title: Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: the significance of baseline glomerular filtration rate.
abstract: BACKGROUND
  The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (TTx) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure.
  
  
  METHODS
  This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediaminetetraacetic acid clearance.
  
  
  RESULTS
  In 21 patients with a baseline mGFR of 20 to 29 ml/min/1.73 m(2), renal function improved in the everolimus group compared with the control group ((ΔmGFR 6.7 ± 9.0 vs -1.6 ± 5.1 ml/min/1.73 m(2); p = 0.03). Amongst 173 patients with moderate renal impairment (mGFR 30-59 ml/min/1.73 m(2)), renal function improvement was also greater amongst everolimus patients than in controls (ΔmGFR 5.1 ± 11.1 vs -0.5 ± 8.7 ml/min/1.73 m(2); p < 0.01). In 55 patients with mGFR 60 to 89 ml/min/1.73 m(2), mGFR did not change significantly in either group. Improvement in mGFR was limited to patients with a median time since TTx of less than 4.6 years and was also influenced by CNI reduction during the study period.
  
  
  CONCLUSIONS
  Everolimus introduction and reduced CNI significantly improved renal function amongst maintenance TTx patients with pre-existing advanced renal failure. This beneficial effect was limited to patients undergoing conversion in less than 5 years after TTx, indicating a window of opportunity that is appropriate for pharmacologic intervention with everolimus.
authors.affiliation: Oslo University Hospital Rikshospitalet, Oslo, Norway. satish.arora@medisin.uio.no
authors.forename: Satish
authors.initials: S
authors.lastname: Arora
authors.forename: Einar
authors.initials: E
authors.lastname: Gude
authors.forename: Vilborg
authors.initials: V
authors.lastname: Sigurdardottir
authors.forename: Svend Aage
authors.initials: SA
authors.lastname: Mortensen
authors.forename: Hans
authors.initials: H
authors.lastname: Eiskjær
authors.forename: Gerdt
authors.initials: G
authors.lastname: Riise
authors.forename: Lena
authors.initials: L
authors.lastname: Mared
authors.forename: Oystein
authors.initials: O
authors.lastname: Bjørtuft
authors.forename: Bjørn
authors.initials: B
authors.lastname: Ekmehag
authors.forename: Kjell
authors.initials: K
authors.lastname: Jansson
authors.forename: Svein
authors.initials: S
authors.lastname: Simonsen
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Dag
authors.initials: D
authors.lastname: Solbu
authors.forename: Martin
authors.initials: M
authors.lastname: Iversen
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors*; D000368:Aged; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D051437:Renal Insufficiency / Q000503:physiopathology / Q000517:prevention & control*; D012537:Scandinavian and Nordic Countries; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus; D016559:Tacrolimus