title: Microvascular endothelial injury and dysfunction during ischemic acute renal failure.
abstract: The pathophysiology of ischemic acute renal failure (ARF) appears to involve a complex interplay between renal hemodynamics, tubular injury, and inflammatory processes. While the current paradigm of the pathophysiology of ischemic ARF invokes both sublethal and lethal tubular injury as being of paramount importance to diminished renal function, a growing body of evidence supports the contribution of altered renal vascular function in potentially initiating and subsequently extending the initial tubular injury. We propose that the "extension phase" of ischemic ARF involves alterations in renal perfusion, continued hypoxia, and inflammatory processes that all contribute to continued tubular cell injury. Vascular endothelial cell injury and dysfunction play a vital part in this extension phase. In the constitutive state the endothelium regulates migration of inflammatory cells into tissue, vascular tone and perfusion, vasopermeability, and prevents coagulation. Upon injury, the endothelial cell loses its ability to regulate these functions. This loss of regulatory function can have a subsequent detrimental impact upon renal function. Vascular congestion, edema formation, diminished blood flow, and infiltration of inflammatory cells have been documented in the corticomedullary junction of the kidney, but linking their genesis to vascular endothelial injury and dysfunction has been difficult. However, new investigative approaches, including multiphoton microscopy and the Tie2-GFP mouse, have been developed that will further our understanding of the roles endothelial injury and dysfunction play in the pathophysiology of ischemic ARF. This knowledge should provide new diagnostic and therapeutic approaches to ischemic ARF.
authors.affiliation: Division of Nephrology, Department of Medicine, and the Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, Indiana, USA. tsutton2@iupui.edu
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Sutton
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Fisher
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Molitoris
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D008833:Microcirculation / Q000502:physiology