Tac-MMF Versus CsA-MMF/CsA-AZA-Based Regimens in Development of De Novo Complement-Binding Anti-HLA Antibodies After Kidney Transplantation.

BACKGROUND: Immunosuppressive regimens with tacrolimus or cyclosporine A (CsA) were compared for graft-related outcomes in conjunction with complement-binding de novo donor-specific antibodies (DSAs).

METHODS: Non-sensitized adult patients without rejection episodes within 3 months after transplantation were screened for the presence of de novo DSAs and C1q binding. Clinical and biopsy data were retrospectively obtained.

RESULTS: The analysis included 118 patients (68 tacrolimus, 50 CsA), with mean age and follow-up of 36.1 ± 11.4 and 7.2 ± 4.8 years, respectively. As compared with tacrolimus, the CsA group had higher rates of both class II DSAs and C1q-binding DSAs (20% vs 4.4%, P = .008, and 18% vs 0%, P = .003, respectively). Rates of chronic antibody-mediated rejection (cAMR), proteinuria >500 mg/g, and levels of creatinine both at last visits were also higher in the CsA group (20% vs 0%, P = .002, 30% vs 5.9%, P = .005, 1.67 ± 1.31 vs 1.18 ± 0.45 mg/dL, P = .019, respectively).Class II DSAs and C1q-binding class II DSAs were significantly correlated with the clinical outcomes (creatinine levels, proteinuria, and cAMR).

CONCLUSIONS: Compared with tacrolimus, CsA appears to pose a higher risk for the development of de novo anti-HLA antibodies with C1q-binding properties and, consequently, adverse graft-related outcomes.