Kidney failure leads to the accumulation of metabolites in the blood compartment. This build-up of metabolites has been associated with increased mortality and morbidity in these patients; thus, these metabolites are commonly called uremic toxins. The retention of some uremic toxins in the blood results from a strong interaction with serum albumin, preventing their clearance using standard hemodialysis techniques. Adsorbents are considered the next-generation technology for clearing uremic toxins from the blood, and iron oxide magnetic nanoparticles are a promising material due to a high surface area that is easily modified and the ability to remove them from blood with an external magnetic field. Plasma protein adsorption and clot formation kinetics were determined for unmodified and albumin-modified iron oxide magnetic nanoparticles. Albumin was selected because it can bind uremic toxins, and it is commonly used to passivate surfaces. Coatings were formed and characterized using transmission electron microscopy, thermogravimetric analysis, and zeta-potential analysis. Clotting kinetics, total protein assays, and immunoblots were used to analyze the effect surface modification has on protein adsorption events. Unmodified nanoparticles showed rapid clotting and more adsorbed protein compared to albumin-coated iron oxide nanoparticles. Immunoblots show that modified particles showed changes in albumin, protein C, Immunoglobulin G, transferrin, fibrinogen, α1-antitrypsin, vitronectin, plasminogen, prothrombin, and antithrombin levels compared to unmodified controls. The hemocompatibility of adsorbent materials is essential to their clinical application in clearing the blood of uremic toxins.
4 December 2024 in ACS Biomaterials Science & Engineering
When the kidneys are injured, uremic toxins (UTXs) accumulate in the body, affecting other tissues and causing a loss of essential body functions. This study investigated the adsorption of blood plasma-laden uremic toxins on the surface of PCL fibers to assess their potential as an alternative to membrane dialysis materials. Using plasma containing 25 uremic toxins at a concentration similar to that found in end-stage kidney disease patients, we analyzed the adsorbed proteins and examined clot formation in normal and toxin-treated plasma in the presence of PCL fiberss. Our findings revealed that the presence of uremic toxins significantly increased the adsorption of proteins on PCL fiber meshes, without leading to increased clot formation. This suggests a lack of enzymatic activation despite the higher protein adsorption. Additionally, our study indicates that unmodified PCL surfaces have the potential to trigger a strong humoral immune response, underscoring the importance of understanding these interactions for the development of personalized treatment approaches for patients with kidney failure.