A kidney disease biomarker known as neutrophil gelatinase-associated lipocalin (NGAL) is gaining attention as an early, accurate indicator of acute kidney injury (AKI) following its successful use in a recent study.
The finding is noteworthy because it suggests that a blood test for NGAL can detect acute kidney damage earlier than currently used kidney function tests, such as serum creatinine.
AKI manifests as a sudden decrease in kidney function that, if left untreated, can sometimes cause permanent damage to the kidneys or become life-threatening. People can develop AKI from a number of different causes, including trauma, burns, drug toxicity, sepsis, shock, or contrast dyes used during imaging procedures. Factors that can increase the risk of developing AKI include diabetes, high blood pressure, heart disease, lung disease, and pre-existing chronic kidney disease.
NGAL is a protein that was originally found in neutrophils, a type of white blood cell. It is also found in many other tissues in the body, including kidney cells. Part of the reason NGAL is such a good indicator of AKI is that its levels rise rapidly in response to kidney injury, typically within 2-4 hours.
In contrast, the most commonly used markers of kidney function today, such as BUN, cystatin C, and creatinine, often do not change until well after damage or injury has already occurred. Early detection of AKI is critical because injury occurs rapidly over a period of hours to days, unlike that seen with chronic kidney disease that develops over months to years.
Published in the September issue of the Clinical Journal of the American Society of Nephrology, the study evaluated more than 600 patients who were admitted to the hospital from the emergency department between March and November of 2008. These 600 patients were selected from over 4,700 people and included those who had normal or only mildly abnormal kidney function at admission.
Selected study patients had conditions that would require at least two days of hospitalization, which would allow multiple blood samples to be collected and analyzed. NGAL levels, cystatin C, and creatinine levels were measured in each of the blood samples, and patients were followed until they were discharged.
After the patients were discharged, the scientists used clinical criteria to classify them according to one of four diagnoses, primarily based on changes in serum creatinine: 1) normal kidney function 2) stable chronic kidney disease 3) reversible transient kidney dysfunction (increase in serum creatinine that returned to normal within 3 days), or 4) AKI (increase in creatinine that persisted for at least 3 days).
Participants who were diagnosed with AKI using clinical criteria, about 20% of the patients, showed the highest levels of NGAL in their blood, and the NGAL level increased with severity of AKI.
The NGAL levels of the people in the AKI group were notably higher (median range 146-175 ng/mL for the various times) than levels of participants with normal kidney function (63-69 ng/mL) and compared to those categorized as having reversible transient kidney dysfunction (79-86 ng/mL).
NGAL levels were already higher 6 hours after admission in those developing AKI and reached their highest values 6-12 hours after admission. During the first two days in the hospital, however, serum creatinine levels did not change significantly and did not identify patients with AKI.
The researchers concluded that adding NGAL evaluation to clinical criteria not only significantly improves prediction of AKI but also distinguishes AKI from reversible transient kidney dysfunction.
NGAL is one of several newer kidney function biomarkers being evaluated, and the results of the recent study suggest that it is an effective biomarker for predicting AKI. Future research is needed to determine if predicting AKI with NGAL testing may lead to the prevention or reversal of the kidney damage through early detection and treatment. One of the authors of the study holds a patent for the NGAL test, which has been approved in parts of Europe and Asia but is currently pending approval from the FDA in the U.S.
Additional independent studies need to be performed to more fully understand its clinical applications. For example, since the current study did not look at patients with more severe acute kidney injury, or at patients with advanced chronic kidney injury, it is not clear how well the test would work in other groups of patients.
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