• Richard A Zager.
• The Fred Hutchinson Cancer Research Center, and the University of Washington, Seattle, WA, USA.
• Nephrol. Dial. Transplant. 2013 Aug 1;28(8):1985-93.

AbstractFollowing the induction of ischemic or toxin-mediated acute kidney injury (AKI), cellular adaptations occur that 're-program' how the kidney responds to future superimposed insults. This re-programming is not simply a short-lived phenomenon; rather it can persist for many weeks, implying that a state of 'biologic memory' has emerged. These changes can be both adaptive and maladaptive in nature and they can co-exist in time. A beneficial adaptation is the emergence of acquired cytoresistance, whereby a number of physiologic responses develop that serve to protect the kidney against further ischemic or nephrotoxic attack. Conversely, some changes are maladaptive, such as a predisposition to Gram-negative or Gram-positive bacteremia due to a renal tubular up-regulation of toll-like receptor responses. This latter change culminates in exaggerated cytokine production, and with efflux into the systemic circulation, extra-renal tissue injury can result (so-called 'organ cross talk'). Another maladaptive response is a persistent up-regulation of pro-inflammatory, pro-fibrotic and vasoconstrictive genes, culminating in progressive renal injury and ultimately end-stage renal failure. The mechanisms by which this biologic re-programming, or biologic memory, is imparted remain subjects for considerable debate. However, injury-induced, and stable, epigenetic remodeling at pro-inflammatory/pro-fibrotic genes seems likely to be involved. The goal of this editorial is to highlight that the so-called 'maintenance phase' of acute renal failure is not a static one, somewhere between injury induction and the onset of repair. Rather, this period is one in which the induction of 'biologic memory' can ultimately impact renal functional recovery, extra-renal injury and the possible transition of AKI into chronic, progressive renal disease.

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