von Einsiedel Johannes, Thölking Gerold, Wilms Christian, Vorona Elena, Bokemeyer Arne, Schmidt Hartmut H, Kabar Iyad, Hüsing-Kabar Anna
Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, 48149 Münster, Germany.
Department of Internal Medicine and Nephrology, University Hospital of Münster Marienhospital Steinfurt, 48565 Steinfurt, Germany.
J Clin Med. 2020 Jun 1;9(6):1654. doi: 10.3390/jcm9061654.
Renal impairment is a typical side effect of tacrolimus (Tac) treatment in liver transplant (LT) recipients. One strategy to avoid renal dysfunction is to increase the concentration/dose (C/D) ratio by improving drug bioavailability. LT recipients converted from standard-release Tac to MeltDose Tac (LCPT), a novel technological formulation, were able to reduce the required Tac dose due to higher bioavailability. Hence, we hypothesize that such a conversion increases the C/D ratio, resulting in a preservation of renal function. In the intervention group, patients were switched from standard-release Tac to LCPT. Clinical data were collected for 12 months after conversion. Patients maintained on standard-release Tac were enrolled as a control group. Twelve months after conversion to LCPT, median C/D ratio had increased significantly by 50% ( < 0.001), with the first significant increase seen 3 months after conversion ( = 0.008). In contrast, C/D ratio in the control group was unchanged after 12 months (1.75 vs. 1.76; = 0.847). Estimated glomerular filtration rate (eGFR) had already significantly deteriorated in the control group at 9 months (65.6 vs. 70.6 mL/min/1.73 m at study onset; = 0.006). Notably, patients converted to LCPT already had significant recovery of mean eGFR 6 months after conversion (67.5 vs. 65.3 mL/min/1.73 m at study onset; = 0.029). In summary, conversion of LT recipients to LCPT increased C/D ratio associated with renal function improvement.
肾功能损害是肝移植（LT）受者接受他克莫司（Tac）治疗的典型副作用。避免肾功能障碍的一种策略是通过提高药物生物利用度来提高浓度/剂量（C/D）比。从标准释放Tac转换为新型技术制剂MeltDose Tac（LCPT）的LT受者，由于生物利用度更高，能够减少所需的Tac剂量。因此，我们假设这种转换会提高C/D比，从而保护肾功能。在干预组中，患者从标准释放Tac转换为LCPT。转换后收集12个月的临床数据。继续使用标准释放Tac的患者作为对照组。转换为LCPT 12个月后，C/D比中位数显著增加了50%（<0.001），转换后3个月首次出现显著增加（=0.008）。相比之下，对照组12个月后的C/D比没有变化（1.75对1.76；=0.847）。对照组在9个月时估计肾小球滤过率（eGFR）已经显著恶化（研究开始时为65.6对70.6 mL/min/1.73 m²；=0.006）。值得注意的是，转换为LCPT的患者在转换6个月后平均eGFR已经有显著恢复（研究开始时为67.5对65.3 mL/min/1.73 m²；=0.029）。总之，LT受者转换为LCPT可提高C/D比并改善肾功能。
