Kidney ischaemia reperfusion injury in the rat: the EGTI scoring system as a valid and reliable tool for histological assessment

Background: The widely adopted Jablonski scoring system for reporting histological damage in kidney ischaemia reperfusion injury (IRI) provides a limited score documenting the degree of necrosis within tubular cells. IRI is a complex process that involves damage to various cellular components of the renal cortex and therefore there is a need to develop a more detailed scoring system. The aims of this study were to evaluate a new comprehensive histology scoring system (comprising Endothelial, Glomerular, Tubular, and Interstitial (EGTI)components), in rat models of IRI. Methods: Twenty-seven adult male Lewis rats underwent surgery: Left unilateral IRI (45-minutes left renal pedicle cross-clamping)(n=5); Left unilateral sham(n=5); Bilateral IRI (45-minutes bilateral renal pedicle cross-clamping)(n=9); and Bilateral sham(n=8). Kidney tissue was retrieved at 48 hours. Paraffin sections were examined under H&E staining. RNA extraction and RT-qPCR analysis were performed for acute kidney injury (AKI) markers. Serum creatinine was measured before and at 48 hours post reperfusion for the bilateral model rats. Results: Forty-five minutes of IRI in the rat caused marked histological damage at 48 hours when compared with sham controls. This was characterized by acute tubular necrosis, endothelial cell disruption and loss, interstitial damage with inflammation, cast formation and necrosis, and glomerular capsule thickening. The EGTI scores correlated significantly with serum creatinine at 48 hours, and expression of AKI markers (NGAL and KIM-1). In addition to this, each individual component on the EGTI histology scoring system correlated significantly with serum creatinine at 48 hours, and expression of NGAL and KIM-1. Discussion: The EGTI histology scoring system appears reliable and more informative in assessing the degree of damage observed in kidney IRI. Separate scoring parameters for Endothelial, Glomerular, Tubular, and Interstitial injury showed sensitivity to IRI, and permit quantitative analysis of injury and protection in different segments of the kidney.