*Purpose: Advances are desperately needed to increase the supply of transplantable kidneys for the 100,000 patients on the waiting list. Whole organ engineering is one approach that holds tremendous promise and to date, the most successful approach utilizes perfusion decellularization to provide the ideal kidney extracellular matrix scaffold that maintains the organ’s native vasculature and architecture, and allows recellularization with human cells. A critical component and the focus of the current study is to demonstrate the ability to functionally revascularize clinically relevant whole kidney matrix with human endothelial cells and provide sustained in vivo perfusion following orthotopic implantation.

*Methods: Kidneys recovered from adult pigs were decellularized via detergent perfusion through the vasculature. The porcine matrix was seeded with human umbilical vein endothelial cells (HUVECs) and cultured using a custom perfusion recellularization bioreactor until sufficient cellular coverage of the vasculature was obtained. Functional testing of the renal vascular bed was performed using an ex vivo porcine blood flow model. Re-endothelialized kidney grafts were transplanted orthotopically in a pig model and evaluated with angiography at days 3, 7, 10, and 14 days before explantation.

*Results: A minimum glucose consumption rate of 20 mg/hr was determined to represent a threshold above which kidney grafts were determined to have sufficient histological vascular coverage with endothelial cells and thromboresistance with vascular patency when assessed using short term ex vivo blood loops. At 7 days post in vivo implantation, 83.3% (n=5/6 pigs) of kidney grafts maintained renal perfusion during follow-up angiography and one kidney graft remained patent through day 14, which is the longest reported perfusion for a recellularized kidney graft.

*Conclusions: These results lay the foundation for the future long-term success of human-scale recellularized kidney grafts, and move the field closer to an alternative for kidney allotransplantation.

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