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肾移植受者从他克莫司晚期转换为基于贝拉西普的免疫抑制方案可改善肾功能、酸碱紊乱和矿物质-骨代谢。

Late conversion from tacrolimus to a belatacept-based immuno-suppression regime in kidney transplant recipients improves renal function, acid-base derangement and mineral-bone metabolism.

作者信息

Schulte Kevin, Vollmer Clara, Klasen Vera, Bräsen Jan Hinrich, Püchel Jodok, Borzikowsky Christoph, Kunzendorf Ulrich, Feldkamp Thorsten

机构信息

Department of Nephrology and Hypertension, University Hospital Schleswig-Holstein, Christian-Albrechts University Kiel, Schittenhelmstr. 12, 24105, Kiel, Germany.

Nephropathology, Institute for Pathology, Hannover Medical School, Hanover, Germany.

出版信息

J Nephrol. 2017 Aug;30(4):607-615. doi: 10.1007/s40620-017-0411-0. Epub 2017 May 24.

Abstract

BACKGROUND

Calcineurin inhibitor (CNI)-induced nephrotoxicity and chronic graft dysfunction with deteriorating glomerular filtration rate (GFR) are common problems of kidney transplant recipients. The aim of this study was to analyze the role of belatacept as a rescue therapy in these patients.

METHODS

In this retrospective, observational study we investigated 20 patients (10 females, 10 males) who were switched from a CNI (tacrolimus) to a belatacept-based immunosuppression because of CNI intolerance or marginal transplant function. Patient follow-up was 12 months.

RESULTS

Patients were converted to belatacept in mean 28.8 months after transplantation. Reasons for conversion were CNI intolerance (14 patients) or marginal transplant function (6 patients). Mean estimated GFR (eGFR) before conversion was 22.2 ± 9.4 ml/min at baseline and improved significantly to 28.3 ± 10.1 ml/min at 4 weeks and to 32.1 ± 12.6 ml/min at 12 months after conversion. Serum bicarbonate significantly increased from 24.4 ± 3.2 mmol/l at baseline to 28.7 ± 2.6 mmol/l after 12 months. Conversion to belatacept decreased parathyroid hormone and phosphate concentrations significantly, whereas albumin levels significantly increased. In 6 cases an acute rejection preceded clinically relevant CNI toxicity; only two patients suffered from an acute rejection after conversion. Belatacept was well tolerated and there was no increase in infectious or malignant side effects.

CONCLUSION

A late conversion from a tacrolimus-based immunosuppression to belatacept is safe, effective and significantly improves renal function in kidney transplant recipients. Additionally, the conversion to belatacept has a beneficial impact on acid-base balance, mineral-bone and protein metabolism, independently of eGFR.

摘要

背景

钙调神经磷酸酶抑制剂(CNI)诱导的肾毒性以及肾小球滤过率(GFR)恶化导致的慢性移植肾功能障碍是肾移植受者常见的问题。本研究的目的是分析贝拉西普作为这些患者挽救治疗的作用。

方法

在这项回顾性观察研究中,我们调查了20例患者(10例女性,10例男性),他们因CNI不耐受或移植功能边缘状态而从CNI(他克莫司)转换为基于贝拉西普的免疫抑制治疗。患者随访12个月。

结果

患者在移植后平均28.8个月转换为贝拉西普。转换原因是CNI不耐受(14例患者)或移植功能边缘状态(6例患者)。转换前的平均估计GFR(eGFR)在基线时为22.2±9.4 ml/分钟,转换后4周显著改善至28.3±10.1 ml/分钟,转换后12个月为32.1±12.6 ml/分钟。血清碳酸氢盐从基线时的24.4±3.2 mmol/L显著增加至12个月后的28.7±2.6 mmol/L。转换为贝拉西普显著降低了甲状旁腺激素和磷酸盐浓度,而白蛋白水平显著升高。6例患者在临床上相关的CNI毒性之前发生了急性排斥反应;转换后只有2例患者发生了急性排斥反应。贝拉西普耐受性良好,感染或恶性副作用没有增加。

结论

从基于他克莫司的免疫抑制治疗晚期转换为贝拉西普是安全、有效的,并且显著改善了肾移植受者的肾功能。此外,转换为贝拉西普对酸碱平衡、矿物质-骨和蛋白质代谢有有益影响,与eGFR无关。

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