IMMUNOSUPPRESSIVE THERAPY IN HIGH-RISK TRANSPLANT PATIENTS

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Abstract
Numerous studies have demonstrated that renal allograft survival is reduced in African-Americans (AAs). This posthoc racial subgroup analysis (AAs vs. non-AAs) tested whether mycophenolate mofetil (MMF) might have favorable implications for the treatment of AA renal allograft recipients. Patients received a triple therapy regimen of corticosteroids, cyclosporine, and azathioprine (AZA) 1-2 mg/kg/day, MMF 2 g/day (MMF 2 g), or MMF 3 g/day (MMF 3 g). AAs in the AZA group had the highest biopsy-proven rejection/treatment failure (BPR/TF) rate (57.5% vs. 43.5% for non-AAs). AAs in the MMF 3 g group showed a significant reduction in BPR/TF (57.5% vs. 24.2%, P=0.0008). BPRs were more frequent for AAs in either the AZA (47.5%) or MMF 2 g group (31.8%) than in the MMF 3 g group (12.1%), whereas rejections were reduced for non-AAs receiving either MMF dosage (AZA, 35.5%; MMF 2 g, 15.7%; MMF 3 g, 18.8%). AAs in the AZA group experienced BPR/TF earlier than AAs in the MMF 3 g group (median onset at 64 days vs. > 183 days, P=0.0012). But AAs in the MMF 3 g experienced BPR/TF the latest among the six subgroups of treatment and race. AAs had more severe rejection episodes and higher serum creatinine levels at 6 months after transplant, regardless of treatment group. Dose-dependent prevention of acute rejection in AAs is best afforded by a dosage of MMF at 3 g/day, whereas 2 g/day provides a superior benefit/risk ratio for non-AAs. MMF at 3 g/day thus provides an improvement over conventional immunosuppressive strategies in reducing the frequency of acute rejections in this immunologically high-risk group.