Active Molecular Interception: De Novo Designed Proteins as a New Paradigm in the Management of Uremic Toxins

Abstract

Chronic kidney disease (CKD) constitutes a major global public health challenge whose therapeutic management relies almost exclusively on renal replacement therapies (RRT) based on physical principles of filtration, diffusion, and passive convection. Although hemodialysis and peritoneal dialysis are effective in controlling fluid balance and small solutes, they exhibit significant limitations in the removal of protein-bound uremic toxins (PBUTs), which substantially contribute to cardiovascular and systemic morbidity and mortality. This work proposes a disruptive hypothesis: the implementation of active metabolic modulators based on de novo designed proteins. Unlike conventional mechanical clearance, this strategy envisions the use of computationally engineered proteins with thermodynamic affinities exceeding that of albumin to selectively sequester specific toxins or catalyze their degradation within the bloodstream. This approach represents the transition from passive depuration to active molecular control, grounded in recent advances in synthetic biology, deep learning, and computational protein design. The present proposal is conceptual in nature and requires progressive experimental validation in in vitro and ex vivo models prior to any translational consideration.