New Approaches to the Removal of Protein-Bound Toxins from Blood Plasma of Uremic Patients

Abstract

The article is devoted to the theoretical aspects of the development of the effective method for the removal of protein-bound uremic toxins. It is shown that the methods of flow and differential scanning microcalorimetry are sufficient enough for the evaluation of the degree of ligand loading of human serum albumin with protein-bound uremic toxins. The molecules of albumin isolated from blood plasma of the patients being kept on chronic dialysis are demonstrating significant alterations of conformation and complex-forming properties, the correction of which by conventional methods of extracorporeal detoxification (exhaustive dialysis, treatment on synthetic SCN carbons) are practically ineffective. Deliganding of uremic albumin may be successfully performed on conventional carbon haemosorbents upon preliminary separation of blood plasma and its dilution with acetate buffer 1:1 at pH = 5.08. Treatment of the whole blood of patients onto new mass-fractal deliganding carbon, i.e., hemosorbents of HSGD trademark. These HSGD haemosorbents quite effectively could be used for restoration of main parameters of uremic HAS molecules conformation and ligand-binding activity simultaneously with hemodialysis upon the protection by locally performed citrate anticoagulation as an easier and cheaper method for the removal of protein-bound uremic toxins.

Elimination of Endogenous Toxin, Creatinine from Blood Plasma Depends on Albumin Conformation: Site Specific Uremic Toxicity & Impaired Drug Binding

“…The toxin renders the strongest influence on the endotherms (more pronounce for basic isomer of HSA, Figure 1D) by transforming the unimodal curve of its melting to a bimodal one. As it follows from Figure 1, on reaching from normal to maximal uremic condition, the melting curve was practically identical to that for the complex “albumin-nonconjugated bilirubin” [37].…”

Cardiotoxicity of Uremic Toxins: A Driver of Cardiorenal Syndrome

“…Most are small (MW of < 500 Da) and bound to albumin (MW ~66,500 Da [ 29 ]). Retention of protein-bound molecules can competitively inhibit albumin binding of some drugs [ 30 , 31 , 32 ], thereby increasing risk of drug toxicity in uremic patients. Removal of these compounds is also severely limited by conventional or high-flux hemodialysis.…”

Activation and structural and adsorption features of activated carbons with highly developed micro-, meso- and macroporosity

“…(Rodriguez-Reinoso 2006;Marsh et al 1997;Bansal et al 1988;Silvestre-Albero et al 2010). Superactivated carbon materials gained special importance in medicine, particularly, in the problem of removal of strongly protein-bound toxins and proinflammatory cytokines from whole blood and blood plasma (Sarnatskaya et al 2002(Sarnatskaya et al , 2007. However, certain regularities in the structure-property relationships for activated and superactivated carbons need additional investigations.…”