Hematologic Side Effects of Azathioprine and Mycophenolate in Kidney Transplantation

Abstract

Background Immunosuppressive therapy post–kidney transplantation is usually used continuously and should be regularly monitored. Inadequate dosages of immunosuppressive drugs and lack of regular monitoring can lead to either severe side effects or allograft rejection. Aim To study the hematologic adverse effects and differences between azathioprine and mycophenolate used as maintenance immunosuppressive therapy. Materials and method Fifty-nine (32 male and 27 female) renal transplant patients were enrolled in the study. Patients were transplanted and followed at the University Clinic Cologne, Germany. The mean patient age was 48 ± 2.03 years (standard error of the mean) during the study period, and the mean age at transplantation was 46.8 ± 2.04 years. All patients received mycophenolate for 270 days, and then shifted to an azathioprine-based regimen for 720 days. Both regimens contained prednisolone and cyclosporine. The mean dose of mycophenolate and azathioprine was 20.03 mg/kg/d and 1.3 mg/kg/d, respectively. Data were collected and arranged in Excel Microsoft program, and the statistical analysis was carried out by SPSS V16 package. Analysis of variance and paired t test were used to compare the means of changes that occurred before and after the day 0. P value of ≤.5 were considered statistically significant. Results White blood cells increased significantly after the transplantation during mycophenolate period (9.2 × 10 3, P = .001, .017), while after the shift it tended to decrease, although the change was not statistically significant. On the contrary, absolute leukocyte count decreased after starting azathioprine, and the decrease was statistically significant 12 months after ( P = .006). MCV was stable during mycophenolate (89.1 ± 0.31 fl), but increased significantly following the switch to azathioprine (91.8 ± 0.02 fl, P < .000). Hemoglobin increased after transplantation and continued to increase steadily, although at −270 day, hemoglobin level was significantly lower than day 0 level ( P = .001), and the hematocrit showed the same trend. Serum iron increased significantly ( P = .000–.005), and serum transferrin saturation increased also significantly during azathioprine ( P = .000–.001), respectively. Thrombocyte count did not change significantly under the two regimes. There was no evidence of hemolysis, and reticulocyte percentage ranged between 1.3% and 2%. Bilirubin and the liver enzymes were almost normal in all the patients. Conclusion Mycophenolate and azathioprine hematologic adverse effect are not significantly different as long as close observation and follow-up are performed. Therefore, mycophenolate- and azathioprine-based maintenance regimens can be used interchangeably without significant hematologic adverse effects.