Low tacrolimus dose requirements in renal transplant recipients in the omani population: implications for pharmacogenetics?

Clinical observations suggested that the dose requirements for some immunosuppressive drugs might be lower in some Eastern populations. We performed a study of 50 among 162 patients who were converted from a cyclosporine-based immunosuppression regimen to one based on tacrolimus. The reasons for conversion were as follows: acute rejection (n = 23), hirsutism and gingival hypertrophy (n = 12), chronic allograft nephropathy (n = 4), hypertension (n = 3), and other reasons (n = 8). Target levels were 10-15 ng/mL for patients with acute rejection and 5-8 ng/mL for patients after the first year of transplantation. We measured 180 tacrolimus blood levels in 44 patients using the IMx Abbott system of mean weight 64.5 kg and mean daily dose of 4.89 +/- 2.56 mg with mean blood levels of 11.31 +/- 5.22 ng/mL. Thus, to achieve the above-mentioned levels the average dose was 0.076 mg/kg, which is lower than that generally recommended to achieve 5-8 ng/mL levels, namely, 0.15 mg/kg. In this study, we did not address the reasons for these findings. The possibilities include dietary factors influencing the absorption of tacrolimus, and genetic polymorphisms in the Omani population that affect drug levels through several possible pharmacogenetic/genomic mechanisms. We intend to perform such studies in the future.

High incidence of early posttransplantation diabetes mellitus in an eastern population.

The prevalence of diabetes mellitus (DM) in the Gulf region is among the highest in the world. In the general population of Oman, the rate is approximately 11.7% with an additional 6.1% of the population having an abnormal glucose tolerance. This study reviewed the data for 162 adults who received kidney transplants between 2001 and 2004. The immunosuppression regimen was cyclosporine, mycophenolate mofetil (MMF), and steroids. The mean age of the group was 40.2 years. Twenty-two patients (13.6%) had DM prior to transplantation. Within the first 2 months after transplantation, 45 (32%) of the remaining 140 patients required insulin, and 10 (7.1%) required oral agents. A further 16 patients (11.4%) displayed blood glucose levels >11 mmol/L, but required only a special diet for control. The data indicate that 50% of recent adult kidney recipients in Oman receiving cyclosporine develop posttransplantation DM. This major problem in our transplant population requires special attention. Protocols with minimal steroid use and/or steroid withdrawal may be beneficial for the Oman kidney recipient population.