Decreased acute rejection and improved renal allograft survival using sirolimus and low-dose calcineurin inhibitors without induction therapy.
BACKGROUND
Chronic nephrotoxicity of calcineurin inhibitors (CNIs) causes irreversible renal dysfunction and shortens renal transplant survival. We conducted a retrospective cohort study to test a hypothesis that de novo CNI minimization combined with sirolimus (SRL) improves graft survival in renal transplant patients without antibody induction therapy.


METHODS
Between october 2000 and august 2007, we performed 100 cases of renal transplantation with de novo CNI (either cyclosporine or tacrolimus) minimization combined with sirolimus (SRL group). The initial target trough levels were 100-200 ng/ml for cyclosporine (CSA) and 4-8 ng/mL for tacrolimus (TAC). SRL was given at a loading dose of 6 mg plus 2 mg/day for maintenance. The results for the SRL group were compared to those of 104 transplant recipients given standard CNI- (CsA- or TaC-) based immunosuppressive regimens including mycophenolate mofetil (MMF group) during the same period.


RESULTS
The 1-year rejection-free survival (94.8%) and 5-year graft survival (87.7%) rates of the SRL group were significantly better than those of the MMF group (85.5% and 75.2%, respectively). On univariate analyses, 6-month estimated glomerular filtration rate (eGFR), acute rejection and SRL therapy had a significant impact on graft survival, and SRL therapy and tacrolimus therapy had a significant impact on rejection-free survival. Multivariate analyses identified 6-month eGFR as the only prognostic factor for graft survival. Acute rejection and SRL therapy were significant for post-transplant renal function.


CONCLUSIONS
De novo CNI minimization combined with SRL could decrease acute rejection and improve renal function and graft survival after renal transplantation without the use of antibody induction therapy.
Tsai
Meng-Kun
MK
Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Wu
Fe-Lin Lin
FL
Lai
I-Rue
IR
Lee
Chih-Yuan
CY
Hu
Rey-Heng
RH
Lee
Po-Huang
PH
D000208:Acute Disease; D000328:Adult; D065095:Calcineurin Inhibitors; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus