title: An mTOR-inhibitor-based protocol and calcineurin inhibitor (CNI)-free treatment in kidney transplant recipients from donors after cardiac death: good renal function, but high incidence of conversion to CNI.
abstract: Donor after cardiac death (DCD) grafts have excellent survival despite the high incidence of delayed graft function (DGF). We assessed the feasibility of a mammalian target of rapamycin inhibitor (mTOR-I) protocol in uncontrolled DCD kidney transplantation and compared it with brain-dead donor (DBD) transplantation under calcineurin inhibitor (CNI) treatment. This retrospective study (2002-2011) included 109 Maastricht category II DCD patients and 218 standard-criteria DBD as controls. Immunosuppression consisted of polyclonal antibody induction, mycophenolate mofetil, prednisone, and mTOR-I (starting on day 6) in the DCD group and tacrolimus in the DBD group. DGF occurred in 72.5% of the DCD group vs. 26.1% of the DBD group (P = 0.001). Patient survival at 1 year was 99.1% vs. 95.9% (P = 0.112), and graft survival was 89% vs. 92.2% (P = 0.253). Patient survival at 5 years was 85.3% vs. 90.1% (P = 0.340) and graft survival was 85.5% vs. 78.8% (P = 0.166). During the first year, 46.8% (n = 51) of DCD patients were converted to CNI therapy. Serum creatinine at 1 year was 1.5(1.26-2) mg/dl vs. 1.4(1.16-1.8) mg/dl (P = 0.078). At 1 year, the acute rejection rate was 7.3% vs. 12.5% (P = 0.766). mTOR-I-based therapy was not associated with inferior graft function or higher rejection rates than standard CNI therapy. DCD kidney transplantation with an mTOR-I-based protocol is feasible but is associated with a high conversion rate to CNI-based therapy.
authors.affiliation: Nephrology and Renal Transplant Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Sánchez-Escuredo
authors.affiliation: Nephrology and Renal Transplant Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Fritz
authors.initials: F
authors.lastname: Diekmann
authors.affiliation: Nephrology and Renal Transplant Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Revuelta
authors.affiliation: Nephrology and Renal Transplant Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Esforzado
authors.affiliation: Nephrology and Renal Transplant Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Ricart
authors.affiliation: Nephrology and Renal Transplant Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Frederic
authors.initials: F
authors.lastname: Cofán
authors.affiliation: Nephrology and Renal Transplant Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Jose-Vicente
authors.initials: JV
authors.lastname: Torregrosa
authors.affiliation: Urology Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Lluis
authors.initials: L
authors.lastname: Peri
authors.affiliation: Donation and Transplant Coordination Unit, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Ruiz
authors.affiliation: Nephrology and Renal Transplant Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Campistol
authors.affiliation: Nephrology and Renal Transplant Department, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Oppenheimer
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D051799:Delayed Graft Function; D000068338:Everolimus / Q000494:pharmacology / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000706:statistics & numerical data; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000453:epidemiology; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: calcineurin inhibitor; conversion; donors after cardiac death; mammalian target of rapamycin inhibitor