Low Glucose Degradation Product Solutions Research Articles

Associations of neutral pH, low-GDP peritoneal dialysis solutions with patient survival, transfer to haemodialysis and peritonitis.

Peritoneal dialysis (PD) solutions containing low levels of glucose degradation products (GDPs) are associated with attenuation of peritoneal membrane injury and vascular complications. However, clinical benefits associated with neutral-pH, low-GDP (N-pH/L-GDP) solutions remain unclear. Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the associations between N-pH/L-GDP solutions and all-cause mortality, cause-specific mortality, transfer to haemodialysis (HD) for ≥30days and PD peritonitis in adult incident PD patients in Australia and New Zealand between 1 January 2005 and 31 December 2020 using adjusted Cox regression analyses. Of 12814 incident PD patients, 2282 (18%) were on N-pH/L-GDP solutions. The proportion of patients on N-pH/L-GDP solutions each year increased from 11% in 2005 to 33% in 2017. During the study period, 5330 (42%) patients died, 4977 (39%) experienced transfer to HD and 5502 (43%) experienced PD peritonitis. Compared with the use of conventional solutions only, the use of any form of N-pH/L-GDP solution was associated with reduced risks of all-cause mortality {adjusted hazard ratio [aHR] 0.67 [95% confidence interval (CI) 0.61-0.74]}, cardiovascular mortality [aHR 0.65 (95% CI 0.56-0.77)], infection-related mortality [aHR 0.62 (95% CI 0.47-0.83)] and transfer to HD [aHR 0.79 (95% CI 0.72-0.86)] but an increased risk of PD peritonitis [aHR 1.16 (95% CI 1.07-1.26)]. Patients who received N-pH/L-GDP solutions had decreased risks of all-cause and cause-specific mortality despite an increased risk of PD peritonitis. Studies assessing the causal relationships are warranted to determine the clinical benefits of N-pH/L-GDP solutions.

Variation in Peritoneal Dialysis–Related Peritonitis Outcomes in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS)

Peritoneal dialysis (PD)-associated peritonitis is a significant PD-related complication. We describe the likelihood of cure after a peritonitis episode, exploring its association with various patient, peritonitis, and treatment characteristics. Observational prospective cohort study. 1,631 peritonitis episodes (1,190 patients, 126 facilities) in Australia, New Zealand, Canada, Japan, Thailand, the United Kingdom, and the United States. Patient characteristics (demographics, patient history, laboratory values), peritonitis characteristics (organism category, concomitant exit-site infection), dialysis center characteristics (use of icodextrin and low glucose degradation product solutions, policies regarding antibiotic self-administration), and peritonitis treatment characteristics (antibiotic used). Cure, defined as absence of death, transfer to hemodialysis (HD), PD catheter removal, relapse, or recurrent peritonitis within 50 days of a peritonitis episode. Mixed-effects logistic models. Overall, 65% of episodes resulted in a cure. Adjusted odds ratios (AOR) for cure were similar across countries (range, 54%-68%), by age, sex, dialysis vintage, and diabetes status. Compared with Gram-positive peritonitis, the odds of cure were lower for Gram-negative (AOR, 0.41 [95% CI, 0.30-0.57]), polymicrobial (AOR, 0.30 [95% CI, 0.20-0.47]), and fungal (AOR, 0.01 [95% CI, 0.00-0.07]) peritonitis. Odds of cure were higher with automated PD versus continuous ambulatory PD (AOR, 1.36 [95% CI, 1.02-1.82]), facility icodextrin use (AOR per 10% greater icodextrin use, 1.06 [95% CI, 1.01-1.12]), empirical aminoglycoside use (AOR, 3.95 [95% CI, 1.23-12.68]), and ciprofloxacin use versus ceftazidime use for Gram-negative peritonitis (AOR, 5.73 [95% CI, 1.07-30.61]). Prior peritonitis episodes (AOR, 0.85 [95% CI, 0.74-0.99]) and concomitant exit-site infection (AOR, 0.41 [95% CI, 0.26-0.64]) were associated with a lower odds of cure. Sample selection may be biased and generalizability may be limited. Residual confounding and confounding by indication limit inferences. Use of facility-level treatment variables may not capture patient-level treatments. Outcomes after peritonitis vary by patient characteristics, peritonitis characteristics, and modifiable peritonitis treatment practices. Differences in the odds of cure across infecting organisms and antibiotic regimens suggest that organism-specific treatment considerations warrant further investigation.

Longitudinal Changes of NF-\u03baB Downstream Mediators and Peritoneal Transport Characteristics in Incident Peritoneal Dialysis Patients

The role of intra-peritoneal mediators in the regulation peritoneal transport is not completely understood. We investigate the relation between longitudinal changes in dialysis effluent level of nuclear factor kappa-B (NF-κB) downstream mediators and the change in peritoneal transport over 1 year. We studied 46 incident PD patients. Their peritoneal transport characteristics were determined after starting PD and then one year later. Concomitant dialysis effluent levels of interleukin-6 (IL-6), cyclo-oxygenase-2 (COX-2) and hepatocyte growth factor (HGF) are determined. There were significant correlations between baseline and one-year dialysis effluent IL-6 and COX-2 levels with the corresponding dialysate-to-plasma creatinine level at 4 hours (D/P4) and mass transfer area coefficient of creatinine (MTAC). After one year, patients who had peritonitis had higher dialysis effluent IL-6 (26.6 ± 17.4 vs 15.1 ± 12.3 pg/ml, p = 0.037) and COX-2 levels (4.97 ± 6.25 vs 1.60 ± 1.53 ng/ml, p = 0.007) than those without peritonitis, and the number of peritonitis episode significantly correlated with the IL-6 and COX-2 levels after one year. In contrast, dialysis effluent HGF level did not correlate with peritoneal transport. There was no difference in any mediator level between patients receiving conventional and low glucose degradation product solutions. Dialysis effluent IL-6 and COX-2 levels correlate with the concomitant D/P4 and MTAC of creatinine. IL-6 and COX-2 may contribute to the short-term regulation of peritoneal transport.

Is oxidative stress an issue in peritoneal dialysis?

During the last two decades, oxidative stress (OS) has emerged as a novel risk factor for a variety of adverse events, including atherosclerosis and mortality in chronic kidney disease (CKD) patients. Increased OS occurs even in early stages of the disease, progresses with deterioration of renal function and is further aggravated by hemodialysis (HD), due to the bioincompatibility of the method. Compared to HD, peritoneal dialysis (PD) is a more biocompatible dialysis modality, characterized by a significantly reduced, but still high, OS status. The culprit for OS in PD is mainly the composition of PD solutions (low pH, lactate buffer, increased osmolarity and high glucose concentration). After heat sterilization of PD solutions, formation of glucose degradation products (GDPs) and advanced glycation end-products (AGEs) trigger inflammation and enhance OS. Chronic exposure of the peritoneum to this toxic, hyperglycemic environment leads to OS-derived morphologic damage of peritoneal cells, loss of ultrafiltration capacity and decreased technique survival. Moreover, OS is linked with peritonitis, loss of residual renal function, inflammation, atherosclerosis, cardiovascular (CV) disease, and increased mortality. To ameliorate OS status in PD, a multitargeted approach is necessary that includes use of neutral pH, low GDP, low lactate and iso-ismolar PD solutions, strict glycemic control, optimal volume management and, probably supplementation with antioxidants, N-acetylcysteine being the most promising among them.

Biocompatible dialysis fluids for peritoneal dialysis.

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

The Effect of Neutral Peritoneal Dialysis Solution with Low Glucose-Degradation-Product on the Fluid Status and Body Composition--A Randomized Control Trial.

BackgroundPrevious studies report conflicting results on the benefit of peritoneal dialysis (PD) patients treated with low glucose degradation product (GDP) solution. The effects of low GDP solution on body fluid status and arterial pulse wave velocity (PWV) have not been studied.MethodsWe randomly assigned 68 incident PD patients to low GDP (Intervention Group) or conventional solutions (Control Group); 4 dropped off before they received the assigned treatment. Patients were followed for 52 weeks for changes in ultrafiltration, residual renal function, body fluid status and arterial PWV.ResultAfter 52 weeks, Intervention Group had higher overhydration (3.1 ± 2.6 vs 1.9 ± 2.2 L, p = 0.045) and extracellular water volume (17.7 ± 3.9 vs 15.8 ± 3.1 L, p = 0.034) than Control Group. There was no significant difference in PWV between groups. There was no significant difference in residual renal function between the Groups. Intervention Group had lower ultrafiltration volume than Control Group at 4 weeks (0.45 ± .0.61 vs 0.90 ± 0.79 L/day, p = 0.013), but the difference became insignificant at later time points. Intervention Group had lower serum CRP levels than Control Group (4.17 ± 0.77 vs 4.91 ± 0.95 mg/dL, p < 0.0001).ConclusionIncident PD patients treated with low GDP solution have less severe systemic inflammation but trends of less ultrafiltration, and more fluid accumulation. However, the effects on ultrafiltration and fluid accumulation disappear with time. The long term effect of low GDP solution requires further study.Trial RegistrationClinicalTrials.gov NCT00966615

Update on Peritoneal Dialysis: Core Curriculum 2016

Update on Peritoneal Dialysis: Core Curriculum 2016

Effect of Neutral-pH, Low-Glucose Degradation Product Peritoneal Dialysis Solutions on Residual Renal Function, Urine Volume, and Ultrafiltration: A Systematic Review and Meta-Analysis.

Neutral-pH, low-glucose degradation products solutions were developed in an attempt to lessen the adverse effects of conventional peritoneal dialysis solutions. A systematic review was performed evaluating the effect of these solutions on residual renal function, urine volume, peritoneal ultrafiltration, and peritoneal small-solute transport (dialysate to plasma creatinine ratio) over time. Multiple electronic databases were searched from January of 1995 to January of 2013. Randomized trials reporting on any of four prespecified outcomes were selected by consensus among multiple reviewers. Eleven trials of 643 patients were included. Trials were generally of poor quality. The meta-analysis was performed using a random effects model. The use of neutral-pH, low-glucose degradation products solutions resulted in better preserved residual renal function at various study durations, including >1 year (combined analysis: 11 studies; 643 patients; standardized mean difference =0.17 ml/min; 95% confidence interval, 0.01 to 0.32), and greater urine volumes (eight studies; 598 patients; mean difference =128 ml/d; 95% confidence interval, 58 to 198). There was no significant difference in peritoneal ultrafiltration (seven studies; 571 patients; mean difference =-110; 95% confidence interval, -312 to 91) or dialysate to plasma creatinine ratio (six studies; 432 patients; mean difference =0.03; 95% confidence interval, 0.00 to 0.06). The use of neutral-pH, low-glucose degradation products solutions results in better preservation of residual renal function and greater urine volumes. The effect on residual renal function occurred early and persisted beyond 12 months. Additional studies are required to evaluate the use of neutral-pH, low-glucose degradation products solutions on hard clinical outcomes.

Bicarbonate versus lactate solutions for acute peritoneal dialysis.

The high mortality rate among critically ill patients with acute kidney injury (AKI) remains an unsolved problem in intensive care medicine, despite the use of renal replacement therapy (RRT). Increasing evidence from clinical studies in adults and children suggests that the new peritoneal dialysis (PD) fluids may allow for better long-term preservation of peritoneal morphology and function. Formation of glucose degradation products (GDPs) can be reduced and even avoided with the use of newer "biocompatible" solutions. However, it is still unclear if there are any differences in using conventional (lactate) solutions compared with low GDP (bicarbonate) solutions for acute PD. To look at the benefits and harms of bicarbonate versus lactate solutions in acute PD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1966), EMBASE (from 1980), Latin American and Caribbean Health Sciences Literature Database LILACS (from 1982), and reference lists of articles.Date of last search: 6 May 2014. Randomised controlled trials (RCTs) comparing bicarbonate to lactate solution for acute PD. Two authors independently assess the methodological quality of studies. One author abstracted data onto a standard form, and a second author checked data extraction. We used the random-effects model and expressed the results as relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). We included one study (20 patients) in this review. In shock patients, bicarbonate did not differ from lactate with respect to mortality (RR 0.50, 95% CI 0.06 to 3.91); however there were significant differences in blood lactate (MD -1.60 mmol/L, 95% CI -2.04 to -1.16), serum bicarbonate (MD 5.00 mmol/L, 95% CI 3.26 to 6.74) and blood pH (MD 0.12, 95% CI 0.06 to 0.18). In non-shock patients there was a significance difference in blood lactate (MD -0.60 mmol/L, 95% CI -0.85 to -0.35) but not in serum bicarbonate (MD 1.10 mmol/L, 95% CI -0.27 to 2.47) or blood pH (MD -0.02, 95% CI -0.02 to -0.06). Other outcomes could not be analysed because of the limited data available. There is no strong evidence that any clinical advantage for patients requiring acute PD for AKI when comparing conventional (lactate) with low GDP dialysis solutions (bicarbonate).

Solutions for peritoneal dialysis in children: recommendations by the European Pediatric Dialysis Working Group

The purpose of this article is to provide recommendations on the choice of peritoneal dialysis (PD) fluids in children by the European Pediatric Dialysis Working Group. The literature on experimental and clinical studies with PD solutions in children and adults was analyzed together with consensus discussions within the group. A grading was performed based on the international KDIGO nomenclature and methods. The lowest glucose concentration possible should be used. Icodextrin may be applied once daily during the long dwell, in particular in children with insufficient ultrafiltration. Infants on PD are at risk of ultrafiltration-associated sodium depletion, while anuric adolescents may have water and salt overload. Hence, the sodium chloride balance needs to be closely monitored. In growing children, the calcium balance should be positive and dialysate calcium adapted according to individual needs. Limited clinical experience with amino acid-based PD fluids in children suggests good tolerability. The anabolic effect, however, is small; adequate enteral nutrition is preferred. CPD fluids with reduced glucose degradation products (GDP) content reduce local and systemic toxicity and should be preferred whenever possible. Correction of metabolic acidosis is superior with pH neutral bicarbonate-based fluids compared with single-chamber, acidic, lactate-based solutions. Prospective comparisons of low GDP solutions with different buffer compositions are still few, and firm recommendations cannot yet be given, except when hepatic lactate metabolism is severely compromised.

Determinants of Peritoneal Membrane Function Over Time

Changes to peritoneal membrane function over time result in the development of ultrafiltration failure in a proportion of PD patients and pose a risk for the rarer condition of encapsulating peritoneal sclerosis. These changes are characterized by an increase in the transport rate for small solutes owing to increased vascularity and/or peritoneal blood flow and in more severe cases a reduction in the osmotic conductance of the membrane that likely reflects progressive fibrosis. Both of these processes are preceded by exposure of the membrane to glucose when using conventional dialysis solutions, although this usually is necessitated and likely exacerbated by loss of residual renal function and recurrent peritonitis. Mediators of membrane injury and thus potential biomarkers include inflammatory cytokines, notably local interleukin-6 production, which also appears to determine solute transport characteristics at the start of peritoneal dialysis, local production of vascular endothelial growth factor, and transforming growth factor β-associated epithelial to mesenchymal transition of the mesothelium leading to membrane fibrosis. Low glucose degradation product solutions may ameliorate the mesothelial injury associated with high glucose exposure, but evidence that they prevent or delay changes in membrane function over time is lacking. In the meantime, avoidance of excessive glucose exposure, preservation of residual renal function, and prevention of peritonitis remain the most logical treatment strategies for this problem.

Peritoneal Dialysis in Diabetics: There Is Room for More

End stage renal disease diabetic patients suffer from worse clinical outcomes under dialysis-independently of modality. Peritoneal dialysis offers them the advantages of home therapy while sparing their frail vascular capital and preserving residual renal function. Other benefits and potential risks deserve discussion. Predialysis intervention with early nephrology referral, patient education, and multidisciplinary support are recommended. Skilled and updated peritoneal dialysis protocols must be prescribed to assure better survival. Optimized volume control, glucose-sparing peritoneal dialysis regimens, and elective use of icodextrin are key therapy strategies. Nutritional evaluation and support, preferential use of low-glucose degradation products solutions, and prescription of renin-angiotensin-aldosterone system acting drugs should also be part of the panel to improve diabetic care under peritoneal dialysis.

Rationale and design of the balANZ trial: A randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function

BackgroundThe main hypothesis of this study is that neutral pH, low glucose degradation product (GDP) peritoneal dialysis (PD) fluid better preserves residual renal function in PD patients over time compared with conventional dialysate.Methods/DesignInclusion criteria are adult PD patients (CAPD or APD) aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance®) or conventional dialysis solution (Stay.safe®) for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial.DiscussionThis investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients.Trial RegistrationAustralian New Zealand Clinical Trials Registry Number: ACTRN12606000044527

Biocompatibility and Tolerability of a Purely Bicarbonate-Buffered Peritoneal Dialysis Solution

Novel peritoneal dialysis solutions are characterized by a minimal content of glucose degradation products and a neutral pH. Many studies have shown the biocompatibility of neutral lactate-buffered solutions; however, until now, the effect of purely bicarbonate-buffered solutions has not been intensively studied in vivo. This study was an open label, prospective, crossover multicenter trial to investigate the biocompatibility of a purely bicarbonate-buffered solution (bicPDF) by measuring biocompatibility parameters such as cancer antigen 125 (CA125) in peritoneal effluent. 55 patients were enrolled in the study. After a 2-week run-in phase, 53 patients could be randomized into 2 groups, starting with either standard lactate-buffered peritoneal dialysis fluid (SPDF) for 12 weeks (phase 1) and then switching to bicPDF for 12 weeks (phase 2), or vice versa. Overnight peritoneal effluents were collected at baseline and at the end of phases 1 and 2 and were tested for CA125, hyaluronic acid, vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), interferon gamma (IFNgamma), and transforming growth factor-beta(1) (TGF-beta1). Total ultrafiltration and residual renal function were also assessed. At the end of the study, pain during fluid exchange and dwell was evaluated using special questionnaires. 34 patients completed the study; 27 of them provided data for analysis of the biocompatibility parameters. CA125 levels in overnight effluent were significantly higher with bicPDF (61.9 +/- 33.2 U/L) than with SPDF (18.6 +/- 18.2 U/L, p < 0.001). Hyaluronic acid levels were significantly lower after the use of bicPDF (185.0 +/- 119.6 ng/mL) than after SPDF (257.4 +/- 174.0 ng/mL, p = 0.013). Both TNF-alpha and TGF-beta1 showed higher levels with the use of bicPDF than with SPDF. No differences were observed for IL-6, VEGF, or IFNgamma levels. We observed an improvement in the glomerular filtration rate with the use of bicPDF but no differences were observed for total fluid loss. Pain scores could be analyzed in 23 patients: there was no difference between the solutions. The use of a purely bicarbonate-buffered low-glucose degradation product solution significantly changes most of the peritoneal effluent markers measured, suggesting an improvement in peritoneal membrane integrity. Additionally, it seems to have a positive effect on residual renal function.

Biocompatible peritoneal dialysis solutions: do they indeed affect the outcome?

Numerous studies have confirmed beneficial effects of polyglucose dialysis solution (PG-DS), an amino acid dialysis solution (AA-DS), and bicarbonate (bic) or bicarbonate/lactate (bic/lac) buffered solutions on selected components of peritoneal bioavailability or clinical parameters of peritoneal dialysis (PD) patients. Few adverse effects have also been described. A question arises whether these solutions affect the PD outcome. A better controlled fluid status of PD patients associated with the use of PG-DS has been shown in a double-blind randomized controlled trial. Continuous cyclic PD patients treated with the PG-DS did not show changes in solute kinetics and peritoneal membrane markers remained unaltered. The use of PG-DS in anuric automated PD patients was associated with less impaired membrane function. A prospective, randomized, controlled study on the AA-DS in malnourished continuous ambulatory PD patients did not show significant effects of the AA-DS on patient survival, hospitalization rate, C-reactive protein levels, total urea Kt/V, ultrafiltration and drop-out rates, but nutritional status improved or was stable. Improved acid-base balance with bic-buffered solutions was shown in patients treated with automated PD or continuous PD. A registry-based study suggests better survival of patients treated with a neutral pH, low glucose degradation product solution, but there were no differences in dialysis technique survival, peritonitis-free survival, or peritonitis rates. However, reduced peritonitis rate was also reported with the use of bic/lac solutions. Current concepts of PD solutions involve efforts to use fluids which combine the advantages of PG-DS, AA-DS and bic-buffered solutions. Large-scale studies should be continued to improve biocompatibility of peritoneal solutions and to establish their effect on the clinical outcome.

Changing prescribing practice in CAPD patients in Korea: increased utilization of low GDP solutions improves patient outcome

Novel, biocompatible peritoneal dialysis (PD) solutions have become available in recent years. In 2001, low glucose degradation products (GDP), neutral pH solutions became commercially available in Korea. To date, there are no reports regarding the large scale adoption of these solutions in clinical practice and regarding what, if any, impact these solutions have on patient outcomes. Using a database of almost 4000 patients treated by PD in Korea, we conducted a prospective, longitudinal observational study documenting the patterns of use of one novel low GDP solution (balance, Fresenius Medical Care, St Wendel, Germany) in 1909 PD incident patients between 1 January 2002 and midyear 2005. Outcomes including patient and technique survival and peritonitis rates were analysed using univariate and multivariate analysis. Prescription of low GDP solutions reached between 70 and 80% by the year 2003 and persisted at this level. Patients prescribed low GDP PD solution tended to be younger and were more likely to be treated in centres with larger enrollment in the database. Survival of diabetic patients treated with the new PD solution was identical to that of the non-diabetic patients treated with standard PD fluids (PDF) and treatment with low GDP PDF independently reduced the relative risk (RR) of death (RR = 0.613; CI 0.50-0.74; P < 0.00001) in a proportional hazards model which included age, diabetes and centre experience. In a univariate analysis, low GDP PD solution was associated with a longer technique survival (P = 0.049) but this effect was not significant in multivariate analysis. No significant differences in peritonitis-free interval or peritonitis rate could be attributed to the prescribed PDF. Prescription of low GDP, pH-neutral PD solutions has rapidly increased in Korea. This change has resulted in a significant improvement in patient and technique survival without any measurable change in peritonitis incidence or rate. Reasons for the improved patient survival cannot be determined from this analysis and require further study.

Clinical biocompatibility of a neutral peritoneal dialysis solution with minimal glucose-degradation products--A 1-year randomized control trial

Chronic utilization of a bio-incompatible peritoneal dialysis (PD) solution with acidic pH and a high content of glucose degradation product (GDP) has been implicated as a contributing cause of peritoneal failure. We compared a newly formulated solution of neutral pH and low levels of GDP to a standard PD solution. Fifty new PD patients were randomized to a conventional lactate-buffered fluid (control) and a pH neutral, lactate-buffered, low GDP solution (balance). Patients were followed for 12 months. Serum samples were assayed for C-reactive protein (CRP). PD effluent was collected and assayed for cancer antigen-125 (CA125) and hyaluronan (HA). Clinical end points were the residual renal function and dialysis adequacy indices. After 52 weeks of treatment, PD fluid CA125 rose from 2.45 +/- 0.96 to 14.30 +/- 2.17 U/ml (P < 0.001), and HA declined from 2.26 +/- 0.60 to 1.45 +/- 0.32 mug/ml (P = 0.07) in the balance group. The balance group had a higher PD fluid CA-125 (14.30 +/- 2.17 vs 7.36 +/- 2.23 U/ml, P = 0.007), lower HA (1.45 +/- 0.32 vs 2.55 +/- 0.32 mug/ml, P = 0.007), and lower serum CRP level (1.77 +/- 0.42 vs 7.73 +/- 2.42 mg/l, P = 0.026) than the control group at 52 weeks. There was no difference in dialysis adequacy indices, ultrafiltration volume, urine output, residual renal function, peritonitis rate or need of hospitalization in 1 year. As compared to conventional PD solution, the use of balance, a neutral pH, low GDP solution resulted in a superior profile of PDE mesothelial cell marker and a lower degree of systemic inflammation, and the difference was maintained for 1 year. It remains to be determined whether these effects could result in better long-term clinical outcome.

Effect of Glucose Degradation Products on the Peritoneal Membrane in a Chronic Inflammatory Infusion Model of Peritoneal Dialysis in the Rat

Long-term use of the peritoneal membrane as a dialyzing membrane is hampered by its eventual deterioration. One of the contributing factors is glucose degradation products (GDPs) in the dialysis solution. In this study, we evaluated the effect of a low GDP solution on peritoneal permeability, the structural stability of the peritoneal membrane, and vascular endothelial growth factor (VEGF) production in a chronic inflammatory infusion model of peritoneal dialysis (PD) in the rat. Male Sprague-Dawley rats were divided into 3 groups: a conventional solution group (group C, n = 12), a test solution group (group T, n = 12), and a normal control group (group NC, n = 8). Group T rats were infused with low GDP solution (2.3% glucose solution with two compartments), and group C rats with conventional dialysis solution (2.3% glucose solution), adjusted to pH 7.0 before each exchange. Animals were infused through a permanent catheter with 25 mL of dialysis solution. In both groups, peritoneal inflammation was induced by infusing dialysis solution supplemented with lipopolysaccharide on days 8, 9, and 10 after starting dialysate infusion. Peritoneal membrane function was assessed before and 6 weeks after initiating dialysis using the 1-hour peritoneal equilibration test (PET) employing 4.25% glucose solution. Both VEGF and transforming growth factor beta1 (TGFbeta1) in the dialysate effluent were measured by ELISA. The number of vessels in the omentum was counted after staining with anti-von Willebrand factor, and the thickness of submesothelial matrix of the trichrome-stained parietal peritoneum was measured. Peritoneal tissue was analyzed for VEGF protein using immunohistochemistry. At the end of 6 weeks, the rate of glucose transport (D/D0, where D is glucose concentration in the dialysate and D0 is glucose concentration in the dialysis solution before it is infused into the peritoneal cavity) was higher in group T (p < 0.05) than in group C. Dialysate-to-plasma ratio (D/P) of protein was lower in group T (p < 0.05) than in group C; D/P(urea), D/P(sodium), and drain volumes did not differ significantly between groups C and T. Dialysate VEGF and TGFbeta levels were lower in group T (p < 0.05) than in group C. Immunohistochemical studies also revealed less VEGF in the peritoneal membranes of group T. There were significantly more peritoneal blood vessels in group C (p < 0.05) than in group T, but the thickness of submesothelial matrix of the parietal peritoneum was not different between the two groups. The VEGF levels in the dialysate effluent correlated positively with the number of blood vessels per field (r = 0.622, p < 0.005). Using a chronic inflammatory infusion model of PD in the rat, we show that dialysis with GDP-containing PD fluid is associated with increased VEGF production and peritoneal vascularization. Use of low GDP solutions may therefore be beneficial in maintaining the function and structure of the peritoneal membrane during long-term PD.