title: Sirolimus experience in heart transplantation.
abstract: BACKGROUND
  Sirolimus is a potent, nonnephrotoxic immunosuppressant with antiproliferative activity in nonimmune cells. Recent data support the conversion in late renal failure secondary to calcineurin inhibitors (CNIs), with limited experience in de novo regimens in patients with predictive factors of postoperative renal impairment.
  
  
  OBJECTIVE
  We evaluated our experience of sirolimus-based immunosuppression administered to 25 heart transplant recipients.
  
  
  METHODS
  A retrospective analysis of 25 heart transplant recipients who received sirolimus included 17 conversions due to late CNI-related chronic renal dysfunction, six patients with a de novo regimen, and two patients who developed posttransplant pulmonary neoplasms. The conversion from CNI to sirolimus was started with 2 mg, with an average time after transplantation of 78 +/- 43 months and a mean baseline serum creatinine level of 2.1 +/- 0.45 mg/dL. The mean clinical follow-up was 17 +/- 9 months postconversion, and included echocardiography and laboratory studies. In the de novo group successive endomyocardial biopsies were performed during the first semester.
  
  
  RESULTS
  Serum creatinine fell from 2.1 +/- 0.45 mg/dL to 1.8 +/- 0.51 mg/dL (P = .012). Mean sirolimus levels were 15 +/- 9 ng/mL (doses 2.2 +/- 0.4 mg). This improvement continued until 3 months (creatinine 1.5 +/- 0.35 P < .01)/sirolimus levels 11.7 +/- 5 ng/mL [1.9 +/- 0.7 mg]), with maintenance at 6 months (1.58 +/- 0.3 mg/dL/14 +/- 4 ng/mL [1.85 +/- 0.7 mg]) and 1-year postconversion (1.53 +/- 0.39 mg/dL; P = .019/10.7 +/- 2.5 ng/mL [1.5 +/- 0.7 mg]). De novo, after a mean follow-up of 13 months (range 3 to 35), sirolimus appeared to increase the incidence of a moderate histological grade of rejection without hemodynamic compromise. Side effects were common (63%), including peripheral edema, skin eruptions, and pericardial effusion. Only one patient discontinued treatment, due to intestinal intolerance. Four patients died during follow-up: two because of lung neoplasms and two because of progressive graft vessel disease.
  
  
  CONCLUSIONS
  Sirolimus improved late CNI-related chronic renal dysfunction. Kidney function was preserved using a de novo CNI-free immunosuppressive regimen for recent cardiac transplant recipients.
authors.affiliation: Department of Cardiology, University Hospital Virgen del Rocío, Seville, Spain. arandios@hotmail.com
authors.forename: A
authors.initials: A
authors.lastname: Aranda-Dios
authors.forename: E
authors.initials: E
authors.lastname: Lage
authors.forename: J M
authors.initials: JM
authors.lastname: Sobrino
authors.forename: M V
authors.initials: MV
authors.lastname: Mogollón
authors.forename: A
authors.initials: A
authors.lastname: Guisado
authors.forename: S
authors.initials: S
authors.lastname: Cabezón
authors.forename: R
authors.initials: R
authors.lastname: Hinojosa
authors.forename: A
authors.initials: A
authors.lastname: Hernández
authors.forename: A
authors.initials: A
authors.lastname: Ordóñez
mesh_terms: D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D005260:Female; D016027:Heart Transplantation / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus