The effect of prolonged of warm ischaemic injury on renal function in an experimental ex vivo normothermic perfusion system

Abstract

Background: Donation after circulatory death (DCD) kidney transplants inevitably sustain a degree of warm ischaemic injury, which is manifested clinically as delayed graft function. The aim of this study was to define the effects of prolonged periods of warm ischaemic injury on renal function in a normothermic haemoperfused kidney model.

Methods: Porcine kidneys were subjected to 15, 60, 90 (n = 6 per group) and 120 min (n = 4) of in situ warm ischaemia (WI) and then retrieved, flushed with cold preservation fluid and stored in ice for 2 h. Kidneys then underwent 3 h of normothermic reperfusion with a whole blood-based perfusate using an ex vivo circuit developed from clinical grade cardiopulmonary bypass technology.

Results: Creatinine clearance, urine output and fractional excretion of sodium deteriorated sequentially with increasing warm time. Renal function was severely compromised after 90 or 120 min of WI but haemodynamic, metabolic and histological parameters demonstrated the viability of kidneys subjected to prolonged warm ischaemia.

Conclusions: Isolated kidney perfusion using a warm, oxygenated, red cell-based perfusate allows an accurate ex vivo assessment of the potential for recovery from warm ischaemic injury. Prolonged renal warm ischaemic injury caused a severe decrement in renal function but was not associated with tissue necrosis.

Figure 1

a Mean renal blood flow during 3 h of reperfusion. Kidneys were subjected to 15, 60, 90 and 120 min of warm ischaemia (WI) followed by 2 h of static cold storage (SCS). *P < 0.05 15 min versus 60, 90 and 120 min groups. b Area under the curve renal blood flow. Kidneys were subjected to 15, 60, 90 and 120 min of warm ischaemia (WI) followed by 2 h of static cold storage (SCS). P = 0.084.

Figure 2

Mean serum creatinine levels during 3 h. Kidneys were subjected to 15, 60, 90 and 120 min of warm ischaemia (WI) followed by 2 h of static cold storage (SCS). *P = 0.004, 0.001, 15 min versus 90 and 120 min groups at 2 and 3 h of reperfusion, respectively.

Figure 3

Mean creatinine clearance at 1, 2 and 3 h of reperfusion. Kidneys were subjected to 15, 60, 90 and 120 min of warm ischaemia (WI) followed by 2 h of static cold storage (SCS). *P < 0.05 15 min versus 90 and 120 min.

Figure 4

Mean fractional excretion of sodium at 1, 2 and 3 h of reperfusion. Kidneys were subjected to 15, 60, 90 and 120 min of warm ischaemia (WI) followed by 2 h of static cold storage (SCS). * P = 0.003 15 min versus 90 and 120 min. **P = 0.005, 0.007 15 min versus 120 min group, respectively.

Figure 5

Mean urine output at 1, 2 and 3 h or reperfusion. Kidneys were subjected to 15, 60, 90 and 120 min of warm ischaemia (WI) followed by 2 h of static cold storage (SCS). *P < 0.001 15 min versus 60, 90 and 120 min. **P = 0.002, 0.001 15 min versus 90 and 120 min, respectively.