bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Osteodystrophy in Peritoneal Dialysis: Special Considerations
Authors: Levy Ronen , Gal-Moscovici Anca
Published: February 2020

Bone disease is one of the most challenging complications in patients with chronic kidney disease. Today, it is considered to be part of a complex systemic disorder manifested by disturbances of mineral metabolism and vascular calcifications called chronic kidney disease – mineral bone disorder (CKD-MBD).

The term renal osteodystrophy is reserved to define the specific bone lesion in CKD-MBD, whose spectrum ranges from high turnover to low turnover disease. Phosphate retention, decreased serum calcium, and 1,25-dihydroxy vitamin D synthesis are involved in the pathogenesis of high bone turnover. However, the various therapeutic approaches (calcium supplements, phosphate binders, and vitamin D metabolites, among others), the renal replacement modality (hemodialysis or continuous ambulatory peritoneal dialysis), and the types of patients to whom dialysis is offered (more patients who are diabetic or older, or both) may influence the evolution of the bone disorder. As a result, recent studies have reported a greater prevalence of adynamic forms of renal osteodystrophy, especially in diabetic and peritoneal dialysis patients.

The present article reviews, for patients treated with peritoneal dialysis, the pathophysiologic mechanisms involved in the evolution and perpetuation of this bone disease and the therapeutic modalities for treating and preventing adynamic bone.
Vitamin D and Peritoneal Dialysis
Authors: Banks Mindy , Sprague Stuart M.
Published: February 2020

Chronic kidney disease – mineral and bone disorder (CKD–MBD) is a cause of significant morbidity and mortality in patients with long-standing kidney disease. Management of secondary hyperparathyroidism includes the use of phosphorus-binding agents and treatment with activated vitamin D compounds, better referred to as vitamin D receptor agonists (VDRAs). In an effort to maximize the therapeutic response while reducing the adverse effects of calcitriol, the naturally synthesized hormone, the use of intravenous administration and several selective VDRAs have been developed. Recently, oral preparations of these selective VDRAs have become available, enabling their use in the peritoneal dialysis (PD) population. The present report reviews the data concerning the use of oral VDRAs for the treatment of hyperparathyroidism in PD patients. The data, although limited, appear to support the use of oral paricalcitol as the VDRA in PD patients. In addition, traditional teaching focuses only on therapy with VDRAs, ignoring vitamin D replacement in CKD stage 5. However, given the potential benefits of calcidiol (25-OH-D) repletion and the rampant 25-OH-D deficiency in the PD population, our opinion is that screening for and treating that deficiency should extend beyond early CKD and also include PD patients.
Calcium Balance with Automated Peritoneal Dialysis
Authors: Granja Carlos Andres , Francis Jean , Simon David , Bushinsky David , Finkelstein Fredric O.
Published: February 2020

Background

Calcium balance in chronic kidney disease patients on peritoneal dialysis (PD) has not been well studied. This issue is particularly important, given the careful attention now being paid to vascular calcification, the increasing use of cinacalcet therapy (with accompanying reductions in serum Ca levels), the increasing use of vitamin D and its analogs (which increase Ca), and the increasing use of Ca-containing phosphate binders. The present study was conducted to examine the factors influencing transperitoneal calcium balance during continuous cycling peritoneal dialysis (CCPD) therapy, with particular attention to net ultrafiltration (UF) and serum ionized Ca (iCa).

Patients and Methods

This open, prospective cohort study included 40 medically stable patients maintained on CCPD for at least 3 months. Most patients used low-Ca (2.5 mEq/L) PD fluid; the Ca content of PD fluid for patients on icodextrin-based solutions was 3.5 mEq/L. Patients were instructed to record the quantity of dialysate instilled in a 24-hour period and net UF, and to bring a well-mixed aliquot of PD drainage to the dialysis unit. Concentrations of iCa and dialysate Ca were measured. Total Ca instilled into and drained from the PD fluid was calculated, and then the transperitoneal calcium balance was determined.

Results

Significant correlations were noted between transperitoneal calcium balance and both serum iCa ( r = –0.360) and the UF rate ( r = –0.708). Of the patients whose iCa was over 5 mg/dL, 71% were in negative calcium balance; of those with iCa levels below 5 mg/dL, 62% were in positive calcium balance. Of patients with UF below 1000 mL daily, 58% were in positive calcium balance; of those with 1000 mL UF or more, net Ca gain was noted in only 38%.

Conclusions

The present study demonstrates the importance of UF and iCa in determining transperitoneal Ca transport. These findings are of particular importance given the widening use of calcimimetic agents, vitamin D analogs, and Ca-based phosphate binders (all of which alter iCa) and the potential association between UF rate and outcome in PD patients.
Long-term Intervention with Heparins in a Rat Model of Peritoneal Dialysis
Authors: Schilte Margot N. , Loureiro Jesus , Keuning Eelco D. , ter Wee Piet M. , Celie Johanna W.A.M. , Beelen Robert H.J. , Van Den Born Jacob
Published: February 2020

Background

Peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane, particularly new vessel formation and fibrosis. In addition to anticoagulant effects, heparin displays anti-inflammatory and angiostatic properties. Therefore, the effects of administration of heparins on function and morphology of the peritoneal membrane were studied in a rat PD model.

Methods

Rats received 10 mL conventional PD fluid (PDF) daily, with or without the addition of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) in the PDF (1 mg/10 mL intraperitoneally) via a mini access port. Untreated rats served as controls. After 5 weeks, a 90-minute functional peritoneal transport test was performed and tissues and peritoneal leukocytes were taken.

Results

PD treatment induced loss of ultrafiltration ( p < 0.01), a twofold increase in glucose absorption ( p < 0.03), increased urea transport ( p < 0.02), and loss of sodium sieving ( p < 0.03), which were also found in the PDF + heparin groups. Increased peritoneal cell influx and hyaluronan production ( p < 0.02) as well as an exchange of mast cells and eosinophils for neutrophils after PD treatment were observed in PD rats; addition of heparin did not affect those changes. Mesothelial regeneration, submesothelial blood vessel and matrix formation, and accumulation of tissue macrophages were seen in PD animals. Spindle-shaped vimentin-positive and cytokeratin-negative cells indicated either partial injury and denudation of mesothelial cells or epithelial-to-mesenchymal transition. Neither UFH nor LMWH affected any of these morphological changes.

Conclusion

Within 5 weeks, PD treatment induces a chronic inflammatory condition in the peritoneum, evidenced by high transport, leukocyte recruitment, tissue remodeling, and induction of spindle-shaped cells in the mesothelium. Addition of LMWH or UFH to the PDF did not prevent these adverse PDF-induced peritoneal changes.
Substituting Citrate for Lactate in Peritoneal Dialysis Fluid Improves Ultrafiltration in Rats
Authors: Cavallini Nicola , Wieslander Anders , Braide Magnus
Published: February 2020

Background

Exposure to peritoneal dialysis (PD) fluid induces an inflammatory response in the peritoneal cavity. Blockers of complement and coagulation have improved ultrafiltration in animal models of PD. Citrate is a clinically established anticoagulant that also blocks complement activation.

Objective

The aim of the present study was to evaluate the effects on ultrafiltration of a gradual substitution of citrate for lactate in an experimental model of PD.

Methods

Fractions (0, 5, 10, and 15 mmol/L) of the 40 mmol/L lactate buffer of filter-sterilized 2.5% glucose PD fluid were replaced by citrate. The modified fluids were compared in a rat model of single PD fluid exposure through an indwelling catheter. The initial kinetics of citrate and ionized calcium were evaluated in separate, single, short time dwell experiments.

Results

Replacing 10 and 15 mmol/L of the lactate buffer by sodium citrate significantly increased osmotic ultrafiltration (by 24.7% ± 7.7% at 10 mmol/L), net ultrafiltration, and glucose retention at 4 hours of dwell time in the rat model. Osmotic ultrafiltration was significantly correlated to citrate concentration and glucose concentration. Citrate was rapidly eliminated from the peritoneal cavity, concentrations falling to less than half in 1 hour and concentrations of calcium ions concomitantly normalized.

Conclusions

Substituting citrate for lactate induced a dose-dependent increase in ultrafiltration. Mechanisms probably involve the relation between diffusion and ultrafiltration, leading to increased glucose retention. The increase in ultrafiltration was quantitatively important at a citrate concentration (10 mmol/L) that is compatible with clinical applications of citrate.
Subclinical Peripheral Artery Disease in Patients Undergoing Peritoneal Dialysis: Risk Factors and Outcome
Authors: Liu Jiung-Hsiun , Lin Hsin-Hung , Yang Ya-Fei , Liu Yao-Lung , Kuo Huey-Liang , Wang I-Kuan , Chou Che-Yi , Huang Chiu-Ching
Published: February 2020

Background

Peripheral artery disease (PAD) is highly prevalent among patients in end-stage renal disease. The ankle–brachial index (ABI) is believed to be highly correlated with the subclinical PAD of lower extremities but little is known about the associated risk factors and outcome for PAD and ABI in patients on peritoneal dialysis (PD).

Methods

We performed a cohort study of 153 patients from a single center receiving stable PD for more than 3 months. These patients were screened for subclinical PAD using the ABI measurement. The ABI was measured and a ratio of <0.9 was considered abnormal. Clinical outcomes included actuarial patient and technique survival in this study.

Results

30 patients were classified into a subclinical PAD group. The prevalence of PAD (subclinical and overt) in our PD center was 19.61% (30/153). Advanced age, preexisting diabetes, preexisting cardiovascular and/or cerebrovascular disease (CVD), lower renal Kt/V urea, lower renal creatinine clearance (WCrCl), lower serum albumin level, and higher serum triglyceride level were risk factors for PAD in our PD center. Bivariate analysis showed that ABI was positively correlated with residual renal Kt/V urea and WCrCl, but was not correlated with peritoneal Kt/V urea and WCrCl. Patient and technique survival rates were significantly lower in the low ABI group than in the normal ABI group.

Conclusions

ABI is highly correlated with advanced age, preexisting diabetes, preexisting CVD, serum albumin, serum triglyceride, and residual renal clearance in PD patients. Also, lower ABI is independently associated with a high risk of patient mortality and PD technique failure.
Oxidative Stress in Children on Peritoneal Dialysis
Authors: Zwolińska Danuta , Grzeszczak Wladyslaw , Szczepańska Maria , Makulska Irena , Kiliś–Pstrusińska Katarzyna , Szprynger Krystyna
Published: February 2020

Objectives

Enhanced oxidative stress has been observed in dialysis and predialysis adult patients with chronic kidney disease (CKD), which resulted in increased mortality and morbidity within this population. Not much attention in the literature has been paid to nonenzymatic antioxidant defense in children with CKD on peritoneal dialysis (PD). The aim of the present study was to describe the plasma, erythrocyte, and dialysate concentrations of oxidized (GSSG) and reduced glutathione (GSH) and vitamins A, E, and C in a pediatric PD population.

Patients

10 children on PD and 27 age-matched healthy subjects were enrolled in the study.

Results

Erythrocyte and plasma GSH concentrations were lower in PD patients, erythrocyte concentration of GSSG remained unchanged, and plasma GSSG was significantly higher in children on PD. Children on PD exhibited decreased plasma concentrations of antioxidant vitamins compared to healthy subjects. Moreover, we documented loss of vitamins A, E, and C into ultrafiltrate.

Conclusion

Such low plasma levels of vitamins A, E, and C and simultaneously decreased activity of erythrocyte GSH may be responsible for the increased oxidative stress occurring in children with CKD on PD.
Pulmonary Hypertension in Peritoneal Dialysis Patients: Prevalence and Risk Factors
Authors: Ünal Aydin , Sipahioglu Murat , Oguz Fatih , Kaya Mehmet , Kucuk Hamit , Tokgoz Bulent , Buyukoglan Hakan , Oymak Oktay , Utas Cengiz
Published: February 2020

Aim

To investigate the prevalence of pulmonary arterial hypertension (PAH) and the possible contributing factors for PAH in patients receiving regular continuous ambulatory peritoneal dialysis (CAPD).

Patients and Methods

The study included 135 CAPD patients and 15 disease-free controls. Patients that had chronic obstructive pulmonary disease, severe mitral or aortic valve disease, connective tissue disease, history of pulmonary embolism, left ventricular ejection fraction <50%, or chest wall or parenchymal lung disease were excluded. All patients and controls were examined using echocardiography and bioelectrical impedance analysis. PAH was defined as systolic pulmonary artery pressure (PAP) >35 mmHg at rest.

Results

Mean systolic PAP was higher in the CAPD patients than in the controls (19.66 ± 11.66 vs 14.27 ± 4.55 mmHg, p = 0.001). PAH was detected in 17 (12.6%) of the 135 CAPD patients. Mean systolic PAP was significantly higher in patients with PAH than in those without PAH (42.00 ± 9.13 vs 16.44 ± 7.83 mmHg, p = 0.001). Serum albumin level and ejection fraction were lower in patients with PAH than in those without PAH ( p = 0.001 and 0.003 respectively). The ratio of extracellular water/total body water (ECW/TBW), which can reflect hydration status, was significantly higher in patients with PAH than in those without PAH ( p = 0.008). In the PD group, no patients were hypovolemic; 51 (37.8%) of the 135 PD patients were hypervolemic and 84 (62.2%) were normovolemic. Only 3 of the 17 patients with PAH were normovolemic; the rest were hypervolemic. Mean systolic PAP was significantly higher in hypervolemic PD patients (24.57 ± 14.19 mmHg) than in normovolemic PD patients (16.68 ± 7.61 mmHg) ( p = 0.001). PAP correlated with ECW/TBW ( r=0.317, p = 0.001) and left ventricular mass index (LVMI; r=0.286, p = 0.001). On the other hand, it inversely correlated with serum albumin level ( r = –0.281, p = 0.001), hemoglobin level ( r = –0.165, p = 0.044), and ejection fraction ( r = –0.263, p = 0.001). Serum albumin level, ECW/TBW, and LVMI were found in multivariate analysis to be independent risk factors for PAP.

Conclusion

PAH is a frequent cardiovascular complication in CAPD patients. Serum albumin level, hypervolemia, and LVMI are major risk factors for PAH. Therefore, strategies for treatment of hypervolemia, left ventricular hypertrophy, and hypoalbuminemia should be enhanced to prevent the development of PAH in CAPD patients.
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.
Analytical Interferences in Point-of-Care Testing Glucometers by Icodextrin and its Metabolites: An Overview
Authors: Floré Katelijne M.J. , Delanghe Joris R.
Published: February 2020

Current point-of-care testing (POCT) glucometers are based on various test principles. Two major method groups dominate the market: glucose oxidase-based systems and glucose dehydrogenase-based systems using pyrroloquinoline quinone (GDH-PQQ) as a cofactor. The GDH-PQQ-based glucometers are replacing the older glucose oxidase-based systems because of their lower sensitivity for oxygen. On the other hand, the GDH-PQQ test method results in falsely elevated blood glucose levels in peritoneal dialysis patients receiving solutions containing icodextrin ( e.g., Extraneal; Baxter, Brussels, Belgium). Icodextrin is metabolized in the systemic circulation into different glucose polymers, but mainly maltose, which interferes with the GDH-PQQ-based method. Clinicians should be aware of this analytical interference. The POCT glucometers based on the GDH-PQQ method should preferably not be used in this high-risk population and POCT glucose results inconsistent with clinical suspicion of hypoglycemic coma should be retested with another testing system.
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.
Effects of Twice-Daily Icodextrin Administration on Blood Pressure and Left Ventricular Mass in Patients on Continuous Ambulatory Peritoneal Dialysis
Authors: Sav Tansu , Oymak Oktay , Inanc Mehmet Tugrul , Dogan Ali , Tokgoz Bulent , Utas Cengiz
Published: February 2020

Background

Hypervolemia is a risk factor for left ventricular hypertrophy and hypertension in peritoneal dialysis patients. Icodextrin improves volume control by increasing ultrafiltration in peritoneal dialysis patients.

Aim

To examine the effects of twice-daily icodextrin administration on blood pressure and left ventricular hypertrophy in peritoneal dialysis patients with hypervolemia and ultrafiltration failure.

Method and Results

Administration of icodextrin twice daily resulted in a significant reduction in the left ventricular mass index (LVMI) of patients by the end of the third month ( p < 0.05). The reduction in LVMI was also significant for the once-daily icodextrin group ( p < 0.05). Mean blood pressure of patients receiving icodextrin twice daily was significantly reduced ( p < 0.05). By the end of the third month no significant changes were observed in mean blood pressure of the patients using once-daily icodextrin ( p > 0.05). No statistically significant changes were observed in weekly total creatinine clearances or Kt/V of patients in either group at the end of 3 months (NS).

Conclusion

Twice-daily icodextrin administration was clinically beneficial as shown by reduced blood pressure and prevention of the progress of left ventricular hypertrophy without causing any decrease in dialysis adequacy or any side effects. The icodextrin metabolite results did not suggest any further increase in their values when comparing once- to twice-daily administration of icodextrin. Although prescription of icodextrin once daily may yield good clinical results in the long term, this study showed that it may be more efficient to use twice-daily icodextrin for at least a specific period for the purpose of obtaining quicker results in patients with ultrafiltration failure, serious hypervolemia, or hard-to-control blood pressure conditions.
Dialytic Phosphate Removal: A Modifiable Measure of Dialysis Efficacy in Automated Peritoneal Dialysis
Authors: Schmitt Claus P. , Borzych Dagmara , Nau Barbara , Wühl Elke , Zurowska Aleksandra , Schaefer Franz
Published: February 2020

Background

Although hyperphosphatemia is one of the few established risk factors for cardiovascular mortality in patients on dialysis, the relationship between peritoneal dialysis (PD) prescription and dialytic phosphate removal is largely unexplored.

Methods and Patients

We analyzed 24-hour clearances ( n = 60) together with peritoneal equilibration tests (PETs) ( n = 52) performed in children and adolescents ( n = 35) on automated PD.

Results

Dialytic phosphate clearance was more closely correlated with 2-hour and 4-hour dialysate-to-plasma ratio (D/P) of phosphate in the PETs ( r = 0.44 and r = 0.52, both p < 0.0001) than with 2-hour and 4-hour D/P creatinine ( r = 0.26 and r = 0.27, both p < 0.05). Dialytic 24-hour phosphate clearance was independently predicted by total fluid turnover (partial R2 = 0.48, p < 0.001), the number of cycles ( r = 0.52, p < 0.001), 2-hour D/P phosphate (partial R2 = 0.07, p = 0.001), dwell time (partial R2 = 0.05, p = 0.01), and achieved ultrafiltration (partial R2 = 0.05, p = 0.005). 4-hour D/P phosphate and 24-hour phosphate clearance were significantly lower in hyperphosphatemic children (3.38 ± 1.17 vs 4.56 ± 1.99 L/1.73 m2/day, p < 0.05), whereas creatinine equilibration and clearance rates were not distinctive.

Conclusion

Dialytic phosphate removal is an important modifiable determinant of phosphate control in automated PD. It strongly depends on total dialysate turnover and the prescribed number of cycles and is more adequately predicted by phosphate than by creatinine equilibration characteristics. Due to the deleterious effects of hyperphosphatemia, dialytic phosphate removal should be monitored routinely.
Bicarbonate-Based Peritoneal Dialysis Solution has Less Effect on Ingestive Behavior than Lactate-Based Peritoneal Dialysis Solution
Authors: Zheng Zhi-Hua , Anderstam Björn , Yu Xueqing , Qureshi Abdul Rashid , Heimbürger Olof , Lindholm Bengt
Published: February 2020

Objective

The anorexia seen in peritoneal dialysis (PD) patients may be due partially to factors of dialysis solutions, such as pH and buffering agent. We tested the effects of different PD solutions in an experimental rat model for appetite.

Design

The intraoral intake of a sucrose solution from an implanted intraoral cannula in freely moving male Wistar rats was used to evaluate appetite at 30 minutes and 120 minutes after intraperitoneal (IP) infusion of bicarbonate (25 mmol/L)/lactate (15 mmol/L)-based PD solution (P) and conventional lactate (40 mmol/L)-based PD solution (D) with different concentrations of glucose. We also tested different buffer solutions containing lactate and bicarbonate with different pH but with no glucose.

Results

The IP infusion as such and the 30 mL volume did not inhibit appetite; however, appetite was significantly less inhibited by P than by D in the 1.36%, 2.27%, and 3.86% solutions ( p < 0.05). Furthermore, intraoral intake was significantly higher in rats receiving IP solution with bicarbonate buffer (pH 7.4) than with lactate buffer ( p < 0.05), whereas there was no significant difference in intraoral intake for lactate with pH 5.5, pH 6.6, or pH 7.4.

Conclusions

The bicarbonate/lactate solution inhibited appetite less than the lactate solution; this was due partially to the use of bicarbonate. The results show possible benefit on appetite of reducing the lactate concentration in PD solutions.
Vascular and Other Tissue Calcification in Peritoneal Dialysis Patients
Authors: Wang Angela Yee-Moon
Published: February 2020

Cardiovascular disease is the leading cause of mortality in patients with end-stage renal disease (ESRD) and is attributed to a combination of traditional and non-traditional cardiovascular risk factors. In recent years, there has also been an increasing recognition of a very high prevalence of cardiovascular calcification in the ESRD population, including in patients receiving long-term peritoneal dialysis (PD). Numerous observational cohort studies have demonstrated the prognostic importance of cardiovascular calcifications in these patients. The mechanisms are not completely understood, but are likely multifactorial. The present article reviews the prevalence, clinical course, prognostic significance, and some contributing factors for vascular and valvular calcification in ESRD patients, including patients receiving PD therapy.
How to Assess Transport in Animals?
Authors: Rippe Bengt
Published: February 2020

The general principles for assessing solute and fluid transport across the peritoneum in animal models are not different from those in human studies. Animal models allow for extensive standardization of experimental conditions and also for sampling of peritoneal tissues for analysis. The present review will focus on ( 1 ) the scaling issue between various species, ( 2 ) how to measure intraperitoneal volume in animal models, ( 3 ) the impact of an indwelling catheter, ( 4 ) the difference between acute and chronic experiments, and ( 5 ) the particular problems associated with transport measurements in mice. If done correctly and after proper scaling, mass transfer area coefficients and clearance measurements show marked similarity among different species. Although animal models only partly mimic human peritoneal dialysis, they are valuable tools for understanding the basic physiology and biology of peritoneal dialysis.
Clinical Advantages of Peritoneal Dialysis
Authors: Tokgoz Bulent
Published: February 2020

Chronic peritoneal dialysis (PD) continues to be an option in the treatment of end-stage renal disease (ESRD). Medical, social, and logistic considerations are needed to determine the most suitable dialysis option for an ESRD patient. Peritoneal dialysis has been advancing in terms of technique, new exchange systems, and a new generation of solutions. A survival advantage for PD patients has been noted over the first 1 – 2 years after the onset of the dialysis. Most patients may need both dialytic modalities in time, and therefore the sequence of the treatment options is important. Compared with hemodialysis patients, PD patients seem much more satisfied in most of the studies that evaluate quality of life during treatment. A preference for PD may be more advantageous in the pre-transplantation period. Moreover, much lower doses of erythropoietin have been shown to be sufficient for PD patients. Also, PD has been reported to protect residual renal functions better in many studies.