ABSTRACTS from 16th International COnference on ... - CRRT Online

Thinking Outside of the Box: A Novel Strategy to Prevent Shock Induced AKI
Todd Costantini MD
11:30-11:45
Thursday, February 16
Educational Objectives:
1. Describe the role of tight junction proteins in maintaining epithelial barrier function.
2. Define the anti-inflammatory properties of efferent vagal nerve signaling.
3. Describe the ability of vagal nerve stimulation to limit shock-induced acute kidney injury.
Content Description:
Acute Kidney Injury (AKI) is a common clinical consequence of shock which is associated with increased morbidity
and mortality in the critically ill population. Tubular epithelial cells play an important role in driving the
inflammatory response of the kidney, which is characterized by pro-inflammatory cytokine secretion and an
innate immune response which further drives AKI. Vagal nerve stimulation (VNS) has been shown to exert
potent anti-inflammatory effects in multiple models of shock. We have recently demonstrated that VNS prevents
intestinal barrier failure and gut inflammation after injury through modulation of intestinal epithelial tight junction
proteins. We hypothesized that VNS may represent a novel strategy to limit shock-induced AKI. This series
of experiments demonstrates the ability of VNS to limit kidney inflammation and prevent injury-induced changes
in epithelial tight junction protein expression.
Suggested Reading:
1. Costantini TW, Bansal V, Krzyzaniak M, Putnam JG, Peterson CY, Loomis WH, Wolf P, Baird A, Eliceiri BP,
Coimbra R: Vagal nerve stimulation protects against burn-induced intestinal injury through activation of enteric
glia cells, Am J Physiol Gastrointest Liver Physiol 2010, 299:G1308-1318.
2. Tracey KJ: Physiology and immunology of the cholinergic antiinflammatory pathway, J Clin Invest 2007,
117:289-296.
3. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW,
Tracey KJ: Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin, Nature 2000,
405:458-462.
4. Turner JR: Molecular basis of epithelial barrier regulation: <strong>from</strong> basic mechanisms to clinical application, Am
J Pathol 2006, 169:1901-1909.
5. Bonventre JV, Yang L: Cellular pathophysiology of ischemic acute kidney injury, J Clin Invest 2011,
121:4210-4221.
6. Bansal V, Costantini T, Ryu SY, Peterson C, Loomis W, Putnam J, Elicieri B, Baird A, Coimbra R:
Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury, J Trauma
2010, 68:1059-1064.
7. Costantini TW, Fraga G, Fortlage D, Wynn S, Fraga A, Lee J, Doucet J, Bansal V, Coimbra R: Redefining
renal dysfunction in trauma: implementation of the Acute Kidney Injury Network staging system, J Trauma
2009, 67:283-287.
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