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

^a Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW, UK
^b Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol BS10 9NT, UK
^c Department of Histopathology, North Bristol NHS Trust, Southmead Hospital, Bristol BS10 9NT, UK
^d Department of Medical Physics and Bioengineering, University Hospitals Bristol NHS Foundation Trust, Bristol General Hospital, Bristol BS1 6SY, UK

Received 23 December 2008; received in revised form 28 April 2009; accepted 19 May 2009.

^_* Corresponding author. Tel.: +44 1173420502; fax: +44 1173423288. (Email: gavin.murphy{at}bristol.ac.uk).

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 ⁵¹Cr-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.

Key Words: Acute kidney injury • Cardiopulmonary bypass • Endothelial activation