Donor Resuscitation Time, Kidney Transplant, and Selection Bias: Les reins ont des raisons que la raison ne connaît pas (with Apologies to Blaise Pascal).

The superior outcome of kidney transplant to other renal replacement modalities is well understood. However, the continued limited availability of deceased donor kidneys remains problematic. Although it is well established that many of the underutilized types of donated organs can be used more aggressively, most unutilized organs are not perfect—whatever that means—and parsing out which organs are reasonable for a given recipient or center in real-time is not as straightforward.1-7 Although there is no doubt that we have broadened the net of what is considered a reasonable organ, it can be difficult to determine what combined factors might be just a little too risky in the limited time allowed during allocation. Furthermore, the unintended and somewhat punitive impact of strict regulatory outcome standards, when coupled with logistical hurdles for timely organ offer and engraftment, compounds the difficulty of placing organs that do not readily appear straightforward.1-3 Deceased donors often have some degree of kidney injury or insufficiency, which should not be surprising in a population that is both getting old and physiologically shutting down—the donors are deceased after all. Rather than just relying on broad labeling, figuring out which type and what degree of injury are acute or reversible versus permanent or chronic is of utmost importance. Recent efforts in the systemically capture more nuanced data, including data as macroscopic as deceased donor dialysis and extracorporeal membrane oxygenation use8 will improve the ability to discern the impact of such factors in the US Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Worldwide, national databases have overlapping but wonderfully discretely different data granularities that shed much-needed light on controversies that require large numbers to elucidate. In this issue, Dubourg et al utilize data from the national CRISTAL registry of the French Agence de la biomédecine to hone down on data from a subset of such donors.9 They analyzed 1469 kidney transplant patients from brain-dead donors with resuscitated cardiac arrest as the cause of death or as an intercurrent event and found that kidney recipients from donors with a <3-d interval between cardiac arrest and organ recovery were more likely to suffer from delayed graft function (DGF), whereas short cold ischemia times, machine perfusion storage, and the absence of cardiac comorbidities were protective. These data suggest that the additional interval time allows for better resuscitation of the donors, with the potential impact of the decreased DGF resulting in better allograft survival. As with any retrospective registry analysis, the selection bias for the organs that are utilized can be a significant factor. It is probable that at least part of the effect measured results from the additional time that allows better selection or matching of the donors to recipients, although the utility of additional resuscitation time is intuitive as well. Additionally, it is likely that donors who had to go to recovery sooner were more likely to be unstable, with the predictable result of more DGF. That said, it is likely that the additional time resulted in more brain death testing, which may have the additional benefit of allowing donors with undiagnosed brain death the chance to donate their organs under conditions more conducive to less DGF than the donor-after-circulatory-death process. Of note, although DGF is associated with inferior outcomes, some types of perirecovery kidney injury have less effect. For example, acute kidney injury that is not compounded by underlying chronic kidney disease is more likely to recover.10 On appearances, the present study seems to contradict that. However, consistent with the hypothesis that reversible injury is reversible, Dubourg et al9 found that donors with arrests associated with underlying cardiovascular disease—a patient population with a higher incidence of kidney disease11 were more likely to result in recipient DGF. Additionally, as has been repeatedly shown, pumping the kidneys resulted in less DGF—likely resulting in both physiological changes such as vasodilation and selection bias for kidneys that demonstrate better pump parameters.4,12 This study is not a prospective interventional study. There are numerous factors that impact the time to organ recovery, many of which are not alterable. Donors may become too unstable to risk waiting longer, critical care beds may be vital for other emergent patients, family constraints may result in suboptimal organ allocation time, and the timing of recovery may be a compromise between the availability of coordinating recovery teams. Additionally, a hospital may not be able to engage in regular operations during a critical care bed crunch, and this study does not address the system impact of potential donors who utilized these critical care resources but do not go on to donate kidneys. However, as the authors point out, even if the study findings result from the additional time for organ assessment and donor-recipient matching—that is, from selection bias—it does not invalidate the potential benefit of this additional resuscitation time from both a patient and system perspective. Although transplant does not exist in a healthcare vacuum, it can have broad population benefits beyond those readily apparent. First, DGF is resource-intensive and best minimized in the context of maximized appropriate kidney utilization because these resources can potentially be utilized elsewhere. The same can be said for dialysis usage in general. Additionally, although there may be times when the need for critical care resources may briefly tip away from transplant, such as what happened with the first wave of the COVID-19 pandemic in early 2020, it must be remembered that a single well-resuscitated organ and tissue donor may positively impact hundreds of people. Further quantification of the relationship between additional donor critical care usage and interval downstream organ and tissue recipient benefit would help healthcare systems prioritize needed critical care resources.