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Pediatric Nephrology

, Volume 21, Issue 7, pp 989–994 | Cite as

Urinary neutrophil gelatinase-associated lipocalcin in D+HUS: a novel marker of renal injury

  • Howard TrachtmanEmail author
  • Erica Christen
  • Avital Cnaan
  • Jilma Patrick
  • Volker Mai
  • Jaya Mishra
  • Aditya Jain
  • Nathan Bullington
  • Prasad Devarajan
  • Investigators of the HUS-SYNSORB Pk Multicenter Clinical Trial
Original Article

Abstract

Background: Diarrhea-associated hemolytic uremic syndrome (D+HUS) causes acute renal failure. Neutrophil gelatinase-associated lipocalcin (NGAL) is an early indicator of kidney injury. Objective: To determine if urinary NGAL excretion is a biomarker of severe renal injury and predicts the need for dialysis in D+HUS. Methods: Patients were randomly selected from among participants in the SYNSORB Pk trial. Urine samples were collected daily if available during the first week of hospitalization. NGAL levels were determined by ELISA. Results: 34 children, age 5.9±3.9 yr, were studied; ten (29%) required dialysis. Patients were categorized based on urinary NGAL concentration within five days of hospitalization - <200 ng/ml and ≥200 ng/ml. Twenty patients (58%) had increased urinary NGAL excretion. The severity of D+HUS at enrollment was similar in the two groups. However, children with increased urinary NGAL levels had higher peak BUN and creatinine concentrations (P<0.01) and required dialysis more often, 9/20 versus 1/14 (P=0.024) compared to children with normal excretion. Conclusion: The majority of patients with D+HUS have renal tubular epithelial injury, as evidenced by elevated urinary NGAL excretion. Urinary NGAL levels below 200 ng/ml within five days of hospitalization may be an adjunctive marker that defines less severe renal involvement.

Keywords

Diarrhea-associated hemolytic uremic syndrome (D+HUS) Neutrophil gelatinase-associated lipocalcin (NGAL) Acute renal failure Dialysis Biomarker 

Notes

Acknowledgements

This work was presented at the Annual Meeting of the American Society of Nephrology, Philadelphia, PA, November 2005. It was supported, in part, by grant DK52147 (HT). PD 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.

References

  1. 1.
    Trachtman H, Christen C (1999) Hemolytic uremic syndrome: current understanding of the pathogenesis and therapeutic trials and interventions. Curr Opin Pediatr 11:162–168CrossRefGoogle Scholar
  2. 2.
    Tarr PI, Gordon CA, Chandler WL (2005) Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365:1073–1086PubMedGoogle Scholar
  3. 3.
    Kaplan BA, Meyers KE, Schulman S (1998) The pathogenesis and treatment of hemolytic uremic syndrome. J Am Soc Nephrol 9:1126–1133PubMedGoogle Scholar
  4. 4.
    Andreoli SP, Trachtman H, Acheson DWK, Siegler RL, Obrig TG (2002) Hemolytic uremic syndrome: epidemiology, pathophysiology, and therapy. Pediatr Nephrol 17:293–298CrossRefGoogle Scholar
  5. 5.
    Trachtman H, Cnaan A, Christen E, Gibbs K, Zhao S, Acheson DWK, Weiss R, Kaskel FJ, Spitzer A, Hirschman GH (2003) Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome in children: A randomized clinical trial. JAMA 290:1337–1344CrossRefGoogle Scholar
  6. 6.
    Siegler RL (1994) Spectrum of extra-renal involvement in postdiarrheal hemolytic–uremic syndrome. J Pediatr 125:511–518CrossRefGoogle Scholar
  7. 7.
    Garg AX, Suri RS, Barrowman N, Rehman F, Matsell D, Rosas-Arellano MP, Salvadori M, Haynes RB, Clark WF (2003) Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: A systematic review, meta-analysis, and meta-regression. JAMA 290:1360–1370CrossRefGoogle Scholar
  8. 8.
    Ray PE, Liu XH (2001) Pathogenesis of Shiga toxin-induced hemolytic uremic syndrome. Pediatr Nephrol 16:823–839CrossRefGoogle Scholar
  9. 9.
    Kiyokawa N, Taguchi T, Mori T, Uchida H, Sato N, Takeda T, Fujimoto J (1998) Induction of apoptosis in normal renal tubular epithelial cells by Escherichia coli Shiga toxins 1 and 2. J Infect Dis 178:178–184CrossRefGoogle Scholar
  10. 10.
    Hughes AK, Stricklett PK, Kohan DE (1998) Cytotoxic effect of Shiga toxin-1 on human proximal tubule cells. Kidney Int 54:426–437CrossRefGoogle Scholar
  11. 11.
    Noris M, Remuzzi G (2005) Hemolytic uremic syndrome. J Am Soc Nephrol 16:1035–1050CrossRefGoogle Scholar
  12. 12.
    Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P (2003) Identification of neutrophil gelatinase-associated lipocalcin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 14:2534–2543CrossRefGoogle Scholar
  13. 13.
    Mishra J, Mori K, Ma Q, Kelly C, Yang J, Mitsnefes M, Barasch J, Devarajan P (2004) Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalcin. J Am Soc Nephrol 15:3073–3082CrossRefGoogle Scholar
  14. 14.
    Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, 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 lipocalcin–siderophore–iron complex rescues the kidney ischemia–reperfusion injury. J Clin Invest 115:610–621CrossRefGoogle Scholar
  15. 15.
    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 lipocalcin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238CrossRefGoogle Scholar
  16. 16.
    Te Loo DM, Monnens LA, van den Heuvel LP, Gubler MC, Kockx MM (2001) Detection of apoptosis in kidney biopsies of patients with D+ hemolytic uremic syndrome. Pediatr Res 49:413–416CrossRefGoogle Scholar
  17. 17.
    Nestoridi E, Kushak RI, Duguerre D, Grabowski EF, Ingelfinger JR (2005) Up-regulation of tissue factor activity on human proximal tubular epithelial cells in response to Shiga toxin. Kidney Int 67:2254–2266CrossRefGoogle Scholar
  18. 18.
    Schulman SL, Kaplan BS (1996) Management of patients with hemolytic uremic syndrome demonstrating severe azotemia but not anuria. Pediatr Nephrol 10:671–674CrossRefGoogle Scholar
  19. 19.
    Lameire N, Van Biesen W, Vanholder R (2005) Acute renal failure. Lancet 365:417–430CrossRefGoogle Scholar
  20. 20.
    Ohlsson S, Wieslander J, Segelmark M (2003) Increased circulating levels of proteinase 3 in patients with anti-neutrophilic cytoplasmic autoantibodies-associated systemic vasculitis in remission. Clin Exp Immunol 131:528–535CrossRefGoogle Scholar

Copyright information

© IPNA 2006

Authors and Affiliations

  • Howard Trachtman
    • 1
    Email author
  • Erica Christen
    • 1
  • Avital Cnaan
    • 2
  • Jilma Patrick
    • 3
  • Volker Mai
    • 3
  • Jaya Mishra
    • 4
  • Aditya Jain
    • 4
  • Nathan Bullington
    • 4
  • Prasad Devarajan
    • 4
  • Investigators of the HUS-SYNSORB Pk Multicenter Clinical Trial
  1. 1.Department of Pediatrics (Division of Nephrology)Schneider Children’s Hospital of the North Shore-Long Island Jewish Medical CenterNew YorkUSA
  2. 2.Department of Biostatistics and EpidemiologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  3. 3.Department of Epidemiology and Preventive MedicineUniversity of MarylandBaltimoreUSA
  4. 4.Department of Pediatrics (Division of Nephrology)Cincinnati Children’s Hospital Medical CenterCincinnatiUSA

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