Blood Test IDs Acute Kidney Injury in ED

A test that measures blood levels of neutrophil gelatinase-associated lipocalin (NGAL) accurately distinguished between acute kidney injury and reversible transient kidney dysfunction in the ED, researchers reported.

Among 616 patients with varying urgent health issues presenting to a hospital emergency department, the highest median levels of plasma NGAL were seen in those with acute kidney injury (146-174 ng/ml at various time points); levels also increased with acute kidney injury (AKI) severity (207-244 ng/ml for AKI Network stage 2 or greater disease).

Plasma NGAL also discriminated between patients with AKI, those with normal kidney function, and those with transient azotemia (area under the curve, 0.85 and 0.73, respectively); a plasma NGAL level of 133 ng/ml or greater was associated with a 10-fold increase in AKI risk, Prasad Devarajan, MD, and colleagues from Cincinnati Children's Hospital Medical Center and the Hospital Fernando Fonseca in Lisbon, Portugal wrote in the Sept. 5 issue of the Clinical Journal of the American Society of Nephrology.

AKI has been increasing in both the hospital and community settings, but diagnosis of the condition remains problematic, the researchers wrote.

Serum creatinine (SCr) is routinely used in emergency departments to diagnose AKI, but it's a delayed marker that rises only after kidney injury has been established, and there are other downsides to the test, Devarajan told MedPage Today.

"Especially in the community-acquired setting, it is very common to see an increase in SCr," he said. "In this setting it is very important to be able to distinguish between true, intrinsic AKI and transient, reversible kidney injury ... [I]n both cases SCr is going to be elevated."

Along with colleagues at Cincinnati Children's Hospital, Devarajan developed the NGAL test as a biomarker of early AKI. In earlier studies, the researchers showed it to be useful in a variety of hospital settings, including adult ICU and heart failure patients.

      Devarajan holds patents on the test, which is being commercially developed by the point-of-care diagnostic and services company Alere, Inc. of Waltham, Massachusetts. The test has been approved in parts of Europe and Asia, and the FDA is currently considering Alere's application in the U.S.

In the newly published study, the researchers examined the accuracy of plasma NGAL as a marker of AKI in patients with urgent health issues presenting to the ED.

     The study included 616 patients who presented to the ED of Fernando Fonseca Hospital and were admitted for treatment from March to November of 2008. Baseline renal function by SCr, medical history and demographic characteristics were obtained from hospital electronic records.

     Prospective renal function assessment was carried out by measuring SCr, serum cystatin C (SCysC), and plasma NGAL at 0, 6, 12, 24, and 48 hours from hospital admission.

     Plasma NGAL levels among patients with AKI remained significantly higher than in patients with normal kidney function for all time points  P menor a 0.001. When the combined group of AKI plus transient kidney injury patients was examined, the values of plasma NGAL remained significantly different from patients with normal kidney function P menor a 0.001 for all time points and the test was able to differentiate AKI from transient injury P menor a 0.001 for all time points.

Among the other findings:

·         Higher levels of plasma NGAL were associated with more severe AKI using AKI Network classification (median values ranging between 69 and 75, 125.5 and 148, 168 and 195, and 301.5 and 328.5 ng/ml for AKI Network stages 0,1,2, and 3, respectively.

·         ROC curves were generated to assess the discriminative ability of the NGAL test for diagnosing AKI. The area under the curves (AUCs) for AKI prediction were 0.77, 0.81, 0.82, 0.79 and 0.78 at 0, 6, 12, 24, and 48 hours, respectively. The AUC for discriminating between patients with AKI and those with normal kidney function was 0.85 (95% CI, 0.81-0.90) at the 12-hour time point.

·         The addition of plasma NGAL to the clinical model yielded a net reclassification improvement of 94.3% and an integrated discrimination improvement of 0.122.

·         When patients were classified into three grades of risk according to plasma NGAL levels  menor de 97 ng/ml was considered low risk and mayor que 133 ng/ml was considered high risk), those in the high risk category were found to have a 10-fold greater risk of AKI  odds ratio, 9.8; 95% CI, 5.6-16.9.

"When pNGAL concentrations are in the gray zone  mayor que 97 ng/ml to menos de 133 ng/ml we propose the recognition of risk factors that are independent predictors of AKI, including age, chronic kidney disease and comorbidities like cardiovascular disease," the researchers wrote. "Thus, patients with these risk factors may be considered at high risk of AKI, even when plasma NGAL levels are in the gray zone."

Devarajan said the findings prove the test could improve the clinical management of patients suspected of having AKI in the emergency treatment setting.

"The incidence of AKI varies from 20% to 40% in critical care patients and it is a significant cause of death," he said. "This test could markedly increase our ability to discriminate between true, intrinsic AKI and other conditions."

Tomado de Medpagetoday.com