Local Postoperative Graft Inflammation in Pancreas Transplant Patients With Early Graft Thrombosis

Kristina Rydenfelt; Gisle Kjøsen; Rune Horneland; Judith Krey Ludviksen; Trond Geir Jenssen; Pål-Dag Line; Tor Inge Tønnessen; Tom Eirik Mollnes; Håkon Haugaa; Søren Erik Pischke

doi:10.1097/TXD.0000000000001567

Local Postoperative Graft Inflammation in Pancreas Transplant Patients With Early Graft Thrombosis

Transplant Direct. 2023 Dec 12;10(1):e1567. doi: 10.1097/TXD.0000000000001567. eCollection 2024 Jan.

Authors

Kristina Rydenfelt^{1

2}, Gisle Kjøsen^{2

3}, Rune Horneland⁴, Judith Krey Ludviksen⁵, Trond Geir Jenssen^{2

6}, Pål-Dag Line^{2

4}, Tor Inge Tønnessen^{1

2}, Tom Eirik Mollnes^{5

7

8}, Håkon Haugaa^{1

3

9}, Søren Erik Pischke^{1

2

7}

Affiliations

¹ Division of Emergencies and Critical Care, Department of Anesthesia and Intensive Care Medicine, Oslo University Hospital, Oslo, Norway.
² Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Division of Emergencies and Critical Care, Department of Research and Development, Oslo University Hospital, Oslo, Norway.
⁴ Department of Transplantation Medicine, Section of Transplantation Surgery, Oslo University Hospital, Oslo, Norway.
⁵ Research Laboratory, Nordland Hospital, Bodø, Norway.
⁶ Department of Transplantation Medicine, Section of Nephrology, Oslo University Hospital, Oslo, Norway.
⁷ Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway.
⁸ Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
⁹ Department of Intensive Care Nursing, Lovisenberg University College, Oslo, Norway.

Abstract

Background: Graft thrombosis is the main cause of early graft loss following pancreas transplantation, and is more frequent in pancreas transplant alone (PTA) compared with simultaneous pancreas-kidney (SPK) recipients. Ischemia-reperfusion injury during transplantation triggers a local thromboinflammatory response. We aimed to evaluate local graft inflammation and its potential association with early graft thrombosis.

Methods: In this observational study, we monitored 67 pancreas-transplanted patients using microdialysis catheters placed on the pancreatic surface during the first postoperative week. We analyzed 6 cytokines, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8, interferon gamma-induced protein 10 (IP-10), macrophage inflammatory protein 1β (MIP-1β), IL-10, and the complement activation product complement activation product 5a (C5a) in microdialysis fluid. We compared the dynamic courses between patients with pancreas graft thrombosis and patients without early complications (event-free) and between PTA and SPK recipients. Levels of the local inflammatory markers, and plasma markers C-reactive protein, pancreas amylase, and lipase were evaluated on the day of thrombosis diagnosis compared with the first week in event-free patients.

Results: IL-10 and C5a were not detectable. Patients with no early complications (n = 34) demonstrated high IL-1ra, IL-6, IL-8, IP-10, and MIP-1β concentrations immediately after surgery, which decreased to steady low levels during the first 2 postoperative days (PODs). Patients with early graft thrombosis (n = 17) demonstrated elevated IL-6 (P = 0.003) concentrations from POD 1 and elevated IL-8 (P = 0.027) concentrations from POD 2 and throughout the first postoperative week compared with patients without complications. IL-6 (P < 0.001) and IL-8 (P = 0.003) were higher on the day of thrombosis diagnosis compared with patients without early complications. No differences between PTA (n = 35) and SPK (n = 32) recipients were detected.

Conclusions: Local pancreas graft inflammation was increased in patients experiencing graft thrombosis, with elevated postoperative IL-6 and IL-8 concentrations, but did not differ between PTA and SPK recipients. Investigating the relationship between the local cytokine response and the formation of graft thrombosis warrants further research.