Acute renal failure after whole body ischemia is characterized by inflammation and T cell-mediated injury.

Acute renal failure (ARF) commonly occurs after whole body ischemia. Most experimental models of ARF have relied on the isolated renal artery clamping model; however, there is a pressing need to develop and understand the pathogenesis of new models with more "clinical relevance." We evaluated a new murine model of ARF after whole body ischemia reperfusion injury (WBIRI). WBIRI was induced by an infusion of potassium chloride and a cardiac arrest period of 10 min. Resuscitation was achieved by cardiac compressions, ventilation, epinephrine, and fluids. WBIRI leads to a significant increase in serum creatinine (SCr) and renal tubular injury by 24 h. Renal myeloperoxidase (MPO) levels increased at 24 h after WBIRI. Increased expression of the proinflammatory genes, ICAM-1 and IL-6, was also observed in the kidney following WBIRI. On the basis of recent data that T cells are important mediators of isolated renal IRI, WBIRI was evaluated in T cell-deficient nu/nu mice. T cell-deficient mice had a significantly reduced rise in SCr and decreased tubular injury compared with wild-type mice. T cell-deficient mice had a decrease in ICAM-1 expression after WBIRI, but no decrease in renal MPO. This study describes a new, clinically relevant, model of ARF after WBIRI in mice and identifies the T cell as an important mediator of renal injury following WBIRI. Reduced ICAM-1 expression may provide a mechanism for this involvement.