title: Calcineurin inhibitor-free immunosuppression based on antithymocyte globulin and mycophenolate mofetil in cadaveric kidney transplantation: results after 5 years.
abstract: Kidney grafts from suboptimal donors are more likely to suffer the nephrotoxic side-effects of cyclosporine than kidneys from standard donors. In an attempt to avoid the use of cyclosporine, we carried out a prospective study in low-immunological risk recipients of suboptimal kidneys, using an immunosuppressive protocol combining Thymoglobuline in induction with a bi-therapy of mycophenolate mofetil (MMF) and steroids. Patients with panel reactive antibodies (PRA) <50% receiving a first renal transplant from a suboptimal donor (age >or=50, non heart beating, arterial hypertension, or acute renal failure) or a kidney at risk of delayed graft function (DGF) because of a prolonged cold ischaemia time (CIT) of 24 h or more, were eligible for this trial. Between September 1996 and December 1999, 30 patients were enrolled for the trial and treated with MMF 2 g orally, pre-operatively, and 3 g daily, post-operatively; Thymoglobuline 2 mg/kg IV pre-operatively, 1.5 mg/kg IV the next day, and for doses of 1 mg/kg IV given on alternate days; and prednisolone 0.25 mg/kg per day, reduced progressively from the end of the first month to 0.1 mg/kg per day by 3 months post-transplant. Cyclosporine was added only if rejection grade II or higher, or a reduction in MMF below 1 g daily, occurred. Ten patients (30%) suffered from DGF, and one kidney suffered primary non function. Seven patients (24%) suffered acute rejection (six were biopsy proven, 3 grade I and 3 grade II). MMF dosage was reduced in 28 patients because of adverse events, and calcineurin inhibitors were introduced in 16 patients. There were 14 episodes of opportunistic infection (cytomegalovirus (CMV 10), Herpes zoster 2, Listeria monocytogenes 1, Pseudomonas aeuruginosa 1), and 7 malignancies (skin 2, thyroid 1, lung 1, Kaposi's sarcoma 2, post-transplantation lymphoproliferative disorder 1). Mean serum creatinine was 178, 199, 213, and 218 micromol/l at 1, 2, 3 and 5 years after transplantation, respectively. Actuarial patient and graft (after censoring for death) survival was 94% and 83% after 1 year and 79% and 65% after 5 years, respectively. These results show that with the combination of MMF, Thymoglobuline and steroids the use of cyclosporine can be delayed, and in a few cases completely avoided, with good efficacy in terms of prevention of rejection and recovery of renal function. Regardless of acceptable patient and graft survival, side-effects of MMF at the doses used in this protocol were common and led to overimmunosuppression in the long-term. Starting MMF at low dose, MPA monitoring and probably CMV prophylaxis may improve the results of this regimen.
authors.affiliation: Nephrology Department, Hospital of Bellvitge, CSUB, Feixa Llarga s/n, L'Hospitalet de Llobregat, 08907, Barcelona, Spain. grinyo@ibernet.com
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
authors.forename: Salvador
authors.initials: S
authors.lastname: Gil-Vernet
authors.forename: Josep M
authors.initials: JM
authors.lastname: Cruzado
authors.forename: Ana
authors.initials: A
authors.lastname: Caldés
authors.forename: Lluis
authors.initials: L
authors.lastname: Riera
authors.forename: Daniel
authors.initials: D
authors.lastname: Serón
authors.forename: Inés
authors.initials: I
authors.lastname: Rama
authors.forename: Joan
authors.initials: J
authors.lastname: Torras
mesh_terms: D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002102:Cadaver; D065095:Calcineurin Inhibitors; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D009369:Neoplasms / Q000139:chemically induced; D009894:Opportunistic Infections / Q000139:chemically induced; D011446:Prospective Studies; D016019:Survival Analysis; D014019:Tissue Donors
chemical_list: D000961:Antilymphocyte Serum; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid