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Risk Factors for Early Pancreatic Allograft Thrombosis Following Simultaneous Pancreas-Kidney Transplantation: A Systematic Review.

ABSTRACT: Simultaneous pancreas-kidney (SPK) transplantation remains the most effective treatment for providing consistent and long-term euglycemia in patients having type 1 diabetes with renal failure. Thrombosis of the pancreatic vasculature continues to contribute significantly to early graft failure and loss. We compared the rate of thrombosis to graft loss and systematically reviewed risk factors impacting early thrombosis of the pancreas allograft following SPK transplantation. We searched the MEDLINE, EMBASE, The Cochrane Library, and PREMEDLINE databases for studies reporting thrombosis following pancreas transplantation. Identified publications were screened for inclusion and synthesized into a data extraction sheet. Sixty-three studies satisfied eligibility criteria: 39 cohort studies, 22 conference abstracts, and 2 meta-analyses. Newcastle-Ottawa Scale appraisal of included studies demonstrated cohort studies of low bias risk; 1127 thrombi were identified in 15 936 deceased donor, whole pancreas transplants, conferring a 7.07% overall thrombosis rate. Thrombosis resulted in pancreatic allograft loss in 83.3% of reported cases. This review has established significant associations between donor and recipient characteristics, procurement and preservation methodology, transplantation technique, postoperative management, and increased risk of early thrombosis in the pancreas allograft. Further studies examining the type of organ preservation fluid, prophylactic heparin protocol, and exocrine drainage method and early thrombosis should also be performed.

SUBMITTER: Blundell J

PROVIDER: S-EPMC7573738 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Risk Factors for Early Pancreatic Allograft Thrombosis Following Simultaneous Pancreas-Kidney Transplantation: A Systematic Review.

Blundell Jian J Shahrestani Sara S Lendzion Rebecca R Pleass Henry J HJ Hawthorne Wayne J WJ

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20200101

Simultaneous pancreas-kidney (SPK) transplantation remains the most effective treatment for providing consistent and long-term euglycemia in patients having type 1 diabetes with renal failure. Thrombosis of the pancreatic vasculature continues to contribute significantly to early graft failure and loss. We compared the rate of thrombosis to graft loss and systematically reviewed risk factors impacting early thrombosis of the pancreas allograft following SPK transplantation. We searched the MEDLI ...[more]

PMID: 33052066

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Project description:BackgroundPancreas 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.MethodsWe measured C-reactive protein (CRP), plasma markers of activated coagulation and complement, and cytokines preoperatively and daily during the first postoperative week.ResultsPreoperatively, 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).ConclusionThe 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 registrationhttps://clinicaltrials.gov/ct2/show/NCT01957696, identifier NCT01957696.

Project description:Aims/hypothesisThe study aimed to assess the impact on neuropathy of simultaneous pancreas and kidney transplantation (SPK) in individuals with type 1 diabetes.MethodsThis longitudinal observational study examined neuropathic symptoms, deficits, quantitative sensory testing, neurophysiology, corneal confocal microscopy and skin biopsy results in 32 healthy (non-diabetic) control participants, 29 individuals with type 1 diabetes and severe diabetic peripheral neuropathy [DPN] and 36 individuals with type 1 diabetes after SPK.ResultsFollowing SPK, HbA1c, eGFR, triacylglycerols and HDL improved significantly (all p < 0.05). Compared with the DPN group, which remained unchanged over the 36 month study period, corneal confocal microscopy assessments improved over 36 months following SPK, with increasing corneal nerve fibre density of 5/mm2 (95% CI 1.8, 8.2; p = 0.003) and corneal nerve fibre length of 3.2 mm/mm2 (95% CI 0.9, 5.5; p = 0.006). The Neuropathy Symptom Profile and peroneal nerve conduction velocity also improved significantly by 36 months compared with DPN (2.5; 95% CI 0.7, 4.3; p = 0.008 and 4.7 m/s; 95% CI 2.2, 7.4; p = 0.0004, respectively), but with a temporal delay compared with the corneal confocal microscopy assessments. Intraepidermal nerve fibre density did not change following SPK; however, mean dendritic length improved significantly at 12 (p = 0.020) and 36 (p = 0.019) months. In contrast, there were no changes in the Neuropathy Disability Score, quantitative sensory testing or cardiac autonomic function assessments. Except for a small decrease in corneal nerve fibre density in the healthy control group, there were no changes in any other neuropathy measure in the healthy control or DPN groups over 36 months.Conclusions/interpretationSPK is associated with early and maintained small nerve fibre regeneration in the cornea and skin, followed by an improvement in neuropathic symptoms and peroneal nerve conduction velocity.

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Risk Factors for Early Pancreatic Allograft Thrombosis Following Simultaneous Pancreas-Kidney Transplantation: A Systematic Review.

Publications

Risk Factors for Early Pancreatic Allograft Thrombosis Following Simultaneous Pancreas-Kidney Transplantation: A Systematic Review.

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