Characteristics of organ donors and logistics of organ procurement for short- and long-term outcomes in abdominal organ transplantation

Organ transplantation is a medical procedure in which a patient’s dysfunctional organ is replaced with a graft that is usually received from an organ donor. Solid- organ transplantation is the best treatment option especially in end-stage kidney and liver failure. Pancreas transplantation, on the other hand, is the only curative treatment for Type I diabetes. To this day, most organs are gifted from brain-dead donors. These donors suffer from a brain death-derived release of inflammatory mediators and sympathetic nervous system hyperactivation, called the cytokine and autonomic storm. These reactions are thought to harm transplantable organs. Although the management of a brain-dead donor has been nearly perfected, limitations remain in our knowledge of the features of the donor and the timing of organ procurement. Therefore, no consensus exists on the ideal organ procurement time, and currently, logistics drive the timetables of organ procurement and transplantation. The most significant restrictive factor in organ transplantation is the deficiency of organ donors. Hence, clinicians need to consider using transplants from older and more frail donors. The transplanted organ should nevertheless be relatively healthy to provide a treatment instead of an additional burden for the patient. Donor age and medical conditions currently guide acceptance for transplantation. These characteristics have been used to develop risk scores to predict the graft prognosis, but unfortunately, these have proven to be inaccurate in predicting graft loss. This research investigated how the time between brain death and organ procurement (procurement interval) associates with the outcomes of kidney, liver, and pancreas transplants. It also examined the extent of the brain-dead donor’s impact on kidney transplant loss in the early post-transplantation period. A risk measure of brain-dead donor age and disease, the Kidney Donor Profile Index (KDPI), was utilized as a determinant of the kidney graft quality. The study cohorts consisted of kidney, liver, and pancreas transplant registries from the US and Finland. Associations of donor-related factors with transplant outcomes, such as graft survival, patients’ death, acute rejections, and delayed function, were evaluated by means of multivariable models. The analyses were adjusted for confounding factors. In the first study of kidney transplants, multivariable models showed that in both cohorts, longer intervals were associated with improved graft survival. The probability of delayed graft function dove to the lowest point at 20 to 50 hours of the procurement interval, implying a sweet spot for kidney procurement at approximately 1-2 days after brain death. The procurement interval was uncorrelated with acute rejection rates, which was analyzable for the Finnish cohort only. The second study of liver transplants revealed a longer procurement interval after brain death to associate with enhanced graft survival up to 50 hours. However, this association was not evident in the Finnish cohort with relatively short intervals. Longer procurement intervals in either cohort were not associated with short-term outcomes, such as intrahepatic biliary strictures, acute rejections, or recipient kidney injuries. The association between the procurement interval and short-term liver function, measured with the Model for Early Allograft Function score, improved with a longer interval. The ideal timing for liver procurement seems to follow brain death after 50 hours. The third study showed that pancreas transplants, commonly derived from ideal organ donors, also benefited from longer procurement intervals. This was observed as longer graft survival and less acute rejections with no apparent upper limit of procurement interval. The fourth study focused on evaluating the deceased donor’s impact on the risk of early kidney graft loss. Losing a kidney transplant shortly after transplantation is catastrophic, and most often results from bleeding, graft thrombosis, or rejection. A recipient for a kidney transplant is chosen so that tissue compatibility and graft survival are optimized. Thus, the healthiest kidneys are often allocated to the youngest and the frailest kidneys to the oldest recipients. The selection of the recipient for the kidney transplant is therefore not random. This study attempted to remove the selection bias of non-random donor-recipient pairing and statistically weighted transplantations with propensity scoring methods to scourge out the inherent association of graft quality with early kidney graft loss. After weighting, the association between graft quality and early kidney graft loss remained relatively unchanged. In all patient groups, kidney graft loss and death in the early post-transplantation period were rare, but fragility of the graft significantly increased the risk of these complications. Based on the findings of this thesis, all abdominal organ transplants were unharmed from longer procurement intervals. On the contrary, the results of Studies I through III strongly pointed to improved outcomes with delayed procurements. Therefore, organ procurement can be safely delayed and might even be encouraged in many situations where hospital logistics allow. To optimize the vital functions of the donor and repair possible organ damage, the recommended time for organ procurement appears to be around two days after brain death. Furthermore, the risk of early kidney graft loss increases with unideal grafts, but losing a graft within a year after transplantation is still relatively rare.

Grantor dc:publisher

Helsingin yliopisto

Year dc:date.issued

2024

Author dc:creator

• Eerola, Verner

• lääketiede

Statement dc:rights

• Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
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Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10138/575146

OAI record oai:identifier

https://helda.helsinki.fi/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Ahelda.helsinki.fi%3A10138%2F575146