Blog entry by Arif Khwaja
In the UK the growth in kidney transplantation in recent years has been predominantly fueled by both increasing live-related transplantation and increasing use of donors after circulatory death (DCDs - or what were previously known as non-heartbeating donors). Around a third of kidneys used in the UK are DCDs, but the use of DCDs has varied across centres with some being enthusiastic proponents whilst others such as being more cautious. Of course the main concerns amongst clinicians is whether such kidneys are as 'good' as kidneys donated after brain death (DBD), with concerns over the impact of anoxic, warm iscahemia time coupled with prolonged cold ischaemia on long term graft survival. A recent analysis of UK Transplant Registry data by Summers and colleagues in the Lancet sheds some light on what the outcomes are in such kidneys.
The investigators analysed 1768 DCDs and 4127 DBDs transplanted between 2005 and 2010. DCD kidneys had a higher rate of delayed graft function (DGF) than DBDs (49% vs 24%) but patient and graft survival at 3 years were no different. The 12 month eGFR (which maybe a reasonable surrogate for longer term graft survival) was significantly lower in the DCD group vs the DBD group (mean eGFR =48mls/min vs 50mls/min, p<0.04). Kidneys from donors over the age of 60 years were twice as likely to result in graft failure compared to those under the age of 40, irrespective of whether they were DBDs or DCDs.
In contrast to age, cold storage time (> 24 hours vs<12 hours) did impact adversely on graft survival in DCDs but not in DBDs. i.e. warm ischaemia seems to 'prime' the kidney for further damage resulting from prolonged cold storage. Whilst there has been promising data from a large, well conducted European RCT showing that hypothermic perfusion improves DGF, kidney function and graft survival, this study only included a small number of kidneys were DCDs. In contrast, a UK RCT study specifically evaluating machine perfusion in DCDs, showed no impact of hypothermic machine perfusion on DGF, patient and graft survival at 1 year.
What are the implications of this work?
Well firstly it can reassure clinicians and patients that short-term (i.e. 3 year) outcomes are the same for DBDs and DCDs and that in this timeframe the age of the donor rather than whether they are a DCD or DBD is what matters. Therefore increasing the use of DCDs may increase the overall donor pool and access to transplantation. The price of this maybe slightly worse graft function at 3 years and applying this registry data to individual patient-decision making in the middle of the night will always be fiendishly difficult for transplant surgeons - taking into account recipient comorbidity and age etc will remain paramount.
Secondly its clear that the cold storage time does adversely impact on outcomes of DCDs and this therefore needs to be taken into account when devising an allocation policy for DCDs. Whilst national allocation of DBDs seems sensible, national (rather than regional) allocation of DCDs with inevitable prolongation of cold storage time may simply lead to worse outcomes. This data casts considerable doubt on current deliberations in the UK to move towards a national allocation scheme for DCDs unless guarantees can be made about cold storage time.