Hyperuricemia-induced alterations in albumin’s drug-binding capacity: clinical insights and review of spectroscopic approaches

Hyperuricemia, marked by elevated uric acid (UA) levels, induces conformational changes in human serum albumin (HSA)—the primary plasma protein mediating the transport of diverse endogenous and exogenous ligands. Such structural modifications can significantly alter HSA–ligand interactions, thereby influencing drug pharmacokinetics, efficacy, and safety. This article combines a pilot clinical investigation with a comprehensive review of recent spectroscopic studies. We synthesize current evidence from fluorescence, circular dichroism, infrared, Raman, nuclear magnetic resonance, and radiochemical assays to illustrate how hyperuricemia and related metabolic disturbances affect HSA’s binding behavior. In our pilot study of 220 patients, radiolabeled ligand-binding assays (LOQ ≈ 0.3 nM) demonstrated a 20–30% reduction in HSA binding capacity among hyperuricemic individuals compared to normouricemic controls. Тhese radiochemical findings provide a functional snapshot of altered albumin-binding <i>ex vivo</i>. By integrating these preliminary data with mechanistic insights from advanced spectroscopic literature, we underscore the translational potential of protein-binding analysis. In particular, we highlight its relevance for biomarker discovery, drug dosing optimization, and precision medicine strategies in high-risk populations.