Diaz-Riera Elisa, García-Arguinzonis Maisa, López Laura, Garcia-Moll Xavier, Badimon Lina, Padró Teresa
Cardiovascular-Program ICCC, Research Institute-Hospital Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.
Faculty of Medicine, University of Barcelona (UB), Barcelona, Spain.
Front Cardiovasc Med. 2022 Jun 9;9:829490. doi: 10.3389/fcvm.2022.829490. eCollection 2022.
Renal function in acute decompensated heart faiulre (ADHF) is a strong predictor of disease evolution and poor outcome. Current biomarkers for early diagnostic of renal injury in the setting of ADHF are still controversial, and their association to early pathological changes needs to be established. By applying a proteomic approach, we aimed to identify early changes in the differential urine protein signature associated with development of renal injury in patients hospitalised due to ADHF.
Patients (71 [64-77] years old) admitted at the emergency room with ADHF and hospitalised were investigated ( = 64). Samples (urine/serum) were collected at hospital admission (day 0) and 72 h later (day 3). Differential serum proteome was analysed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionisation-time of flight (MALDI-ToF/ToF). Validation studies were performed using ELISA.
Proteomic analysis depicted urinary vitamin D binding protein (uVDBP) as a two spots protein with increased intensity in ADHF and significant differences depending on the glomerular filtration rate (GFR). Urinary VDBP in patients with ADHF at hospitalisation was > threefold higher than in healthy subjects, with the highest levels in those patients with ADHF already presenting renal dysfunction. At day 3, urine VDBP levels in patients maintaining normal renal function dropped to normal values ( = 0.03 vs. day 0). In contrast, urine VDBP levels remained elevated in the group developing renal injury, with values twofold above the normal range ( < 0.05), while serum creatinine and GF levels were within the physiological range in this group. Urinary VDBP in ADHF positively correlated with markers of renal injury such as cystatin C and Kidney Injury Molecule 1 (KIM-1). By ROC analysis, urinary VDBP, when added to cystatin C and KIM-1, improved the prediction of renal injury in patients with ADHF.
We showed increased urine VDBP in patients with ADHF at hospital admission and a differential uVDBP evolution pattern at early stage of renal dysfunction, before pathological worsening of GFR is evidenced.
急性失代偿性心力衰竭（ADHF）患者的肾功能是疾病进展和不良预后的有力预测指标。目前用于ADHF患者肾损伤早期诊断的生物标志物仍存在争议，其与早期病理变化的关联有待确定。通过蛋白质组学方法，我们旨在识别因ADHF住院患者中与肾损伤发展相关的差异尿蛋白特征的早期变化。
对因ADHF入住急诊室并住院的患者（年龄71[64 - 77]岁，n = 64）进行研究。在入院时（第0天）和72小时后（第3天）采集样本（尿液/血清）。通过二维电泳和基质辅助激光解吸电离飞行时间质谱（MALDI-ToF/ToF）分析差异血清蛋白质组。使用酶联免疫吸附测定（ELISA）进行验证研究。
蛋白质组学分析显示尿维生素D结合蛋白（uVDBP）为双斑点蛋白，在ADHF患者中强度增加，且根据肾小球滤过率（GFR）存在显著差异。ADHF患者住院时的尿VDBP水平比健康受试者高出三倍以上，在已出现肾功能不全的ADHF患者中水平最高。在第3天，肾功能维持正常的患者尿VDBP水平降至正常（与第0天相比，P = 0.03）。相反，发生肾损伤组的尿VDBP水平仍保持升高，高于正常范围两倍（P < 0.05），而该组血清肌酐和GFR水平在生理范围内。ADHF患者的尿VDBP与肾损伤标志物如胱抑素C和肾损伤分子1（KIM-1）呈正相关。通过ROC分析，当将尿VDBP与胱抑素C和KIM-1联合使用时，可改善对ADHF患者肾损伤的预测。
我们发现ADHF患者入院时尿VDBP升高，并且在GFR出现病理恶化之前，肾功能不全早期阶段存在差异uVDBP演变模式。
