title: Sirolimus monotherapy effectiveness in liver transplant recipients with renal dysfunction due to calcineurin inhibitors.
abstract: BACKGROUND
  Among the adverse effects of different calcineurin inhibitors (CIs), nephrotoxicity is the most common (incidence: 18.1% at 13 y from liver transplantation) and depends on a variable degree of tubular-interstitial injury accompanied by focal glomerular sclerosis. A new immunosuppressive drug was introduced in solid organ transplant management, Sirolimus (SRL). It is a nonnephrotoxic immunosuppressor.
  
  
  METHODS
  Twenty-six patients who developed nephrotoxicity owing to CIs, showing an increment of serum creatinine levels (>1.8 mg/dL) were switched to SRL monotherapy, initially at a dosage between 3 and 5 mg/d, and subsequently adapted to achieve trough level between 8 to 10 ng/mL.
  
  
  RESULTS
  Patients were followed-up for a mean period of 40.3 months (range, 8.4 to 76.7) from liver transplantation. Mean follow-up after switch was 27.5 months (range, 2 to 71.2). Immunosuppression therapy was converted after a mean period of 12.8 months (range, 0.2 to 43.4). Serum creatinine, urea, and estimated glomerular filtration rate were significantly improved.
  
  
  CONCLUSIONS
  Patients developing renal dysfunction after liver transplantation may be successfully treated by conversion from CI to SRL. Hypertriglyceridemia and hypercholesterolemia represent the principal side effects from SRL, but are treatable. Furthermore, SRL can significantly improve glucose tolerance.
authors.affiliation: Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia, Modena, Italy. f.diben@virgilio.it
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Di Benedetto
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Sandro
authors.forename: Nicola
authors.initials: N
authors.lastname: De Ruvo
authors.forename: Mario
authors.initials: M
authors.lastname: Spaggiari
authors.forename: Roberto
authors.initials: R
authors.lastname: Montalti
authors.forename: Roberto
authors.initials: R
authors.lastname: Ballarin
authors.forename: Gianni
authors.initials: G
authors.lastname: Cappelli
authors.forename: Giorgio E
authors.initials: GE
authors.lastname: Gerunda
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D065095:Calcineurin Inhibitors; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced; D015228:Hypertriglyceridemia / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D020123:Sirolimus; D016559:Tacrolimus