Researchers at the Yale School of Medicine recently received a five-year, $4 million grant from the National Institutes of Health to study new methods of diagnosis for acute kidney injury, AKI.
Led by Chirag Parikh, associate professor of medicine, the Yale team — working with researchers at four other centers around the nation — is investigating three new biomarkers for AKI. The current method of diagnosis uses serum creatinine, a biomarker that does not show up in tests until two or three days after kidney injury, as it is an indicator of a functional problem with filtration rather than cellular injury, Parikh said.
“This is a key disconnect in the field,” he said. “When trying to identify patients who have acute kidney injuries, we have to wait until filtration is affected before we can pick it up.”
Peter Aronson, professor of medicine and director of nephrology training and faculty development, contrasted the lengthy process of AKI diagnosis with the simpler diagnosis of a heart attack. He said that if cardiologists had to wait for weeks to detect an attack, it would be too late to operate on it. But during a heart attack the damaged cells release particular enzymes that can be detected very quickly by doctors, allowing for immediate treatment, he said.
The aim of Parikh’s project was to develop a similar test that would enable more rapid diagnosis, Aronson said.
“If you could detect when the injury has happened at a much earlier stage, maybe then it would be possible to do intervention studies to hasten the recovery of patients,” Aronson said.
Parikh said the project is called TRIBE, or Translational Research Investigating Biomarker Endpoints, and will enroll a total of 1,800 subjects undergoing cardiac surgery.
During bypass surgery, Parikh said, surgeons redirect the blood outside the body, reducing blood flow to organs such as the kidneys and causing injury. At the point of AKI, the biomarkers under investigation will begin to be released by the body. The researchers will then collect blood and urine samples from patients immediately after surgery and compare the levels of biomarkers with changes in serum creatinine.
Parikh said he has been researching biomarkers for the past several years, having begun working with them while doing his Ph.D. in clinical investigation. He said his work is the type sought after as translational research by NIH, whose laboratory findings can be directly applied to clinical care, he said.
The long-term goal of the research is to make the new biomarker tests clinically available, said Parikh. If the results are positive, the next step is obtaining FDA approval, then developing new therapies around the biomarkers.
“Hopefully, the primary data will indicate that these markers are quite sensitive and specific and that they go up rapidly after the injury,” said Steven Coca, a medical school research fellow and co-investigator in the study. “We’re hoping if these markers can be validated, it will pave the way for interventions that have a theoretical basis and proven efficacy.”
But Parikh said there might be unintentional consequences of his research as well. The biomarkers could conceivably help doctors predict death, the duration of a patient’s hospital stay or the likelihood of infection by a different disease.
The other centers simultaneously conducting the tests are the London Health Sciences Center in Ontario, Canada, the University of Colorado, the University of Cincinnati and Duke University.