A kidney injury biomarker called "neutrophil gelatinase-associated lipocalin" (NGAL) in urine or blood detected early subclinical acute kidney injury (AKI) and its adverse outcomes in critically ill patients who did not have diagnostic increases in serum creatinine. Early NGAL testing may therefore allow earlier conventional medical interventions or introduction of novel therapies to improve the prognosis of AKI, according to a study published April 26 in the Journal of the American College of Cardiology (JACC).
Results of the retrospective study—which included pooled data from 2,322 critically ill adult and pediatric patients—also justify recommending a reassessment of what defines AKI, according to researchers from 13 international medical organizations collaborating on the study.
"This study describes a new biomarker (NGAL) that completely outperforms the current serum creatinine-based criteria for the early detection of AKI and its devastating clinical outcomes," said Prasad Devarajan, MD, director of nephrology and hypertension at Cincinnati Children's Hospital Medical Center. "This has enormous implications because AKI affects about 30 percent of all critically ill patients, in whom current therapeutic options are limited and unacceptably delayed," added Devarajan.
The critically ill patients whose data researchers analyzed primarily had Type 1 cardiorenal syndrome, a common condition in which heart dysfunction causes kidney injury. The researchers were surprised to learn that 40 percent of the patients showed unexpected early increases in urine or blood NGAL levels, but no increases in serum creatinine.
In a significant proportion of patients at renal risk, acute tubular damage may occur without loss of excretory function. Such NGAL positive patients are at greater risk of adverse outcomes, including death and renal replacement therapy, both in the presence or absence of an increase in serum creatinine. These patients might be reasonably classified as having AKI, even though they do not fulfill current AKI consensus criteria. Their detection and the size of their cohort justify re-assessment of the concept and definition of AKI, according to Devarajan and colleagues.
NGAL-positive patients were 16 times more likely to need dialysis, three times more likely to die during hospitalization, and on average they spent three extra days in intensive care and eight extra days in the hospital, noted the researchers.
"Our findings suggest an important analogy between the troponin/creatine kinase relationship in acute myocardial infarction and the NGAL/creatinine relationship in AKI for the identification of previously undetected organ injury," said Rinaldo Bellomo, MD, director of intensive care research at Austin Hospital, Melbourne, Australia and senior author of the study. "Just as the increased diagnostic sensitivity of troponin has dramatically altered the definition, diagnosis and management of acute myocardial infarction, similar concepts might apply to NGAL and AKI," Bellomo said.
The researchers plan to pursue a prospective multi-center study to further verify the effectiveness of the NGAL test as a prognostic biomarker in a large population of patients in critical care settings.