Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW, UK.
Eur J Cardiothorac Surg. 2009 Nov;36(5):849-55. doi: 10.1016/j.ejcts.2009.05.042. Epub 2009 Aug 18.
Acute kidney injury (AKI) post-cardiac surgery is associated with mortality rates approaching 20%. The development of effective treatments is hindered by the poor homology between rodent models, the mainstay of research into AKI, and that which occurs in humans. This pilot study aims to characterise post-cardiopulmonary bypass (CPB) AKI in an animal model with potentially greater homology to cardiac surgery patients.
Adult pigs, weighing 50-75 kg, underwent 2.5 h of CPB. Pigs undergoing saphenous vein grafting procedures served as controls. Pre-CPB measures of porcine renal function were within normal ranges for adult humans. The effect of CPB on renal function; a 25% reduction in (51)Cr-EDTA clearance (p=0.068), and a 33% reduction in creatinine clearance (p=0.043), was similar to those reported in clinical studies. CPB resulted in tubular epithelial injury (median NAG/creatinine ratio 2.6 u mmol(-1) (interquartile range (IQR): 0.81-5.43) post-CPB vs 0.48 u mmol(-1) (IQR: 0.37-0.97) pre-CPB, p=0.043) as well as glomerular and/or proximal tubular injury (median albumin/creatinine ratio 6.8 mg mmol(-1) (IQR: 5.45-13.06) post-CPB vs 1.10 mg mmol(-1) (IQR: 0.05-2.00) pre-CPB, p=0.080). Tubular injury scores were significantly higher in kidneys post-CPB (median score 2.0 (IQR: 1.0-2.0) relative to vein graft controls (median score 1.0 (IQR 1.0-1.0), p=0.019). AKI was associated with endothelial injury and activation, as demonstrated by reduced DBA (dolichos biflorus agglutinin) lectin and increased endothelin-1 and vascular cell adhesion molecule (VCAM) staining.
The porcine model of post-CPB AKI shows significant homology to AKI in cardiac surgical patients. It links functional, urinary and histological measures of kidney injury and may offer novel insights into the mechanisms underlying post-CPB AKI.
心脏手术后急性肾损伤（AKI）的死亡率接近 20%。由于啮齿动物模型与人类发生的 AKI 之间缺乏同源性，有效治疗方法的发展受到阻碍，而啮齿动物模型是 AKI 研究的主要方法。本初步研究旨在用一种与心脏手术患者更具同源性的动物模型来描述体外循环（CPB）后 AKI。
体重 50-75kg 的成年猪进行了 2.5 小时的 CPB。接受大隐静脉移植手术的猪作为对照组。CPB 前的猪肾功能测量值在成人的正常范围内。CPB 对肾功能的影响是（51）Cr-EDTA 清除率降低 25%（p=0.068），肌酐清除率降低 33%（p=0.043），与临床研究报告的结果相似。CPB 导致肾小管上皮损伤（CPB 后中位 NAG/肌酐比值 2.6 u mmol(-1)（IQR：0.81-5.43）比 CPB 前 0.48 u mmol(-1)（IQR：0.37-0.97），p=0.043），以及肾小球和/或近端肾小管损伤（CPB 后中位白蛋白/肌酐比值 6.8 mg mmol(-1)（IQR：5.45-13.06）比 CPB 前 1.10 mg mmol(-1)（IQR：0.05-2.00），p=0.080）。CPB 后肾脏的肾小管损伤评分明显更高（中位数评分 2.0（IQR：1.0-2.0）与静脉移植对照组（中位数评分 1.0（IQR 1.0-1.0）相比，p=0.019）。DBA（菜豆凝集素）凝集素的减少和内皮素-1 和血管细胞黏附分子（VCAM）染色的增加表明 AKI 与内皮细胞损伤和激活有关。
CPB 后 AKI 的猪模型与心脏手术患者的 AKI 具有显著的同源性。它将肾脏损伤的功能、尿和组织学测量联系起来，可能为 CPB 后 AKI 的发病机制提供新的见解。
