NGAL May Help Identify Renal Dysfunction in Suspected Sepsis

NEW ORLEANS — Plasma neutrophil gelatinase-associated lipocalin shows promise as an early biomarker for development of acute renal dysfunction in patients presenting to the emergency department with suspected sepsis.

A rise in serially measured serum creatinine is the standard indicator of acute renal injury currently used in clinical practice, but it can be an unreliable and late-appearing biomarker, Dr. Nathan I. Shapiro said at the annual meeting of the Society for Academic Emergency Medicine.

Neutrophil gelatinase-associated lipocalin (NGAL) is a protein produced by activated neutrophils that increases in infectious illnesses and is further inducible during renal ischemia, explained Dr. Shapiro of Beth Israel Deaconess Medical Center, Boston.

He presented data from the Prospective Observational Emergency Medicine Study (POEMS) involving 661 adults who presented with suspected sepsis to 10 participating academic emergency departments. The primary outcome was development of acute renal injury as indicated by a rise in serum creatinine of more than 0.5 mg/dL within 72 hours after an initial measurement obtained upon arrival at the ED.

Of the 661 patients, 24 (3.6%) developed renal dysfunction within 72 hours, of whom 6 went on to require renal replacement therapy. The median initial plasma NGAL among those who developed renal dysfunction was 456 ng/mL, compared with 144 ng/mL in those who did not.

NGAL was a strong predictor of subsequent renal dysfunction. A plasma NGAL greater than 150 ng/mL was 96% sensitive and 51% specific for renal dysfunction. Serum creatinine was a much less potent predictor; achieving a 96% sensitivity using creatinine required setting the cutoff at 0.7 mg/dL, which resulted in a poor specificity of 17%, Dr. Shapiro reported.

Plasma NGAL also predicted in-hospital mortality. In a multivariate analysis adjusted for patient age, sex, race, and serum creatinine level, the odds of in-hospital mortality increased threefold with each quartile for NGAL greater than the lowest.

The major study limitation was that only 24 cases of acute renal dysfunction occurred. Further studies with larger numbers of cases will be required, he concluded.

POEMS was funded by Biosite, now Inverness Medical Innovations Inc., which is developing a rapid plasma NGAL test. Dr. Shapiro received a research grant from the company to conduct the study. Abbott Laboratories is developing a urine NGAL test. Both tests are intended for early identification of patients at risk of developing acute renal injury after surgery, trauma, or critical illness, so that timely preventive therapy can be initiated.

A plasma NGAL greater than 150 ng/mL was 96% sensitive and 51% specific for renal dysfunction. DR. SHAPIRO