Gandolfo, M. T. et al. Foxp3+ regulatory T cells participate in repair of ischemic acute kidney injury. Kidney Int. 76, 717–729 (2009).

Park, S. W. et al. Human activated protein C attenuates both hepatic and renal injury caused by hepatic ischemia and reperfusion injury in mice. Kidney Int. 76, 739–750 (2009).

Credit: © Stockxpert

Activated protein C (APC) and T regulatory (TREG) cells provide protective or reparative functions in the ischemic kidney, according to two new studies. In one study, Hamid Rabb and colleagues used a mouse model of acute kidney injury (AKI) to demonstrate that TREG cells participate in tissue repair. In the other, H. Thomas Lee and colleagues demonstrated that APC attenuates AKI. Both groups say their findings improve understanding of the mechanisms of ischemic injury and provide new approaches to improve outcomes in AKI.

Previous studies have revealed that T cells can be either deleterious or beneficial in AKI. The discovery of anti-inflammatory TREG cells in the kidney led Rabb's group to hypothesize that TREG cells could slow inflammation and accelerate repair in AKI. To assess the effects of TREG cells in AKI, the researchers performed interventional studies 24 h after ischemic injury. “We used this delayed time-point to minimize possible effects on early injury. As most patients are seen by nephrologists after the development of AKI, it is very important clinically to be able to accelerate the repair of established AKI”, explains Rabb. The researchers found that depletion of TREG cells delayed tubular repair and enhanced inflammation, while infusion of TREG cells accelerated tubular repair and reduced inflammation. “These findings demonstrate that TREG cell manipulation can accelerate recovery from established AKI”, says Rabb.

Lee, from the second study group, says that the large number of patients with both liver disease and renal insufficiencies led him to study the mechanisms of kidney disease associated with liver failure. For this study, the researchers developed a mouse model in which AKI was induced by hepatic ischemia. “Administration of APC protected against endothelial apoptosis and AKI”, explains Lee.

Both groups plan further studies to elucidate the mechanisms by which these factors exert their beneficial effects.