bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcutaneous Administration of Darbepoetin Alfa Effectively Maintains Hemoglobin Concentrations at Extended Dose Intervals in Peritoneal Dialysis Patients
Authors: Fang Yu-Wei , Chang Chung-Hsin 
Published: February 2020

Objective Darbepoetin alfa is an erythropoietic-stimulating protein with a threefold longer half-life than recombinant human erythropoietin (rHuEPO) and can be used less frequently in the treatment of renal anemia. The purpose of this single-center single-arm study was to determine whether darbepoetin alfa, when administered at extended dose intervals, is as effective as rHuEPO for the treatment of renal anemia in patients on peritoneal dialysis. Methods Patients on peritoneal dialysis for at least 3 years receiving stable rHuEPO therapy were shifted to darbepoetin alfa administered every week, or every other week, using the recommended 200:1 conversion factor. The doses of darbepoetin alfa were titrated to maintain hemoglobin within ±1.0 g/dL of patients’ baseline values and within a range of 9.0 – 12.0 g/dL for up to 24 weeks (20-week dose titration period followed by 4-week evaluation period). The primary end point was the change in hemoglobin levels between baseline and evaluation period. Results 73 patients completed the study; mean age was 52.1 years; 30 males. Mean baseline and evaluation period hemoglobin levels were similar (9.56 ± 1.11 vs 9.73 ± 1.41 g/dL, p = 0.248). Mean rHuEPO dose was 92.9 IU/kg/week (equivalent to 0.46 μg/kg/week darbepoetin alfa), which was higher than darbepoetin alfa dose during the evaluation period (0.46 vs 0.34 μg/kg/week, p = 0.038). In addition, ferritin levels decreased (483 ± 26 vs 396 ± 19 ng/dL, p = 0.014). The other parameters, such as albumin, C-reactive protein, transferrin saturation, Kt/V, and weekly creatinine clearance showed no statistical difference between the two regimens. No serious or major adverse effects were observed with darbepoetin alfa during the study. Conclusions Using lower dosage and frequency, darbepoetin alfa effectively maintains hemoglobin levels in peritoneal dialysis patients previously maintained on erythropoietin beta. Similar effects on hemoglobin can be maintained with even lower levels of ferritin during darbepoetin alfa use. These results show that darbepoetin alfa is safe, effective, and convenient in treating renal anemia in peritoneal dialysis patients.
Evaluation of Taurine as an Osmotic Agent for Peritoneal Dialysis Solution
Authors: Nishimura Hideki , Ikehara Osamu , Naito Takashi , Higuchi Chieko , Sanaka Tsutomu 
Published: February 2020

Objective The development of a glucose-free peritoneal dialysis (PD) solution is important because glucose has been associated with functional and morphological damage to the peritoneal membrane. The ultrafiltration (UF) and biocompatibility of new PD solutions containing taurine (PD-taurine) instead of glucose as an osmolite were tested in a rat PD model. Methods To determine the solution's UF ability, different concentrations of taurine in PD solutions were compared to glucose-based PD solutions (PD-glucose) by giving single intraperitoneal injections for 2, 4, and 6 hours. To examine the biocompatibility of PD-taurine, the rats were divided into 3 groups: a 3.86% PD-glucose group, a 3.5% PD-taurine group and a not dialyzed group. The rats were given 10-mL injections of PD fluids intraperitoneally 3 times daily for 7 days. A peritoneal equilibration test (PET) was performed using a 1.9% xylitol solution at the time the rats were sacrificed. Mesothelial cell monolayers were obtained from the animals and studied based on a population analysis. Results The net UF of PD-taurine increased in a dose-dependent manner; the 3.5% PD-taurine solution was equivalent to the 3.86% PD-glucose solution after 4 hours. The PET showed that the drainage volume and the D4/D0 ratio for xylitol after 4 hours with PD-taurine solution were significantly greater than with the PD-glucose solution ( p < 0.001 and p < 0.001 respectively). Mesothelial and fibroblast-like cell proliferation was significantly less with PD-taurine than with PD-glucose ( p < 0.01). Conclusions These results indicate that PD-taurine resulted in net UF equivalent to that of PD-glucose and was more biocompatible than PD-glucose with respect to the peritoneal membrane.
HPMCs Induce Greater Intercellular Delocalization of Tight Junction-Associated Proteins Due to a Higher Susceptibility to H2O2 Compared with HUVECs
Authors: Horiuchi Takashi , Matsunaga Kazuya , Banno Masatoshi , Nakano Yusuke , Nishimura Kohei , Hanzawa Chika , Miyamoto Kei-ichi , Nomura Shinsuke , Ohta Yuji 
Published: February 2020

Background Reactive oxygen species (ROS) have been speculated as possible inducers of structural or functional changes that lead to a hyperpermeable state in patients on long-term peritoneal dialysis. This study aimed to compare localization of tight junction-associated proteins (TJPs), which relate to solute permeability characteristics, between human peritoneal mesothelial cell (HPMC) monolayers and human umbilical vein endothelial cell (HUVEC) monolayers under oxidative stress. Methods HPMCs and HUVECs were cultured on a polymer mesh until transepithelial electrical resistance reached a plateau. Solute permeation tests were conducted using FITC-labeled dextrans. Localization of TJPs was observed under a confocal laser scanning microscope. These experiments were carried out with/without 0.1 mmol/L H2O2. In addition, ROS production as well as the amounts of intracellular reductive glutathione (GSH) and oxidative glutathione were measured. Results When the monolayers were exposed to 0.1 mmol/L H2O2/medium for 2 hours, the HPMC monolayer revealed a significant reduction in transepithelial electrical resistance (from 32.5 ± 3.4 to 17.4 ± 4.9 Ω cm ) with delocalization of TJPs, particularly occludins. The HUVEC monolayer remained stable and exhibited an unremarkable change in TJP organization. Compared to the HUVEC monolayer, the HPMC monolayer exhibited two- to threefold higher 2′,7′–dichlorofluorescein intensities that increased in a dose-dependent manner. HUVECs contained approximately 2.5-times more GSH than HPMCs. This supported the lesser production of ROS when exposed to 0.1 mmol/L H2O2 for 24 hours. HUVECs used 8.03 nmol/mg GSH protein to maintain TJP localization, while only 3.75 nmol/mg GSH protein was available for the HPMCs. Conclusion The HUVEC monolayer, which was less permeable to middle-to-high molecular weight solutes, was more tolerant against ROS stress than the HPMC monolayer. Availability of intracellular GSH is an important issue in maintaining the integrity of the mesothelium.
Association of Peritoneal Dialysis Clinic Size with Clinical Outcomes
Authors: Plantinga Laura C. , Fink Nancy E. , Finkelstein Fredric O. , Powe Neil R. , Jaar Bernard G. 
Published: February 2020

Objective Very few studies have addressed the relationship between number of peritoneal dialysis (PD) patients treated at a clinic (PD clinic size) and clinical outcomes. In a national prospective cohort study of incident PD patients ( n = 236, from 26 clinics), we examined whether being treated at a larger PD clinic [>50 PD patients ( n = 3 clinics) vs <50 PD patients ( n = 23 clinics)] was associated with better patient outcomes, including fewer switches to hemodialysis, fewer cardiovascular events, lower cardiovascular mortality, and lower all-cause mortality. Methods Multivariable Cox models were used to assess relative hazards (RHs) for modality switches, cardiovascular events, cardiovascular deaths, and all-cause deaths by PD clinic size. All models were adjusted for demographics, comorbidities, laboratory values, and clinic years in operation. Results Being treated at a clinic with >50 patients was associated with fewer switches to hemodialysis (RH = 0.13, 95% CI 0.06 – 0.31) and fewer cardiovascular events (RH = 0.62, 95% CI 0.06 – 0.98). No associations of PD clinic size with cardiovascular or all-cause mortality were seen. Conclusion PD patients treated at clinics with greater numbers of PD patients may have better outcomes in terms of technique failure and cardiovascular morbidity. PD clinic size may act as a proxy of greater PD experience, more focus on the modality, and better PD practices at the clinic, resulting in better outcomes.
The Honeypot Study Protocol: A Randomized Controlled Trial of Exit-Site Application of Medihoney Antibacterial Wound Gel for the Prevention of Catheter-Associated Infections in Peritoneal Dialysis Patients
Authors: Johnson David W. , Clark Carolyn , Isbel Nicole M. , Hawley Carmel M. , Beller Elaine , Cass Alan , de Zoysa Janak , McTaggart Steven , Playford Geoffrey , Rosser Brenda , Thompson Charles , Snelling Paul ,   The HONEYPOT Study Group
Published: February 2020

Objectives The primary objective of this study is to determine whether daily exit-site application of standardized antibacterial honey (Medihoney Antibacterial Wound Gel; Comvita, Te Puke, New Zealand) results in a reduced risk of catheter-associated infections in peritoneal dialysis (PD) patients compared with standard topical mupirocin prophylaxis of nasal staphylococcal carriers. Design Multicenter, prospective, open label, randomized controlled trial. Setting PD units throughout Australia and New Zealand. Participants The study will include both incident and prevalent PD patients (adults and children) for whom informed consent can be provided. Patients will be excluded if they have had ( 1 ) a history of psychological illness or condition that interferes with their ability to understand or comply with the requirements of the study; ( 2 ) recent (within 1 month) exit-site infection, peritonitis, or tunnel infection; ( 3 ) known hypersensitivity to, or intolerance of, honey or mupirocin; ( 4 ) current or recent (within 4 weeks) treatment with an antibiotic administered by any route; or ( 5 ) nasal carriage of mupirocin-resistant Staphylococcus aureus. Methods 370 subjects will be randomized 1:1 to receive either daily topical exit-site application of Medihoney Antibacterial Wound Gel (all patients) or nasal application of mupirocin if staphylococcal nasal carriage is demonstrated. All patients in the control and intervention groups will perform their usual exit-site care according to local practice. The study will continue until 12 months after the last patient is recruited (anticipated recruitment time is 24 months). Main Outcome Measures The primary outcome measure will be time to first episode of exit-site infection, tunnel infection, or peritonitis, whichever comes first. Secondary outcome measures will include time to first exit-site infection, time to first tunnel infection, time to first peritonitis, time to infection-associated catheter removal, catheter-associated infection rates, causative organisms, incidence of mupirocin-resistant microbial isolates, and other adverse reactions. Conclusions This multicenter Australian and New Zealand study has been designed to provide evidence to help nephrologists and their PD patients determine the optimal strategy for preventing PD catheter-associated infections. Demonstration of a significant improvement in PD catheter-associated infections with topical Medihoney will provide clinicians with an important new prophylactic strategy with a low propensity for promoting antimicrobial resistance.
Treatment of Peritoneal Dialysis-Related Peritonitis with Ciprofloxacin Monotherapy: Clinical Outcomes and Bacterial Susceptibility over Two Decades
Authors: Fontán Miguel Pérez , Cambre Helena Díaz , Rodríguez-Carmona Ana , Muñiz Andrés López , Falcón Teresa García 
Published: February 2020

Background There is controversy about the preferred initial antibiotic therapy for peritoneal dialysis (PD)-related peritonitis. Quinolones have been used extensively in this setting, yet their long-term effectiveness is unknown. Aim To analyze the results of a protocol of treatment of PD-related peritonitis with ciprofloxacin, maintained over two decades. Method We analyzed the clinical outcome of 682 episodes of bacterial peritonitis treated with intraperitoneal ciprofloxacin monotherapy, and the time course of bacterial susceptibility to this antimicrobial, in a historical cohort of 641 PD patients (1988-2007). Main outcome variables included changes to initial therapy and rates of hospital admission, catheter removal, relapse, reinfection, PD dropout, and mortality. For comparisons we divided the study period into phases A (1988-1994), B (1995-2000), and C (2001-2007). Results The incidence of Staphylococcus aureus peritonitis decreased, while the incidences of polymicrobial and negative-culture peritonitis increased after phase A. In vitro susceptibility to ciprofloxacin decreased significantly only among coagulase-negative staphylococci (87.0% susceptible strains in phase A vs 70.0% in B and 70.1% in C, p = 0.006). Overall success rates (catheter not removed and ongoing PD after the episode) remained stable, at over 85%. However, the proportion of patients treated solely with ciprofloxacin declined from 75.7% (A) to 47.3% (B) to 32.4% (C) ( p < 0.0005) and admission rates increased from 12.7% to 16.8% to 24.9% respectively ( p = 0.001). These changes affected all the etiologic groups except culture-negative peritonitis. In vitro resistance to ciprofloxacin was a marker of multiresistance and correlated strongly with clinical outcome of peritonitis. Among isolates susceptible to ciprofloxacin, changing initial therapy for any reason also predicted a poor outcome. Conclusions Following satisfactory early results, the effectiveness of ciprofloxacin as monotherapy for PD-related peritonitis has declined markedly in the long term. This decline cannot be explained solely by a decrease of in vitro susceptibility to this antimicrobial, which was significant only among coagulase-negative staphylococci. Resistance to ciprofloxacin is a strong marker of in vitro multiresistance and poor clinical outcome of peritonitis.
Tissue Factor and Factor V Involvement in Rat Peritoneal Fibrosis
Authors: Saito Hiroki , Kitamoto Masayuki , Kato Kozue , Liu Ning , Kitamura Hisayo , Uemura Kazuhide , Nogaki Fumiaki , Takeda Toshiya , Mori Noriko , Ono Takahiko 
Published: February 2020

Objective Fibrin deposition on the peritoneum has been frequently observed in peritoneal fibrosis induced by long-term peritoneal dialysis. The present study was conducted to clarify the contribution of factor Xa through tissue factor and factor V expression in peritoneal fibrosis. Methods Wistar rats were intraperitoneally injected with chlorhexidine gluconate (CG) every day. For the interventional study, the factor Xa inhibitor fondaparinux was subcutaneously administered. After 28 days of CG injection, peritoneal specimens were examined by immunohistochemical analyses and in situ hybridization. Results The peritoneal submesothelial compact zone was observed to be markedly thicker in the CG-injected groups than in the normal group, and that thickness was dose dependent. Immunohistochemical study revealed massive fibrin, fibronectin, and type IV collagen depositions in the CG-injected groups, which was markedly higher than that in the normal group. Macrophage infiltration and staining for tissue factor, factor V, factor X, and protease-activated receptor-2 were intense in the CG-injected groups and negative/trace in the normal group. Tissue factor and factor V mRNAs were abundant in cells in the thickened peritoneum. A double-labeling experiment revealed that tissue factor was observed mainly in macrophages, and factor V was abundantly distributed in the fibrotic tissue together with macrophages. Fondaparinux treatment decreased the thickness of submesothelial fibrotic tissue, and size and number of CD31-positive vessels. Conclusion These results suggest that expression of tissue factor and factor V in infiltrated macrophages, together with factor X deposition, may progress angiogenesis and accumulation of extracellular matrix components, partly via profibrotic and procoagulant mechanisms in the peritoneum after inflammatory stimulation.
Amino Acid-Based Peritoneal Dialysis Solutions for Malnutrition: New Perspectives
Authors: Tjiong Hoey Lan , Swart Roel , van den Berg Jacobus W. , Fieren Marien W. 
Published: February 2020

Protein and energy malnutrition is frequently found in patients on maintenance dialysis and is associated with an increased risk of death. Among a variety of factors involved in the development of protein and energy malnutrition, such as acidosis, insulin resistance, inflammation, and dialysate protein losses, insufficient intake of proteins and energy as a result of anorexia plays a prominent role. Amino acid (AA)-based peritoneal dialysis (PD) solutions can induce an anabolic response in malnourished patients on continuous ambulatory PD if enough calories are ingested simultaneously. Poor appetite, however, may impede the intake of sufficient calories. Peritoneal dialysis solutions containing a mixture of AAs and glucose in a proper ratio can serve as a source of proteins and calories. Such a dialysis solution can be used in fasting patients on nocturnal automated PD as part of a regular dialysis schedule. Using a sophisticated technique involving stable isotopes, this dialysis mixture has been found to induce acute anabolic changes in whole body protein metabolism. Such a metabolic response is similar to that induced by food. Intraperitoneal AAs, in common with ingested proteins, can induce generation of hydrogen ions and urea through oxidation of specific AAs. Supplying AAs together with calories could bring about utilization of AAs for the synthesis of proteins rather than the oxidation of AAs, thereby limiting production of acid and urea. Using dialysis solutions with a buffer concentration of 40 mmol/L further contributes to maintaining acid–base homeostasis. We advocate consideration of usage of AA/glucose dialysate when PD patients cannot comply with dietary requirements. To evaluate the long-term effects of this approach on morbidity and mortality, clinical trials with large groups of patients are needed.
The Variability in Ultrafiltration Achieved with Icodextrin, Possibly Explained
Authors: Venturoli Daniele , Jeloka Tarun K. , Ersoy Fevzi F. , Rippe Bengt , Oreopoulos Dimitrios G. 
Published: February 2020

Background A recent study by Jeloka et al. (Perit Dial Int 2006; 26:336–40) highlighted the high variability in maximum ultrafiltered volume (UFmax) and the corresponding dwell time (tmax) obtained using 7.5% icodextrin solution. We aimed to pinpoint the possible sources of this phenomenon by simulating the icodextrin ultrafiltration (UF) profiles according to the three-pore model of peritoneal transport. Method The individual UF time courses observed in the study by Jeloka et al. ( n = 29) were first characterized by linear and quadratic regression. We were then able to identify four main patterns. These were then adapted to UF profiles generated by the three-pore model by systematically altering the values of some model parameters, namely, the mass transfer area coefficient (MTAC or PS) for icodextrin/glucose, the peritoneal UF coefficient (LpS), the plasma colloid osmotic pressure gradient (ΔΠ), and the macromolecular clearance out of the peritoneal cavity (ClLF). Results Modifications in the PS values caused only marginal variations in UFmax and tmax, while more significant changes were produced by altering LpS and ClLF. However, far more evident was the importance of changes in ΔΠ In fact, lowering ΔΠ to 14 mmHg caused a steady increase in UF with 10 – 14 hour dwells. On the contrary, the UF profiles became nearly “flat” when ΔΠ was increased to 30 mmHg. The parallel shifts induced by altering icodextrin metabolite concentrations did not markedly influence UFmax or tmax. Conclusion The UF pattern in icodextrin dwells seem to be mainly determined by the plasma colloid osmotic pressure, while only moderate changes can be seen with alterations in LpS and ClLF. The result is not completely unexpected considering that icodextrin acts by inducing a strong colloid osmotic gradient. A number of clinical studies would be needed, however, in order to prove this hypothesis.
Icodextrin Improves Metabolic and Fluid Management in High and High-Average Transport Diabetic Patients
Authors: Paniagua Ramón , Ventura María-de-Jesús , Ávila-Díaz Marcela , Cisneros Alejandra , Vicenté–Martínez Marlén , Furlong María-del-Carmen , García-González Zuzel , Villanueva Diana , Orihuela Oscar , Prado-Uribe María-del-Carmen , Alcántara Guadalupe , Amato Dante 
Published: February 2020

Background Icodextrin-based solutions (ICO) have clinical and theoretical advantages over glucose-based solutions (GLU) in fluid and metabolic management of diabetic peritoneal dialysis (PD) patients; however, these advantages have not yet been tested in a randomized fashion. Objective To analyze the effects of ICO on metabolic and fluid control in high and high-average transport diabetic patients on continuous ambulatory PD (CAPD). Patients and Methods A 12-month, multicenter, open-label, randomized controlled trial was conducted to compare ICO ( n = 30) versus GLU ( n = 29) in diabetic CAPD patients with high-average and high peritoneal transport characteristics. The basic daily schedule was 3 × 2 L GLU (1.5%) and either 1 × 2 L ICO (7.5%) or 1 × 2 L GLU (2.5%) for the long-dwell exchange, with substitution of 2.5% or 4.25% for 1.5% GLU being allowed when clinically necessary. Variables related to metabolic and fluid control were measured each month. Results Groups were similar at baseline in all measured variables. More than 66% of the patients using GLU, but only 9% using ICO, needed prescriptions of higher glucose concentration solutions. Ultrafiltration (UF) was higher (198 ± 101 mL/day, p < 0.05) in the ICO group than in the GLU group over time. Changes from baseline were more pronounced in the ICO group than in the GLU group for extracellular fluid volume (0.23 ± 1.38 vs –1.0 ± 1.48 L, p < 0.01) and blood pressure (systolic 1.5 ± 24.0 vs –10.4 ± 30.0 mmHg, p < 0.01; diastolic 1.5 ± 13.5 vs –6.2 ± 14.2 mmHg, p < 0.01). Compared to baseline, patients in the ICO group had better metabolic control than those in the GLU group: glucose absorption was more reduced (–17 ± 44 vs –64 ± 35 g/day) as were insulin needs (3.6 ± 3.4 vs – 9.1 ± 4.7 U/day, p < 0.01), fasting serum glucose (8.3 ± 36.5 vs –37 ± 25.8 mg/dL, p < 0.01), triglycerides (54.5 ± 31.9 vs –54.7 ± 39.9 mg/dL, p < 0.01), and glycated hemoglobin (0.79% ± 0.79% vs –0.98% ± 0.51%, p < 0.01). Patients in the ICO group had fewer adverse events related to fluid and glucose control than patients in the GLU group. Conclusion Icodextrin represents a significant advantage in the management of high transport diabetic patients on PD, improving peritoneal UF and fluid control and reducing the burden of glucose overexposure, thereby facilitating metabolic control.