POSTTRANSPLANT DIABETES-MELLITUS AND METHYLPREDNISOLONE PHARMACOKINETICS IN AFRICAN-AMERICAN AND CAUCASIAN RENAL-TRANSPLANT RECIPIENTS

Post-transplant diabetes among renal transplant recipients is more pre valent in the African-American population. However, it is unknown if m ethylprednisolone (a commonly prescribed glucocorticoid in transplant patients) pharmacokinetics is altered among African-American renal all ograft recipients compared to Caucasian counterparts. Therefore, the o bjectives of this study were to identify the occurrence of post-transp lant diabetes in our clinic population and to characterize the pharmac okinetics of methylprednisolone among our African-American and Caucasi an renal transplant recipients. A retrospective chart survey was done on African-American and Caucasian recipients with stable renal functio n and no history of diabetes pre-transplantation in order to character ize the occurrence of post-transplant diabetes in our clinical populat on. The survey was conducted from January 1985 to January 1992 in reci pients with graft survival of at least 3 months. Post-transplant diabe tes was defined as two fasting glucose serum concentrations greater th an 140 mg/dl or one random serum glucose concentration greater than 20 0 mg/dl which was confirmed by a fasting serum glucose value greater t han 140 mg/dl and a 2 hour post-prandial greater than 200 mg/dl. A 24- hour pharmacokinetic evaluation was conducted in a sub-group of Africa n-American and Caucasian patients after intravenous administration of methylprednisolone. Over the survey period, 75 renal transplants (30 f emales; 45 males) were performed and 50 of these transplant recipients (24 females; 26 males) were not diabetic prior to the allograft place ment. Of these 50 patients, 22 males and 17 females fulfilled the incl usion criteria established for the retrospective survey. Post-transpla nt diabetes was noted only in male patients (1 Caucasian; 7 African-Am erican), and was controlled with diet in the single Caucasian patient and the 3 African-American patients. Insulin was required in the other 4 African-American patients. A sub-group of the surveyed patients (7 Caucasians; 8 African-American) consented to a pharmacokinetic study. The Caucasian patients had a mean methylprednisolone clearance of 319/-168 ml/h/kg and a mean volume of distribution of 1.3+/-0.4 l/kg. The 8 African-American patients exhibited a mean methylprednisolone clear ance of 202+/-73 ml/h/kg (p<0.05) and a mean volume of distribution of 1.0+/-0.4 l/kg (p>0.05). In our clinic population, the occurrence of post-transplant diabetes was approximately 16%. This finding exhibited a male predominance with occurrence in African-American males statist ically greater (p<0.05) than Caucasian males. A lower clearance of met hylprednisolone was observed in the African-American male recipients w hen compared to Caucasian male patients. The reduced clearance of this immunosuppressive agent may have resulted in increased drug exposure in this selected group of renal transplant recipients. Although the de velopment of posttransplant diabetes is multi-factorial, the altered d isposition of methylprednisolone may partially contribute to the manif estation of this disease.