C3d‐positive donor‐specific antibodies have a role in pretransplant risk stratification of cross‐match‐positive HLA‐incompatible renal transplantation: United Kingdom multicentre study

• DOI: 10.1111/tri.13663
• Publication Date: 2020-06-01T20:52:48Z
• Authors: Adarsh Babu; Natasha Khovanova; Olivia Shaw; Sian Griffin; David Briggs; Nithya S. Krishnan; Simon Fletcher; Christopher Imray; Adrienne Seitz; Richard Baker; Matthew Wellberry...; Brendan Clarke; Katherine Cullen; Tracey Rees; Frankie Edwards; Emma Burrows; Louise Howe; Chloe Martin; Anthony Dorling; Daniel Zehnder; Robert M. Higgins; Daniel A. Mitchell; Sunil Daga
• Keywords: Graft Rejection; Graft Survival; graft survival; 610; risk stratification; renal transplantation; Kidney Transplantation; Risk Assessment; Tissue Donors; United Kingdom; C3d; donor-specific antibodies; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; HLA Antigens; Isoantibodies; 617; Humans; cross-match; RD

Anti-HLA-antibody characteristics aid to risk-stratify patients and improve long-term renal graft outcomes. Complement activation by donor-specific antibody (DSA) is an important characteristic that may determine renal allograft outcome. There is heterogeneity in graft outcomes within the moderate to high immunological risk cases (cross-match-positive). We explored the role of C3d-positive DSAs in sub-stratification of cross-match-positive cases and relate to the graft outcomes. We investigated 139 cross-match-positive living-donor renal transplant recipients from four transplant centres in the United Kingdom. C3d assay was performed on serum samples obtained at pretreatment (predesensitization) and Day 14 post-transplant. C3d-positive DSAs were found in 52 (37%) patients at pretreatment and in 37 (27%) patients at Day 14 post-transplant. Median follow-up of patients was 48 months (IQR 20.47-77.57). In the multivariable analysis, pretreatment C3d-positive DSA was independently associated with reduced overall graft survival, the hazard ratio of 3.29 (95% CI 1.37-7.86). The relative risk of death-censored five-year graft failure was 2.83 (95% CI 1.56-5.13). Patients with both pretreatment and Day 14 C3d-positive DSAs had the worst five-year graft survival at 45.5% compared with 87.2% in both pretreatment and Day 14 C3d-negative DSA patients with the relative risk of death-censored five-year graft failure was 4.26 (95% CI 1.79, 10.09). In this multicentre study, we have demonstrated for the first time the utility of C3d analysis as a distinctive biomarker to sub-stratify the risk of poor graft outcome in cross-match-positive living-donor renal transplantation.