Abstract: End-stage renal disease（ESRD） due to various chronic kidney diseases has a high morbidity and mortality rate. Cognitive impairment（CI） affects negatively long-term prognosis and quality-of-life. However, the mechanisms and intervention strategies for CI have remained elusive. This review focused upon the central role of uremic toxins in inducing endothelial dysfunction, an imbalance of bone metabolism and remote sensing and signaling through cardiovascular and neurotoxic effects. Furthermore, it elaborated upon dynamic retinal vascular analysis, optimal blood purification protocol, pharmacological management and nutritional interventions, aiming at improving cognitive function and prognosis of ESRD patients.