Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, UK.
Am J Physiol Renal Physiol. 2011 Sep;301(3):F605-14. doi: 10.1152/ajprenal.00145.2011. Epub 2011 Jun 8.
Anemia during cardiopulmonary bypass (CPB) is strongly associated with acute kidney injury in clinical studies; however, reversal of anemia with red blood cell (RBC) transfusions is associated with further renal injury. To understand this paradox, we evaluated the effects of reversal of anemia during CPB with allogenic RBC transfusion in a novel large-animal model of post-cardiac surgery acute kidney injury with significant homology to that observed in cardiac surgery patients. Adult pigs undergoing general anesthesia were allocated to a Sham procedure, CPB alone, Sham+RBC transfusion, or CPB+RBC transfusion, with recovery and reassessment at 24 h. CPB was associated with dilutional anemia and caused acute kidney injury in swine characterized by renal endothelial dysfunction, loss of nitric oxide (NO) bioavailability, vasoconstriction, medullary hypoxia, cortical ATP depletion, glomerular sequestration of activated platelets and inflammatory cells, and proximal tubule epithelial cell stress. RBC transfusion in the absence of CPB also resulted in renal injury. This was characterized by endothelial injury, microvascular endothelial dysfunction, platelet activation, and equivalent cortical tubular epithelial phenotypic changes to those observed in CPB pigs, but occurred in the absence of severe intrarenal vasoconstriction, ATP depletion, or reductions in creatinine clearance. In contrast, reversal of anemia during CPB with RBC transfusion prevented the reductions in creatinine clearance, loss of NO bioavailability, platelet activation, inflammation, and epithelial cell injury attributable to CPB although it did not prevent the development of significant intrarenal vasoconstriction and endothelial dysfunction. In conclusion, contrary to the findings of observational studies in cardiac surgery, RBC transfusion during CPB protects pigs against acute kidney injury. Our study underlines the need for translational research into indications for transfusion and prevention strategies for acute kidney injury.
体外循环期间的贫血与临床研究中的急性肾损伤密切相关；然而，用红细胞（RBC）输血来纠正贫血与进一步的肾损伤相关。为了理解这一悖论，我们在一种新的大型动物模型中评估了体外循环期间用异体 RBC 输血纠正贫血对心脏手术后急性肾损伤的影响，该模型与心脏手术患者中观察到的情况具有显著的同源性。接受全身麻醉的成年猪被分配到 Sham 手术、单独 CPB、Sham+RBC 输血或 CPB+RBC 输血组，在 24 小时时进行恢复和重新评估。CPB 会导致稀释性贫血，并导致猪的急性肾损伤，其特征是肾内皮功能障碍、一氧化氮（NO）生物利用度丧失、血管收缩、髓质缺氧、皮质 ATP 耗竭、肾小球激活血小板和炎症细胞的隔离以及近端肾小管上皮细胞应激。即使在没有 CPB 的情况下输血也会导致肾脏损伤。其特征是内皮损伤、微血管内皮功能障碍、血小板激活，以及与 CPB 猪中观察到的皮质管状上皮表型变化相当，但发生在严重的肾内血管收缩、ATP 耗竭或肌酐清除率降低的情况下。相反，在 CPB 期间用 RBC 输血纠正贫血可防止 CPB 引起的肌酐清除率降低、NO 生物利用度丧失、血小板激活、炎症和上皮细胞损伤，尽管它不能防止发生严重的肾内血管收缩和内皮功能障碍。总之，与心脏手术的观察性研究结果相反，CPB 期间输血可保护猪免受急性肾损伤。我们的研究强调了对输血适应证和急性肾损伤预防策略进行转化研究的必要性。
