Renal Protection with Isoflurane

Abstract

To the Editor: Hashiguchi et al. (1) recently reported that “isoflurane has a preconditioning effect against renal ischemia/reperfusion injury.” We have previously demonstrated that several inhaled anesthetics protect against renal ischemia and reperfusion injury only when administered during renal ischemia and reperfusion (2). In our study, pretreatment with any of the inhaled anesthetics failed to provide renal protection. We pretreated the animals with volatile anesthetics for 1 h and allowed the animals to awaken completely before anesthetizing them with pentobarbital for renal ischemia and reperfusion studies. Therefore, the washout of volatile anesthetics from the kidney was nearly complete when renal ischemia was induced. In the study by Hashiguchi et al., animals in the “ischemia/isoflurane group received 1.5% isoflurane for 20 min before renal ischemia.” Given the minimal time for isoflurane washout, it is likely that there was residual isoflurane in the renal parenchyma. This is not true pretreatment, but a combination of pretreatment and co-treatment during renal ischemia. Hashiguchi et al. (1) concluded that isoflurane pretreatment reduced renal ischemia reperfusion injury via inhibition of ERK and JNK phosphorylation. However, after ischemia and reperfusion of several organs, including the kidney, there is increased phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK and JNK (3,4) via increased generation of reactive oxygen species. The degree of phosphorylation is correlated with the severity of ischemia and reperfusion injury. A reduction in injury generates fewer reactive oxygen species during reperfusion, leading to reduced phosphorylation of MAPKs. It is possible that the reduction in ERK and JNK phosphorylation is an epi-phenomenon, and not the mechanism of isoflurane protection. Finally, Hashiguchi et al. describe two renal ischemia protocols: bilateral renal ischemia for plasma creatinine measurement and histology, and unilateral renal ischemia for immunoblotting studies. Bilateral and unilateral renal ischemia have fundamental outcome differences and should not be used interchangeably (5,6). Although both bilateral and unilateral protocols are presented in the Methods, only the bilateral renal ischemia data were presented in the article. H. Thomas Lee, MD, PhD Charles W. Emala, MD Department of Anesthesiology College of Physicians and Surgeons of Columbia University Department of Anesthesiology Columbia University New York, NY [email protected]