Effect of Glucose Degradation Products (GDP) on Endothelial Dysfunction

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Failure, Chronic; Disorders Associated With Peritoneal Dialysis
• Intervention / Treatment: Drug: Balance, Fresenius Medical Care, Germany

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of, 700-721
    • Division of Nephrology and Department of Internal Medicine, Kyungpook National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kyungpook National University Hospital
• Collaborators: Ministry of Health & Welfare, Korea; Fresenius Medical Care Korea
• Investigators: Study Chair: Yong-Lim Kim, Professor, Kyungpook National University Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: March 11, 2011
• First Submitted That Met QC Criteria: March 14, 2011
• First Posted (Estimate): March 15, 2011

Study Record Updates

• Last Update Posted (Estimate): March 17, 2011
• Last Update Submitted That Met QC Criteria: March 16, 2011
• Last Verified: April 1, 2007

More Information

Terms related to this study

• Keywords: Inflammation; Endothelial dysfunction; Peritoneal dialysis; Glucose degradation products; Soluble adhesion molecules
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: IEDI MCS; A084001 (Other Grant/Funding Number: Ministry for Health and Welfare, Republic of Korea (A084001))