Low-salt diet and kidney regeneration in mice
What it found
In mice, a low-salt diet activated a program in macula densa cells that led to kidney tissue regeneration.
The authors suggest this might help protect the kidney.
What they found
Studies in people
Human kidney CCN1
In human kidneys, CCN1 was found in macula densa cells, but levels were lower in people with chronic kidney disease. Low CCN1 in urine was linked to worse kidney function.
Low-salt diet in people
Clinical studies have shown that a low-salt diet reduces protein in urine in people with chronic kidney disease, and combining it with ACE inhibitors worked better than either alone.
Animal and lab studies
Regeneration triggered
Feeding mice a low-salt diet activated regeneration pathways in macula densa cells, recruiting progenitor cells that became blood vessel, interstitial, and epithelial cells.
Neuron-like properties
Macula densa cells showed neuron-like features, including calcium signals and gene activity related to nerve function. These signals were linked to changes in the diameter of nearby kidney arterioles.
Kidney protection factors
Factors released by macula densa cells, such as CCN1, reduced protein in urine and lessened kidney damage in a mouse model of kidney disease.
What the authors conclude
“These findings suggest that dietary sodium restriction and/or targeting MD signaling might attenuate glomerular injury.”
Also in their conclusions
- They suggest that dietary sodium restriction and/or targeting macula densa signaling might attenuate glomerular injury.
- They note that a simple intervention, such as dietary sodium restriction, perhaps in combination with renin-angiotensin system blockade, might promote a favorable profile of macula densa signaling that would enhance glomerular health.
- They advise that potential adverse effects from chronic activation of these regenerative and angiogenic signaling pathways must also be considered.
How it was done
The authors wanted to understand how macula densa cells, which sense salt in the kidney, might coordinate tissue regeneration and repair.
They used mice, imaging techniques, and genetic tracing to see how low-salt feeding affected macula densa cells and kidney tissue. They also tested factors released by these cells in a mouse model of kidney disease.
What it can’t tell you
- Most of the experiments were in mice, so the results may not be the same in people.
- The human data are from observations, so they cannot prove that low CCN1 causes kidney disease or that raising it would help.
- It is not yet known whether these effects in people are due to macula densa factors or if giving such factors would be an effective treatment.
Who paid
- Conflicts
- Conflict of interest: The authors have declared that no conflict of interest exists.
- Authors work at
- Nanyang Technological University, Singapore; Duke-NUS Medical School, Singapore
The paper
- Title
- Hold the salt for kidney regeneration
- Type
- Study
- Evidence
- Studies in people · animals · lab
- Summarised from
- Full text
- Cite
- Xia Y, Coffman TM (2024). Hold the salt for kidney regeneration. The Journal of clinical investigation. doi:10.1172/JCI181397Free full textPubMed 38828728DOI
Summary written 26 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error