176 Enzymatic conversion of blood group O human kidneys to rare Bombay type during hypothermic machine perfusion

Abstract Background ABO blood grouping compatibility restrictions present one of the first hurdles to recipient-donor matching in transplantation. While blood group O individuals would usually be described as ‘universal’ donors, a rare blood group called Bombay type is incompatible even with blood group O. Here, we describe the first use of a bacterial fucosidase enzyme called FucOB to convert human blood group O kidneys to the rare Bombay type during ex vivo hypothermic machine perfusion (HMP). Methods Four blood group O human kidneys declined for transplantation and offered for research were recruited to this study. The kidneys underwent 24h HMP with 5ug/ml FucOB and H antigen loss was assessed in serial biopsies throughout perfusion using immunofluorescence microscopy. Functional perfusion parameters were assessed continuously during perfusion, namely renal blood flow (RBF), mean arterial pressure (MAP) and intrarenal resistance (IRR). Results Haemodynamic parameters during 24h HMP were stable, with mean RBF of 70±6 ml/min/100g (mean ± SD), MAP of 22±1mmHg, and IRR of 0.19±0.02 mmHg/ml/min/100g. The mean temperature during perfusion was 3.5±0.3oC. Regarding blood group antigen expression, strong H antigen staining was observed in pre-perfusion samples. After 6h HMP + FucOB, H antigen expression was absent from the renal vasculature, demonstrating conversion to Bombay type. Conclusions This work successfully showed H antigen removal from human kidneys during HMP. This demonstrates the expansion of enzymatic blood group antigen conversion to provide transplant solutions to rare blood types.