Intrapatient Variability (IPV) and the Blood Concentration Normalized by the Dose (C/D Ratio) of Tacrolimus-Their Correlations and Effects on Long-Term Renal Allograft Function.

Abstract

Tacrolimus, in combination with mycophenolate mofetil and glucocorticoids, is the basis of immunosuppressive therapy after renal transplantation. Tacrolimus intrapatient variability (IPV) and the blood concentration normalized by the dose (concentration/dose ratio, C/D ratio) both have an effect on the function of the transplanted kidney. In this study, we examined whether the metabolism rate affected IPV, whether the C/D ratio value was stable in the long-term follow-up, and whether it could be used for IPV measurements. In addition, our study population was examined for the effect of the C/D ratio and IPV on long-term renal function. The C/D ratio and IPV were examined in 170 patients at appointments held at 3, 6, 12 and 24 months after RTx. The average time post renal transplantation was 70 months. Renal function defined as creatinine concentration at the last appointment was examined. Results: the mean C/D ratio in the study group was 1.63. A negative correlation between the C/D ratio and creatinine concentration at the end of the follow-up was observed. Between the C/D ratio < and ≥1.63 groups, significant differences in creatinine concentration at the last appointment were found. No relationship was identified between the mean C/D ratio and IPV. The C/D ratio values increased significantly over a longer post-transplant period (12, 24, 60 and 120 m). We did not find a correlation between the mean IPV and the creatinine concentration from the last appointment. Our study group was divided into terciles according to IPV, while no renal graft function differences were found at the same appointment. Conclusion: the C/D ratio is useful for assessing the effects of the metabolism rate of tacrolimus on the long-term renal graft function. The C/D ratio does not affect the IPV value. IPV calculated from variability of the C/D ratio does not influence transplanted kidney function. The C/D changes over time.