Research has shown that boosting the kidney’s intrinsic repair mechanisms is a strategy to treat renal injury. In a study entitled “Sox9 Activation Highlights a Cellular Pathway of Renal Repair in the Acutely Injured Mammalian Kidney” , published in Cell Reports, a research team from the Eli and Edythe Broad-CIRM Center for Regenerative Medicine and Stem Cell Research of the University of Southern California led by Andrew P. McMahon identified one such mechanism.

Acute kidney injury (AKI) normally occurs in people hospitalized as a result of an organ transplant, sepsis, nephrotoxic agents or impaired urinary flow. AKI can be fatal in 50%-70% of the cases although in the remaining situations it can be reversed by endogenous repairing mechanisms. “Currently, no treatment exists to treat AKI per se. Identifying the kidney’s intrinsic mechanisms of repair is critical for developing treatments to kickstart the kidneys after AKI, a serious condition with an in-hospital mortality rate exceeding 50 percent,” said study’s first author Sanjeev Kumar.

This research team found that some of the proximal tubular epithelial (PTE) damaged cells within the nephron, the functional unit of the kidney, may survive, proliferate and repair damaged nephrons. Using an animal model of renal injury, researchers identified a specific early injury response signature within PTE cells, the Sox9 gene. The team labeled and tracked cells expressing the Sox9 gene, discovering they give rise to the cell population that restores kidney function. Sox9 activity also labeled regions of kidney damage after post-injury normalization of kidney function. As a final proof of Sox9 key role in kidney repair, inactivation of this gene before AKI prevented kidney function recovery.

In this study, Sox9 was identified as a molecular link between formation and repair of the mammalian nephron. “As such, a Sox9-directed mechanism may represent an expedient, alternative repair process designed to rapidly recruit any surviving mature cell type post-injury into a transient reparative state,” the authors concluded. In the future, therapies that activate Sox-9 may help to increase survival in patients with AKI.