PMID- 25708913
OWN - NLM
STAT- MEDLINE
DCOM- 20160609
LR  - 20211203
IS  - 1724-6059 (Electronic)
IS  - 1121-8428 (Linking)
VI  - 28
IP  - 5
DP  - 2015 Oct
TI  - Efficacy of everolimus with reduced-exposure cyclosporine in de novo kidney 
      transplant patients at increased risk for efficacy events: analysis of a 
      randomized trial.
PG  - 633-9
LID - 10.1007/s40620-015-0180-6 [doi]
AB  - The efficacy of de novo everolimus with reduced-exposure calcineurin inhibitor 
      (CNI) was examined in kidney transplant subpopulations from the A2309 study that 
      were identified to be at increased risk for efficacy events. A2309 was a 
      24-month, multicenter, open-label trial in which 833 de novo kidney transplant 
      recipients were randomized to everolimus targeting 3-8 or 6-12 ng/ml with 
      reduced-exposure cyclosporine (CsA), or mycophenolic acid (MPA) with 
      standard-exposure CsA, all with basiliximab induction. The composite efficacy 
      endpoint was treated biopsy-proven acute rejection (BPAR), graft loss, death, or 
      loss to follow-up. Cox proportional hazard modeling showed male gender, younger 
      recipient age, black race, delayed graft function, human leukocyte antigen (HLA) 
      mismatch >/=3 and increasing donor age to be significantly predictive for the 
      composite efficacy endpoint at months 12 or 24 post-transplant. CsA exposure was 
      53-75 % lower, and 46-75 % lower, in patients receiving everolimus 3-8 ng/ml or 
      receiving everolimus 6-12 ng/ml, respectively, versus MPA-treated patients. The 
      incidence of the composite endpoint was similar in all three treatment groups 
      within each subpopulation analyzed. The incidence of treated BPAR was similar 
      with everolimus 3-8 ng/ml or MPA in all subpopulations, but less frequent with 
      everolimus 6-12 ng/ml versus MPA in patients with HLA mismatch >/=3 (p = 0.049). 
      This post hoc analysis of a large, randomized trial suggests that a de novo 
      regimen of everolimus with reduced-exposure CsA maintains immunosuppressive 
      efficacy even in kidney transplant patients at increased risk for efficacy events 
      despite substantial reductions in CsA exposure.
FAU - Carmellini, Mario
AU  - Carmellini M
AD  - Department of Surgery and Bioengineering, University of Siena, Siena, Italy. 
      mario.carmellini@unisi.it.
AD  - Centro Trapianti di Rene, Az. Osped Universitaria Senese Ospedale S Maria alle 
      Scotte, U.O.C. Chirugira dei Trpianti-Dip. Chirugria Gen. e Spec, Viale Bracci 1, 
      53100, Siena, Italy. mario.carmellini@unisi.it.
FAU - Garcia, Valter
AU  - Garcia V
AD  - Hospital Don Vicente Scherer, Santa Casa de Misericordia do Porto Alegre, Porto 
      Alegre, Brazil.
FAU - Wang, Zailong
AU  - Wang Z
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Vergara, Marcela
AU  - Vergara M
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Russ, Graeme
AU  - Russ G
AD  - Renal Unit, The Queen Elizabeth Hospital, Woodville, Australia.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150224
PL  - Italy
TA  - J Nephrol
JT  - Journal of nephrology
JID - 9012268
RN  - 0 (Immunosuppressive Agents)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 9HW64Q8G6G (Everolimus)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Biopsy
MH  - Cyclosporine/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Drug Therapy, Combination
MH  - Everolimus/*administration & dosage
MH  - Female
MH  - Follow-Up Studies
MH  - Graft Rejection/*drug therapy/pathology
MH  - Humans
MH  - Immunosuppression Therapy/*methods
MH  - Immunosuppressive Agents/administration & dosage
MH  - Kidney/pathology
MH  - Kidney Failure, Chronic/surgery
MH  - Kidney Transplantation/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Risk Factors
MH  - Time Factors
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - Calcineurin inhibitor
OT  - Cyclosporine
OT  - Efficacy
OT  - Everolimus
OT  - High risk
OT  - Kidney transplantation
OT  - Rejection
OT  - Sparing
EDAT- 2015/02/25 06:00
MHDA- 2016/06/10 06:00
CRDT- 2015/02/25 06:00
PHST- 2014/10/24 00:00 [received]
PHST- 2015/02/05 00:00 [accepted]
PHST- 2015/02/25 06:00 [entrez]
PHST- 2015/02/25 06:00 [pubmed]
PHST- 2016/06/10 06:00 [medline]
AID - 10.1007/s40620-015-0180-6 [pii]
AID - 10.1007/s40620-015-0180-6 [doi]
PST - ppublish
SO  - J Nephrol. 2015 Oct;28(5):633-9. doi: 10.1007/s40620-015-0180-6. Epub 2015 Feb 
      24.