Effect of Glucose Degradation Products (GDP) on Endothelial Dysfunction
|Kidney Failure, Chronic Disorders Associated With Peritoneal Dialysis||Drug: Balance, Fresenius Medical Care, Germany||Phase 4|
|Study Design:||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|
- Inflammation-endothelial-dysfunction index (IEDI) [ Time Frame: 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.
- Individual component markers of IEDI [ Time Frame: Baseline and 12 months ]individual component markers of the IEDI including sICAM-1, sVCAM-1, and hs-CRP
- RRF [ Time Frame: Baseline and 12 months ]residual renal function (RRF) as average of urea and creatinine clearances by 24 hour urine collection
- peritoneal clearance [ Time Frame: Baseline and 12 months ]peritoneal clearance as weekly Kt/V urea and creatinine clearance
- peritoneal ultrafiltration [ Time Frame: Baseline and 12 months ]peritoneal ultrafiltration volume
- peritoneal transport status [ Time Frame: Baseline and 12 months ]dialysate-to-plasma ratio of creatinine at 4 hours of peritoneal equilibration test
- serum albumin [ Time Frame: Baseline and 12 months ]
- LBM [ Time Frame: Baseline and 12 months ]lean body mass (LBM) estimated from creatinine kinetics
- nPNA [ Time Frame: Baseline and 12 months ]normalized protein equivalent of nitrogen appearance (nPNA)
- SGA [ Time Frame: Baseline and 12 months ]subjective global assessment (SGA) with a four item and seven-point scale
- Blood pressure [ Time Frame: Baseline and 12 months ]systolic and diastolic blood pressure
- use of antihypertensive medications [ Time Frame: Baseline and 12 months ]number of antihypertensive medications
- peritonitis rates [ Time Frame: 12 months ]peritonitis rates
- technique survival [ Time Frame: 12months ]technique survival by Kaplan-Meier survival analysis with Log-Rank test.
- patient survival [ Time Frame: 12 months ]patient survival by Kaplan-Meier survival analysis with Log-Rank test.
|Study Start Date:||October 2005|
|Study Completion Date:||April 2008|
|Primary Completion Date:||April 2008 (Final data collection date for primary outcome measure)|
|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 Name: Balance, Fresenius Medical Care
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01315314
|Korea, Republic of|
|Division of Nephrology and Department of Internal Medicine, Kyungpook National University Hospital|
|Daegu, Korea, Republic of, 700-721|
|Study Chair:||Yong-Lim Kim, Professor||Kyungpook National University|