Ilias I N Doxiadis1, Dave Roelen, Frans H J Claas. 1. aEurotransplant Reference Laboratory, The Netherlands bDepartment of Immunohaematology and Blood, Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
PURPOSE OF REVIEW: Highly sensitized patients on the kidney waitlist have the least chance to receive a cross-match negative offer and, once transplanted, have a lower patient and graft survival. Until recently, complement-dependent cytotoxicity (CDC) was the standard method to define if a patient is sensitized or not. The introduction of more sensitive solid-phase assays (SPAs) to detect human leukocyte antigen (HLA) antibodies has led to a dramatic increase in the number of the patients on the waitlist. This review advocates the use of the 'old-fashioned' CDC to define the degree of sensitization and as the tool for allocation of kidneys to highly sensitized patients. RECENT FINDINGS: HLA-antibody screening using CDC is a cumbersome method that needs a high degree of expertise. SPA is easier, more reproducible and accessible to a large number of laboratories. The dogma that donor-specific antibodies (DSAs) are a contraindication for transplantation disappeared. The presence of SPA-DSA is rather a risk factor for complications than a contraindication. The opinion on the clinical relevance of SPA-DSA differs between the centers. SUMMARY: A proper designation of highly sensitized patients is crucial since it impacts the allocation. CDC-DSA is generally considered a contraindication for transplantation, whereas SPA-DSA remains controversial. The lack of consensus between centers is partly due to the heterogeneity of the HLA antibodies involved, the lack of standardization in antibody titer, the immunoglobulin (sub)class and the epitopes recognized. Until the issues are resolved, one should be careful to use the information generated in SPA for the allocation of kidneys and focus on the 'old CDC' that has shown to be effective in the past.
PURPOSE OF REVIEW: Highly sensitized patients on the kidney waitlist have the least chance to receive a cross-match negative offer and, once transplanted, have a lower patient and graft survival. Until recently, complement-dependent cytotoxicity (CDC) was the standard method to define if a patient is sensitized or not. The introduction of more sensitive solid-phase assays (SPAs) to detect human leukocyte antigen (HLA) antibodies has led to a dramatic increase in the number of the patients on the waitlist. This review advocates the use of the 'old-fashioned' CDC to define the degree of sensitization and as the tool for allocation of kidneys to highly sensitized patients. RECENT FINDINGS: HLA-antibody screening using CDC is a cumbersome method that needs a high degree of expertise. SPA is easier, more reproducible and accessible to a large number of laboratories. The dogma that donor-specific antibodies (DSAs) are a contraindication for transplantation disappeared. The presence of SPA-DSA is rather a risk factor for complications than a contraindication. The opinion on the clinical relevance of SPA-DSA differs between the centers. SUMMARY: A proper designation of highly sensitized patients is crucial since it impacts the allocation. CDC-DSA is generally considered a contraindication for transplantation, whereas SPA-DSA remains controversial. The lack of consensus between centers is partly due to the heterogeneity of the HLA antibodies involved, the lack of standardization in antibody titer, the immunoglobulin (sub)class and the epitopes recognized. Until the issues are resolved, one should be careful to use the information generated in SPA for the allocation of kidneys and focus on the 'old CDC' that has shown to be effective in the past.