Researchers find out how high blood pressure medication harms kidneys

Commonly prescribed drugs to treat high blood pressure have been shown to damage the kidneys' ability to filter and cleanse blood over time, but the exact mechanism behind this dangerous side effect has remained a mystery. Researchers at the University of Virginia School of Medicine say they have solved the mystery.

The UVA researchers found that these drugs actually rewire the kidneys, preventing them from doing their important job of filtering blood. The kidneys produce more of a hormone called renin; nerve endings overgrow; the cells lining the kidneys' tiny blood vessels become too large; scarring forms and spreads; and inflammation sets in, which the scientists say "can cause enormous damage to the kidneys."

The result, described in a paper by the researchers in the journal Circulation Research, is a “silent but serious” vascular disease in which the kidneys become like zombies, transforming into something unwanted and harmful while failing to perform their critical functions.

Now that the cause is known, researchers say the next step is to find a way to use effective blood pressure-lowering drugs known as renin-angiotensin system inhibitors (RAS inhibitors) while preventing kidney damage.

"The most commonly used and considered safe high blood pressure drugs can damage the kidneys," said Dr. R. Ariel Gomez of the UVA Children's Health Research Center. "We need to understand exactly how long-term use of RAS inhibitors affects the kidneys."

RAS inhibitors, which include drugs like enalapril, lisinopril, ramipril and others, are often prescribed to patients when they are first diagnosed with high blood pressure, a condition that affects 120 million people in the United States, or nearly half the adult population, according to the Centers for Disease Control and Prevention. High blood pressure can lead to heart attacks, strokes and other vascular diseases.

These drugs work by relaxing blood vessels and allowing blood to circulate freely. Researchers say they are widely used and generally considered safe, but not without risks. Doctors have long warned patients that some high-pressure drugs can cause kidney damage, which often manifests as decreased urination, swelling of the legs or feet, or cramps.

Now that scientists understand what causes changes in the kidneys, they can look for ways to prevent them.

"These findings may open new avenues to prevent side effects in hypertension treatment," said one of the researchers, Dr. Maria Luisa S. Sequeira-Lopez.