OBJECTIVE: We investigated the clinical outcome of AHG/FCXM negative recipients transplanted with donor specific HLA antibodies (DSA)-positive vs.recipients who were DSA-negative.MATERIALS AND METHODS: From May 2006 to November 2010, 796 recipients received live and deceased renal allografts.Thirty-seven of these recipients were transplanted after negative AHG and FCXMs but who also presented pre-transplant with single antigen bead/Luminex identified DSA in their sera.A control group of 447 renal allograft recipients transplanted during the same time period were DSA-negative.DSA-positive recipients received induction therapy of either anti-thymocyte globulin or basiliximab in combination with methylprednisolone.Maintenance therapy for all recipients consisted of sirolimus and cyclosporine or cyclosporine mieroemulsion in combination with mycophenolate.Both groups received prednisone 5 mg daily by day 30 after a tapered dose.RESULTS: At a mean follow-up of one year post-transplant (range 1 to 46 months) the patient survivals for the DSAnegative vs.DSA-positive recipients were 98% vs.100%.Of note was the 100% graft survival for living donor recipients (n=10) whereas 1 of 10 regrafts and 3 of 21 primary deceased donor grafts were lost for DSA-positive recipients.DSA-positive recipients with good allograft function had a mean serum creatinine of 1.25 mg/dl (range of 0.8 to 2.0 mg/dl).Two patients developed resolvable acute cellular rejections while six patients had antibody mediated rejection (AbMR).Of these 6 patients, 3 African-American females lost their grafts despite intensive therapy with plasmapheresis, rituximab and IVIg therapy.Two of these immunologic graft losses also experienced delayed graft function (DGF).In contrast one Hispanic and two Caucasian females with immediate graft function subsequently developed AbMR, but responded well to therapeutic intervention.One Caucasian male lost the allograft due to nonimmunologic renal graft thrombosis.The pre-transplant DSA titers (1:2 to 1:32) and/or fluorescence intensities (9,000 to 2,000) of Ab-DSA specific beads were not predictive of the incidence of DGF, rejection or graft loss.CONCLUSIONS: DSA-positive but FCXM-negative recipients can be successfully transplanted.The presence of DSA in patients who had a negative FCXM did not predict the clinical outcome after renal transplantation.DSApositive, African-American females developing DGF appear to have a high risk of AbMR and eventual graft loss.