How Kidneys Help Body Retain Water And Salt

In the present study, the researchers examined whether similar problems occur in people with LRBA deficiency. They also investigated in detail how LRBA helps the kidneys retain water and salt in the body, using patient data, genetically modified mice, and cultured cells.

The researchers first examined data from people with LRBA deficiency and found that some produced unusually large amounts of urine. Among patients whose urine concentration had been measured, their kidneys were unable to concentrate urine sufficiently despite ongoing water loss from chronic diarrhea.

This showed that the kidney abnormality previously observed in mice also occurs in humans. In other words, these patients may not only lose water through diarrhea, but may also have difficulty returning enough water from the kidneys to the body.

So what is happening inside the kidneys?

As urine is formed, the kidneys return water to the body, thereby concentrating the urine and preventing excessive water loss. One of the proteins involved in this process is AQP4. In this study, the research team demonstrated for the first time that LRBA regulates AQP4 and supports water reabsorption in the kidneys.

The researchers also found that LRBA is involved in the reabsorption of both water and salt. When salt levels in the body are low, a protein called SPAK helps the kidneys reabsorb sodium. LRBA prevents SPAK from being broken down and helps it move to the part of the cell where it needs to work.

This means that when LRBA does not function properly, the kidneys have difficulty returning enough water and salt to the body. LRBA therefore acts as a regulator, supporting different mechanisms that help the body retain water and salt in different ways.

The findings suggest that dehydration in people with LRBA deficiency may result not only from water loss caused by chronic diarrhea and other symptoms, but also from the kidneys’ reduced ability to retain water and salt. Careful management of water and salt balance may be especially important when patients become unwell.

The researchers also found that, in mice carrying a specific genetic mutation, treatment with a drug that encourages the kidneys to return water to the body improved their ability to concentrate urine. If future studies can identify which patients are likely to benefit from this approach, the findings could eventually lead to treatments tailored to a person’s genetic mutation and kidney condition.

LRBA has mainly been known as a molecule involved in immune function. However, LRBA is a very large molecule that can interact with many different proteins, suggesting that it may have a wide range of functions throughout the body beyond the immune system.

Until now, we have not fully understood why such a wide variety of symptoms occur in LRBA deficiency, in which LRBA function is impaired. I believe that uncovering the many roles of LRBA one by one will provide important clues to understanding the mechanisms underlying the disease.

We will continue working to reveal the full range of LRBA’s functions, with the goal of gaining a deeper understanding of LRBA deficiency and ultimately contributing to better clinical care and treatment for patients.

(Fumiaki Ando, Assistant Professor, Department of Nephrology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo)

Science for All showcases cutting-edge research at Science Tokyo and highlights the ideas, people, and possibilities shaping the future.

Science for All showcases cutting-edge research at Science Tokyo and highlights the ideas, people, and possibilities shaping the future.