New kidney research from the University of Virginia School of Medicine raises concerns that long-term use of drugs, often prescribed to treat high blood pressure and heart failure, could contribute to kidney damage.

Patients should continue to take the drugs, which include the well-known and widely used ACE inhibitors, the researchers say. But scientists are pushing for studies to better understand the drugs’ long-term effects.

Our studies show that renin-producing cells are responsible for the damage. We are now focused on understanding how these cells, so important to protecting us from drops in blood pressure and maintaining our well-being, undergo such transformation and cause kidney damage. It is important to find out which substances these cells produce that lead to uncontrolled vascular growth. “

Maria Luisa Sequeira Lopez MD, Department of Pediatrics and Child Health Research Center, UVA

The causes of kidney damage

Chronic high blood pressure affects one billion people worldwide. The UVA researchers wanted to better understand why severe forms of the disease are often associated with thickening of the arteries and small blood vessels in the kidney and leading to organ damage.

They found that specialized kidney cells called renin cells play an important role. These cells usually produce renin, a vital hormone that helps the body regulate blood pressure. But harmful changes in the renin cells can cause the cells to invade the walls of the kidney’s blood vessels. The renin cells then trigger the formation of another cell type, smooth muscle cells, which cause the vessels to thicken and stiffen. The result: the blood cannot flow through the kidney as it should.

The researchers also found that long-term use of drugs that inhibit the renin-angiotensin system, such as ACE inhibitors or angiotensin receptor blockers, have a similar effect. These drugs are used extensively for many purposes, including treating high blood pressure, congestive heart failure, and heart attacks, and preventing serious heart problems. However, long-term use of the drugs was associated with hardened kidney vessels in both laboratory mice and humans, the scientists found.

The researchers point out that the drugs can be life-saving for patients, so they emphasize the importance of continuing to take them. However, they say additional studies are needed to better understand the long-term effects of the drugs on the kidneys.

“It would be important to conduct prospective, randomized controlled trials to determine the extent of functional and tissue damage in patients taking blood pressure control drugs,” said Ariel Gomez, MD, of the Department of Pediatrics and Child Health Research Center at UVA. “It is imperative to find out what molecules these cells make so we can counteract them to prevent the damage while treating high blood pressure with the drugs available today.”

Results published

The researchers have published their results in the journal JCI Insight. The article was selected as the cover story. The research team consisted of Hirofumi Watanabe, Alexandre G. Martini, Evan A. Brown, Xiuyin Liang, Silvia Medrano, Shin Goto, Ichiei Narita, Lois J. Arend, Sequeira-Lopez, and Gomez.

The research was supported by the National Institutes of Health, Grants P50 DK 096373, R01 DK 116718, R01 DK 116196, R01 DK 096373, and R01 HL 148044; and the Japan Society for the Promotion of Science Overseas Research Fellowships.


University of Virginia Health System

Journal reference:

Watanabe, H., et al. (2021) The inhibition of the renin-angiotensin system causes concentric hypertrophy of the renal arterioles in mice and humans. JCI insight.


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