The clearance of urea poses a formidable challenge, and its excessive accumulation can cause various renal diseases. Urease demonstrates remarkable efficacy in eliminating urea, but cannot be reused. This study aimed to develop a composite vector system comprising microcrystalline cellulose (MCC) immobilized with urease and metal−organic framework (MOF) UiO-66-NH 2 , denoted as MCC@UiO/U, through the dynamic defect generation strategy. By utilizing competitive coordination, effective immobilization of urease into MCC@UiO was achieved for efficient urea removal. Within 2 h, the urea removal efficiency could reach up to 1500 mg/g, surpassing an 80% clearance rate. Furthermore, an 80% clearance rate can also be attained in peritoneal dialyzate from patients. MCC@UiO/U also exhibits an exceptional bioactivity even after undergoing 5 cycles of perfusion, demonstrating remarkable stability and biocompatibility. This innovative approach and methodology provide a novel avenue and a wide range of immobilized enzyme vectors for clinical urea removal and treatment of kidney diseases, presenting immense potential for future clinical applications.