Patients with end-stage renal disease (ESRD) treated with peritoneal dialysis (PD) have similar long-term survival as of patients treated with in-center hemodialysis but have better patient-reported outcomes and the therapy can be delivered at a lower societal cost. The use of PD for the treatment of ESRD is increasing in the United States but annually, 20% of patients still transfer to hemodialysis from PD-related complications (technique failure).
Successful management of ESRD with PD requires the movement of adequate amounts of solutes and fluid across the peritoneal membrane. The data to date suggest that the variability in peritoneal membrane function and injury may, in part, be genetically determined. However, candidate gene association studies have produced inconsistent results, have examined a limited number of mechanistic pathways, and a small proportion of the variation in a handful of genes. Hence, there is a need to comprehensively determine whether the variability in peritoneal membrane function is determined genetically. Identification of common genetic variants associated with peritoneal membrane function and injury has the potential to lead to the development of biomarkers for early detection of peritoneal membrane injury, and/or identify therapeutic targets to preserve peritoneal membrane function in the future. Given the importance of peritoneal membrane function to successful PD, there is a critical need to better understand the biology of peritoneal membrane function and how it is influenced by genetic variation. Thus, the central hypothesis of this proposal is that common genetic variants explain the inter-individual variability in peritoneal membrane function in patients undergoing PD.