Alemtuzumab and sirolimus in renal transplantation: six-year results of a single-arm prospective pilot study

Am J Transplant. 2014 Mar;14(3):677-84. doi: 10.1111/ajt.12572.

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.

Publication types

  • Comparative Study

MeSH terms

  • Alemtuzumab
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Survival / drug effects
  • Graft Survival / physiology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use
  • Pilot Projects
  • Postoperative Complications / etiology
  • Postoperative Complications / prevention & control*
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Sirolimus / therapeutic use*
  • Survival Rate

Substances

  • Antibodies, Monoclonal, Humanized
  • Immunosuppressive Agents
  • Alemtuzumab
  • Mycophenolic Acid
  • Sirolimus