Effect of Glucose Degradation Products (GDP) on Endothelial Dysfunction

Kidney Failure, Chronic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01315314
• Other study ID #: IEDI MCS
• Secondary ID: A084001
• Status: Completed
• Phase: Phase 4
• First received: March 11, 2011
• Last updated: March 16, 2011
• Start date: October 2005
• Est. completion date: April 2008

Study information

• Verified date: April 2007
• Source: Kyungpook National University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 146
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Disorders Associated With Peritoneal Dialysis
• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Drug:
• Balance, Fresenius Medical Care, Germany
low glucose degradation product (GDP)-containing peritoneal dialysis fluid (PDF)

Locations

Country	Name	City	State
Korea, Republic of	Division of Nephrology and Department of Internal Medicine, Kyungpook National University Hospital	Daegu

Sponsors (3)

Lead Sponsor	Collaborator
Kyungpook National University	Fresenius Medical Care Korea, Ministry of Health & Welfare, Korea

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inflammation-endothelial-dysfunction index (IEDI)	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.	Baseline and 12 months	No
Secondary	Individual component markers of IEDI	individual component markers of the IEDI including sICAM-1, sVCAM-1, and hs-CRP	Baseline and 12 months	No
Secondary	RRF	residual renal function (RRF) as average of urea and creatinine clearances by 24 hour urine collection	Baseline and 12 months	No
Secondary	peritoneal clearance	peritoneal clearance as weekly Kt/V urea and creatinine clearance	Baseline and 12 months	No
Secondary	peritoneal ultrafiltration	peritoneal ultrafiltration volume	Baseline and 12 months	No
Secondary	peritoneal transport status	dialysate-to-plasma ratio of creatinine at 4 hours of peritoneal equilibration test	Baseline and 12 months	No
Secondary	serum albumin		Baseline and 12 months	No
Secondary	LBM	lean body mass (LBM) estimated from creatinine kinetics	Baseline and 12 months	No
Secondary	nPNA	normalized protein equivalent of nitrogen appearance (nPNA)	Baseline and 12 months	No
Secondary	SGA	subjective global assessment (SGA) with a four item and seven-point scale	Baseline and 12 months	No
Secondary	Blood pressure	systolic and diastolic blood pressure	Baseline and 12 months	No
Secondary	use of antihypertensive medications	number of antihypertensive medications	Baseline and 12 months	No
Secondary	peritonitis rates	peritonitis rates	12 months	No
Secondary	technique survival	technique survival by Kaplan-Meier survival analysis with Log-Rank test.	12months	No
Secondary	patient survival	patient survival by Kaplan-Meier survival analysis with Log-Rank test.	12 months	No