PMID- 28141897
OWN - NLM
STAT- MEDLINE
DCOM- 20180214
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Print)
IS  - 1600-6135 (Linking)
VI  - 17
IP  - 9
DP  - 2017 Sep
TI  - Association of Clinical Events With Everolimus Exposure in Kidney Transplant 
      Patients Receiving Low Doses of Tacrolimus.
PG  - 2363-2371
LID - 10.1111/ajt.14215 [doi]
AB  - A key objective in the use of immunosuppression after kidney transplantation is 
      to attain the optimal balance between efficacy and safety. In a phase 3b, 
      multicenter, randomized, open-label, noninferiority study, the incidences of 
      clinical events, renal dysfunction, and adverse events (AEs) were analyzed at 12 
      months in 309 de novo renal transplant recipients receiving everolimus (EVR), 
      low-dose tacrolimus (LTac), 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. AEs 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 LTac, to achieve balanced efficacy 
      and safety in renal transplant recipients. TRIAL REGISTRATION: NCT01025817.
CI  - (c) 2017 The Authors. American Journal of Transplantation published by Wiley 
      Periodicals, Inc. on behalf of American Society of Transplant Surgeons.
FAU - Shihab, F
AU  - Shihab F
AD  - University of Utah, Salt Lake City, UT.
FAU - Qazi, Y
AU  - Qazi Y
AD  - University of Southern California, Los Angeles, CA.
FAU - Mulgaonkar, S
AU  - Mulgaonkar S
AD  - Barnabas Health, Livingston, NJ.
FAU - McCague, K
AU  - McCague K
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ.
FAU - Patel, D
AU  - Patel D
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ.
FAU - Peddi, V R
AU  - Peddi VR
AD  - California Pacific Medical Center, San Francisco, CA.
FAU - Shaffer, D
AU  - Shaffer D
AD  - Vanderbilt University Medical Center, Nashville, TN.
LA  - eng
SI  - ClinicalTrials.gov/NCT01025817
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20170304
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Everolimus/*therapeutic use
MH  - Female
MH  - Follow-Up Studies
MH  - Glomerular Filtration Rate
MH  - Graft Rejection/*drug therapy/epidemiology
MH  - Graft Survival/*drug effects
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Kidney Failure, Chronic/*surgery
MH  - Kidney Function Tests
MH  - *Kidney Transplantation
MH  - Male
MH  - Middle Aged
MH  - Postoperative Complications
MH  - Prognosis
MH  - Risk Factors
MH  - Tacrolimus/*therapeutic use
MH  - Transplant Recipients
MH  - Young Adult
PMC - PMC5600116
OTO - NOTNLM
OT  - calcineurin inhibitor: tacrolimus
OT  - clinical research/practice
OT  - immunosuppressant
OT  - immunosuppressive regimens
OT  - kidney transplantation/nephrology
OT  - mechanistic target of rapamycin (mTOR)
OT  - mechanistic target of rapamycin: everolimus
OT  - minimization/withdrawal
EDAT- 2017/02/01 06:00
MHDA- 2018/02/15 06:00
PMCR- 2017/09/15
CRDT- 2017/02/01 06:00
PHST- 2016/11/03 00:00 [received]
PHST- 2017/01/04 00:00 [revised]
PHST- 2017/01/24 00:00 [accepted]
PHST- 2017/02/01 06:00 [pubmed]
PHST- 2018/02/15 06:00 [medline]
PHST- 2017/02/01 06:00 [entrez]
PHST- 2017/09/15 00:00 [pmc-release]
AID - S1600-6135(22)25129-6 [pii]
AID - AJT14215 [pii]
AID - 10.1111/ajt.14215 [doi]
PST - ppublish
SO  - Am J Transplant. 2017 Sep;17(9):2363-2371. doi: 10.1111/ajt.14215. Epub 2017 Mar 
      4.