Proteomic Analysis of Peritoneal Dialysate Fluid in Patients with Different Types of Peritoneal Membranes

Abstract

Efficacy of peritoneal dialysis is determined by solute transport through peritoneal membranes. With the use of the peritoneal equilibration test (PET), peritoneal membranes can be classified as high (H), high average (HA), low average (LA), and low (L) transporters, based on the removal or transport rate of solutes, which are small molecules. Whether there is any difference in macromolecules (i.e., proteins) removed by different types of peritoneal membranes remains unclear. We performed a gel-based differential proteomics study of peritoneal dialysate effluents (PDE) obtained from chronic peritoneal dialysis (CPD) patients with H, HA, LA, and L transport rates (n=5 for each group; total n=20). Quantitative analysis and ANOVA with Tukey's posthoc multiple comparisons revealed five proteins whose abundance in PDE significantly differed among groups. These proteins were successfully identified by matrix-assisted laser desorption ionization quadrupole time-of-flight (MALDI-Q-TOF) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) analyses, including serum albumin in a complex with myristic acid and triiodobenzoic acid, alpha1-antitrypsin, complement component C4A, immunoglobulin kappa light chain, and apolipoprotein A-I. The differences among groups in PDE levels of C4A and immunoglobulin kappa were clearly confirmed in a validation set of the other 24 patients (n=6 for each group) using ELISA. These data may lead to better understanding of the physiology of peritoneal membrane transport in CPD patients. Extending the study to a larger number of patients with subgroup analyses may yield additional information of the peritoneal dialysate proteins in association with dialysis adequacy, residual renal function, nutritional status, and risk of peritoneal infection.