Vasoreactivity as a Measure of Kidney Viability During Ex Vivo Normothermic Machine Perfusion

Normothermic machine perfusion (NMP) could serve as a platform to assess deceased-donor kidney viability before transplantation, yet it remains unclear which parameters indicate renal viability. As vascular integrity is important for adequate renal function after transplantation, this study aimed to investigate the influence of warm ischemic injury on vascular smooth muscle cell (VSMC) responsiveness to vasoactive drugs during NMP.

Fourteen porcine kidneys (n = 7 per group) were exposed to either 30 or 60 min of warm ischemia (WI), followed by 3.5 h of cold machine perfusion. After cold perfusion, kidneys underwent 4 h of NMP (37°C). During NMP, vasoactive drugs were sequentially infused into the renal artery at 30-min intervals, starting with epoprostenol (10 μg), followed by dopamine (1 mg), sodium nitroprusside (2 mg), acetylcholine (1 mg), norepinephrine (10 μg), and finally verapamil (2.5 mg).

Renal blood flow during NMP changed significantly in both groups after administration of dopamine, acetylcholine, norepinephrine, and verapamil, but not following epoprostenol and sodium nitroprusside infusion. In kidneys subjected to 30 min of WI, the response to dopamine and norepinephrine was more pronounced, and oxygen consumption and blood pH were higher compared to kidneys that sustained 60 min of WI.

This study indicates that prolonged WI damage diminishes the contractility of VSMCs through the α-adrenergic receptors. Our findings suggest that the renal vascular responses to dopamine and norepinephrine, as well as decreased oxygen consumption and blood pH, could serve as objective indicators to quantify warm ischemic injury during renal NMP.