INDIVIDUALIZATION OF MAINTENANCE IMMUNOSUPPRESSION THERAPY EQUALIZES ACUTE REJECTION RISK IN AFRICAN AMERICAN (AA) VERSUS NON-AA RENAL ALLOGRAFT RECIPIENTS

Abstract

303 Subset analyses from US multicenter Tacrolimus (FK) and Mycophenolate mofetil (MMF clinical trials found that maintenance immunosuppression (MRx) with either Prednisone (P)+FK+Azathioprine(Aza) or P+Cyclosporine (Cy)+MMF (3gm/d) was associated with one year acute rejection (AR) rates of 23% and 12%, respectively, in African American (AA) recipients (recips) of cadaveric (CAD) renal allografts (Transplantation 1997;64:1277 & 1998;65:515). Because these regimens increase net immunosuppression relative to dual, P-Cy MRx, uniform use of one or the other on an indefinite basis raises long-term concerns regarding both costs and the risk of immunodeficient complications. As such, the present study was undertaken to determine if equally beneficial outcomes can be obtained in AA vs nonAA recips managed with an individualized approach to MRx governed by an intent to treat all recips with P-Cy and selective utilization of more potent regimens. The study population was comprised of 22 AA and 80 nonAA, adult 1′ CAD recips transplanted between 9/1/93 and 12/31/98. Mean follow-up was 36 ± 17 (SD) mo (range 1-64 mo). Recip age ranged from 23-74 yrs (mean 46 ± 12 [SD] yrs). All recips received antibody (Ab) induction (89% with the Nashville Rabbit polyclonal preparation). Individualized Cy dosage schedules were determined on the basis of pharmacokinetic profiles and established prior to stopping Ab. Indications for FK and/or MMF were inadequate Cy PK profiles, adverse reactions to Cy, or clinician bias re. immunologic and acute nephrotoxic risk. MMF was used on a temporizing (temp) or indefinite (indef) basis. Results are summarized in the following table:TableThe data suggest that Ab induction, Cy PK profiling, and selective use of MRx regimens more potent than P-Cy can provide equivalent outcomes in AA vs nonAA recips without compromising one year outcome standards set by the FK and MMF clinical trials. With up to 90% of recips ultimately able to be carried on P + Cy or FK, individualizing MRx engenders long-term benefits with respect to aggregate costs, risk of immunodeficient complications, and the burden of polypharmacy.