Effect of Glucose Degradation Products (GDP) on Endothelial Dysfunction

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of neutral pH and low glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF) on systemic inflammation and endothelial dysfunction markers in incident PD patients.

Detailed Description
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New peritoneal dialysis fluids (PDF) with neutral pH and low glucose degradation products (GDPs) are used in patients on peritoneal dialysis (PD). Low GDP fluids are reported to be more biocompatible than conventional PDF. Determination of biocompatibility has mainly focused on local peritoneal effects; recently, there has been interest in evaluating the systemic biocompatibility of these fluids. In recent analyses of two retrospective cohorts of Korean PD patients, significant survival advantage was shown for patients treated with the biocompatible PDF compared to patients treated with conventional PDF. However, the mechanisms of survival advantage with low GPD PDF in these observational studies are difficult to assess. Additionally, it is not clear that new PDFs favorably impact risk markers of cardiovascular disease (CVD). Epidemiologic studies identified an independent association between inflammation and risk of cardiovascular events and mortality; this association has been confirmed in patients with advanced chronic kidney diseases (CKD).Other evidence showed that clinically overt vascular events are preceded by endothelial dysfunction and increases in circulating markers of endothelial activation, including vascular cellular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1.Moreover, there is an association between inflammation and elevated levels of soluble VCAM-1 and ICAM-1 in patients with or at risk of atherosclerosis. Elevated levels of soluble adhesion molecules are found in ESRD patients, especially in patients with CVD and malnutrition. The investigators hypothesized that conventional PDF as well as uremia itself lead to local peritoneal changes such as peritoneal neoangiogenesis and fibrosis, effects related to ultrafiltration failure and subsequently volume overload. In addition, direct effect of GDPs and/or increased systemic levels of AGEs activate endothelial cells and increase levels of vascular adhesion molecules and inflammation. Both local and systemic effects of PDF are possibly associated with increased cardiovascular risks and mortality in PD patients. This study aims to examine the effects of neutral pH and low GDP-containing PDF on systemic inflammation and endothelial dysfunction in incident PD patients in a randomized, controlled study.

Official Title
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Effects of Neutral pH and Low Glucose Degradation Product-containing Peritoneal Dialysis Fluid on Systemic Markers of Inflammation and Endothelial Dysfunction: a Randomized, Controlled 1-year Follow-up Study

Conditions
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Kidney Failure, Chronic, Disorders Associated With Peritoneal Dialysis

Intervention / Treatment
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* Drug: Balance, Fresenius Medical Care, Germany


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged over 18 years and less than 75 years Within 90 days of initiation of first renal replacement treatment for ESRD Selected for maintenance management by CAPD Having provided informed consent Physically and mentally capable of performing the therapy Exclusion Criteria: Patients were excluded if deemed to have less than 80% likelihood of survival for at least 1 year episodes of peritonitis within prior 30 days any malignancy other than treated skin carcinoma uncontrolled congestive heart failure recent (within 60 days) myocardial infarction or cerebrovascular accident active systemic vasculitic disease including systemic lupus erythematosus, polyarteritis nodosa, ANCA-nephritis, active rheumatoid disease, or active venous thrombotic-embolic disease any acute infection at the time of enrollment active or actively treated tuberculosis recent (within 30 days) systemic bacterial infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: conventional PDF (Stay safe)<br> | |
| Active Comparator: low GDP PDF (Balance)<br> | Drug: Balance, Fresenius Medical Care, Germany<br>* low glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF)<br>* Other names: Balance, Fresenius Medical Care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammation-endothelial-dysfunction index (IEDI) | Inflammation-endothelial-dysfunction index (IEDI) is a composite score derived from measurement of serum levels of CRP (high sensitivity assay), soluble VCAM-1 and soluble ICAM-1. Changes between the groups will be tested by analysis of covariance (ANCOVA) with baseline values as covariates. Serial data will also be analyzed using a linear mixed model. | Baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Individual component markers of IEDI | individual component markers of the IEDI including sICAM-1, sVCAM-1, and hs-CRP | Baseline and 12 months | 
| RRF | residual renal function (RRF) as average of urea and creatinine clearances by 24 hour urine collection | Baseline and 12 months | 
| peritoneal clearance | peritoneal clearance as weekly Kt/V urea and creatinine clearance | Baseline and 12 months | 
| peritoneal ultrafiltration | peritoneal ultrafiltration volume | Baseline and 12 months | 
| peritoneal transport status | dialysate-to-plasma ratio of creatinine at 4 hours of peritoneal equilibration test | Baseline and 12 months | 
| serum albumin |  | Baseline and 12 months | 
| LBM | lean body mass (LBM) estimated from creatinine kinetics | Baseline and 12 months | 
| nPNA | normalized protein equivalent of nitrogen appearance (nPNA) | Baseline and 12 months | 
| SGA | subjective global assessment (SGA) with a four item and seven-point scale | Baseline and 12 months | 
| Blood pressure | systolic and diastolic blood pressure | Baseline and 12 months | 
| use of antihypertensive medications | number of antihypertensive medications | Baseline and 12 months | 
| peritonitis rates | peritonitis rates | 12 months | 
| technique survival | technique survival by Kaplan-Meier survival analysis with Log-Rank test. | 12months | 
| patient survival | patient survival by Kaplan-Meier survival analysis with Log-Rank test. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucose degradation products, Inflammation, Endothelial dysfunction, Soluble adhesion molecules, Peritoneal dialysis