Kidney failure occurs when the kidneys can no longer effectively filter waste compounds from the blood, leading to a systemic accumulation of uremic toxins that disrupt hemostasis. Non-specific protein adsorption at the blood-material interface is well-known to direct subsequent host responses. Thus, to develop blood-contacting materials that may become an alternative to traditional dialysis membranes, we explored the effect that uremic toxins have on the adsorption of plasma proteins to Janus membranes. A human plasma system infused with 26 major uremic toxins was designed to replicate the concentrations found in kidney failure patients. This system allowed for the analysis of adsorbed human plasma proteins and clot formation in normal and toxin-treated plasma in the presence of polycaprolactone (PCL)/ethylene vinyl alcohol (EVOH) nanofibers. The findings revealed that uremic toxins significantly increased protein adsorption on PCL/EVOH nanofiber meshes without causing increased clot formation, indicating a lack of enzymatic activation despite higher protein adsorption. Furthermore, the study suggested that unmodified PCL/EVOH surfaces have the potential to trigger a strong humoral immune response, emphasizing the need to understand these interactions for the development of personalized treatment strategies for patients with kidney failure.