Leucocyte depletion improves renal function in porcine kidney hemoreperfusion through reduction of myeloperoxidase+ cells, caspase-3, IL-1ß, and tubular apoptosis.

ABSTRACT

BACKGROUND: Leucocytes play crucial roles in ischemia reperfusion injury that is inevitable in kidney transplantation. Leucocyte-depleted hemoreperfusion improved post-ischemic renal function was demonstrated in our previous study and its underlying mechanisms were further investigated in this study. METHODS: Porcine kidneys were subjected to 7 min warm ischemia and 2 h cold storage, and preserved by hemoreperfusion with or without leucocyte depletion for 6 h on an isolated organ perfusion system. RESULTS: Tubulointerstitial damage was improved by leucocyte depletion, which was accompanied by reduced myeloperoxidase+ cell infiltration up to 91%. Apoptotic cells in tubular and interstitial areas were increased by hemoreperfusion, but tubular apoptosis was decreased by leucocyte depletion. The raised caspase-3 activity by hemoreperfusion was almost completely abolished by leucocyte depletion. In addition, the expression of IL-1ß active subunit was enhanced by hemoreperfusion, but partially reduced by leucocyte depletion, although IL-1ß precursor and HSP70 were increased by hemoreperfusion regardless of leucocyte depletion. Furthermore, myeloperoxidase+ cells were associated with caspase-3 activity, both of which were positively correlated with tubular apoptosis, IL-1ß active subunit, tubulointerstitial damage, and serum creatinine, while HSP70 was linked to renal blood flow. CONCLUSIONS: Leucocyte depletion improved post-ischemic renal function and structure was mainly due to reduced infiltration of myeloperoxidase+ cells, which was associated with decreased apoptosis, caspase-3 activity and IL-1ß activation.