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Kidney Transplant Rejection—Pathophysiology, Prevention, and Emerging Therapies
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Kidney Transplant Rejection—Pathophysiology, Prevention, and Emerging Therapies

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "General Surgery".

Deadline for manuscript submissions: closed (8 June 2023) | Viewed by 22813

Special Issue Editor

Dr. Nada Alachkar

E-Mail Website
Guest Editor
Division of Nephrology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Interests: recurrent glomerular diseases in transplanted kidney biopsy; incompatible kidney transplant; high immunologic risk kidney transplant; biomarkers in kidney transplant; outcome of deceased donor kidney transplant recipients with positive crossmatch; highly sensitized patients; responses to desensitization treatments and post-transplant outcomes; late AMR; responses to therapy and outcome; recurrence of atypical HUS; the role of eculizumab; the recurrence of focal segmental glomerulosclerosis post-kidney transplantation
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Special Issue Information

Dear Colleagues,

Acute and chronic rejections of the kidney transplant remain a major cause of allograft failure, resulting in high mortality and morbidities.

There has been a significant improvement in our understanding of the different types of rejections, including T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), and mix rejection (which involves both types). Additionally, a tremendous amount of work has focused on the pathophysiology, prevention, treatment, and outcome of these rejections.

However, despite all these efforts, there is still a significant gap in our understanding and management of these rejections. This gap arises from the fact that the immune system is very complicated and redundant; therefore, a specific targeted therapy may not be enough to subside the immune response associated with rejection, which may lead to chronic changes, allograft dysfunction, or failure.

In this review, we will highlight up-to-date approved data on the pathophysiology, prevention, and therapies (both established and emerging) of kidney transplant rejections.

We aim to provide a source of knowledge to the clinicians and researchers to improve the management of patients and highlight unmet needs.

Dr. Nada Alachkar
Guest Editor

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Keywords

  • kidney transplant
  • allograft rejection
  • T-cell-mediated rejection
  • antibody-mediated rejection
  • mix rejection
  • transplant immunology
  • kidney graft dysfunction

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Published Papers (4 papers)

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Review

17 pages, 2170 KiB  
Review
Preventing Rejection of the Kidney Transplant
by Divyanshu Malhotra and Priyanka Jethwani
J. Clin. Med. 2023, 12(18), 5938; https://doi.org/10.3390/jcm12185938 - 13 Sep 2023
Cited by 7 | Viewed by 2652
Abstract
With increasing knowledge of immunologic factors and with the advent of potent immunosuppressive agents, the last several decades have seen significantly improved kidney allograft survival. However, despite overall improved short to medium-term allograft survival, long-term allograft outcomes remain unsatisfactory. A large body of [...] Read more.
With increasing knowledge of immunologic factors and with the advent of potent immunosuppressive agents, the last several decades have seen significantly improved kidney allograft survival. However, despite overall improved short to medium-term allograft survival, long-term allograft outcomes remain unsatisfactory. A large body of literature implicates acute and chronic rejection as independent risk factors for graft loss. In this article, we review measures taken at various stages in the kidney transplant process to minimize the risk of rejection. In the pre-transplant phase, it is imperative to minimize the risk of sensitization, aim for better HLA matching including eplet matching and use desensitization in carefully selected high-risk patients. The peri-transplant phase involves strategies to minimize cold ischemia times, individualize induction immunosuppression and make all efforts for better HLA matching. In the post-transplant phase, the focus should move towards individualizing maintenance immunosuppression and using innovative strategies to increase compliance. Acute rejection episodes are risk factors for significant graft injury and development of chronic rejection thus one should strive for early detection and aggressive treatment. Monitoring for DSA development, especially in high-risk populations, should be made part of transplant follow-up protocols. A host of new biomarkers are now commercially available, and these should be used for early detection of rejection, immunosuppression modulation, prevention of unnecessary biopsies and monitoring response to rejection treatment. There is a strong push needed for the development of new drugs, especially for the management of chronic or resistant rejections, to prolong graft survival. Prevention of rejection is key for the longevity of kidney allografts. This requires a multipronged approach and significant effort on the part of the recipients and transplant centers. Full article
(This article belongs to the Special Issue Kidney Transplant Rejection—Pathophysiology, Prevention, and Emerging Therapies)
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13 pages, 899 KiB  
Review
Current Therapies in Kidney Transplant Rejection
by Sami Alasfar, Lavanya Kodali and Carrie A. Schinstock
J. Clin. Med. 2023, 12(15), 4927; https://doi.org/10.3390/jcm12154927 - 27 Jul 2023
Cited by 13 | Viewed by 8600
Abstract
Despite significant advancements in immunosuppressive therapies, kidney transplant rejection continues to pose a substantial challenge, impacting the long-term survival of grafts. This article provides an overview of the diagnosis, current therapies, and management strategies for acute T-cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). [...] Read more.
Despite significant advancements in immunosuppressive therapies, kidney transplant rejection continues to pose a substantial challenge, impacting the long-term survival of grafts. This article provides an overview of the diagnosis, current therapies, and management strategies for acute T-cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). TCMR is diagnosed through histological examination of kidney biopsy samples, which reveal the infiltration of mononuclear cells into the allograft tissue. Corticosteroids serve as the primary treatment for TCMR, while severe or steroid-resistant cases may require T-cell-depleting agents, like Thymoglobulin. ABMR occurs due to the binding of antibodies to graft endothelial cells. The most common treatment for ABMR is plasmapheresis, although its efficacy is still a subject of debate. Other current therapies, such as intravenous immunoglobulins, anti-CD20 antibodies, complement inhibitors, and proteasome inhibitors, are also utilized to varying degrees, but their efficacy remains questionable. Management decisions for ABMR depend on the timing of the rejection episode and the presence of chronic changes. In managing both TCMR and ABMR, it is crucial to optimize immunosuppression and address adherence. However, further research is needed to explore newer therapeutics and evaluate their efficacy. Full article
(This article belongs to the Special Issue Kidney Transplant Rejection—Pathophysiology, Prevention, and Emerging Therapies)
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13 pages, 1065 KiB  
Review
Emerging Therapies for Antibody-Mediated Rejection in Kidney Transplantation
by Farah Abuazzam, Casey Dubrawka, Tarek Abdulhadi, Gwendolyn Amurao, Louai Alrata, Dema Yaseen Alsabbagh, Omar Alomar and Tarek Alhamad
J. Clin. Med. 2023, 12(15), 4916; https://doi.org/10.3390/jcm12154916 - 26 Jul 2023
Cited by 4 | Viewed by 3665
Abstract
Despite the advances in immunosuppressive medications, antibody-mediated rejection (AMR) continues to be a major cause of kidney allograft failure and remains a barrier to improving long-term allograft survival. Recently, there have been significant advances in the understanding of the pathophysiological process of AMR, [...] Read more.
Despite the advances in immunosuppressive medications, antibody-mediated rejection (AMR) continues to be a major cause of kidney allograft failure and remains a barrier to improving long-term allograft survival. Recently, there have been significant advances in the understanding of the pathophysiological process of AMR, along with the development of new therapeutic options. Additionally, surveillance protocols with donor-derived cell-free DNA and gene profile testing have been established, leading to the early detection of AMR. A multitude of clinical trials are ongoing, opening numerous opportunities for improving outcome in kidney transplant recipients. In this brief review, we discuss the emerging therapies for managing both active and chronic active AMR and highlight the ongoing clinical trials. Full article
(This article belongs to the Special Issue Kidney Transplant Rejection—Pathophysiology, Prevention, and Emerging Therapies)
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17 pages, 1026 KiB  
Review
Pathophysiology of Rejection in Kidney Transplantation
by Christina L. Tamargo and Sam Kant
J. Clin. Med. 2023, 12(12), 4130; https://doi.org/10.3390/jcm12124130 - 19 Jun 2023
Cited by 7 | Viewed by 7123
Abstract
Kidney transplantation has been the optimal treatment for end-stage kidney disease for almost 70 years, with increasing frequency over this period. Despite the prevalence of the procedure, allograft rejection continues to impact transplant recipients, with consequences ranging from hospitalization to allograft failure. Rates [...] Read more.
Kidney transplantation has been the optimal treatment for end-stage kidney disease for almost 70 years, with increasing frequency over this period. Despite the prevalence of the procedure, allograft rejection continues to impact transplant recipients, with consequences ranging from hospitalization to allograft failure. Rates of rejection have declined over time, which has been largely attributed to developments in immunosuppressive therapy, understanding of the immune system, and monitoring. Developments in these therapies, as well as an improved understanding of rejection risk and the epidemiology of rejection, are dependent on a foundational understanding of the pathophysiology of rejection. This review explains the interconnected mechanisms behind antibody-mediated and T-cell-mediated rejection and highlights how these processes contribute to outcomes and can inform future progress. Full article
(This article belongs to the Special Issue Kidney Transplant Rejection—Pathophysiology, Prevention, and Emerging Therapies)
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