Effect of Red Cell Transfusions on Future Kidney Transplantation

Abstract

SummaryRed cell transfusions, erythropoiesis-stimulating agents (ESAs), and intravenous iron therapy all have a place in the treatment of anemia associated with CKD. Their relative merits and uses are subject to many clinical and nonclinical factors. New concerns associated with the use of ESA therapy make it likely that the use of blood transfusions will increase, refueling previous debates about their associated risks. Data on whether red cell transfusions increase sensitization to HLA antigens, rendering subsequent transplantation more problematic, are mainly derived from older literature. Older data suggested that women were more at risk of HLA sensitization than men, particularly those with previous multiple pregnancies, although recent U.S. Renal Data System data have challenged this. HLA sensitization prolongs the waiting time for transplantation and reduces graft survival. Leukocyte depletion of red cells does not appear to reduce the risk of HLA sensitization. This review summarizes much of the data on these issues, as well as highlighting the need for further research on the potential risks for blood transfusion in patients with CKD.

Clinical Role of Human Leukocyte Antigen in Health and Disease

“…In the same time, after transplantation, the presence of preformed HLA antibodies is associated with an increased risk of early and late graft loss. Also, the pre-existing donor-specific HLA antibodies identified by Luminex at the time of transplantation are associated with a higher incidence of antibodymediated rejection and inferior graft survival [78][79][80][81]. ...............................................................................................................................................................…”

Luminex® and Its Applications for Solid Organ Transplantation, Hematopoietic Stem Cell Transplantation, and Transfusion^*

“…However, in recent years new concerns regarding the use of these drugs in chronic kidney disease patients arose, critically discussing the life-threatening side effects like stroke that might outweigh the beneficial rise in erythropoietin-induced hemoglobin [50]. If these studies hold up in the future, an increase in the use of red blood cell products which is associated with the risk of sensitization could be awaited.…”

Oral Hypoxia–Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD

“…Specifically, RBC transfusions may allosensitize patients with CKD, reducing likelihood to receive a transplant (18)(19)(20). These potential consequences of untreated/ undertreated anemia coupled with ESA safety concerns call for safer, effective, and accessible treatment for CKD anemia (21).…”

“…In a placebo-controlled, phase 2a, 4-week treatment study, roxadustat increased Hb levels in a dose-dependent manner and improved iron homeostasis while modestly and transiently increasing endogenous EPO levels within or near physiologic range (22). We now report data from an open label, phase 2b study of roxadustat administered for [16][17][18][19][20][21][22][23][24] weeks to patients with NDD-CKD who were anemic, further exploring dose and frequency strategies to determine the optimal dose and regimen for phase 3 studies.…”