Introduction: The decedent model is limited by (i) the short period in which the decedent can be followed before hormonal, metabolic, and hemodynamic instability affect both the native and transplanted organs, and (ii) the major inflammatory response that occurs. Both factors can result in confusing data. The two studies of pig kidney transplantation (Tx) carried out to date in decedents, where follow-up was for only 3 days, illustrate these points (1,2). Although hyperacute rejection did not occur in the pig kidney grafts, this added little to what was already known from numerous in vitro studies in the pig-to-human model and in vivo studies in pig-to-nonhuman primate models.

Methods and Results: The first study (at NYU), involving two separate kidney transplants in two different decedents, was unfortunately limited by its design. (i) The native kidneys were not excised, making it difficult to determine pig kidney function. (ii) The kidney was from a GTKO pig and therefore was of little current relevance. (iii) Although no histopathological features of rejection were reported (except C4d staining in one kidney), if features of rejection had been present, this would have been attributed to the use of a GTKO (rather than a TKO) pig. (iv) There were absolutely no features suggesting inflammation associated with brain-death, questioning the reliability of the assays used.
The second study (at UAB), involving the Tx of both kidneys (from a TKO pig, weighing 160kg, with 6 transgenes) into the same recipient, was surprisingly unsuccessful. Neither kidney produced much urine nor excreted any creatinine. The serum creatinine rose from 2 to >6mg/dL and the BUN from 50 to >150mg/dL. Histopathological features of a thrombotic microangiopathy, leading to a consumptive coagulopathy (and “exsanguinating hemorrhage”), probably resulted because the experiment was not begun until the decedent had been brain-dead for 5 days, by which time the sequelae of brain death, e.g., increasing acidosis, were advanced. However, these events could have resulted from a xenogeneic immune response.
In neither study (i) was optimal immunosuppressive therapy (co-stimulation pathway blockade) administered, nor (ii) were the native recipient kidneys examined histologically, which may have differentiated the effects of brain death from those of a xenogeneic immune response.

Conclusions: The confusing results may be interpreted incorrectly by the transplant community, the regulators, and industry, and could cast unjustified doubts on the efficacy and safety of xenoTx. Although there are rare reports of brain-dead subjects being maintained for weeks of even months (e.g., to maintain survival of a fetus), xenoTx in such a decedent would likely not provide conclusive data acceptable to regulators. The studies had a positive effect in that they stimulated public interest, and made the transplant community, the regulators, and the public aware that clinical trials may soon be warranted.