UVA researchers discover how blood pressure medications affect the kidneys

Researchers at the University of Virginia School of Medicine have discovered how long-term treatment of high blood pressure with commonly prescribed drugs can damage the kidneys’ ability to filter and clean the blood. The findings could open the door to better ways to manage high blood pressure and other blood vessel diseases.

A group of drugs, known as renin-angiotensin system (RAS) inhibitors, block the effects of the renin enzyme, relaxing blood vessels and allowing blood to flow more easily. They are widely used as first-line antihypertensive (high blood pressure) medications. But long-term use can cause terrible damage to the kidneys, causing scarring and other dramatic changes in the body that change the organ’s focus from filtering blood to producing renin.

No longer able to filter waste blood, the Frankensteined kidney becomes a “pathological neuro-immune endocrine organ,” as UVA researchers describe it in a new scientific paper, which can cause serious health problems. But they say their discovery lays the groundwork for ways to protect the kidneys and better treat high blood pressure.

Commonly used and believed to be safe blood pressure medications may damage the kidneys. We need to properly understand the effects of long-term use of RAS inhibitors on the kidneys. “

R. Ariel Gomez, MD, researcher at the UVA Child Health Research Center

Controlling high blood pressure

High blood pressure affects more than 1.3 billion people worldwide. This condition forces the heart to work harder and can cause many other serious problems, such as stroke, myocardial infarction, kidney damage and vision loss.

The renin-angiotensin system (RAS) plays an important role in controlling blood pressure. Renin is a hormone enzyme produced by kidney cells that is stimulated when blood pressure drops.

RAS inhibitors are widely and effectively used to control high blood pressure. They are very safe when their use is controlled by a doctor, but patients are always advised to contact their doctor if they notice signs of kidney damage such as decreased urination, swelling in the legs or feet or confused.

The possible effects of chronic inhibition of the RAS in the kidney are known, but experts are not sure what causes these harmful changes. The new discovery of UVA provides answers: Overstimulation of renin-producing cells in the kidney causes the cells to revert to an invasive, embryonic state. In this situation, these cells that line the small arteries of the kidney begin to grow significantly. They begin to release renin and substances that cause other changes: New blood vessels grow like weeds; immature smooth muscle cells build up; scarring occurs around small blood vessels, called arterioles; and inflammatory cells are involved. The result is “quiet but serious” vascular disease, the researchers note in their new paper.

“Our 3D imaging clearly revealed that chronic RAS inhibition leads to hyperinnervation of the renal arteries, as well as arteriolar hypertrophy and infiltration of immune cells,” said researcher Manako Yamaguchi, PhD. “This neuro-immune-endocrine interaction synergistically promotes the increased production of renin to maintain blood pressure homeostasis, but, on the other hand, severe arteriolar hypertrophy reduces the kidney’s blood purification function.”

By understanding what causes harmful changes in the kidneys, scientists are now in a position to find ways to prevent them. That could lead to better ways to treat high blood pressure without unwanted side effects, the researchers hope.

“Our next goal is to clarify the whole picture of interactions between renin cells, smooth muscle cells, nerves and inflammatory cells under RAS inhibition,” said researcher Maria Luisa S. Sequeira- Lopez, MD. “These findings may open up new ways to prevent adverse outcomes in the treatment of hypertension.”

Published kidney damage studies

An article describing the discovery is featured as an outside story in the scientific journal Circulation Research. The UVA research team was composed of Yamaguchi, Lucas Ferreira de Almeida, Hiroki Yamaguchi, Xiuyin Liang, Jason P. Smith, Silvia Medrano, Sequeira Lopezand Gomez.

Research was supported by the National Institutes of Health, grants R01HL148044, R01DK116718, P50DK 096373 and P50DK096373. Scientists have no financial interest in the work.