A groundbreaking study by USC researchers has found that a low-salt diet can stimulate kidney regeneration in mice, potentially leading to new treatments for chronic kidney disease. The discovery highlights the crucial role of macula densa cells and offers innovative therapeutic possibilities.
A study led by University of Southern California Stem Cell scientist Janos Peti-Peterdi has discovered a novel method to stimulate kidney regeneration through a low-salt diet. The research, recently published in The Journal of Clinical Investigation, could pave the way for innovative treatments for chronic kidney disease (CKD), a condition that affects 850 million people globally.
In an intricate experiment, Peti-Peterdi and his team observed that a loss of salt and body fluid can trigger the innate regenerative capabilities of kidneys in mice. This remarkable discovery hinges on macula densa (MD) cells, a specialized group of kidney cells that monitor salt levels and govern vital kidney functions.
“Our personal and professional mission is to find a cure for kidney disease, a growing global epidemic affecting one out of seven adults, which translates to 850 million people worldwide or about 2 million in the Los Angeles area,” Peti-Peterdi, a professor of physiology, neuroscience and medicine at USC’s Keck School of Medicine, said in a news release. “Currently, there is no cure for this silent disease. By the time kidney disease is diagnosed, the kidneys are irreversibly damaged and ultimately need replacement therapies, such as dialysis or transplantation.”
An Evolutionary Perspective
The researchers took an unconventional approach by studying the evolutionary biology of healthy kidneys rather than focusing solely on diseased organs.
“From an evolutionary biology perspective, the primitive kidney structure of the fish turned into more complicated and more efficiently working kidneys to absorb more salt and water,” added Peti-Peterdi.
By emulating the conditions faced by species transitioning from sea to land, the team aimed to recreate the evolutionary changes that made kidneys more efficient. They subjected lab mice to a highly restricted salt diet, further enhancing the effects with an ACE inhibitor, a common drug that lowers salt and fluid levels.
Groundbreaking Results
The results were promising. The team noted significant regenerative activity in the MD cells. When they blocked the signaling pathways of these cells with specific drugs, the regeneration halted, underscoring the pivotal role of MD cells in kidney repair.
Further analyses revealed that MD cells share genetic and structural features with nerve cells, which are known to be crucial for the regeneration of other organs like the skin. Key genes, such as Wnt, NGFR and CCN1, showed positive responses to the low-salt diet, promoting kidney regeneration. Notably, patients with CKD had significantly reduced activity of CCN1.
Potential Therapeutic Impact
To explore potential therapeutic applications, the team treated mice with a specific type of CKD, called focal segmental glomerulosclerosis, using the identified proliferative genes and MD cells cultured in low-salt conditions. The treatments fostered notable improvements, with MD cell therapy showing the most promising results.
“We feel very strongly about the importance of this new way of thinking about kidney repair and regeneration,” Peti-Peterdi added. “And we are fully convinced that this will hopefully end up soon in a very powerful and new therapeutic approach.”
Moving Forward
The study included collaboration from multiple institutions, with co-authors from USC, the University of Michigan, the University of Pittsburgh School of Medicine, the University of Cologne, the University of Illinois at Chicago, Yale University School of Medicine, Johns Hopkins University and the University of Oxford.
The team is optimistic about translating these findings into human therapies. With chronic kidney disease lacking a cure, this research offers a novel and promising avenue for future treatments.