The Effect of Everolimus Versus Mycophenolate Upon Proteinuria Following Kidney Transplant and Relationship to Graft Outcomes. Issue 2 (3rd December 2012)

• Record Type: Journal Article
• Authors: Wiseman, A. C.; McCague, K.; Kim, Y.; Geissler, F.; Cooper, M.
• Is Part Of: American journal of transplantation. Volume 13:Issue 2(2013:Feb.)
• Page Start: 442
• Page End: 449
• Publication Date: 2012-12-03
• Subjects: Everolimus -- GFR -- graft survival -- proteinuria; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/j.1600-6143.2012.04334.x
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : 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. Abstract : In a post‐hoc analysis of a large randomized multicenter trial, the authors find a dose‐dependent relationship of everolimus exposure and proteinuria, and describe the evolution of proteinuria from 3 to 24 months following transplant in CNI‐containing regimens with everolimus or mycophenolate.