The nature and discriminatory value of urinary neutrophil gelatinase-associated lipocalin in critically ill patients at risk of acute kidney injury
- 759 Downloads
Different molecular forms of urinary neutrophil gelatinase-associated lipocalin (NGAL) have recently been discovered. We aimed to explore the nature, source and discriminatory value of urinary NGAL in intensive care unit (ICU) patients.
We simultaneously measured plasma NGAL (pNGAL), urinary NGAL (uNGAL), and estimated monomeric and homodimeric uNGAL contribution using Western blotting-validated enzyme-linked immunosorbent assays [uNGALE1 and uNGALE2] and their calculated ratio in 102 patients with the systemic inflammatory response syndrome and oliguria, and/or a creatinine rise of >25 μmol/L.
Measurements and main results
Bland–Altman analysis demonstrated that, despite correlating well (r = 0.988), uNGAL and uNGALE1 were clinically distinct, lacking both accuracy and precision (bias: 266.23; 95 % CI 82.03–450.44 ng/mg creatinine; limits of agreement: −1,573.86 to 2,106.32 ng/mg creatinine). At best, urinary forms of NGAL are fair (area under the receiver operating characteristic [AUROC] ≤0.799) predictors of renal or patient outcome; most perform significantly worse. The 44 patients with a primarily monomeric source of uNGAL had higher pNGAL (118.5 ng/ml vs. 72.5 ng/ml; p < 0.001), remaining significant following Bonferroni correction.
uNGAL is not a useful predictor of outcome in this ICU population. uNGAL patterns may predict distinct clinical phenotypes. The nature and source of uNGAL are complex and challenge the utility of NGAL as a uniform biomarker.
KeywordsAcute kidney injury Oliguria Critical illness Intensive care Biomarker Systemic inflammatory response syndrome
This study was supported by the Austin Hospital Intensive Care Trust Fund. The ELISA testing was funded by a grant from the Swedish Medical Research Council to Uppsala University.
Conflicts of interest
Shengyuan Xu holds patents with, and receives royalties from, Diagnostics Development. Per Venge holds patents with, and stock in, P&M Venge AB. He has received royalties from Phadia. The remaining authors declare that they have no conflicts of interest.
- 3.Nickolas TL, O’Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, Buchen C, Khan F, Mori K, Giglio J, Devarajan P, Barasch J (2008) Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 148:810–819PubMedCrossRefGoogle Scholar
- 6.Zhang X, Gibson B Jr, Mori R, Snow-Lisy D, Yamaguchi Y, Campbell SC, Simmons MN, Daly TM (2012) Analytical and biological validation of a multiplex immunoassay for acute kidney injury biomarkers. Clin Chim Acta 415C:88–93Google Scholar
- 8.Dent CL, Ma Q, Dastrala S, Bennett M, Mitsnefes MM, Barasch J, Devarajan P (2007) Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Crit Care 11:R127PubMedCrossRefGoogle Scholar
- 24.Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60PubMedCrossRefGoogle Scholar
- 26.Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004) Acute renal failure: definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8:R204–R212PubMedCrossRefGoogle Scholar
- 38.Shapiro NI, Trzeciak S, Hollander JE, Birkhahn R, Otero R, Osborn TM, Moretti E, Nguyen HB, Gunnerson K, Milzman D, Gaieski DF, Goyal M, Cairns CB, Kupfer K, Lee SW, Rivers EP (2010) The diagnostic accuracy of plasma neutrophil gelatinase-associated lipocalin in the prediction of acute kidney injury in emergency department patients with suspected sepsis. Ann Emerg Med 56(52–59):e51Google Scholar
- 40.Bagshaw SM, Bennett M, Haase M, Haase-Fielitz A, Egi M, Morimatsu H, D’Amico G, Goldsmith D, Devarajan P, Bellomo R (2010) Plasma and urine neutrophil gelatinase-associated lipocalin in septic versus non-septic acute kidney injury in critical illness. Intensive Care Med 36:452–461PubMedCrossRefGoogle Scholar
- 43.Endre ZH, Pickering JW, Walker RJ, Devarajan P, Edelstein CL, Bonventre JV, Frampton CM, Bennett MR, Ma Q, Sabbisetti VS, Vaidya VS, Walcher AM, Shaw GM, Henderson SJ, Nejat M, Schollum JB, George PM (2011) Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function. Kidney Int 79:1119–1130PubMedCrossRefGoogle Scholar
- 47.Royakkers AA, Bouman CS, Stassen PM, Korevaar JC, Binnekade JM, van de Hoek W, Kuiper MA, Spronk PE, Schultz MJ (2012) Systemic and urinary neutrophil gelatinase-associated lipocalins are poor predictors of acute kidney injury in unselected critically ill patients. Crit Care Res Pract 2012:712695PubMedGoogle Scholar
- 49.Constantin JM, Futier E, Perbet S, Roszyk L, Lautrette A, Gillart T, Guerin R, Jabaudon M, Souweine B, Bazin JE, Sapin V (2010) Plasma neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in adult critically ill patients: a prospective study. J Crit Care 25(176):e171–e176Google Scholar
- 52.Haase M, Haase-Fielitz A, Bellomo R, Mertens PR, (2010) Neutrophil gelatinase-associated lipocalin as a marker of acute renal disease. Curr Opin HematolGoogle Scholar