Washington, DC - An investigational immunoassay for neutrophil gelatinase-associated lipocalin (NGAL) can identify acute renal failure after cardiopulmonary bypass (CPB) support and stratify for related clinical risk much sooner after surgery than is possible using serial serum creatinine measurements, according to researchers [1].

Urine levels of the biomarker, obtained two to four hours after CPB and measured using a standard automated immunoassay analyzer, were significantly predictive of acute renal failure severity and duration in a series of 196 children who underwent surgery for congenital defects. In contrast, a renal-failure diagnosis as determined by serum creatinine took up to 72 hours, report the study's authors, led by Dr Michael Bennett (Cincinnati Children's Hospital Medical Center, OH).

"It identifies the problem days before the current gold standard of care," senior author Dr Prasad Devarajan (Cincinnati Children's Hospital) told heartwire, and "gives the physician a window of about two or three days to do something about it."

The group's prospective study was published online March 12, 2008 in the Clinical Journal of the American Society of Nephrology. According to Devarajan, it's the first published experience of the NGAL immunoassay performed on a standard, commercially available analyzer (ARCHITECT, Abbott Diagnostics).

"All you need from the patient is one drop of urine. You send it down to the lab, and you get an answer in 30 minutes," said Devarajan, whose center is one of two listed in the report as having a commercial stake in the NGAL immunoassay should it be approved by the FDA.

He and his colleagues acknowledge, however, that their "provocative" findings would have to be confirmed in large, randomized trials of "adults with the usual confounding variables and comorbid conditions that normally accumulate with increasing age."

After validating the immunoassay's performance relative to a more established but time-consuming and cumbersome ELISA for NGAL and finding a 99% correlation between the two methods, the group prospectively used it in the 196 children undergoing CPB-supported procedures. None were diabetic or had compromised renal function before surgery.

Acute renal failure, defined as a >50% increase in serum creatinine, developed within three days of CPB in 99 patients, or 51% of the cohort. It was evident within 24 hours in only seven cases and within 48 hours in 60 cases.

Mean urinary immunoassay-measured NGAL levels among patients who ultimately developed renal failure jumped 15-fold within two hours of CPB, 25-fold within four hours, and 26-fold within six hours compared with baseline levels (p<0.0001 at each time point). Levels remained significantly higher than baseline out to 48 hours.

In a multivariate analysis that controlled for age, sex, and CPB duration, NGAL levels at two hours and four hours independently predicted duration of renal failure, and six-hour levels predicted both renal-failure duration and hospital length of stay (p<0.0001 in each case); four-hour readings also predicted hospital length of stay (p=0.0007).

"For urine NGAL at two hours after CPB, sensitivity and specificity were optimal at the 100-ng/mL cutoff, with an area under the curve of 0.93 for the prediction of [acute renal failure], indicative of an excellent biomarker," according to the authors.

"The ability to predict which patients will develop [acute renal failure] after CPB could enable early initiation of interventions to change the dismal outcomes associated with this all-too-common clinical problem," they write.