Mechanisms and treatment of cold-storage-induced microvascular obstructions in normothermic machine perfusion of human kidney

Human kidneys which were accepted for transplantation and subsequently not used were subjected to ex vivo normothermic machine perfusion. During perfusion it was found the tubular epithelia synthesized fibrinogen which led to red blood cell aggregation and pathologic plugging of renal microvasculature. Sequential ex vivo delivery of plasminogen and tissue plasminogen activator (tPA) during normothermic machine perfusion effectively lyses these fibrinogen-mediated plugs. Pairs of human kidneys were subjected to ex vivo normothermic perfusion. One kidney in each pair was treated and the other not. Samples were taken pre- and post-perfusion for RNASeq.