An initial evaluation of post-cardiopulmonary bypass acute kidney injury in swine

Gavin J Murphy, Hua Lin, Richard J Coward, Tibor Toth, Robin Holmes, David Hall, Gianni D Angelini

Research output: Contribution to journalArticle (Academic Journal)

25 Citations (Scopus)

Abstract

OBJECTIVE: 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.

METHODS AND RESULTS: 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.

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)849 - 855
Number of pages7
JournalEuropean Journal of Cardio-Thoracic Surgery
Volume36
Issue number5
DOIs
Publication statusPublished - Nov 2009

Bibliographical note

Publisher: Elsevier

Structured keywords

  • Centre for Surgical Research

Keywords

  • Acute Kidney Injury
  • Animals
  • Biological Markers
  • Cardiopulmonary Bypass
  • Disease Models, Animal
  • Female
  • Glomerular Filtration Rate
  • Kidney Tubules
  • Pilot Projects
  • Sus scrofa

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