Protein Test May Predict Risk of Postop Acute Kidney Injury

By Gene Emery

January 30, 2020

(Reuters Health) - Testing for a protein seen in people with chronic kidney problems can predict whether a patient is likely to develop acute renal failure after heart surgery, angiography or intensive care unit admission, researchers report in The New England Journal of Medicine.

Finding a way to neutralize the effects of that protein, known as suPAR (soluble urokinase-type plasminogen activator receptor), may help doctors protect patients against kidney injury, a strategy that is already showing promise in tests on mice, chief author Dr. Salim Hayek of the University of Michigan in Ann Arbor told Reuters Health in a telephone interview.

"There seems to be a synergistic effect" of suPAR, coauthor Dr. David Leaf of The Brigham and Women's Hospital in Boston told Reuters Health by phone. "High levels alone may not cause damage, but if you have an injury on top of that (such as the stress caused by surgery) you may be at increased risk."

"We still need to develop a drug or device to remove the protein from the blood," he said. "We are actively pursuing investigations using devices to lower those levels. But we're still a few years from doing that."

"This is a field that hasn't had any progress in decades," Dr. Hayek said. "We're hoping this will be very impactful for millions of patients who undergo these high-risk surgeries."

Acute kidney injury appears quickly in about 10% to 15% of all hospitalized patients. That rate can go as high as 40% with heart surgery and 50% when patients are admitted to the ICU.

"It's a very common and often-devastating condition among hospitalized patients," said Dr. Leaf, director of clinical and translational research in acute kidney injury at Brigham.

"This is what we dread as physicians because there's not a lot we can do about it," said Dr. Hayek, a cardiologist at Michigan's Frankel Cardiovascular Center. "Knowing we could potentially do something about it is a big deal."

suPAR seems to be the first marker to predict acute renal injury beforehand.

The connection between suPAR and acute kidney injury was seen regardless of age, race, gender, how sick patients were or how healthy their kidneys were in the first place. The degree of injury varied by the type of stress the patient was subjected to.

Among 3,827 patients undergoing coronary angiography, the rate of acute kidney injury was 14% for those with the highest suPAR levels and 4% for patients in the lowest quartile.

For 250 patients who underwent cardiac surgery, the risk of acute kidney injury was 40% among those with the highest suPAR levels versus 16% for those with the lowest.

And among 692 intensive care unit patients, 53% with the highest suPAR levels developed acute kidney injury versus 15% of patients with the lowest levels.

"Effects were more variable among patients admitted to the ICU that may have had illness that was less discrete and with more variability," said Dr. Titte Srinivas of University Hospitals Cleveland Medical Center, who was not involved in the research.

In the mouse tests, treatment with a monoclonal antibody designed to neutralize suPAR seemed to protect the mice from kidney injury.

That suggests that bringing suPAR levels down before surgery might lower the odds of kidney damage, said Dr. Frank Tacke of Charite University Medicine Berlin in a Journal editorial.

SOURCE: The New England Journal of Medicine, online January 29, 2020.