Vascular endothelial cell changes in postcardiac surgery acute kidney injury

Am J Physiol Renal Physiol. 2018 May 1;314(5):F726-F735. doi: 10.1152/ajprenal.00319.2017. Epub 2017 Dec 20.

Abstract

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.

Keywords: cardiopulmonary bypass; endothelium; glycocalyx; kidney injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / physiopathology
  • Adenosine / metabolism
  • Animals
  • Antigens, CD / metabolism
  • Cadherins / metabolism
  • Capillary Permeability
  • Cardiac Surgical Procedures / adverse effects*
  • Cardiopulmonary Bypass / adverse effects*
  • Disease Models, Animal
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Female
  • Glomerular Filtration Rate
  • Glycocalyx / metabolism*
  • Glycocalyx / pathology
  • Glycosaminoglycans / metabolism
  • Kidney / blood supply*
  • Microcirculation
  • Renal Circulation
  • Sus scrofa
  • Thrombomodulin / metabolism

Substances

  • Antigens, CD
  • Cadherins
  • Glycosaminoglycans
  • Thrombomodulin
  • cadherin 5
  • Adenosine