Costimulation Blockade in Kidney Transplant Recipients

Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for infection. The ‘net state of immune suppression’ is a conceptual framework of all factors contributing to infectious risk. Assays which measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking. The best measures of integrated immune function may be quantitative viral loads to assess the individual’s ability to control latent viral infections. Few studies address adjustment of immunosuppression during active infections. Thus, confronted with infection in solid organ recipients, the management of immunosuppression is based largely on clinical experience. This review examines known measures of immune function and the immunologic effects of common immunosuppressive drugs and available studies reporting modification of drug regimens for specific infections. These data provide a conceptual framework for the management of immunosuppression during infection in organ recipients.

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“…Belatacept Fusion protein of cytotoxic T-lymphocyte associated protein-4-immunoglobulin, preventing T-cell co-stimulation [115].…”

Section: Glucocorticoidsmentioning

confidence: 99%

“…Blocks CD28 binding to CD80/CD86 thereby preventing co-stimulation required for T-cell activation [115].…”

Section: Glucocorticoidsmentioning

confidence: 99%

Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the “Net State of Immunosuppression”

Roberts

Fishman

2020

Clinical Infectious Diseases

127

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“…Belatacept, a cytotoxic T lymphocyte antigen 4-immunoglobulin fusion protein that inhibits T cell function, allows the minimization or discontinuation of endothelial toxic immunosuppressants such as CNIs and mTORis ( 90 , 91 ). However, a higher risk of acute kidney transplant rejection compared with current standard immunosuppressive therapy has been observed after conversion to belatacept in kidney transplant rejection ( 92 ).…”

Section: Treatment Of Post-transplant Thrombotic Microangiopathymentioning

confidence: 99%

Thrombotic Microangiopathy After Kidney Transplantation: An Underdiagnosed and Potentially Reversible Entity

2021

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Thrombotic microangiopathy is a rare but serious complication that affects kidney transplant recipients. It appears in 0.8–14% of transplanted patients and negatively affects graft and patient survival. It can appear in a systemic form, with hemolytic microangiopathic anemia, thrombocytopenia, and renal failure, or in a localized form, with progressive renal failure, proteinuria, or arterial hypertension. Post-transplant thrombotic microangiopathy is classified as recurrent atypical hemolytic uremic syndrome or de novo thrombotic microangiopathy. De novo thrombotic microangiopathy accounts for the majority of cases. Distinguishing between the 2 conditions can be difficult, given there is an overlap between them. Complement overactivation is the cornerstone of all post-transplant thrombotic microangiopathies, and has been demonstrated in the context of organ procurement, ischemia-reperfusion phenomena, immunosuppressive drugs, antibody-mediated rejection, viral infections, and post-transplant relapse of antiphospholipid antibody syndrome. Although treatment of the causative agents is usually the first line of treatment, this approach might not be sufficient. Plasma exchange typically resolves hematologic abnormalities but does not improve renal function. Complement blockade with eculizumab has been shown to be an effective therapy in post-transplant thrombotic microangiopathy, but it is necessary to define which patients can benefit from this therapy and when and how eculizumab should be used.

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“…The importance of CD40/CD40L signaling to kidney transplantation has been well studied in that CD40 acts as a co-stimulatory molecule associated with adaptive immunity as well as allograft rejection [14]. Usages of CD40 and CD40L blockade antibodies have been well reviewed in other reports [14,114,128,129]. CD40/CD40L contributes to antibody-mediated rejection (AMR) that is caused by donor-specific HLA antibody (DSA), although targeting CD40L alone is not sufficient to inhibit the production of DSA [114].…”

Section: Cd40 and Cd40l Blockade In Kidney Transplantationmentioning

confidence: 99%

CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease

Zhang

Breidenbach

Russell

et al. 2020

JCM

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The cluster of differentiation 40 (CD40) is activated by the CD40 ligand (CD40L) in a variety of diverse cells types and regulates important processes associated with kidney disease. The CD40/CD40L signaling cascade has been comprehensively studied for its roles in immune functions, whereas the signaling axis involved in local kidney injury has only drawn attention in recent years. Clinical studies have revealed that circulating levels of soluble CD40L (sCD40L) are associated with renal function in the setting of kidney disease. Levels of the circulating CD40 receptor (sCD40), sCD40L, and local CD40 expression are tightly related to renal injury in different types of kidney disease. Additionally, various kidney cell types have been identified as non-professional antigen-presenting cells (APCs) that express CD40 on the cell membrane, which contributes to the interactions between immune cells and local kidney cells during the development of kidney injury. Although the potential for adverse CD40 signaling in kidney cells has been reported in several studies, a summary of those studies focusing on the role of CD40 signaling in the development of kidney disease is lacking. In this review, we describe the outcomes of recent studies and summarize the potential therapeutic methods for kidney disease which target CD40.

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Costimulation Blockade in Kidney Transplant Recipients

Cited by 23 publications

References 146 publications

Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the “Net State of Immunosuppression”

Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the “Net State of Immunosuppression”

Thrombotic Microangiopathy After Kidney Transplantation: An Underdiagnosed and Potentially Reversible Entity

CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease

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