High blood pressure changes how the kidneys metabolise lysine

Tech Science 1. nov 2022 2 min MD, Associate Professor, Associate professor, AIAS-COFUND Fellow Markus Rinschen Written by Kristian Sjøgren

Researchers investigated the metabolism of the kidneys of people with high blood pressure and kidney disease. The results show that high blood pressure and kidney disease are especially associated with changes in how the kidneys metabolise lysine, an amino acid. Giving lysine to people with high blood pressure may be a way to protect the kidneys.

The kidneys are a very important organ and have an essential role in filtering fluid and monitoring all the nutrients in the body.

However, the kidneys are vulnerable, and high blood pressure can lead to kidney disease, with the kidneys no longer functioning optimally.

Researchers have now investigated what high blood pressure actually does to the kidneys and how it leads to changes in the way the kidneys metabolise various amino acids, including the essential amino acid lysine.

This discovery provides new insight into how to treat people with high blood pressure to prevent kidney damage.

“The kidneys used to be considered boring organs, but today we understand much better how important they are. Diseases such as obesity, type 2 diabetes and even muscle diseases adversely affect the kidneys. Conversely, many drugs used to treat people with type 2 diabetes, including SGLT2 inhibitors, benefit the kidneys and the risk of developing kidney disease,” explains a researcher behind the study, Markus Rinschen, Aarhus Institute of Advanced Studies, Aarhus University.

The research has been published in Nature Communications.

High blood pressure affects metabolism in the kidneys

The researchers had previously investigated all the metabolites in the kidneys and determined how they are affected by high blood pressure and kidney disease.

In the previous study, the researchers found that the metabolism of lysine appeared to be altered in animal models of high blood pressure and kidney disease.

In the new study, the researchers wanted to take a step further and determine exactly what happens to how the kidneys metabolise lysine when people have high blood pressure by examining this in both animal models and humans.

“Metabolites are metabolised in a very complex process because this happens so quickly. The metabolites are constantly converted into new products, which are recycled or excreted, and determining what happens can be difficult. No one had previously carried out a complete study of how healthy people and people with high blood pressure metabolise lysine,” says Markus Rinschen.

Lysine helps the body to remove harmful substances

The researchers gave rats with or without high blood pressure isotope-labelled lysine so that they could monitor the metabolism of lysine and compare this between healthy and diseased animals.

The results showed that high blood pressure accelerates lysine metabolism and that the kidneys combine lysine with various molecules from the metabolism of glucose and fatty acids.

This means that through lysine metabolism, the kidneys remove sugar metabolites and fatty acid metabolites such as malonyl-CoA from the body and excrete them through the urine as lysine conjugates.

“This is good, because the sugar metabolites can otherwise react with proteins and thus damage them. Instead, the sugar metabolites bind to free lysine and are thus rendered harmless and excreted,” explains Markus Rinschen.

Lysine might protect the kidneys of people with high blood pressure

The researchers also administered large doses of lysine to rats with high blood pressure and kidney disease and found that more lysine created more lysine conjugates with sugar and fatty acid metabolites.

The effect was also greater than when healthy rats received the same amount of lysine.

The accelerated metabolism thus appears to be a defence mechanism to protect the kidneys against damage induced by sugar and fatty acid metabolites in connection with high blood pressure, but this requires that lysine is present in the kidneys in ample quantities.

The researchers also examined people with high blood pressure who had a high risk of developing kidney disease and found results similar to those of rats with high blood pressure leading to accelerated lysine metabolism.

“Overall, our results indicate that lysine metabolism is greatly increased among people with high blood pressure and that this influences the risk of kidney disease, but we also found that lysine supplementation can clean up harmful metabolites from the metabolism of sugar and fatty acids and can thereby protect the kidneys of vulnerable people,” says Markus Rinschen.

Nevertheless, Markus Rinschen says that people should not rush out and buy a lot of lysine, since more research is needed before making such recommendations.

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