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

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Leukocyte Reduction of Red Blood Cell Transfusions Does Not Decrease Allosensitization Rates in Potential Kidney Transplant Candidates J Am Soc Nephrol 15: 818–824, 2004 Leukocyte Reduction of Red Blood Cell Transfusions Does not Decrease Allosensitization Rates in Potential Kidney Transplant Candidates MARTIN KARPINSKI,* DENISE POCHINCO,† IGA DEMBINSKI,† WILLIE LAIDLAW,† JAMES ZACHARIAS,* and PETER NICKERSON*† *Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; and †Immunogenetics Laboratory, Winnipeg Blood Center, Winnipeg, Manitoba, Canada Abstract. A significant proportion of potential kidney trans- as being at high risk of allosensitization (previous pregnancy, plant candidates continue to periodically require blood trans- transplant, or five or more previous transfusions) or at low risk fusions that carry a risk of allosensitization. Leukocyte reduc- (no previous allogeneic exposures) (high risk: non-LR 52% tion (leukoreduction) of blood products has been proved to versus LR 55%; low risk: non-LR 10% versus LR 8%). Mul- reduce transfusion-associated allosensitization in patients with tivariate analysis revealed previous pregnancy to be the only hematologic malignancies; however, the effect in potential significant risk factor associated with transfusion-associated kidney transplant candidates is unknown. A total of 112 kidney allosensitization (relative risk, 8.2; 95% confidence interval, transplant candidates who received red blood cell transfusions 2.4 to 24.0; P ϭ 0.0001). Leukoreduction, in particular, was while on the transplant waiting list were identified retrospec- not associated with any protective effect. In summary, leukore- tively. Sixty received a transfusion before leukoreduction (non- duction of red blood cell transfusions does not confer any LR), and 52 received a transfusion after the local implemen- protection against transfusion-associated allosensitization for tation of universal leukoreduction of blood products (LR). potential kidney transplant candidates. Physicians who care for There was no difference in transfusion-associated allosensiti- patients with ESRD must continue to practice careful transfu- zation rates in patients who received a transfusion during the sion avoidance while alternative strategies to minimize trans- two eras (non-LR 27% [16 of 60] versus LR 33% [17/52]; NS). fusion associated allosensitization are sought. Likewise, no difference was observed in subgroups identified Despite the fact that recombinant erythropoietins have substan- Allosensitization is associated with significant barriers to tially decreased the need for transfusions in patients with successful transplantation in patients with ESRD, including ESRD, United Network for Organ Sharing (UNOS) data indi- prolonged waiting times and inferior graft outcomes (6–8). cate that approximately 30% of wait-listed transplant candi- Accordingly, any measure to limit allosensitization would rep- dates continue to receive red blood cell (RBC) transfusions at resent a substantial advance for ESRD patients. Of the three some point before transplantation (1, 2). In the past, some principal causes of allosensitization—pregnancy, transplanta- transplant programs administered deliberate pretransplant tion, and transfusions—only the last is perhaps modifiable. transfusions aimed at optimizing graft outcomes (i.e., the ben- Leukocyte reduction of blood products (leukoreduction) re- eficial transfusion effect); however, more recent data indicate duces the transfused load of allogeneic leukocytes and has that this beneficial effect is no longer apparent, perhaps as a been proved to limit transfusion-associated allosensitization in result of improving graft outcomes overall (2–5). Concerns of patients with hematologic malignancies undergoing chemo- transfusion-associated allosensitization persist for potential therapy (9). transplant candidates, and it is likely that the majority of The impact of RBC leukoreduction on allosensitization in current transfusions are administered for other clinical ESRD patients is unknown. The few studies that have exam- indications. ined this practice either have been uncontrolled or have screened for allosensitization using technically inferior anti- Received October 9, 2003. Accepted December 12, 2003. HLA antibody screening techniques (10, 11). Several recent Correspondence to Dr. Martin Karpinski, University of Manitoba, Room studies have highlighted the superior sensitivity of flow cyto- GE421B, Health Sciences Centre, 820 Sherbrook Street, Winnipeg, MB, metric anti-HLA antibody screening (FlowPRA) (12–14). We Canada R3A 1R9. Phone: 204-787-1524; Fax: 204-787-3326; E-mail:[email protected] thus set out, in this retrospective cohort study, to use sensitive 1046-6673/1503-0818 flow cytometric techniques to determine whether universal Journal of the American Society of Nephrology RBC leukoreduction has reduced the incidence of transfusion- Copyright © 2004 by the American Society of Nephrology associated allosensitization in potential kidney transplant can- DOI: 10.1097/01.ASN.0000115399.80913.B1 didates within our center. J Am Soc Nephrol 15: 818–824, 2004 Leukocyte Reduction and Allosensitization Rates 819 Materials and Methods flow cytometric technique (FlowPRA; OneLambda). Both screening Universal Leukoreduction in Canada assays were performed in the Immunogenetics Laboratory at the All blood products within Manitoba are distributed by a single Winnipeg Blood Centre using standard techniques previously de- agency, Canadian Blood Services, and since September 1999, all RBC scribed (13). A patient was considered sensitized before a transfusion Ն units distributed within Manitoba have been leukoreduced in compli- when the AHG-CDC PRA was 10% and/or when the FlowPRA ance with a nationwide Health Canada directive (15). This directive assay revealed any detectable anti-HLA antibodies. Transfusion-as- was issued in response to numerous lines of evidence indicating that sociated sensitization was defined as the de novo appearance of a leukoreduction of blood products likely reduces the incidence of positive FlowPRA or as an increment in the FlowPRA value of Ն several adverse transfusion reactions, including allosensitization. The 10%. Winnipeg Blood Centre now performs universal prestorage leukore- duction of RBC units with commercially available in-line filtration Statistical Analyses systems (Leukotrap WB and RC PL; Pall Medical, East Hills, NY), Statistical analysis was performed using Statview 5.0 software and the maximum accepted residual white blood cell (WBC) count is (SAS Institute, Cary, NC). Values are reported as mean Ϯ SEM or, Ͻ ϫ 6 ϫ 9 5 10 /unit (normal WBC content approximately 5 10 /unit). where indicated, as medians and ranges. The ␹2 test was used for Internal quality control testing is applied to at least 1% of all units, and comparison of categorical variables, whereas the t test was applied to ϫ the actual residual WBC content is observed to be approximately 3 comparisons of continuous variables. P Յ 0.05 was considered to be 5 10 /unit (unpublished data, Canadian Blood Services/Pall Corp.). significant, and values Ͼ0.10 are reported as nonsignificant (NS). In the multivariate analysis of risk factors for allosensitization, univariate Study Procedures risk factors associated with the outcome with P Յ 0.10 were allowed This study was approved by the University of Manitoba Biomed- into the final model. These included a ϩve FlowPRA before transfu- ical Research Ethics Board. The study population consisted of patients sion, previous pregnancy, previous transplantation, previous transfu- who were on the Manitoba renal transplant waiting list and had sions, and the number of RBC units transfused in the episode under received RBC transfusions while wait-listed for transplantation. None study. Leukoreduction was considered in the models despite being of the transfusions administered was prescribed as deliberate pretrans- found to be nonsignificant in univariate analysis. Pregnancy and plant transfusions aimed at optimizing graft outcomes. Sera for anti- previous transfusions were considered as both categorical and contin- HLA antibody screening on wait-listed patients were collected bi- uous variables in the models analyzed. There was no demonstrable monthly during the period of study as well as 2 to 4 wk after any relationship between increasing numbers of pregnancies or transfu- transfusion. Serum collection and transfusions are tracked meticu- sions and an increasing incidence of allosensitization, and the overall lously by local transplant coordinators and Immunogenetics Labora- strength of the model was superior when these were considered as tory technologists. Adult transplant candidates who received RBC categorical variables. For these reasons, five or more previous trans- transfusions between January 1996 and June 2003 thus were identified fusions was chosen as the transfusion variable, and this cutoff is also for retrospective study, and of 112 wait-listed ESRD patients identi- supported by previous studies (16). fied, 60 received RBC units before the implementation of universal leukoreduction and 52 thereafter. Individuals who were broadly sen- sitized (FlowPRA Ն80%) before transfusion were excluded (n ϭ 3). Results Patient data and transfusion records were abstracted from Manitoba During the period of study, 112 individuals on the renal Renal Program database. transplant waiting list received RBC transfusions and had appropriate pre- and posttransfusion serum samples collected Anti-HLA Antibody Screening for anti-HLA antibody screening. Sixty patients received a Transfusion-associated
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