New research from the School of Medicine suggests that long-term use of certain blood pressure medications can cause kidney damage. Research suggests that high blood pressure drugs – known as angiotensin-converting enzyme inhibitors designed to lower blood pressure by relaxing veins and arteries – are associated with hardening renal vessels. Blood vessels supply oxygen to the kidney, so the hardening of the vessels limits full kidney function.
Two researchers from the University’s Department of Pediatrics and Child Health – Ariel Gomez MD and Maria Luisa Sequeira-Lopez – have been working on this research since the 1990s at the Pediatric Center of Excellence in Nephrology. Both researchers went to medical school at the University of Buenos Aires Medical School in Argentina before completing their residency in pediatrics.
Their latest research focuses on renin cells, specialized kidney cells that are essential for the development of blood vessels and structures that supply the kidney. Long-term antihypertensive drugs block the hormonal system that regulates blood pressure, which their research suggests can cause malformations in the kidney vessels. For this reason, blood pressure medications are known to be dangerous during pregnancy.
Research by Gomez and Sequeira-Lopez suggests that long-term use of certain blood pressure medications could have potentially dangerous side consequences for more than just pregnancies. As their name suggests, these drugs work to lower blood pressure by preventing the ACE from producing angiotensin II, a protein that raises blood pressure by narrowing blood vessels. Inhibiting this feedback loop causes the kidneys to produce more renin in response.
“[The kidneys] will continue to produce renin, increasing the number [of renin cells], and they will also make matrix proteins,” Sequeira-Lopez said. “It ends up making the kidney vessels sick. So it’s something that can happen, [it] occurs in mice and could occur in humans.
The long-term increase in renin production generates an increase in Smooth muscle cells, which causes the blood vessels in the kidney to thicken and stiffen, preventing normal blood flow. This is called renal stenosis.
Sequeira-Lopez said the next steps in their research will be to find a way to prevent stenosis from occurring by continuing to study renin cells and finding factors or proteins that cause these potential side consequences.
Gomez and Sequira-Lopez’s research uses mice, renin in culture and biopsy cells, but the pair noted the need for clinical studies of effects in humans.
“There should be clinical studies that better study kidney function,” Sequeira-Lopez said. “There is evidence that [kidney damage] could also occur in humans from studies of biopsies in the past. But, we need to move on and do better studies and make sure that the kidneys are protected as well as your life.
Sequeira-Lopez stressed that people shouldn’t stop taking their blood pressure medications long-term because they’re essential for preventing high blood pressure and heart disease. Right now, protecting against these medical issues is a top priority. Research in this lab aims to find better drugs for the future that can reverse fibrosis – the thickening and scarring of kidney tissue – helping to heal blood vessels.
Research physician Dr. Alexandre Martini said he joined Gomez’s lab four years ago because Gomez is one of the world leaders in the study of renin-producing cells and the University provides the resources it needs.
“At U.Va., I have the environment to do this kind of research.” said Martin. “With techniques that are very new, it would be very difficult to have access to the outside. But here at U.Va., we have a lot of good people who work with the techniques.
The success of this work is an inspiration to pre-med students interested in neprology, said college freshman Will Gansereit.
“I am interested in nephrology and therefore to be able to have these resources here at U.Va. is really cool. said Ganserit. “It’s a revolutionary research community.”
“Today it is impossible to do science alone,” Martini said. “We are still getting contributions from other groups and other techniques, especially sequencing analysis that bioinformaticians are contributing to. So it’s not just a team, it’s a network to improve science.