The effect of everolimus versus mycophenolate upon proteinuria following kidney transplant and relationship to graft outcomes.

Although mTOR inhibitor use has been associated with proteinuria in kidney transplant recipients, dose dependency and impact on allograft function are unknown. In a post hoc analysis, we compared rates of proteinuria 3 months posttransplant among everolimus (EVR) and mycophenolate (MPA) treatment arms and used a time-dependent model to correlate the risk of proteinuria to EVR trough levels up to 24 months posttransplant. eGFR and graft loss was compared by proteinuria status at 3 months. Of 833 randomized patients, 24%, 36% and 19% of lower exposure EVR (1.5 mg/day), higher exposure EVR (3.0 mg/day) and MPA-treated patients had proteinuria ≥ 300 mg/g Cr at 3 months, respectively. EVR 1.5 was not associated with an increase in risk of proteinuria (HR 1.20; p = 0.19) unlike EVR 3.0 (HR 1.84; p < 0.001) versus MPA. EVR trough levels >8 ng/mL were significantly associated with proteinuria compared to 3-8 ng/mL (HR 1.86; p < 0.001). Those patients with proteinuria at 3 months and those who developed proteinuria thereafter had lower eGFR and higher graft loss at 24 months, regardless of treatment arm. We identify a dose-dependent effect of EVR with the risk of proteinuria; however, its independent impact upon eGFR and graft survival at 2 years was not evident.