Background: Pre-existing humoral barriers challenge the transplantation of living donor kidneys (LDK) into highly sensitized ABO- and human leukocyte antigen (HLA)-incompatible recipients. Conditioning these LDK recipients' immune systems is required before they undergo transplantation. We hypothesized that medical desensitization would yield higher post-transplantation rates of infection.Methods: We conducted a study in which matched controls consisting of non-desensitized (NDS) LDK recipients were compared with desensitized (DS) receipients. Pre-transplantation desensitization included treatment with rituximab and mycophenolate mofetil followed by intravenous immunoglobulin (IVIg) and plasmapheresis. All participants in the study underwent induction therapy and maintenance immunosuppression. Primary outcomes included infection (opportunistic, local, systemic) within 12 mo after transplantation.Results: Twenty-five patients underwent desensitization and LDK transplantation. Graft survival in the DS and NDS groups of patients was 96% and 98%, respectively. The mean 3- and 12-mo serum creatinine concentrations in the DS and NDS groups were 1.1±0.2 mg/dL and 1.2±0.3 mg/dL and 0.95±0.4 mg/dL and 0.73±0.8 mg/dL (p=0.3 and p=0.01), respectively. Thirty-six percent of the patients in the DS group had one or more infections, vs. 28% of those in the NDS group (p=0.1). No difference was observed in the frequency of opportunistic or systemic infections in the two groups. Local infections were statistically significantly more frequent in the DS group (60% vs. 30%, respectively; p=0.02).Conclusion: Pre-operative desensitization in highly sensitized LDK recipients is followed by a similar incidence of opportunistic and systemic infections as in NDS patients. Local infections were significantly more frequent in the DS than in the NDS patients in the study. With careful monitoring of infectious complications, pre-transplant desensitization permits LDK transplantation into highly sensitized patients.