title: The Cairo kidney center protocol for rapamycin-based sequential immunosuppression in kidney transplant recipients: 2-year outcomes.
abstract: OBJECTIVE
  This study examines the outcomes of de novo kidney transplants treated by a sequential protocol, designed to target the succession of immunologic events following engraftment.
  
  
  METHODS
  A total of 113 sequential live-donor recipients were randomized into 2 arms. Patients in arm A received prednisolone, cyclosporine, and sirolimus for 3 months (phase 1), followed by replacement of cyclosporine with mycophenolate mofetil (phase 2). Those in arm B (controls) received prednisolone/cyclosporine/mycophenolate mofetil throughout the study. The primary endpoints were patient and graft survival rates at 2 years. Secondary endpoints included biopsy-proven acute rejection, early and late graft function, hypertension, and adverse reactions.
  
  
  RESULTS
  The 2-year intent-to-treat patient and graft survival rates (95.8% vs 91.4% and 94.6% vs 90.2%) were numerically but not significantly higher in arm A. The overall incidence of biopsy-proven acute rejection was numerically lower (13.5% vs 18.9%), yet it occurred exclusively with cyclosporine C2 levels below 770 ng/mL (P = .28). Mean time for serum creatinine to reach 132 micromol/L was significantly longer in arm A (7.3 vs 2.9 days). Graft function at 2 years (eGFR, 70.2 vs 55.9 mL/min) and number of drugs needed to control blood pressure (mean 1.7 vs 2.25) were significantly more favorable in group A. Significant adverse effects for patients in arm A included proteinuria (36.8% vs 18.6%), hyperlipidemia (peak cholesterol > 7.75 mmol/L in 32.9% vs 23.7% of patients) and thrombocytopenia (platelet count < 100 x 109/L in 32.9% vs 13.5 % of patients).
  
  
  CONCLUSIONS
  The described protocol reduced the incidence of biopsy-proven acute rejection in patients after kidney transplant, particularly in those with adequate cyclosporine blood levels. Despite the significantly higher incidence of certain adverse effects (ie, delayed graft function, proteinuria, hyperlipidemia, and transient thrombocytopenia), patient and graft survival rates at 2 years were numerically, though not statistically, improved in patients in arm A. At 2-year analysis, compared with patients in the control arm (arm B), graft function significantly improved in patients in arm A, and the number of drugs needed to control blood pressure was significantly lower.
authors.affiliation: The Cairo Kidney Center, Cairo, Egypt. Rashad.barsoum@gmail.com
authors.forename: Rashad S
authors.initials: RS
authors.lastname: Barsoum
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Morsey
authors.forename: Irene R
authors.initials: IR
authors.lastname: Iskander
authors.forename: Manal M
authors.initials: MM
authors.lastname: Morgan
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Fayad
authors.forename: Nasr T
authors.initials: NT
authors.lastname: Atalla
authors.forename: Hani
authors.initials: H
authors.lastname: Wafik
authors.forename: Renne A
authors.initials: RA
authors.lastname: Grace
authors.forename: Noha
authors.initials: N
authors.lastname: Adel
authors.forename: Soha S
authors.initials: SS
authors.lastname: Khalil
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation / Q000276:immunology / Q000379:methods*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011239:Prednisolone / Q000008:administration & dosage; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D009173:Mycophenolic Acid; D020123:Sirolimus