Improving the Supply and Quality of Deceased-Donor Organs for Transplantation
Tullius SG, Rabb H. N Engl J Med. 2018;378:1920-1929.
A timely review article, summarizing the potential improvements that can be made to decrease the discard rate of deceased-donor organs.
Deceased-donor organs are generally discarded if considered suboptimal. The Kidney Donor Risk Profile Index is widely used to predict outcome, and a score of 85% or more are discarded frequently. Using these organs will particularly impact on the highly sensitized patients, as well as patients who are on the waiting list for more than 10 years. A variety of reasons can deem the organ unsuitable, from older-age donors to infectious risk or increased warm ischemic time. The authors point out that with death rates between 20% and 40% on the waiting list, it is time for clinicians to think of innovative ways to deal with these suboptimal organs and to reduce the discard rate.
Although age is not limiting donor utilization in countries like Spain, there are several places elsewhere in the world where donors older than 65 or 70 years might not be used. Spanish results with older donors are not yet well reported, although we know, in general, that using these kidneys for older recipients result in better outcomes.1 Eliminating harmful senescent cells, which are more prevalent in older organs, might improve organ function. This is a potential research area that needs to be developed in more detail.
Similarly, new preservation methods have the option to improve organs retrieved from donors after circulatory death and normothermic perfusion will hopefully impact positively to reduce discard rates from donors after circulatory death organs.
Lastly, the authors point out that donors with high infectious risk can successfully be used, including hepatitis C virus– and human immunodeficiency virus–positive organs. The key is probably to select the best recipient for all these organs and to adjust regulatory frameworks to allow for a wider use of discarded organs.
A huge potential exists to improve organ quality in the brain-dead donor, including improved hemodynamic stabilization, hormonal factors, and metabolic factors.
- Tullius SG, Milford E. Kidney allocation and the aging immune response. N Engl J Med. 2011;364:1369–1370.
A Randomized Trial of Normothermic Preservation in Liver Transplantation
Nasralla D, Coussio CC, Mergental H, et al. Nature. 2018;557:50-56.
Suboptimal livers do not tolerate conventional cold storage very well and organ viability is difficult to assess. In this study, 334 livers were randomized to 2 groups. In the first group, 170 livers were perfused with oxygenated blood, medications, and nutrients at normal body temperature (normothermic machine perfusion [NMP]). In the second group, 164 livers were allocated to static cold storage (SCS). Livers donated after circulatory death (DCD), as well as livers from brain-dead donors (DBD), were allowed into the study. The discard rate in the SCS group was 24.1% compared with the 11.7% in the NMP arm.
Peak aspartate aminotransferase AST was reduced by 49.4% in the NMP arm at day 7 compared with the SCS arm. There was no significant difference in the rate of nonanastomotic bile duct strictures for DBD livers (NMP, 7.4% vs SCS, 5.4%).
The DCD liver donors represent a large untapped source of organ donors worldwide and had been used less often because of increased risk of ischemic cholangiopathy compared with DBD livers.1
The effects of NMP demonstrated in this study are unequivocal with respect to the primary endpoint, implying a benefit in livers currently used for transplantation. However, the greatest benefit may be realized by applying this technology to livers outside current acceptance criteria, to transplant organs currently deemed untransplantable.
- Jay CL, Lyuksemburg V, Ladner DP, et al. Ischemic cholangiopathy after controlled donation after cardiac death liver transplantation: a meta-analysis. Ann Surg. 2011;253:259–264.