A growing number of patients on the kidney transplant waiting list are broadly human
leukocyte antigen (HLA) sensitized (HS). These patients are unlikely to have a compatible
donor. Therefore they wait longer and have increased morbidity and mortality. Desensitization
with intravenous immune globulin (IVIG) and rituximab with alemtuzumab induction improves
transplant rates and achieves good allograft outcomes. However, HS patients are at risk for
viral infections after transplant. We have previously shown an increased incidence of BKV
infections after desensitization with HS patients having higher peak viral loads.
Cytomegalovirus (CMV) and polyomavirus BK (BKV) infections place HS renal transplant
recipients at particular risk. Allograft rejection is associated with both CMV and BKV
infection. This is of particular concern for HS patients as they are at an increased risk of
rejection at baseline. Furthermore, the frequent development of leukopenia after
transplantation often requires the CMV prophylactic agent to be discontinued along with
lowering immunosuppression. This increases the risk of CMV infection and allograft rejection.
Everolimus was approved for rejection prophylaxis in combination with calcineurin inhibitors
(CNI). CNI used in the study that led to drug's approval was cyclosporine. There are several
trials nearing it's completion that utilize low dose tacrolimus instead. In 2012 Novartis
published data from several trials showing superior outcomes using everolimus + low dose
tacrolimus. This combination is currently approved in EU. It is also a combination that is
standard of care (SOC) at our center for patients on everolimus.
This study aims to demonstrate that use of everolimus as part of a maintenance
immunosuppression regimen may decrease viral infections without lowering overall
immunosuppression thus improving allograft function and survival.