雷帕霉素靶蛋白与钙调神经磷酸酶抑制剂为基础的免疫抑制对原位肝移植后实测与估算肾小球滤过率的影响

The Effect of Mammalian Target of Rapamycin Versus Calcineurin Inhibitor-based Immunosuppression on Measured Versus Estimated Glomerular Filtration Rate After Orthotopic Liver Transplantation.

作者信息

Zitta Sabine, Schaffellner Silvia, Gutschi Jürgen, Meinitzer Andreas, Kniepeiss Daniela, Artinger Katharina, Reibnegger Gilbert, Rosenkranz Alexander R, Wagner Doris

机构信息

1 Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. 2 Clinical Division of Transplant Surgery, Department of Surgery, Medical University of Graz, Graz, Austria. 3 Department of Laboratory Medicine, Medical University of Graz, Graz, Austria. 4 Department of Physiological Chemistry, Medical University of Graz, Graz, Austria. 5 Division for General Surgery, Department of Surgery, Medical University of Graz, Graz, Austria.

出版信息

Transplantation. 2015 Jun;99(6):1250-6. doi: 10.1097/TP.0000000000000521.

DOI:10.1097/TP.0000000000000521

PMID:25606796

Abstract

INTRODUCTION

Mammalian target of rapamycin (mTOR) inhibitors have been proposed to preserve renal function in patients after orthotopic liver transplantation (OLT) based on estimated glomerular filtration rate (eGFR). The presented study evaluated their effect on renal function in comparison to calcineurin inhibitors (CNIs) defined by measured GFR.

METHODS

Renal function was measured in patients on mTOR-based (n=28) or on CNI-based (n=51) immunosuppression after OLT by performing inulin clearance (IC) as well as eGFR based on the Modification of Diet in Renal Disease (MDRD4) Study and the chronic kidney disease epidermiology (CKD-EPI) formula at baseline, 6, 12, 18, and 24 months. Statistical analysis was performed by using analysis of variance and serial measurement testing.

RESULTS

The MDRD4 and the IC values differed significantly at study inclusion in both groups (mTOR and CNI group, P=0.001), whereas the CKD-EPI and the IC values did not. Estimated GFR by the MDRD4 results declined throughout the study period in patients on CNI and in patients on mTOR (CNI, 81 vs. 61 mL/min/1.73 m(2), P=0.01; 82 vs. 60 mL/min/1.73 m(2), P=0.01), whereas CKD EPI and measured GFR did not change throughout the study period in the CNI.

CONCLUSION

The use of eGFR especially the MDRD-based formula, in OLT patients, leads to incorrect interpretation of their renal function.

摘要

引言

基于估算肾小球滤过率（eGFR），雷帕霉素哺乳动物靶点（mTOR）抑制剂已被提议用于原位肝移植（OLT）术后患者的肾功能保护。本研究评估了其与以实测肾小球滤过率（GFR）定义的钙调神经磷酸酶抑制剂（CNIs）相比，对肾功能的影响。

方法

对OLT术后接受基于mTOR（n = 28）或基于CNI（n = 51）免疫抑制治疗的患者，在基线、6个月、12个月、18个月和24个月时，通过菊粉清除率（IC）以及基于肾病饮食改良（MDRD4）研究和慢性肾脏病流行病学（CKD-EPI）公式的eGFR来测量肾功能。采用方差分析和系列测量检验进行统计分析。

结果

两组（mTOR组和CNI组）在研究纳入时，MDRD4和IC值差异显著（P = 0.001），而CKD-EPI和IC值无差异。在整个研究期间，基于MDRD4结果估算的GFR在接受CNI治疗的患者和接受mTOR治疗的患者中均下降（CNI组，从81降至61 mL/min/1.73 m²，P = 0.01；从82降至60 mL/min/1.73 m²，P = 0.01），而在接受CNI治疗的患者中，CKD-EPI和实测GFR在整个研究期间未发生变化。