title: Long-Term Follow-Up of De Novo Use of mTOR and Calcineurin Inhibitors After Kidney Transplantation.
abstract: BACKGROUND
  Long-term efficacy and safety of de novo use of the mammalian target of rapamycin inhibitors (mTORi) have been evaluated primarily using registry data.
  
  
  METHODS
  This was a pooled retrospective analysis of data obtained from 10 prospective randomized trials in de novo kidney transplant recipients (n = 581) receiving calcineurin inhibitors (CNIs) combined with sirolimus (n = 329), everolimus (n = 128), or antimetabolites (n = 124).
  
  
  RESULTS
  There were no differences in patient (84.5 versus 80.9 versus 89.7%, P = 0.996), graft (65.4 versus 59.5 versus 73.1%, P = 0.868), and biopsy-confirmed acute rejection-free (78.1 versus 77.3 versus 79.0%, P = 0.976) survivals, respectively. The incidence of cytomegalovirus infection was lower (6 versus 3 versus 11%, P = 0.024) but treatment discontinuation was higher among patients receiving mTORi (66.0 versus 47.7 versus 31.5%, P < 0.001), respectively. At 5 years, median estimated glomerular filtration rate (49.6 versus 43.9 versus 53.2 mL/min, P = 0.006) was lower and the proportion of patients with proteinuria (53 versus 40 versus 23%, P < 0.001) was higher among patients receiving mTORi, respectively.
  
  
  CONCLUSIONS
  The efficacy of de novo use of mTORi is comparable with that of antimetabolites in kidney transplant recipients receiving calcineurin inhibitor. Apart from the lower cytomegalovirus infection rate, the safety profile is unfavorable, showing higher treatment discontinuation rates and higher incidence of proteinuria.
authors.affiliation: *Division of Nephrology, Hospital do Rim, Universidade Federal de Sao Paulo; †Department of Pathology, Universidade Federal de Sao Paulo; and ‡Division of Urology, Hospital do Rim, Universidade Federal de Sao Paulo, Brazil.
authors.forename: Mayara Ivani
authors.initials: MI
authors.lastname: de Paula
authors.forename: José Osmar
authors.initials: JO
authors.lastname: Medina Pestana
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nicolau Ferreira
authors.forename: Marina
authors.initials: M
authors.lastname: Pontello Cristelli
authors.forename: Marcello
authors.initials: M
authors.lastname: Fabiano Franco
authors.forename: Wilson Ferreira
authors.initials: WF
authors.lastname: Aguiar
authors.forename: Hélio
authors.initials: H
authors.lastname: Tedesco-Silva
authors.forename: Claudia
authors.initials: C
authors.lastname: Rosso Felipe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000068338:Everolimus / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus