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慢性肾脏病合并疑似子痫前期妇女中血管生成因子的临床应用价值。

Clinical usefulness of angiogenic factors in women with chronic kidney disease and suspected superimposed preeclampsia.

机构信息

Medical Research Unit in Reproductive Medicine, Unidad de Investigación Médica en Medicina Reproductiva, UMAE-Hospital de Ginecología y Obstetricia "Dr. Luis Castelazo Ayala", Instituto Mexicano del Seguro Social (IMSS), Don Luis # 111, Col. Nativitas, D.F., 03500, Mexico, Mexico.

Posgrado e Investigación Biomedicina y Biotecnología Molecular, Instituto Politécnico Nacional, Ciudad de México, Mexico.

出版信息

J Nephrol. 2022 Jul;35(6):1699-1708. doi: 10.1007/s40620-022-01299-9. Epub 2022 Mar 30.

Abstract

BACKGROUND

Preeclampsia is a condition often superimposed to CKD.

OBJECTIVE

The purpose of this study was to evaluate the clinical characteristics and outcomes of pregnant women with chronic kidney disease (CKD) with suspected superimposed preeclampsia, stratified according to the degree of their angiogenic imbalance, as assessed by the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio.

METHODS

Using a cross-sectional design, we studied 171 pregnancies in patients with CKD and with suspected superimposed preeclampsia, admitted to a teaching hospital. Patients were divided into three groups based on their degree of angiogenic imbalance, evaluated by the sFlt-1/PlGF ratio: no angiogenic imbalance (sFlt-1/PlGF ratio≤ 38), mild angiogenic imbalance (sFlt-1/PlGF ratio> 38 to < 85), and severe angiogenic imbalance (sFlt-1/PlGF ratio≥ 85). Superimposed preeclampsia and preeclampsia-related adverse outcomes were defined according to The American College of Obstetricians and Gynecology criteria.  Measurements of sFlt-1 and PlGF were performed on single serum samples using the Elecsys sFlt-1 and PlGF assays (Roche Diagnostics). Serum soluble endoglin (sEng) levels were also determined (ELISA R&D Systems, Minneapolis, MN). Glomerular filtration rate (GFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, whenever possible on pre-prengancy data.

RESULTS

Patients with severe angiogenic imbalance had higher rates of confirmed superimposed preeclampsia and preeclampsia-related adverse maternal and perinatal outcomes (p < 0.001) when compared to patients with no or mild angiogenic imbalance. A significant trend towards higher serum sEng levels was observed as the degree of angiogenic imbalance increased. Interestingly, the rate of progression to superimposed preeclampsia increased progressively as the degree of angiogenic imbalance increased (no 11.8%, mild 60.0%, and severe 100%).

CONCLUSION

In women with CKD and suspected superimposed preeclampsia, severe angiogenic imbalance was associated with confirmed superimposed preeclampsia or progression to superimposed preeclampsia. Patients with no angiogenic imbalance displayed lower rates of progression to superimposed preeclampsia, whereas outcomes were intermediate, supporting a systematic use of sFlt-1/PlGF ratio, and other biomarkers in the clinical management of CKD pregnacies.

摘要

背景

子痫前期是一种常合并慢性肾脏病(CKD)的疾病。

目的

本研究旨在评估根据可溶性 fms 样酪氨酸激酶-1(sFlt-1)/胎盘生长因子(PlGF)比值评估的血管生成失衡程度,对疑似合并子痫前期的慢性肾脏病(CKD)孕妇的临床特征和结局进行分层。

方法

采用横断面设计,研究了 171 例就诊于教学医院的 CKD 合并疑似合并子痫前期的孕妇。根据 sFlt-1/PlGF 比值将患者分为三组,评估其血管生成失衡程度:无血管生成失衡(sFlt-1/PlGF 比值≤38)、轻度血管生成失衡(sFlt-1/PlGF 比值>38 至<85)和重度血管生成失衡(sFlt-1/PlGF 比值≥85)。根据美国妇产科医师学会(ACOG)标准定义合并子痫前期和子痫前期相关不良结局。使用 Elecsys sFlt-1 和 PlGF 检测(罗氏诊断)在单个血清样本中检测 sFlt-1 和 PlGF。也测定了血清可溶性内皮糖蛋白(sEng)水平(ELISA R&D Systems,明尼苏达州明尼阿波利斯)。尽可能使用孕前数据,根据慢性肾脏病流行病学合作研究(CKD-EPI)公式计算肾小球滤过率(GFR)。

结果

与无或轻度血管生成失衡的患者相比,重度血管生成失衡患者确诊合并子痫前期和子痫前期相关不良母婴和围产儿结局的发生率更高(p<0.001)。随着血管生成失衡程度的增加,血清 sEng 水平显著升高。有趣的是,随着血管生成失衡程度的增加,进展为合并子痫前期的发生率逐渐增加(无 11.8%,轻度 60.0%,重度 100%)。

结论

在 CKD 合并疑似合并子痫前期的女性中,严重的血管生成失衡与确诊合并子痫前期或进展为合并子痫前期相关。无血管生成失衡的患者进展为合并子痫前期的发生率较低,而结局居中,支持系统使用 sFlt-1/PlGF 比值和其他生物标志物进行 CKD 妊娠的临床管理。

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