Monitoring of tacrolimus concentration after kidney or heart transplantation - the importance of intra-subject variability parameters

Abstract

Background. Properly managed immunosuppression in post-transplant therapy is a necessary for minimizing the risk of organ rejection. Aim of the study. Steady-state tacrolimus (TAC) trough concentration (Cssmin) analysis in the first month following heart or kidney transplantation. The intra-individual coefficient of variation (CV) was calculated, correlations with biochemical parameters were searched and recommendations/current guidelines for optimizing TAC dosing based on evidence-based medical databases (EBM) were presented. Material and methods. 24 patients aged 24-79 years (mean 47,1±13,9 years) were selected for retrospective analysis; 12 after heart transplant and 12 after kidney transplant. TAC dosing was the same in the patient groups and did not change during the analysis (first month); in heart recipients it was 2 mg/day and 1 mg/day in kidney recipients. Whole blood Cssmin TAC (steady state) was measured four times in all patients; the first in the 15th day of treatment, the second in 16-18, the third in 17-19, the fourth in 18-21. The QMS Tacrolimus immunoassay was used to analyze TAC concentration using the Indiko Plus automated chemistry analyzer. Results. The median Cssmin TAC value was 6,9-15,6 ng/mL after heart transplant and 8,7-16,0 ng/mL after kidney transplant. The CV range of patients after heart transplantation was 4-60%, while after kidney transplantation it was 8-40%. CV>30% (a higher risk of acute rejection) after heart transplant concerned 25% of patients and 15% after kidney transplant. The analysis of organ survival in heart and kidney recipients showed 83% and 100%, respectively, at an average of 2,7±0,5 and 3,25±2,5 years after transplantation. There were no significant correlations (p>0,05) between CV and selected biochemical parameters. Conclusion. CV>30% may indicate a large variability in the pharmacokinetics of TAC and thus, the need to optimize the dosage/physiological parameters affecting its concentration values. It seems necessary to improve the personalization of immunosuppressive therapy with TAC, taking into account individual parameters of extra- and intra-individual variability, in order to obtain better therapeutic results and avoid acute/chronic rejection, accelerated in time of organ transplant loss and/or the occurrence of additional side effects of TAC.

Keywords

• heart transplantation
• kidney transplantation
• tacrolimus
• intra-individual coefficient of variation