Reversal of anemia with allogenic RBC transfusion prevents post-cardiopulmonary bypass acute kidney injury in swine

Abstract

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.

Interactions of Cardiopulmonary Bypass and Erythrocyte Transfusion in the Pathogenesis of Pulmonary Dysfunction in Swine

“…Biochemical changes in the supernatant, plasma hemoglobin using spectromorphometry, and erythrocyte adenosine triphosphate concentrations using high-performance liquid chromatography, were assessed at weekly intervals, as previously described. 13,15 The hemolysis index was defined as plasma (hemoglobin × hematocrit)/donor unit hemoglobin. Scanning electron microscopy was performed of stored porcine erythrocytes at days 0, 14, and 42 of storage.…”

“…Blots were quantified by densitometry normalized to β-Actin (SantaCruz Biotechnology), as previously described. 13 …”

“…13,14,17 The study outcomes to assess pulmonary dysfunction were prespecified secondary outcomes in these experiments, however, no power calculation was performed a priori, and our analysis should be considered exploratory.…”

“…CPB was performed, as described previously. 13,14 Total CPB time was 2.5 h. Anesthesia, surgical incisions, and monitoring were performed as for transfusion experiments. After 30 min of CPB or sham procedure, 500 ml of crystalloid or allogeneic erythrocytes were transfused over 2 h during the remainder of the intervention period.…”

Diagnostic and therapeutic medical devices for safer blood management in cardiac surgery: systematic reviews, observational studies and randomised controlled trials

“…33 Experimental studies have shown that these changes cause inflammatory organ injury through complex mechanisms including platelet and monocyte activation, endothelial injury and oxidative stress and the loss of microcirculatory autoregulation. [255][256][257][258] This results in paradoxical tissue hypoxia, despite apparently adequate oxygen delivery, tissue inflammation and organ dysfunction. The most important change that occurs in stored red cells over time is the depletion of high-energy phosphates.…”