Clinical trial NCT01315314: Effect of Glucose Degradation Products (GDP) on Endothelial Dysfunction
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Failure, Chronic
Disorders Associated With Peritoneal Dialysis
Keywords: Glucose degradation products
Inflammation
Endothelial dysfunction
Soluble adhesion molecules
Peritoneal dialysis
Lead sponsor: Kyungpook National University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Health & Welfare, Korea
name: Fresenius Medical Care Korea
First posted: 2011-03-15
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Inflammation-endothelial-dysfunction index (IEDI)
timeFrame: Baseline and 12 months
Secondary outcomes:
measure: Individual component markers of IEDI
timeFrame: Baseline and 12 months
measure: RRF
timeFrame: Baseline and 12 months
measure: peritoneal clearance
timeFrame: Baseline and 12 months
measure: peritoneal ultrafiltration
timeFrame: Baseline and 12 months
measure: peritoneal transport status
timeFrame: Baseline and 12 months
measure: serum albumin
timeFrame: Baseline and 12 months
measure: LBM
timeFrame: Baseline and 12 months
measure: nPNA
timeFrame: Baseline and 12 months
measure: SGA
timeFrame: Baseline and 12 months
measure: Blood pressure
timeFrame: Baseline and 12 months
measure: use of antihypertensive medications
timeFrame: Baseline and 12 months
measure: peritonitis rates
timeFrame: 12 months
measure: technique survival
timeFrame: 12months
measure: patient survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
facility: Division of Nephrology and Department of Internal Medicine, Kyungpook National University Hospital
Study officials:
affiliation: Kyungpook National University Hospital
name: Yong-Lim Kim, Professor
role: STUDY_CHAIR
References: