Vascular endothelial cell changes in postcardiac surgery acute kidney injury

• Published in: American journal of physiology. Renal physiology Vol. 314; no. 5; pp. F726 - F735
• Main Authors: Qureshi, Saqib H, Patel, Nishith N, Murphy, Gavin J
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.05.2018
• Subjects: Acute Kidney Injury - etiology; Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; Acute Kidney Injury - physiopathology; Adenosine; Adenosine - metabolism; Anesthesia; Animals; Antigens, CD - metabolism; Cadherins; Cadherins - metabolism; Capillary Permeability; Cardiac Surgical Procedures - adverse effects; Cardiopulmonary Bypass - adverse effects; Creatinine; Disease Models, Animal; Endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; Epitopes; Female; Genotype & phenotype; Glomerular Filtration Rate; Glycocalyx - metabolism; Glycocalyx - pathology; Glycosaminoglycans; Glycosaminoglycans - metabolism; Heart surgery; Homeostasis; Kidney - blood supply; Kidney diseases; Kidneys; Membrane proteins; Microcirculation; Microvasculature; Neck; Perfusion; Permeability; Phenotypes; Proteins; Proteinuria; Renal Circulation; Renal cortex; Structure-function relationships; Sus scrofa; Thrombomodulin; Thrombomodulin - metabolism; Wheat germ; glycocalyx; cardiopulmonary bypass; endothelium; kidney injury
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00319.2017

Acute kidney injury (AKI) is common complication of cardiac surgery; however, the phenotype of this condition is poorly defined. The aim of this study was to characterize changes in endothelial structure and function that underlie postcardiopulmonary bypass (post-CPB) AKI. Adult pigs ( n = 16) were randomized to undergo the following procedures ( n = 8 per group): group 1: sham operation, neck dissection with 2.5 h of general anesthesia; and group 2: CPB, 2.5 h of cardiopulmonary bypass. CPB resulted in the depletion of specific epitopes of glycosaminoglycans side chains of the endothelial glycocalyx: Dolichos biflorus agglutinin: mean difference (MD) [95% confidence interval (CI)], P value: -0.26 (-0.42, -0.09), P = 0.0024, Triticum vulgaris (wheat germ) agglutinin: -0.83 (-1.2, -0.38), P = 0.0005, and Ulex europaeus agglutinin 1: -0.25 (-0.49, -0.009), P = 0.041; endothelial membrane protein: thrombomodulin: -3.13 (-5.6, -0.65), P = 0.02; and adherens junction: VE-cadherin: -1.06 (-1.98, -0.145), P = 0.02. CPB also resulted in reductions in microvascular cortical perfusion: -0.62 (-1.02, -0.22), P = 0.006, and increased renal cortex adenosine levels: 2.32 (0.83, 3.8), P = 0.0059. These changes were accompanied by significant reduction in creatinine clearance at 1.5 h postintervention, MD 95% CI; -51.7 (-99.7, -3.7), P = 0.037, and at 24 h, MD (95% CI): -47.3 (-87.7, -7.6), P = 0.023, and proteinuria immediately postintervention MD (95% CI): 18.79 (2.17, 35.4), P = 0.03 vs. sham. In our experimental CPB model, endothelial injury was associated with loss of autoregulation, increase in microvascular permeability, and reduced glomerular filtration. Interventions that promote endothelial homeostasis may have clinical utility in the prevention of postcardiac surgery AKI.