title: Deferred pre-emptive switch from calcineurin inhibitor to sirolimus leads to improvement in GFR and expansion of T regulatory cell population: a randomized, controlled trial.
abstract: BACKGROUND
  Measures to prevent chronic calcineurin inhibitor (CNI) toxicity have included limiting exposure by switching to sirolimus (SIR). SIR may favorably influence T regulator cell (T(reg)) population. This randomized controlled trial compares the effect of switching from CNI to SIR on glomerular filtration rate (GFR) and T(reg) frequency.
  
  
  METHODS
  In this prospective open label randomized trial, primary living donor kidney transplant recipients on CNI-based immunosuppression were randomized to continue CNI or switched to sirolimus 2 months after surgery; 29 were randomized to receive CNI and 31 to SIR. All patients received mycophenolate mofetil and steroids. The main outcome parameter was estimated GFR (eGFR) at 180 days. T(reg) population was estimated by flowcytometry.
  
  
  RESULTS
  Baseline characteristics in the two groups were similar. Forty-eight patients completed the trial. At six months, patients in the SIR group had significantly higher eGFR as compared to those in the CNI group (88.94 ± 11.78 vs 80.59 ± 16.51 mL/min, p = 0.038). Patients on SIR had a 12 mL/min gain of eGFR of at the end of six months. Patients in the SIR group showed significant increase in T(reg) population at 30 days, which persisted till day 180. There was no difference in the adverse events in terms of number of acute rejection episodes, death, infections, proteinuria, lipid profile, blood pressure control and hematological parameters between the two groups. Four patients taking SIR developed enthesitis. No patient left the study or switched treatment because of adverse event.
  
  
  CONCLUSIONS
  A deferred pre-emptive switch over from CNI to SIR safely improves renal function and T(reg) population at 6 months in living donor kidney transplant recipients. Registered in Clinical Trials Registry of India (CTRI/2011/091/000034).
authors.affiliation: Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Bansal
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Yadav
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.forename: Mukut
authors.initials: M
authors.lastname: Minz
authors.forename: Vinay
authors.initials: V
authors.lastname: Sakhuja
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Jha
mesh_terms: D000328:Adult; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D057915:Drug Substitution; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology / Q000601:surgery; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
chemical_list: D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D019703:Calcineurin; D009173:Mycophenolic Acid; D020123:Sirolimus