Department of Infectious Diseases, Murska Sobota General Hospital, 9000, Murska Sobota, Slovenia.
Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000, Ljubljana, Slovenia.
Emerg Microbes Infect. 2018 May 16;7(1):89. doi: 10.1038/s41426-018-0090-5.
Hemorrhagic fever with renal syndrome (HFRS) is characterized by endothelial dysfunction with capillary leakage without obvious cytopathology in the capillary endothelium. The aim of the study was to analyze the kinetics of vascular endothelial growth factor (VEGF) and its soluble receptor (sVEGFR-2) in HFRS patients infected with Dobrava (DOBV) or Puumala virus (PUUV). VEGF and sVEGFR-2 levels were measured in daily plasma and urine samples of 73 patients with HFRS (58 with PUUV, 15 with DOBV) and evaluated in relation to clinical and laboratory variables. In comparison with the healthy controls, initial samples (obtained in the first week of illness) from patients with HFRS had higher plasma and urine VEGF levels, whereas sVEGFR-2 levels were lower in plasma but higher in urine. VEGF levels did not differ in relation to hantavirus species, viral load, or the severity of HFRS. The comparison of VEGF dynamics in plasma and urine showed the pronounced secretion of VEGF in urine. Significant correlations were found between daily VEGF/sVEGFR-2 levels and platelet counts, as well as with diuresis: the correlations were positive for plasma VEGF/sVEGFR-2 levels and negative for urine levels. In addition, patients with hemorrhagic manifestations had very high plasma and urine VEGF, together with high urine sVEGFR-2. Measuring the local secretion of sVEGFR-2 in urine might be a useful biomarker for identifying HFRS patients who will progress to severe disease.
肾综合征出血热（HFRS）的特征是内皮功能障碍伴毛细血管渗漏，而毛细血管内皮无明显细胞病理学改变。本研究旨在分析感染 Dobrava（DOBV）或普马拉病毒（PUUV）的 HFRS 患者血管内皮生长因子（VEGF）及其可溶性受体（sVEGFR-2）的动力学。测量了 73 例 HFRS 患者（58 例 PUUV，15 例 DOBV）的每日血浆和尿液样本中的 VEGF 和 sVEGFR-2 水平，并与临床和实验室变量相关进行了评估。与健康对照组相比，HFRS 患者的初始样本（在发病第一周获得）具有更高的血浆和尿液 VEGF 水平，而血浆中 sVEGFR-2 水平较低，但尿液中水平较高。VEGF 水平与汉坦病毒种类、病毒载量或 HFRS 的严重程度无关。血浆和尿液中 VEGF 动力学的比较表明 VEGF 在尿液中大量分泌。每日 VEGF/sVEGFR-2 水平与血小板计数以及尿量之间存在显著相关性：血浆 VEGF/sVEGFR-2 水平呈正相关，而尿液水平呈负相关。此外，有出血表现的患者具有非常高的血浆和尿液 VEGF，同时尿液 sVEGFR-2 水平也很高。测量尿液中 sVEGFR-2 的局部分泌可能是识别将发展为严重疾病的 HFRS 患者的有用生物标志物。
