Post-transplant diabetes mellitus and methylprednisolone pharmacokinetics in African-American and Caucasian renal transplant recipients

Post-transplant diabetes among renal transplant recipients is more prevalent in the African-American population. However, it is unknown if methylprednisolone (a commonly prescribed glucocorticoid in transplant patients) pharmacokinetics is altered among African-American renal allograft recipients compared to Caucasian counterparts. Therefore, the objectives of this study were to identify the occurrence of post-transplant diabetes in our clinic population and to characterize the pharmacokinetics of methylprednisolone among our African-American and Caucasian renal transplant recipients. A retrospective chart survey was done on African-American and Caucasian recipients with stable renal function and no history of diabetes pre-transplantation in order to characterize the occurrence of post-transplant diabetes in our clinical populaton. The survey was conducted from January 1985 to January 1992 in recipients with graft survival of at least 3 months. Post-transplant diabetes was defined as two fasting glucose serum concentrations greater than 140 mg/ dl or one random serum glucose concentration greater than 200 mg/dl which was confirmed by a fasting serum glucose value greater than 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 African-American and Caucasian patients after intravenous administration of methylprednisolone. Over the survey period, 75 renal transplants (30 females; 45 males) were performed and 50 of these transplant recipients (24 females; 26 males) were not diabetic prior to the allograft placement. Of these 50 patients, 22 males and 17 females fulfilled the inclusion criteria established for the retrospective survey. Post-transplant diabetes was noted only in male patients (1 Caucasian; 7 African-American), 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 clearance 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 statistically greater (p < 0.05) than Caucasian males. A lower clearance of methylprednisolone was observed in the African-American male recipients when 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 development of post-transplant diabetes is multi-factorial, the altered disposition of methylprednisolone may partially contribute to the manifestation of this disease.