The calcineurin inhibitors (CNIs) [cyclosporin A (CsA) and tacrolimus (Tac)] are currently the most widely prescribed drugs for maintenance of immunosuppression after renal transplantation. These immunosuppressants are associated with side effects such as hyperlipidemia. We evaluated the differential effects of different CNIs on serum lipid parameters in renal transplant patients. Moreover, the aim of this study is to investigate the relationships between doses and blood levels of CNIs, and blood levels of CNIs and lipid parameters retrospectively. Two groups of 98 non-diabetic renal transplant patients, each treated with different CNIs, were studied: group A (n = 50, mean age: 31 ± 10 years), CsA, mycophenolate mofetil/azathioprin, steroid; group B (I = 48, mean age: 34 ± 12 years), Tac, mycophenolate mofetil/azathioprin, steroid. In renal transplant patients, CNIs blood levels and doses were examined at 1, 3, 6, 9, and 12 months after transplantation. Biochemical laboratory parameters including plasma lipids [total-cholesterol (CHOL), low-density lipoprotein (LDL)-CHOL, high-density lipoprotein (HDL)-CHOL, and triglycerides (TG)], CNI levels and doses were examined at 1, 3, 6, 9, and 12 months after transplantation. None of the patients received anti-lipidemic drugs during the study period. Blood levels of CNIs were detectable in all whole-blood samples by Cloned- Enzyme-Donor Immunoassay (CEDIA). The relationship between CNIs blood levels and CHOL, (LDL)-CHOL, HDL-CHOL, TG were evaluated. The mean serum CHOL levels and LDL-CHOL levels of patients in group A were found significantly higher than the patients in group B during the 12 month of follow up (p < 0.05). There was no significant difference in TG and HDL-CHOL plasma levels between group A and group B (p > 0.005). In group A the daily dose of CsA was significantly correlated with the mean blood levels of CsA at the 1st and 3rd months (r = 0.387, p = 0.005; r = 0.386, p = 0.006), respectively. In group A, the daily dose of CsA was significantly correlated with the mean serum TG levels during the 12 month of follow up (r = 0.420, p = 0.003). In group B, the daily dose of Tac was significantly correlated with the mean blood level of Tac (r = 0.335, p = 0.020) at the 1st month. No correlation was found between mean Tac blood levels and lipid parameters during the 12-month of follow up (p > 0.05). Significant positive correlation was observed between the CsA blood levels and LDL-CHOL levels (r = 0.338, p = 0.027) at the 3rd month. In the renal transplant patients with well functioning grafts, CsA therapy is associated with increased CHOL and LDL-CHOL ratio which represents an increased atherogenic risk tended to be associated with CsA. Serum LDL-CHOL levels may be effected by blood CsA levels.
Keywords: Calcineurin inhibitors; Cardiovascular diseases; Lipid metabolism; Renal transplantation.