Study 2: steroid withdrawal in African American kidney transplant recipients receiving sirolimus and tacrolimus: analysis of renal function beyond 1 year

S teroid withdrawal in African American kidney transplant recipients has traditionally resulted in high rates of acute rejection. Conversely, we have previously reported excellent short-term outcomes among 30 African Americans withdrawn from prednisone between 3 and 5 months after primary kidney transplantation and maintained on a regimen of concentration-controlled doses of sirolimus (SRL) (target trough concentrations, 10-15 ng/mL) and tacrolimus (TAC) (target trough concentrations, 5-8 ng/ mL). After a mean follow-up of 14 months, only 2 of 30 patients (6.7%) experienced biopsy-proven acute rejection and 90% of patients remained steroid-free. This cohort of patients has now been followed up for 12 to 35 months (mean, 24 7 months). Acute rejection, prompting renewal of steroid therapy, has occurred in 4 patients (13%), including episodes in 2 patients occurring at 15 and 16 months, respectively, after steroid withdrawal. Two of the 4 episodes of acute rejection occurred in the setting of prolonged delayed graft function and were discovered on “protocol” biopsies. The other 2 episodes were related to gross noncompliance. There has been a single graft loss and no deaths (97% graft survival, 100% patient survival). Prednisone was renewed for medical reasons unrelated to rejection in 2 other patients, including 1 with a late case of hemolytic uremic syndrome and another with intractable bone pain prompting discontinuation of TAC. At last follow-up, 24 of 30 patients (80%) remained steroid-free. For the cohort of 29 patients with functioning grafts, serum creatinine concentration increased from 1.4 0.44 mg/dL before steroid withdrawal to 2.2 1.8 mg/dL at last follow-up (P .028). For the 24 patients who remain off prednisone and free of clinically overt acute rejection, serum creatinine concentration has increased from 1.44 0.4 to 1.65 0.4 mg/dL (P .006). Multiple linear regression was performed to determine the influence of age, gender, body weight, delayed graft function (occurring in 24% of patients), acute rejection, pretransplant panel reactive antibody (ranging from 0% to 84%), and the number of human leukocyte antigen mismatches (A, B, and DR loci) on serum creatinine level at last follow-up. For the entire cohort, independent correlates of serum creatinine level at last follow-up were acute rejection (P .0001), pretransplant panel reactive antibody levels (P .05), and body weight (P .004). For the steroid-free group, the independent correlates of serum creatinine at last follow-up were delayed graft function (P .05), panel reactive antibody (P .05), and male gender (P .003). Conclusion: Results of this uncontrolled study suggest that use of SRL and TAC allows the withdrawal of steroid therapy in African American kidney transplant recipients with a low incidence of acute rejection up to 3 years after transplantation. However, steroid withdrawal may be associated with longterm deterioration of renal function, even in the absence of clinically overt acute rejection. In addition to acute rejection, delayed graft function and pretransplant sensitization contribute to declining renal function over time and might be considered relative contraindications to withdrawing steroid therapy from African American kidney transplant recipients in future studies. From the Departments of Medicine and Surgery, University Hospitals of Cleveland, Cleveland, OH. © 2003 Elsevier Inc. All rights reserved. 0955-470X/03/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.029