Protein testing can predict the risk of postoperative acute kidney injury


(Reuters Health) – Tests to detect a protein seen in people with chronic kidney problems can predict whether a patient is likely to develop acute renal failure after cardiac surgery, angiography or admission to the intensive care unit, researchers report in The New England Journal of Medicine.
Finding a way to neutralize the effects of that protein, known as suPAR (soluble urokinase-like plasminogen activator receptor), can help doctors protect patients against kidney injury, a strategy that is already promising in tests in mice, Dr. Salim, lead author. 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, co-author Dr. David Leaf of Brigham and Women's Hospital in Boston told Reuters Health by phone. "High levels alone cannot cause harm, but if you have an injury in addition to that (such as stress caused by surgery) you may be at greater risk."
"We still need to develop a medication or device to remove the protein from the blood," he said. "We are actively conducting research using devices to reduce those levels. But we still have a few years left to do so."

"This is a field that has not made any progress in decades," said Dr. Hayek. "We hope this is very impressive for millions of patients who undergo these high-risk surgeries."

Acute kidney injury appears rapidly in about 10% to 15% of all hospitalized patients. This rate can reach 40% with cardiac surgery and 50% when patients enter the ICU.
"It is a very common and often devastating condition among hospitalized patients," said Dr. Leaf, director of clinical and translational research in acute kidney injury in Brigham.
"This is what we fear as doctors because there isn't much we can do about it," said Dr. Hayek, a cardiologist at the Frankel Cardiovascular Center in Michigan. "Knowing that we could potentially do something about it is a big problem."

SuPAR seems to be the first marker that predicts acute kidney injury beforehand.
The connection between suPAR and acute kidney injury was observed regardless of age, race, sex, how sick the patients were or how healthy their kidneys were in the first place. The degree of injury varied according to the type of stress the patient was subjected to.
Among 3,827 patients undergoing coronary angiography, the rate of acute renal injury was 14% for those with the highest levels of suPAR 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 levels of suPAR versus 16% for those with the lowest.

And among 692 patients in the intensive care unit, 53% with the highest levels of suPAR developed acute kidney damage compared to 15% of patients with the lowest levels.

"The effects were more variable among the patients admitted to the ICU who may have had a less discreet disease and with more variability," said Dr. Titte Srinivas of the University Hospital Medical Center of Cleveland, who was not involved in the investigation.

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

That suggests that reducing suPAR levels before surgery could reduce the chances 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.


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