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Biocompatible Peritoneal Dialysis Fluids: Clinical Outcomes

Authors:
Yeoungjee Cho at Princess Alexandra Hospital (Queensland Health)
Yeoungjee Cho
Sunil V Badve at Queensland Health
Sunil V Badve
Carmel Hawley at Queensland Health
Carmel Hawley
Kathryn Wiggins at The Royal Melbourne Hospital
Kathryn Wiggins
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Peritoneal dialysis (PD) is a preferred home dialysis modality and has a number of added advantages including improved initial patient survival and cost effectiveness over haemodialysis. Despite these benefits, uptake of PD remains relatively low, especially in developed countries. Wider implementation of PD is compromised by higher technique failure from infections (e.g., PD peritonitis) and ultrafiltration failure. These are inevitable consequences of peritoneal injury, which is thought to result primarily from continuous exposure to PD fluids that are characterised by their "unphysiologic" composition. In order to overcome these barriers, a number of more biocompatible PD fluids, with neutral pH, low glucose degradation product content, and bicarbonate buffer have been manufactured over the past two decades. Several preclinical studies have demonstrated their benefit in terms of improvement in host cell defence, peritoneal membrane integrity, and cytokine profile. This paper aims to review randomised controlled trials assessing the use of biocompatible PD fluids and their effect on clinical outcomes.
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... GDPs as a major factor in the bioincompatibility of peritoneal solutions 10 tially negative effects on both the structural and functional deterioration of peritoneum and systemic metabolic disturbance, leading to treatment failure and an increase in cardiovascular morbidity and mortality 11 . Residual renal function (RRF) plays a vital role in the prognosis of patients on dialy-sis4, which evaluates the excretion of small solute and middle-molecular uremic toxins 5 , salt and water homeostasis, acid-base balance, nutritional status and associated survival [6][7][8] . Accumulating evidence from epidemiological and experimental researches 10,[12][13][14] reveals that low-GDP peritoneal dialysis solutions (LS) may play a role in retarding RRF loss in PD patients 14 . ...
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.
Article
  • Aug 2022
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<0.0001), particularly in one year of treatment (p<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.
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... Glucose is the primary osmotic medium used in most PD solutions, and most PD patients undergo ultrafiltration through the use of high concentrations of glucose. Long-term exposure to a high concentration of glucose alters the structure and function of the peritoneal membrane, which may result in the development of peritoneal fibrosis and eventually cause peritoneal failure in PD patients (2,3). Certain studies have revealed that the immune function of the peritoneal cavity may be crucial for the development of PD-related perineal fibrosis (4,5). ...
High glucose contributes to the polarization of peritoneal macrophages to the M2 phenotype in�vivo and in�vitro
Article
Full-text available
  • May 2020
Glucose is the primary osmotic medium used in most peritoneal dialysis (PD) solutions, and long‑term exposure to high glucose is a major contributor to peritoneal fibrosis. Our previous study revealed that M2 macrophages participate in the development of PD‑related fibrosis in a rat model. In the present study, the effects of high glucose on peritoneal macrophage polarization in vivo and in vitro were further evaluated. Continuous ambulatory PD (CAPD) patients with an overnight dwell of 1.5 or 2.5% glucose dialysate were recruited for this study. Overnight effluent samples from patients with CAPD (2,000 ml) were centrifuged to collect cells from the peritoneal cavity. J774A.1 cells (murine macrophages from ascites) were cultured in different concentrations of glucose. Macrophage phenotype markers were detected by flow cytometry. The levels of cytokines in PD effluent and the supernatant of murine macrophages were detected by enzyme‑linked immunosorbent assays. The activity of arginase was determined by quantitative colorimetric analysis. In total, 107 CAPD subjects (92 patients using 1.5% glucose dialysate and 15 patients using 2.5% glucose dialysate) were recruited. The percentage of M1 macrophages (CD14‑ and CCr7‑positive cells) in the 1.5 and 2.5% glucose dialysate groups was 23.0±13.3 and 24.9±12.0%, respectively. The difference was not significant (P>0.05). The percentage of M2 macrophages (CD14‑ and CD206‑positive cells) in the 1.5% glucose dialysate group (36.2±11.4%) was significantly decreased compared to the 2.5% glucose dialysate group (43.2±7.4%) (P<0.05). Murine macrophages were cultured in a high‑glucose in vitro environment, and the percentage of M1 macrophages in 138.8 mmol/l glucose medium significantly increased over time. The percentage of M2 macrophages increased in a glucose concentration‑dependent and time‑dependent manner. Arginase 1 in murine macrophages and the level of transforming growth factor β1 in the supernatant increased in a glucose concentration‑dependent manner. In conclusion, high glucose contributed to the polarization of peritoneal macrophages to the M2 phenotype, which may play an important role in the pathogenesis of PD‑related fibrosis.
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... G lucose is the most common osmotic medium used in peritoneal dialysis (PD) solutions and is used in varying concentrations (75.5 to 214 mmol/L) to induce ultrafiltration (1,2). Glucose in PD solutions is absorbed and contributes to a number of potential systemic adverse effects, including poor glycemic control, weight gain, dyslipidemia, and increased cardiovascular risk (3)(4)(5)(6)(7)(8)(9)(10). Furthermore, the glucose in PD solutions causes damaging local membrane effects, such as membrane thickening and vasculopathy, and immunological effects, such as stimulated inflammatory cytokine secretion and impaired phagocytosis (11,12), perhaps through the effects of advanced glycosylated end-product (AGE) formation and direct cytotoxicity of glucose degradation products (GDPs) on the peritoneum (3,(13)(14)(15)(16)(17)(18)(19)(20). ...
Associations Between Peritoneal Glucose Exposure, Glucose Degradation Product Exposure, and Peritoneal Membrane Transport Characteristics in Peritoneal Dialysis Patients: Secondary Analysis of the balANZ Trial
Article
  • Aug 2018
Background: Glucose is the most commonly used osmotic medium in peritoneal dialysis (PD) solutions, and its use has been associated with both local and systemic adverse effects. Previous, single-center, observational cohort studies have reported conflicting findings regarding whether a relationship exists between peritoneal glucose exposure and peritoneal small solute transport rate. Methods: In this secondary analysis of the balANZ multi-center, multinational, randomized controlled trial of a neutral pH, ultra-low glucose degradation product (biocompatible) versus conventional PD solutions over a 2-year period, the relationship between time varying peritoneal glucose exposure and change in peritoneal solute transport rate, (measured as dialysate to plasma creatinine ratio at 4 hours [D:PCr4h]), was evaluated using multivariable, multilevel linear regression. Baseline peritoneal glucose exposure was also assessed as either a continuous or categorical variable. Results: The study included 165 patients (age 58.1 ± 14.2 years, 55% male, 33% diabetic). Peritoneal glucose exposure increased over time (coefficient 1.49, 95% confidence interval [CI] 1.07 - 1.92 and was not significantly associated with change in D:PCr4h (coefficient 0.00004, 95% CI -0.0001 - 0.0002, p = 0.68). Similar results were found when peritoneal glucose exposure was examined as a baseline continuous or categorical variable. A significant 2-way interaction was observed with PD solution type, whereby a progressive increase in D:PCr4h was seen in the patients receiving conventional PD solution, but not in those receiving biocompatible solution. Conclusions: Increases in peritoneal solute transport rate in PD patients over time were not associated with peritoneal glucose exposure, although a strong and positive association with PD solution glucose degradation product content was identified. Peritoneal glucose exposure may be a less important consideration than peritoneal glucose degradation product exposure with respect to peritoneal membrane function over time.
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... In addition, the buffer compartment of the Physioneal PD bag contains lactate and bicarbonate. On the other hand, the buffer compartment of the Balance PD solution contains bicarbonate but not lactate (31). In addition, the greater stability of ceftazidime observed in our study due to the presence of heparin cannot be ruled out. ...
Stability of Ceftazidime and Heparin in Four Different Types of Peritoneal Dialysis Solutions
Article
  • Nov 2017
Background: Intraperitoneal (IP) administration of ceftazidime is recommended for the treatment of peritoneal dialysis-associated peritonitis (PDAP) from Pseudomonas. Patients with PDAP may also need IP heparin to overcome problems with drainage of turbid peritoneal dialysis (PD) fluids and blockage of catheters with fibrin. Physico-chemical stability of ceftazidime and heparin, and biological stability of heparin in many types of PD solutions is unknown. Therefore, we investigated the stability of ceftazidime and heparin in 4 types of PD solutions. Methods: A total of 12 PD bags (3 for each type of solution) containing ceftazidime and heparin were prepared and stored at 4°C for 120 hours, and then at 25°C for 6 hours, and finally at 37°C for 12 hours. An aliquot was withdrawn after predefined time points and analyzed for the concentration of ceftazidime and heparin using high-performance liquid-chromatography (HPLC). Samples were assessed for pH, color changes, particle content, and anticoagulant activity of heparin. Results: Ceftazidime and heparin retained more than 91% of their initial concentration when stored at 4°C for 120 hours followed by storage at 25°C for 6 hours and then at 37°C for 12 hours. Heparin retained more than 95% of its initial activity throughout the study period. Particle formation was not detected at any time under the storage conditions. The pH and color remained essentially unchanged throughout the study. Conclusions: Ceftazidime-heparin admixture retains its stability over long periods of storage at different temperatures, allowing its potential use for PDAP treatment in outpatient and remote settings.
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The Evolution of Peritoneal Dialysis Solutions
Chapter
  • Jul 2021
The use of peritoneal dialysis (PD) solutions was first described by Wegner, a German investigator in the late nineteenth century. He injected hypertonic and hypotonic solutions into the peritoneal cavity of a guinea pig and observed that hypertonic solutions increased the volume in the cavity and hypotonic solutions decreased the volume. Wegner’s findings triggered interest in the use of solutions for the treatment of uremia. Several scientists followed suit; Ganter used saline to treat uremia, and Heusser added dextrose to increase ultrafiltration (UF). Rhoads added lactate in PD solutions as a buffer to correct acidosis in 1938. The use of PD solutions has continued to evolve to the present day in the quest for formulating an optimal dialysate. The durability of PD as a dialysis modality depends on the type of solution utilized and its long-term effects on the peritoneal membrane. Many have argued that biocompatible solutions are ideal because they are proposed to limit the long-term degradation of the peritoneal membrane.
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Peritoneal Dialysis
Chapter
  • Aug 2019
Peritoneal dialysis (PD) as a treatment for end‐stage kidney disease (ESKD) is a relatively simple and very effective technique. This chapter discusses the importance of having an individualised treatment for each patient, which is structured around both clinical and lifestyle needs. It provides an overview of the anatomy and physiology of the peritoneum and practical aspects of the therapy, and different therapy options on PD. The chapter also discusses complications and patient education and training. As the therapy is predominately performed by the patients themselves, in the community, the main focus is on providing patients with not only an individualised treatment, but also adequate psychological and nursing care which are essential elements for the successful treatment of those needing PD and their families. PD offers equal survival compared with haemodialysis for younger patients with diabetes during early years of dialysis. Fluid removal and fluid balance can be enhanced in patients on PD.
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Biocompatible dialysis fluids for peritoneal dialysis
Article
  • Oct 2018
Background: 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. Objectives: This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD. Search methods: 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. Selection criteria: 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. Data collection and analysis: 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. Main results: 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. Authors' conclusions: 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.
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Peritoneal solute transport predicts survival on CAPD independently of residual renal function
Article
Full-text available
  • Apr 1998
  • NEPHROL DIAL TRANSPL
BACKGROUND: Loss of residual renal function has a profound effect on the survival of peritoneal dialysis patients. Less is known of the impact of peritoneal function. The purpose of this study was to investigate the influence of solute transport on clinical outcome in CAPD patients. METHODS: Two hundred and ten consecutive patients commencing CAPD since 1990 were enrolled into a single centre prospective longitudinal observational study of urea, protein, and peritoneal kinetics. On entry, and at 6-monthly intervals, estimations were made of weight, body mass index (BMI), plasma albumin, Kt/V, residual renal function (RRF), NPCR, low-molecular-weight solute transport (D/Pcreat), and peritoneal protein losses. All patients were censored in 1996, regardless of treatment modality. RESULTS: During the 6-year follow up period (median 22 months) there were 51 deaths, and the actuarial survival was 58% at 5 years. Urea, protein and peritoneal kinetics varied with time on dialysis: as anticipated there was a reduction in Kt/V, attributable to loss of RRF, whereas plasma albumin was stable for the first 2 years of treatment, but subsequently started to decline, a trend that became significant at 42 months. Peritoneal kinetics stabilized within the first 6 months of treatment and then showed a trend of increased solute transfer with time on treatment, which became significant by the end of the study. Comparing survivors with non-survivors Kt/V and RRF were similar at the start of treatment, but loss of RRF occurred significantly earlier in non-survivors than survivors (0.37 vs 0.68, P=0.02 at 6 months, 0.19 vs 0.54, P=0.01 at 12 months). D/Pcreat was also identical at commencement of treatment, but subsequently whilst survivors had stable solute transfer, non-survivors had consistently higher solute transfer beyond 6 months that reached increasing significance after 18 months, (0.70 vs 0.67, P=0.05 at 18 months, 0.72 vs 0.66, P=0.03 at 24 months). A Cox proportional hazard model constructed for the variables age, sex, BMI, albumin, Kt/V and D/Pcreat at 6 months of treatment indicated that low Kt/V (P=0.004), high D/Pcreat (P=0.013) and age (P=0.028) were independent predictors of death. CONCLUSION: There is good reason to believe that high peritoneal solute transport is an independent marker of poor outcome in CAPD patients.
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Recent Peritonitis Associates with Mortality among Patients Treated with Peritoneal Dialysis
Article
Full-text available
  • May 2012
  • J AM SOC NEPHROL
Peritonitis is a major complication of peritoneal dialysis, but the relationship between peritonitis and mortality among these patients is not well understood. In this case-crossover study, we included the 1316 patients who received peritoneal dialysis in Australia and New Zealand from May 2004 through December 2009 and either died on peritoneal dialysis or within 30 days of transfer to hemodialysis. Each patient served as his or her own control. The mean age was 70 years, and the mean time receiving peritoneal dialysis was 3 years. In total, there were 1446 reported episodes of peritonitis with 27% of patients having ≥ 2 episodes. Compared with the rest of the year, there were significantly increased odds of peritonitis during the 120 days before death, although the magnitude of this association was much greater during the 30 days before death. Compared with a 30-day window 6 months before death, the odds for peritonitis was six-fold higher during the 30 days immediately before death (odds ratio, 6.2; 95% confidence interval, 4.4-8.7). In conclusion, peritonitis significantly associates with mortality in peritoneal dialysis patients. The increased odds extend up to 120 days after an episode of peritonitis but the magnitude is greater during the initial 30 days.
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Effects of Biocompatible versus Standard Fluid on Peritoneal Dialysis Outcomes
Article
Full-text available
  • Mar 2012
  • J AM SOC NEPHROL
The clinical benefits of using "biocompatible" neutral pH solutions containing low levels of glucose degradation products for peritoneal dialysis compared with standard solutions are uncertain. In this multicenter, open-label, parallel-group, randomized controlled trial, we randomly assigned 185 incident adult peritoneal dialysis patients with residual renal function to use either biocompatible or conventional solution for 2 years. The primary outcome measure was slope of renal function decline. Secondary outcome measures comprised time to anuria, fluid volume status, peritonitis-free survival, technique survival, patient survival, and adverse events. We did not detect a statistically significant difference in the rate of decline of renal function between the two groups as measured by the slopes of GFR: -0.22 and -0.28 ml/min per 1.73 m(2) per month (P=0.17) in the first year in the biocompatible and conventional groups, respectively, and, -0.09 and -0.10 ml/min per 1.73 m(2) per month (P=0.9) in the second year. The biocompatible group exhibited significantly longer times to anuria (P=0.009) and to the first peritonitis episode (P=0.01). This group also had fewer patients develop peritonitis (30% versus 49%) and had lower rates of peritonitis (0.30 versus 0.49 episodes per year, P=0.01). In conclusion, this trial does not support a role for biocompatible fluid in slowing the rate of GFR decline, but it does suggest that biocompatible fluid may delay the onset of anuria and reduce the incidence of peritonitis compared with conventional fluid in peritoneal dialysis.
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The Clinical Usefulness of Peritoneal Dialysis Fluids with Neutral pH and Low Glucose Degradation Product Concentration: An Open Randomized Prospective Trial
Article
  • Mar 2008
Background Long-term peritoneal dialysis (PD) is associated with the development of various structural and functional changes to the peritoneal membrane when bioincompatible conventional peritoneal dialysis fluids (PDFs) are used. In this study, we looked at patients that were treated with conventional PDFs and then changed to novel biocompatible PDFs with a neutral pH and a low concentration of glucose degradation products (GDPs) to investigate whether this change could result in the arrest or reversal of peritoneal membrane deterioration. Methods In an open label, randomized prospective trial, the clinical effects of conventional PDFs and biocompatible PDFs with neutral pH and very low concentration of GDPs were compared in 104 patients equally divided between both study PDFs. Blood and effluent dialysate samples, peritoneal equilibration tests, and adequacy evaluation were undertaken at baseline, 4, 8, and 12 months. The target variables were the ratio of dialysate-to-plasma (D/P) creatinine, peritoneal ultrafiltration, residual renal function, dialysis adequacy indices, and effluent cancer antigen 125 (CA125). Results D/P creatinine values were not different in the two groups. Peritoneal ultrafiltration was significantly higher in the low-GDP PDF group than in the conventional PDF group at all follow-up times (4 months: 9.1 ± 4.3 vs 6.0 ± 3.0; 8 months: 8.3 ± 3.4 vs 6.0 ± 3.0; 12 months: 8.9 ± 3.3 vs 6.1 ± 3.3 mL/g dextrose/day; p < 0.05). Peritoneal Kt/V urea values and total weekly Kt/V urea values at 4 months were significantly higher in the low-GDP PDF group than in the conventional PDF group. Residual renal function was not statistically significant. Effluent CA125 levels were significantly higher in the low-GDP PDF group at all follow-up visits (4 months: 37.8 ± 20.8 vs 22.0 ± 9.5; 8 months: 41.2 ± 20.3 vs 25.9 ± 11.3; 12 months: 40.4 ± 21.4 vs 28.6 ± 13.0 U/mL; p < 0.05). Among anuric patients, peritoneal ultrafiltration at 4, 8, and 12 months, total weekly Kt/V at 4 and 8 months, and CA125 levels at all follow-up visits were significantly higher in patients treated with low-GDP PDF than those treated with conventional PDF. However, among anuric patients, D/P creatinine showed no significant differences between the low-GDP PDF group and the conventional PDF group. Conclusion The use of biocompatible PDFs with neutral pH and low GDP concentration can contribute to improvement of peritoneal ultrafiltration and peritoneal effluent CA125 level, an indicator of peritoneal membrane integrity in PD patients.
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A Combination of Biocompatible Peritoneal Dialysis Solutions and Residual Renal Function, Peritoneal Transport, and Inflammation Markers: A Randomized Clinical Trial
Article
  • Jul 2012
  • AM J KIDNEY DIS
Background: The benefits of biocompatible peritoneal dialysis (PD) fluids, particularly for residual renal function (RRF), are controversial. Moreover, the clinical effects of a PD regimen consisting of different biocompatible PD fluids have not been fully established. Study design: Prospective, randomized, controlled, open-label study. Setting & participants: Patients with end-stage kidney disease newly started on continuous ambulatory PD therapy (N = 150). Intervention: A 12-month intervention with 3 biocompatible PD fluids (a neutral-pH, low glucose degradation product, 1.5% glucose solution; a solution with 1.1% amino acid; and a fluid with 7.5% icodextrin) or conventional PD fluid. Outcomes: The primary outcome was change in RRF and daily urine volume. Secondary outcomes were peritoneal transport and inflammation markers. Measurements: RRF, daily urine volume, serum and dialysate cytokine levels. Results: RRF(3.24 ± 1.98 vs 2.88 ± 2.43 mL/min/1.73 m(2); P = 0.9) and rate of decline in RRF (-0.76 ± 1.77 vs -0.91 ± 1.92 mL/min/1.73 m(2) per year; P = 0.6) did not differ between the biocompatible- and conventional-PD-fluid groups. However, patients using the biocompatible PD fluids had better preservation of daily urine volume (959 ± 515 vs 798 ± 615 mL/d in the conventional group, P = 0.02 by comparison of difference in overall change by repeated-measures analysis of variance). Their dialysate-plasma creatinine ratio at 4 hours was higher at 12 months (0.78 ± 0.13 vs 0.68 ± 0.12; P = 0.01 for comparison of the difference in overall change by repeated-measures analysis of variance). They also had significantly higher serum levels of adiponectin and overnight spent dialysate levels of cancer antigen 125, adiponectin, and interleukin 6 (IL-6). No differences between the 2 groups were observed for serum C-reactive protein and IL-6 levels. Limitations: Unblinded, relatively short follow-up; no formal sample-size calculations. Conclusions: Use of a combination of 3 biocompatible PD fluids for 12 months compared with conventional PD fluid did not affect RRF, but was associated with better preservation of daily urine volume. The biocompatible PD fluids also lead to changes in small-solute transport and an increase in dialysate cancer antigen 125, IL-6, adiponectin, and systemic adiponectin levels, but have no effect on systemic inflammatory response. The clinical significance of these changes, while of great interest, remains to be determined by further studies.
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Low glucose degradation products dialysis solution modulates the levels of surrogate markers of peritoneal inflammation, integrity, and angiogenesis: preliminary report
Article
  • Oct 2003
  • NEPHROLOGY
The presence of glucose degradation products (GDPs) in peritoneal dialysis (PD) fluids has many adverse effects, namely clinically significant abdominal pain or discomfort during infusion, inhibition of cell proliferation, impairment of inflammatory cell function, cytotoxicity, and the induction of vascular endothelial growth factor (VEGF). In a prospective, randomized, controlled trial comparing a low GDP PD solution (pH 7.0, two compartment bag: low GDP) to conventional PD solution (pH 5.5: high GDP), the overnight dialysate levels of the markers of inflammation/wound healing (hyaluronic acid (HA)), mesothelial cell mass/membrane integrity (cancer antigen 125 (CA125)), and angiogenesis (VEGF) were assessed over a 12-month period. Twenty-six newly commencing continuous ambulatory peritoneal dialysis (CAPD) patients were randomly assigned to either the Low GDP group (n = 16) or the High GDP group (n = 10). Standard peritoneal permeability analysis for membrane transport characteristics and dialysis adequacy with nutritional status (serum albumin, nPCR) were evaluated at 1, 6, and 12 months. In patients treated with high GDP solution, there was significant increase in VEGF with time (time = 1 month, 67.2 ± 10.8; time = 6 months, 189.8 ± 90.2; and time = 12 months, 169.3 ± 83.1 pg/mg of protein; P < 0.05). There was no significant change of VEGF with time in the low GDP group. Significantly higher concentrations of CA125 (65.5 ± 10.4 vs. 19.7 ± 2.6 at 1 month, P < 0.0001; 66.6 ± 9.8 vs. 29.7 ± 5.0 at 6 months, P < 0.01; 68.7 ± 10.5 vs. 30.7 ± 10.0 U/mL at 12 months, P < 0.01) and lower concentrations of HA (114.6 ± 18.8 vs. 254.3 ± 69.2 at 1 month, P < 0.05; 417.5 ± 57.2 vs. 1277.5 ± 367.9 ng/mg of protein at 12 month, P < 0.05) were observed in the low GDP group compared with the high GDP group. In conclusion, continuous therapy with the low GDP solution modulates the levels of surrogate markers of peritoneal inflammation, integrity and angiogenesis. The results strongly suggest that the use of a low GDP solution would be beneficial to maintain the function and structural integrity of the peritoneal membrane.
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New Peritoneal Dialysis Solutions and Solutions on the Horizon
Chapter
  • May 2009
Magnesium is an important cation involved in several enzymatic reactions. The serum concentration of magnesium in dialysis patients depends on dietary intake and on the concentration of the cation in the dialysis solution. Normal values of total serum magnesium range from 0.65 to 0.98mmol/L, while its diffusible fraction is about 55–60% of the total. Commercially available continuous ambulatory peritoneal dialysis (CAPD) solutions contain 0.25–0.75mmol/L of magnesium. In such conditions, when 0.75mmol/L magnesium and 1.5% glucose solutions are used in CAPD, a slight magnesium uptake from the dialysis solution usually occurs by diffusive gradient [1]. Kwong et al., however, have reported a negative dialytic balance with the same solution [2].
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