Protective mechanisms of hypothermic machine perfusion (MP) remain largely unknown. Vascular branches of the renal arteries of 6 kidneys in 320 donors were unexpectedly injured during back table preparation, the injured portions of the kidneys lack perfusion (similar to CS), and the vascularized portions went through MP. The expression of α-smooth muscle actin in vascular smooth muscle in the MP portions was significantly lower, and the thickness of renal tubular epithelial cells in the MP portions also decreased. Furthermore, electron microscopy showed that the MP portions had less edema in podocytes and less structural damage and edema of mitochondria in renal tubular epithelial cells. To further elucidate mechanisms, the left kidney of rabbits underwent warm ischemia for 35 min, and then preserved by either CS or MP (4[deg] for 4 hours) in vivo followed by the right nephrectomy and 24 hours' reperfusion, the specimen was collected. The animal experiments demonstrated similar results to finding with the human kidneys. Furthermore, expression of flow based gene markers Krüppel-like Factors 2 (KLF2), eNOS, p-AKT and SOD in MP group were significantly higher than CS group(P<0.05), while the rate of apoptosis and expression of apoptosis and inflammation protein markers P-TβRII, p-SMAD-2/3, p-P38, p-JNK, p-ERK, TNF-a, IL-6 and MDA were lower in MP group (P<0.05). In conclusion, hypothermic machine perfusion through upregulating expression of KLF2 ameliorates vasospasm via p-AKT pathway and edema of podocytes and Renal Tubular Epithelial Cells by down-regulating the expression of TGF-β/p-SMAD and MAPK pathway.

CITATION INFORMATION: Zhong Z, Ko D, Wang Y, Ye Q. Hypothermic Machine Perfusion Ameliorates Vasospasm and Edema of Podocytes and Renal Tubular Epithelial Cells Through Upregulating Expression of Krüppel-Like Factors 2. Am J Transplant. 2016;16 (suppl 3).

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