OPTIONS AND OUTCOMES IN THE SENSITIZED KIDNEY RECIPIENT

C. Lefaucheur¹, A. Loupy², G.S. Hill², J. Andrade³, C. Antoine¹, D. Charron³, C. Suberbielle³, D. Glotz^1
1Nephrology And Kidney Transplantation, Saint-Louis Hospital, Paris/FRANCE, ²Histopathology, Georges Pompidou European Hospital, Paris/FRANCE, ³Immunology And Histocompatibility, Saint-Louis Hospital, Paris/FRANCE

Body: Introduction: The transplantation of patients sensitized to HLA is a major problem in kidney transplantation. The objective of this study is to appraise the clinical impact of the strength of preformed HLA antibodies quantified by contemporary solid-phase assays. Methods: We conducted a prospective observational single-center study analysing the occurrence of acute antibody-mediated rejection and survival of patients and grafts, in kidney transplant patients with pre-existing donor-specific HLA antibodies (HLA-DSA) detected by Luminex single antigen assays, on the peak and current sera. Between January 1998 and June 2006, 402 consecutive deceased-donor kidney transplants performed in our hospital were enrolled. The patients were eligible to receive a kidney allograft based on a negative NIH lymphocytotoxic crossmatch test the day of transplant. Results: Eight year graft survival of patients with preformed HLA-DSA was significantly worse (60.8%) than in sensitized patients without HLA-DSA (92.5%) and in non-sensitized patients (83.6%, p<.0001). The ROC curves analyses of HLA DSA strength in the prediction of antibody-mediated rejection showed that peak HLA-DSA Luminex mean fluorescence intensity (MFI) had a higher predictive value for acute antibody-mediated rejection than did current HLA-DSA MFI (area under the curve of 0.94 ± 0.02 vs 0.86 ± 0.04 respectively, p=.028). We determined that an MFI of 465 on the peak serum is associated with maximal specificity and sensitivity regarding the occurrence of acute antibody-mediated rejection. The relative risk of acute antibody-mediated rejection increased significantly with increasing MFI of the highest ranked peak HLA-DSA: from 1 for MFI < 465 up to 113 (95% CI, 30.8 to 414; p<.001) for patients with MFI > 6000. Graft survival decreased with rising MFI of the highest ranked HLA-DSA detected on peak pre-graft serum (log rank test, p<.001, Figure). Patients with MFI>3000 have 3.8 increased risk of graft loss than those with MFI<3000 (95% CI, 3.5 to 18.4, p<.0001). These results were also valid in patients without episode of acute antibody-mediated rejection (relative risk of 2.8, 95% CI, 1.5 to 16.9, p=.009). Conclusion: We found an increased risk for both antibody-mediated rejection and graft loss according to peak HLA-DSA strength. The prediction of antibody-mediated rejection was better using peak serum than with current serum. Quantification of these antibodies allows stratification of immunologic risk thus helping to define acceptable grafts in sensitized patients.

Disclosure: All authors have declared no conflicts of interest.