Packed Red Blood Cell and Whole Blood Perfusates during Ex Vivo Normothermic Perfusion for Assessment of High-Risk Donor Kidneys

Key Points Compared with whole blood (WB) kidneys perfused with a packed red blood cells perfusate exhibited superior kidney functional parameters. Metabolomics assessment showed drastic metabolic aberration in the WB group involving amino acid, carbohydrate, and mitochondrial energy metabolism. Tissue lipid profiling demonstrated that WB was associated with accumulation of tissue membrane/structure components including glycerolipids and ceramides. Background Ex vivo normothermic perfusion (EVNP) with a blood-based perfusate has the potential to both assess viability of and repair high-risk organs before transplantation. The optimal perfusate is yet to be established. Methods We assessed hemodynamic, functional, and metabolic changes of eight paired high-risk human kidneys perfused with either a leukocyte-depleted packed red blood cell (PRBC) or a whole blood (WB) perfusate during a 3-hour EVNP. Results After a mean cold ischemia time of 54 hours, all kidneys showed high renal blood flow through perfusion. Renal resistance increased for both groups during the first hour and then decreased to similar terminal values. The kidneys perfused with PRBC had 55 ml/min greater renal blood flow (95% confidence interval, 21 to 89; P = 0.004) and higher total urine output (145 versus 25 ml, P = 0.002) compared with the WB group. Urinary acute kidney biomarkers of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 were also significantly lower (mean differences of 281 and 2.1 ng/ml, respectively; P < 0.01) in the PRBC perfused kidneys. Compared with PRBC, within-group tissue metabolic profiling revealed a similar (23% versus 18%) but a more pronounced alteration involving (branched chain) amino acid and mitochondrial energy metabolism in the WB group. Similarly, lipid profile temporal changes showed that WB groups were highlighted by elevation of plasma membrane and structure lipids including glycerolipids, sphingolipids, and steroids. The PRBC group had minimal temporal tissue lipid profile changes. Conclusions Compared with WB, PRBC perfusion is superior in mitigating postischemia damage and facilitating function and metabolic recovery of high-risk kidneys subjected to long cold ischemia times during a 3-hour EVNP.