Effects of endothelin receptor antagonism in an experimental model of renal transplantation

Aim: Uncontrolled Donation after Circulatory Death (uDCD) donors provide a large potential source of kidneys but there is reluctance to use them due to prolonged warm ischaemic times. Endothelin-1, a potent vasoconstrictor, is a major contributor to ischaemic injury. This study aimed to investigate the benefit of endothelin receptor blockade in an experimental model of uDCD transplantation. Methods: Porcine kidneys underwent 60 minutes warm ischaemia and 2 hours cold ischaemia followed by 3 hours of reperfusion with autologous blood without (control, n = 6) and with (n = 6) 500μg BQ-123, a selective ETA endothelin receptor antagonist. Markers of renal function and injury were analysed. Results: Renal blood flow was significantly higher in the experimental group at 15–30 minutes of reperfusion (29.6–37.7 vs. 13.1–18.2 ml/min/100 g, p = 0.02), after which, although higher throughout, statistical significance was lost. Urine output, creatinine clearance and oxygen consumption were also higher in the experimental group throughout but statistical significance was only seen in the 1st hour urine output (83 vs. 32 ml/hr, p = 0.01). Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) levels were not different between the groups. Conclusion: Kidneys can recover from warm ischaemic injury. BQ-123 appeared to improve perfusion and function initially but did not have a sustained effect or significant overall benefit.