Biological Determinants of Peritoneal Dialysis (Bio-PD)

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.

Study Overview

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

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 Type: Observational
• Enrollment (Anticipated): 4865

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adults undergoing maintenance Peritoneal Dialysis therapy.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Discovery for Aim One; 2173 subjects will be involved in the discovery cohort.	Other: Peritoneal Equilibrium Test; These will be done as part of standard of care procedures. PETs will not be performed solely for research purposes.; Other: 4 hour dwell of 2.5/4.25% dextrose solution; If a PET is not performed annually as part of standard of care, subjects will undergo a 4 hour timed dwell with either 2.5 or 4.25% dextrose solution. This will be for the purposes of sample collection and/or measurement of ultrafiltration capacity.
Replication for Aim One; 1673 subjects will comprise the replication cohort.	Other: Peritoneal Equilibrium Test; These will be done as part of standard of care procedures. PETs will not be performed solely for research purposes.; Other: 4 hour dwell of 2.5/4.25% dextrose solution; If a PET is not performed annually as part of standard of care, subjects will undergo a 4 hour timed dwell with either 2.5 or 4.25% dextrose solution. This will be for the purposes of sample collection and/or measurement of ultrafiltration capacity.
Discovery for Aim Two; 824 subjects will be involved in the discovery cohort.	Other: Peritoneal Equilibrium Test; These will be done as part of standard of care procedures. PETs will not be performed solely for research purposes.; Other: 4 hour dwell of 2.5/4.25% dextrose solution; If a PET is not performed annually as part of standard of care, subjects will undergo a 4 hour timed dwell with either 2.5 or 4.25% dextrose solution. This will be for the purposes of sample collection and/or measurement of ultrafiltration capacity.
Replication for Aim Two; 538 subjects will comprise the replication cohort.	Other: Peritoneal Equilibrium Test; These will be done as part of standard of care procedures. PETs will not be performed solely for research purposes.; Other: 4 hour dwell of 2.5/4.25% dextrose solution; If a PET is not performed annually as part of standard of care, subjects will undergo a 4 hour timed dwell with either 2.5 or 4.25% dextrose solution. This will be for the purposes of sample collection and/or measurement of ultrafiltration capacity.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2015
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: February 12, 2016
• First Submitted That Met QC Criteria: February 26, 2016
• First Posted (Estimate): February 29, 2016

Study Record Updates

• Last Update Posted (Actual): December 10, 2021
• Last Update Submitted That Met QC Criteria: December 8, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Genetic; Peritoneal Dialysis; End Stage Renal Disease (ESRD); Peritoneal Membrane; Peritoneal Equilibrium Test; Ultrafiltration Capacity
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: STUDY00002027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No