Identification and Therapeutic Management of Highly Sensitized Patients Undergoing Renal Transplantation

• Published in: Drugs (New York, N.Y.) N.Y.), 2012-07, Vol.72 (10), p.1335-1354
• Main Authors: Huber, Lu, Lachmann, Nils, Dürr, Michael, Matz, Mareen, Liefeldt, Lutz, Neumayer, Hans-H., Schönemann, Constanze, Budde, Klemens
• Format: Article
• Language: English
• Subjects: Antibodies; Antigens; Biological and medical sciences; Blood & organ donations; Blood Group Incompatibility - diagnosis; Blood Group Incompatibility - prevention & control; Cytotoxicity; Desensitization, Immunologic; Flow cytometry; Graft Survival - immunology; Histocompatibility Testing; HLA Antigens - immunology; Humans; Immunology; Internal Medicine; Isoantibodies - blood; Kidney Transplantation - immunology; Kidney transplants; Laboratories; Leukocytes; Medical sciences; Medicine; Medicine & Public Health; Patients; Pharmacology/Toxicology; Pharmacotherapy; Plasmapheresis; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Therapy In Practice; Tissue Donors
• ISSN: 0012-6667; 1179-1950
• DOI: 10.2165/11631110-000000000-00000

Sensitization is generally referred to as the development of alloantibodies, specifically anti-human leukocyte antigen (HLA) immunoglobulin G (IgG) antibodies, most commonly caused by pregnancy, blood transfusion or a previous transplant. Despite being a well known phenomenon, there has not been a general consensus on its definition, monitoring or management. Today, 25% of the patients waitlisted for kidney transplant in the US have a panel reactive antibody (PRA) of >10% while, in the Eurotransplant zone, 14% have a PRA of >5%. Sensitized patients have more difficulty in finding a well HLA-matched donor, and have a higher risk of experiencing longer waiting times, more rejection episodes and eventually inferior long-term graft or patient survival. We review the currently available strategies in identifying and managing highly sensitized patients undergoing renal transplantation. We discuss the progress and limitations in laboratory techniques to elaborate on challenges in defining sensitized patients. The main management options (i.e. the Acceptable Mismatch Program, donor exchange programmes and the desensitization approach) and their mechanisms, related policies, advantages and outcomes, as well as medications and methods being investigated, are updated. In addition, particular emphasis is given to sensitization prevention, a practice that is neglected with our increasing ability to suppress the immune system.