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

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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.

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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.

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Authors and Affiliations

  1. Department of Pediatrics (Division of Nephrology), Schneider Children’s Hospital of the North Shore-Long Island Jewish Medical Center, New Hyde Park, New York, NY, USA

    Howard Trachtman & Erica Christen

  2. Department of Biostatistics and Epidemiology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Avital Cnaan

  3. Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, MD, USA

    Jilma Patrick & Volker Mai

  4. Department of Pediatrics (Division of Nephrology), Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Jaya Mishra, Aditya Jain, Nathan Bullington & Prasad Devarajan

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  1. Howard Trachtman
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  2. Erica Christen
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  3. Avital Cnaan
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  4. Jilma Patrick
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  5. Volker Mai
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  6. Jaya Mishra
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  7. Aditya Jain
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  8. Nathan Bullington
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  9. Prasad Devarajan
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Consortia

Investigators of the HUS-SYNSORB Pk Multicenter Clinical Trial

Corresponding author

Correspondence to Howard Trachtman.

Appendix

Appendix

List of participating centers

Administrative center: Howard Trachtman MD, Principal Investigator; Erica Christen RN, Project Coordinator, Schneider Children’s Hospital, New Hyde Park, NY; Data Coordinating Center: Avital Cnaan PhD (Director), Kathleen Gibbs, MSIS, Children’ Hospital of Philadelphia, Philadelphia, PA; Microbiology Core Laboratory: David Acheson MD (Director), Ramona Chitrakar, Thao Ngo, Fred Smith, Michelle Nieves, Sam Caraballo, Tufts-New England Medical Center, Boston, MA; Jilma Patrick, University of Maryland, Baltimore, MD; Data Safety Monitoring Board: Julie Ingelfinger MD (Chairperson), Gladys Hirschman MD, Josephine Briggs MD, John Kusek MD, Daniel Cattran MD, Mitchell B. Cohen MD, Katherine Freeman PhD, Thomas Greene PhD, Solomon Moshe MD; Participating Centers: Howard Trachtman MD, Schneider Children’s Hospital, New Hyde Park, NY; Seth Schulman MD, Children’s Hospital of Philadelphia, Philadelphia, PA; James Springate MD, Children’s Hospital of Buffalo, Buffalo, NY; Frederick Kaskel MD PhD, Montefiore Medical Center, Bronx, NY; Dilys Whyte MD, State University of NY Hospital at Stony Brook, Stony Brook, NY; Robert Weiss MD, New York Medical College/Westchester County Medical Center, Valhalla, NY; Charles McKay MD, duPont Hospital for Children, Wilmington, DE; Lewis Reisman MD, St. Barnabas Hospital for Children, Livingston, NJ; Eduardo Perelstein MD, Cornell University Medical Center, New York, NY; Manju Chandra MD, North Shore University Hospital, Manhasset, NY; Jose Salcedo MD, St. Joseph’s Children’s Hospital, Patterson, NJ; Lynne Weiss MD, Robert Wood Johnson University Hospital, New Brunswick, NJ; William Varade MD, State University of NY Rochester Medical Center, Rochester, NY; Douglas Ford MD, Denver Children’s Hospital, Denver, CO; James Chan MD, Medical College of Virginia, Richmond, VA; Irene Restaino MD, Children’s Hospital of the King’s Daughters, Norfolk, VA; Shashi Nagaraj MD, Wake Forest University/North Carolina Baptist Hospital, Winston-Salem, NC; Victoria Norwood MD, University of Virginia Medical Center, Charlottesville, VA; John Foreman MD, Duke University Medical Center, Durham, NC; Michael Moritz MD, Children’s Hospital of Pittsburgh, Pittsburgh, PA; John Mahan MD, Columbus Children’s Hospital, Columbus, OH; Marva Moxey-Mims MD, Children’s National Medical Center, Washington DC; Barry Warshaw MD, Egleston Children’s Hospital, Atlanta, GA; Verna Yiu MD, University of Alberta Hospital, Edmonton, Alberta, Canada; Andrew Brem MD, Rhode Island Hospital, Providence, RI; Sharon Bartosh MD, University of Wisconsin Hospital, Madison, WI; Sharon Andreoli MD, University of Indiana/Riley Children’s Hospital, Indianapolis, IN; Lawrence Milner MD, Tufts New England Medical Center, Boston, MA; Jens Goebel MD, University of Kentucky Medical Center, Lexington, KY; Dianne Muchant MD, West Virginia University Medical Center, Morgantown, WV; Coral Hanevold MD, Medical College of Georgia, Augusta, GA.

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Trachtman, H., Christen, E., Cnaan, A. et al. Urinary neutrophil gelatinase-associated lipocalcin in D+HUS: a novel marker of renal injury. Pediatr Nephrol 21, 989–994 (2006). https://doi.org/10.1007/s00467-006-0146-y

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