Transplanting patients with a positive donor‐specific crossmatch: A single center's perspective

Abstract

An increasing number of individuals with end-stage renal disease have become sensitized to human leukocyte antigens (HLA). Sensitization can have a profound impact on the likelihood of obtaining a requisite negative crossmatch (-XM) with a potential donor. Technologic breakthroughs in our ability to diagnose antibody-mediated rejection (AMR) and monitor anti-HLA antibodies has set the stage for a renascence in the understanding and treatment of individuals who harbor donor-specific antibody (DSA). Promising early results from single institutions that have developed preconditioning protocols allowing successful transplantation of XM (+) patients have encouraged other centers to adopt these protocols. Sensitized patients represent a great challenge for the clinician and there is much that remains unknown about the assessment and treatment of these patients. We have successfully preconditioned and transplanted more than 80 patients over a 5-yr period. As our understanding of these patients has increased, we have progressed from a 'one size fits all' approach to therapy to more rational, individualized treatment plans that take into account the varying immunologic risk that each patient possesses. In this article we have summarized our evolving experience with the assessment, treatment, transplantation, and monitoring of patients who undergo preconditioning for a (+) XM with a live donor.

Treatment Update of Sensitized Pediatric Kidney Transplant Recipients: A Review

“…Montgomery and associates determined the numbers of plasmapheresis/CMVIg treatments before and after transplant based on starting DSA titer (Table 1). 16 Plasmapheresis has a transient effect on the DSA titer, and a rebound of antibodies occurs after its discontinuation. Thus, plasmapheresis is not suggested for desensitization of recipients with deceased-donor transplant.…”

“…Montgomery and associates suggested a desensitizing protocol including rituximab and plasmapheresis/CMVIg (Figure 1). 16 The use of rituximab in this protocol can reduce the risk of immunologic complications during transplant and the number of treatments before or at the time of transplant. 16 …”

“…11,20,21 Some centers have used Cytomegalovirus-Ig (CMVIg) in place of IVIG. 16 Cytomegalovirus-Ig has an additional anti-CMV effect. There are no wellcontrolled trials comparing the efficacy of these products, and the idea that administration of CMVIg has additional immunomodulatory effects.…”

“…Thus, we must know these risk factors, including previous early graft loss, multiple donor reactive antibodies, rising DSA titer at the time of desensitization starting, rebound DSA titer between treatments, multiple sensitizing events, and high-risk transplants (eg, husband to wife and child to mother transplants). 16 The presence of DSA reactive to DRW52 and DRW53 HLA antigens causes the resistance to desensitizing protocols. 8,33 Additionally, comorbid conditions in other organs such as heart and liver should be recognized, because these conditions can result in complications during desensitization protocols such as plasmapheresis.…”

“…These desensitizing methods include high-dose intravenous immunoglobulin (IVIG), [8][9][10][11] plasmapheresis alone, plasmapheresis/low-dose IVIG, [12][13][14] plasmapheresis/rituximab, plasmapheresis/ immunosuppressive agents, 15 immunoadsorption, immunosuppressive medicines such as alkylating agents, and infusion of rituximab. 13,14,16 Each desensitizing protocol has some strengths and weaknesses. Infections and rebound of anti-donor antibodies (after cessation of desensitizing treatment) are major problems of these protocols.…”