Aggravation of fibrin deposition and microthrombus formation within the graft during kidney transplantation

T Berg ,Stephan J L Bakker,Marius C Van Den Heuvel,Jelle Adelmeijer,Harry Van Goor,Janneke Wiersema-Buist,Ton Lisman,Gertrude J Nieuwenhuijs-Moeke,Robert A Pol

doi:10.1038/s41598-021-97629-1

T Berg , Stephan J L Bakker + Show 7 more

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https://doi.org/10.1038/s41598-021-97629-1

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Abstract

In kidney transplantation, microthrombi and fibrin deposition may lead to local perfusion disorders and subsequently poor initial graft function. Microthrombi are often regarded as donor-derived. However, the incidence, time of development, and potential difference between living donor kidneys (LDK) and deceased donor kidneys(DDK), remains unclear. Two open-needle biopsies, taken at preimplantation and after reperfusion, were obtained from 17 LDK and 28 DDK transplanted between 2005 and 2008. Paraffin-embedded sections were immunohistochemically stained with anti-fibrinogen antibody. Fibrin deposition intensity in peritubular capillaries(PTC) and glomeruli was categorized as negative, weak, moderate or strong and the number of microthrombi/mm2 was quantified. Reperfusion biopsies showed more fibrin deposition (20% to 100% moderate/strong, p < 0.001) and more microthrombi/mm2 (0.97 ± 1.12 vs. 0.28 ± 0.53, p < 0.01) than preimplantation biopsies. In addition, more microthrombi/mm2 (0.38 ± 0.61 vs. 0.09 ± 0.22, p = 0.02) and stronger fibrin intensity in glomeruli (28% vs. 0%, p < 0.01) and PTC (14% vs. 0%, p = 0.02) were observed in preimplantation DDK than LDK biopsies. After reperfusion, microthrombi/mm2 were comparable (p = 0.23) for LDK (0.09 ± 0.22 to 0.76 ± 0.49, p = 0.03) and DDK (0.38 ± 0.61 to 0.90 ± 1.11, p = 0.07). Upon reperfusion, there is an aggravation of microthrombus formation and fibrin deposition within the graft. The prominent increase of microthrombi in LDK indicates that they are not merely donor-derived.

Highlights

In kidney transplantation, microthrombi and fibrin deposition may lead to local perfusion disorders and subsequently poor initial graft function
We further investigated whether fibrin deposition and microthrombus formation is associated with donor type or intraoperative use of heparin
All biopsies and patient data were obtained from the TransplantLines biobank (NCT03272841), a prospective cohort study and biobank that includes all types of solid organ transplant recipients as well as organ donors

Summary

Introduction

Microthrombi and fibrin deposition may lead to local perfusion disorders and subsequently poor initial graft function. The prominent increase of microthrombi in LDK indicates that they are not merely donor-derived It is well known in kidney transplantation, that microthrombi can be observed in preimplantation biopsies of kidney grafts. It is unclear whether the donor-derived microthrombi persist or disappear or if new microthrombi arise when the graft is reperfused. Disappearance is rather unlikely, since ischemia/reperfusion injury (IRI), which is inevitable in transplantation and is associated with a procoagulatory response, potentially enhances formation of microthrombi and deposition of fibrin. Activation of hemostasis with subsequent microthrombus formation in deceased organ donors may be one of the reasons living donor kidneys (LDK) are of better quality than deceased donor kidneys (DDK). We further investigated whether fibrin deposition and microthrombus formation is associated with donor type or intraoperative use of heparin

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