Serum NGAL predicts AKI, mortality in patients presenting to ED

Use of serum neutrophil gelatinase-associated lipocalin (NGAL) can help identify acute kidney injury and predict 3-month mortality among patients presenting to the emergency department (ED) with “normal” creatinine, reports a Singapore study.

“[O]ur findings provide support for the use of NGAL as a biomarker for AKI in the ED,” the researchers said. “We have also provided additional evidence of the utility of NGAL in a multiethnic Asian population.”

Of the 784 patients enrolled, 107 (13.6 percent) had AKI. Patients with AKI had increased mean serum NGAL levels compared with those without (670.0 vs 490.3 ng/dL; p<0.001). NGAL levels >490 ng/dL for AKI had a sensitivity of 59 percent (95 percent confidence interval [CI], 49‒68) and specificity of 65 percent (95 percent CI, 61‒68). [Singapore Med J 2023;64:479-486]

In addition, the need for renal replacement therapy rose by 21 percent per 100-ng/dL increase in NGAL (p<0.001), while the chances of dying within 3 months grew 10 percent per 100-ng/dL increase in NGAL (p=0.028). Notably, no significant association was seen between NGAL levels and major adverse cardiac events.

“Serum NGAL was significantly raised in patients with AKI compared with those without AKI, confirming the utility of serum NGAL in differentiating these two patient groups,” the researchers said.

“Moreover, incorporating variables such as metabolic comorbidities and atheropathic tendencies in our clinical model enhanced its predictive value by 20.2 percent from AUC 0.62 to 0.75 at an NGAL cutoff of 490 ng/dL,” they added.

“Knowing that incorporating metabolic comorbidities and atheropathic tendencies improves pretest probability for AKI, clinicians could take into account these variables when interpreting NGAL results,” the researchers noted.

Biomarker

In previous studies, increased serum NGAL has been suggested as a single unequivocal biomarker for AKI, similar to troponin T for acute myocardial infarction (sensitivity, 0.85; specificity, 0.80). [N Engl J Med 1996;335:1333-1341; CMAJ 2005;173:1191-1202; N Engl J Med 2009;361:858-867]

In the current study, results across patient subgroups revealed a specificity of 0.61‒0.81 and a sensitivity of 0.39‒0.70 with NGAL. These values, unfortunately, were not sufficient for a rule-in or rule-out test.

“However, taking into consideration the prevalence of AKI in these subgroups, our results reveal that NGAL had a much higher negative predictive value (0.85–0.99) than positive predictive value (0.18–0.67),” the researchers said.

In low to medium pretest probability settings, serum NGAL may be used to rule out AKI, knowing that congestive cardiac failure and systemic inflammatory response syndrome have been established as predictors of AKI development, according to the researchers.

“In other words, in a broad cohort of undifferentiated patients presenting to the ED, low serum NGAL may be more suitably used for ruling out AKI, analogous to D-dimer for venous thromboembolism,” they said. “Nevertheless, more studies are needed to validate the use of NGAL as a rule-out test.” [Cochrane Database Syst Rev 2016;2016:CD010864]

This single-centre prospective cohort study was conducted at Singapore General Hospital and included patients (aged ≥21 years, estimated glomerular filtration rate <60 mL/min/1.73 m²) presenting to the ED from July 2011 to August 2012. Participants had congestive cardiac failure, systemic inflammatory response syndrome, or required hospitalization.

The researchers who diagnosed AKI were blinded to experimental measurements. They measured serum NGAL as a point-of-care test.