Effect of Glucose Degradation Products (GDP) on Endothelial Dysfunction

Sponsor

Kyungpook National University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01315314

Collaborator

Ministry of Health & Welfare, Korea (Other), Fresenius Medical Care Korea (Industry)

146

Enrollment

Location

Arms

Duration (Months)

4.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Failure, Chronic Disorders Associated With Peritoneal Dialysis	Drug: Balance, Fresenius Medical Care, Germany	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

146 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2005

Actual Primary Completion Date :

Apr 1, 2008

Actual Study Completion Date :

Apr 1, 2008

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Inflammation-endothelial-dysfunction index (IEDI) [Baseline and 12 months]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.