Experimental Drug Could Be Big Advance Against Kidney Disease

Posted December 19, 2023

Experimental Drug Could Be Big Advance Against Kidney Disease

Early results from a trial of a new kidney disease medication show it significantly reduces levels of a urine marker of kidney damage.

The experimental drug -- called BI 690517 for now -- cut levels of the liver protein albumin in the urine in half for patients with chronic kidney disease.

Albumin levels in urine have long been used to gauge kidney disease progression.

"We think these are high-impact findings" that could change practice, said study lead author Dr. Katherine Tuttle, a clinical professor of nephrology at the University of Washington School of Medicine in Seattle.

The study was funded by the drug's developer, Boehringer Ingelheim, and published Dec. 15 in The Lancet journal.

According to the National Kidney Foundation, chronic kidney disease occurs when the paired organs lose their ability to perform crucial functions, such as clearing the body of waste, maintaining mineral balance in the body and helping to maintain healthy blood pressure. The condition is often linked to other long-term issues, such as heart disease and diabetes.

Often, people with chronic kidney disease require dialysis to survive.

As Tuttle's team explained, the body uses a hormone called aldosterone to help regulate sodium and potassium levels and stabilize blood pressure. Too much aldosterone puts this process out of whack, however, and that can speed the progression of kidney disease.

The trouble is, two standard medications for kidney disease, ACE inhibitors and angiotensin receptor blockers (ARBs), can also send aldosterone levels soaring.

"We've known for several decades that aldosterone is a major driver of inflammation and fibrosis in the kidney and also in the heart. It has just been very hard to target therapeutically,"Tuttle explained in a university news release.

BI 690517 works by lowering aldosterone production.

The new trial involved 586 patients with chronic kidney disease. All were already taking an ACE inhibitor or an ARB, and half also got one of a newer class of diabetes medications, in this case empagliflozin (Jardiance).

Drugs like BI 690517 can raise risks for a dangerous condition called hyperkalemia, the researchers explained, but empagliflozin can counter that effect.

"That gave us the opportunity to test BI 690517 for efficacy at increasing the protection of kidneys and also to reduce the major side effect that had limited the use" of this class of drugs, Tuttle noted.

In the trial, patients first got empagliflozin or a matched placebo for two months. They were then randomly assigned to get to either BI 690517 at a daily dose of either 3 milligrams (mg), 10 mg or 20 mg, or a matched placebo, for another three-and-a-half months.

Healthy reductions in levels of albumin in urine -- a decline of 30% or more -- suggested BI 690517 was helping the kidneys.

According to the study, half of people who got BI 690517 alone gained this level of benefit, and that number rose to 70% among folks who got BI 690517 plus empagliflozin.

And while rates of hyperkalemia were higher among people who received BI 690517 versus those on placebo, most of those cases turned out to be mild, the research team said.

Speaking in a university news release, Tuttle was cautiously optimistic that BI 690517 might someday free some patients from dialysis.

"Seventy-five percent of all people on dialysis have diabetes or hypertensive kidney disease, and these agents -- if we can get it right in terms of awareness and access and detection at a stage where it's treatable -- might make dialysis almost obsolete," she said. "This is in reach."

More information

Find out more about chronic kidney disease at the National Institute of Diabetes and Digestive and Kidney Diseases.

SOURCE: University of Washington School of Medicine and UW Medicine, news release, Dec. 15, 2023