Acute kidney injury (AKI) greatly increases patients’ risk for in-hospital death, and its incidence is increasing. However, emergency physicians face a challenge in quickly triaging patients because serum creatinine (sCr), the current standard for assessing kidney function, can take hours or days to respond to acute kidney damage. Discussed in this issue of Strategies, recent research supports the growing interest in urinary neutrophil gelatinase-associated lipocalin (uNGAL).
Caused by sepsis, surgery, cardiogenic shock, trauma, and drugs, onset of AKI can be swift and often deadly. For those that survive, AKI leads to an increased risk of chronic kidney disease, end-stage renal disease and mortality. Yet the very definition of AKI—changes in the levels of sCr and urine output—place emergency department (ED) patients at a disadvantage, since observing these changes takes hours. In addition, sCr values can be affected by muscle mass, nutritional status, medications, and other factors. As a result, researchers have focused their attention on several promising urinary biomarkers more directly related to kidney injury. A rising star among these markers, uNGAL was the top performer in recent research comparing five urinary biomarkers of nephron damage (J Am Coll Cardiol 2012;59:246–55).
The multicenter prospective study compared five urinary biomarkers for diagnosing AKI in the ED and found that all five were elevated, but uNGAL was the best predictor of the severity and duration of AKI, with a sensitivity of 68% and specificity of 81% at a 104 ng/mL cutoff. “Due to the limitations of serum creatinine, there is intense interest in identifying and developing novel biomarkers that more accurately and quickly detect acute kidney injury and kidney function in general,” said Thomas Nickolas, MD MS, lead author of the paper. “We chose the ED because we felt that a good biomarker should be able to detect acute kidney injury in a broad range of patients in a real world environment. Our findings demonstrate that urinary NGAL is an excellent predictor of acute kidney injury and predicts clinical outcomes.” Nickolas is an assistant professor of clinical medicine at Columbia University Medical Center at New York-Presbyterian Hospital.
Nickolas and his colleagues from the New York City-area collaborated with researchers at Charité-Universitätsmedizin, Max Delbruck Center for Molecular Medicine in Berlin, Germany. In a cohort of 1,635 emergency room patients from the U.S. and the Helios Clinics in Berlin, the researchers took a single measure of five urinary biomarkers: uNGAL, kidney injury molecule-1 (KIM-1), urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C. All of the biomarkers were elevated in cases of intrinsic AKI (iAKI), a term that indicates severe, cellular level kidney damage. uNGAL was most accurate in the diagnosis of iAKI and best predicted its duration and severity, and along with KIM-1, most accurately predicted death or the need to start dialysis during hospitalization. The researchers measured uNGAL using the Abbott ARCHITECT-NGAL assay, which is currently available only outside of the U.S.
The study shows that uNGAL could be most useful when an emergency physician lacks a patient’s full medical history or when sCr is in the middle range, according to Nickolas. The baseline sCr for many patients in the ED is unknown, making a patient’s elevated sCr difficult to interpret in that setting. This could make uNGAL useful for triaging patients more quickly. “Physicians in the ED need to know whether or not the patient needs to be hospitalized and where in the hospital that patient should go,” Nickolas said. “uNGAL can be a useful adjudication method to help understand how patients should be treated.”
While sCr level at presentation and the ratio of presenting-to-baseline sCr highly detected iAKI patients, presenting sCr could not predict iAKI when in the middle tertile of its range. “Furthermore, only 64.5% of patients had documented baseline sCr values at the time of presentation to the ED, highlighting the difficulties of interpreting single measurements of sCr in triage,” the authors wrote.
More studies are needed to demonstrate how earlier diagnosis of AKI would affect outcomes. In most cases, there is no quick fix for AKI, noted John Lieske, MD, a professor of medicine and director of the Mayo Clinic Renal Testing Laboratory. “Unfortunately, we do not have a magic bullet right now for AKI,” Lieske said. “We don’t have a drug or intervention that once patients have a low level of kidney injury, we can just turn that around. That’s where people are struggling right now for what the exact role for these new markers will be.” Lieske was not associated with the study.
According to Nickolas, the study shows the potential of uNGAL to make sure patients get the right level of care. “If someone had an elevated creatinine and a high urinary NGAL, you probably would check urine output, perform an ultrasound, and admit that patient to the intensive care unit,” he said. “On the other hand, a patient with elevated creatinine and a low urinary NGAL probably doesn’t need to be admitted to a higher level of care.”
Nickolas also believes that uNGAL will prove useful in assessing therapies for AKI. “We do not have any medications right now that have been shown to be effective in treating AKI. And we feel that’s because we’re detecting it too late,” he said. “We think that the next step for urinary NGAL and the other biomarkers considered in this study is using them to detect early AKI and then evaluating what interventions really work.”
Columbia University and Cincinnati Children’s Hospital have licensed uNGAL to Abbott for use in the diagnosis of AKI, and Nickolas has served as a consultant with Abbott.