Observations on recovery of renal function following treatment for acute rejection
The characteristics of rejection and rejection response have not been systematically described in renal transplant recipients. The Efficacy Endpoints Conference Database contains characteristics from 953 episodes of rejection occurring at 19 North American, European, and Australian transplant centers. This database was used to profile renal transplant rejection episodes treated with primary steroid therapy, primary antilymphocyte antibody therapy, and rescue antilymphocyte antibody therapy. Primary steroid therapy was used in 88% of the rejection episodes. A successful response was more common in recipients without fever (72% v 61%; P < 0.004), in recipients experiencing less than a Banff Grade III rejection (92% v 75%; P = 0.009), and was more likely associated with graft function at 1 year following the rejection than rejection episodes that failed steroid therapy (89% v 82%; P = 0.013). Steroid success was statistically identifiable by day 2 of therapy and clinically useful by day 3; serum creatinine on these days of therapy is shown as a ratio of the rejection creatinine (102% v 112% day 1, success v failure, P< 0.002; 104% v122% day 2, success v failure, P < 0.0001; 105% v125% day 3, success vfailure, P < 0.0001). Response to primary antilymphocyte antibody therapy reached significance at day 5 of therapy when serum creatinine decreased below the rejection creatinine level in antilymphocyte successes but remained at or above the rejection creatinine in those who failed the therapy (90% v 135%; P < 0.01). For rescue antilymphocyte antibody therapy, a response was evident after 5 days of therapy (approximately day 9 to 10 of rejection) when serum creatinine began to decline and continued lower throughout the 10-day course of antilymphocyte antibody therapy (day 14 to 15 of rejection; serum creatinine 3.0 mg/dL v 4.4 mg/dL for success v failure; P < 0.004). Serum creatinine was lower throughout the first year following therapy in each success group (steroids, antilymphocyte antibody therapy as primary or as rescue), and a greater percentage of failures of any of the three therapies resulted in graft loss. Interestingly, 1-year graft survival was not different in the patients who were treated with antilymphocyte antibody therapy as primary than those who received these antirejection agents as rescue therapy (81% and 84%, respectively). The Efficacy Endpoints Conference Database provides an essential tool for profiling acute rejection in renal transplantation and should lead to improved evaluation of rejection therapies.