remove waste and balance fluid and electrolytes. The loss of mesothelial cells from the basement membrane is one of the major characteristics in peritoneal membrane structural change. Thus, if the reduction of peritoneal mesothelial cell mass in peritoneal dialysis patients is monitored, signs of ultrafiltration failure and peritoneal fibrosis can be detected early. One of biomarkers that can be used to indicate the change in peritoneal mesothelial cell mass is CA125, which is produced by mesothelial cells. In this article, we review the measurement and clinical use of CA125 in peritoneal dialysate effluent. Additionally, we address the data and studies on the association between dialysate CA125 levels and factors related to ultrafiltration failure and peritoneal fibrosis, including the parameters used to monitor the functional status of the peritoneal membrane. Our review shows that dialysate CA125 can be used to evaluate the peritoneal membrane in noninfected patients to predict peritoneal fibrosis, and it can also be used as a biomarker of biocompatible dialysis solutions.

Influence of peritoneal dialysis solution biocompatibility on long-term survival of patients on continuous ambulatory peritoneal dialysis and the technique itself

Morbidity and mortality of continous ambulatory peritoneal dialysis (CAPD) patients is still very high. The aim of the study was to evaluate the effects of peritoneal dialysis (PD) solutions (standard vs biocompatible) on long-term patients' and the techique survival. A total of 42 stable patients on CAPD participated in this cross-sectional study. They were prospectively followed-up during the twelve years. Patients with severe anemia (Hb < 10 g/L) and malignant disease ware excluded. Twenty one (50%/0) patients were treated with the standard PD solutions (CAPDP-1) while the other 21 (500/0) were treated with biocompatible PD solutions [(lower level of glucose degradation products, lower concentration of Ca(2+) and neutral pH (CAPDP-2)]. All patients were analyzed for a presence of vascular calcification, nutrition status, and parameters of inflammation after 2.5 +/- 0.6 years of starting CAPD, and these variables considered in the analysis as risk factors. The patients from the group CAPDP-2 compared to those from the group CAPDP-1 had lower level of high-sensitivity C-reactive protein (hs-CRP) (p = 0.003), and better nutritional status as confirmed by the mid-arm circumference (p = 0.015), and mid-arm muscle circumference (p = 0.002) and subjective global assessment (p = 0.000). Also, they had lower vascular calcifications as confirmed by intima media thickness (IMT) (p = 0.003), degree of carotid narrowing (p = 0.001) and calcified plaques of common carotid arteries (CCA) (p = 0.008). Kaplan-Meier analysis confirmed better survival of patients from the group CAPDP-2 than those from the group CAPDP-1 (1-, 5-, and 10-year patients survival rate was: 100%, 61.9% and 14.3% for the group CAPDP-1, and 100%, 85.7%, and 52.4% for the group CAPDP-2, respectively; p = 0.0345). The 1-, 5-, and 10-year technique survival rate was: 100%, 71.4%, and 38.1% for the group CAPDP-1, and 100%, 85.7%, and 76.2% for the group CAPDP-2, respectively; (p = 0.0719). Duration of dialysis, serum triglyceride and cardiovascular score (quantitative scoring system consisting of: ejection fraction (EF) of left ventricle < 50%; IMT > 1 mm; carotid narrowing degree > 50%, presence of carotid plaques in both common carotide, ischaemic heart disease, cerebrovascular event and peripheral vascular disease with or without amputation) were independent predictors of overall patient survival. Duration of dialysis was only independent predictor of overall technique survival. Although patients treated with biocompatible solutions showed significantly better survival, the role of biocompatibility of CAPD solutions in patients and technique survival have to be confirmed. Namely, multivariate analysis confirmed that duration of dialysis, serum triglyceride and cardiovascular score significantly predicted overall CAPD patients survival, while only duration of dialysis was found to be independent predictor of overall techique survival.

Free water transport in children on peritoneal dialysis is higher with more biocompatible dialysis solutions, higher with older age and declines with time

Water transport in peritoneal dialysis occurs through small pores and aquaporins. Free water transport (FWT) occurs through aquaporins only and gives a reflection of peritoneal aquaporin function. In this study, FWT in children was calculated for the first time in different settings. A prospective cohort study was performed; 87 peritoneal equilibrium tests (PETs) were analysed in 65 patients. Three subgroups were analysed: patients with their first PET; patients in their second year on dialysis; patients in their third year on dialysis or thereafter. Patients using 3.86% glucose solution with low pH/high glucose degradation products (GDP) were compared to patients using 3.86% glucose solution with neutral pH/low GDP. Sixteen patients using neutral pH/low GDP solution were followed longitudinally. FWT was calculated using the dialysate/plasma ratio of sodium. The proportional contribution of FWT was significantly higher in patients using dialysis solution with neutral pH/low GDP solution compared to patients using solutions with low pH/high GDP (50 versus 40%). Transcapillary ultrafiltration (TCUF) showed the same trend but was not statistically significant. Total FWT was higher as well. Higher FWT was observed with older age. In the longitudinal group, TCUF and water transport through small pores declined, while FWT remained stable in the first 1.5 years. The contribution of FWT increased in this period (48-61%), then slowly declined again to baseline level during the third year. Total FWT and relative contribution of FWT were significantly higher with neutral pH/low GDP solution. This can reflect a better preservation of aquaporins. The decline in the contribution of FWT in long-term dialysis could hypothetically implicate aquaporin dysfunction or different trafficking of aquaporins.

The impact of dialysis solution biocompatibility on ultrafiltration and on free water transport in rats

This study compares different peritoneal dialysis fluids (PDF) in rats over a short contact time. For greater accuracy, net ultrafiltration (UF) and peritoneal transport indices, mass transfer area coefficient (MTAC) were scaled for the in vivo peritoneal surface area recruited (ivPSA) measured by microcomputerized tomography. Wistar rats underwent nephrectomy (5/6ths), were randomized into two groups and given 1.5% glucose PDF, either conventional acidic lactate (n = 14) or pH neutral bicarbonate (BicaVera) (n = 13); MTAC and UF were measured using a 90-min peritoneal equilibrium test (PET), fill volume (IPV) of 10 ml/100 g; small pore fluid transport was determined from sodium balance and used to calculate free water transport (FWT). Each ivPSA value was significantly correlated with the actual IPV, which varied from one rat to another. At 90 min of contact, there was no difference in recruited ivPSA in relation to PDFs. There was a difference (p < 0.01) in net UF/ivPSA 0.45 vs. 1.41 cm(2)/ml for bicarbonate versus lactate, as there was in the proportion of FWT with bicarbonate (42 ± 5% of net UF) compared to lactate (29 ± 4% of net UF). Net UF for individual values of ivPSA differs between conventional PDF and more biocompatible solutions, such as bicarbonate PDF. This observed change in UF cannot be fully explained by differences in glucose transport. The changes in FWT may be explained by the impact of the PDF biocompatibility on aquaporin function.

3-Deoxygalactosone, a new glucose degradation product in peritoneal dialysis fluids: Identification, quantification by HPLC/DAD/MSMS and its pathway of formation

Heat sterilization of peritoneal dialysis (PD) fluids leads to the formation of glucose degradation products (GDPs), which considerably impair long-term application of PD. Knowledge of the exact composition of GDPs present in a PD fluid is important to improve the biocompatibility of dialysis solutions. The present study conducted a targeted screening for novel GDPs with α-dicarbonyl structure in PD fluids. Thus, 3-deoxygalactosone (3-DGal) was identified for the first time in PD fluids. Quantification of 3-DGal was achieved by high-performance liquid chromatography (HPLC)/DAD/MSMS after derivatization with o-phenylendiamine to yield the quinoxaline derivative. Baseline separation of all α-dicarbonyl GDPs, particularly of the diastereomers 3-deoxyglucosone (3-DG) and 3-DGal, required the application of a polar, phenyl-based RP column for HPLC and additional pH-gradient elution. Concentrations of 3-DGal ranged between 55.8 and 136.9 μM in single-chamber PD fluids, and between 2.5 and 12.4 μM in double-chamber PD fluids. In solutions containing glucose, 3-DGal is formed from 3-DG via the intermediate 3,4-dideoxyglucosone-3-ene (3,4-DGE). Further studies are now required to determine the (patho-)physiological properties of 3-DGal.

Katheterassoziierte Komplikationen bei der Peritonealdialyse – Infektiöse und nicht infektiöse Komplikationen sowie Prophylaxe

Katheterassoziierte Infektionen sind eine wichtige Ursache für einen Wechsel von Peritonealdialysepatienten zur Hämodialyse. Eine Frühdiagnose dieser Infektionen und einer eventuellen Tunnelbeteiligung (mittels Sonografie des Kathetertunnels) sind ebenso wichtig wie eine rechtzeitige adäquate Therapie. Schmerzen beim Dialysatein- oder -auslauf können durch vorzeitigen Abbruch des Dialysatauslaufes, Umstellung auf Tidal-Peritonealdialyse oder Wechsel zu biokompatibleren Dialyselösungen behandelt werden. Bei Dialysatauslaufproblemen kann man zunächst Laxanzien und Antiflatulenzien verabreichen und die Patienten können im Falle einer Katheterdislokation gymnastische Übungen durchführen. Bei einer persistierenden Fehllage des Katheters ist eine Relokalisation mittels Führungsdraht oder Laparoskopie oder ein Wechsel des Katheters notwendig. Beim Auftreten eines Dialysatlecks an der Katheteraustrittsstelle sollte man die Peritonealdialyse unterbrechen. Sie kann meist nach ein paar Tagen mit reduziertem Füllvolumen oder nach der Umstellung auf eine automatisierte Peritonealdialyse fortgeführt werden. In seltenen Fällen ist eine kontinuierliche Drainage der Peritonealhöhle oder eine chirurgische Revision (besser Katheterwechsel) notwendig. Die Erfahrung des Peritonealdialyseteams und des Chirurgen sind aus prophylaktischer Sicht für das Katheterüberleben bedeutender als das verwendete Kathetermodell oder die Implantationsmethode. Eine korrekte Anlage der Austrittsstelle und die Patientennachschulung bezüglich des Verbandswechsels haben eine große Bedeutung. Aktuelle Guidelines empfehlen die tägliche Anwendung einer antibiotischen Salbe an der Peritonealdialysekatheter-Austrittsstelle.

Mesure par μTDM et dilution de nanocolloïdes-99mTc de la surface péritonéale chez le rat insuffisant rénal au cours d’une expérience de dialyse péritonéale

Peritoneal dialysis takes an important place for the management of patients with end-stage renal failure, especially for young children. The optimization of its efficiency needs to use biocompatible dialysis solutions but also to improve peritoneal surface area (PSA) recruitment. Small animals experimental models are an essential step for PSA measurements. We propose a fast method using in vivo microcomputerized tomography (μCT) and isotopic dilution method to evaluate the PSA.

The Peritoneum: From Histological Studies to Mesothelial Transplant through Animal Experimentation

Normal peritoneal anatomy is dramatically altered by several stimuli, one of which is the presence of peritoneal dialysis solutions (PDS) in the abdomen (1‐3). The distress induced by these commercial dialysis solutions manifests as rapid mesothelial changes, vascular alterations, and peritoneal sclerosis (PS) (4,5). These alterations start with the beginning of dialysis treatment and are accelerated by episodes of peritonitis, leading to gradual replacement of peritoneum by fibrous tissue (6,7). Efforts have been made to understand the role of commercial PDS and to prepare more biocompatible dialysis solutions (8‐10). Mesothelial cell cultures allow us to study the behavior of these cells in normal conditions and during peritoneal dialysis (PD), but to explore the submesothelial layer it is necessary to experiment

Icodextrin and Intraperitoneal Inflammation

The peritoneum is impaired by exposure to biocompatible dialysis solutions. Because icodextrin peritoneal dialysis fluid (PDF) is made from cornstarch, a possibility that it induces intraperitoneal inflammation has been reported. In the present study, patients on glucose PDF were switched to icodextrin PDF and then switched back to glucose PDF. Icodextrin PDF-induced intraperitoneal inflammation was investigated based on changes in peritoneal permeability and inflammatory reactions. The subjects were 7 stable peritoneal dialysis patients (4 men, 3 women), with a mean age of 59.1 +/- 3.8 years (range: 55.2 - 64.6 years). The mean duration of peritoneal dialysis was 58.3 +/- 27.4 months (range: 34.3 - 97.7 months), and the cause of end-stage renal disease was chronic glomerulonephritis in all patients. For the overnight dwell, glucose PDF was changed to icodextrin PDF, and the patients returned to glucose PDF 30 months later. To evaluate peritoneal permeability, a peritoneal equilibrium test (PET) was performed, and dialysate-to-plasma (D/P) ratios of creatinine (Cr), beta(2)-microglobulin (beta2M), albumin, immunoglobulin G (IgG), and alpha(2)-macroglobulin (alpha2M) were measured in the overnight dialysate and serum. As markers of inflammation and fibrinolysis or coagulation, interleukin-6 (IL-6) and fibrinogen degradation products (FDPs) were measured in overnight effluent. The evaluations were made every 6 months for 36 months. A significant elevation in FDP levels was detected in overnight effluent 6 months after the switch to icodextrin PDF, and IL-6 levels tended to increase. The D/P ratios of Cr, beta2M, and albumin were also significantly increased, and the D/P ratios of IgG and alpha2M tended to increase. The D/P ratio of Cr as measured by PET was slightly increased, but the elevation was not significant. In 5 patients, after icodextrin PDF was switched back to glucose PDF at 30 months, the D/P ratios of Cr, beta2M, albumin, IgG, and alpha2M in overnight effluent were significantly reduced. The FDP levels decreased slightly in those patients. In the remaining 2 patients, the D/P ratios of Cr on PET and of Cr, beta2M, albumin, IgG, and alpha2M in overnight effluent, and the FDP and IL-6 levels in overnight effluent were markedly elevated after the switching from glucose to icodextrin PDF, and they remained high after the switch back to glucose PDF. One of these 2 patients developed pre-EPS and was treated with prednisolone and concomitant hemodialysis. The other was switched from peritoneal dialysis to hemodialysis. Icodextrin dialysis solution may induce an inflammatory reaction in the peritoneum. Further investigation is necessary for the long-term use of icodextrin PDF.

Correlation between dialysis solution type and cardiovascular morbidity rate in patients undergoing continuous ambulatory peritoneal dialysis

Peritoneal dialysis (PD) patients have an increased risk for cardiovascular diseases. The aim of the study was to evaluate the cardiovascular changes in patients undergoing chronic PD and the eventual existing differences depending on biocompatibility of dialysis solutions. After 3 +/- 2 years of starting PD, 21 PD patients on the treatment with bioincompatible dialysis solutions (conventional glucose- based solutions: PDP-1), average age 47.43 +/- 12.87 years, and 21 PD patients on the treatment with biocompatible dialysis solutions (neutral solutions with lower level of glucose degradation products, lower concentration of Ca2+ and neutral pH: PDP-2), average age 68.62 +/- 13.98 years, participated in the longitudinal study. The average number of episodes of peritonitis was similar in both groups: 1 episode per 36 months of the treatment. The control group included 21 patients with preterminal phase of chronic renal failure (Glomerular Filtration Rate: 22.19 +/- 10.73 ml/min), average age 65.29 +/- 13.74 years. All the patients underwent transthoracal echocardiography (in order to detect: eject fraction (EF), left ventricular hypertrophy (LVH), and valvular calcification (VC) and B-mode ultrasonography of common carotid artery (CCA): IMT, lumen narrowing, and plaque detection. The values of EF were: in PDP-1 group 62.05 +/- 5.65%, in PDP-2 group 53.43 +/- 7.47%, and in the control group 56.71 +/- 8.12% (Bonferroni test, p = 0.001). The recorded LVH was: in PDP-1 group in 47.6% of the patients; in PDP-2 group in 61.9% of the patients; and in control the group in 52.4% (chi2 test; p = 0.639). The detected VC was: in PDP-1 in 52.4% of the patients, in PDP-2 group in 42.9% of the patients, and in the control group in 23.8% of the patients (chi2 test; p = 0.776). The IMT was: in PDP-1 group 1.26 +/- 0.54 mm, in PDP-2 group 1.23 +/- 0.32, and in the control group 1.25 +/- 0.27 mm (Bonferroni test; p = 0.981). An average lumen narrowing was: in PDP-1 group 13.78 +/- 18.26%, in PDP-2 group 18.57 +/- 22.98%, and in the control group 25.00 +/- 28.02% (Kruskal Wallis test; p = 0.413). Calcified plaques of CCA were detected in PDP-1 group in 61.9% of the patients, in PDP-2 group in 85.7%, of the patients and p = 0.159). Generally, PD had a significant influence on cardiovascular morbidity in the treated patients, especially on the left ventricular function and peripheral atherosclerosis. The age of the patients had more influence on acceleration of atherosclerosis than the length of dialysis or biocompatibility of dialysis solutions.

Randomized controlled study of biocompatible peritoneal dialysis solutions: Effect on residual renal function

Residual kidney function is important for patient and technique survival in peritoneal dialysis (PD). Biocompatible dialysis solutions are thought to improve function and viability of peritoneal mesothelial cells and to preserve residual renal function (RRF). We conducted a randomized controlled study comparing use of biocompatible (B) with standard (S) solutions in 93 incident PD patients during a 1-year period. The demographics, comorbidities, and RRF of both groups were similar. At 3 and 12 months, 24-h urine samples were collected to measure volume and the mean of urea and creatinine clearance normalized to body surface area. Surrogate markers of fluid status, diuretic usage, C-reactive protein concentration, peritonitis episodes, survival data, and peritoneal equilibrium tests were also collected. Changes in the normalized mean urea and creatinine clearance were the same for both groups, with no significant differences in secondary end points. Despite non-randomized studies suggesting benefits of these newer biocompatible solutions, we could not detect any clinically significant advantages. Additional studies are needed to determine if advantages are seen with longer term use.

Impact of new dialysis solutions on peritonitis rates

Peritonitis remains a major cause of morbidity among patients on peritoneal dialysis (PD), yet there is little information about the effect of new biocompatible dialysis solutions on peritonitis rates and treatment. In our unit, information on each peritonitis episode is prospectively collected. Since 2003, bicarbonate/lactate dialysate has been gradually introduced for new patients and for patients experiencing abdominal pain with conventional lactate solutions. From 2002 to 2005, data from 121 episodes of peritonitis (71 automated PD and 50 continuous ambulatory PD) were analyzed; 107 episodes occurred in patients using standard lactate dialysate and 14 episodes in patients using bicarbonate/lactate solution. Patients using bicarbonate/lactate had a significantly lower peritonitis rate of 1 per 52.5 patient-months compared to those using standard lactate dialysate (1 per 26.9 patient-months) (P=0.0179). Response to treatment, however, was not affected by the type of dialysate; cure rates (71.4 and 69.1%, respectively) and recurrence rates (21.4 and 15.8%, respectively) were not significantly different. Catheter removal was required in three (21.4%) patients using bicarbonate/lactate and 23 (22.4%) patients using lactate solution. Use of biocompatible dialysate appears to reduce the peritonitis rate by 50%, although this has to be confirmed in a randomized study. The type of dialysate, on the other hand, does not affect response to treatment.