Thölking Gerold, Hüls Sophia, Schütte-Nütgen Katharina, Jehn Ulrich, Pavenstädt Hermann, Reuter Stefan, Koch Raphael
Department of Internal Medicine and Nephrology, Herz-Jesu-Hospital Münster-Hiltrup, 48165 Münster-Hiltrup, Germany.
Department of Internal Medicine and Nephrology, University Hospital of Münster Marienhospital Steinfurt, 48565 Steinfurt, Germany.
J Clin Med. 2025 Apr 8;14(8):2542. doi: 10.3390/jcm14082542.
: The tacrolimus (Tac) concentration-to-dose ratio (C/D ratio) has been described as a predictive marker for several outcome parameters after renal transplantation (RTx). Different C/D ratio values are used to define fast (low C/D ratio) and slow Tac metabolizers (high C/D ratio). In this study, the R package was used to determine the optimal C/D ratio cut-off value to define the Tac metabolism type with a high predictive value for the development of renal function. : The data of 389 RTx patients who received an initial immunosuppression with immediate-release tacrolimus (IR-Tac), mycophenolate, prednisolone, and an induction with basiliximab were analyzed. The Tac C/D ratio (ng/mL × 1/mg) of all patients was calculated 3 months after RTx and the maximally selected Wilcoxon statistic was applied to determine the optimal C/D ratio cut-off value for renal function development over a 5-year follow-up. : A C/D ratio of 0.94 provided the optimal differentiation between fast and slow Tac metabolism in relation to renal function development at 1, 2, 3, and 4 years of follow-up, and at 0.95 five years after RTx. : As fast Tac metabolism is associated with the development of an impaired renal function, it is essential to identify patients at risk early after RTx. In order to keep the application simple for clinical routine, we suggest calculating the C/D ratio 3 months after RTx and using 1.0 (≤1.0 = fast metabolizer) as the cut-off, which is very close to the optimal value.
他克莫司（Tac）浓度与剂量之比（C/D比）已被描述为肾移植（RTx）后多个结局参数的预测标志物。不同的C/D比值用于定义快速（低C/D比）和缓慢Tac代谢者（高C/D比）。在本研究中，使用R软件包确定最佳C/D比临界值，以定义对肾功能发展具有高预测价值的Tac代谢类型。分析了389例接受速释他克莫司（IR-Tac）、霉酚酸酯、泼尼松龙初始免疫抑制并使用巴利昔单抗诱导的RTx患者的数据。在RTx后3个月计算所有患者的Tac C/D比（ng/mL×1/mg），并应用最大选择Wilcoxon统计量确定5年随访期间肾功能发展的最佳C/D比临界值。在随访1、2、3和4年时，以及RTx后5年时，C/D比为0.94能在快速和缓慢Tac代谢与肾功能发展之间提供最佳区分。由于快速Tac代谢与肾功能受损的发展相关，因此在RTx后尽早识别有风险的患者至关重要。为了使临床常规应用简单，我们建议在RTx后3个月计算C/D比，并使用1.0（≤1.0 = 快速代谢者）作为临界值，该值非常接近最佳值。
