Improvement in outcomes in renal transplant patients with de novo donor specific anti-HLA antibodies (dnDSA) is needed. This analysis aims to identify surrogate endpoints following dnDSA onset that could aid clinical trial design and evaluation of new therapies.

Methods: 341 consecutive HLA-mismatched, pre-transplant DSA negative, primary renal transplant patients transplanted between 3/99 and 12/10 were included in the analysis. Serum was collected pre-transplant and post-transplant at 1, 3, 6, 9, 12 months and bi-annually, thereafter. The sera were retrospectively tested for the presence of HLA IgG and IgG3 antibodies via LABScreen single antigen bead assay. Actual 3-year graft survival analysis is death-censored.

Results: In the 99 patients with ≥ 3-years post-dnDSA follow-up, the 1-year and 3-year graft survival following DSA onset in was 90% and 72%, respectively (Fig A). Patients with both HLA Class I and II dnDSA had the poorest survival (Fig B). Variables to test as surrogate predictors of allograft loss at 3-years post-DSA were selected (Table 1). Individually, 25% decline in glomerular filtration rate (eGFR) at 1-year post-DSA (HR 7.1, p<0.001) and acute rejection by 1-year post-DSA (HR 3.9, p=0.001) were the top two predictors of 3-year post-DSA graft loss. When combined, the composite variable of acute rejection (with or after DSA) AND 25% decline in eGFR was highly predictive of graft loss at 3 years post-DSA (HR 8.5, p<0.001) with a PPV of 80% and NPV of 83% (Fig C).

Conclusion: Based on our findings the combined endpoint of developing acute rejection (Mixed or AMR) and 25% eGFR decline at 1-year post-DSA carried the highest risk of graft failure at 3-years post-DSA. Additionally, the pathway to failure following dnDSA seems to include conversion to IgG3+ DSA. Those patients without these findings may not need immediate treatment.

« Back to 2015 American Transplant Congress