Kidney transplantation with sirolimus and mycophenolate mofetil-based immunosuppression: 5-year results of a randomized prospective trial compared to calcineurin inhibitor drugs.
BACKGROUND
We report the 5-year outcomes from a randomized prospective trial in primary adult renal allograft recipients, designed to evaluate calcineurin inhibitor (CNI)-free immunosuppression on kidney transplant function.


METHODS
Sixty-one patients were randomized to either sirolimus (n=31) or cyclosporine (n=30) after basiliximab induction and mycophenolate mofetil (MMF) with steroids. Sirolimus was concentration controlled at 10-12 ng/mL for at least 6 months.


RESULTS
After 5 years, sirolimus-MMF-steroids compared to cyclosporine-MMF-steroids provides similar patient survival (87.1 vs. 90%, P=0.681), acute rejection rates (12.9 vs. 23.3%, P=0.22), total cholesterol (209.1 vs. 204.3 mg/dL, P=0.973), urine protein/creatinine ratios (0.398 vs. 0.478 mg/dL, P=0.72), and overall medical and surgical morbidity (P=NS). Although unadjusted patient survival was similar, sirolimus based CNI-free patients had longer death censored graft survival (96.4 vs. 76.7%, P=0.0265), higher glomerular filtration rate (GFR) by the abbreviated Modified Diet in Renal Disease (66.7 vs. 50.7 cc/min, P=0.0075), and fewer graft losses from chronic allograft nephropathy. The Banff chronic scores at two years were strong predictors of 5-year GFR. At 5 years, there were six de novo (three solid organ, three skin) cancers in the CNI group and only two de novo (one skin, one leukemia, no solid organ) cancers in the sirolimus group (P=NS).


CONCLUSIONS
This study of low to moderate risk patients demonstrates that excellent 5-year kidney transplant outcomes can be achieved without CNI drugs, when therapeutic drug monitoring of sirolimus is employed. The application of CNI drug avoidance protocols to high-risk recipients (retransplants, highly sensitized, etc.), extrarenal allograft recipients, or alternative drug regimens such as steroid or MMF elimination should be subjected to controlled trials.
Flechner
Stuart M
SM
Transplant Center/Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. flechns@ccf.org
Goldfarb
David
D
Solez
Kim
K
Modlin
Charles S
CS
Mastroianni
Barbara
B
Savas
Kathy
K
Babineau
Denise
D
Kurian
Sunil
S
Salomon
Daniel
D
Novick
Andrew C
AC
Cook
Daniel J
DJ
D000212:Acyclovir / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000517:prevention & control; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020123:Sirolimus / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
D000998:Antiviral Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D015774:Ganciclovir; D020123:Sirolimus; D000212:Acyclovir