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Cardiovascular Research Initiative Launched
TRANSLATIONAL RESEARCH
| Test Enables Rapid Diagnosis
Of Acute Kidney Failure Urine protein discovered by Columbia-led team will allow physicians to make rapid diagnoses to save kidneys, lives |
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“When someone comes in with chest pain, we know within hours, and usually minutes, if that person is having a heart attack,” Dr. Canetta says. “But if the patient is having the equivalent of a heart attack in the kidney, we often can’t make that diagnosis until days later.” Now, a new test developed by a multidisciplinary team will allow physicians to quickly differentiate between sudden kidney failure and less threatening conditions. The test measures a small protein in urine called NGAL. The test was developed by a team led by Jonathan Barasch, MD, PhD, associate professor of medicine, Thomas Nickolas, MD, assistant professor of clinical medicine, and Prasad Devarajan, MD, director of nephrology and hypertension at Cincinnati Children’s Hospital. In a trial of more than 650 emergency patients, NGAL singled out those with acute kidney failure from all other patients in a matter of hours. The findings were published in the June Annals of Internal Medicine. Other members of the team include Dr. Canetta, Jun Yang, MD, PhD, a third-year resident at St. Luke’s-Roosevelt; P&S students Matthew O’Rourke P&S ’08 and Meghan Sise P&S ’09; and college students Nicholas Barasch and Charles Buchen. “We saw that a single measurement of NGAL was a better diagnostic test than a single measurement of serum creatinine, which can’t discriminate between a healthy kidney, chronically damaged kidney and one in acute failure,” says Dr. Barasch, who found a connection between NGAL and kidneys several years ago. “NGAL levels were 30 times higher in patients later diagnosed with acute kidney failure than in those without renal injury, chronic but quiescent injury or simple volume depletion.” Finding a faster indicator has been a high priority ever since nephrologists began using serum creatinine as an indicator of kidney failure in the 1930s. High serum creatinine may point to a poorly functioning kidney, but it is also influenced by other factors such as age, race, and some medications. A rapid increase in creatinine over time is indicative of failing kidneys, yet two to three days can pass before this is apparent clinically. For many patients, by the time the diagnosis is made, the damage to their kidneys has already been done. Twenty percent to 60 percent of patients with acute kidney injury require dialysis, and mortality rates range from 15 percent in the community setting, to between 50 percent and 80 percent where there is multi-organ failure, and more than 80 perent in the post-operative setting. In the current study, about 65 percent of patients with NGAL protein in the urine needed care from a nephrologist, another 32 percent needed dialysis, and 29 percent required care in the intensive care unit. “This is an area of true need,” Dr. Nickolas says, “About one-fifth of hospitalized patients have some degree of acute kidney injury, and the rate is increasing. We need to have a better test that points us in the right direction sooner so we have a chance to save some of these patients’ kidneys.” Better detection of acute kidney failure is not only needed to expedite treatment, but also to improve current treatments, just as the EKG and troponin tests have done with heart attack therapies. “Thanks to early diagnosis, treatments for heart attack patients have been developed and proven,” Dr. Canetta says. “If it took two to three days to detect a heart attack, cardiac catheterization – which doesn’t help much by then – never would have been proven effective.” Many new treatments for acute kidney failure have worked well in animal studies, but those results have not been replicated in people. “It’s been disappointing. We think those therapies may have worked better if they were introduced earlier,” Dr. Nickolas says. “But right now we can’t test new ideas in the early stages of the disease because we don’t even know who has the disease.” Before the NGAL test can be put into use, the results of the Columbia study must be confirmed by a multi-center trial, already in progress, and the NGAL assay must be transformed into a hospital-ready test and approved by the FDA. This work was funded by the NIH and the Emerald Foundation. —Susan Conova |
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| Student Papers on NGAL Test Win Prizes A paper on the NGAL test presented by Matthew O’Rourke, P&S’08, won 1st prize at the 2007 Dean’s Day for Medical Student Research meeting and the Louis Gibofsky Memorial Prize for research in Nephrology, Immunology or Transplant Immunobiology at 2008 P&S graduation. Meghan Sise, P&S’09, won “Outstanding Clinical Science Poster Presentation” at the 34th Annual Eastern-Atlantic Student Research Forum and the “American Medical Association Foundation Award for Overall Excellence in Clinical Research” and the “McLaughlin Award from the Institute for Human Infections and Immunity for Best Oral Presentation in Immunology or Infectious Diseases” at the 49th Annual National Student Research Forum. Both students were Fellows of the Doris Duke Clinical Research Program, directed by Donald Landry, MD, PhD, professor of medicine and interim chairman of the Department of Medicine. |
