Instability of Urinary NGAL During Long-Term Storage

Abstract

We read with interest the recent study by Wagener et al1Wagener G. Gubitosa G. Wang S. et al.Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery.Am J Kidney Dis. 2008; 52: 425-433Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar on perioperative measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL) in 426 adult cardiac surgery patients enrolled during a 20-month study period. In this study, the predictive value of urinary NGAL for subsequent acute kidney injury (AKI) was not much above chance (area under receiver operating characteristic curve, 0.57 to 0.61). The postoperative urinary NGAL peak concentration was about 2.000 ng/mL.1Wagener G. Gubitosa G. Wang S. et al.Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery.Am J Kidney Dis. 2008; 52: 425-433Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar In a former study by Wagener et al,2Wagener G. Jan M. Kim M. et al.Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery.Anesthesiology. 2006; 105: 485-491Crossref PubMed Scopus (480) Google Scholar in a similar patient cohort of 81 individuals enrolled during a 4-month study period, the predictive value of urinary NGAL for subsequent AKI was fair to good (area under receiver operating characteristic curve, 0.74 to 0.80). The postoperative urinary NGAL peak concentration was about 6.000 ng/mL.2Wagener G. Jan M. Kim M. et al.Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery.Anesthesiology. 2006; 105: 485-491Crossref PubMed Scopus (480) Google Scholar It is obvious that, in the more recent cohort,1Wagener G. Gubitosa G. Wang S. et al.Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery.Am J Kidney Dis. 2008; 52: 425-433Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar the urinary NGAL concentrations were lower by about 66% compared with the former cohort.2Wagener G. Jan M. Kim M. et al.Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery.Anesthesiology. 2006; 105: 485-491Crossref PubMed Scopus (480) Google Scholar In the recent study, patients with AKI had similar urinary NGAL concentrations as patients without AKI in the former study.2Wagener G. Jan M. Kim M. et al.Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery.Anesthesiology. 2006; 105: 485-491Crossref PubMed Scopus (480) Google Scholar In this regard, in a collaborative laboratory study on the stability of urinary NGAL, Grenier et al3Grenier F, Ali S, Syed H, et al: Multi-site evaluation of an assay in development for NGAL (neutrophil gelatinase-associated lipocalin) on the Abbott ARCHITECT© Analyzer. American Association of Clinical Chemists Annual Meeting, Washington, DC, July 27-31, 2008 (abstr)Google Scholar found that urinary NGAL concentrations stored at −20°C for 6 months decreased randomly and with high variability over the whole range of concentrations (10 to 1,000 ng/mL) when compared to samples from the same cohort simultaneously stored at −80°C (Fig 1). Urinary NGAL concentrations from samples stored at −20°C were reduced on average by 40%, but not uniformly. A loss of discriminatory power of urinary NGAL under such storage conditions, as in the recent study,1Wagener G. Gubitosa G. Wang S. et al.Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery.Am J Kidney Dis. 2008; 52: 425-433Abstract Full Text Full Text PDF PubMed Scopus (223) Google Scholar would be the likely consequence. Accordingly, the results of this latest study must be interpreted with great caution. Financial Disclosure: None. In Reply to ‘Instability of Urinary NGAL During Long-Term Storage' and ‘NGAL and Cardiac Surgery–Associated Acute Kidney Injury'American Journal of Kidney DiseasesVol. 53Issue 3PreviewWe appreciate the comments by Haase-Fielitz et al.1 The urinary neutrophil gelatinase-associated lipocalin (NGAL) concentrations in the present studies2,3 are lower than in our previous study published in Anesthesiology4 because the 2006 study used an immunoblotting technique and not ELISA (enzyme-linked immunosorbent assay) to quantify NGAL. Immunoblotting has a lower sensitivity and specificity than ELISA and may therefore account for this difference. ELISA for NGAL was not available at the time of our first study, but NGAL levels measured by ELISA correlated well with immunoblotting in 396 samples that were processed both ways (Spearman rank correlation coefficient, 0.776 [95% CI, 0.76 to 0.83]; P < 0.001; Fig 1). Full-Text PDF