title: Low-dose calcineurin inhibitor regimen combined with mammalian target of rapamycin inhibitors preserves kidney functions in renal transplant recipients without allograft nephropathy.
abstract: OBJECTIVE
  The present study was designed to investigate the effect of low-dose calcineurin inhibitor (CNI) tacrolimus combined with a mammalian target of rapamycin (mTOR) inhibitor on renal function in transplant recipients without allograft nephropathy.
  
  
  METHODS
  Twelve patients including seven men (58.3%) of overall mean age of 34.8 ± 14.1 years underwent renal transplantation and were switched to a new second-line treatment of low-dose CNI combined with an mTOR inhibitor, either sirolimus or everolimus.
  
  
  RESULTS
  The underlying cause of renal failure was not clear in half of the cases; for the others it was chronic glomerulonephritis, diabetic nephropathy, polycystic kidney disease, or hypovolemia. After 6 months of the new therapy, there was a significant increase in calculated creatinine clearance levels compared to baseline (75.5 ± 21.9 vs 89.6 ± 19.1 mL/min; P < .001), but no significant change in serum creatinine (1.3 ± 0.4 vs 1.2 ± 0.3 mg/dL) or urinary protein excretion (187.5 ± 142.0 vs 394.0 ± 326.4 mg/g). For almost all patients, proteinuria remained stable, but in two patients, it developed but responded to enalapril treatment. Dose decrement was required for four patients with hyperlipidemia (50%); one patient experienced new-onset hyperlipidemia that responded to treatment. One patient developed a urinary tract infection that responded to antibiotic treatment. None of the patients developed an acute rejection episode.
  
  
  CONCLUSIONS
  Low-dose CNI combined with an mTOR inhibitor, as a replacement for mycophenolate mofetil or enteric-coated mycophenolate sodium, seemed to prevent renal dysfunction for at least 6 months among renal transplant patients without allograft nephropathy.
authors.affiliation: Kent Hospital, Izmir, Turkey. hilmiserdar@superonline.com
authors.forename: S
authors.initials: S
authors.lastname: Kacar
authors.forename: A
authors.initials: A
authors.lastname: Gurkan
authors.forename: C
authors.initials: C
authors.lastname: Karaca
authors.forename: C
authors.initials: C
authors.lastname: Varılsuha
authors.forename: S
authors.initials: S
authors.lastname: Tilif
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014421:Turkey; D014552:Urinary Tract Infections / Q000209:etiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D003404:Creatinine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D016559:Tacrolimus