Biological Determinants of Peritoneal Dialysis

Completed

• Conditions: End-Stage Kidney Disease
• Interventions: Other: Peritoneal Equilibrium Test; Other: 4 hour dwell of 2.5/4.25% dextrose solution

• Registration Number: NCT02694068
• Lead Sponsor: University of Washington

Brief Summary

Peritoneal Dialysis (PD) is a technique for treating kidney failure where fluid is instilled into the body's peritoneal cavity. Fluid and solutes travel across the peritoneal membrane, and the function of this membrane is critical to successful PD. Studies have shown that certain demographic and clinical variables explain a very small part of the variability in baseline function. This study will further explore the common genetic variants that determine the baseline peritoneal membrane function in patients starting treatment with PD and change in function upon treatment .

This study will incorporate data from subjects' first ever peritoneal equilibrium test (PET), changes in the transfer of water across the peritoneal membrane over time, demographic information, and results from laboratory analysis of DNA, blood, and dialysate. The investigators hope that this study will provide information on the biological pathways that account for variability in the peritoneal membrane. This could ultimately lead to the development of biomarkers to identifying individuals at risk for decline in peritoneal membrane function over time and/or be used to identify novel therapeutic targets to preserve or enhance membrane function. Identifying the biological pathways will also increase the understanding of vascular biology, angiogenesis, and fibrosis that could be applied to other tissues and other diseases.

Detailed Description

This study will comprise of patient populations from pre-existing biorepositories and prospectively enrolled subjects. DNA will be analyzed from cohorts with data and DNA already collected and available, while prospective sites will collect plasma, DNA, and spent dialysate for further analysis. Clinical data related to the subjects' first ever Peritoneal Equilibrium Test (PET), demographic information, change in ultrafiltration capacity over time, will be correlated with various genetic markers of interest.

Blood and dialysate will be collected at the first study visit, and there will be no additional sample collection. These samples will be collected as part of a PET during a standard of care study visit, or during a timed 4 hour dwell of 2.5% or 4.25% dextrose solution. Annually, subjects will either undergo a PET as standard of care or perform an additional 4 hour dwell as part of the study. These subsequent measures will be utilized to determine change in ultrafiltration capacity over time.

This study has two specific aims:

Aim 1: To identify and validate genetic loci that influence the peritoneal solute transfer rate (PSTR) at start of PD.

Aim 2: To identify and validate genetic loci in pre-specified biologic pathways with change in peritoneal ultrafiltration capacity.

If subjects grant permission, Genome Wide Association Studies (GWAS) results may be transferred to the NIH database of genotypes and phenotypes (dbGaP). Additionally, subjects may agree that remaining samples will be maintained at the University of Washington Kidney Research Institute in a repository for use in future research studies.

Study Timeline

• Study Start: 2015-09-15
• Study First Submitted: 2016-02-12
• Study First Submitted QC: 2016-02-26
• Study First Posted: 2016-02-29
• Primary Completion: 2019-08-01
• Study Completion: 2019-08-01
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-08
• Last Update Posted: 2021-12-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4865

Inclusion Criteria

• Adults over the age of 20 who are able to provide consent
• Record of a PET within 6 months of starting PD treatment

Exclusion Criteria

• None

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Discovery for Aim One	Peritoneal Equilibrium Test	2173 subjects will be involved in the discovery cohort.
Discovery for Aim One	4 hour dwell of 2.5/4.25% dextrose solution	2173 subjects will be involved in the discovery cohort.
Replication for Aim Two	Peritoneal Equilibrium Test	538 subjects will comprise the replication cohort.
Replication for Aim One	4 hour dwell of 2.5/4.25% dextrose solution	1673 subjects will comprise the replication cohort.
Discovery for Aim Two	4 hour dwell of 2.5/4.25% dextrose solution	824 subjects will be involved in the discovery cohort.
Discovery for Aim Two	Peritoneal Equilibrium Test	824 subjects will be involved in the discovery cohort.
Replication for Aim One	Peritoneal Equilibrium Test	1673 subjects will comprise the replication cohort.
Replication for Aim Two	4 hour dwell of 2.5/4.25% dextrose solution	538 subjects will comprise the replication cohort.

Primary Outcome Measures

Name	Time	Method
Four-hour Dialysate to Plasma ratio of creatinine	Prior to study participation or within 6 months of enrollment	From Peritoneal Equilibration Test performed at the time of start of PD
Change in peritoneal ultrafiltration capacity over time	Once per year (up to 3 years)	This will be determined from annual assessments of the peritoneal ultrafiltration capacity with a four-hour timed dwell with 4.25%/2.5% dextrose.

Trial Locations

Locations (1)

University of Washington; 🇺🇸 Seattle, Washington, United States