Impact of Early Blood Transfusion After Kidney Transplantation on the Incidence of Donor-Specific Anti-HLA Antibodies

I. Ferrandiz; N. Congy-Jolivet; A. Del Bello; B. Debiol; K. Trébern-Launay; L. Esposito; D. Milongo; G. Dörr; L. Rostaing; N. Kamar

Disclosures

American Journal of Transplantation. 2016;16(9):2661-2669. 

In This Article

Patients and Methods

Between January 2008 (i.e. the date when the solid-phase Luminex assay was set up at our institution) and December 2012, 750 kidney transplantations were performed at our institution. Patients excluded from the study were those who had detectable anti-HLA antibodies before transplantation (n = 260), those with a nonrenal organ transplant (n = 10), those who received combined transplantation (n = 45) and those who underwent ABO-incompatible transplantation (n = 12). Hence, 423 patients who were not anti-HLA–sensitized and had a negative crossmatch at transplantation were considered for inclusion in this study. Of these, 23 patients required an allograft nephrectomy within the first month after transplantation because of vascular thrombosis, and three other patients had a primary nonfunctional graft; these patients were also excluded from the analyses. In addition, seven other patients who required an allograft nephrectomy between 1 mo and 1 year after transplantation were excluded from the study because nephrectomy can cause anti-HLA antibodies to develop, especially after immunosuppression is withdrawn. The causes of graft loss that required allograft nephrectomy were severe acute rejection (n = 1), relapse of the initial glomerular disease (n= 1), an infectious kidney–allograft–artery aneurysm (n= 1), septic shock (n= 1), urological complications (n= 1), kidney–allograft–artery dissection after angioplasty (n= 1) and chronic allograft dysfunction (n= 1). All seven patients had received blood products after transplantation, but none had developed anti-HLA antibodies before graft loss and allograft nephrectomy. The median time between transplantation and allograft nephrectomy was 94 days (range: 37–388 days).

A total of 390 patients were included in the study. The patient characteristics are presented in Table 1. Patients were followed up until 1 year after transplantation or until graft loss or death if it occurred within the first year after transplant.

A blood transfusion was decided on at the discretion of the physician. Data regarding blood transfusions performed within the first year after transplantation were obtained from the blood bank for each patient. Because all patients were followed up at our institution, the probability of a patient having a blood transfusion elsewhere was very low. All transfused blood components were leukodepleted. Separation of leukocytes from blood cells was done using a leukodepletion filter. Controls were systematically done to ensure that the residual leukocyte count was below 1 × 106. A transfusion event was defined as a transfusion of one component or several components once or several times within a 1-week period. The volume of each packed RBC unit was 250–300 mL. The volume of each packed platelet unit was 300–400 mL.

Clinical data were, in part, obtained from the DIVAT database (Donneés Informatisées et Validées en Transplantation, http://www.divat.fr).

At our center, most patients are included in clinical trials. Consequently, the use and type of induction therapy as well as the type of initial immunosuppression was determined according to the ongoing clinical trial when the patients received their transplants.

At our center, anti-HLA antibodies are routinely assessed annually after transplantation and each time a patient presents with impaired kidney function. AMR was defined by the presence of histological features of humoral rejection (i.e. microcirculation injury and positive C4d staining) with or without the presence of anti-HLA DSAs.

Immunological Analyses

Luminex® assays determined the specificity of class I HLAs in A/B and class II DR/DQ IgG antibodies in the recipients' sera (centrifuged at 10 000g for 10 min) using LABScreen single-antigen HLA class I and II detection tests (One Lambda, Canoga Park, CA), according to the manufacturer's instructions. The presence and specificity of antibodies were then detected using a LABScan 100® (One Lambda), and the mean fluorescence intensity (MFI; baseline) for each sample in each bead was evaluated. The baseline value was calculated as follows: (raw sample MFI–raw negative serum control MFI)–(negative-bead raw MFI sample–negative-bead raw MFI negative serum control). A baseline value of >500 was considered positive. The immunodominant DSA was defined as the DSA with the highest MFI.

Statistical Analyses

Reported values represent the mean (plus or minus standard deviation) or the median (range). Proportions were compared using the Fisher exact test. Quantitative variables were compared using the Mann–Whitney nonparametric test or the Student t-test. The predictive factors for developing a DSA and for presenting with AMR were determined by univariate and multivariate regression analyses. Factors associated in univariate analyses (at a significance of p < 0.05) with the detection of DSAs after transplantation or with AMR were selected for inclusion in the multivariate analyses. A p-value of <0.05 was considered statistically significant.

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