Effect of Glucose Degradation Products (GDP) on Endothelial Dysfunction

Kyungpook National University

Status and phase

Completed

Phase 4

Conditions

Disorders Associated With Peritoneal Dialysis

Kidney Failure, Chronic

Treatments

Drug: Balance, Fresenius Medical Care, Germany

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01315314

A084001 (Other Grant/Funding Number)

IEDI MCS

Details and patient eligibility

About

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.

Full 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.

Enrollment

146 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No 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.