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      One good match permits another—why HLA-matched blood transfusion makes sense

      Clinical Kidney Journal
      Oxford University Press

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          Abstract

          Standard management of patients with chronic renal impairment includes the avoidance of transfusion of allogeneic red cells where practicable. This encourages erythropoiesis and minimizes exposure to human leukocyte antigen (HLA) molecules present in the transfusion [1]. Where patients become sensitized to HLA following exposure to donor material, this can limit the availability of potential kidney donors from the deceased donor pool. Significantly, there is also potential to be sensitized to living-related donors. We describe a case which led our service to alter our blood transfusion practice. A 7-year-old male with both Leber's congenital amaurosis (LCA) and infantile pyknodysostosis developed profound marrow failure causing chronic ongoing anaemia which required multiple blood transfusions. His renal function deteriorated from tubulo-interstitial nephritis and is now approaching end stage (eGFR 18 mL/min/1.73 m2). The chronic anaemia eventually responded to high doses of recombinant erythropoietin. He has two siblings, one of whom has LCA, and another has pyknodysostosis. There are no suitable living donors, so the child is awaiting a deceased donor. Following repeated transfusions, he has developed antibodies to several HLA molecules with a calculated panel reactivity of 50%, excluding 71% of the UK population as suitable donors. This will likely prolong the waiting time for a suitable deceased donor, impacting on his duration of renal replacement therapy and long-term prognosis. Following recognition that HLA sensitization could devastate the available donor pool, and the fact that leukodepletion has been shown not to reduce sensitization in renal patients awaiting transplant [2] (potentially due to soluble and red-cell-bound HLA) [3], we addressed our transfusion policy. In a limited number of patients, we requested washed red cells, assuming that this would reduce the presence of soluble HLAs in the serum. Further discussion led to more definitive management of the avoidance of allosensitization by using HLA-matched red cells for transfusion as first suggested 25 years ago [4]. A recent study demonstrated matching for HLA-A-, HLA-B- and HLA-DR-negated sensitization in 37 patients [5]. Concerns about HLA-matched transfusions include the availability of suitable units and the cost-benefit, given the additional expense in provision. The increased risk of sensitization in paediatric patients, the predictable need for occasional transfusion, the high probability of paediatric recipients needing more then one graft in a lifetime and the subsequent high number of quality-adjusted life years contribute to our justification that matching red cells for HLA-A, HLA-B and HLA-DR is a sensible approach for the paediatric end-stage renal population. Authors' contribution B.C.R., S.A.J. and N.E.M. were involved in the clinical care of the patient. V.C. performed the PRA analysis and typing and J.P.W. facilitated the HLA matching. All authors contributed to the manuscript. Conflict of interest statement None declared.

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          Most cited references13

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          Allosensitization rate of male patients awaiting first kidney grafts after leuko-depleted blood transfusion.

          Blood transfusions are generally avoided for potential renal transplant recipients due to risk of human leukocyte antigen (HLA) allosensitization. Despite the near universal use of erythropoiesis-stimulating agents, there are still occasions when patients require blood transfusions for reasons such as resistance to erythropoiesis-stimulating agents or cardiovascular instability. The risk of allosensitization in renal patients is believed to be lower with leuko-depleted blood. We sought to quantify the risk of blood transfusion per se in male renal patients on the transplant waiting list for their first kidney graft, using sensitive solid phase antibody detection.
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            Effect of one-HLA-DR-antigen-matched and completely HLA-DR-mismatched blood transfusions on survival of heart and kidney allografts.

            Blood transfusions can influence the survival of organ allografts favorably, in spite of the danger of sensitization. We investigated the influence of HLA compatibility between blood donors and transfusion recipients on the production of HLA antibodies and on graft survival. Among recipients of transfusions who shared one HLA-DR antigen with their respective donors, antibodies developed in 6 of 28 who had received one transfusion, in 2 of 16 who had received three transfusions, and in 4 of 24 who had undergone renal transplantation. Among recipients who were mismatched with their donors for both HLA-DR antigens, the rate of sensitization was significantly higher in all three of these groups (18 of 30, P = 0.02; 12 of 16, P = 0.0007; and 12 of 22, P = 0.001). The survival of kidney allografts among graft recipients who were given transfusions and shared one HLA-DR antigen with their blood donors (81 percent at five years) was significantly higher than among recipients who were given transfusions and were mismatched for both HLA-DR antigens (57 percent; P = 0.02) or among recipients who were not given transfusions (45 percent; P = 0.001). There was no difference in graft survival between patients who received transfusions mismatched for two HLA-DR antigens and those who were not given transfusions. We conclude that allograft survival can be improved by pretransplantation blood transfusion when the transfusion recipients share at least one HLA-DR antigen with their donors. In view of the increased rate of sensitization and the lack of improvement in graft survival, the transfusion of blood mismatched for two HLA-DR antigens appears to be contraindicated in candidates for transplantation.
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              Class I HLA molecules on human erythrocytes. Quantitation and transfusion effects.

              HLA class I molecules were quantitated on erythrocytes from individuals expressing either high or low levels of such antigens. Quantitative determinations were accomplished using 125I-labeled Fab fragments of the anti-HLA monoclonal antibody W6/32 in a competitive binding assay. The experimental conditions of the test system were established using red cells from an individual found to express high levels of red cell HLA when examined by flow cytometry. The competitive binding assay met the requirements of ligand specificity and specific binding saturability. Scatchard analysis revealed that there were 1684 +/- 39 (mean +/- SD) HLA molecules/red cell. In two other donors in whom erythrocyte HLA was undetectable by flow cytometry specific binding of the 125I-W6/32 Fab fragments was clearly demonstrated, indicating the presence of HLA on red cells of these donors as well. The number of HLA molecules/red cell was estimated to be between 100 and 200 for these individuals. Thus, in a blood transfusion unit, the number of HLA molecules contributed by the red cells is comparable to that of the leukocytes. Blood highly depleted of leukocytes and platelets and selected from donors with low amounts of red cell HLA was not beneficial (when transfused to selected patients) in that their sensitizing effects were not significantly different from regular blood transfusions. These results show that the amount of HLA antigens on red cells, while low if compared with other cell types, is significant in terms of the absolute antigenic content of blood transfusions. They also show that transfusion of blood units containing HLA antigens in concentrations as low as can be achieved with current technology were not useful in preventing HLA sensitization in patients at risk.
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                Author and article information

                Journal
                27293581
                4898346
                10.1093/ckj/sft074
                http://creativecommons.org/licenses/by-nc/4.0/

                Nephrology
                Nephrology

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