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1型糖尿病肾移植患者多神经病变标志物的评估及胰岛移植的影响:神经生理学和皮肤活检纵向分析

Evaluation of polyneuropathy markers in type 1 diabetic kidney transplant patients and effects of islet transplantation: neurophysiological and skin biopsy longitudinal analysis.

作者信息

Del Carro Ubaldo, Fiorina Paolo, Amadio Stefano, De Toni Franceschini Luisa, Petrelli Alessandra, Menini Stefano, Martinelli Boneschi Filippo, Ferrari Stefania, Pugliese Giuseppe, Maffi Paola, Comi Giancarlo, Secchi Antonio

机构信息

Department of Neurology and Clinical Neurophysiology, San Raffaele Scientific Institute, Milan, Italy.

出版信息

Diabetes Care. 2007 Dec;30(12):3063-9. doi: 10.2337/dc07-0206. Epub 2007 Sep 5.

Abstract

OBJECTIVE

The purpose of this study was to evaluate whether islet transplantation may stabilize polyneuropathy in uremic type 1 diabetic patients (end-stage renal disease [ESRD] and type 1 diabetes), who received a successful islet-after-kidney transplantation (KI-s).

RESEARCH DESIGN AND METHODS

Eighteen KI-s patients underwent electroneurographic tests of sural, peroneal, ulnar, and median nerves: the nerve conduction velocity (NCV) index and amplitudes of both sensory action potentials (SAPs) and compound motor action potentials (CMAPs) were analyzed longitudinally at 2, 4, and 6 years after islet transplantation. Skin content of advanced glycation end products (AGEs) and expression of their specific receptors (RAGE) were also studied at the 4-year follow-up. Nine patients with ESRD and type 1 diabetes who received kidney transplantation alone (KD) served as control subjects.

RESULTS

The NCV score improved in the KI-s group up to the 4-year time point (P = 0.01 versus baseline) and stabilized 2 years later, whereas the same parameter did not change significantly in the KD group throughout the follow-up period or when a cross-sectional analysis between groups was performed. Either SAP or CMAP amplitudes recovered in the KI-s group, whereas they continued worsening in KD control subjects. AGE and RAGE levels in perineurium and vasa nervorum of skin biopsies were lower in the KI-s than in the KD group (P < 0.01 for RAGE).

CONCLUSIONS

Islet transplantation seems to prevent long-term worsening of polyneuropathy in patients with ESRD and type 1 diabetes who receive islets after kidney transplantation. No statistical differences between the two groups were evident on cross-sectional analysis. A reduction in AGE/RAGE expression in the peripheral nervous system was shown in patients receiving islet transplantation.

摘要

目的

本研究旨在评估胰岛移植是否可使接受肾后胰岛移植(KI-s)成功的尿毒症1型糖尿病患者(终末期肾病[ESRD]和1型糖尿病)的多发性神经病变病情稳定。

研究设计与方法

18例KI-s患者接受了腓肠神经、腓总神经、尺神经和正中神经的神经电生理检查:在胰岛移植后2年、4年和6年纵向分析神经传导速度(NCV)指数以及感觉动作电位(SAP)和复合运动动作电位(CMAP)的波幅。在4年随访时还研究了晚期糖基化终末产物(AGEs)的皮肤含量及其特异性受体(RAGE)的表达。9例仅接受肾移植(KD)的ESRD和1型糖尿病患者作为对照。

结果

KI-s组的NCV评分在4年时间点前有所改善(与基线相比P = 0.01),并在2年后稳定下来,而KD组在整个随访期间该参数无显著变化,组间横断面分析时亦是如此。KI-s组的SAP或CMAP波幅有所恢复,而KD对照组患者的波幅则持续恶化。KI-s组皮肤活检的神经束膜和神经血管中AGE和RAGE水平低于KD组(RAGE的P < 0.01)。

结论

胰岛移植似乎可预防接受肾移植后胰岛移植的ESRD和1型糖尿病患者多发性神经病变的长期恶化。横断面分析显示两组之间无明显统计学差异。接受胰岛移植的患者外周神经系统中AGE/RAGE表达降低。

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