HLA DSA detected after kidney transplantation(KT) correlate with outcome, but not all are equal and produce the same functional consequences. Early complement-binding DSA were asssociated with ABMR and loss, but information is scarce on late complement-binding DSA. We evaluated C3d and C1q-binding DSA long-term after KT and their impact on graft survival, function and histology.

METHODS: Prospective study of 440 active KT (transplanted 1979-2012) with HLA antibody tests from 2008 to 10/15 or graft-loss. 1-4 samples per patient analyzed with Screening beads, and Single Antigen Beads when needed. DSA were assesed for C3d and C1q-binding capacity. Demographics and clinical data were collected. For analysis, we selected the first time point with C3d+DSA, first DSA when C3d- or first test time in the absence of DSA (median time post-KT 31 months).

RESULTS: KT were55+12 years-old, 37.7%women, 16%re-transplants, creat 1.73mg/dl, MDRD4-FGE 45.6 ml/min and urine protein/creatinine: 331 mg/g at study point.After excluding 11 KT(inadequate sampling or DSA I only), 379 had no DSA and 51 showed DSA II: 34 C3d+ and 17 C3d-DSA. At 63 months median follow-up, C3d+DSA KT showed worse death-censored graft survival than no DSA KT(61.8 vs 89.6%,p=0.000), but C3d-neg DSA did not (82.4%,p=0.13). C3d+DSA had higher proteinuria (498.9+85.5 vs 129.5+33.4, p=0.02). C3d+ and C3d- KT were similar in age, gender, transplant number, pretransplant DSA (when present,100% and 71% C3d+), acute rejection rate, immunosuppression, creatinine and GFR at DSA time.

Most DSA were DQ despite C3d, but C3d+ were stronger than C3d-(MFI:13800+5842 vs 6365+5424,p=0.000). Of 34 patients with biopsies before loss, C3d+DSA KT showed more ABMR than C3d-DSA (83.33 vs 60%,p=0.19) with higher microinflammation(p=0.06) but similar rate of C4d+ or chronic transplant glomerulopathy.

C1q was tested in 43 KT with DSAII: 25 C1q+ and 18 neg. Results were concordant with C3d in 81.4%. Of 8 discordant patients:7 C1q-C3d+: 2 lost grafts, 4 had ABMR on biopsies, only 1 had no ABMR; 1 C1q+C3d- patient had a biopsy without AMR.

CONCLUSIONS: C3d+DSAII late after KT identify recipients at higher risk of graft-loss and ABMR. Based on outcomes, C1q lacked to categorize adequately a significant number of DSAII patients compared with C3d.

CITATION INFORMATION: Crespo M, Redondo D, Garcia C, Gimeno J, Perez M, Mir M, Hernandez J, Yelamos J, Faura A, Pascual J. Impact of C3d and C1q-Binding DSA Detected Long-Term After Kidney Transplantation. Am J Transplant. 2016;16 (suppl 3).

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