title: Early sirolimus therapy in renal transplant recipients at high risk: is it justified?
abstract: BACKGROUND
  We studied early sirolimus (SRL) therapy in renal transplant recipients at high risk after administration of antithymocyte globulin or interleukin-2 receptor blockade induction.
  
  
  METHODS
  In 45 patients, SRL therapy was started within 1 month after transplantation. The primary indications for conversion of treatment from calcineurin inhibitors (CNIs)-mycophenolate mofetil (MMF)-steroid to SRL-MMF-steroid were biopsy-proved rejection (after treatment), CNI toxicity, CNI elimination, and acute tubular necrosis. Pediatric, geriatric, and other patients with medical comorbidities were not excluded.
  
  
  RESULTS
  Post-SRL rejection episodes were reported in 22.2% of recipients including 15.6% who were resistant to steroid therapy. Mean (SD) follow-up after SRL therapy was 59.9 (8.1) months. Proteinuria greater than 2 g/d (P = .001), leukopenia (P < .001), hyperlipidemia (P < .001), and transaminases values (P = .02) increased significantly after SRL therapy. Graft survival was 88.8%, and patient survival was 93.3%. There was significant improvement in serum creatinine concentration and estimated creatinine clearance by the end of the study (P < .001). A high incidence of adverse effects and infections was noted post-SRL therapy, and the drug was discontinued in 31% of patients because of multiple adverse effects. At multivariate analysis, age, hypertension, nutritional status, bone marrow suppression, hyperlipidemia, and graft dysfunction were identified as risk factors for worse graft and patient outcome.
  
  
  CONCLUSIONS
  Early treatment with combined SRL-MMF-steroid may be effective as a CNI-free immunosuppression regimen in patients at high risk; however, there is a high rate of adverse effects during long-term follow-up.
authors.affiliation: Hamed Al-Essa Organ Transplantation Centre, Ibn Sina Hospital, Safat, Kuwait. medhatmohamed2000@yahoo.com
authors.forename: M A
authors.initials: MA
authors.lastname: Halim
authors.forename: T
authors.initials: T
authors.lastname: Al-Otaibi
authors.forename: K V
authors.initials: KV
authors.lastname: Johny
authors.forename: M H
authors.initials: MH
authors.lastname: Hamid
authors.forename: S
authors.initials: S
authors.lastname: Al-Waheeb
authors.forename: H
authors.initials: H
authors.lastname: Hasaneen
authors.forename: W H
authors.initials: WH
authors.lastname: Awadain
authors.forename: K M
authors.initials: KM
authors.lastname: Nawas
authors.forename: A
authors.initials: A
authors.lastname: El-Sayed
authors.forename: T
authors.initials: T
authors.lastname: Said
authors.forename: M P
authors.initials: MP
authors.lastname: Nair
authors.forename: M R N
authors.initials: MR
authors.lastname: Nampoory
mesh_terms: D000328:Adult; D001706:Biopsy; D002102:Cadaver; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011507:Proteinuria / Q000453:epidemiology; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014019:Tissue Donors / Q000706:statistics & numerical data; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus