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Association of Clinical Events With Everolimus Exposure in Kidney Transplant Patients Receiving Low Doses of Tacrolimus
Author(s) -
Shihab F.,
Qazi Y.,
Mulgaonkar S.,
McCague K.,
Patel D.,
Peddi V. R.,
Shaffer D.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14215
Subject(s) - medicine , everolimus , hazard ratio , immunosuppression , tacrolimus , urology , adverse effect , renal function , kidney transplantation , transplantation , confidence interval
A key objective in the use of immunosuppression after kidney transplantation is to attain the optimal balance between efficacy and safety. In a phase 3 b, multicenter, randomized, open‐label, noninferiority study, the incidences of clinical events, renal dysfunction, and adverse events ( AE s) were analyzed at 12 months in 309 de novo renal transplant recipients receiving everolimus ( EVR ), low‐dose tacrolimus ( LT ac), and prednisone. Cox proportional hazard regression modeling was used to estimate the probability of clinical events at specified combinations of time‐normalized EVR and Tac trough concentrations. At 12 months, the highest incidence of treated biopsy‐proven acute rejection ( tBPAR ) and graft loss occurred most often in patients with EVR trough concentration <3 ng/ mL (64.7% and 10.5%, respectively). At 1 month and 12 months, increasing EVR levels were associated with fewer tBPAR events (both p < 0.0001). Low estimated glomerular filtration rate ( eGFR ) and decreased eGFR occurred more often in patients with lower EVR and higher Tac levels. AE s were most often observed in patients with EVR levels <3 ng/ mL . This study supports maintaining an EVR trough concentration of 3–8 ng/ mL , when combined with LT ac, to achieve balanced efficacy and safety in renal transplant recipients. Trial registration: NCT 01025817.