Kwiatkowska Ewa, Ciechanowski Kazimierz, Domański Leszek, Dziedziejko Violetta, Przybyciński Jarosław, Pawlik Andrzej
Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, 70-111 Szczecin, Poland.
Deparment of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland.
Biomedicines. 2022 Nov 8;10(11):2860. doi: 10.3390/biomedicines10112860.
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.
他克莫司与霉酚酸酯和糖皮质激素联合使用，是肾移植后免疫抑制治疗的基础。他克莫司的患者内变异性（IPV）以及剂量标准化后的血药浓度（浓度/剂量比，C/D比）均对移植肾的功能有影响。在本研究中，我们考察了代谢率是否影响IPV、C/D比值在长期随访中是否稳定以及它是否可用于IPV测量。此外，我们对研究人群考察了C/D比和IPV对长期肾功能的影响。在肾移植（RTx）后3、6、12和24个月的随访中，对170例患者的C/D比和IPV进行了检测。肾移植后的平均时间为70个月。检测了末次随访时定义为肌酐浓度的肾功能。结果：研究组的平均C/D比为1.63。观察到随访结束时C/D比与肌酐浓度之间呈负相关。在C/D比<1.63组和≥1.63组之间，末次随访时的肌酐浓度存在显著差异。未发现平均C/D比与IPV之间存在关联。在移植后的较长时期（12、24、60和120个月），C/D比值显著升高。我们未发现平均IPV与末次随访时的肌酐浓度之间存在相关性。根据IPV将我们的研究组分为三分位数，而在同一随访时未发现肾移植功能存在差异。结论：C/D比对评估他克莫司代谢率对长期肾移植功能的影响有用。C/D比不影响IPV值。由C/D比的变异性计算出的IPV不影响移植肾功能。C/D比随时间变化。
