Loss of regulatory T cell function on anti-inflammation is correlated with increased risk of acute kidney injury development in patients with primary glomerulonephritis.

Inflammation is believed to play a major role in the pathophysiology of acute kidney injury (AKI). The injury induces the generation of inflammatory mediators like cytokines and chemokines by tubular and endothelial cells which contribute to the recruiting of leukocytes into the kidneys. Early AKI risk evaluation is limited to demographic characteristics and past clinical histories, and no specific treatment is available. To better identify patients at risk of developing AKI, and devise more targeted treatment and prevention regimen, we tracked 158 primary glomerulonephritis patients for their occurrence of AKI, and analyzed the characteristics of their adaptive immune system. We found that in patients that later developed AKI, peripheral blood T cell composition is shifted toward IFN-g-producing Th1-like cells. While the composition of CD4(+)CD25(+) T cells were similar between patients that later developed AKI and patients without AKI development, in patients that later developed AKI, their CD4(+)CD25(+) T cells secreted less regulatory cytokine IL-10, and was unable to suppress proinflammatory cytokine production by CD4(+) T cells, while in patients without AKI development, CD4(+)CD25(+) T cells were able to suppress CD4(+) T cell-mediated IFN-g and IL-17 expression under stimulation, partially through IL-10 secretion. Collectively, we identified a defect in CD4(+)CD25(+) T cell regulatory function in patients at risk of developing AKI.