Disorders Associated With Peritoneal Dialysis, Kidney Failure, Chronic
Conditions
Keywords
Glucose degradation products, Inflammation, Endothelial dysfunction, Soluble adhesion molecules, Peritoneal dialysis
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.
Interventions
DRUGBalance, Fresenius Medical Care, Germany
low glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF)
Sponsors
Ministry of Health & Welfare, Korea
Fresenius Medical Care Korea
Kyungpook National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Individual component markers of IEDI | Baseline and 12 months | individual component markers of the IEDI including sICAM-1, sVCAM-1, and hs-CRP |
| 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. |
| nPNA | Baseline and 12 months | normalized protein equivalent of nitrogen appearance (nPNA) |
Countries
South Korea
Outcome results
None listed