Biological Determinants of Peritoneal Dialysis

End-Stage Kidney Disease

Peritoneal Dialysis, Genetic, Peritoneal Membrane, Peritoneal Equilibrium Test, Ultrafiltration Capacity, End Stage Renal Disease (ESRD)

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.

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.

United States