Data_Sheet_1_Vitamin D Binding Protein and Renal Injury in Acute Decompensated Heart Failure.PDF

BackgroundRenal 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.Materials and MethodsPatients (71 [64–77] years old) admitted at the emergency room with ADHF and hospitalised were investigated (N = 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.ResultsProteomic 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 (P = 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 (P < 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.ConclusionWe 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.

背景：急性失代偿性心力衰竭（ADHF）患者的肾脏功能是疾病进展和不良预后的强烈预测指标。目前，在ADHF背景下用于早期诊断肾脏损伤的生物标志物尚存在争议，且其与早期病理变化的相关性尚需确立。通过应用蛋白质组学方法，本研究旨在识别因ADHF住院患者的肾脏损伤发展过程中尿液蛋白质标志物的早期变化。材料与方法：纳入了71名（年龄64-77岁）因ADHF急诊入院并住院的患者（N=64）。在入院时（第0天）和72小时后（第3天）收集样本（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）分析了差异血清蛋白质组。使用ELISA方法进行了验证研究。结果：蛋白质组学分析表明，尿维生素D结合蛋白（uVDBP）在ADHF患者中表现为两个蛋白斑点，其强度增加，并且与肾小球滤过率（GFR）存在显著差异。在ADHF住院患者中，尿VDBP水平高于健康对照组三倍以上，其中已出现肾脏功能不全的患者水平最高。在第3天，维持正常肾脏功能的患者的尿VDBP水平降至正常值（P=0.03 vs. 第0天）。相反，出现肾脏损伤的患者的尿VDBP水平保持升高，值是正常范围的两倍以上（P<0.05），而该组的血清肌酐和GFR水平均在生理范围内。ADHF患者的尿VDBP与肾脏损伤标志物如胱抑素C和肾脏损伤分子1（KIM-1）呈正相关。通过ROC分析，尿液VDBP与胱抑素C和KIM-1相结合，可改善对ADHF患者肾脏损伤的预测。结论：我们发现在ADHF患者入院时尿液VDBP升高，并且在肾脏功能障碍早期阶段，即在GFR病理恶化之前，uVDBP的变化模式存在差异。