A recent study led by USC Stem Cell scientist Janos Peti-Peterdi, published in the Journal of Clinical Investigation, has revealed that loss of salt and body fluid can stimulate kidney regeneration in mice. This regenerative response is linked to a small population of kidney cells in the macula densa (MD), a region that senses salt and regulates key kidney functions like filtration and hormone secretion.

Revolutionary discovery to help manage kidney disease

Janos Peti-Peterdi, a professor at the Keck School of Medicine of USC, emphasizes the urgency of finding a cure for kidney disease, which currently doesn’t have a cure, leading to dependence on transplants and dialysis.

Researchers, including first author Georgina Gyarmati, adopted an innovative approach by studying the evolutionary development of healthy kidneys instead of focusing on diseased kidneys. Peti-Peterdi explains that the evolution of kidneys from primitive to more advanced kidneys resulted in the development of MD cells, crucial for maintaining efficient kidney function.

In their study, the researchers fed lab mice a very low salt diet and an ACE inhibitor, further reducing salt and fluid levels for up to two weeks. They observed regenerative activity in the MD region, which was inhibited by drugs blocking MD signals, underscoring the MD’s role in kidney regeneration. The analysis of mouse MD cells revealed genetic and structural similarities to nerve cells, which are known to regulate the regeneration of other organs.

Certain gene signals enhanced by low salt for kidney regeneration

The scientists identified specific gene signals, including Wnt, NGFR, and CCN1, in mouse MD cells, enhanced by a low-salt diet to regenerate kidney structure and function. They found that CCN1 activity was significantly reduced in chronic kidney disease (CKD) patients. Testing the therapeutic potential, the team administered CCN1 and MD cells grown in low-salt conditions to mice with focal segmental glomerulosclerosis, a type of CKD.

Both treatments improved kidney structure and function, with MD cell treatment showing the most significant improvements, likely due to additional unknown regenerative factors secreted by MD cells. Peti-Peterdi is optimistic about this novel approach to kidney repair and regeneration.