Bruce A Molitoris Robert Bacallao

Ischemia remains the major cause of acute renal failure (ARF) in the adult population [1]. Clinically a reduction in glomerular filtration rate (GFR) secondary to reduced renal blood flow can reflect prerenal azotemia or acute tubular necrosis (ATN). More appropriate terms for ATN are acute tubular dysfunction or acute tubular injury, as necrosis only rarely is seen in renal biopsies, and renal tubular cell injury is the hallmark of this process. Furthermore, the reduction in GFR during acute tubular dysfunction can now, in large part, be related to tubular cell injury. Ischemic ARF resulting in acute tubular dysfunction secondary to cell injury is divided into initiation, maintenance, and recovery phases. Recent studies now allow a direct connection to be drawn between these clinical phases and the cellular phases of ischemic ARF (Fig. 13-1). Thus, renal function can be directly related to the cycle of cell injury and recovery.

Renal proximal tubule cells are the cells most injured during renal ischemia (Fig. 13-2) [2,3]. Proximal tubule cells normally reabsorb 70% to 80% of filtered sodium ions and water and also serve to selectively reabsorb other ions and macromolecules. This vectorial transport across the cell from lumen to blood is accomplished by having a surface membrane polarized into apical (brush border membrane) and basolateral membrane domains separated by junctional complexes (Fig. 13-3) [4]. Apical and basolateral membrane domains are biochemically and functionally different with respect to many parameters, including enzymes, ion channels, hormone receptors, electrical resistance, membrane transporters, membrane lipids, membrane fluidity, and cytoskeletal associations. This epithelial cell polarity is essential for normal cell function, as demonstrated by the vectorial transport of sodium from the lumen to the blood (see Fig. 13-3). The establishment

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