Abstract

Introduction: Alemtuzumab, a monoclonal antibody used in approximately 13% of kidney transplants, allows for early glucocorticoid withdrawal. High risk patients, defined by a presence of elevated Panel Reactive Antibody (PRA), are at greater risk for rejection, poorer graft outcomes, and have been shown to benefit from induction with alemtuzumab. The aim of this study is to assess the outcomes of immunologically sensitive kidney transplant recipients after induction with alemtuzumab and early steroid withdrawal.
Methods: A retrospective analysis of 668 transplant recipients, all receiving alemtuzumab induction, from March 2006 through November 2015 was performed. High risk patients (defined as elevated PRA >20%) were compared to those with a low PRA (PRA <20%). Outcomes, such as patient survival, graft survival, and rejection were assessed.
Results: Death-censored graft survival at 1-year was greater than 90% for both groups (p=0.343). Graft survival at 3- and 5- years was significantly lower in the high PRA group (3 years: 79.3%, 5 years: 73.2%) compared to the low PRA group (3 years: 91.3%, 5 years: 85.9%) (p=0.003, p=0.013). Overall death-censored graft survival for the high PRA group (77.6%) was also significantly lower than the low PRA group (87.5%, p=0.007). We noted no statistical difference between groups for other negative outcomes such as patient death or delayed graft function.
Conclusion: Alemtuzumab and subsequent steroid withdrawal is effective at reducing short term poor outcome disparities between high PRA and low PRA recipients. However, graft survival after the second year, and increasing rejection rates prior to the fifth year, demonstrates that the short term effectiveness of alemtuzumab does not translate into long term graft maintenance in patients with elevated PRA. This evidence suggests further investigation into the effectiveness of alemtuzumab induction with steroid withdrawal regimens in patients with an elevated PRA.

Keywords: Alemtuzumab; PRA; Immunosuppression