The surface membrane of proximal tubular cells is organized into distinct apical and basolateral membrane domains. The establishment and maintenance of these biochemically, structurally and physiologically distinct domains involves a multi-stage process involving cell-cell, cell-ECM interactions, and polarized targeting mechanisms. Ischemia, via cellular ATP depletion, results in a series of structural, biochemical and functional alterations that lead to loss of proximal tubular cell surface membrane polarity. Of central importance is the rapidly-occurring, duration-dependent disruption and dissociation of the actin cytoskeleton and associated surface membrane structures. This results in numerous cellular alterations including loss of cell-cell contact, cell-extracellular matrix adhesion and surface membrane polarity. Redistribution of surface membrane proteins and lipids into the alternate domain results in the cells inability to function properly. Repair of these disorders involves re-establishment of the actin cytoskeleton and apical and basolateral surface membrane domains. Recent information indicates growth factors may play a role in hastening this repair process.