Abstract
NO is involved in normal kidney function and perturbed in acute kidney injury (AKI). We hypothesized that urinary concentration of NO metabolites, nitrite, and nitrate would be lower in children with early AKI presenting to the emergency department (ED), when serum creatinine (SCr) was uninformative. Patients up to 19 y were recruited if they had a urinalysis and SCr obtained for routine care. Primary outcome, AKI, was defined by pediatric Risk, Injury, Failure, Loss of function, End-stage renal disease (pRIFLE) criteria. Urinary nitrite and nitrate were determined by HPLC. A total of 252 patients were enrolled, the majority (93%) of whom were without AKI. Although 18 (7%) had AKI by pRIFLE, 50% may not have had it identified by the SCr value alone at the time of visit. Median urinary nitrate was lower for injury versus risk (p = 0.03); this difference remained significant when the injury group was compared against the combined risk and no AKI groups (p = 0.01). Urinary nitrite was not significantly different between groups. Thus, low urinary nitrate is associated with AKI in the pediatric ED even when SCr is normal. Predictive potential of this putative urinary biomarker for AKI needs further evaluation in sicker patients.
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Abbreviations
- AKI:
-
acute kidney injury
- eCCl:
-
estimated creatinine clearance
- ED:
-
emergency department
- NGAL:
-
neutrophil gelatinase-associated lipocalin
- NOx:
-
combined nitrite and nitrate concentration
- pRIFLE:
-
AKI outcome as measured by the pediatric RIFLE criteria: risk, injury, failure, loss of function, end-stage renal disease
- pRIFLE-I:
-
injury
- pRIFLE-R:
-
risk
- prifle-f:
-
failure
- ROC:
-
receiver operator characteristic
- SCr:
-
serum creatinine
References
Lameire N, Van Biesen W, Vanholder R 2005 Acute renal failure. Lancet 365: 417–430
Devarajan P 2006 Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol 17: 1503–1520
Devarajan P 2007 Emerging biomarkers of acute kidney injury. Contrib Nephrol 156: 203–212
Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL 2007 Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 71: 1028–1035
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–R212
Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A, Acute Kidney Injury Network 2007 Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11: R31
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: 810–819
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.e1
Di Grande A, Giuffrida C, Carpinteri G, Narbone G, Pirrone G, Di Mauro A, Calandra S, Noto P, Le Moli C, Alongi B, Nigro F 2009 Neutrophil gelatinase-associated lipocalin: a novel biomarker for the early diagnosis of acute kidney injury in the emergency department. Eur Rev Med Pharmacol Sci 13: 197–200
Self WH, Barrett TW 2010 Novel biomarkers: help or hindrance to patient care in the emergency department?. Ann Emerg Med 56: 60–61
Du Y, Zappitelli M, Mian A, Bennett M, Ma Q, Devarajan P, Mehta R, Goldstein SL 2011 Urinary biomarkers to detect acute kidney injury in the pediatric emergency center. Pediatr Nephrol 26: 267–274
Goligorsky MS, Brodsky SV, Noiri E 2002 Nitric oxide in acute renal failure: NOS versus NOS. Kidney Int 61: 855–861
Kwon O, Hong SM, Ramesh G 2009 Diminished NO generation by injured endothelium and loss of macula densa nNOS may contribute to sustained acute kidney injury after ischemia-reperfusion. Am J Physiol Renal Physiol 296: F25–F33
Bryan NS, Grisham MB 2007 Methods to detect nitric oxide and its metabolites in biological samples. Free Radic Biol Med 43: 645–657
Zappitelli M, Parikh CR, Akcan-Arikan A, Washburn KK, Moffett BS, Goldstein SL 2008 Ascertainment and epidemiology of acute kidney injury varies with definition interpretation. Clin J Am Soc Nephrol 3: 948–954
Kelm M 1999 Nitric oxide metabolism and breakdown. Biochim Biophys Acta 1411: 273–289
Elli M, Soylemezoglu O, Erbas D, Bakkaloglu SA, Buyan N, Ozkaya O, Hasanoglu E 2005 Plasma and urine nitric oxide levels in healthy Turkish children. Pediatr Nephrol 20: 1605–1609
Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q, Devarajan P, Parikh CR, Goldstein SL 2007 Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care 11: R84
Washburn KK, Zappitelli M, Arikan AA, Loftis L, Yalavarthy R, Parikh CR, Edelstein CL, Goldstein SL 2008 Urinary interleukin-18 is an acute kidney injury biomarker in critically ill children. Nephrol Dial Transplant 23: 566–572
Rahma M, Kimura S, Yoneyama H, Kosaka H, Nishiyama A, Fukui T, Abe Y 2001 Effects of furosemide on the tubular reabsorption of nitrates in anesthetized dogs. Eur J Pharmacol 428: 113–119
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Supported by the Thrasher Research Fund for the Early Career Award (NR-0058) [A.I.M.].
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Mian, A., Du, Y., Garg, H. et al. Urinary Nitrate Might Be an Early Biomarker for Pediatric Acute Kidney Injury in the Emergency Department. Pediatr Res 70, 203–207 (2011). https://doi.org/10.1203/PDR.0b013e31822188b4
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DOI: https://doi.org/10.1203/PDR.0b013e31822188b4
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