Association of immunosuppressive agents and cytomegalovirus infection with de novo donor-specific antibody development within 1 year after renal transplantation.

The association between immunosuppressive therapy or cytomegalovirus (CMV) infection and detection of de novo donor-specific antibody (dnDSA) at 1 year after transplantation was evaluated. The impact of dnDSA positivity at 1 year after transplantation on long-term death-censored renal graft survival was also evaluated. One hundred and sixty adults receiving living renal allografts were studied. Inclusion criteria were renal graft survival for at least 1 year and a standard regimen of immunosuppressive therapy with tacrolimus, mycophenolate mofetil (MMF), steroids, and basiliximab. DSA were measured retrospectively by the Luminex assay. The coefficient of variation (CV) was calculated and receiver operating characteristic (ROC) analysis was employed to clarify the association of tacrolimus with development of dnDSA. Seven of the 160 patients (4.4%) were positive for dnDSA. The intra-patient minimum trough level of tacrolimus (cutoff value: 3.2 ng/mL) was associated with development of dnDSA. Discontinuation of MMF and treatment of CMV infection were more frequent in patients with dnDSA than in those without dnDSA. In multivariate analysis, a low trough level of tacrolimus, discontinuation of MMF, and treatment of CMV infection within 1 year after transplantation were independently associated with detection of dnDSA at 1 year. In patients with or without dnDSA at 1 year, the 10-year allograft survival rate was 51.4 versus 87.9%, respectively (P = 0.002). A lower tacrolimus trough level, discontinuation of MMF, and treatment of CMV infection were associated with dnDSA positivity. Further investigation is needed to determine whether a new immunosuppressive regimen that avoids these factors can reduce dnDSA positivity.