Re: a case-control comparison of the results of renal transplantation from heart-beating and non-heart-beating donors.

Abstract

COMMENTARY The results of the Leicester group confirm the plea for the use of kidneys from non-heart-beating (NHB) donors. It is the second study that proofs with matched-controls that there is no difference in long-term outcome between heart-beating (HB) and NHB donor kidneys, theirs in a single center, ours in a multicenter study (1). What is special in this Leicester program and what makes it so successful? (1) Most of the NHB donor kidneys come from category 2 donors therefore the exact amount of ischemia can only be guessed. They do not test their NHB donor kidneys in a test setting other than inspecting the gross macroscopy at procurement, resulting in a high discard rate of three of four kidneys. Nevertheless the results are outstanding and merit the efforts: the center transplants annually more than 40 patients who would be only 30 without the NHB program. (2) They have an adjusted immunosuppressive protocol for NHB donor kidneys, avoiding the full dose of the calcineurin inhibitors and keeping the immunosuppression adequate by adding azathioprine. The reduced dose calcineurin inhibitors could not prevent the high percentage of delayed graft function, with 80% one of the highest reported. The speculation of the authors that the delayed graft function in NHB donation is different from the HB delayed graft function merits confirmation. It is quite likely that the delayed graft function in NHB is in the majority of cases due to the ischemia, while in HB kidneys it might be immunologically induced through the chain of events of brain-death and has therefore impact on the long-term outcome. (3) Not to miss a rejection they biopsy on weekly intervals in case the kidney has not started to function. The comparable rejection rates between the NHB and HB group suggest that this is a good protocol. There is one disturbing finding in the study: at 2 and 5 years the serum creatinine is significantly higher in the NHB group compared with the HB group. This suggests that not all of the ischemic damage sustained by the kidneys is reversible. The impact of this finding needs further study and comparison with matched controls. Our data (1) do not confirm this Leicester finding. The authors do not use 10 min of “no touch” to mark the transit of treating a patient and working with a donor, neither do they mention the use of heparin and/or vasodilators. Both issues have been debated extensively by the Institute of Medicine of the US National Academy of Sciences and recommendations (2) are now available. It seems wise that in Europe these recommendations are followed either in the same or in an adjusted protocol. In an editorial in the Lancet, Vanrenterghem (3) recommends to be cautious in the approach to use NHB donors. The main reason for this caution is .... not to jeopardize well-functioning donor programs.... Evidently the author is concerned that NHB donation might cause a “[lsquo]scandal[rsquo]” and have a negative influence on organ donation, especially HB donation. However, it is difficult to understand why the ethics of NHB donation, when openly discussed and well described as is the case in the US (2) would have a higher risk of causing a scandal than HB donation. With more experience the ethical problems in NHB donation will surface and be discussed to full consent in the society. After all, death with an arrested heart is in some situations simpler to explain than brain death and family consent might be easier reached. Vanrenterghem underestimates the potential of NHB donation in reversing the shortage of kidneys for transplantation. In the Netherlands for the past 2 years 16% of the postmortem kidneys were from NHB donors and these kidneys were mainly contributed through three of the seven transplant centers. The main hurdle for worldwide application of NHB donation is the uncertainty whether the ischemic damage will be reversible, i.e., if the percentage of never function can be brought down to 5% or less as is the case in HB kidney donation. The only answer is viability testing and although the Leicester group succeeds with very simple means, they for sure discard too many kidneys, that with better viability testing would pass and be transplanted. I question whether we will be able to perform this testing at low temperature since metabolism is so severely inhibited at 4°C. In our opinion (4) the future is in warm machine preservation at near normothermia. Not only functional testing becomes a possibility; repair of the ischemic damage might be an option as well. Until we have this warm preservation available, we have to rely on what is possible with the current cold preservation techniques (5) of great help in category 1 and 2 of the Maastricht criteria.