Immunosuppressive regimens and their effects on renal allograft outcome

The distribution and effectiveness of different immunosuppression protocols among recipients of first cadaver donor renal transplants reported to the UNOS Scientific Renal Transplant Registry whose graft survived at least 14 days after transplantation were analyzed. The results showed that between 1988-1993, 50-60% of recipients received triple therapy regimens including cyclosporine, azathioprine and prednisone (CAP). An additional 20% received CAP with antibody induction therapy (OKT3 or ALG). After 1993, there was an increase in the use of other drug combinations which include FK506 and, more recently, Neoral and mycophenylate mofetil. Patient survival was 90% at 3 years regardless of the immunosuppressive protocol. The 3-year graft survival rate was 75% under cyclosporine-based protocols, but was 79% for more recent recipients treated with FK506 (p = 0.015). Antibody induction protocols were not used more frequently for high-risk patients, including those with broadly reactive anti-HLA antibodies, pediatric recipients, transplants with delayed graft function and those with prolonged cold ischemia times. When induction therapies were reported for these higher risk transplants, there was no noticeable improvement in graft survival rates after excluding failures within the first 2 weeks. Any benefit of antibody induction must therefore be manifest with the first 2 weeks after transplantation. Induction protocols significantly reduced the incidence of rejection episodes (prior to hospital discharge) from 31% for those treated with CAP to 12% for those with antibody induction (p < 0.01), however, 24% of those given induction had at least one rejection between discharge and 6 months compared with only 18% of those treated with CAP without induction (p < 0.01). Although graft outcomes might be significantly influenced by the dosing and timing of immunosuppressive drugs, among the different combinations of drugs analyzed, only FK506 resulted in improved graft survival and half life. With the rapid proliferation of newer drugs and immunosuppressive strategies during 1996, it will be interesting to follow the course of these very recent transplants with regard to the effectiveness of changing immunosuppression.