Claudins and renal adaptation to salt deficiency
Kidneys constantly filter the blood to recapture useful substances, including sodium, an essential component of salt, before they are excreted in the urine. This recycling occurs via two pathways: through the cells themselves, or between them, via tiny spaces sealed by proteins called claudins. These proteins, long considered simple structural clips, have emerged in recent years as key players in sodium reabsorption.
Claudin-3, a key player in sodium reabsorption
Professor Eric Feraille’s research team focused on a specific region of the kidney, the collecting duct, which fine-tunes the amount of sodium retained. The scientists studied the role of one of the claudins, claudin-3. Their study, recently published in Acta Physiologica, reveals that claudin-3 is not a simple structural component but is regulated by a hormone, aldosterone. In the case of a low-salt diet, the increase in claudin-3 helps to strengthen the impermeability between cells and prevent any sodium backflow.
In a low-salt diet, the increase in claudin-3 (shown in yellow, right-hand image) helps to strengthen the impermeability between cells and prevent any sodium reabsorption. © piece of Figure 2, Sassi et al. 2026 Acta Physiologica.
A kidney capable of compensating
To confirm the role of this protein, the researchers studied genetically modified mice that do not produce claudin-3. Surprisingly, even without it, these animals maintain a normal sodium balance on a low-salt diet. The kidney compensates by strengthening other mechanisms, notably other claudins (claudin-4, 8 and 10) and sodium channels present on the cell surface.
This reveals a coordinated adaptive network, where claudins do not function in isolation and are capable of stepping in to maintain sodium balance.
What are the implications?
These results illustrate the kidney’s remarkable ability to adapt to variations in salt intake. They also suggest that abnormalities in claudin regulation could contribute to conditions such as high blood pressure or certain kidney diseases. Understanding these mechanisms paves the way for future therapeutic strategies.