The effect of early everolimus administration on the renal function while reducing the dosage of calcineurin inhibitors in liver transplant recipients in a long-term follow-up

V. Syutkin, A. Salienko, O. Olisov, S. Zhuravel, M. Novruzbekov
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引用次数: 1

Abstract

Introduction. The lifelong use of calcineurin inhibitors in liver transplant recipients leads to an increased incidence of chronic kidney disease.Objective. To compare the changes in glomerular filtration rate over five years in liver transplant recipients between those on everolimus with a reduced exposure to calcineurin inhibitors and those on standard doses of calcineurin inhibitors.Material and methods. Fourteen liver transplant recipient switched to everolimus with a minimization of calcineurin inhibitors exposure in the first months after liver transplantation from February 2009 to February 2015 who had received that therapy continuously for at least 60 months were included in the case-control study. Twenty eight liver transplant recipients (matched by sex, etiology of the underlying disease, calcineurin inhibitors) who were followed-up for at least 60 months after liver transplantation, who had received no dose of everolimus, in whom the glomerular filtration rate could be calculated at all points of analysis were selected as a comparison group (1:2). Glomerular filtration rate was calculated immediately before liver transplantation; 12, 24, 36, 48, and 60 months after liver transplantation. The glomerular filtration rate after liver transplantation was also calculated for liver transplant recipients from the main group immediately before the conversion to everolimus.Results. Before liver transplantation, the median of glomerular filtration rate in the main group of liver transplant recipients was lower (81.2 ml/min) than in the comparison group (97.5 ml/min, p=0.01). After liver transplantation, the renal function worsened in both groups of patients. In a pairwise comparison, the medians of glomerular filtration rate were statistically significantly lower after 12 months, 24 months, 36 months, 48 months after liver transplantation, than before liver transplantation. The median of glomerular filtration rate at the time of immunosuppression conversion was 44.3 ml/min. After the conversion of immunosuppression, the median of glomerular filtration rate gradually increased, and after 36 months the differences in glomerular filtration rate reached statistical significance compared with the level before conversion (69.4 ml/min;p=0.048). These differences still increased after 60 months after conversion (72.3 ml/min; p=0.041).Conclusion. Long-term administration of everolimus with minimization of calcineurin inhibitors exposure with the early conversion to this immunosuppression regime provides a steady improvement in renal function in liver transplant recipients with a low glomerular filtration rate in the preoperative and early post-transplant period.
长期随访观察早期依维莫司在减少钙调磷酸酶抑制剂剂量的同时对肝移植受者肾功能的影响
介绍。肝移植受者终身使用钙调磷酸酶抑制剂可导致慢性肾脏疾病的发病率增加。比较使用依维莫司减少钙调磷酸酶抑制剂和使用标准剂量钙调磷酸酶抑制剂的肝移植受者在5年内肾小球滤过率的变化。材料和方法。从2009年2月至2015年2月,14名肝移植受者在肝移植后的第一个月内改用依维莫司,并将钙调磷酸酶抑制剂暴露量降至最低,这些患者连续接受依维莫司治疗至少60个月,纳入病例对照研究。选择28名肝移植受者(按性别、基础疾病病因、钙调磷酸酶抑制剂匹配),在肝移植后随访至少60个月,未接受依维莫司剂量,在所有分析点均可计算肾小球滤过率的患者作为对照组(1:2)。肝移植前立即计算肾小球滤过率;肝移植后12、24、36、48和60个月。在转入依维莫司前,计算主组肝移植术后的肾小球滤过率。肝移植前,肝移植受者主组肾小球滤过率中位数(81.2 ml/min)低于对照组(97.5 ml/min, p=0.01)。肝移植后两组患者肾功能均恶化。两两比较,肝移植后12个月、24个月、36个月、48个月肾小球滤过率中位数均低于肝移植前。免疫抑制转化时肾小球滤过率中位数为44.3 ml/min。免疫抑制转化后,肾小球滤过率中位数逐渐升高,36个月后肾小球滤过率与转化前比较差异有统计学意义(69.4 ml/min;p=0.048)。转换后60个月,这些差异仍在增加(72.3 ml/min;.Conclusion p = 0.041)。长期服用依维莫司,尽量减少钙调磷酸酶抑制剂的暴露,并早期转换到这种免疫抑制方案,可以稳定地改善术前和移植后早期肾小球滤过率低的肝移植受者的肾功能。
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