Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Gabriel Oniscu, Karolinska Institutet, Sweden
- Second opponent: Professor Asger Granfeldt, Aarhus University, Denmark
- Third member and chair of the evaluation committee: Associate Professor Lise Mørkved Helsingen, University of Oslo
Chair of the Defence
Associate Professor Sheraz Yaqub, University of Oslo
Principal Supervisor
Section Chief Physician Håkon Haugaa, Oslo University Hospital
Summary
Graft thrombosis in pancreas transplantation: early detection and the role of thromboinflammation
Pancreas transplantation is a treatment for difficultly regulated type 1 diabetes, often performed alongside kidney transplantation when complicated by kidney failure. Graft thrombosis is a major cause of early pancreas graft failure. Detecting graft thrombosis in time to intervene is challenging, as standard patient monitoring (blood samples, imaging, and symptom assessment) is often insufficient. The molecular mechanisms of graft thrombosis and an increased risk in solitary pancreas transplants remain poorly understood.
This thesis investigates if sensors attached to the pancreas graft can detect complications, whether measurements from the pancreas surface and pancreas tissue correlate, and explores the thromboinflammatory response during the first week post-transplantation.
Sixty-seven pancreas transplant patients at Oslo University Hospital were monitored using microdialysis catheters attached to the pancreas graft for bedside analyses. Patients with complications showed significant changes in glucose metabolite levels before clinical symptoms or changes in standard blood samples, though no specific metabolic pattern indicated graft thrombosis. Additionally, a pig experiment confirmed correlation between biomarkers from the pancreatic surface and tissue samples.
In the pancreas recipients, thromboinflammatory markers increased and normalized within 72 hours postoperatively, except for complement activation, which remained elevated. Higher inflammatory responses were observed in solitary pancreas recipients, but further studies are needed to establish clinical relevance. Early increased complement activation in plasma was linked to higher graft thrombosis risk, and patients with graft thrombosis had elevated proinflammatory cytokines at the graft. These findings suggest complex interactions between coagulation and inflammation in graft thrombosis formation. While medical prevention has focused on coagulation, new targets may lie within the inflammatory response.
Additional information
Contact the research support staff.