Abstract
We hypothesized that neutrophil gelatinase-associated lipocalin (NGAL) is an early predictive biomarker of contrast-induced nephropathy (CIN). We prospectively enrolled 91 children (age 0–18 years) with congenital heart disease undergoing elective cardiac catheterization and angiography with contrast administration (CC; Ioversol). Serial urine and plasma samples were analyzed in a double-blind fashion by NGAL enzyme-linked immunosorbent assay (ELISA). CIN, defined as a 50% increase in serum creatinine from baseline, was found in 11 subjects (12%), but detection using increase in serum creatinine was only possible 6–24 h after CC. In contrast, significant elevation of NGAL concentrations in urine (135 ± 32 vs. 11.6 ± 2 ng/ml without CIN, p < 0.001) and plasma (151 ± 34 vs. 36 ± 4 without CIN, p < 0.001) were noted within 2 h after CC in those subjects. Using a cutoff value of 100 ng/ml, sensitivity, specificity, and area under the receiver-operating characteristic (ROC) curve for prediction of CIN were excellent for the 2-h urine NGAL (73%, 100%, and 0.92, respectively) and 2-h plasma NGAL (73%, 100%, and 0.91, respectively). By multivariate analysis, the 2-h NGAL concentrations in the urine (R 2 = 0.52, p < 0.0001) and plasma (R 2 = 0.72, p < 0.0001) were found to be powerful independent predictors of CIN. Patient demographics and contrast volume were not predictive of CIN.
Similar content being viewed by others
References
Goldstein SL (2006) Pediatric acute kidney injury: it’s time for real progress. Pediatr Nephrol 21:891–895
Nguyen MT, Devarajan P (2007) Biomarkers for the early detection of acute kidney injury. Pediatr Nephrol DOI 10.1007/s00467-007-0470-x
Nash K, Hafeez A, Hou S (2002) Hospital-acquired renal insufficiency. Am J Kidney Dis 39:930–936
Pannu N, Wiebe N, Tonelli M (2006) Prophylaxis strategies for contrast-induced nephropathy. JAMA 295:2765–2779
McCullough PA, Adam A, Becker CR, Davidson C, Lameire N, Stacul F, Tumlin J, CIN Consensus Working Panel (2006) Epidemiology and prognostic implications of contrast-induced nephropathy. Am J Cardiol 98(Suppl):5K–13K
McCullough PA, Adam A, Becker CR, Davidson C, Lameire N, Stacul F, Tumlin J, CIN Consensus Working Panel (2006) Risk prediction of contrast-induced nephropathy. Am J Cardiol 98(Suppl):27K–36K
Hui-Stickle S, Brewer ED, Goldstein SL (2005) Pediatric ARF epidemiology at a tertiary care center from 1999–2001. Am J Kidney Dis 45:96–101
Solomon R (2007) Contrast media nephropathy - how to diagnose and how to prevent? Nephrol Dial Transplant 22:1812–1815
Murphy SW, Barrett BJ, Parfrey PS (2000) Contrast nephropathy. J Am Soc Nephrol 11:177–182
Devarajan P (2007) Emerging biomarkers of acute kidney injury. Contrib Nephrol 156:203–212
Stacul F, Adam A, Becker CR, Davidson C, Lameire N, McCullough PA, Tumlin J (2006) Strategies to reduce the risk of contrast-induced nephropathy. Am J Cardiol 98(Suppl):59K–77K
Supavekin S, Zhang W, Kucherlapati R, Kaskel FJ, Moore LC, Devarajan P (2003) Differential gene expression following early renal ischemia-reperfusion. Kidney Int 63:1714–1724
Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P (2003) Identification of NGAL as a novel urinary biomarker for ischemic injury. J Am Soc Nephrol 4:2534–2543
Devarajan P, Mishra J, Supavekin S, Patterson LT, Potter SS (2003) Gene expression in early ischemic renal injury: clues towards pathogenesis, biomarker discovery and novel therapeutics. Mol Genet Metab 80:365–376
Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P (2004) Neutrophil gelatinase-associated lipocalin (NGAL): a novel urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 24:307–315
Mishra J, Mori K, Ma Q, Kelly C, Yang J, Mitsnefes M, Barasch J, Devarajan P (2004) Amelioration of ischemic acute renal injury by NGAL. J Am Soc Nephrol 15:3073–3082
Mori K, Lee HT, Rapoport D, Drexler I, Foster K, Yang J, Schmidt-Ott, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D’Agati V, Devarajan P, Barasch J (2005) Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia. J Clin Invest 115:610–621
Mishra J, Ma Q, Kelly C, Mitsnefes M, Mori K, Barasch J, Devarajan P (2006) Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol 21:856–863
Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury following cardiac surgery. Lancet 365:1231–1238
Parikh CR, Jani A, Mishra J, Ma Q, Kelly C, Barasch J, Edelstein CL, Devarajan P (2006) Urine NGAL and IL-18 are predictive biomarkers for DGF following kidney transplantation. Am J Transplant 6:1639–1645
Trachtman H, Christen E, Cnaan A, Patrick J, Mai V, Mishra J, Jain A, Bullington N, Devarajan P (2006) Urinary NGAL in D+HUS: A novel marker of renal injury. Pediatr Nephrol 21:989–994
Brunner HI, Mueller M, Rutherford C, Passo MH, Witte D, Grom A, Mishra J, Devarajan P (2006) Urinary NGAL as a biomarker of nephritis in childhood-onset SLE. Arthritis Rheum 54:2577–2584
Mitsnefes M, Kathman T, Mishra J, Kartal J, Khoury P, Nickolas T, Barasch J, Devarajan P (2007) Serum NGAL as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol 22:101–108
Xu S, Venge P (2000) Lipocalins as biomarkers of disease. Biochim Biophys Acta 1482:298–307
Schmidt-Ott KM, Mori K, Kalandadze A, Li JY, Paragas N, Nicholas T, Devarajan P, Barasch J (2006) NGAL-mediated iron traffic in kidney epithelia. Curr Opin Nephrol Hypertens 15:442–449
Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, Barasch J (2007) Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 18:407–413
Liu Q, Nilsen-Hamilton M (1995) Identification of a new acute phase protein. J Biol Chem 270:22565–22570
Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S (2006) Neutrophil gelatinase-associated lipocalin and renal function after percutaneous coronary interventions. Am J Nephrol 26:287–292
Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S (2007) Neutrophil gelatinase-associated lipocalin (NGAL) correlations with cystatin C, serum creatinine and eGFR in patients with normal serum creatinine undergoing coronary angiography. Nephrol Dial Transplant 22:295–296
Herget-Rosenthal S, Marggraf G, Husing J, Goring F, Pietruck F, Janssen O, Philipp T, Kribben A (2004) Early detection of acute renal failure by serum cystatin C. Kidney Int 66:1115–1122
Duan SB, Wu HW, Luo JA, Liu FY (1999) Assessment of renal function in the early stages of nephrotoxicity induced by iodinated contrast media. Nephron 83:122–125
Hampel DJ, Sansome C, Sha M, Brodsky S, Lawson WE, Goligorsky MS (2001) Toward proteomics in uroscopy: urinary protein profiles after radiocontrast medium administration. J Am Soc Nephrol 12:1026–1035
Acknowledgements
Dr. Devarajan is supported by grants from the NIH/NIDDK (RO1-DK53289, P50-DK52612, R21-DK070163), a Grant-in-Aid from the American Heart Association Ohio Valley Affiliate, and a Translational Research Initiative Grant from Cincinnati Children’s Hospital Medical Center. We are indebted to our patients and their families for their participation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hirsch, R., Dent, C., Pfriem, H. et al. NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatr Nephrol 22, 2089–2095 (2007). https://doi.org/10.1007/s00467-007-0601-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-007-0601-4