Comparison of Two Models for Evaluation Histopathology of Experimental Renal Ischemia L.F. Tirapelli, D.F. Barione, B.F.M. Trazzi, D.P.C. Tirapelli, P.C. Novas, C.S. Silva, M. Martinez, R.S. Costa, S. Tucci, Jr, H.J. Suaid, A.J. Cologna, and A.C.P. Martins ABSTRACT Renal ischemia/reperfusion (I/R) injury is one of the frequent causes of acute renal failure (ARF) due to the complex, interrelated sequence of events, that result in damage to and death of kidney cells. Cells of the proximal tubular epithelium are especially susceptible to I/R injury, leading to acute tubular necrosis, which plays a pivotal role in the pathogenesis of ARF. Several models have been explicated to assess morphological changes, including those of Jabonski et al. and Goujon et al. We compared the 2 models for histopathological evaluation of 30- or 120-minute periods of renal ischemia followed by 24-hour reperfusion in rats. Several changes were observed after application of the 2 models: proximal tubular cell necrosis, loss of brush border, vacuolization, denudation of tubular basement membrane as a consequence of flattening of basal cells, and presence of intratubular exfoliated cells in the lumen of proximal convoluted tubules at various stages of degeneration (karyorexis, kariopyknosis and karyolysis). Evaluating tubular lesions after 2 periods of experimental ischemia with light microscopy allowed us to conclude that the Goujon classification better characterized the main changes in cortical renal tubules after ischemia. A CUTE RENAL FAILURE (ARF) is a common con- dition that develops in 5% of hospitalized patients, including about 10% who eventually require renal replace- ment therapy. 1 Among critical care patients who survive, acute renal failure, 2% to 10% develop terminal renal failure requiring long-term dialysis. 2,3 The occurrence of acute renal failure is associated with increased early and late mortality rates, and also high financial costs. 3–5 Renal ischemia/reperfusion (I/R) injury is one of the fre- quent causes of ARF. The kidneys are particularly susceptible to ischemic injury in renal transplantation, 6 suprarenal aneu- rysm repair, 7 renal artery reconstruction, contrast agent– induced nephropathy, 8 cardiac arrest, and shock. Subsequent to renal transplantation, I/R injury is a major cause of early graft rejection, which adversely affects the long-term survival of the graft. Complex mechanisms underlie renal I/R injury. Ischemia initiates a complex, interrelated sequence of events, resulting in injury to and death of renal cells due to cessation of blood flow, deoxygenation, and reperfusion events. Al- though reperfusion is essential for renal tissue survival, it causes additional damage that contributes to the renal dys- function. 9 –11 Proximal tubular epithelial cells are especially susceptible to I/R injury, leading to acute tubular necrosis, which plays a pivotal role in the pathogenesis of ARF. 12 Histological changes are known to be aggravated by increasing ischemia time and afterward by reperfusion. 13–17 True extension of the lesions is seen at 24 to 72 hours after reperfusion. 13–15 Nevertheless, histological examination at just 10 to 30 minutes after organ revascularization shows a striking correlation between the ischemia time and the severity of histological damage. 16,17 A number of models have assessed morphological changes, including those of Jablonski et al. 13 and of Goujon et al. 15 The former analyzed the functional and morphologic effects on rat From the Department of Surgery and Anatomy (L.F.T., D.F.B., D.P.C.T., P.C.N., S.T., H.J.S., A.J.C., A.C.P.M.), Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil; Medical School (B.F.M.T.), University of Marı´lia, São Paulo, Brazil; Department of Pathology and Legal Medicine (R.S.C.), Medical School of Ribeirão Preto, Institute of Superior Education COO (C.S.S.), Course of Physiotherapy, and Department of Morphology and Pathology (M.M.), University Federal of São Carlos, São Paulo, Brazil. Address reprint requests to Prof Luı´s Fernando Tirapelli, Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900 – CEP 14049-900, Ribeirão Preto, São Paulo, Brazil. E-mail: tirapeli@fmrp.usp.br © 2009 Published by Elsevier Inc. 0041-1345/09/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2009.09.061 Transplantation Proceedings, 41, 4083– 4087 (2009) 4083