Vuiblet V, Nguyen T T, Wynckel A, Fere M, Van-Gulick L, Untereiner V, Birembaut P, Rieu P, Piot O
UMR CNRS 7369 MEDyC, Université de Reims Champagne-Ardenne, Reims, France.
Analyst. 2015 Nov 7;140(21):7382-90. doi: 10.1039/c5an00821b.
HydroxyEthyl Starch (HES) has been one of the most commonly used colloid volume expanders in intensive care units for over 50 years. The first and second generation HES, with a high molecular weight (≥200 kD) and a high degree of substitution (≥0.5), has been associated with both renal dysfunction and osmotic nephrosis-like lesions in histological studies. Recently, third generation HES (130 kD/<0.5) has also been shown to impair renal function in critically ill adult patients although tubular accumulation of HES has never been proven in the human kidney. Our objective was to demonstrate the potential of Raman micro-imaging to bring out the presence of third generation-HES in the kidney of patients having received the volume expander.
Four biopsies presenting osmotic nephrosis-like lesions originated from HES-administrated patients with impaired renal function were compared with HES-negative biopsies (n = 10) by Raman microspectroscopy.
The first step was dedicated to the identification of a specific vibration of HES permitting the detection of the cellular and tissue accumulation of the product. This specific vibration at 480 cm(-1) is assigned to a collective mode of the macromolecule; it is located in a spectral region with a limited contribution from biological materials. Based on this finding, HES distribution within tissue sections was investigated using Raman micro-imaging. Determination of HES positive pixels permitted us to clearly distinguish positive cases from HES-free biopsies (proportions of positive pixels from the total number of pixels: 23.48% ± 28 vs. 0.87% ± 1.2; p = 0.004).
This study shows that Raman spectroscopy is a candidate technique to detect HES in kidney tissue samples currently manipulated in nephrology departments. In addition, on the clinical aspect, our approach suggests that renal impairment related to third generation HES administration is associated with osmotic nephrosis-like lesions and HES accumulation in the kidney.
羟乙基淀粉（HES）50多年来一直是重症监护病房中最常用的胶体扩容剂之一。第一代和第二代HES，具有高分子量（≥200 kD）和高取代度（≥0.5），在组织学研究中与肾功能障碍和渗透性肾病样病变有关。最近，第三代HES（130 kD/<0.5）也被证明会损害危重症成年患者的肾功能，尽管尚未在人类肾脏中证实HES的肾小管蓄积。我们的目的是证明拉曼显微成像技术检测接受扩容剂治疗患者肾脏中第三代HES的潜力。
通过拉曼光谱对4例来自接受HES治疗且肾功能受损患者的呈现渗透性肾病样病变的活检组织与10例HES阴性活检组织进行比较。
第一步致力于识别HES的特定振动，以检测该产物在细胞和组织中的蓄积。480 cm(-1)处的这种特定振动归因于大分子的集体模式；它位于生物材料贡献有限的光谱区域。基于这一发现，使用拉曼显微成像研究了组织切片内HES的分布。HES阳性像素的测定使我们能够清楚地将阳性病例与无HES的活检组织区分开来（阳性像素占总像素数的比例：23.48%±28 vs. 0.87%±1.2；p = 0.004）。
本研究表明拉曼光谱是检测肾脏病学科目前处理的肾脏组织样本中HES的一种候选技术。此外，在临床方面，我们的方法表明与第三代HES给药相关的肾功能损害与渗透性肾病样病变和肾脏中HES蓄积有关。
