title: Alemtuzumab and sirolimus in renal transplantation: six-year results of a single-arm prospective pilot study.
abstract: mTOR inhibitors avoid calcineurin nephrotoxicity, but sirolimus de novo is associated with unacceptable side effects and higher rejection rates. We have investigated a modified strategy: alemtuzumab induction with tacrolimus and mycophenolate maintenance, switching from tacrolimus to sirolimus at 6 months and stopping mycophenolate at 12 months. Here, we report the 6-year follow-up of 30 patients prospectively recruited to this single-arm pilot study and compare outcomes to a matched contemporaneous control group of 30 patients who received standard induction and calcineurin-inhibitor-based immunosuppression.Six-year patient and graft survival were 83% and 80%(alemtuzumab) versus 77% and 70% (control). Rejection rates in the first 6 months were similar in alemtuzumab (6.6%) and control groups (10%). A higher than expected incidence of rejection in the alemtuzumab group following cessation of mycophenolate at 1 year (17%) was mitigated in later patients by retaining low dose mycophenolate. Mean eGFR was higher in the alemtuzumab group at all time points but not significantly (p¼0.16). Tacrolimus levels in the first 6 months were significantly higher in the contemporaneous control group (p<0.001). Alemtuzumab induction with initial treatment with tacrolimus enables conversion to sirolimus without the side effects and incidence of acute rejection seen in earlier protocols.
authors.forename: A I
authors.initials: AI
authors.lastname: Sutherland
authors.forename: M Z
authors.initials: MZ
authors.lastname: Akhtar
authors.forename: M
authors.initials: M
authors.lastname: Zilvetti
authors.forename: J
authors.initials: J
authors.lastname: Brockmann
authors.forename: S
authors.initials: S
authors.lastname: Ruse
authors.forename: S V
authors.initials: SV
authors.lastname: Fuggle
authors.forename: S
authors.initials: S
authors.lastname: Sinha
authors.forename: P
authors.initials: P
authors.lastname: Harden
authors.forename: P J
authors.initials: PJ
authors.lastname: Friend
mesh_terms: D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use; D010865:Pilot Projects; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D009173:Mycophenolic Acid; D020123:Sirolimus