Peritoneal dialysis (PD) is a modality of renal replacement therapy in which the high volumes of available PD effluent (PDE) represents a rich source of biomarkers for monitoring disease and therapy. Although this information could help guiding the management of PD patients, little is known about the potential of PDE to define pathomechanism-associated molecular signatures in PD. Here we use a high-performance multiplex proteomics approach based on depletion of highly abundant plasma proteins and enrichment of low abundance proteins for PDE samples from PD patients of a phase 2 randomized clinical trial, who received either standard PD fluid or a novel PD fluid (added alanyl-glutamine (AlaGln)) in an open-label, randomized, single-center, cross-over clinical trial.