title: Timing of conversion to mammalian target of rapamycin inhibitors is crucial in liver transplant recipients with impaired renal function at transplantation.
abstract: BACKGROUND
  Renal dysfunction, primarily related to long-term use of calcineurin inhibitor-based immunosuppression, is the most common complication after liver transplantation.
  
  
  OBJECTIVE
  To evaluate whether liver transplant recipients with impaired kidney function at transplantation can benefit from early conversion to mammalian target of rapamycin inhibitor therapy (mTORi) compared with patients with late induction of mTORi-based therapy.
  
  
  METHODS
  Between 2003 and 2008, therapy was changed to an mTORi-based regimen in 57 patients. Patients were divided into 4 groups: group 1, early conversion (≤3 months after orthotopic liver transplantation) to mTORi therapy, and with impaired perioperative renal function; group 2, early conversion to mTORi therapy, and with normal perioperative renal function; group 3, late conversion to mTORi therapy, and with impaired perioperative renal function; and group 4, late conversion to mTORi therapy, and with normal perioperative renal function.
  
  
  RESULTS
  One month after conversion, the mean (SD) increase in calculated glomerular filtration rate in groups 1 (early conversion) and 3 (late conversion) was comparable: 8 (9) mL/min vs 7 (10) mL/min. At month 3, the increase in calculated glomerular filtration rate between groups 1 and 3 was significant (15 [11] mL/min vs 9 [15] mL/min; P = .04), an effect that persisted at month 6 (16 [12] mL/min vs 10 [12] mL/min; P = .05) and month 12 (22 [14] mL/min vs 12 [15] mL/min; P = .04).
  
  
  CONCLUSIONS
  In liver transplant recipients with perioperatively impaired renal function, early conversion to mTORi therapy should be performed because this approach seems to be more effective in improving long-term renal function.
authors.affiliation: Department of General and Visceral Surgery, University of Muenster, Germany. christina.schleicher@ukmuenster.de
authors.forename: C
authors.initials: C
authors.lastname: Schleicher
authors.forename: D
authors.initials: D
authors.lastname: Palmes
authors.forename: M
authors.initials: M
authors.lastname: Utech
authors.forename: E
authors.initials: E
authors.lastname: Bonrath
authors.forename: N
authors.initials: N
authors.lastname: Senninger
authors.forename: H
authors.initials: H
authors.lastname: Schmidt
authors.forename: H
authors.initials: H
authors.lastname: Wolters
mesh_terms: D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D000068338:Everolimus; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000209:etiology / Q000276:immunology; D008107:Liver Diseases / Q000145:classification / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D003404:Creatinine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus