Kidney transplantation in highly sensitized patients.
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).
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.
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.
Comprehensive Transplant Center, Kidney Transplant Program and Transplant Immunotherapy Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA sjordan@cshs.org Stan.Jordan@cshs.org.
Stanley C
SC
Jordan
Comprehensive Transplant Center, Kidney Transplant Program and Transplant Immunotherapy Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Jua
J
Choi
Comprehensive Transplant Center, Kidney Transplant Program and Transplant Immunotherapy Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Ashley
A
Vo
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000069286:Bortezomib / Q000627:therapeutic use; D003165:Complement System Proteins / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods*; D006084:Graft Rejection / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods*; D000069283:Rituximab / Q000627:therapeutic use
D061067:Antibodies, Monoclonal, Humanized; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000069283:Rituximab; D000069286:Bortezomib; D003165:Complement System Proteins; C481642:eculizumab
C1-inhibitor; IL-6; IVIG; antibody-mediated rejection; complement; desensitization; eculizumab; immunotherapy; kidney transplant; rituximab