Ischemia-reperfusion injury has multiple effects on a transplanted allograft, including delayed or impaired graft function, compromised long-term survival, and an association with an increased incidence of rejection. Eculizumab, a monoclonal antibody blocking terminal complement activation, has been postulated to be an effective agent in the prevention or amelioration of IRI. We performed a single-center prospective, randomized controlled trial involving 57 pediatric kidney transplant recipients between 2012 and 2016. The immunosuppressive protocol included two doses of alemtuzumab; half of the patients were randomized to receive a single dose of eculizumab prior to transplantation. Maintenance immunosuppression was based on a combination of low-dose tacrolimus and mycophenolate, without steroids. Eculizumab-treated patients had a significantly better early graft function, less arteriolar hyalinosis and chronic glomerulopathy on a protocol biopsies taken on day 30, 1 year, and 3 years after transplantation. In the eculizumab group, four non-vaccinated children lost their grafts during the course of a flu-like infection. Eculizumab is associated with better early graft function and improved graft morphology; however, there was an unacceptably high number of early graft losses among the eculizumab-treated children. While a promising strategy, the best approach to complement inhibition remains to be established.

Recipient lymphocytes are crucial for direct and indirect pathways of allorecognition. We proposed that the administration of alemtuzumab several weeks pretransplantation could eradicate peripheral lymphatic cells and promote donor-specific acceptance. This was a single-center, retrospective review of 101 consecutive living donor kidney transplantations in pediatric patients (age 7 months-18 years), performed between September 2006 and April 2010. IS protocol included two 30 mg doses of alemtuzumab: The first was given 12-29 days prior to transplantation, and the second at the time of transplantation. Maintenance IS was based on combination of low-dose CNI and mycophenolate, with steroids tapered over the first 5 days post-transplantation. Patients were followed for 7.8±1.3 years, and protocol biopsies were taken 1 month, 1, 3, and 5 years post-transplant. The Kaplan-Meier 8-year patient and graft survival rates in the cyclosporine-treated patients were 82.0±7.3% and 71.6±7.3, and in the tacrolimus-treated patients were 97.2±5.4 and 83.8±6.0%. Biopsy-proven acute rejection developed in 35% of cyclosporine-treated patients and in 8% of tacrolimus-treated patients. Alemtuzumab pretreatment prior to LRD kidney transplantation, followed by maintenance immunosuppression with tacrolimus and MMF, is associated with reasonable long-term results in pediatric patients.

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