Abstract
Premature infants are at unique risk for developing acute kidney injury (AKI) due to incomplete nephrogenesis, early exposure to nephrotoxic medications, and coexisting conditions such as patent ductus arteriosus (PDA) and respiratory distress syndrome (RDS). Unfortunately, laboratory testing for the diagnosis of AKI in this population is problematic because of the physiology of both the placenta and the extra-uterine premature kidney. Recent research has led to the development of promising biomarkers for the early detection of AKI in children but there are no published reports in neonates. Our goal was to determine whether urine neutrophil gelatinase-associated lipocalin (NGAL) was detectable in premature infants and to correlate levels with gestational age, birth weight (BW), or indomethacin exposure. We enrolled 20 infants in four BW groups: 500–750, 751–1000, 1001–1250, and 1251–1500 g. Urine was collected every day for the first 14 d of life. Neonates born at earlier gestational ages and lower BWs had higher urine NGAL levels (p < 0.01). We conclude that urine NGAL is easily obtained in premature infants and that it correlates significantly with both BW and gestational age. The use of urinary NGAL as a biomarker of AKI in premature infants warrants further investigation.
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Abbreviations
- AKI:
-
acute kidney injury
- BW:
-
birth weight
- NEC:
-
necrotizing enterocolitis
- NGAL:
-
neutrophil gelatinase-associated lipocalin
- PDA:
-
patent ductus arteriosus
- RDS:
-
respiratory distress syndrome
- UOP:
-
urine output
- VLBW:
-
very low birth weight
References
Tommiska V, Heinonen K, Ikonen S, Kero P, Pokela ML, Renlund M, Virtanen M, Fellman V 2001 A national short-term follow-up study of extremely low birth weight infants born in Finland in1996–1997. Pediatrics 107: e2
Drukker A, Guignard JP 2002 Renal aspects of the term and preterm infant: a selective update. Curr Opin Pediatr 14: 175–182
Bueva A, Guignard JP 1994 Renal function in preterm neonates. Pediatr Res 36: 572–577
Gallini F, Maggio L, Romagnoli C, Marrocco G, Tortorolo G 2000 Progression of renal function in preterm neonates with gestational age ≤32 weeks. Pediatr Nephrol 15: 119–124
Gouyon JB, Guignard JP 2000 Management of acute renal failure in newborns. Pediatr Nephrol 14: 1037–1044
Abitbol CL, Bauer CR, Montane B, Chandar J, Duara S, Zilleruelo G 2003 Long-term follow-up of extremely low birth weight infants with neonatal renal failure. Pediatr Nephrol 18: 887–893
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
Nguyen MT, Ross GF, Dent CL, Devarajan P 2005 Early prediction of acute renal injury using urinary proteomics. Am J Nephrol 25: 318–326
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 neutrophil gelatinase-associated lipocalin as a novel urinary biomarker for ischemic injury. J Am Soc Nephrol 14: 2534–2543
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
Mori K, Lee HT, Rapoport D, Drexler I, Foster K, Yang J, Schmitt-Ott KM, 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 kidney from ischemia-reperfusion injury. J Clin Invest 115: 610–621
Schmidt-Ott KM, Mori K, Kalandadze A, Li JY, Paragas N, Nicholas T, Devarajan P, Barasch J 2006 Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia. Curr Opin Nephrol Hypertens 15: 442–449
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 after 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
Hirsch R, Dent C, Pfriem H, Allen J, Beekman RH, Ma Q, Bennett M, Mitsnefes M, Devarajan P 2007 NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatr Nephrol 22: 2089–2095
Trachtman H, Christen E, Cnaan A, Patrick J, Mai V, Mishra J, Jain A, Bullington N, Devarajan P 2006 Urinary neutrophil gelatinase-associated lipocalin 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
Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q, Devarajan P, Parikh CR, Goldstein SL 2007 Urine NGAL is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care 11: R84
Mitsnefes MM, Kathman TS, Mishra J, Kartal J, Khoury PR, Nickolas TL, Barasch J, Devarajan P 2007 Serum NGAL as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol 22: 101–108
Devarajan P 2006 Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol 17: 1503–1520
Hewitt SM, Dear J, Star RA 2004 Discovery of protein biomarkers for renal diseases. J Am Soc Nephrol 15: 1677–1689
Acknowledgements
We thank the Neonatal Network Research Coordinators for their assistance in study design and screening for research subjects and the nursing staffs at Good Samaritan Hospital, University Hospital, and Cincinnati Children's Hospital for assistance in the specimen procurement.
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Lavery, A., Meinzen-Derr, J., Anderson, E. et al. Urinary NGAL in Premature Infants. Pediatr Res 64, 423–428 (2008). https://doi.org/10.1203/PDR.0b013e318181b3b2
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DOI: https://doi.org/10.1203/PDR.0b013e318181b3b2
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