The authors thank Vives et al. for their interest in our Clinical Concepts and Commentary article.1
Biomarkers in medicine are a rapidly evolving field that have generated a tremendous amount of interest for the promise of early, accurate diagnoses of a variety of conditions ranging from traumatic brain injury to acute kidney injury (AKI). Biomarkers in AKI have historically been studied in patient populations with a known and well-timed renal insult, like cardiopulmonary bypass or iodinated contrast exposure. The performance of a majority of these biomarkers tends to be poorer when studied in more heterogeneous populations than the original study population.2Neutrophil gelatinase-associated lipocalin (NGAL) is no exception.
In the original article, we acknowledge the NGAL data in adult patients undergoing cardiopulmonary bypass is less clear than in the pediatric population, perhaps because of the associated comorbidities and their known and unknown influence on NGAL levels in adults.1
The association of increased NGAL levels in patients developing AKI postcardiopulmonary bypass is well documented in several studies, including the recent publication by the NGAL Meta-analysis Investigator Group.3This largest meta-analysis to date used pooled data from 19 studies and found NGAL consistently to be a useful early predictor of AKI in a broad-based patient population, even though the area under the receiver-operating characteristic curve was 0.77 (as pointed out by Vives et al.) . Receiver-operating characteristic analysis has been used to select the optimal threshold under a variety of clinical circumstances, balancing the inherent tradeoffs that exist between sensitivity and specificity.4Currently there is no clear consensus on the plasma or urinary threshold levels to label patients as high risk for AKI-cardiopulmonary bypass. This may be in part to the variability in the cutoff values determined using research assays versus commercial standardized NGAL assays.
There have been more than 15 biomarkers described for AKI, and one of the likely reasons that NGAL is at the forefront is because of the availability of a commercial assay, rather than pure research assays, that allows clinicians and researchers across the globe to study AKI in varying patient populations.1This also means that limitations of NGAL are likely to be reported in a higher frequency as we study it in more heterogeneous populations (e.g. , intensive care unit patients and emergency department admissions).5
We agree with the astute observation of the authors that in reality we may need a panel of biomarkers to better define the problem. We stated this in our article as well. Further studies are needed to validate and define the particular panels of biomarkers for AKI after cardiopulmonary bypass.
