Abstract
To determine the clinical relevance in kidney transplantation (Tx) of preformed HLA donor specific antibodies (DSA) revealed by Luminex single antigen beads assay (SAB). We analyzed 298 recipients (R) transplanted in a single center, between 2001 and 2006, with negative T and B CDC crossmatches (XM) and without any information regarding Luminex-detected antibodies. Stored pre-Tx sera of 165 R with ELISA PRA 0% and of 133 R with ELISA PRA 50% were screened with Labscreen Mixed and the positive ones were tested with the SAB assay (One Lambda). In the SAB assay, reactions with MFI >300 were recorded as positive; DSAs were defined as Abs against HLA-A, B or DR mismatches. Graft survival (GS) curves (Kaplan-Meier) were compared with the log-rank test; Cox regression analysis was used to calculate risk of graft loss. No difference in GS was detected among R with PRA ELISA and Luminex 0% (N = 165), PRA ELISA 50% without DSA (N = 44), PRA ELISA 50% with DSA 300-1,500 MFI (N = 19): overall 1-y and 8-y GS of 92.1% and 76.3%, respectively; R with DSA >1,500 MFI against HLA class I only (29) or class I and class II (N = 33) presented significanly (p < 0.001) lower 1-y and 8-y GS: 75.8% and 51.6%, respectively. We could not analyze the impact of isolated HLA class II DSA because only 8 R felt into this category. HLA class I DSA >1500 MFI conferred a relative risk of 4.4 for graft loss at one year and of 3.0 for late graft loss in R with functional kidneys at one year. In addition, R with HLA class I DSA >1500 MFI presented lower estimated glomerular filtration rates (Cockroft-Gault formula), at the first month (43.0 ± 9.9 vs. 56.0 ± 20.3 ml/min, p < 0.001) and at first year (56.6 ± 17.2 vs. 65.0 ± 21.2 ml/min, p < 0.01) post-Tx. HLA class I DSAs with MFIs up to 1,500 do not affect Tx outcome, whereas DSAs with MFIs >1,500, although not associated with immediate graft loss, confer risk for graft dysfunction already at the end of the first month, and a risk for long-term graft loss.
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