Department of Nephrology/Hypertension, Inselspital, University of Bern, Bern, Switzerland.
J Thorac Cardiovasc Surg. 2010 Mar;139(3):692-700. doi: 10.1016/j.jtcvs.2009.11.015.
Acute kidney injury is a well-known complication with high morbidity and mortality after cardiopulmonary bypass. Cardiopulmonary bypass-associated acute kidney injury is still poorly understood.
Thirty-six patients undergoing elective cardiopulmonary bypass were enrolled. Spot urine samples before and after cardiopulmonary bypass were collected. Acute kidney injury was defined according to the RIFLE classification. To identify differentially regulated proteins after cardiopulmonary bypass, we first analyzed the urinary proteome before and after cardiopulmonary bypass. To identify differentially regulated proteins in acute kidney injury, we next compared the urinary proteome obtained on the first postoperative day between patients with and without acute kidney injury. Difference fluorescence gel electrophoresis was used to compare protein profiles and mass spectrometry to identify individual proteins.
After cardiopulmonary bypass, inflammation-associated (zinc-alpha-2-glycoprotein, leucine-rich alpha-2-glycoprotein, mannan-binding lectin serine protease 2, basement membrane-specific heparan sulfate proteoglycan, and immunoglobulin kappa) or tubular dysfunction-associated (retinol-binding protein, adrenomedullin-binding protein, and uromodulin) proteins were differentially regulated. Acute kidney injury developed in 6 of 36 patients. A modified urinary albumin was increased, and zinc-alpha-2-glycoprotein and a fragment of adrenomedullin-binding protein were decreased in patients with acute kidney injury. Decreased excretion of zinc-alpha-2-glycoprotein in patients with acute kidney injury was confirmed by Western blot and enzyme-linked immunosorbent assay in an independent cohort of 22 patients with and 46 patients without acute kidney injury.
Cardiopulmonary bypass leads to increased urinary excretion of inflammatory proteins and markers of tubular injury. Zinc-alpha-2-glycoprotein is a potentially useful predictive marker for acute kidney injury after cardiopulmonary bypass surgery.
体外循环后急性肾损伤是一种发病率和死亡率都很高的已知并发症。体外循环相关性急性肾损伤仍知之甚少。
纳入 36 例行择期体外循环的患者。体外循环前后采集尿液标本。根据 RIFLE 分类定义急性肾损伤。为了鉴定体外循环后差异调节的蛋白质,我们首先分析了体外循环前后的尿液蛋白质组。为了鉴定急性肾损伤中差异调节的蛋白质,我们接下来比较了有和无急性肾损伤的患者术后第一天的尿液蛋白质组。差异荧光凝胶电泳用于比较蛋白质图谱,质谱用于鉴定单个蛋白质。
体外循环后,炎症相关(锌-α-2-糖蛋白、富含亮氨酸α-2-糖蛋白、甘露糖结合凝集素丝氨酸蛋白酶 2、基底膜特异性硫酸乙酰肝素蛋白聚糖和免疫球蛋白κ)或管状功能障碍相关(视黄醇结合蛋白、肾上腺髓质素结合蛋白和尿调素)蛋白质发生差异调节。36 例患者中有 6 例发生急性肾损伤。急性肾损伤患者的改良尿白蛋白增加,锌-α-2-糖蛋白和肾上腺髓质素结合蛋白的片段减少。在另一组 22 例有和 46 例无急性肾损伤的患者中,通过 Western blot 和酶联免疫吸附试验证实了急性肾损伤患者锌-α-2-糖蛋白排泄减少。
体外循环导致炎症蛋白和管状损伤标志物尿液排泄增加。锌-α-2-糖蛋白是体外循环后急性肾损伤的一个潜在有用的预测标志物。