The conditioning effect of ex vivo normothermic perfusion in an experimental kidney model

Abstract

Background: A short period of isolated normothermic perfusion (NP) can be used to improve the condition of the kidney after periods of warm and cold ischemic injury. However, the mechanisms underlying this beneficial effect have not been determined.

Materials and methods: Porcine kidneys were retrieved after 10 min of warm ischemic injury and stored by either static cold storage (CS) for 24 h (control) or CS for 23 h followed by 1 h of NP at 38°C with leukocyte-depleted autologous blood (NP). After preservation, kidneys in both groups underwent 3 h of ex vivo reperfusion to assess the injury (n = 6).

Results: NP kidneys had significantly lower levels of intrarenal resistance (NP 2.28 ± 1.1 versus control 3.86 ± 1.2 mm Hg/mL/h; P = 0.040), maintained their acid base homeostasis (P = 0.080), and had higher levels of oxygen consumption (NP 42.6 ± 19.5 versus control 20.8 ± 5.7 mL/min/g; P = 0.026) and reduced tubular injury (P = 0.008) compared with kidneys in the control group during reperfusion. There were no significant differences in the levels of inflammatory cytokines (interleukin [IL]-1β, IL-8, or tumor necrosis factor-α; P > 0.05) or in renal function (creatinine clearance NP 2.6 ± 1.3 versus control 3.0 ± 1.5 mL/min/100 g; P = 0.070). However, levels of IL-6 were significantly raised in the NP group after reperfusion (P = 0.016). Levels of heat shock protein 70 were upregulated after 1 h of NP and expression increased during reperfusion to a significantly higher level than in the control group (P = 0.045).

Conclusion: Kidneys undergoing a short period of NP had improved metabolic function and less tubular injury compared with static cold-stored kidneys. The increased expression of heat shock protein 70 and IL-6 suggests that NP may upregulate mechanisms that condition the kidney.