Kolonko Aureliusz, Więcek Andrzej
Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, 40-027 Katowice, Poland.
J Clin Med. 2025 Jun 13;14(12):4223. doi: 10.3390/jcm14124223.
Optimal tacrolimus dosing in the early post-transplant period is still challenging. We prospectively studied the possible associations between selected parameters of recipient body composition, markers of intestinal permeability and tacrolimus dosing and blood level in kidney transplant recipients (KTRs) treated with three different tacrolimus formulations. When discharged from hospital immediately after kidney transplantation, markers of intestinal permeability, body composition parameters and tacrolimus blood level were assessed in 165 KTRs treated with Prograf, Advagraf or Envarsus. In the stepwise multivariate analysis performed in patients treated with Prograf, only age independently influenced the tacrolimus exposure expressed as area under the curve (AUC). In patients treated with Advagraf, eGFR (r = 0.291; < 0.05), antithymocyte globulin (vs. basiliximab) induction (r = 0.445; < 0.001), lipopolysaccharide (LPS) level (r = 0.393; < 0.01) and drug dose (r = 0.433; < 0.01) were independently associated with tacrolimus AUC. In patients treated with Envarsus, only age (r = -0.365; < 0.05) and fatty-acid-binding protein (FABP-2) level (r = -0.364; < 0.05) were independently associated with the tacrolimus AUC. We confirmed the significant association between markers of intestinal permeability and tacrolimus exposure in KTRs who underwent early post-transplant conversion from Prograf to Advagraf or Envarsus. This may suggest that the planned tacrolimus conversion from the twice-daily to the once-daily formulation should be performed later (at least 3 months after transplantation) to avoid unnecessary tacrolimus blood level instability.
肾移植术后早期他克莫司的最佳给药方案仍具有挑战性。我们前瞻性地研究了接受三种不同他克莫司制剂治疗的肾移植受者（KTR）的受体身体成分选定参数、肠道通透性标志物与他克莫司给药剂量及血药浓度之间的可能关联。肾移植术后立即出院时，对165例接受普乐可复、新山地明或安斯泰来治疗的KTR进行了肠道通透性标志物、身体成分参数及他克莫司血药浓度评估。在接受普乐可复治疗的患者中进行的逐步多变量分析显示，只有年龄独立影响以曲线下面积（AUC）表示的他克莫司暴露量。在接受新山地明治疗的患者中，估算肾小球滤过率（eGFR，r = 0.291；P < 0.05）、抗胸腺细胞球蛋白（与巴利昔单抗相比）诱导治疗（r = 0.445；P < 0.001）、脂多糖（LPS）水平（r = 0.393；P < 0.01）及药物剂量（r = 0.433；P < 0.01）与他克莫司AUC独立相关。在接受安斯泰来治疗的患者中，只有年龄（r = -0.365；P < 0.05）和脂肪酸结合蛋白（FABP-2）水平（r = -0.364；P < 0.05）与他克莫司AUC独立相关。我们证实在移植后早期从普乐可复转换为新山地明或安斯泰来的KTR中，肠道通透性标志物与他克莫司暴露量之间存在显著关联。这可能提示，他克莫司从每日两次给药方案转换为每日一次给药方案的计划应推迟进行（至少在移植后3个月），以避免他克莫司血药浓度出现不必要的波动。
