Leukocyte Reduction of Red Blood Cell Transfusions Does not Decrease Allosensitization Rates in Potential Kidney Transplant Candidates

Abstract

Abstract. A significant proportion of potential kidney transplant candidates continue to periodically require blood transfusions that carry a risk of allosensitization. Leukocyte reduction (leukoreduction) of blood products has been proved to reduce transfusion-associated allosensitization in patients with hematologic malignancies; however, the effect in potential kidney transplant candidates is unknown. A total of 112 kidney transplant candidates who received red blood cell transfusions while on the transplant waiting list were identified retrospectively. Sixty received a transfusion before leukoreduction (non-LR), and 52 received a transfusion after the local implementation of universal leukoreduction of blood products (LR). There was no difference in transfusion-associated allosensitization rates in patients who received a transfusion during the two eras (non-LR 27% [16 of 60] versus LR 33% [17/52]; NS). Likewise, no difference was observed in subgroups identified as being at high risk of allosensitization (previous pregnancy, transplant, or five or more previous transfusions) or at low risk (no previous allogeneic exposures) (high risk: non-LR 52% versus LR 55%; low risk: non-LR 10% versus LR 8%). Multivariate analysis revealed previous pregnancy to be the only significant risk factor associated with transfusion-associated allosensitization (relative risk, 8.2; 95% confidence interval, 2.4 to 24.0; P ϭ 0.0001). Leukoreduction, in particular, was not associated with any protective effect. In summary, leukoreduction of red blood cell transfusions does not confer any protection against transfusion-associated allosensitization for potential kidney transplant candidates. Physicians who care for patients with ESRD must continue to practice careful transfusion avoidance while alternative strategies to minimize transfusion associated allosensitization are sought.Despite the fact that recombinant erythropoietins have substantially decreased the need for transfusions in patients with ESRD, United Network for Organ Sharing (UNOS) data indicate that approximately 30% of wait-listed transplant candidates continue to receive red blood cell (RBC) transfusions at some point before transplantation (1, 2). In the past, some transplant programs administered deliberate pretransplant transfusions aimed at optimizing graft outcomes (i.e., the beneficial transfusion effect); however, more recent data indicate that this beneficial effect is no longer apparent, perhaps as a result of improving graft outcomes overall (2-5). Concerns of transfusion-associated allosensitization persist for potential transplant candidates, and it is likely that the majority of current transfusions are administered for other clinical indications.

Effect of Red Cell Transfusions on Future Kidney Transplantation

“…Previous studies have also reported that leukoreduction of blood products is ineffective in decreasing sensitization in previously transplanted patients and in potential kidney transplant candidates (48)(49)(50). A possible reason for this finding is that the number of HLA molecules contributed by the red blood cells is similar to that of the leukocytes (51).…”

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

“…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.…”

“…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).…”

Detection of presensitization in recipients of kidney transplants

“…However, in some situations clinical need for a blood transfusion outweighs the risk of sensitization, so appropriate patient therapy protocols must be provided with regards to the risk of allosensitization after leukodepleted as well as standard blood transfusions. Additionally, resolution of the allosensitization problem can be obtained through: a brief course of immunosuppression beginning at the time of transfusion, usage of HLA matched transfusions and introduction of less allogenic blood substitutes or modified blood products in the future [26]. In conclusion, in the group of patients awaiting kidney transplants who received transfusions, the positive correlation between the number of received blood units and the level of preformed antibodies was determined.…”

“…In the 1980s, SanFilippo et al [25] conducted a randomized study transfusing renal transplant candidates with either standard or leukoreduced red blood cell units and found no difference in allosensitization rate. According to study of Karpinski et al, [26] no significant difference in the rate of transfusion-associated allosensitization in renal transplant candidates who received either standard or leukoreduced red blood cell transfusions were found (27% versus 33%, respectively). According to Vamvakas,[27] despite the reduction of leukocytes in the received blood products, the rates of alloimmunization in different studies vary considerably and range from 7% to 44% among recipients of leukocyte-reduced blood transfusions and from 20% to 50% among control recipients of non-leukoreduced blood components.…”