Dataset Information

Thromboinflammatory response is increased in pancreas transplant alone versus simultaneous pancreas-kidney transplantation and early pancreas graft thrombosis is associated with complement activation.

ABSTRACT:

Background

Pancreas transplant alone (PTA) recipients are more affected by pancreas graft thrombosis, and graft loss compared to simultaneous pancreas-kidney (SPK) recipients. The pathophysiology is unknown, but an increased immune response has been suggested in the PTA recipients. In this observational study, we compared perioperative thromboinflammation between PTA (n=32) and SPK (n=35) recipients, and between PTA recipients with (n=14) versus without (n=18) early graft thrombosis.

Methods

We measured C-reactive protein (CRP), plasma markers of activated coagulation and complement, and cytokines preoperatively and daily during the first postoperative week.

Results

Preoperatively, coagulation and complement activation markers were comparable between PTA and SPK recipients, while cytokine concentrations were higher in SPK recipients (TNF, IL-8, IP-10, MCP-1, MIP-1α; all p<0.05). On the first postoperative day, PTA recipients had higher coagulation activation, measured as thrombin-antithrombin complex (TAT), than SPK recipients (p=0.008). In the first postoperative week, PTA recipients showed higher relative cytokine release (IL-6, IL-8, G-CSF, IP-10, MCP-1, and MIP-1α; all p<0.05) while SPK recipients showed higher absolute cytokine concentrations (TNF, IL-1ra, IL-8, MIP-1α, and IL-4; all p<0.05). PTA and SPK recipients showed similar terminal complement complex (TCC, sC5b-9) activation. On the first postoperative day, TCC (OR 1.2 [95% CI 1.0-1.5] for 0.1 CAU/ml increase, p=0.02) and CRP (OR 1.2 [95% CI 1.0-1.3] for 10 mg/L increase, p=0.04) were associated with an increased risk of early graft thrombosis. TCC was specific for graft thrombosis, while CRP increased with several complications. PTA recipients with compared to those without graft thrombosis had higher TCC pre- (p=0.04) and postoperatively (p=0.03).

Conclusion

The relative increase in postoperative thromboinflammatory response was more pronounced in PTA recipients. Complement activation was associated with an increased risk of graft thrombosis. This study indicates that innate immune activation rather than elevated levels may affect early postoperative pancreas graft thrombosis.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT01957696, identifier NCT01957696.

SUBMITTER: Rydenfelt K

PROVIDER: S-EPMC10090504 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Thromboinflammatory response is increased in pancreas transplant alone versus simultaneous pancreas-kidney transplantation and early pancreas graft thrombosis is associated with complement activation.

Rydenfelt Kristina K Kjøsen Gisle G Horneland Rune R Ludviksen Judith Krey JK Jenssen Trond Geir TG Line Pål-Dag PD Tønnessen Tor Inge TI Mollnes Tom Eirik TE Haugaa Håkon H Pischke Søren Erik SE

Frontiers in immunology 20230329

<h4>Background</h4>Pancreas transplant alone (PTA) recipients are more affected by pancreas graft thrombosis, and graft loss compared to simultaneous pancreas-kidney (SPK) recipients. The pathophysiology is unknown, but an increased immune response has been suggested in the PTA recipients. In this observational study, we compared perioperative thromboinflammation between PTA (n=32) and SPK (n=35) recipients, and between PTA recipients with (n=14) versus without (n=18) early graft thrombosis.<h4> ...[more]

PMID: 37063904

Similar Datasets

Project description:BackgroundGraft 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.MethodsIn 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.ResultsIL-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.ConclusionsLocal 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.

Project description:BackgroundCoronary heart disease due to arteriosclerosis is the leading cause of death in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to evaluate the effect of simultaneous pancreas kidney transplantation (SPKT) compared to kidney transplantation alone (KTA) on survival, cardiovascular function and metabolic outcomes.MethodsA cohort of 127 insulin-dependent diabetes mellitus (IDDM) patients with ESRD who underwent either SPKT (n = 100) or KTA (n = 27) between 1998 and 2019 at the University Hospital of Leipzig were retrospectively evaluated with regard to cardiovascular and metabolic function/outcomes as well as survival rates. An additional focus was placed on the echocardiographic assessment of systolic and diastolic cardiac function pretransplant and during follow-up. To avoid selection bias, a 2:1 propensity score matching analysis (PSM) was performed.ResultsAfter PSM, a total of 63 patients were identified; 42 patients underwent SPKT, and 21 patients received KTA. Compared with the KTA group, SPKT recipients received organs from younger donors (p < 0.05) and donor BMI was higher (p = 0.09). The risk factor-adjusted hazard ratio for mortality in SPKT recipients compared to KTA recipients was 0.63 (CI: 0.49-0.89; P < 0.05). The incidence of pretransplant cardiovascular events was higher in the KTA group (KTA: n = 10, 47% versus SPKT: n = 10, 23%; p = 0.06), but this difference was not significant. However, the occurrence of cardiovascular events in the SPKT group (n = 3, 7%) was significantly diminished after transplantation compared to that in the KTA recipients (n = 6, 28%; p = 0.02). The cardiovascular death rate was higher in KTA recipients (19%) than in SPK recipients with functioning grafts (3.3%) and comparable to that in patients with failed SPKT (16.7%) (p = 0.16). In line with pretransplant values, SPKT recipients showed significant improvements in Hb1ac values (p = 0.001), blood pressure control (p = < 0.005) and low-density lipoprotein/high-density lipoprotein (LDL/HDL) ratio (p = < 0.005) 5 years after transplantation. With regard to echocardiographic assessment, SPKT recipients showed significant improvements in left ventricular systolic parameters during follow-up.ConclusionsNormoglycaemia and improvement of lipid metabolism and blood pressure control achieved by successful SPKT are associated with beneficial effects on survival, cardiovascular outcomes and systolic left ventricular cardiac function. Future studies with larger samples are needed to make predictions regarding cardiovascular events and graft survival.

Dataset Information

Thromboinflammatory response is increased in pancreas transplant alone versus simultaneous pancreas-kidney transplantation and early pancreas graft thrombosis is associated with complement activation.

Background

Methods

Results

Conclusion

Clinical trial registration

Publications

Thromboinflammatory response is increased in pancreas transplant alone versus simultaneous pancreas-kidney transplantation and early pancreas graft thrombosis is associated with complement activation.

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