Effect of Glucose Degradation Products (GDP) on Endothelial Dysfunction
Condition: Kidney Failure, Chronic; Disorders Associated With Peritoneal Dialysis
MeSH terms: Renal Insufficiency; Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Balance, Fresenius Medical Care, Germany
Intervention type(s): Drug
Intervention description(s): low glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF)
Other intervention name(s): Balance, Fresenius Medical Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Glucose degradation products; Inflammation; Endothelial dysfunction; Soluble adhesion molecules; Peritoneal dialysis