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. 2011 Oct;11(10):2132-43.
doi: 10.1111/j.1600-6143.2011.03640.x. Epub 2011 Aug 3.

Revisiting traditional risk factors for rejection and graft loss after kidney transplantation

T B Dunn  1 , H Noreen, K Gillingham, D Maurer, O G Ozturk, T L Pruett, R A Bray, H M Gebel, A J Matas
Affiliations

Revisiting traditional risk factors for rejection and graft loss after kidney transplantation

T B Dunn et al. Am J Transplant. 2011 Oct.

Abstract

Single-antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single-antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third-party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death-censored graft survival (DCGS) and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization.

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Conflict of interest statement

Disclosure

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

Figures

Figure 1
Figure 1
CMR (panels A–C) and AMR (panels D–F) free survival. P values are overall. Compared with Group 1, pairwise analysis showed Group 3 to have significantly more CMR (p=0.003, HR 2.2) and AMR (p<0.0001, HR 5.5). There was a trend toward more CMR in Group 2B (p=0.08).
Figure 2
Figure 2
Actuarial patient survival rates. Compared with Group 1, pairwise analysis showed significant differences in patient survival rates for Group 2A (p=0.02, HR 4.4), Group 2B (p=0.004, HR=6.3) and Group 3 (p=0.0006, HR=10.0).
Figure 3
Figure 3
Actuarial death censored graft survival rates were different overall. Pairwise analysis showed only Group 3 to be different from Group 1 (p=0.008, HR 2.9).
Figure 4
Figure 4
Creatinine clearance (Cockroft-Gault) over time. Differences between groups were significant at each post-transplant anniversary (year 1 p=0.01, year 2 =0.002, year 3 =0.0005, year 4 p=0.0048, and year 5 p=0.003).
Figure 5
Figure 5
Immunologic graft loss by group when AMR negative (A) or positive (B). There were no differences between groups when the AMR outcome was the same. Graft survival within study groups was significantly worse when AMR occurred (Group 1p<0.0001, Group 2B p=0.04, Group 3, p=0.003).
Figure 6
Figure 6
CMR and AMR outcomes for 3rd party sensitized recipients with pkPRA>0 (Group 2B). There were no significant differences in mean PRA (peak or D0 ) between nonrejecters and rejecters.
Figure 7
Figure 7
Primary vs retransplant rejection rates: CMR (panel A–C) and AMR (panel D–F). Rejection free graft survival is similar for third party sensitized recipients, and significantly worse for donor sensitized primary transplants.
Figure 8
Figure 8
CMR (panel A–D) and AMR (panel E–H) rates by donor source. LD=living donor, DD=deceased donor.
See this image and copyright information in PMC

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