Background: Studies assessing the risk of pre-transplant antibodies are generally restricted to low levels of donor specific antibody (DSA). Here we analyze pre-transplant HLA DSA, C1q binding, and anti-AT1R antibodies in kidney recipients transplanted prior to the use of solid phase antibody assays and flow cytometric crossmatching.

Methods: Single antigen bead (SAB) and anti-AT1R antibody testing was performed on 202 pre-transplant sera from kidney recipients transplanted based on a negative CDC crossmatch, prior to the adoption of SAB and flow cytometric crossmatching (1999-2009). Type (class I, II, and anti-AT1R) and strength (MFI) of pre-transplant antibodies were compared in patients with short graft survival or rejection of any kind (<1 year; n=76) to those with long-term graft survival/no rejection (>5 years; n=126).

Results: 32.9% (25/76) of patients with early graft loss or rejection had pre-transplant DSA compared to 18.3% (23/126) with extended graft survival and no rejection (p<0.04). For patients with pre-transplant DSA, mean Sum MFI was higher (p<0.001) in those with early graft/rejection, 27,915 ± 36,122 (inter-quartile range (IQR): 1,538-35,221), than in those with extended graft survival and no rejection, 8,533 ± 11,690 (IQR: 903-14,266), (p<0.001). Interestingly, 5.6% (7/126) of patients with extended graft survival and no rejection had pre-transplant DSA with Sum MFI values > 5,000, and there was no clear association between complement fixing ability (C1q binding) and outcome. Higher Sum MFI values were associated with greater odds of early graft failure (OR=1.08 [1.02, 1.16] per 1,000 MFI). 19.4% (13/67) of patients with early graft loss or rejection had pre-transplant anti-AT1R antibody compared to 18.3% (23/126) of the extended survival/no rejection cohort. Pre-transplant anti-AT1R antibodies were not significantly associated with early graft loss or rejection either alone or when HLA DSA were also present.

Conclusion: Early graft loss/rejection is associated with increased levels of pre-transplant HLA DSA, although some patients with high HLA DSA levels experienced no rejection or graft loss within the first 5 years of transplant. Outcomes in DSA positive groups showed no association with C1q binding ability. Pre-transplant AT1R antibodies had no significant association with allograft survival or rejection.

CITATION INFORMATION: Redfield R, Astor B, Jung-Hynes B, Mandelbrot D, Kaufman D, Djamali A, Ellis T. A Novel Study to Determine the Association of Pre-Transplant Donor Specific Antibody and AT₁R Antibody with Kidney Transplant Outcomes Prior to Adoption of Solid Phase Antibody Assays. Am J Transplant. 2016;16 (suppl 3).

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