Hyperhomocysteine: a key mediator linking chronic kidney disease to parkinson’s disease

Abstract Background Chronic kidney disease affects more than 10% of the global population and is associated with elevated Parkinson’s disease risk, substantially compromising patients’ quality of life. However, the precise pathophysiological mechanisms underlying this association remain unclear. This review aims to synthesize current evidence and explore the potential pathophysiological mechanisms linking chronic kidney disease to the pathogenesis of Parkinson’s disease. Main Body Hyperhomocysteinemia, characterized by elevated homocysteine levels, is a common metabolic disturbance in both chronic kidney disease and Parkinson’s disease. In CKD, impaired renal clearance and metabolic dysfunction lead to homocysteine accumulation. This review examines the hypothesis that hyperhomocysteinemia serves as a key biochemical mediator, linking the two diseases by driving neurodegenerative processes central to Parkinson’s disease pathogenesis, including oxidative stress, chronic neuroinflammation, and neuronal apoptosis, which culminate in dopaminergic neurodegeneration. Conclusions This review delineates the pathogenic pathways linking CKD to Parkinson’s disease through hyperhomocysteinemia, positioning it as a plausible and actionable intermediary. Addressing hyperhomocysteinemia has emerged as a rational strategy with the potential to elucidate disease mechanisms and mitigate Parkinson’s disease risk in the vulnerable chronic kidney disease population.