Conventional Peritoneal Dialysis Research Articles

#2490 Analyzing the morphology of mesothelial cells when exposed to peritoneal dialysis solutions

Abstract Background and Aims Glucose remains the predominant osmotic agent in peritoneal dialysis (PD), yet its prolonged use is associated with an inevitable decline in peritoneal filtration capacity. Persistent contact with glucose during dialysis can induce significant morphological and functional changes in the peritoneum. In this study, we explore the morphological alterations in mesothelial cells exposed to both conventional glucose-based PD solutions and an innovative biocompatible PD solution (XyloCore) containing L-carnitine and Xylitol. Method Met5A mesothelial cells were seeded and cultured on a polyester filter (with a pore size of 0.4 micrometers, Transwell, 12 well type, Millipore) utilizing a full medium. The impact of PD solutions, differentiating between glucose-based and XyloCore, was assessed on cells cultivated on transwells. These cells were exposed to PD solutions on the apical side and to culture medium on the basal side. The cells were then employed for proteomic and metabolomic assessments and were also fixed and scrutinized through scanning electron microscopy (SEM). Results Through unsupervised hierarchical clustering analysis, discernable proteomic distinctions emerged between wild-type (WT) cells (control) and cells exposed to either glucose-based PD solution or XyloCore. In SEM analysis, control cells exhibited a distinct flat epithelial appearance. Contrastingly, subjecting WT cells to treatment with a glucose-based PD solution induced significant alterations in cellular morphology. Notably, cells displayed elongated shapes, loosening of cell-cell contacts, and a consistent denuding of the culture surface. In contrast, XyloCore maintained a better cellular morphology and mitigated cell detachment. Conclusion Preserving the integrity of the mesothelial barrier is crucial for maintaining peritoneal ultrafiltration capacity. The findings suggest that glucose-based PD solutions trigger early morphological changes in cell shape and cell-cell contacts, likely stemming from alterations in cytoskeleton or adhesion molecules. The exploration of new osmotic agents in clinical practice holds paramount significance for the future of peritoneal dialysis.

The association between embedded catheter implantation and hospitalization costs for peritoneal dialysis initiation: a retrospective cohort study.

Compared with the conventional peritoneal dialysis (PD) catheter insertion, embedding PD catheter implantation is one of the procedures for planned PD initiation. However, facilities where embedded PD catheter implantation is available are limited, and the impact of embedded PD catheter implantation on hospitalization cost and length of hospitalization is unknown. This retrospective single-center cohort study included 132 patients with PD initiation between 2005 and 2020. The patients were divided into two groups: 64 patients in the embedding group and 68 patients in the conventional insertion group. We created a multivariable generalized linear model (GLM) with the gamma family and log-link function to evaluate the association among catheter embedding, the duration and medical costs of hospitalization for PD initiation. We also evaluated the effect modification between age and catheter embedding. Catheter embedding (β coefficient - 0.13 [95% confidence interval - 0.21, - 0.05]) and age (per 10years 0.08 [0.03, 0.14]) were significantly associated with hospitalization costs. Catheter embedding (- 0.21 [- 0.32, - 0.10]) and age (0.11 [0.03, 0.19]) were also identified as factors significantly associated with length of hospitalization. The difference between the embedding group and the conventional insertion group in hospitalization costs for PD initiation (P for interaction = 0.060) and the length of hospitalization (P for interaction = 0.027) was larger in young-to-middle-aged patients than in elderly patients. Catheter embedding was associated with lower hospitalization cost and shorter length of hospitalization for PD initiation than conventional PD catheter insertion, especially in young-to-middle-aged patients.

The influence of different peritoneal dialysis techniques on wound infection in patients with peritoneal dialysis tube.

More and more research has started to investigate the effect of peritoneal dialysis treatment on the incidence of pericatheter wound complications in chronic kidney disease (CKD). This meta-study evaluated the effect of emergency peritoneal dialysis (EPD) with conventional peritoneal dialysis (CPD) in patients with catheter-related complications. We looked up 4 databases: PubMed, EMBASE, Cochrane, and Web of Science, and analysed the data with RevMan 5. There were a total of 15 studies with 3034 participants. While the quality of the research included was fairly good, the evidence was mediocre. In the meta-analyses, the risk of leak in the conduit with PD was very high (OR, 2.48; 95% CI, 1.72, 3.59, p < 0.00001). However, for those treated with urgent medical method prior to initiation of PD, the risk for peritonitis, catheter dysfunction and bleeding was similar compared with CPD. Based on limited information, immediate initiation of PDs is advised in order to increase the quality of life for people in urgent need, except if there is no consideration for loss of fluid. The low quality of the evidence is holding up the evidence. This research, however, is also informative because of the large number of available data. Consequently, additional high quality, large, randomized controlled studies are required to establish.

The benefits of peritoneal dialysis (PD) solution with low-glucose degradation product in residual renal function and dialysis adequacy in PD patients: A meta-analysis.

The peritoneal effects of low-glucose degradation product (GDP)-containing peritoneal dialysis (PD) solutions have been extensively described. To systematically evaluate the efficacy and safety of low GDP solution for PD patients, specifically the effect on residual renal function (RRF) and dialysis adequacy, we conducted a meta-analysis of the published randomized controlled trials (RCTs). Different databases were searched for RCTs that compared low GDP-PD solutions with conventional PD solutions in the treatment of PD patients with continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). The outcomes of RCTs should include RRF and may include small solute clear-ance, peritoneal transport status, nutritional status, and all-cause mortality. Seven studies (632 patients) were included. Compared with the conventional solution, low-GDP solution preserved RRF in PD patients over time (MD 0.66 mL/min, 95% CI 0.34 to 0.99; p&lt;0.0001), particularly in one year of treatment (p&lt;0.01), and improved weekly Kt/V (MD 0.11, 95% CI 0.05 to 0.17; p=0.0007) without an increased 4-hour D/Pcr (MD 0.00, 95% CI -0.02 to 0.02; p=1.00). Notably, the MD of RRF and urine volume between the two groups tended to decrease as time on PD progressed up to 24 months. Patients using low GDP PD solutions did not have an increased risk of all-cause mortality (MD 0.97, 95% CI 0.50 to 1.88; p=0.93). Our meta-analysis confirms that the low GDP PD solution preserves RRF, improves the dialysis adequacy without increasing the peritoneal solute transport rate and all-cause mortality. Further trials are needed to deter-mine whether this beneficial effect can affect long-term clinical outcomes.

MO696INCREMENTAL PERITONEAL DIALYSIS: BENEFICIAL EFFECTS

Abstract Background and Aims Incremental peritoneal dialysis (Incr_Dial) is a renal replacement therapy strategy based on lower dose prescription rather than the standard “full dose” (Full_Dial). Individualized clearance goals were achieved combining residual renal function (RRF) and peritoneal clearance. Maintaining RRF is a crucial issue to peritoneal dialysis (PD) patients and the best PD strategy to preserve it is subject to debate. The aim of this study is to compare Incr_Dial and Full_Dial in terms of RRF preservation and other clinical outcomes. Method This was a single-center, retrospective descriptive study. We included a cohort of incident and prevalent adult PD patients in the PD Unit between January – December of 2020. Patients without a follow-up &amp;lt; six months and who started PD at another center were excluded. Patients were assigned according to their first PD protocol in two groups – Group A: Incr_Dial protocol (continuous ambulatory PD: less than four dwells daily, less than 2 L dwell volumes, less than seven days a week treatment, or some combination of these; automated PD: without a long dwell, less than 10 L daily delivered by cycler and day dwells, treatment for less than 7 days a week or some combination of these); Group B: Full_Dial protocol. Statistical analysis was performed using SPSS 20.0. Statistical significance level p &amp;lt;0.05. Results Among 84 PD patients, 68% underwent incremental PD (Group A) and 31% underwent conventional full-dose PD (Group B). The mean age was 55.9±15.4 years, 60.7% were male and 32.5% diabetic. There were no statistically significant differences between the two groups regarding: demographic characteristics, comorbidities (diabetes, hypertension, cardiac insufficiency or ischemic heart disease) and drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and/or loop diuretics). The median Incr_Dial duration to achieve PD full dose was 10.2 months (IQ 5.1-17). At the beginning of PD, there was no statistically significant difference in diuresis between both groups (A: 1.79L vs B: 1.2L, p=0.07), however after 6 months of PD there was a superior urinary output in Group A (A: 1.67L vs B: 1.1L, p=0.037). Group A (Incr_Dial) was also associated with a superior renal clearance of creatinine at the beginning (A: 81 L/sem/1.73m2 vs B: 56.8L/sem/1.73m2, p=0.021) and after 12 months (A: 70.7L/sem/1.73m2 vs B: 26.3 L/sem/1.73m2, p&amp;lt;0.01); and superior Kt/V renal/week at the beginning (A: 1.48 vs B: 1.02, p=0.02) and after 12 months (A: 1.28 vs B: 0.49, p&amp;lt;0.001). There are no differences between mortality (A: 1.9% vs B: 12%, p=0.094), peritonitis-free time (A: 158 days vs B: 236 days, p=0.133) and the numbers of peritonitis per year (A: 0.32 vs B: 0.5, p=0.940). However, the rate of hospital admissions per year was lower in Group A (A: 0.22 vs B: 0.70, p=0.001). Conclusion Incremental PD is a safe strategy of renal replacement therapy to start PD. In our PD population, it showed similar patient survival rates and a significantly less hospital admissions. Incremental PD was also beneficial for preserving RRF when compared to full-dose PD.

Case series of acute peritoneal dialysis in the prone position for acute kidney injury during the Covid-19 pandemic: Prone to complications?

Patients with kidney failure and acute respiratory distress syndrome (ARDS) requiring prone position have not been candidates for peritoneal dialysis (PD) due to concern with increased intra-abdominal pressure, reduction in respiratory system compliance and risks of peritoneal fluid leaks. We describe our experience in delivering acute PD during the surge in Covid-19 acute kidney injury (AKI) in the subset of patients requiring prone positioning. All seven patients included in this report were admitted to the intensive care unit with SARS-CoV-2 infection leading to ARDS, AKI and multisystem organ failure. All required renal replacement therapy, and prone positioning to improve ventilation/perfusion mismatch. All seven were able to continue PD despite prone positioning without any detrimental effects on respiratory mechanics or the need to switch to a different modality. Fluid leakage was noted in 71% of patients, but mild and readily resolved. We were able to successfully implement acute PD in ventilator-dependent prone patients suffering from Covid-19-related AKI. This required a team effort and some modifications in the conventional PD prescription and delivery.

Comparison of clinical outcome between incremental peritoneal dialysis and conventional peritoneal dialysis: a propensity score matching study

Background Incremental peritoneal dialysis (iPD) can be useful in patients with residual renal function (RRF). RRF was well preserved and similar survival was shown in iPD compared to conventional PD (cPD) in previous study. However, the long-term survival of iPD remains unclear compared to cPD in diabetic patients. This study evaluated whether patient survival, hospitalization and peritonitis, and PD survival in iPD were lower than cPD or not. Methods We conducted a 12-year retrospective observational study of 303 PD patients (232 cPD and 71 iPD) using propensity score matching by age, gender, and diabetes mellitus (DM). Finally, 78 cPD patients and 39 iPD patients were included and 44 patients had DM. Incremental PD was defined as starting PD with two or three manual exchanges per day. Results The median duration of iPD was 24.1 months and iPD had higher RRF than cPD. Compared to cPD, the patient survival, PD survival and hospitalization benefits were not found in iPD but diabetic iPD patients had significantly longer survival and less hospitalization. Cumulative risk for peritonitis was lower iPD and PD duration of iPD was longer than those of cPD. The iPD was an independent factor associated with survival in patients with DM. Conclusions Incremental PD may be a safe PD modality to initiate and maintain PD in less uremic patients with tolerable RRF. Incremental PD would be a benefit for survival in diabetic patients. Further prospective studies are necessary to confirm the effectiveness of iPD in PD patients with similar RRF.

Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid.

Understanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) efficacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein loss in a recent clinical trial. Transepithelial resistance and 10 kDa and 70 kDa dextran transport were measured in primary human endothelial cells (HUVEC) exposed to conventional acidic, glucose degradation products (GDP) containing PDF (CPDF) and to low GDP containing PDF (LPDF) with and without AlaGln. Zonula occludens-1 (ZO-1) and claudin-5 were quantified by Western blot and immunofluorescence and in mice exposed to saline and CPDF for 7 weeks by digital imaging analyses. Spatial clustering of ZO-1 molecules was assessed by single molecule localization microscopy. AlaGln increased transepithelial resistance, and in CPDF exposed HUVEC decreased dextran transport rates and preserved claudin-5 and ZO-1 abundance. Endothelial clustering of membrane bound ZO-1 was higher in CPDF supplemented with AlaGln. In mice, arteriolar endothelial claudin-5 was reduced in CPDF, but restored with AlaGln, while mesothelial claudin-5 abundance was unchanged. AlaGln supplementation seals the peritoneal endothelial barrier, and when supplemented to conventional PD fluid increases claudin-5 and ZO-1 abundance and clustering of ZO-1 in the endothelial cell membrane.

In vitro efficacy and safety of a system for sorbent-assisted peritoneal dialysis.

A system for sorbent-assisted peritoneal dialysis (SAPD) was designed to continuously recirculate dialysate via a tidal mode using a single lumen peritoneal catheter with regeneration of spent dialysate by means of sorbent technology. We hypothesize that SAPD treatment will maintain a high plasma-to-dialysate concentration gradient and increase the mass transfer area coefficient of solutes. Thereby, the SAPD system may enhance clearance while reducing the number of exchanges. Application is envisaged at night as a bedside device (12 kg, nighttime system). A wearable system (2.0 kg, daytime system) may further enhance clearance during the day. Urea, creatinine, and phosphate removal were studied with the daytime and nighttime system (n = 3 per system) by recirculating 2 liters of spent peritoneal dialysate via a tidal mode (mean flow rate: 50 and 100 mL/min, respectively) for 8 h in vitro. Time-averaged plasma clearance over 24 h was modeled assuming one 2 liter exchange/day, an increase in mass transfer area coefficient, and 0.9 liters ultrafiltration/day. Urea, creatinine, and phosphate removal was 33.2 ± 4.1, 5.3 ± 0.5, and 6.2 ± 1.8 mmol, respectively, with the daytime system and 204 ± 28, 10.3 ± 2.4, and 11.4 ± 2.1 mmol, respectively, with the nighttime system. Time-averaged plasma clearances of urea, creatinine and phosphate were 9.6 ± 1.1, 9.6 ± 1.7, and 7.0 ± 0.9 mL/min, respectively, with the nighttime system and 10.8 ± 1.1, 13.4 ± 1.8, and 9.7 ± 1.6 mL/min, respectively, with the daytime and nighttime system. SAPD treatment may improve removal of uremic toxins compared with conventional peritoneal dialysis, provided that peritoneal mass transport will increase.

P1130A CELLULAR MODEL OF HUMAN MESOTHELIUM TO STUDY OF WATER TRANSPORT DURING PERITONEAL DIALYSIS AND THE BIOCOMPATIBILITY OF INNOVATIVE GLUCOSE-SPARING SOLUTIONS.

Abstract Background and Aims The three pore model postulates that the endothelium of peritoneal capillaries is the major limiting barrier regulating water transport across peritoneal membrane during peritoneal dialysis (PD). We hypothesize that the mesothelium may represent an additional selective barrier to water diffusion in PD. We previously demonstrated that the water channel AQP1 is expressed in vivo by mesothelial cells. Here, we characterized an immortalized cell line of human mesothelium (HMC) to study the functional role of the water channel AQP1 in mediating water transport during PD and also to test the biocompatibility of glucose-sparing PD solutions (Xylocore), containing xylitol and L-carnitine as the main osmotic agents. Method Cells were grown onto porous cell culture inserts to achieve polarization. Polarization was demonstrated by expression of the tight junction markers Zo-1 and occludin. Transepithelial water transport was measured by TEA+-sensitive microelectrodes. HMC cell monolayers were exposed to PD solutions at the apical side for 8 hours. The biocompatibility of conventional versus innovative PD solutions was evaluated by MTT-test, measurement of transepithelial electrical resistance (TEER) and production of pro-inflammatory cytokines by by Luminex xMAP technology. Results HMC cells showed polarized expression of Na+/K+-ATPase and tight junctions markers but no endogenous expression of AQP1. HMC showed a low TEER (40Ω/cm2) compared to renal cells not expressing AQP1(1000Ω/cm2). However, the transepithelial water transport was comparable between the two cell types. Experiments in HMCs transfected with AQP1 cDNA, suggested that the water permeability of HMC was increased by two-fold in the presence of AQP1. Biocompatibility assays indicated that in conventional dialysis solutions glucose concentration decreased cell viability in a dose-dependent manner. Glucose concentration also strongly decreased the TEER, suggesting reduction of the barrier integrity, and increased pro-inflammatory cytokines production. Interestingly, substitution of part of the glucose with xylitol and L-carnitine minimized these effects. Conclusion These results suggest that the mesothelium may represent an additional selective barrier regulating water transport through the water channel AQP1 in PD. Importantly, we also demonstrate that the formulation of glucose-sparing PD solutions containing xylitol and L-carnitine better preserve mesothelial cells viability and may represent a useful means to prolong the dialysis life of patients undergoing peritoneal dialysis.

Vasculopathy plays an important role during the development and relapse of encapsulating peritoneal sclerosis with conventional peritoneal dialysis solutions.

Encapsulating peritoneal sclerosis (EPS) is an uncommon but life-threatening complication of peritoneal dialysis (PD) therapy. The causative factors of EPS remain unclear. Pathological studies of the peritoneum affected by EPS and relationships with clinical factors including PD solutions remain lacking. The objective of this study was to examine peritoneal samples from EPS patients and to identify the associations of peritoneal pathology with different clinical factors. Peritoneal specimens were obtained at the time of surgical enterolysis in Tsuchiya General Hospital from 1993 to 2016. A total of 223 PD patients were enrolled and analyzed. Tissues were fixed with formalin and processed with hematoxylin and eosin and Masson's trichrome staining, as well as immunohistochemical staining for CD31 and CD68. Evaluations could be made in 174 patients who received surgical enterolysis. Conventional or pH-neutral low-glucose degradation product PD solutions were utilized during PD treatment. The conventional PD solution group showed less angiogenesis (P = 0.013) but more severe vasculopathy, in the form of a lower ratio of luminal diameter to vessel diameter (L/V ratio) (P < 0.001) in association with longer PD treatment. Multivariate Cox proportional hazard models revealed that L/V ratio (per 0.1 increase, hazard ratio = 0.88, 95% confidence interval 0.77-0.99, P = 0.047) was significantly associated with a lower incidence of EPS relapse. In contrast, most of the cases in the pH-neutral solution group showed milder vasculopathy. The pathology of EPS differed between conventional and pH-neutral solution groups. Vasculopathy was related to the development and relapse of EPS in the conventional solution group.

A cellular model of human mesothelium to study the physiology of water transport during peritoneal dialysis and the biocompatibility of innovative glucose‐sparing solutions.

The three pore model postulates that the endothelium of peritoneal capillaries is the major limiting barrier regulating water transport across peritoneal membrane during peritoneal dialysis (PD).We hypothesize that the mesothelium may represent an additional selective barrier to water diffusion in PD.We characterized an immortalized cell line of human mesothelium (HMC) to study the functional role of the water channel AQP1 expressed in vivo by mesothelial cells and also to test the biocompatibility of glucose‐sparing PD solutions containing xylitol and carnitine as the main osmotic agents.Transepithelial water transport was measured by TEA+‐sensitive microelectrodes. The biocompatibility of conventional versus innovative PD solutions was evaluated by MTT‐test, measurement of transepithelial electrical resistance (TEER) and production of pro‐inflammatory cytokines.HMCs showed polarized expression of Na+/K+‐ATPase and tight junctions markers but no endogenous expression of AQP1.HMC showed a low TEER compared to renal cells not expressing AQP1. However, the transepithelial water transport was comparable between the two cell types.Experiments in HMCs transfected with AQP1 cDNA, suggest that the water permeability of HMC is strictly dependent of the presence of AQP1.Biocompatibility assays indicate that conventional dialysis solutions with high glucose significantly reduce both cell viability and TEER, and increase pro‐inflammatory cytokines production.Interestingly, innovative PD solutions minimize these effects. These results suggest that the mesothelium may represent an additional selective barrier regulating water transport in PD. Importantly, we also demonstrated that the formulation of glucose‐sparing PD solutions containing xylitol and carnitine better preserve mesothelial cells viability and may represent a useful means to prolong the dialysis life of patients undergoing peritoneal dialysis.Support or Funding InformationApulian Region NATURe project Code: XUANRO4

Randomized controlled trials for comparison of laparoscopic versus conventional open catheter placement in peritoneal dialysis patients: a meta-analysis

BackgroundThe application of laparoscopic catheterization technology in peritoneal dialysis (PD) patients has recently increased. However, the advantages and disadvantages of laparoscopic versus conventional open PD catheter placement are still controversial. The aim of this meta-analysis is to assess the complications of catheterization in PD patients and to provide a reference for choosing a PD-catheter placement technique in the clinic.MethodsWe searched numerous databases, including Embase, PubMed, CNKI and the Cochrane Library, for published randomized controlled trials (RCTs).ResultsEight relevant studies (n = 646) were included in the meta-analysis. The pooled results showed a lower incidence of catheter migration (OR: 0.42, 95% CI: 0.19 to 0.90, P: 0.03) and catheter removal (OR: 0.41, 95% CI: 0.21 to 0.79, P: 0.008) but a higher incidence of bleeding (OR: 3.25, 95% CI: 1.18 to 8.97, P: 0.02) with a laparoscopic approach than with a conventional approach. There was no significant difference in the incidence of omentum adhesion (OR: 0.32, 95% CI: 0.05 to 2.10, P: 0.24), hernia (OR: 0.38, 95% CI: 0.09 to 1.68, P: 0.20), leakage (OR: 0.69, 95% CI: 0.38 to 1.26, P: 0.23), intestinal obstruction (OR: 0.96, 95% CI: 0.48 to 1.91, P: 0.90) or perforation (OR: 0.95, 95% CI: 0.06 to 15.42, P: 0.97). The statistical analysis showed no significant difference in early (OR: 0.44, 95% CI: 0.15 to 1.33, P: 0.15), late (OR: 0.89, 95% CI: 0.41 to 1.90, P: 0.76) or total (OR: 0.68, 95% CI: 0.42 to 1.12, P: 0.13) peritonitis infections between the 2 groups, and there are no no significant difference in early (OR: 0.39, 95% CI: 0.06 to 2.36, P: 0.30), late (OR: 1.35, 95% CI: 0.78 to 2.33, P: 0.16) or total (OR: 1.20, 95% CI: 0.71 to 2.02, P: 0.17) tunnel or exit-site infections between the 2 groups.ConclusionLaparoscopic catheterization and conventional open catheter placement in PD patients have unique advantages, but laparoscopic PD catheterization may be superior to conventional open catheter placement. However, this conclusion needs to be confirmed with further large-sample-size, multi-centre, high-quality RCTs.

Removal of Protein-Bound Uremic Toxins by Liposome-Supported Peritoneal Dialysis.

Background:Protein-bound uremic toxins (PBUTs) are poorly cleared by peritoneal dialysis (PD). This study aimed to enhance PBUT removal in PD by adding a binder to the peritoneal dialysate and to evaluate the feasibility and efficacy of liposome-supported PD (LSPD) to increase the removal of PBUTs compared with albumin PD.Methods:Removal of p-cresyl sulfate (PCS), indoxyl sulfate (IS), and indole-3-acetic acid (3-IAA) was first evaluated in an in vitro PD model using artificial plasma preloaded with test solutes. Male Sprague-Dawley rats (n = 24) were then subjected to 5/6 nephrectomy and fed for 16 weeks to establish end-stage renal failure, after which they were treated with either conventional glucose-based PD, albumin-based PD, or liposome-based PD. Removal of PBUTs and small water-soluble solutes was determined during a 6-hour PD dwell.Results:In vitro experiments showed that adding albumin as a toxin binder to the dialysate markedly increased the removal of PCS, IS, and 3-IAA compared with the control. The uptake capacity of liposomes was comparable with that of albumin for PCS and 3-IAA, though slightly inferior for IS. In vivo PD in uremic rats demonstrated that LSPD resulted in higher intraperitoneal concentrations and more total mass removal for PBUTs than the conventional glucose-based PD, which was comparable with albumin PD.Conclusions:Supplementing conventional glucose-based PD solutions with a binder could efficiently increase the removal of PBUTs. This preliminary study suggested that LSPD may be a promising alternative to albumin PD for increasing PBUT removal in the development of next-generation PD solutions for PD patients.

Incremental Peritoneal Dialysis May be Beneficial for Preserving Residual Renal Function Compared to Full-dose Peritoneal Dialysis

Maintaining residual renal function (RRF) is a crucial issue in peritoneal dialysis (PD). Incremental dialysis is the practice of initiating PD exchanges less than four times a day in consideration of RRF, and increasing dialysis dose in a step-wise manner as the RRF decreases. We aimed to compare the outcomes of incremental PD and full-dose PD in terms of RRF preservation and other outcomes. This was a single-center, observational study. Data were extracted retrospectively from a cohort of incident PD patients over 16 years old who started PD between 2007 and 2015 in the PD Unit of Seoul National University Hospital. We used inverse probability weighting (IPW) adjustment based on propensity scores to balance covariates between the incremental and full-dose PD groups. Multivariate, time-dependent Cox analyses were performed. Among 347 incident PD patients, 176 underwent incremental PD and 171 underwent conventional full-dose PD. After IPW adjustment, the incremental PD group exhibited a lower risk of developing anuria (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.43–0.88). Patient survival, technique survival, and peritonitis-free survival were all similar between these groups (P > 0.05 by log-rank test). Incremental PD was beneficial for preserving RRF and showed similar patient survival when compared to conventional full-dose PD.

Urgent-start peritoneal dialysis and patient outcomes: a systematic review and meta-analysis.

The present study was aimed at illustrating short- or long-term patient outcome among individuals with urgent-start peritoneal dialysis (PD) compared with those with conventional PD. We searched the PubMed, EMBASE, Cochrane Controlled Trials Register and China National Knowledge Infrastructure databases. Cohort studies were investigated comparing the effects of urgent start of PD (<14 days after catheter insertion) to those of conventional start of PD (≥14 days after catheter insertion). Risks of bias across studies were evaluated using Newcastle-Ottawa Quality Assessment Scale. We calculated the pooled risk ratios and mean differences with 95% confidence intervals for dichotomous data and continuous data, respectively. Six studies involving 1,242 patients were identified. Compared with conventional PD, urgent-start PD was not associated with a high mortality (RR: 1.25, 95% CI: 0.92 to 1.69; I2=0%, p=0.99) and a higher prevalence of overall mechanical complications (RR: 1.79, 95% CI: 0.85 to 3.78; p=0.12; I2=64%, p=0.02). However, urgent-start PD was associated with a higher prevalence of leakage (RR: 6.72, 95% CI: 2.11 to 21.32; I2=0%, p=0.60). In terms of infectious complications, data analysis of the fixed-effects model showed no difference between the two groups. (RR: 1.36, 95% CI: 0.90 to 2.05, p=0.14), regardless of peritonitis (RR: 1.36, 95% CI: 0.90 to 2.05, p=0.14; I2=0%, p=0.70) or other infections (RR: 1.15, 95% CI: 0.49 to 2.69, p=0.99; I2=0%, p=0.75). Urgent-start PD was not associated with a higher risk of mortality and dialysis-related complications. However, compared with conventional PD, an urgent start of PD may increase the risk of a leak.

The role of icodextrin in peritoneal dialysis: protocol for a systematic review and meta-analysis

BackgroundPrevious meta-analyses have found several advantages of icodextrin compared with glucose in the application of peritoneal dialysis (PD), such as an improvement of peritoneal ultrafiltration during the long dwell and a reduction in episodes of uncontrolled fluid overload. However, the effect of icodextrin on patient-relevant outcomes remains unclear. This review aims to evaluate the benefits and harms of icodextrin in comparison with conventional glucose PD solution in patients with end-stage kidney disease receiving PD.MethodsRandomized controlled trials of icodextrin comparing with conventional glucose solution in patients with end-stage kidney disease who received PD will be deemed eligible. We will conduct systematic searches in MEDLINE, EMBASE, CENTRAL, Ichushi-Web, Chinese and Japanese databases, and in clinical trials registries (ClinicalTrials.gov, International Clinical Trials Registry Platform Search Portal (ICTRP), EU Clinical Trials Register, Japan Registries Network (JPRN), China’s Clinical Trial Registry (ChiCTR)). Furthermore, we will check conference proceedings and search references from relevant studies manually. Relevant pharmaceutical companies, authors, and experts will be contacted in an effort to identify further studies. We will not apply any limitations regarding language, publication status, and publication date when searching for eligible studies. The selection of studies, data extraction, and risk of bias assessment will be carried out by two independent reviewers. Data synthesis will be performed using RevMan 5 software with either a fixed effects model or random-effects model, depending on the presence of heterogeneity. For the assessment of statistical heterogeneity, I2 will be calculated. Sources of clinical heterogeneity will be evaluated through subgroup analyses. If there are ten or more studies included in the meta-analysis, we will investigate the publication bias using funnel plots and Egger’s test. The quality of the body of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.DiscussionWe assume that our systematic review will be more comprehensive compared to those published previously due to contacting the relevant pharmaceutical companies and a systematic search of published and unpublished non-English studies from China, Taiwan, and Japan.Systematic review registrationPROSPERO CRD42018096951

Biocompatible Peritoneal Dialysis: The Target Is Still Way Off.

Peritoneal dialysis (PD) is a cost-effective, home-based therapy for patients with end-stage renal disease achieving similar outcome as compared to hemodialysis. Still, a minority of patients only receive PD. To a significant extend, this discrepancy is explained by major limitations regarding PD efficiency and sustainability. Due to highly unphysiological composition of PD fluids, the peritoneal membrane undergoes rapid morphological and long-term functional alterations, which limit the treatment and contribute to adverse patient outcome. This review is focused on the peritoneal membrane ultrastructure and its transformation in patients with kidney disease and chronic PD, underlying molecular mechanisms, and potential systemic sequelae. Current knowledge on the impact of conventional and second-generation PD fluids is described; novel strategies and innovative PD fluid types are discussed.

Biocompatible dialysis fluids for peritoneal dialysis.

Biocompatible peritoneal dialysis (PD) solutions, including neutral pH, low glucose degradation product (GDP) solutions and icodextrin, have previously been shown to favourably influence some patient-level outcomes, albeit based on generally sub-optimal quality studies. Several additional randomised controlled trials (RCT) evaluating biocompatible solutions in PD patients have been published recently. This is an update of a review first published in 2014. This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD. The Cochrane Kidney and Transplant Specialised Register was searched up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. All RCTs and quasi-RCTs in adults and children comparing the effects of biocompatible PD solutions (neutral pH, lactate-buffered, low GDP; neutral pH, bicarbonate(± lactate)-buffered, low GDP; glucose polymer (icodextrin)) in PD were included. Studies of amino acid-based solutions were excluded. Two authors extracted data on study quality and outcomes. Summary effect estimates were obtained using a random-effects model, and results were expressed as risk ratios and 95% confidence intervals (CI) for categorical variables, and mean differences (MD) or standardised mean differences (SMD) and 95% CI for continuous variables. This review update included 42 eligible studies (3262 participants), including six new studies (543 participants). Overall, 29 studies (1971 participants) compared neutral pH, low GDP PD solution with conventional PD solution, and 13 studies (1291 participants) compared icodextrin with conventional PD solution. Risk of bias was assessed as high for sequence generation in three studies, allocation concealment in three studies, attrition bias in 21 studies, and selective outcome reporting bias in 16 studies.Neutral pH, low GDP versus conventional glucose PD solutionUse of neutral pH, low GDP PD solutions improved residual renal function (RRF) preservation (15 studies, 835 participants: SMD 0.19, 95% CI 0.05 to 0.33; high certainty evidence). This approximated to a mean difference in glomerular filtration rate of 0.54 mL/min/1.73 m2 (95% CI 0.14 to 0.93). Better preservation of RRF was evident at all follow-up durations with progressively greater preservation observed with increasing follow up duration. Neutral pH, low GDP PD solution use also improved residual urine volume preservation (11 studies, 791 participants: MD 114.37 mL/day, 95% CI 47.09 to 181.65; high certainty evidence). In low certainty evidence, neutral pH, low GDP solutions may make little or no difference to 4-hour peritoneal ultrafiltration (9 studies, 414 participants: SMD -0.42, 95% CI -0.74 to -0.10) which approximated to a mean difference in peritoneal ultrafiltration of 69.72 mL (16.60 to 122.00 mL) lower, and may increase dialysate:plasma creatinine ratio (10 studies, 746 participants: MD 0.01, 95% CI 0.00 to 0.03), technique failure or death compared with conventional PD solutions. It is uncertain whether neutral pH, low GDP PD solution use led to any differences in peritonitis occurrence, hospitalisation, adverse events (6 studies, 519 participants) or inflow pain (1 study, 58 participants: RR 0.51, 95% CI 0.24 to 1.08).Glucose polymer (icodextrin) versus conventional glucose PD solutionIn moderate certainty evidence, icodextrin probably reduced episodes of uncontrolled fluid overload (2 studies, 100 participants: RR 0.30, 95% CI 0.15 to 0.59) and augmented peritoneal ultrafiltration (4 studies, 102 participants: MD 448.54 mL/d, 95% CI 289.28 to 607.80) without compromising RRF (4 studies, 114 participants: SMD 0.12, 95% CI -0.26 to 0.49; low certainty evidence) which approximated to a mean creatinine clearance of 0.30 mL/min/1.73m2 higher (0.65 lower to 1.23 higher) or urine output (3 studies, 69 participants: MD -88.88 mL/d, 95% CI -356.88 to 179.12; low certainty evidence). It is uncertain whether icodextrin use led to any differences in adverse events (5 studies, 816 participants) technique failure or death. This updated review strengthens evidence that neutral pH, low GDP PD solution improves RRF and urine volume preservation with high certainty. These effects may be related to increased peritoneal solute transport and reduced peritoneal ultrafiltration, although the evidence for these outcomes is of low certainty due to significant heterogeneity and suboptimal methodological quality. Icodextrin prescription increased peritoneal ultrafiltration and mitigated uncontrolled fluid overload with moderate certainty. The effects of either neutral pH, low GDP solution or icodextrin on peritonitis, technique survival and patient survival remain uncertain and require further high quality, adequately powered RCTs.

Early technical complications and long-term survival of urgent peritoneal dialysis according to break-in periods.

BackgroundGuidelines recommend a break-in period of 2 weeks before starting peritoneal dialysis (PD), but PD within 14 days is also an acceptable and safe alternative to hemodialysis (HD) in patients with an urgent need. However, the effect of the break-in period within 48 hours or later had not been evaluated for early technical complications, long-term maintenance, and survival in patients starting urgent PD.MethodsOf 360 patients with a surgically inserted PD catheter, we evaluated 190 patients who needed urgent PD and 29 patients who received conventional PD at a single center between January 2007 and December 2014 in this retrospective observational study. Enrolled patients were divided according to break-in period of <48 hours (P1) or 2–13 days (P2) before starting urgent PD. The primary endpoint was incidence of early technical complications and secondary endpoints included long-term PD maintenance, and patient survival.ResultsPD was started in 103 patients (54.2%) within 48 hours and in 87 patients (45.8%) within 2 to 13 days. The incidence of early technical complication was significantly higher in P1 group (28.2%) than in P2 group (10.3%) (P = 0.002). The need for a repositioning procedure was significantly greater in P1 group (14.6%) than in P2 group (3.4%) (P = 0.009). However, we observed no significant differences between the two groups with respect to the prevalence of catheter dysfunction requiring change to HD within 6 months or incidence of peritonitis or exit-site infection. There was no significant difference in PD maintenance and patient survival according to the break-in period between P1 and P2 as well as against the control group.ConclusionUrgent PD was associated with a low incidence of early technical complications if start was avoided within 48 hours after catheter insertion, and long-term PD maintenance was independent of the break-in period.