PDF(Pubmed)
Abstract：
UNASSIGNED: The mammalian target of rapamycin (mTOR) inhibitors in combination with calcineurin inhibitors (CNIs), antimetabolites and corticosteroids for immunosuppression after lung transplantation (TPL) have gained importance in patients with chronic kidney disease (CKD). The goal of this study was to characterize lung transplant recipients (LTR) treated with mTOR inhibitors, with a special focus on kidney function.
UNASSIGNED: LTR transplanted at the University Hospital Zurich between December 1992 and April 2022 were analyzed. Demographics, estimated glomerular filtration rate (eGFR) before and after mTOR initiation, TPL circumstances, immunosuppressive regimens, and allograft function were recorded. We used linear regression to calculate the Mitch curves and a linear mixed-effects model to compare the eGFR.
UNASSIGNED: Of all LTR, 70/593 (12%) received mTOR inhibitors. Intolerance or adverse events of antimetabolites were the most common indications for mTOR inhibitor introduction. Discontinuation in 34/70 (49%) was often related to planned or urgent surgery to prevent impaired wound healing. The majority of patients had a preserved baseline eGFR at mTOR inhibitor introduction with CKD Kidney Disease Improving Global Outcomes (KDIGO) stage G1 or 2. The mean annual eGFR decline changed significantly from -16.19 mL/min/1.73 m2/year [95% confidence interval (CI): -22.27 to -10.11] 12 months before to -6.16 mL/min/1.73 m2/year (95% CI: -13.37 to 1.05) 12 months after mTOR initiation (P=0.009) showing better outcomes with earlier mTOR inhibitor initiation after lung TPL.
UNASSIGNED: This retrospective study suggests stabilization of kidney function after mTOR inhibitor initiation in LTR documented by a slower eGFR decline after mTOR inhibitor introduction with better outcomes early after lung TPL. Intolerance or adverse events of antimetabolites are important indications for the introduction of mTOR inhibitors. A relatively high discontinuation rate (49%) can be explained by planned discontinuation of mTOR inhibitors prior to surgery to avoid impaired wound healing.
UNASSIGNED: LTR transplanted at the University Hospital Zurich between December 1992 and April 2022 were analyzed. Demographics, estimated glomerular filtration rate (eGFR) before and after mTOR initiation, TPL circumstances, immunosuppressive regimens, and allograft function were recorded. We used linear regression to calculate the Mitch curves and a linear mixed-effects model to compare the eGFR.
UNASSIGNED: Of all LTR, 70/593 (12%) received mTOR inhibitors. Intolerance or adverse events of antimetabolites were the most common indications for mTOR inhibitor introduction. Discontinuation in 34/70 (49%) was often related to planned or urgent surgery to prevent impaired wound healing. The majority of patients had a preserved baseline eGFR at mTOR inhibitor introduction with CKD Kidney Disease Improving Global Outcomes (KDIGO) stage G1 or 2. The mean annual eGFR decline changed significantly from -16.19 mL/min/1.73 m2/year [95% confidence interval (CI): -22.27 to -10.11] 12 months before to -6.16 mL/min/1.73 m2/year (95% CI: -13.37 to 1.05) 12 months after mTOR initiation (P=0.009) showing better outcomes with earlier mTOR inhibitor initiation after lung TPL.
UNASSIGNED: This retrospective study suggests stabilization of kidney function after mTOR inhibitor initiation in LTR documented by a slower eGFR decline after mTOR inhibitor introduction with better outcomes early after lung TPL. Intolerance or adverse events of antimetabolites are important indications for the introduction of mTOR inhibitors. A relatively high discontinuation rate (49%) can be explained by planned discontinuation of mTOR inhibitors prior to surgery to avoid impaired wound healing.
摘要：
■哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂与钙调磷酸酶抑制剂（CNIs）联合使用，在慢性肾脏病（CKD）患者中，用于肺移植（TPL）后免疫抑制的抗代谢物和皮质类固醇已变得重要。这项研究的目的是表征用mTOR抑制剂治疗的肺移植受体（LTR），特别关注肾功能。
■分析了1992年12月至2022年4月在苏黎世大学医院移植的LTR。人口统计,mTOR启动前后估计的肾小球滤过率(eGFR)，第三方物流情况，免疫抑制方案，并记录同种异体移植功能。我们使用线性回归计算Mitch曲线，并使用线性混合效应模型比较eGFR。
■在所有LTR中，70/593（12%）接受了mTOR抑制剂。抗代谢物的不耐受或不良事件是mTOR抑制剂引入的最常见适应症。34/70（49％）的停药通常与计划或紧急手术有关，以防止伤口愈合受损。大多数患者在mTOR抑制剂引入CKD肾脏疾病改善全球结果（KDIGO）G1或2期时具有保留的基线eGFR。每年平均eGFR下降显著变化，从12个月前的-16.19mL/min/1.73m2/年[95％置信区间（CI）：-22.27至-10.11]到mTOR启动后的-6.16mL/min/1.73m2/年（95％CI：-13.37至1.05）12个月（P=0.009），表明肺TPL后mTOR抑制剂启动较早的结局更好。
■这项回顾性研究表明，在LTR中，mTOR抑制剂启动后肾功能稳定，mTOR抑制剂引入后eGFR下降较慢，肺TPL后早期预后较好。抗代谢物的不耐受或不良事件是引入mTOR抑制剂的重要指征。相对较高的停药率（49％）可以通过在手术前计划停药mTOR抑制剂以避免受损的伤口愈合来解释。
■分析了1992年12月至2022年4月在苏黎世大学医院移植的LTR。人口统计,mTOR启动前后估计的肾小球滤过率(eGFR)，第三方物流情况，免疫抑制方案，并记录同种异体移植功能。我们使用线性回归计算Mitch曲线，并使用线性混合效应模型比较eGFR。
■在所有LTR中，70/593（12%）接受了mTOR抑制剂。抗代谢物的不耐受或不良事件是mTOR抑制剂引入的最常见适应症。34/70（49％）的停药通常与计划或紧急手术有关，以防止伤口愈合受损。大多数患者在mTOR抑制剂引入CKD肾脏疾病改善全球结果（KDIGO）G1或2期时具有保留的基线eGFR。每年平均eGFR下降显著变化，从12个月前的-16.19mL/min/1.73m2/年[95％置信区间（CI）：-22.27至-10.11]到mTOR启动后的-6.16mL/min/1.73m2/年（95％CI：-13.37至1.05）12个月（P=0.009），表明肺TPL后mTOR抑制剂启动较早的结局更好。
■这项回顾性研究表明，在LTR中，mTOR抑制剂启动后肾功能稳定，mTOR抑制剂引入后eGFR下降较慢，肺TPL后早期预后较好。抗代谢物的不耐受或不良事件是引入mTOR抑制剂的重要指征。相对较高的停药率（49％）可以通过在手术前计划停药mTOR抑制剂以避免受损的伤口愈合来解释。
