title: Successful conversion to rapamycin for calcineurin inhibitor-related neurotoxicity following liver transplantation.
abstract: BACKGROUND
  Neurotoxicity is a well-recognized side effect of calcineurin inhibitors. Rapamycin is considered to be significantly less neurotoxic than calcineurin inhibitors (CNIs). The aim of this study was to retrospectively analyze a group of post-liver transplant patients who had been converted to rapamycin because of CNI-related neurotoxicity.
  
  
  METHODS
  Orthotopic liver transplantation (OLT) was performed in 56 consecutive patients between April 1, 2003, and August 15, 2004. Immunosuppression was administered with tacrolimus, mycophenolic acid, and corticosteroids.
  
  
  RESULTS
  Seven patients were converted to rapamycin due to new-onset neurotoxicity or exacerbation of previous neurological symptoms secondary to CNI. None of the patients had toxic levels tacrolimus (>15 ng/mL) at the time of symptoms, which persisted despite reduction of CNI dose. The indications for conversion were: (1) peripheral neuropathy; (2) seizure; (3) metabolic encephalopathy; and (4) central pontine myelinolysis. All patients showed improvement or resolution of their neurological symptoms after conversion to rapamycin. Two patients died, the first due to a hypoxic event and the second due to central pontine myelinolysis with limited improvement and a family decision to withdraw care. There were no complications directly attributed to rapamycin. Specifically, there were no thrombotic events, wound complications, or biliary leaks. Three patients had a rejection episode that was successfully treated with pulse corticosteroids and low-dose tacrolimus (levels < 5 ng/mL).
  
  
  CONCLUSIONS
  Rapamycin can be safely used in OLT recipients with severe neurological symptoms ascribed to or exacerbated by CNIs. Rapamycin monotherapy may be inadequate to control rejection early after transplantation. Rapamycin can be combined with low doses of CNI to prevent rejection.
authors.affiliation: Department of Surgery, Division of Immunology and Organ Transplantation, University of Texas, Health Science Center, Houston, Texas 77030, USA. bence.forgacs@uth.tmc.edu
authors.forename: B
authors.initials: B
authors.lastname: Forgacs
authors.forename: H J
authors.initials: HJ
authors.lastname: Merhav
authors.forename: J
authors.initials: J
authors.lastname: Lappin
authors.forename: L
authors.initials: L
authors.lastname: Mieles
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D065095:Calcineurin Inhibitors; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control; D020123:Sirolimus / Q000627:therapeutic use*; D016019:Survival Analysis; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus