The Impact of Pre-Transplant Red Blood Cell Transfusions in Renal Allograft Rejection

CMS evidence review | evidence_type=Technology Assessment | record_type=technology_assessment | document_id=78 | year=2011

Over 450,000 patients in the United States have end stage renal disease (ESRD). There are important morbidity and survival advantages to receiving renal transplantation versus dialysis. Human leukocyte antigens (HLA) are a set of human major histocompatibility complex derived glycoproteins that are expressed on cell surfaces and allow for discrimination of self from non-self.HLA have been classified into two major groups, Class I (HLA-A, HLA-B, and HLA-C) and Class II (HLA-DP, HLA-DQ, and HLA-DR). Recognition of the antigens displayed by the transplanted organ (alloantigen) is the prime event initiating the immune response against an allograft. Hyperacute rejection is an immediate recipient immune response against an allograft due to preformed recipient antibodies directed against the donor’s HLA. Acute rejection is a cell mediated process that generally occurs within 5 to 90 days after a transplant, although it can rarely occur after this time. Outside of the hyperacute rejection state, humoral rejection can still occur although less frequently than cell mediated acute rejection. Humoral rejection is characterized by B lymphocytes injuring the allograft through immunoglobulin and complement activities. The immunologic processes of chronic rejection are poorly understood but may result from cell-mediated, humoral, or drug-induced allograft damage. There have been major advances in immunosuppressive therapy. Immunosuppressive therapy is broken into three categories: induction therapy, maintenance therapy, and treatment of acute rejection episodes. A major advance was the use of cyclosporine and newer immunosuppressants occur in the mid 1980s and early 1990s. In transplants, the practice of blood transfusion has been shifting back and forth for the last few decades. High-volume use of blood transfusion was originally used in attempts to maintain ESRD patients who were anemic with red cell mass ranges of 20-25 percent. Due to concerns with transfusion-induced infections such as hepatitis and the production of anti-HLA antibodies resulting from the exposure to blood products, efforts were made in the 1970s to avoid the use of blood transfusions in renal transplant recipients. During the pre-cyclosporine era, studies suggested that non-transfused renal graft recipients were at higher risk for graft rejection as compared to those transfused recipients. Subsequently, many studies attempted to define the optimal dose and timing for the transfusion effect. With the introduction of cyclosporine in the early 1980s, leading to improved renal graft and patient survival, the beneficial role of blood transfusions and HLA matching was again being questioned. Meanwhile, some preliminary trials had shown the use of matched pretransplant blood transfusion or donor-specific transfusion (DST) to be beneficial. The evidence supporting the benefits of blood transfusion in renal transplantation is still scattered. It is unclear whether the benefits, if any, of pretransplant blood transfusion may be due to the modulation of immune response in which tolerance is induced.

Associated Medcac: MEDCAC Meeting for The Impact of ESA Use on Renal Transplant Graft Survival - 01/19/2011 Associated Nca: Original Consideration for Erythropoiesis Stimulating Agents (ESAs) for Treatment of Anemia in Adults with CKD Including Patients on Dialysis and Patients not on Dialysis (CAG-00413N) Issue: Over 450,000 patients in the United States have end stage renal disease (ESRD). There are important morbidity and survival advantages to receiving renal transplantation versus dialysis. Human leukocyte antigens (HLA) are a set of human major histocompatibility complex derived glycoproteins that are expressed on cell surfaces and allow for discrimination of self from non-self.HLA have been classified into two major groups, Class I (HLA-A, HLA-B, and HLA-C) and Class II (HLA-DP, HLA-DQ, and HLA-DR). Recognition of the antigens displayed by the transplanted organ (alloantigen) is the prime event initiating the immune response against an allograft. Hyperacute rejection is an immediate recipient immune response against an allograft due to preformed recipient antibodies directed against the donor’s HLA. Acute rejection is a cell mediated process that generally occurs within 5 to 90 days after a transplant, although it can rarely occur after this time. Outside of the hyperacute rejection state, humoral rejection can still occur although less frequently than cell mediated acute rejection. Humoral rejection is characterized by B lymphocytes injuring the allograft through immunoglobulin and complement activities. The immunologic processes of chronic rejection are poorly understood but may result from cell-mediated, humoral, or drug-induced allograft damage. There have been major advances in immunosuppressive therapy. Immunosuppressive therapy is broken into three categories: induction therapy, maintenance therapy, and treatment of acute rejection episodes. A major advance was the use of cyclosporine and newer immunosuppressants occur in the mid 1980s and early 1990s. In transplants, the practice of blood transfusion has been shifting back and forth for the last few decades. High-volume use of blood transfusion was originally used in attempts to maintain ESRD patients who were anemic with red cell mass ranges of 20-25 percent. Due to concerns with transfusion-induced infections such as hepatitis and the production of anti-HLA antibodies resulting from the exposure to blood products, efforts were made in the 1970s to avoid the use of blood transfusions in renal transplant recipients. During the pre-cyclosporine era, studies suggested that non-transfused renal graft recipients were at higher risk for graft rejection as compared to those transfused recipients. Subsequently, many studies attempted to define the optimal dose and timing for the transfusion effect. With the introduction of cyclosporine in the early 1980s, leading to improved renal graft and patient survival, the beneficial role of blood transfusions and HLA matching was again being questioned. Meanwhile, some preliminary trials had shown the use of matched pretransplant blood transfusion or donor-specific transfusion (DST) to be beneficial. The evidence supporting the benefits of blood transfusion in renal transplantation is still scattered. It is unclear whether the benefits, if any, of pretransplant blood transfusion may be due to the modulation of immune response in which tolerance is induced. Other Material: Other Material 1 Questions: Questions Technology Assessment: Download Technology Assessment [PDF, 1MB]