Chronic Allograft Injury: An Overview of Pathogenesis and Treatment Strategies

Madariaga, Hector; Riella, Leonardo V.

doi:10.1159/000468963

Cited by 5 publications

(5 citation statements)

References 46 publications

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“…Currently, there are many methods used for promoting fracture healing in clinics [1,2,[10][11][12]. Surgical intervention and autologous bone transplantation are the gold standard of current treatment in the event of fracture nonunion, but the trauma is so large that some patients may need multiple surgeries for years [13][14][15]. Autologous bone is generally taken from the iliac crest or fibula of the patient, which is more damaging to the patient and is prone to infection after sur-gery.…”

Section: Introductionmentioning

confidence: 99%

“…The cell components in allogeneic bones are mostly dead and do not have their own osteogenic ability. Studies have found that allogeneic bone treatment for nonunion fractures takes about 12 months for allogeneic bone surface union; indeed, internal osteogenesis is very slow, occurring at a rate of only 15-20% within five years, and deep repair hardly occurs [13,14].…”

Section: Introductionmentioning

confidence: 99%

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The Adenosine A2A Receptor Agonist Accelerates Bone Healing and Adjusts Treg/Th17 Cell Balance through Interleukin 6

Zheng

Wang

2020

BioMed Research International

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The aim of this study was to explore the effect of adenosine A2A receptor agonists on fracture healing and the regulation of the immunity system after bone fracture. We implanted fibrin gel containing adenosine A2A receptor agonist CGS 21680/inhibitor ZM 241385/saline locally in rat tibial fracture models, finding that the adenosine A2A receptor agonist could promote fracture healing. At the same time, the adenosine A2A receptor agonist decreased the level of IL-6 in blood and the fracture area, increased Treg cells, and decreased Th17 cells in blood of bone fracture rats. Further, tibial fracture rats implanted with the adenosine A2A receptor agonist gel were injected with IL-6. We found that IL-6 could reverse the effect of adenosine A2A receptor agonists on fracture healing and Treg/Th17 cells in blood. Through the above results, we believe that the adenosine A2A receptor agonist can promote fracture healing and regulate Treg/Th17 cells in blood of rats with fractures. These effects are related to IL-6.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Adenosine A2A Receptor Agonist Accelerates Bone Healing and Adjusts Treg/Th17 Cell Balance through Interleukin 6

Zheng

Wang

2020

BioMed Research International

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“…The risk of de novo DSA after transplantation includes nonadherence, immunosuppression minimization, young recipient, CYP3A5 expressor, recipient with HLA mismatch or high panel reactive antibody, history of previous kidney transplantation, prolonged ischemic time, history of T-cellmediated rejection, and history of allograft inflammation from viral infection [7,13,14 ]. Minimization of de novo DSA risk can prevent patients from developing chronic ABMR which is one of the most important causes of late allograft dysfunction [15].…”

Section: Prevention Of Donor-specific Antibody Developmentmentioning

confidence: 99%

Updated management for antibody-mediated rejection: opportunity to prolong kidney allograft survival

Townamchai

Avihingsanon

2022

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewAntibody-mediated rejection (ABMR) is an important barrier to achieve long-term kidney allograft survival. Human leukocyte antibody (HLA)-incompatibility and ABO-incompatibility are the two main mechanisms of ABMR. Nevertheless, the advances in managing ABMR have changed the paradigm for kidney transplantation. This review aimed to emphasize the HLA-incompatibility and ABO-incompatibility kidney transplant and update the management of ABMR.Recent findingsHLA-incompatibility kidney transplantation is a strong risk factor for ABMR. Donor-specific antibody (DSA) is a surrogate biomarker that prevents long-term allograft survival. The standard treatment for ABMR has unfavorable results. New drugs that target the B cell are a promising approach to treat ABMR. In the past, ABO-incompatibility kidney donor was an absolute contraindication but now, it is widely accepted as an alternative organ resource. The advancement of ABO antibody removal and B-cell depletion therapy has been successfully developed. ABO isoagglutination remains the main biomarker for monitoring ABMR during the transplantation process. C4d staining without inflammation of the kidney allograft is the marker for the accommodation process.SummaryWith the shortage of organ donors, transplant experts have expanded the organ resources and learned how to overcome the immunological barriers by using novel biomarkers and developing new treatments that support long-term graft survival.

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“…(Madariaga and Riella, 2017;Naesens et al, 2009;Riella et al, 2017) In the BENEFIT trial, where a CNIavoidance regimen (co-stimulatory blockade with Belatacept) is compared to the more standard CNI-based regimen (cyclosporine), Vincenti et.al. showed improved long-term renal allograft function over a follow-up period of 7 years with CNI-avoidance in selected patients ( Figure 1.11).…”

Section: Calcineurin Inhibitor Toxicity Impacts On Long-term Allografmentioning

confidence: 99%

Calcineurin inhibitor-induced endothelial cell injury – A role for complement

Teoh

Riedl

Bruno

et al. 2018

Molecular Immunology

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Calcineurin inhibitor (CNI) use significantly reduced acute rejection rates and revolutionized early allograft and patient outcomes post-transplantation. However, known nephro-and vascular toxicity preclude its use and contribute to chronic allograft injury, negatively impacting longer term outcomes. Evolving evidence suggest a role for complement dysregulation in the pathogenesis of CNI-induced endothelial injury. In an in vitro model using Blood Outgrowth Endothelial Cells (BOEC) isolated from healthy donors and a donor with a pathogenic MCP/CD46 variant, we showed that cyclosporine resulted in a dose and time dependent increase in complement deposition, enhanced by anti-CD59 sensitization. We showed for the first time that MCP/CD46 deficient BOECs were genetically predisposed to be more susceptible to cyclosporine-induced complement deposition (multiple-hit hypothesis). We found complement factor H surface dysregulation to play a key role in cyclosporine-induced complement activation on BOEC surfaces, with glycocalyx abolishment possibly being the key mechanism leading to alternative pathway dysregulation.iii

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Chronic Allograft Injury: An Overview of Pathogenesis and Treatment Strategies

Cited by 5 publications

References 46 publications

The Adenosine A2A Receptor Agonist Accelerates Bone Healing and Adjusts Treg/Th17 Cell Balance through Interleukin 6

The Adenosine A2A Receptor Agonist Accelerates Bone Healing and Adjusts Treg/Th17 Cell Balance through Interleukin 6

Updated management for antibody-mediated rejection: opportunity to prolong kidney allograft survival

Calcineurin inhibitor-induced endothelial cell injury – A role for complement

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