Use of Urinary Biomarkers of Renal Ischemia in a Lamb Preclinical Left Ventricular Assist Device Model

Evaluation of thrombogenicity is a critical component in the preclinical testing and development of blood pumps. Left ventricular assist devices (LVADs), because of their device routing, can produce thromboembolic showers to the kidney resulting in renal cortical ischemia or infarctions. Although postmortem evaluation of renal pathology can confirm ischemic events and infarctions, there are no validated and highly sensitive real-time measures of renal ischemia in the preclinical models. In this article, we report the evaluation of urinary biomarkers of ischemic tubular damage in a lamb preclinical LVAD model. We found that urinary excretion of glutathione-S-transferase-π, heat shock protein 1B, and hepatitis A virus cellular receptor 1 homologue precursor (HAVCR1/kidney injury molecule 1) were upregulated in toxic ischemic renal injury as well as in the immediate postoperative period in an LVAD-implanted lamb. These markers were consistent with both gross and histologic pathology, and proved far more sensitive for renal injury than serum blood urea nitrogen or creatinine concentrations.