Kidney transplantation in highly sensitized patients

Abstract

Background: Desensitization, a term loosely referring to a collection of antibody reduction and B-cell depletional therapies aimed at improving rates of transplantation in highly HLA and ABO-incompatible transplant recipients, has seen significant growth in the last decade. Advancements relate to an increasing unmet medical need for FDA-approved therapies, advancements in antibody detection methodologies and improved renal pathological assessments of antibody-mediated rejection (ABMR).

Sources of data, areas of agreement and controversy: Data reviewed include collective summaries of experience with high-dose intravenous immunoglobulin (IVIG), B-cell depletion with rituximab and the use of plasma exchange with low-dose IVIG. Consensus suggests that these protocols are the most commonly used while experiences with other agents (i.e. bortezomib) are evolving. Controversy exists as to the extent of resources required, expense and outcomes of desensitization protocols.

Growing points or areas timely for developing research: Here we review and synthesize data from evolving protocols and summarize developments of novel biologics aimed at modification of B-cells, antibodies and complement activation which will likely improve desensitization and treatment of ABMR.

Keywords: C1-inhibitor; IL-6; IVIG; antibody-mediated rejection; complement; desensitization; eculizumab; immunotherapy; kidney transplant; rituximab.