Impact of improving immunosuppressive treatment on outcome in cadaveric kidney transplantation.
BACKGROUND
Since the advent of cyclosporine-based immunosuppression for cadaveric kidney transplants in 1983, several changes have been made in immunosuppressive management at the University of Wisconsin. Since 1986, OKT3 has been available to treat steroid-resistant rejection; since 1992, OKT3 has been used as an induction agent replacing antilymphocyte globulin; and since 1993, mycophenolate mofetil has been used in 104 patients.


METHODS
The impact of different immunosuppressive strategies on overall and immunologic graft survival (defined as graft loss caused by rejection) was evaluated in 1210 primary cadaveric renal transplants at the University of Wisconsin. Covariables, including degree of human leukocyte antigen matching, age, gender, cause of kidney failure, and early graft dysfunction, were evaluated. The series was subdivided into four eras according to immunosuppressive regimen, and the results were analyzed by era.


RESULTS
Our principal findings are that immunologic graft survival has improved significantly during this series whereas overall graft survival has not. Mycophenolate was associated with a significant decrease in acute rejection. For a given patient, graft loss from rejection becomes less likely over time. Late rejection poses a greater risk than early rejection for graft loss.


CONCLUSIONS
Improving outcomes may be related to improving immunosuppressive treatment, increasing degree of human leukocyte antigen matching, and better early graft function.
Knechtle
S J
SJ
Department of Surgery, University of Wisconsin, Madison, USA.
Heisey
D M
DM
Pirsch
J D
JD
D'Alessandro
A M
AM
Kalayoglu
M
M
Sollinger
H W
HW
D000328:Adult; D000367:Age Factors; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002102:Cadaver; D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use*; D003710:Demography; D005069:Evaluation Studies as Topic; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D014019:Tissue Donors; D014184:Transplantation, Homologous
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D009173:Mycophenolic Acid