Study Demonstrates Detection of Acute Kidney Injury Possible Within Hours of Cardiopulmonary Bypass

Up to 40 percent of adults and children who have cardiac surgery develop acute kidney injury (AKI), often with deadly consequences. That’s partially because it takes several days to determine if the test used to diagnose AKI for 50 years is abnormal – too late to prevent kidney failure.

A new study, however, shows that a panel of biomarkers can be used to detect AKI just hours after initiation of cardiopulmonary bypass – allowing physicians to pinpoint timing of kidney injury and potentially initiate therapy earlier than ever before. The study, conducted by Catherine Krawczeski, MD, a pediatric cardiologist at Cincinnati Children’s Hospital Medical Center, will be published online Nov. 15 in the Journal of the American College of Cardiology.

Publication of the study coincides with her presentation of the data at 4:15 ET, Nov. 15, at the annual meeting of the American Heart Association in Orlando. "These biomarkers not only enhance the potential for appropriately timed therapy but also offer severity and prognostic information at early time points,” says Krawczeski who is also Associate Professor of Pediatrics at the University of Cincinnati College of Medicine.

"Concentrations of one biomarker in urine, NGAL, increased earliest – as little as two hours after bypass – and were most predictive of AKI.”

The Cincinnati Children’s researchers studied 220 children and adolescents who went on cardiopulmonary bypass. Urine samples were obtained before bypass and at regular intervals afterward. AKI, an acute loss of kidney function, occurred in 27 percent of patients. Urine NGAL increased significantly at two hours post-bypass.

Three other biomarkers (IL-18, L-FABP and KIM-1) rose significantly at later points. The study marks the first time researchers have studied all four of these biomarkers together in one group of patients and described "their exact temporal evolution,” says Dr. Krawczeski.

"Biomarkers, especially when used in combination, like a panel, give us the strongest predictive ability – better than using just clinical data and better than just NGAL alone. NGAL provides the earliest information, but the others add predictive ability.”

The best test for kidney injury currently available measures creatinine, a waste product. A high level of creatinine in the blood means the kidney is unable to filter out the chemical. The standard of care is to wait until creatinine rises before diagnosing and treating AKI. Unfortunately, it may take days for the creatinine level to rise after the kidney is injured.

By the time the creatinine test shows kidney injury, the child or adult may already have lost up to 50 percent of kidney function. It isn’t only cardiopulmonary bypass that raises the risk of AKI. As many as one of three critically ill patients develop AKI as a consequence of shock, infection, trauma, surgery, medications or procedures that are toxic to the kidney. Patients may need to spend extra days in the ICU on a ventilator, need dialysis or even need a kidney transplant.

AKI is the number one predictor of death in critically ill patients. Because of the urgent need for a better diagnostic tool, Prasad Devarajan, MD, director of Nephrology and Hypertension at Cincinnati Children’s and a co-author of Dr. Krawczeski’s study, went to the laboratory and discovered that NGAL was a useful biomarker, secreted into the blood and urine and thus allowing for it to be measured non-invasively.

To build on this research, Cincinnati Children’s established the Center for Acute Care Nephrology in 2010. This center brings together a unique team: nephrologists who are pioneering leaders in laboratory and clinical research, working in an unusually collaborative relationship with experts in cardiac and pediatric intensive care.

The center is directed by Stuart Goldstein, MD, who collaborated with Dr. Devarajan in 2007 on an earlier NGAL study and is also a co-author of Dr. Krawczeski’s study.

 Dr. Krawczeski co-directs the center with Dr. Goldstein. Cincinnati Children’s is now launching "proof of concept” studies in the Pediatric Intensive Care Unit to determine whether physicians can make more timely care decisions by relying on the NGAL test. Cincinnati Children’s has also been funded by the National Institutes of Health as one of only nine Pediatric Heart Network core sites in the United States and Canada.

As a member of the consortium, Cincinnati Children’s has proposed studying whether early treatment of AKI with sodium bicarbonate and N-acetylcysteine, an antioxidant, will improve outcomes following cardiopulmonary bypass.