January 31, 2013

Do-it-yourself repair in the kidney

The kidney can mediate its own repair through proliferation of resident immune system cells.

Kidney cross section showing tubule cells (red) and macrophages (green). (Wellcome Images)

Immune system cells – macrophages and dendritic cells – that reside in the kidney help repair the damage of acute kidney injury (AKI), a new study reports.

AKI is an abrupt decrease in renal function and affects about 5 percent of all hospitalized patients. Ming-Zhi Zhang, M.D., assistant professor of Medicine, Raymond Harris, M.D., Ann and Roscoe R. Robinson Chair in Nephrology, and colleagues investigated the role of macrophages and dendritic cells in recovery from AKI. They evaluated two mouse models of kidney injury: ischemia/reperfusion (I/R) injury and a transgenic mouse with injury limited to the proximal tubule cells of the kidney.

The researchers found that circulating immune cells infiltrated the kidney in the I/R model, but not in the selective proximal tubule injury model. In both models, kidney-resident macrophages and dendritic cells proliferated and became “tissue-reparative.” Inhibition of macrophage CSF-1 (colony stimulating factor) signaling blocked this proliferation and differentiation into a reparative phenotype, and inhibited recovery.

The findings in the December Journal of Clinical Investigation demonstrate that the kidney can mediate its own repair through CSF-1 signaling and macrophage/dendritic cell proliferation.

This research was supported by grants from the National Institutes of Health (DK038226, DK051265, DK062794, CA122620), by the NIH-supported Vanderbilt O’Brien Center (DK079341) and by a VA Merit Award.